bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic Resonance Angiography Demonstrates Vascular Healing of Carotid and Vertebral Artery Dissections
Authors: Kasner Scott E. , Hankins Linda L. , Bratina Patti , Morgenstern Lewis B.
Published: June 2011

Background and Purpose
Dissection of the carotid and vertebral arteries is most accurately diagnosed with conventional angiography. MR techniques are sensitive for detecting the abnormalities associated with dissection but may lack specificity. We hypothesized that MR may be useful for serial monitoring of dissection and may therefore guide therapy.

Methods
All patients with angiographically proven carotid and/or vertebral artery dissection from July 1994 to June 1996 were followed for a median duration of 10.5 months. Of these 29 patients (44 vessels), 18 were concurrently evaluated with MR, and a target group of 9 patients (17 vessels) was prospectively followed with MR at 3-month intervals.

Results
In the 18 patients with both imaging studies at baseline, angiography revealed 30 dissected vessels while MR detected 27 (90%). In the target group of 9 patients, initial MR identified 15 of the 17 dissections diagnosed with angiography. Serial MR revealed complete healing in 5 vessels, improvement in 6 vessels, no change in 4 vessels, and worsening in 2 vessels. The radiographic features most likely to resolve were stenosis and mural hematoma, while occlusion and luminal irregularity tended to persist. Late ischemic events occurred in 2 patients, both with persistent MR evidence of dissection, one while subtherapeutic on warfarin therapy and the other occurring 1 week after warfarin was discontinued.

Conclusions
MR is a reliable noninvasive method for following the vascular response to treatment and may guide the course of a clinical trial comparing medical therapies for carotid and vertebral artery dissection.
Extracellular Nucleotide–Induced [Ca
2+
]
i
Elevation in Rat Basilar Smooth Muscle Cells
Authors: Sima Bogdan , Weir Bryce K. A. , Macdonald R. Loch , Zhang He
Published: June 2011

Background and Purpose
Extracellular nucleotides play an important role in the regulation of vascular tone and may be involved in cerebral vasospasm after subarachnoid hemorrhage. The objective of this study was to investigate the receptor subtypes for nucleotides and their mechanisms of [Ca
2+
]
i
mobilization in cerebral vasculature.

Methods
Rat basilar smooth muscle cells were isolated by an enzymatic method. [Ca
2+
]
i
mobilization in freshly isolated cells was monitored using fura 2 microfluorimetry.

Result
Extracellular nucleotides produced a concentration-dependent biphasic [Ca
2+
]
i
response, a large transient peak followed by a slowly decaying plateau. The potency of nucleotides to raise [Ca
2+
]
i
was ATPγS≥UDP≥ATP≈UDP≈TTP, indicating that P
2u
receptors were expressed in the rat basilar smooth muscle cells. The effect of UTP to release Ca
2+
from internal stores was reduced by pertussis toxin, by the phospholipase C inhibitor 2-nitro-4-carboxyphenyl N,N-diphenylcarbamate, and by the Ca
2+
-pump inhibitor thapsigargin. The Ca
2+
entry induced by UTP was partially attenuated by the receptor-operated Ca
2+
channel blocker SK&F96365 and by the voltage-dependent Ca
2+
channel blocker verapamil. P
2
receptor antagonists suramin and, at higher concentrations, pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid reduced the effect of UTP.

Conclusions
The results are the first demonstration that nucleotides activate G protein–coupled P
2u
receptors to mobilize [Ca
2+
]
i
in rat basilar smooth muscle cells.
Intracerebral Hemorrhage After Intravenous t-PA Therapy for Ischemic Stroke
Authors: The NINDS t-PA Stroke Study Group
Published: June 2011

Background and Purpose
We sought to identify variables associated with intracerebral hemorrhage in patients with acute ischemic stroke who receive tissue plasminogen activator (t-PA).

Methods
We performed subgroup analyses of data from a randomized, double-blind, placebo-controlled trial of intravenous t-PA administered to stroke patients within 3 hours of onset. Using multivariable regression modeling procedures, we assessed the relationship of baseline and after-treatment variables with symptomatic and asymptomatic intracerebral hemorrhage during the first 36 hours after treatment.

Results
Overall, t-PA–treated patients had an increase in the absolute risk of symptomatic intracerebral hemorrhage of 6% and a decrease in the absolute risk of 3-month mortality of 4% compared with placebo-treated patients. The only variables independently associated with an increased risk of symptomatic intracerebral hemorrhage in the final multivariable logistic regression model for the 312 t-PA–treated patients were the severity of neurological deficit as measured by the National Institutes of Health Stroke Scale score (five categories; odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2 to 2.9) and brain edema (defined as acute hypodensity) or mass effect by CT before treatment (OR, 7.8; 95% CI, 2.2 to 27.1). This final model correctly predicted those t-PA–treated patients who would or would not have a symptomatic hemorrhage with only 57% efficiency. In the subgroup of patients with a severe neurological deficit, t-PA–treated patients were more likely than placebo-treated patients to have a favorable 3-month outcome (adjusted OR based on multiple outcomes, 4.3; 95% CI, 1.6 to 11.9). These results were similar for the subgroup with edema or mass effect by CT (adjusted OR, 3.4; 95% CI, 0.6 to 20.7). The likelihood of severe disability or death was similar for t-PA–and placebo-treated patients with these two baseline characteristics.

Conclusions
Despite a higher rate of intracerebral hemorrhage, patients with severe strokes or edema or mass effect on the baseline CT are reasonable candidates for t-PA, if it is administered within 3 hours of onset.
Generalized Efficacy of t-PA for Acute Stroke
Authors: The NINDS t-PA Stroke Study Group
Published: June 2011

Background and Purpose
We sought to identify subgroups of stroke patients in whom thrombolytic therapy is particularly hazardous or efficacious.

Methods
We conducted a post hoc subgroup analysis of a randomized, double-blind, placebo-controlled clinical trial of intravenous tissue plasminogen activator (t-PA) for stroke patients presenting within 3 hours after symptom onset. Before treatment, historical, physical, and laboratory findings were summarized. We identified variables that might predict outcome and/or differential response to t-PA therapy. Outcome was measured with four stroke rating scales administered 3 months after treatment. Statistical significance was assessed with a global outcome procedure that considers the results of all four scales simultaneously. Using regression analysis, we compared the information collected before treatment with the global outcome. Multivariable procedures were used to find information that could guide selection of patients for t-PA therapy.

Results
No pretreatment information significantly affected patients’ response to t-PA. The power of the model to detect a treatment interaction was greater than 90%, and therefore the probability of a type II error is very low. Apart from t-PA therapy, outcome was related to age-by-deficit severity interaction, diabetes, age-by-blood pressure interaction, and early CT findings. These variables and interactions altered long-term patient outcome irrespective of t-PA treatment but did not alter the likelihood of responding favorably to t-PA therapy.

Conclusions
Patients should be selected for t-PA thrombolysis according to the guidelines published in the report of the NINDS t-PA Stroke Trial. Further subselection of patients, such as by age or stroke severity, is not supported by our post hoc analysis.
Circadian Rhythm of Heart Rate Variability Is Reversibly Abolished in Ischemic Stroke
Authors: Korpelainen Juha T. , Sotaniemi Kyösti A. , Huikuri Heikki V. , Myllylä Vilho V.
Published: June 2011

Background and Purpose
Acute brain infarction significantly decreases heart rate variability as a result of cardiovascular autonomic dysregulation. However, information regarding circadian rhythms of heart rate and heart rate variability is limited.

Methods
In this prospective study, we analyzed 24-hour circadian rhythm of heart rate and the time and frequency domain measures of heart rate variability in 24 patients with hemispheric brain infarction, 8 patients with medullary brainstem infarction, and 32 age- and sex-matched healthy control subjects. ECG data were obtained from the patients in the acute phase and at 6 months after the infarction.

Results
In the acute phase of stroke, all the components of heart rate variability, ie, standard deviation of RR intervals, total power, high-frequency power, low-frequency power, and very-low-frequency power, were similar at night (from midnight to 6
am
) and during the day (from 9
am
to 9
pm
), indicating that the circadian oscillation of heart rate variability had been abolished. At 6 months after brain infarction, the circadian rhythm had returned and, as in the control subjects, the values at night were significantly higher than those in the daytime. The values in hemispheric and in brainstem infarction did not differ significantly from each other.

Conclusions
These results suggest that circadian fluctuation of heart rate variability is reversibly abolished in the acute phase of ischemic stroke and that it returns during the subsequent 6 months. The loss of the relative vagal nocturnal dominance may contribute to the incidence of cardiac arrhythmias and other cardiovascular complications after acute stroke.
A New Automated Computerized Analyzing System Simplifies Readings and Reduces the Variability in Ultrasound Measurement of Intima-Media Thickness
Authors: Wendelhag Inger , Liang Quan , Gustavsson Tomas , Wikstrand John
Published: June 2011

Background and Purpose
A computerized analyzing system with manual tracing of echo interfaces for measurement of intima-media thickness and lumen diameter in carotid and femoral arteries was previously developed by our research group and has been used for many years in several laboratories. However, manual measurements are not only time consuming, but the results from these readings are also dependent on training and subjective judgement. A further problem is the observed drift in measurements over time. A new computerized technique for automatic detection of echo interfaces was therefore developed. The aim of this study was to evaluate the new automated computerized analyzing system.

Methods
The new system is based on dynamic programming and includes optional interactive modification by the human operator. Local measurements of vessel echo intensity, intensity gradient, and boundary continuity are extracted by image analysis techniques and included as weighed terms in a cost function. The dynamic programming procedure is used for determining the optimal location of the vessel interfaces in a way that the cost function is minimized.

Results
With the new automated computerized analyzing system the measurement results were less dependent on the reader’s experience, and the variability between readers was less compared with the old manual analyzing system. The measurements were also less time consuming.

Conclusions
The new automated analyzing system will not only greatly increase the speed of measurements but also reduce the variability between readers. It should also reduce the variability between different laboratories if the same analyzing program is used. Furthermore, the new system will probably prevent the problem with drift in measurements over time.
Vulnerability to Cerebral Hypoxic-Ischemic Insult in Neonatal but Not in Adult Rats Is in Parallel With Disruption of the Blood-Brain Barrier
Authors: Muramatsu Kanji , Fukuda Atsuo , Togari Hajime , Wada Yoshiro , Nishino Hitoo
Published: June 2011

Background and Purpose
Vulnerability to cerebral hypoxic-ischemic (H-I) insult and its relation to disruption of the blood-brain barrier were investigated in postnatal rats.

Methods
Pups of postnatal day (P) 7, P14, and P21 underwent ligation of a unilateral carotid artery and were exposed to hypoxic conditions. For the detection of early-phase deterioration, brains were perfusion-fixed 24 hours after H-I insult and examined by argyrophil III method. For the detection of later infarction, animals were fixed at 72 hours after the H-I insult.

Results
In either case, tissue damage was detected in the striatum, parietal cortex, and hippocampus. The vulnerability of P7 and P21 rats was remarkable, as compared with P14 rats. Although the developmental status of the vasculature was not significantly different at each age, the permeability of IgG after H-I injury was prominent in P7 rats and to a lesser extent in P14 rats. In P21 rats, however, there was little IgG leakage even 24 hours after the insult. Dexamethasone pretreatment blocked the extravasation of IgG and reduced the damaged tissue in P7 and P14 rats but not in P21 rats. Percentages of reduction in infarcted areas by the dexamethasone became smaller in proportion to ages.

Conclusions
The results suggest that in younger rats vulnerability to H-I insult was in parallel with permeability of the blood-brain barrier, whereas in adults it might be more dependent on cellular vulnerability.
Warfarin Use Among Patients With Atrial Fibrillation
Authors: Brass Lawrence M. , Krumholz Harlan M. , Scinto Jeanne M. , Radford Martha
Published: June 2011

Background and Purpose
Warfarin reduces the rate of stroke among patients with atrial fibrillation. We sought to determine warfarin use within a population sample of elderly patients with atrial fibrillation.

Methods
The Connecticut Peer Review Organization conducted a chart review of Medicare patients aged ≥65 years with a history of atrial fibrillation before a hospitalization during the first 6 months of 1994.

Results
Among 488 patients (308 women; 457 white; 173 aged ≥85 years), 38% (184/488) had a relative contraindication to anticoagulation (history of bleeding, dementia, alcohol use, falls, cancer, or the need for nonsteroidal anti-inflammatory drugs). Among the remaining patients (with known atrial fibrillation, but without a contraindication), only 38% (117/304) had been prescribed warfarin. Of those not prescribed warfarin, 63% (117/187) were also not taking aspirin. There were 272 patients with at least one additional vascular risk factor and no contraindication to anticoagulation. Among these patients at moderate to high risk for stroke, anticoagulation had been prescribed in 40% (109/272). Overall, among those not prescribed warfarin, 58% (95/163) were not taking aspirin. Patients admitted with a stroke were more likely to be significantly underanticoagulated (with international normalized ratio <1.5) (43.5% versus 20.9% for those without stroke;
P
<.005). Anticoagulation was most effective for those with an international normalized ratio ≥2.0.

Conclusions
Warfarin anticoagulation with atrial fibrillation, even among “ideal” candidates, appears dramatically underutilized. In addition, among those prescribed warfarin, patients are often undertreated. Increased warfarin use among patients with atrial fibrillation represents an excellent opportunity for stroke prevention in the elderly.
Long-term Oral Anticoagulation Reduces Bone Mass in Patients with Previous Hemispheric Infarction and Nonrheumatic Atrial Fibrillation
Authors: Sato Yoshihiro , Honda Yoshiaki , Kunoh Haruko , Oizumi Kotaro
Published: June 2011

Background and Purpose
Vitamin K is an essential factor for synthesis of plasma clotting proteins and for site-specific carboxylation of bone Gla protein and other bone matrix proteins. Low vitamin K has been associated with reduced bone mineral density. Warfarin therapy, which inhibits vitamin K–dependent blood-clotting, has been demonstrated to reduce the risk of stroke in nonrheumatic atrial fibrillation. We evaluated vitamin K and bone mineral density in nonrheumatic atrial fibrillation patients who had long-term warfarin therapy after an ischemic stroke.

Methods
Sera were collected from 64 patients with nonrheumatic atrial fibrillation and ischemic stroke who had been treated with warfarin, 63 stroke patients without warfarin, and 39 control subjects. All stroke patients in both groups had hemiplegia. Sera were assayed for vitamins K
1
and K
2
, bone Gla protein, and 25-hydroxyvitamin D. Bone mineral density was determined in both second metacarpals.

Results
Serum vitamin K
1
concentrations (ng/mL) were lower in treated patients (.234±.177 ng/mL) than in untreated patients (.329±.284) or controls (.553±.164). Bone Gla protein was lower in treated patients’ sera (1.241±.799 ng/mL) than in untreated patients (4.476±3.226). Concentrations of 25-hydroxyvitamin D were lower in both patient groups. Bone mineral density was lower on both sides in treated patients than in untreated patients (
P
<.0001). Vitamin K
1
and bone Gla protein were significantly related to bone mineral density bilaterally in treated but not in untreated patients.

Conclusions
Bone mineral density was significantly lower in stroke patients with long-term warfarin treatment than in untreated patients. Both warfarin-induced reduction in vitamin K function and lowered vitamin K
1
concentration are probable causes of this osteopenia.
Causes and Mechanisms of Cerebellar Infarction in Young Patients
Authors: Barinagarrementeria Fernando , Amaya Luis E. , Cantú Carlos
Published: June 2011

Background and Purpose
The incidence of cerebellar infarction in a series of patients with stroke is approximately 1.5%. The average patient age in most reported series is 62 years. The most common etiologies in this age group are atherosclerosis and cardiac embolism. The aim of this study was to determine the causes and mechanisms of cerebellar infarction in patients younger than 40 years.

Methods
We analyzed retrospectively the clinical and radiological data from 21 men and 16 women with cerebellar infarction admitted to our hospital from January 1986 to December 1996. The patients had been studied extensively to determine the etiology of the cerebellar infarction.

Results
In the 37 patients (mean age, 30 years), 29 infarcts were limited to one territory (15 in the posteroinferior cerebellar artery [PICA]; 14 in the superior cerebellar artery); 8 had nonterritorial infarctions. The most common stroke mechanisms in each territory were as follows: PICA: nonatherosclerotic vasculopathic (67%), cardioembolic (20%), and hematologic and cryptogenic (each 7%); superior cerebellar artery: cardioembolic (42%), cryptogenic (31%), migrainous (21%), and nonatherosclerotic vasculopathic and hematologic (each 7%); and mixed territory: nonatherosclerotic vasculopathic (50%), cryptogenic (25%), cardioembolic (12%), and hematologic (12%).

Conclusions
The most common mechanism of cerebellar infarctions was arterial occlusion as a result of intracranial vertebral artery dissection (40%), mainly with PICA involvement. Embolism from a cardiac source resulted primarily from patent foramen ovale and rheumatic valvular disease. Hematologic disturbances and migraine were responsible for a few cases.
A Mutation in Plasma Platelet-Activating Factor Acetylhydrolase (Val
279
→Phe) is a Genetic Risk Factor for Stroke
Authors: Hiramoto Makoto , Yoshida Hidemi , Imaizumi Tadaatsu , Yoshimizu Nobuhiro , Satoh Kei
Published: June 2011

Background and Purpose
Platelet-activating factor (PAF) is a phospholipid with multiple actions that include thrombosis and inflammation. It is inactivated by a plasma enzyme, PAF acetylhydrolase. Deficiency of this enzyme in plasma is caused by a missense mutation in the gene (Val
279
→Phe). We have studied a possible association of this mutation with the risk of stroke.

Subjects and Methods
We studied 120 consecutive patients with cerebral thrombosis. The control group consisted of 134 patients matched for age and sex with minor complaints but without stroke. Genomic DNA was analyzed for the mutant allele by a specific polymerase-chain reaction. Plasma PAF acetylhydrolase activity was determined by the method of Stafforini et al.

Results
The prevalence of the mutant gene was 43.4% in stroke patients (39.2% heterozygotes and 4.2% homozygotes), which was significantly higher than the 25.4% in control subjects (22.4% heterozygotes and 3.0% homozygotes) (χ
2
=9.22,
P
<.01). The prevalence was slightly higher in stroke patients without hypertension than those with hypertension, but the difference was not significant. The patients with family histories of stroke had a slightly higher but not a significant prevalence of the mutant gene as compared with those without family histories of stroke. Plasma PAF acetylhydrolase activity was higher in patients than in control subjects, in normal subjects, or patients with a heterozygous genotype.

Conclusions
These results suggest that plasma PAF acetylhydrolase deficiency may be a risk factor for stroke. This may explain the relatively high prevalence of stroke in Japan, as the mutation is more common among Japanese than Caucasians.
Pseudoxanthoma Elasticum Lesions and Cardiac Complications as Contributing Factors for Strokes in β-Thalassemia Patients
Authors: Aessopos Athanasios , Farmakis Dimitrios , Karagiorga Markisia , Rombos Ioannis , Loucopoulos Dimitrios
Published: June 2011

Background and Purpose
Pseudoxanthoma elasticum (PXE) lesions, which lead to intracranial hemorrhages and cardiac complications, predisposing to thrombotic strokes, are frequent findings in β-thalassemia. Nevertheless, the association of these lesions with strokes in thalassemic patients has not been previously discussed.

Methods
Ten β-thalassemic patients who developed an intracranial hemorrhage or a thrombotic stroke were reviewed.

Results
In the group of the four patients presenting with hemorrhage, one had PXE lesions, one had cardiac abnormalities, and one both PXE and cardiac disorders. In the group presenting with thrombotic stroke, all six patients had cardiac abnormalities and platelet count elevation due to splenectomy. Three also had PXE findings. No other predisposing factor for stroke was present.

Conclusions
Cardiac complications and PXE may be risk factors for strokes in β-thalassemia. Their frequent coexistence leads to a therapeutic dilemma in patients requiring antithrombotic therapy.
Superoxide Dismutase Activity in Serum of Patients With Acute Cerebral Ischemic Injury
Authors: Spranger Matthias , Krempien Sebastian , Schwab Stefan , Donneberg Sybille , Hacke Werner
Published: June 2011

Background and Purpose
Superoxide dismutase (SOD) is one of the major free radical scavenging systems that might play a role in both degenerative and acute diseases of the central nervous system.

Methods
We measured SOD activity in the serum of 41 patients with acute ischemic stroke with a chemiluminometric assay based on the generation of oxygen free radicals by xanthine and xanthine oxidase.

Results
SOD activity was significantly lower in patients with ischemic stroke than in age-matched control patients with nonvascular, neurological illnesses (n=24;
P
<.034, Wilcoxon rank test). The activity was inversely correlated with the size of infarction on CT (
P
=.01, Spearman correlation) and the severity of neurological deficits (
P
<.001, Spearman correlation). The decreased SOD activity recovered within 5 days after stroke to values found in serum of control patients.

Conclusions
Our data suggest that the SOD activity in serum is reduced in stroke patients, and replacement of antioxidative activity could be beneficial in the acute treatment of cerebral ischemia.
Preexisting Dementia in Stroke Patients
Authors: Hénon H. , Pasquier F. , Durieu, MD; O. Godefroy, MD, PhD; C. Lucas, MD; F. Lebert, M
Published: June 2011

Background and Purpose
The link between stroke and degenerative dementia, especially Alzheimer’s disease, is closer than expected by chance. Dementia after stroke may be due to the cumulative effect of vascular and degenerative changes. The prevalence of dementia just before stroke onset remains unsettled. The aim of this study was to determine the frequency of preexisting dementia in stroke patients, associated factors, and consequences on outcome.

Methods
We evaluated the cognitive functioning prior to stroke in 202 consecutive patients with ischemic or hemorrhagic stroke by means of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). We classified in the dementia group patients with IQCODE scores of 104 or more. Six months after stroke onset, survivors underwent a battery of neuropsychological tests.

Results
Thirty-three patients were demented before stroke (16.3%; 95% confidence interval, 11.2 to 21.4). There was no diagnosis of dementia in 32 of these 33 patients. We determined by logistic regression analysis that female sex, family dementia, leukoaraiosis, and cerebral atrophy are independently associated with prestroke dementia. All survivors who had IQCODE scores of 104 or more at the acute stage met criteria for dementia 6 months later.

Conclusions
Our study showed that one sixth of stroke patients have preexisting dementia. Therefore, some patients with so-called “poststroke dementia” probably had unrecognized preexisting dementia.
High Stroke Incidence in the Prospective Community-Based L’Aquila Registry (1994–1998)
Authors: Carolei Antonio , Marini Carmine , Di Napoli Mario , Di Gianfilippo Giacinto , Santalucia Paola , Baldassarre Massimo , Giorgio De Matteis  , di Orio Ferdinando
Published: June 2011

Background and Purpose
Changes in stroke incidence are likely to occur as a consequence of aging of the population, but evidence for this hypothesis is lacking.

Methods
A prospective community-based registry of first-ever strokes (1994 to 1998) classified according to the
International Classification of Diseases, 9th Revision
(ICD-9) was established in the L’Aquila district, central Italy, with a total population of 297 838 (1991 census). Patients were identified by active monitoring of multiple sources, including general practitioners.

Results
In 1994, 819 patients (398 men and 421 women; mean±SD age, 74.8±11.3 years) suffered from a first-ever stroke. Eighty-nine percent of the patients had neuroimaging studies of the brain and were reclassified with the recent
Application of the International Classification of Diseases to Neurology
(ICD-10 NA). The occurrence of subarachnoid hemorrhage, intracerebral hemorrhage, cerebral infarction, and ill-defined events was 2.9%, 14.9%, 80.2%, and 2.0%, respectively. Crude annual incidence of first-ever stroke was 2.75/1000 (95% confidence interval [CI], 2.57 to 2.94) and 24.23/1000 (95% CI, 21.65 to 27.10) in patients older than 80 years. Incidence rates were higher in men and steeply increased with age. The standardized rate was 2.37/1000 for the Italian and 2.28/1000 for the European population. The 30-day case-fatality rate was 25.6% (95% CI, 22.8% to 28.7%). The occurrence of death, disability, and full recovery at 1 year was 36.9%, 38.9%, and 24.2%, respectively. No differences were found in stroke incidence and case-fatality according to income and urban or rural residences.

Conclusions
In our population-based study, we found a high stroke incidence notably in the older age subgroups, suggesting that rather than declining, stroke is only being postponed until later in life.
Cerebral Magnetic Resonance T2 High Intensities in End-Stage Renal Disease
Authors: Suzuki Mikiko , Wada Akira , Isaka Yoshinari , Maki Keishiro , Inoue Toru , Fukuhara Yoshifumi
Published: June 2011

Background and Purpose
The pathophysiological mechanisms that cause cerebral MR T2 high intensities in end-stage renal disease (ESRD) are unclear. We evaluated the incidence and the risk factors of T2-weighted MR brain high intensities in patients with ESRD.

Methods
We examined the degree of T2-weighted MR brain high intensities (high intensity score) and determined the variables that had an independent association with the occurrence of high intensities in 38 patients with ESRD before chronic dialysis treatment, 173 patients with essential hypertension, and 72 normotensive control subjects.

Results
The whole brain high intensity score was significantly higher in patients with ESRD than in the control subjects, but there was no significant difference in high intensity score between the ESRD and the hypertensive groups. Age, hypertension, and smoking were significant independent predictors of high intensities in a multiple logistic regression model. The distribution pattern of high intensities in ESRD patients was very similar to that obtained from hypertensive patients; the high intensity score was highest in the corona radiata and was lowest in the cerebellum.

Conclusions
T2 high intensities on MR images of ESRD may reflect subcortical small-vessel alterations induced by hypertension.
The Calmodulin Antagonist Trifluoperazine in Transient Focal Brain Ischemia in Rats
Authors: Kuroda Satoshi , Nakai Akihito , Kristían Tibor , Siesjö Bo K.
Published: June 2011

Background and Purpose
This study was performed to assess the efficacy and the therapeutic window for the calmodulin antagonist trifluoperazine in experiments involving transient middle cerebral artery (MCA) occlusion.

Methods
Male Wistar rats were subjected to transient (2 hours) MCA occlusion by an intraluminal filament technique. Trifluoperazine (5.0 mg · kg
−1
) was injected intraperitoneally 5 minutes, 1 hour, or 2 hours after the induction of ischemia. Drug administration was repeated 24 hours after the first injection. Neurological scores and infarct volumes were evaluated at 48 hours of reperfusion. The effect of trifluoperazine on cortical blood flow was studied with continuous laser-Doppler flowmetry.

Results
The median value of neurological scores in the control rats (n=7) was 3, while those in the treated groups were 1 (5-minute group; n=7,
P
<.05) and 2 (1-hour and 2-hour groups; each n=7). The percentage of infarct volume in the control rats was 34.8±4.9% (mean±SD), while those in the treated groups were 11.3±12.3% (5-minute group;
P
<.01), 24.8±15.1% (1-hour group), and 28.8±8.3% (2-hour group). Trifluoperazine, given at 5 minutes after ischemia, had no influence on blood flow in the neocortical penumbra during and after ischemia.

Conclusions
The results demonstrate that trifluoperazine markedly reduces infarct volume after 2 hours of MCA occlusion when given 5 minutes after the induction of ischemia. However, the therapeutic window for trifluoperazine seems narrow since the drug had no significant effect when given after 1 or 2 hours.
Differential Hydroxylation of Salicylate in Core and Penumbra Regions During Focal Reversible Cerebral Ischemia
Authors: Solenski Nina J. , Kwan Aij-Lie , Yanamoto Hiroji , Bennett James P. , Kassell Neal F. , Lee Kevin S.
Published: June 2011

Background and Purpose
Free radical-mediated damage during and/or after cerebral ischemia is thought to participate in the elaboration of stroke-related injury. To elucidate the role of this mechanism in cerebral damage, the study presented herein sought to clarify the spatial and temporal features of the free radical response to transient ischemia. With use of a reproducible model of in vivo focal ischemia/reperfusion, the time course of salicylate hydroxylation was measured in ischemic core and penumbra regions.

Methods
Transient focal cerebral ischemia was produced in Sprague-Dawley rats by occluding both carotid arteries and one middle cerebral artery for 3 hours, followed by reperfusion. Cerebral reperfusion was confirmed by visual inspection and iodo[
14
C]antipyrine autoradiography. A microdialysis probe was placed stereotactically in either the ischemic core or ischemic penumbra of the frontoparietal cortex; the probe was perfused with salicylate, and dialysate samples were analyzed by high-performance liquid chromatography for salicylate hydroxylation products.

Results
Salicylate hydroxylation was significantly increased during ischemia and was further increased during 6 hours of reperfusion in the penumbra compared with sham controls. In comparison, a delayed increase in hydroxylation was observed within the ischemic core region only after 3 hours of reperfusion.

Conclusion
A differential generation of salicylate hydroxylation occurs in core and penumbra regions in association with focal ischemia/reperfusion of the rat neocortex. The early and progressive response in the penumbra suggests that free radical mechanisms may be continuously active in the aggravation of injury in the ischemic penumbra during ischemia and reperfusion. In contrast, the relatively delayed onset of hydroxylation in the core region indicates that this mechanism participates primarily in the late stages of ischemic injury in densely ischemic tissue. These findings are consistent with the concept that the role of free radicals in cerebral injury may differ qualitatively and/or quantitatively in areas of total and partial cerebral perfusion.
Effect of Antihypertensive Treatment in Patients Having Already Suffered From Stroke
Authors: Gueyffier François , Boissel Jean-Pierre , Boutitie Florent , Pocock Stuart , Coope John , Cutler Jeffrey , Ekbom Tord , Fagard Robert , Friedman Lawrence , Kerlikowske Karla , Perry Mitchell , Prineas Ronald , Schron Eleanor
Published: June 2011

Background and Purpose
Drug treatment of high blood pressure has been shown to reduce the associated cardiovascular risk. Stroke represents the type of event more strongly linked with high blood pressure, responsible for a high rate of death or invalidity, and with the highest proportion of events that can be avoided by treatment. Hypertensive patients with a history of cerebrovascular accident are at particularly high risk of recurrence. Specific trials of blood pressure lowering drugs in stroke survivors showed inconclusive results in the past.

Methods
We performed a meta-analysis using all available randomized controlled clinical trials assessing the effect of blood pressure lowering drugs on clinical outcomes (recurrence of stroke, coronary events, cause-specific, and overall mortality) in patients with prior stroke or transient ischemic attack.

Results
We identified 9 trials, including a total of 6752 patients: 2 trials included 551 hypertensive stroke survivors; 6 trials of hypertensive patients included a small proportion of stroke survivors (536 patients); 1 trial included stroke survivors, whether hypertensive or not (5665 patients). The recurrence of stroke, fatal and nonfatal, was significantly reduced in active groups compared with control groups consistently across the different sources of data (relative risk of 0.72, 95% confidence interval: 0.61 to 0.85). There was no evidence that this intervention induced serious adverse effect.

Conclusions
Blood pressure lowering drug interventions reduced the risk of stroke recurrence in stroke survivors. Available data did not allow to verify whether such benefit depends on initial blood pressure level. More data are needed before considering antihypertensive therapy in normotensive patients at high cerebrovascular risk.
Risk Factors for Falls of Hospitalized Stroke Patients
Authors: Tutuarima J.A. , van der Meulen J.H.P. , de Haan R.J. , van Straten A. , Limburg M.
Published: June 2011

Background and Purpose
Patients with stroke are at a high risk for falling. We assessed the fall incidence and risk factors for patients hospitalized as the result of an acute stroke.

Methods
We studied a cohort of 720 stroke patients from 23 hospitals in The Netherlands. The data were abstracted from the medical and nursing records.

Results
We studied 346 women and 374 men with a median age of 75 years; 77% of the patients had had a cerebral infarct, 17% had had a hemorrhage, and 6% had had an undefined stroke. We recorded 104 patients (14%) who fell at least once; there were a total of 173 falls. The incidence of falls was 8.9/1000 patients per day. The daily incidence was 6.2/1000 patients for first falls and 17.9/1000 patients for second falls. Heart disease (relative risk [RR], 1.6; 95% confidence interval [CI], 1.0 to 2.4), mental decline (RR, 1.6; 95% CI, 1.0 to 2.4), and urinary incontinence (RR, 2.3; 95% CI, 1.3 to 4.1) were incremental risk factors for first falls, whereas the use of major psychotropic drugs lowered the fall risk (RR, 0.5; 95% CI, 0.3 to 0.8). The fall RR for patients with one previous fall was 2.2 (95% CI, 1.5 to 3.2), adjusted for the other risk factors. Most falls occurred during the day. Approximately 25% of the falls caused slight-to-severe injury, whereas three falls (2%) led to hip fractures.

Conclusions
Stroke patients have a high risk of falling. The identification of patients at risk may be a first step toward the implementation of fall-prevention measures for these patients.
Treadmill Aerobic Exercise Training Reduces the Energy Expenditure and Cardiovascular Demands of Hemiparetic Gait in Chronic Stroke Patients
Authors: Macko R.F. , DeSouza C.A. , Tretter L.D. , Silver K.H. , Smith G.V. , Anderson P.A. , Tomoyasu Naomi , Gorman P. , Dengel D.R.
Published: June 2011

Background and Purpose
Elevated energy costs of hemiparetic gait contribute to functional disability after stroke, particularly in physically deconditioned older patients. We investigated the effects of 6 months of treadmill aerobic exercise training on the energy expenditure and cardiovascular demands of submaximal effort ambulation in stroke patients with chronic hemiparetic gait.

Methods
Nine older stroke patients with chronic hemiparetic gait were enrolled in a 6-month program of low-intensity aerobic exercise using a graded treadmill. Repeated measures of energy expenditure based on steady state oxygen consumption during a standardized 1-mph submaximal effort treadmill walking task were performed before and after training.

Results
Six months of exercise training produced significant reductions in energy expenditure (n=9; 3.40±0.27 versus 2.72±0.25 kcal/min [mean±SEM];
P
<.005) during a given submaximal effort treadmill walking task. Repeated measures analysis in the subset of patients (n=8) tested at baseline and after 3 and 6 months revealed that reductions in energy expenditure were progressive (F=11.1;
P
<.02) and that exercise-mediated declines in both oxygen consumption (F=9.7;
P
<.02) and respiratory exchange ratio (F=13.4;
P
<.01) occurred in a strong linear pattern. These stroke patients could perform the same standardized submaximal exercise task at progressively lower heart rates after 3 months (96±4 versus 87±4 beats per minute) and 6 months of training (82±4 beats per minute; F=35.4;
P
<.002).

Conclusions
Six months of low-intensity treadmill endurance training produces substantial and progressive reductions in the energy expenditure and cardiovascular demands of walking in older patients with chronic hemiparetic stroke. This suggests that task-oriented aerobic exercise may improve functional mobility and the cardiovascular fitness profile in this population.
Relationship Between Carotid Intima-Media Thickness and Symptomatic and Asymptomatic Peripheral Arterial Disease
Authors: Allan Paul L. , Mowbray Philip I. , Lee Amanda J. , Fowkes F. Gerald R.
Published: June 2011

Background and Purpose
Ultrasonic evaluation of intima-media thickness (IMT) is one method of assessing the development of early atherosclerosis. This report describes the distribution of IMT within the general population and is one of the first to investigate its association with noninvasively assessed symptomatic and asymptomatic peripheral arterial disease.

Methods
Ultrasonic evaluation of IMT was included in the 5-year follow-up examination of participants of the Edinburgh Artery Study. Valid readings of IMT were recorded in 1106 subjects aged 60 to 80 years, and the maximum from the right and left sides of the neck was used in the analysis. Existing symptomatic and asymptomatic peripheral arterial disease and coronary heart disease were also assessed at follow-up using previously validated noninvasive techniques.

Results
IMT increased continuously with age (
P
≤.01), and its distribution was positively skewed in both sexes. The results suggest that levels of atherosclerotic development in the common carotid artery are 5 to 10 years more advanced in men than in women. In this population, the overall prevalence of moderate to severe disease was very low (only 1.2% of study participants had IMT values >2 mm). The presence of symptomatic (intermittent claudication) or asymptomatic (ankle brachial pressure index ≤0.9) peripheral arterial disease was significantly associated with increased IMT (
P
≤.05).

Conclusions
Although the prevalence of advanced atherosclerosis was very low, small changes in IMT were associated with clinically significant development of atherosclerosis in the peripheral arteries. However, further longitudinal studies are needed that standardize measurement techniques and would allow accurate comparisons across studies.
Inhibition of PDGF-Mediated Proliferation of Vascular Smooth Muscle Cells by Calcium Antagonists
Authors: Kataoka Satoshi , Alam Rita , Dash Pramod K. , Yatsu Frank M.
Published: June 2011

Background and Purpose
The mechanism by which calcium antagonists (CAs) inhibit proliferation in vascular smooth muscle cells (VSMCs) is not yet fully understood. We investigated the effects of four CAs (clentiazem, verapamil, diltiazem, and nifedipine) on signal transduction pathways activated by platelet-derived growth factor (PDGF). To determine these effects, the levels of inositol phosphates (IPs), protein kinase C (PKC), and the induction of the transcription factor activator protein-1 (AP-1) were measured.

Methods
The mitogenic effect of PDGF on VSMCs was measured by [
3
H]thymidine incorporated into DNA. IP production was monitored by [
3
H]myo-inositol incorporation. PKC activation was determined by measurement of myristoylated, alanine-rich C kinase substrate (MARCKS) phosphorylation in digitonin-permeabilized VSMCs. The induction of AP-1 complex was detected by electrophoretic mobility shift assays.

Results
Each CA significantly inhibited the [
3
H]thymidine incorporation into DNA in unstimulated cells. Similar significant decreases in [
3
H]thymidine incorporation by CAs were observed when cells were stimulated by rPDGF-BB. The phosphorylation of MARCKS mediated by rPDGF-BB was significantly reduced by each CA. Clentiazem and verapamil significantly reduced the expression of AP-1 induced by rPDGF-BB (
P
<.01,
P
<.05). Clentiazem also significantly reduced the expression of AP-1 induced by rPDGF-AB (
P
<.05).

Conclusions
PDGF-mediated proliferation of VSMCs correlates with activation of PKC but not with induction of the AP-1 complexes. In addition, our results suggest that CAs block proliferation of VSMCs by inhibiting DNA synthesis, possibly via PKC.
Selective Impairment of Response to Acetylcholine After Ischemia/Reperfusion in Mice
Authors: Rosenblum William I.
Published: June 2011

Background and Purpose
We previously reported that the endothelium-dependent dilation of pial arterioles by either topical acetylcholine (ACh) or bradykinin (BK) was markedly inhibited after 10 minutes of near total ischemia after bilateral carotid occlusion. The present study tests the responses after 10 minutes of reperfusion and investigates the effect of either oxygen or oxygen radical scavengers on the results.

Methods
Mice were subjected to bilateral carotid ligation or sham ligation. Pial arteriolar diameters were monitored by an image-splitting technique at a craniotomy site. In separate studies, the responses to topically suffused ACh, BK, or sodium nitroprusside (SNP) were tested before ischemia. After 10 minutes of ischemia and 10 minutes of reperfusion, the response was assessed again. Sham-operated mice were observed in each study. Cerebral blood flow was continuously monitored with a laser-Doppler technique. Additional separate studies were conducted as follows: presence of superoxide dismutase plus catalase during ischemia and reperfusion, or increase in the inspired oxygen (arterial oxygen) and oxygen in suffusate.

Results
The response to ACh was significantly impaired after 10 minutes of reperfusion. The responses to BK and SNP were unaffected. Radical scavengers failed to influence the impaired response to ACh. Elevations of arterial and suffusate oxygen levels to over 300 mm Hg failed to prevent the impairment.

Conclusions
After 10 minutes of reperfusion, a selective impairment of the response to ACh remains. The response to another endothelium-dependent dilator, BK, recovered, and the response to endothelium-independent SNP was unaffected. Because neither radical scavengers nor oxygen altered the outcome with respect to ACh, I suggest that neither radical generation nor hypoxia accounts for the selective impairment of dilation by ACh. Rather, I hypothesize that reduced shear during ischemia diminishes the ability of the endothelium to synthesize and/or release the endothelium-derived relaxing factor for ACh. I hypothesize further that this impaired release or synthesis persists throughout the 10-minute period of reperfusion.
A Long-term Follow-up of Stroke Patients
Authors: Wilkinson Peter R. , Wolfe Charles D.A. , Warburton Fiona G. , Rudd Anthony G. , Howard Robin S. , Ross-Russell Ralph W. , Beech Roger R.
Published: June 2011

Background and Purpose
Two hundred ninety-one residents of southeast London, younger than 75 years, suffered their first stroke in 1989/1990. The objectives of this study were to determine the long-term outcome of this cohort of stroke patients in terms of impairment, disability, handicap, and quality of life and their use of services and prevention measures subsequent to their stroke.

Methods
The survivors and their identified caregivers were traced and completed a structured interview questionnaire that included the Barthel Index, modified Rankin Scale, Hospital Anxiety and Depression Scale (HAD), Mini-Mental State Examination, Frenchay Activities Index, and Caregiver Strain Index.

Results
One hundred twenty-three people (42%) were alive, of whom 106 were interviewed. The mean interval between the stroke and the long-term follow-up was 4.9 years. Thirty-one of the survivors (29%) were severely or moderately disabled, 39 (37%) were mildly disabled, and 36 (34%) were functionally independent. Of the 96 people who completed the HAD, 35 (36%) had scores suggesting that they were depressed or had borderline depression. The most likely nontherapy services to have been provided were chiropody and district nursing. Five people had received respite care. Of the 104 subjects for whom information about their home was available, 53 (51%) had had an adaptation. Seventy-five people (71%) had an aid or appliance. Sixty-five people (61%) were on aspirin, and an additional 14 (13%) were on warfarin. Fifty subjects (47%) identified a main caregiver. No one with a moderate or more severe disability was living at home without an identified caregiver.

Conclusions
The levels of both health and social service provision are likely to be inadequate for this population. The use of prevention measures is encouraging. There is a clear need for a coordinated policy to guide assessment and management across sectors.