bluuebunny/crossref_metadata_2025 huggingface dataset:
Subtractive Cloning Identifies Tissue Inhibitor of Matrix Metalloproteinase-1 (TIMP-1) Increased Gene Expression Following Focal Stroke
Authors: Wang Xinkang , Barone Frank C. , White Raymond F. , Feuerstein Giora Z.
Published: June 2011

Background and Purpose
—Differential gene expression has been reported following the onset of focal stroke. To identify de novo expression of ischemia-induced genes, we applied subtractive cDNA library strategy to identify the genes that are selectively upregulated by focal stroke.

Methods
—Spontaneously hypertensive rats were subjected to permanent occlusion of the middle cerebral artery (MCAO). mRNAs prepared from ischemic and nonischemic cortex 2 and 12 hours after MCAO were subtracted, and a subtractive cDNA library was constructed. A cDNA that encodes for tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) was identified in the subtractive cDNA library. The temporal expression of cortical TIMP-1 mRNA was further characterized in ischemic cortex subjected to permanent or temporary (160-minute) MCAO.

Results
—A panel of genes isolated from the subtractive cDNA library was subjected to Southern analysis to confirm ischemia-induced gene expression. TIMP-1 demonstrated robust induction after ischemic injury. Time-course studies revealed that TIMP-1 mRNA was induced threefold over controls at 12 hours (
P
<.001, n=4 animals) and reached a peak level at 2 days after permanent MCAO (sevenfold increase,
P
<.001). Similar induction profile of TIMP-1 mRNA was observed in the ischemic cortex after temporary MCAO followed by reperfusion.

Conclusions
—This work demonstrated the utility of subtractive cDNA library strategy for discovery of genes differentially expressed in focal stroke. Furthermore, our data implicate TIMP-1 in ischemia-induced brain injury.
Duration of Neuroprotective Treatment for Ischemic Stroke
Authors: Dyker A. G. , Lees K. R.
Published: June 2011

Background
—The therapeutic time window for thrombolysis appears to be extremely short, probably because of the hemorrhagic complications associated with late reperfusion of ischemic brain tissue. Other neuroprotective forms of treatment continue to be developed, although their efficacy has yet to be conclusively proved in patients. The duration of treatment in recent phase 3 trials ranges from a single bolus injection to 12 weeks of oral therapy.

Summary of Review
—In this article we discuss the factors that should influence the choice of route and duration of treatment. Excitotoxic injury following stroke evolves over at least 4 hours in rodents and possibly beyond 48 hours in humans. In addition, autoregulation and local cerebral perfusion are deranged for approximately 72 hours in patients with stroke. Neuroprotection should provide cover during this critical time.

Conclusions
—Important considerations influencing drug administration should include the pharmacology of the compound (pharmacokinetics, mechanism of action, preclinical toxicity, and pharmaceutical properties), its safety and tolerability in patients, and the likelihood of continuing or recurrent cerebral ischemia, along with practical issues such as ease of administration and interactions with early rehabilitation and other therapies. Optimization of treatment will be possible only when neuroprotection is confirmed to be effective.
A Randomized Controlled Trial of Rehabilitation at Home After Stroke in Southwest Stockholm
Authors: Holmqvist L. Widén , von Koch L. , Kostulas V. , Holm M. , Widsell G. , Tegler H. , Johansson K. , Almazán J. , de Pedro-Cuesta J.
Published: June 2011

Background and Purpose
—This study describes the methodology, patient outcome, and use of hospital and rehabilitation services at 3 months of a population-based randomized controlled trial. The purpose was to evaluate rehabilitation at home after early supported discharge from the Department of Neurology, Huddinge Hospital, for moderately disabled stroke patients in southwest Stockholm.

Methods
—The patients were eligible if they were continent, independent in feeding, had mental function within normal limits, and had impaired motor function and/or aphasia 1 week after stroke. Patients were randomized either to early supported discharge with continuity of rehabilitation at home for 3 to 4 months or to routine rehabilitation service in a hospital, day care, and/or outpatient care. The home rehabilitation team consisted of two physical therapists, two occupational therapists, and one speech therapist; one of the therapists was assigned as case manager for the patient. The rehabilitation program at home emphasized a task- and context-oriented approach. The activities were chosen on the basis of the patient’s personal interests. Spouses were offered education and individual counseling. A total of 81 patients were followed up for a minimum of 3 months. Patient outcome was assessed by the Frenchay Social Activity Index, Extended Katz Index, Barthel Index, Lindmark Motor Capacity Assessment, Nine-Hole Peg Test, walking speed over 10 m, reported falls, and subjective dysfunction according to the Sickness Impact Profile. Patient use of hospital and home rehabilitation service and patient satisfaction with care were studied.

Results
—Overall there were no statistical significant differences in outcome. Multivariate logistic regression analysis suggested a systematic positive effect for the home rehabilitation group in social activity, activities of daily living, motor capacity, manual dexterity, and walking. A considerable difference in resource use during such a 3-month period was seen. A 52% reduction in hospitalization was observed: from 29 days in the routine rehabilitation group to 14 days in the home rehabilitation group. Patient satisfaction was in favor of the latter group.

Conclusions
—Early supported discharge with continuity of home rehabilitation services for the majority of moderately disabled stroke patients during the first 3-month period after acute stroke is not less beneficial than routine rehabilitation and can be a rehabilitation service of choice if follow-up at 6 and 12 months confirms the suggested effectiveness and considerable reduction in use of health care.
Effect of Chronic Nitric Oxide Deficiency on Angiotensin II–Induced Hypertrophy of Rat Basilar Artery
Authors: Moreau Pierre , Takase Hiroyuki , d’Uscio Livius V. , Lüscher Thomas F.
Published: June 2011

Background and Purpose
—Although in vitro studies suggest that nitric oxide has an inhibitory effect on cellular proliferation and migration, in vivo experiments failed to support this conclusion. The present study was designed to determine the effect of endogenous nitric oxide on angiotensin II–induced hypertrophy of small arteries in vivo.

Methods
—Angiotensin II (200 ng/kg per minute), alone or in combination with
N
ω
-nitro-
l
-arginine methyl ester (L-NAME) (60 mg/kg per day), was administered for 2 weeks in normotensive rats. Basilar arteries were harvested, and their geometry was determined in perfused and pressurized conditions.

Results
—Angiotensin II increased media thickness, media-lumen ratio, and cross-sectional area of the arteries, confirming the presence of hypertrophic remodeling. The concomitant administration of L-NAME, an inhibitor of nitric oxide synthesis, prevented vascular hypertrophy. The remodeling of the basilar artery geometry in the combined treatment was of eutrophic nature, similar to that observed with the administration of L-NAME alone.

Conclusions
—Our results suggest that endogenous nitric oxide does not inhibit angiotensin II–induced vascular hypertrophy in vivo. Nitric oxide may even be a necessary factor for hypertrophy to develop.
Cigarette Smoking and Other Risk Factors for Silent Cerebral Infarction in the General Population
Authors: Howard George , Wagenknecht Lynne E. , Cai Jianwen , Cooper Lawton , Kraut Michael A. , Toole James F.
Published: June 2011

Background and Purpose
—Silent cerebral infarctions (SCIs) have a prevalence between 10% and 40% in the transient ischemic attack population and have been associated with increased mortality and morbidity; however, little is known about the prevalence and risk factors for SCI in the general population. This report focuses on the role of cigarette smoking and other risk factors for SCI in the general population.

Methods
—MRI scans were performed on 1737 participants selected from the general population as part of the Atherosclerosis Risk in Communities Study. Smoking status and other major cerebrovascular risk factors were assessed, and associations between smoking status and SCIs were established with the use of ANCOVA.

Results
—Overall, the prevalence of SCI in this population aged 55 to 70 years was 11%. Cigarette smoking had an ordered association (
P
=0.029) with the presence of SCI, with the odds ratio (OR) of nonsmoking participants exposed to environmental tobacco smoke being 1.06 (95% confidence interval [CI], 0.64 to 1.75) times as great as for nonsmokers not exposed; the OR of past smokers was 1.16 (95% CI, 0.74 to 1.83) times greater, and the OR of current smokers was 1.88 (95% CI, 1.13 to 3.13) times greater. An increased prevalence was also noted among black, older, and hypertensive participants.

Conclusions
—This report is among the first to examine the risk factors for SCI in the general population and finds a relatively high overall prevalence (11%). There is an ordered relationship between increasing exposure to cigarette smoke and the presence of SCI that parallels the relationship between smoking and carotid atherosclerosis. The magnitude of the association with smoking is substantial compared with the effect of hypertension and other traditional cerebrovascular risk factors. The reduction in prevalence of SCI between current and past smokers and the trend that increased pack-years of smoking is related to increased prevalence of SCI are both additional arguments for smoking avoidance and cessation.
Dose Optimization of Intravenous Magnesium Sulfate After Acute Stroke
Authors: Muir Keith W. , Lees Kennedy R.
Published: June 2011

Background and Purpose
—Parenterally administered MgSO
4
is neuroprotective in standard animal models of focal cerebral ischemia and in many other paradigms of brain injury. Previous small clinical trials in stroke patients have explored the safety and tolerability of different infusion regimens. This study was undertaken to optimize the regimen for a multicenter trial.

Methods
— Within 24 hours of the onset of clinically diagnosed stroke, patients were randomized to receive placebo or one of three intravenous MgSO
4
infusions: a loading infusion of 8, 12, or 16 mmol, followed by 65 mmol over 24 hours. Cardiovascular parameters, serum magnesium concentrations, and blood glucose concentrations were determined. Outcome at 30 and 90 days was recorded.

Results
—Twenty-five patients were recruited and treated at a mean time of 20 hours after stroke. No tolerability problems were identified. No effects of magnesium on heart rate, blood pressure, or blood glucose were evident. Serum magnesium concentrations rose to target levels most rapidly in the highest loading infusion group and were maintained in all groups for at least 24 hours.

Conclusions
—MgSO
4
infusions that rapidly elevate the serum magnesium concentration to potentially therapeutic levels are well tolerated and have no major hemodynamic effects in patients with acute stroke. The 16-mmol loading infusion achieved target serum concentrations most rapidly and has been chosen for further trials.
Morbidity of Intracranial Hemorrhage in Patients With Cerebral Arteriovenous Malformation
Authors: Hartmann Andreas , Mast Henning , Mohr J. P. , Koennecke Hans-Christian , Osipov Andrei , Pile-Spellman John , Duong D. Hoang , Young William L.
Published: June 2011

Background and Purpose
—Decisions on invasive arteriovenous malformation (AVM) treatment are currently based on natural-course risk estimates of AVM bleeding and assumptions on morbidity from cerebral hemorrhage in general. However, morbidity of AVM hemorrhage has rarely been reported. We sought to assess the morbidity of intracranial hemorrhage in patients with cerebral AVMs.

Methods
—From a prospective AVM database, 119 patients were analyzed: 115 had a hemorrhage as the diagnostic event, and 27 of them suffered a second hemorrhage during follow-up; an additional 4 patients had other diagnostic symptoms but bled during follow-up. The type (parenchymal, subarachnoid, intraventricular) and location of AVM hemorrhage were determined by CT/MR brain imaging. Disability and neurological impairment were assessed with the Barthel Index, the Rankin Scale, and the National Institutes of Health Stroke Scale, with a mean follow-up time of 16.2 months.

Results
—Of the 115 incident hemorrhages, 34 (30%) were subarachnoid, 27 (23%) parenchymal, 18 (16%) intraventricular, and 36 (31%) in combined locations. In 54 patients (47%; 95% confidence interval [CI], 38% to 56%) the incident hemorrhage resulted in no neurological deficit, and an additional 43 patients (37%; 95% CI, 28% to 46%) were independent in their daily activities (Rankin 1). Fifteen patients (13%; 95% CI, 7% to 19%) were moderately disabled (Rankin 2 or 3), and 3 (3%; 95% CI, 0% to 6%) were severely disabled (Rankin ≥4). Parenchymal hemorrhages were most likely to result in a neurological deficit (52%). Type and morbidity of hemorrhage during follow-up were similar to incident events. Twenty (74%) of 27 patients with both incident and follow-up hemorrhages were normal or independent (Rankin 0 or 1). None of the patients with a hemorrhage during follow-up died during the observation period.

Conclusions
—Hemorrhage from cerebral AVMs appears to have a lower morbidity than currently assumed. This finding encourages a reevaluation of the risks and benefits of invasive AVM treatment.
Effect of the Asymptomatic Carotid Atherosclerosis Study on Carotid Endarterectomy in Florida
Authors: Huber Thomas S. , Wheeler Kevin G. , Cuddeback John K. , Dame Douglas A. , Flynn Timothy C. , Seeger James M.
Published: June 2011

Background and Purpose
—The value of carotid endarterectomy (CEA) has been defined by several recent multicenter trials. The clinical effect of these trials remains undetermined since the Asymptomatic Carotid Atherosclerosis Study (ACAS) Clinical Advisory (dated September 28, 1994).

Methods
—Patients undergoing CEA (ICD-9-CM 38.12) in nonfederal Florida hospitals were identified from the discharge database. Data were analyzed by federal fiscal year (FY, October 1 through September 30), comparing the years following the Advisory (FY95-FY96) to the preceding 3 years (FY92-FY94).

Results
—There was a 68.3% increase in the number of CEAs during FY95-FY96 (mean FY92-FY94, 7 343; mean FY95-FY96, 12 356). This exceeded increases in total hospital discharges (4.5%), surgical discharges (2.2%), and the state’s population (4.7%). The increase in CEAs spanned all patient demographic groups (gender, race, and age), although the magnitude was not consistent (range, 57.8% increase for 55 to 64 age group; 92.9% increase for >84 age group). Concomitantly, there was a significant decrease in mortality (1.2% versus 0.8%), cardiac complication rate (ICD-9-CM 997.1, 4.1% versus 3.0%) and percentage of patients discharged >7 days postoperatively (8.9% versus 4.9%). Mean length of stay declined 28% (5.8 versus 4.1 days), and mean adjusted charges declined 7% ($19 456 versus $18 055). Although the average case was less costly, the increased volume resulted in an estimated $56 million increase in annual hospital payments.

Conclusions
—The dramatic increase in the number of CEAs performed in the state of Florida after release of the ACAS Clinical Advisory suggests a causal relationship and mandates further cost-effectiveness analyses.
Cerebral Blood Flow Velocity in Acute Schizophrenic Patients
Authors: Owega Ammar , Klingelhöfer Jürgen , Sabri Osama , Kunert Hanns Jürgen , Albers Matthias , Saß Henning
Published: June 2011

Background and Purpose
—The aim of this study was to determine whether acutely psychotic first-episode schizophrenics show an increased cerebral blood flow velocity and whether this condition is reversible on psychopathological improvement.

Methods
—In the first of two examinations, transcranial Doppler ultrasonography and assessment with the Positive and Negative Syndrome Scale (PANSS) were performed on 28 acutely psychotic, neuroleptically naive, first-episode schizophrenics. In the second examination, the same patients were assessed psychometrically (PANSS) as well as with Doppler ultrasonography after psychopathological improvement.

Results
—Acutely psychotic first-episode schizophrenics showed a significant increase of the mean velocity on both sides in the middle and anterior cerebral arteries and in the right posterior cerebral artery. Blood flow showed significant correlations with productive psychotic symptoms. After psychopathological improvement there was a bilateral normalization of the mean velocity in the middle, anterior, and posterior cerebral arteries.

Conclusions
—Acutely psychotic first-episode schizophrenics show a significantly increased bilateral cerebral blood flow velocity, which normalizes on psychopathological improvement. There were significant correlations of cerebral blood flow velocity with psychopathology.
Is Visible Infarction on Computed Tomography Associated With an Adverse Prognosis in Acute Ischemic Stroke?
Authors: Wardlaw J.M. , Lewis S.C. , Dennis M.S. , Counsell C. , McDowall M.
Published: June 2011

Background and Purpose
—It is unclear whether visible infarction on a CT scan at any time after the stroke is an adverse prognostic factor once other factors such as stroke severity are taken into consideration. We examined whether visible infarction was associated with a poor outcome after stroke using univariate and multivariate analyses, including easily identifiable clinical baseline variables, and adjusting for time from stroke onset to CT.

Methods
—All inpatients and outpatients with an acute ischemic stroke attending our hospital stroke service were examined by a stroke physician and entered into a register prospectively. The CT scan was coded prospectively for the site and size of any relevant recent visible infarct. The patients were followed up at 6 months to ascertain their functional status with the use of the modified Rankin Scale. Analyses of the effect of visible infarction on the outcomes “dead or dependent” or “dead” at 6 months were performed with adjustment for time from stroke to CT, clinical stroke type (lacunar, hemispheric, or posterior circulation), and in a multiple logistic regression model to adjust for confounding baseline variables such as stroke severity.

Results
—In 993 patients in the stroke registry, visible infarction increased the risk of being dead or dependent at 6 months (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.9 to 3.3) or dead (OR, 4.5; 95% CI, 2.7 to 7.5), both on its own and after adjustment for time from stroke to CT, stroke symptoms, and other important clinical prognostic variables (OR for death or dependence in the predictive model, 1.5; 95% CI, 1.0 to 2.0; OR for death, 2.4; 95% CI, 1.4 to 4.1).

Conclusions
—Visible infarction on CT is an adverse prognostic indicator (albeit of borderline significance) even after adjustment for stroke severity and time lapse between the stroke and the CT scan.
The Need to Quantify Right-to-Left Shunt in Acute Ischemic Stroke
Authors: Serena Joaquín , Segura Tomás , Perez-Ayuso Maria Jesús , Bassaganyas Joan , Molins Albert , Dávalos Antoni
Published: June 2011

Background and Purpose
—Although right-to-left shunt (RLSh) has been reported to be significantly more frequent in young stroke patients with cryptogenic stroke, its relevance in a nonselected population of acute ischemic stroke is not well known. The aim of this study was to determine the importance of the RLSh magnitude as a risk factor for stroke in nonselected patients.

Methods
—Two hundred eight patients hospitalized consecutively with transient ischemic attack or acute cerebral infarction and 100 healthy control subjects were studied. Transcranial Doppler ultrasonography (TCD) was performed in both middle cerebral arteries (MCAs) after intravenous application of agitated saline solution. The magnitude of RLSh was quantified by counting the number of signals in 1 MCA during a Valsalva maneuver. RLSh was classified as “no shunt,” “small” (<10 signals), and “large” (>10 signals), with the latter including the “shower” (>25 signals) and “curtain” (uncountable signals) patterns. Extensive investigations, including contrast transesophageal echocardiography, were carried out on patients diagnosed as suffering from stroke of an uncertain etiology. The importance of RLSh for stroke was assessed by logistic regression analysis.

Results
—Contrast TCD detected a large RLSh in 40 (19.7%) patients and in 21 (21%) control subjects, all with cardiac RLSh characteristics. A large RLSh was present in 4.7% of atherothrombotic strokes, 10.5% of cardioembolic strokes, 15.4% of lacunar strokes, and 45.3% of cryptogenic strokes (
P
<0.001). Although the overall frequency of RLSh was not significantly different between patients and control subjects, the detection of curtain or shower patterns by contrast TCD was associated with a higher risk of stroke (odds ratio , 3.5; 95% confidence interval, 1.29 to 9.87), particularly with cryptogenic stroke (odds ratio, 12.4; 95% confidence interval, 4.08 to 38.09) after adjustment for concomitant vascular risk factors.

Conclusions
—It is essential to quantify RLSh by contrast TCD during the Valsalva maneuver given that only those with shower and curtain patterns are associated with a higher risk of ischemic stroke in a nonselected population.
Relationship Between Intima-Media Thickness in the Common Carotid Artery and Atherosclerosis in the Carotid Bifurcation
Authors: Rosfors Stefan , Hallerstam Staffan , Jensen-Urstad Kerstin , Zetterling Maria , Carlström Christian
Published: June 2011

Background and Purpose
—An increase in intima-media thickness (IMT) in the common carotid artery (CCA) is commonly used as a marker of atherosclerosis. The purpose of this study was to investigate the relationship between IMT in the CCA and atherosclerosis in the carotid bifurcation.

Methods
—182 consecutive patients (mean age, 67 years) referred for carotid duplex scanning were included. We measured IMT and classified plaques by means of a high-resolution ultrasound technique.

Results
—IMT was correlated to age, male gender, ischemic heart disease, and presence of plaques or stenoses in any of the carotid bifurcations. In men, IMT was larger on the left than on the right side. Plaques were seen in 163 carotid bifurcations, in 45 of these with >50% stenosis. On the left side but not on the right, there was a correlation between IMT in the CCA and presence of plaques or stenoses in the carotid bifurcation. Echogenic plaques were more common than echolucent, but the latter caused significantly more stenoses. No relationship was found between plaque echogenicity and IMT.

Conclusions
—IMT of the CCA is correlated to the degree of atherosclerosis in the carotid bifurcations in general and on the left side also to the presence of plaques or stenoses in the left carotid bifurcation. Our results support earlier observations suggesting faster development of carotid atherosclerosis on the left than on the right side. Echogenic plaques were more common and generally smaller than echolucent plaques, but there was no correlation between plaque echogenicity and IMT.
Tacrolimus (FK506) Attenuates Leukocyte Accumulation After Transient Retinal Ischemia
Authors: Tsujikawa Akitaka , Ogura Yuichiro , Hiroshiba Naoko , Miyamoto Kazuaki , Kiryu Junichi , Honda Yoshihito
Published: June 2011

Background and Purpose
—Tacrolimus, an immunosuppressant agent, has been shown to reduce tissue injury and leukocyte accumulation after transient ischemia. This study was designed to evaluate quantitatively the inhibitory effects of tacrolimus on leukocyte rolling and on subsequent leukocyte accumulation in vivo after transient retinal ischemia and the protective effects of tacrolimus on ischemia-induced neural damage.

Methods
—Retinal ischemia was induced for 60 minutes in anesthetized pigmented rats by temporary ligation of the optic sheath. Tacrolimus was administered at 10 minutes after ischemic induction. At 4, 12, 24, and 48 hours after reperfusion, leukocyte behavior in the retinal microcirculation was evaluated in vivo with acridine orange digital fluorography. After 7 days of reperfusion, ischemia-induced retinal damage was evaluated histologically.

Results
—Treatment with tacrolimus suppressed leukocyte rolling; the maximum number of rolling leukocytes was reduced by 60.1% at 12 hours after reperfusion (
P
<0.05). In tacrolimus-treated rats, the velocity of rolling leukocytes was significantly faster than in vehicle-treated rats (
P
<0.01). The subsequent leukocyte accumulation was reduced by 61.6% at 24 hours after reperfusion (
P
<0.01). Histological examination demonstrated the protective effect of tacrolimus on ischemia-induced retinal damage, which was more substantial in the inner retina (
P
<0.01).

Conclusions
—The present study demonstrated the inhibitory effect of tacrolimus on leukocyte rolling and on subsequent leukocyte accumulation and the therapeutic potency to neural injury after transient retinal ischemia.
Proinsulin and Insulin Concentrations in Relation to Carotid Wall Thickness
Authors: Haffner Steven M. , D’Agostino Ralph , Mykkänen Leena , Hales C. N. , Savage Peter J. , Bergman Richard N. , O’Leary Dan , Rewers Marian , Selby Joe , Tracy Russell , Saad Mohammed F.
Published: June 2011

Background and Purpose
—Insulin resistance and hyperinsulinemia have been associated with atherosclerosis. Recent attention has focused on the possible role of proinsulin because most radioimmunoassays for insulin cross-react with proinsulin. Therefore, it is not known which of the two, insulin per se or proinsulin, is more strongly related to atherosclerosis.

Methods
—We examined the relation between fasting proinsulin, fasting split proinsulin, fasting and 2-hour insulin (after oral glucose load), and intima-media wall thickness (IMT) in the common carotid artery (CCA) and internal carotid artery (ICA) in 985 nondiabetic subjects from the Insulin Resistance Atherosclerosis Study, a multiethnic study of insulin resistance and atherosclerosis.

Results
—In the overall population, a weak but significant relation between proinsulin and CCA IMT was observed (
r
=0.07,
P
=0.029). However, the relation between proinsulin and IMT was stronger in Hispanics and non-Hispanic whites than in African Americans. In non-Hispanic whites and Hispanics, significant correlations between CCA and proinsulin (
r
=0.087) and between ICA and proinsulin (
r
=0.101), split proinsulin (
r
=0.092), and fasting insulin (
r
=0.087) were observed. The significant correlations became more attenuated (and nonsignificant) after adjustment for cardiovascular risk factors, especially plasminogen activator inhibitor-1 (PAI-1).

Conclusions
—The association between proinsulin and IMT, while weak, appears to be stronger than the association between insulin and IMT. Adjustment for PAI-1 markedly attenuated the association between proinsulin and IMT, suggesting a possible mediating role for PAI-1 in this association. It is possible that proinsulin may represent a marker of atherosclerosis rather than a causal factor for atherosclerosis. Studies of the insulin resistance syndrome and atherosclerosis that use insulin as a surrogate for insulin resistance should consider the use of specific insulin assays as well as determination of proinsulin concentrations.
Ultrafast Three-Dimensional Ultrasound
Authors: Palombo Carlo , Kozakova Michaela , Morizzo Carmela , Andreuccetti Fabio , Tondini Alessandro , Palchetti Paolo , Mirra Gianluca , Parenti Giuliano , Pandian Natesa G.
Published: June 2011

Background and Purpose
—Three-dimensional (3-D) vascular ultrasound can be expected to improve qualitative evaluation of vessel pathology and to provide quantitative data on vascular morphology and function. The objective of this study was to develop an ultrafast 3-D vascular system and to validate its performance for quantitation of atherosclerosis and assessment of regional arterial distensibility.

Methods
—The quantitative analysis of focal atherosclerotic lesions was validated in vitro on 27 phantoms of fibroadipous plaques of known volume (range, 100 to 600 mm
3
). In vivo reproducibility of plaque volume measurement was tested in 33 patients who had a total of 47 predominantly fibroadipous carotid plaques. Distensibility assessment was validated indirectly through the evaluation of age-related changes in distensibility of common carotid artery in healthy and hypertensive subjects (25 men in each group).

Results
—The volume of plaque phantoms measured from the 3-D data set showed a very close correlation with the true volume (
r
=0.99;
y
=0.96
x
+12.38;
P
<0.01), with the mean difference between the 2 measurements being −3.12±15.1 mm
3
. High reproducibility was found for measurement of carotid plaque volume in vivo: the mean difference between measurements from 2 observers for the same data set was 0.60±11.2 mm
3
. Indexes of arterial distensibility decreased with age in healthy population, whereas this relationship was lost in hypertensive subjects.

Conclusions
—Ultrafast 3-D ultrasound imaging of carotid artery demonstrates good accuracy and reproducibility for atherosclerotic plaque volume measurements. The system also allows the study of age-related degenerative vascular changes.
Mechanisms Underlying Cerebrovascular Effects of Cigarette Smoking in Rats In Vivo
Authors: Iida Mami , Iida Hiroki , Dohi Shuji , Takenaka Motoyasu , Fujiwara Hisayoshi
Published: June 2011

Background and Purpose
—The effects of acute smoking on cerebral circulation are controversial. This study was designed (1) to clarify any differences between the effects of cigarette smoking and nicotine infusion and between the effects of single- and multiple-cigarette smoking on cerebral vessels and (2) to probe the mechanism(s) underlying the vascular responses.

Methods
—In pentobarbital-anesthetized, mechanically ventilated Sprague-Dawley rats, pial vessel diameters were measured with the use of a cranial window preparation. We studied the effects of (1) 60 puffs per minute of mainstream cigarette smoke from cigarettes having 2 nicotine levels (0.1 and 1 mg per cigarette), (2) administration of nicotine (0.05 mg per body IV), and (3) repeated smoking (four 1 mg nicotine–containing cigarettes at 30-minute intervals) (n=6 each).

Results
—Inhalation of smoke from a 0.1 or 1 mg nicotine–containing cigarette for 1 minute caused pial arterioles to constrict at 30 seconds (7.2% and 7.3%, respectively) and then to dilate (peak at 5 to 10 minutes; 4.6% and 17.9%, respectively). Nicotine infusion caused pial vasodilation (35.7%) without an initial vasoconstriction. Repeated smoking suppressed the pial vasodilation but not the initial vasoconstriction. The vasodilation induced by a single cigarette was greatly inhibited by pretreatment with mecamylamine or glibenclamide and attenuated by propranolol or
N
ω
-nitro-
l
-arginine methyl ester; the initial vasoconstriction was inhibited by seratrodast, a thromboxane A
2
receptor antagonist (n=6 in each case).

Conclusions
—Single-cigarette smoking had a significant biphasic effect on cerebral arteriolar tone. The vasodilation was attenuated by repeated smoking. The vasodilation is most likely an effect of nicotine, at least in part mediated via sympathetic activation, NO production, and K
+
channel activation. The vasoconstriction is partially due to thromboxane A
2
induced by cigarette smoke.
Prognostic Value of Motor Evoked Potential Obtained by Transcranial Magnetic Brain Stimulation in Motor Function Recovery in Patients With Acute Ischemic Stroke
Authors: Escudero Joaquín V. , Sancho Jerónimo , Bautista Daniel , Escudero Manuel , López-Trigo Javier
Published: June 2011

Background and Purpose
—The early prognostic application of transcranial magnetic brain stimulation (TMS) for assessing motor and functional recovery in ischemic stroke patients has yielded contradictory results. We performed a prospective study of patients with acute ischemic stroke and motor deficit to evaluate the early prognostic value of TMS in motor and functional recovery.

Methods
—Fifty patients with different degrees of hemiparesis were studied in the first week after ischemic stroke and evaluated by clinical scales (Medical Research Council Scale, Canadian Neurological Scale, Barthel Index), with clinical follow-up over 6 months. TMS (Magstim 200) was performed at the same time, recording the motor evoked potential (MEP) in the thenar eminence muscles, with facilitation by voluntary contraction.

Results
—Of the total group of 50 patients, MEP was absent in 20 and present in 30 (17 with normal and 13 with delayed central conduction time [CCT]). The patients with MEP showed better motor and functional recovery than those without. The MEP provided information on patient recovery, regardless of the initial strength and/or Barthel values. The degree of recovery was better in those patients with normal CCT than in those with delayed CCT.

Conclusions
—MEP obtained by TMS in patients with hemiparesis after acute ischemic stroke is useful as an early prognostic indicator of motor and functional recovery. This technique would allow the early identification of those patients who will have a good recovery, particularly among those with severe initial paresis.
Behavioral Testing Does Not Exacerbate Ischemic CA1 Damage in Gerbils
Authors: Colbourne Frederick , Auer Roland N. , Sutherland Garnette R.
Published: June 2011

Background and Purpose
—Previous research studying ablative lesions has suggested that functional use may exacerbate brain injury. If true, this would have considerable ramifications not only for the mechanistic understanding of neuronal injury but also for the clinical use of physiotherapy. In this report the hypothesis that behavioral use of brain tissue exacerbates ischemic hippocampal injury was tested.

Methods
—Gerbils were subjected to sham operation or 5 minutes of normothermic ischemia. To produce borderline hippocampal CA1 injury and enhance susceptibility to exacerbation, 2 of 3 ischemic groups were cooled (>48 hours) beginning at 6 hours after ischemia. Increased use of the hippocampus was produced by a battery of tests involving 3 novel small mazes, a T maze, and an open field. One hypothermic group was not tested and served as a control.

Results
—Behavioral testing failed to worsen ischemic damage since neuronal loss in the behaviorally tested and untested hypothermic groups was 12% and 8%, respectively, while that in the untreated ischemic group was 81% at a 1-month survival. Accordingly, protected CA1 cells tolerated the neuronal activity associated with behavioral testing. Concomitant with marked CA1 neuroprotection, a significant reduction in behavioral deficits with the hypothermic treatment was observed. Importantly, behavioral testing was found to transiently elevate brain temperature.

Conclusions
—CA1 neuronal survival was unaffected by behavioral testing or the associated mild fever. Hypothermia delayed for 6 hours provided sustainable CA1 neuroprotection.
Evaluation of Cerebral Vascular Disease With Radionuclide Angiography
Authors: Fischer Ronald J. , Miale August
Published: June 2011

Experience with radionuclide angiography (RA) utilizing radiosodium pertechnetate and the scintillation camera as a practical means of evaluating cerebral vascular disease (CVD) is presented. The normal RA patterns were established in more than 500 patients without clinical evidence of CVD. Detailed study of the arterial and venous perfusion patterns in cases of CVD showed that certain discrete changes can be classified. The RA patterns were evaluated in 143 patients with strokes and in 120 patients with transient ischemic attacks (TIA) and correlated with symptomatology, clinical hospital course and cerebral angiograms. Although static brain scanning in patients with strokes is reportedly positive in approximately 42%, such scans are rarely positive (3%) in patients with TIA. However, by using the RA in combination with static camera imaging, in those patients wth documented stroke, positive studies were obtained in more than 80%, a twofold increase compared to previous experience. In patients with TIA, a tenfold (33%) increase in positive studies was found related to CVD and, in addition, another 7% were positive as mass lesions. The data presented stress the importance of establishing specific criteria for analysis of RA as well as the greatly enhanced sensitivity of this combined approach in detecting CVD.
Genetics of Cerebrovascular Accidents
Authors: Alter Milton , Kluznik John
Published: June 2011

The influence of heredity factors in Cerebrovascular accidents was investigated by studying the families of 80 patients with a clinical diagnosis of CVA. The frequency of CVA in parents and siblings of these patients was compared with the frequency in the family of the patient's spouse. The frequency of recognized predisposing illnesses to CVA including hypertension, diabetes and heart disease was also studied. The patients and the spouses were excluded from the study population.

Analysis of the data obtained on 160 parents and 384 sibs of the proband and on 140 parents and 336 sibs of the spouse revealed a frequency of CVA of 10.7% and 8.6% respectively. This difference was not statistically significant. However, when the sibs and parents were analyzed separately the difference between the sibs was significant (p < 0.025), suggesting the possibility that a small added risk of CVA existed for certain close relatives of a CVA victim.

Besides an inherited tendency to CVA, other factors were considered to account for the difference in frequency of CVA. Age, family size and differential reporting of illness failed to account for the difference. However, both hypertension and heart disease occurred with greater frequency in the sibs of the patient. When patients with these predisposing illnesses were excluded and those with CVA alone were compared, it was found that relatives of the patient and the spouse had essentially the same frequency (3.1% and 3.2% respectively). Moreover, hypertension and heart disease were significantly more common in the relatives of the proband. The excess of CVA in the sibs of the proband could, therefore, have been due to an excess of predisposing illnesses such as hypertension and heart disease, and no independent inheritance of CVA was demonstrated. In the absence of certain predisposing illness, close relatives of CVA patients appeared to have no greater risk of CVA than genetically unrelated individuals.
Intracranial Pressure Gradients Associated With Experimental Cerebral Embolism
Authors: BROCK MARIO , BECK JOACHIM , MARKAKIS EVANGELOS , DIETZ HERRMANN
Published: June 2011

In a series of 20 cats unilateral cerebral oil embolism was followed by the development of clinical signs of increased intracranial pressure. Simultaneous bilateral epidural pressure measurements revealed marked pressure gradients between both cerebral hemispheres. Such local (tissue) pressure gradients possibly influence local cerebral blood flow (mainly in the diseased areas) by means of alterations in local tissue perfusion pressure.
The Treatment of Brain Ischemia With Vasopressor Drugs
Authors: WISE GARY , SUTTER ROBERT , BURKHOLDER JAMES
Published: June 2011

Vasopressor drugs were administered to 13 patients soon after the development of focal brain ischemia even though there was no significant decrease in their blood pressure. The neurological function of five patients improved following an increase of their blood pressure to levels of 150 to 170/85 to 100 mm Hg. Focal brain dysfunction recurred whenever the blood pressure was allowed to fall to the initial level during the immediate postinsult period. Significant recovery was maintained in three of these five patients; neurological function in these three did not deteriorate when the blood pressure was allowed to fall to levels of 90/60, 100/70 and 120/80, respectively, after the immediate postischemic period. The critical blood pressure level required for improvement of brain function during the ischemic episode was not lowered by simultaneous treatment with low-molecular-weight dextran, hyperosmotic agents, dexamethasone and aminophylline in case 1 or by treatment with papaverine in case 3.
Abnormal Hemispheric Blood Flow and Metabolism in Cerebrovascular Disease. I. Disordered Patterns of Hemispheric Metabolism
Authors: MEYER JOHN STIRLING , FUKUUCHI YASUO , SHIMAZU KUNIO , OHUCHI TADAO , ERICSSON ARTHUR DALE
Published: June 2011

Hemispheric blood flow (HBF) and metabolism were studied in 46 patients with various types and stages of ischemic cerebrovascular disease and were found to be abnormal in all patients, including those with transient ischemic attacks. Bilateral depression of HBF and metabolism was observed in association with acute unilateral cerebral infarction. Hemispheric respiratory quotient (HRQ) was higher in the ischemic hemisphere than in the healthy side. The degree of elevation of HRQ on the diseased side correlated well with the acuteness of infarction, increasing age of the patients, and the severity of the neurological deficit. However, the HRQ in the healthy hemisphere was lower than unity, which suggests that substances other than glucose were being metabolized. The high hemispheric glucose:oxygen ratio (HG:O) correlated well with the severity of infarction and the age of the patient. Patients with brain stem ischemia had the lowest HBF values, suggesting that central neurogenic vasomotor control had been impaired or that diaschisis was greater in those with brain stem lesions than in patients with other types of lesions. A significant uptake of β-hydroxybutyrate was observed in both the healthy and diseased hemispheres but was highest in the healthy side. Evidence for abnormal cerebral metabolic patterns, such as anaerobic glycolysis, in patients with cerebrovascular disease, and oxidation of nonglucose substances such as β-hydroxybutyrate, are discussed.
Abnormal Hemispheric Blood Flow and Metabolism in Cerebrovascular Disease. II. Therapeutic Trials With 5% CO
2
Inhalation, Hyperventilation and Intravenous Infusion of THAM and Mannitol
Authors: MEYER JOHN STIRLING , FUKUUCHI YASUO , SHIMAZU KUNIO , OHUCHI TADAO , ERICSSON ARTHUR DALE
Published: June 2011

The effects of inhalation of 5% CO
2
in air, active hyperventilation, and intravenous infusion of THAM and mannitol on hemispheric blood flow (HBF) and metabolism were investigated in the ischemic hemispheres of patients with acute and chronic cerebral ischemia and in one with brain tumor. Five percent CO
2
inhalation increased HBF and decreased hemispheric RQ (HRQ) in the ischemic hemisphere. Hyperventilation decreased HBF and increased hemispheric glucose consumption. THAM infusion had no effect on HBF and metabolism, and mannitol increased HBF but had no effect on metabolism in the ischemic hemispheres.

In the patient with brain tumor, 5% CO
2
inhalation caused an "intracerebral steal" probably as a result of increasing intracranial pressure and "squeezing" or displacing of blood from the hemisphere swollen by tumor into the normal hemisphere. Intravenous injection of mannitol increased the blood flow to the hemisphere containing the tumor by temporarily reducing intracranial pressure.
Basilar Arterial Flow Changes Elicited by Hydralazine Hydrochloride, Isoxsuprine Hydrochloride and Nylidrin Hydrochloride
Authors: Mitchell Willis K. , Himwich Williamina A.
Published: June 2011

The influence of infusion of hydralazine, isoxsuprine or nylidrin on blood flow in the basilar artery and on systemic blood pressure was investigated in anesthetized dogs. The drugs were administered individually in 1-mg and 2-mg doses and in various combinations of 1 mg each by injection just proximal to the formation of the basilar artery. Analysis of the data revealed significant increases in blood flow (P<0.05) immediately after injection and a statistically significant (P<0.05) interaction between time and drug. No statistical differences were found in comparisons of the effects of the 1-mg and 2-mg dose levels for any of the drugs. At either dosage isoxsuprine and nylidrin caused a 16% to 28% decrease in systemic blood pressure, while hydralazine effected a more moderate, approximately 5%, decrease. Basilar flow responded to 1-mg combinations of isoxsuprine/hydralazine and nylidrin/hydralazine with a consistent 25% to 30% increase. However, the flow response to nylidrin/isoxsuprine was unpredictable. The data indicate that these substances increased basilar arterial flow by inducing a transient local vasodilatation. The effects of the drug combinations on flow were in general synergistic and positive, and were similar to those after infusion of the individual drugs, except for a somewhat slower initial response and a longer duration.
Can Plasma Skimming or Inconstancy of Regional Hematocrit Introduce Serious Errors in Regional Cerebral Blood Flow Measurements or Their Interpretation?
Authors: Rosenblum William I.
Published: June 2011

Recent reports indicate that in cases of elevated plasma or blood viscosity, red cell velocity through the cerebral microcirculation is unimpaired while plasma transit is retarded. One explanation may be that plasma skimming is increased, with increased shunting of plasma into longer, less direct flow paths, while an increasing proportion of red cells take shorter paths. Such inhomogeneities of flow on a microvascular level can be directly demonstrated in cases of endothelial damage or anoxia, and may produce an altered regional hematocrit.

Measurements of regional cerebral blood flow are dependent upon regional hematocrit because this affects the tissue:blood partition coefficient (λ) of diffusible indicators. Hence changes in regional HCT may produce errors in the calculation of regional blood flow unless the value of λ. is corrected to reflect altered HCT. Moreover, no matter what kind of indicator is used, our functional interpretation of regional blood flow measurements is dependent upon our assumption that the ‘blood’ in the region maintains a constant capacity to carry nutrients like oxygen. Thus the lack of a constant relationship between plasma flow and red cell flow may produce errors either in the measurement or interpretation of regional flow measurements. These errors will increase in importance as blood flow is measured in smaller and smaller volumes of brain.
The Course of Experimental Cerebral Infarction--The Development of Increased Intracranial Pressure
Authors: Halsey James H. , Capra Norman F.
Published: June 2011

In cats being subjected to surgical occlusion of the middle cerebral artery, regional oxygen availability (O
2
a) was monitored continuously from four open-tip platinum electrodes in the ischemic hemisphere and one in the control hemisphere. Extradural pressure over the convexity of the ischemic hemisphere was measured hourly. The animals were killed 24 hours after occlusion. Ten animals developing substantial increases in extradural pressure as a consequence of cerebral infarction were compared with ten which did not. The two groups did not differ in severity of the initial ischemic insult resulting from the arterial ligation, in blood pressure following occlusion, or in hematocrit, P

CO
CO2

, or oxygen saturation.

The most important difference between the two groups was in the course of regional O
2
a in the ischemic hemispheres following occlusion. In the animals which ultimately developed increased intracranial pressure the recovery of regional O
2
a was slower and less complete. After the ninth hour postocclusion O
2
a declined progressively, clearly related to rising intracranial pressure. In the animals which developed increased extradural pressure, it rose progressively to a mean of 40 mm Hg by 24 hours postocclusion. The intracranial pressure changes during the first few hours seemed insufficient to account for the early failure of recovery of regional O
2
a, unless they are viewed as averages which obscure important regional intracerebral pressure changes.