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1.
Eur J Neurol ; 27(8): 1604-1611, 2020 08.
Article in English | MEDLINE | ID: mdl-32335972

ABSTRACT

BACKGROUND AND PURPOSE: Myeloperoxidase (MPO) is an important oxidative enzyme participating in different stages of cardiovascular disease and predicts prognosis. Little is known about its role in acute cerebrovascular events and carotid plaque vulnerability. In this study, the aim was to assess plasma MPO levels in acute stroke patients and their correlation to stroke severity and stroke outcome. METHODS: Plasma MPO levels were assessed in patients presenting with acute brain ischaemia within 36 h of symptom onset (n = 144, mean age 64.7 ± 11.6 years, 67% men) and in patients with moderate-to-severe carotid stenosis undergoing carotid artery stenting (n = 51, mean age 66.3 ± 8.4 years, 75% men). Patients presenting with acute brain ischaemia were assessed serially for stroke severity and disability. RESULTS: Plasma MPO concentrations (ng/ml) were associated with interleukin-6 (r = 0.38, P < 0.0001) and gender (median interquartile range) of 68.6 (49.8-107.0) vs. 59.7 (42.7-85.5) in women vs. men (P = 0.02). In acute brain ischaemia, MPO concentrations were associated with non-lacunar subtype (bottom, middle and top tertiles 37.5%, 71.7% and 71.7% respectively; P = 0.001), with stroke severity (baseline National Institutes of Health Stroke Scale score > 10, bottom, middle and top tertiles 6.3%, vs. 41.7% and 31.3%, respectively; P < 0.006) as well as with stroke severity at days 1-2, days 4-5 and at discharge (P < 0.05 for all), but less with disability at discharge (modified Rankin Scale score ≥ 2, 41.7% vs. 60.4% and 58.7% for the bottom, middle and top tertiles, respectively; P = 0.096). CONCLUSIONS: Amongst patients with acute brain ischaemia, plasma MPO concentrations were associated with stroke severity and non-lacunar subtype, but not with long-term functional disability.


Subject(s)
Brain Ischemia , Carotid Stenosis , Stroke , Aged , Female , Humans , Male , Middle Aged , Peroxidase , Plasma , Treatment Outcome
2.
Neuroepidemiology ; 39(1): 57-62, 2012.
Article in English | MEDLINE | ID: mdl-22777655

ABSTRACT

BACKGROUND: Epidemiological and clinical features of very elderly patients with stroke are still uncertain. Our aim was to study the patient characteristics and outcomes in the very elderly (aged ≥85 years) with a first-ever ischemic stroke in the National Acute Stroke Israeli Survey (NASIS) registry. METHODS: The NASIS registry is a nationwide prospective hospital-based study performed triennially (2004, 2007, 2010). Patients with ischemic stroke aged ≥85 years were compared with those 65-84 years old regarding their baseline characteristics, stroke severity, etiology of stroke and stroke outcomes. Logistic regression analyses were used to adjust for potential confounders. Stroke severity was determined according to the National Institute of Health Stroke Scale (NIHSS) score. RESULTS: The proportion of very elderly (≥85 years) patients among the NASIS population increased from 18.3% in 2004 to 19.9% in 2007 and 24.5% in 2010 (p for trend = 0.005). The percentage of women was higher in patients aged ≥85 years (p < 0.0001). Atrial fibrillation, congestive heart disease and prior disability were significantly more common, while diabetes, current smoking and dyslipidemia were less frequent in the very elderly. The very elderly presented with more severe strokes: 36.3% of the ≥85-year-old patients had an NIHSS score ≥11 compared with 22.0% in the younger age group (p < 0.05). CONCLUSIONS: There is an increasing proportion of very elderly subjects, mostly women, among first-ever ischemic stroke patients. Current information on age-specific aspects of stroke in the very elderly is crucial to set up successful prevention pathways and implementing well-organized stroke care for this population.


Subject(s)
Brain Ischemia/epidemiology , Registries , Stroke/epidemiology , Age Factors , Aged , Aged, 80 and over , Atrial Fibrillation/epidemiology , Cross Infection/epidemiology , Female , Heart Failure/epidemiology , Hospital Mortality , Humans , Israel/epidemiology , Male , Prospective Studies , Risk Factors , Severity of Illness Index , Sex Factors , Survival Rate
3.
Eur J Neurol ; 19(4): 643-7, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22136626

ABSTRACT

BACKGROUND AND PURPOSE: Several studies reported worse outcome for stroke patients arriving on weekends. We compared working hours to off-work hours throughout the week as there is lack of experienced staff and special services during off-hours. METHODS: A nationwide stroke survey project on acute stroke was carried out in all acute care hospitals in Israel during 2004, 2007 and 2010 (2-month each). 'On-hours' were defined as regular Israel working hours and the rest, including holidays, were defined as 'off-hours'. The modified Rankin scale (mRS) at discharge was used for the main analysis on outcome. RESULTS: A total of 4827 acute strokes patients were analyzed (2139 arrived on-hours and 2688 during off-hours). 'Off-hours' patients were 1 year younger (mean 70 vs. 71 years in 'on-hours') had lower rates of prior cardiac interventions, but had higher admission blood pressure levels and had more intracerebral hemorrhages (ICH) (11% vs. 8% in 'on-hours' patients, P < 0.001). Death during hospitalization was recorded in 9% of 'off-hours' vs. 6% of 'on-hours' patient (P = 0.004). Controlling for age, blood pressure, stroke type, pre-stroke mRS, admission NIHSS, and thrombolysis, the relative odds of poor outcome (i.e. mRS ≥ 2) amongst 'off-hours' admissions compared to on-hours was 1.09 (95% CI: 0.92-1.30). Odds ratio amongst ischaemic stroke patients was 1.08 (95% CI: 0.88-1.33). CONCLUSIONS: Off-hours stroke admissions were associated with higher short-term mortality rate, probably due to a higher rate of ICH. After controlling for the latter and other potential confounders, 'off-hours' admissions were not different from 'on-hours' with respect to poor outcome.


Subject(s)
Holidays , Hospitalization/statistics & numerical data , Patient Admission/statistics & numerical data , Stroke/epidemiology , Stroke/therapy , Aged , Aged, 80 and over , Cerebral Hemorrhage , Female , Health Surveys , Humans , Israel/epidemiology , Logistic Models , Male , Middle Aged , Outcome Assessment, Health Care , Stroke/classification , Stroke/mortality
4.
Eur J Neurol ; 19(5): 739-45, 2012 May.
Article in English | MEDLINE | ID: mdl-22181011

ABSTRACT

BACKGROUND AND PURPOSE: Coronary artery calcium is an independent predictor of all-cause mortality. We sought to examine the determinants of intracranial cerebral artery calcification (CAC) and its association with long-term outcome in a large prospective cohort of stroke patients. METHODS: Consecutive patients hospitalized because of acute stroke (ischaemic and intracerebral hemorrhage) or TIA throughout a large medical center were systematically assessed and followed up for 1 year. Intracranial CAC was assessed from baseline brain CT blinded to clinical data. Patients were categorized to no, mild, and severe CAC according to their total CAC score. Determinants of CAC were studied with logistic regression analysis. Risk of death, Barthel Index ≤ 60 or death and living in a nursing facility or death were assessed. RESULTS: Amongst 1049 patients (mean age: 70 ± 13 years, 59% males) CAC was present in 727 (69%) patients. The main determinants of CAC were increasing age (OR 1.4, 95% CI 1.3-1.6, per 5 years), diabetes (OR: 2.1, 1.4-3.0), smoking (1.4, 1.0-2.2), hypertension (1.4, 1.0-2.1), and prior coronary heart disease (1.9, 1.3-2.9). CAC was associated with mortality and poor outcome amongst patients with ischaemic stroke; however, after adjusting for age and stroke severity, no significant association was observed. In patients with intracerebral hemorrhage, outcomes were not related to CAC. CONCLUSIONS: Intracranial CAC is highly prevalent in patients with acute stroke and its main determinants are older age, diabetes, smoking, hypertension, and prior coronary heart disease. Associations between CAC and mortality or poor functional outcome in the first year after ischaemic stroke are mainly age- and stroke severity-driven.


Subject(s)
Calcinosis/diagnosis , Calcinosis/etiology , Cerebral Arteries/pathology , Cerebrovascular Disorders/complications , Aged , Aged, 80 and over , Cerebrovascular Disorders/classification , Cerebrovascular Disorders/epidemiology , Cohort Studies , Epidemiologic Factors , Female , Humans , Magnetic Resonance Imaging , Male , Risk Factors , Severity of Illness Index
5.
Cerebrovasc Dis ; 31(5): 506-10, 2011.
Article in English | MEDLINE | ID: mdl-21411992

ABSTRACT

BACKGROUND: We intended to determine ethnic differences in the characteristics, management and outcome of acute ischemic stroke between the Israeli Arab and Jewish populations. METHODS: A national survey was conducted in 2004 at all 28 hospitals in Israel. Information on demographics, transportation, risk factors, clinical presentation, stroke severity, type and subtype, management and clinical outcome was obtained. Mortality during the 36 months after hospitalization was assessed by matching with national mortality data. RESULTS: Of the 1,540 patients, 169 (11%) were Arabs and 1,371 (89%) were Jews. The mean age of Arab patients was 9 years younger than in Jewish patients (63 ± 11 vs. 72 ± 12 years). Also, Arabs were more likely to be obese (OR = 1.72; 95% CI: 1.19-2.50) and have diabetes (OR = 1.41; 95% CI: 1.01-1.96), while Jews were more likely to have dyslipidemia (OR = 1.56; 95% CI: 1.11-2.17). A greater percentage of the Arab patients arrived at the hospital independently (OR = 3.85; 95% CI: 2.56-5.56) and were less likely to arrive within 3 h of symptom onset (OR = 2.33; 95% CI: 1.39-3.85). Arabs suffered increased rates of lacunar stroke (OR = 1.67; 95% CI: 1.14-2.43) and were discharged home more often (OR = 2.40; 95% CI: 1.35-4.25). No differences in severity of stroke, management, complications, disability or mortality were found between the 2 groups. CONCLUSIONS: The unique characteristics of the Arab and Jewish populations should be considered when planning stroke-care services and culturally oriented public education programs.


Subject(s)
Brain Ischemia/epidemiology , Stroke/epidemiology , Aged , Analysis of Variance , Arabs , Brain Ischemia/complications , Diabetes Mellitus/epidemiology , Disability Evaluation , Dyslipidemias/epidemiology , Ethnicity , Female , Humans , Israel/epidemiology , Jews , Male , Middle Aged , Obesity/epidemiology , Patient Discharge/statistics & numerical data , Risk Factors , Stroke/etiology , Treatment Outcome
6.
AJNR Am J Neuroradiol ; 42(2): 247-254, 2021 01.
Article in English | MEDLINE | ID: mdl-33384294

ABSTRACT

BACKGROUND AND PURPOSE: Artificial intelligence algorithms have the potential to become an important diagnostic tool to optimize stroke workflow. Viz LVO is a medical product leveraging a convolutional neural network designed to detect large-vessel occlusions on CTA scans and notify the treatment team within minutes via a dedicated mobile application. We aimed to evaluate the detection accuracy of the Viz LVO in real clinical practice at a comprehensive stroke center. MATERIALS AND METHODS: Viz LVO was installed for this study in a comprehensive stroke center. All consecutive head and neck CTAs performed from January 2018 to March 2019 were scanned by the algorithm for detection of large-vessel occlusions. The system results were compared with the formal reports of senior neuroradiologists used as ground truth for the presence of a large-vessel occlusion. RESULTS: A total of 1167 CTAs were included in the study. Of these, 404 were stroke protocols. Seventy-five (6.4%) patients had a large-vessel occlusion as ground truth; 61 were detected by the system. Sensitivity was 0.81, negative predictive value was 0.99, and accuracy was 0.94. In the stroke protocol subgroup, 72 (17.8%) of 404 patients had a large-vessel occlusion, with 59 identified by the system, showing a sensitivity of 0.82, negative predictive value of 0.96, and accuracy of 0.89. CONCLUSIONS: Our experience evaluating Viz LVO shows that the system has the potential for early identification of patients with stroke with large-vessel occlusions, hopefully improving future management and stroke care.


Subject(s)
Cerebrovascular Disorders/diagnostic imaging , Image Interpretation, Computer-Assisted/methods , Mobile Applications , Neural Networks, Computer , Stroke/diagnostic imaging , Aged , Cerebrovascular Disorders/complications , Computed Tomography Angiography/methods , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Stroke/etiology
7.
Science ; 265(5172): 679-82, 1994 Jul 29.
Article in English | MEDLINE | ID: mdl-8036518

ABSTRACT

Several paradigms of perceptual learning suggest that practice can trigger long-term, experience-dependent changes in the adult visual system of humans. As shown here, performance of a basic visual discrimination task improved after a normal night's sleep. Selective disruption of rapid eye movement (REM) sleep resulted in no performance gain during a comparable sleep interval, although non-REM slow-wave sleep disruption did not affect improvement. On the other hand, deprivation of REM sleep had no detrimental effects on the performance of a similar, but previously learned, task. These results indicate that a process of human memory consolidation, active during sleep, is strongly dependent on REM sleep.


Subject(s)
Form Perception/physiology , Learning/physiology , Sleep, REM/physiology , Adolescent , Adult , Electrodiagnosis , Female , Humans , Male , Sleep Deprivation/physiology , Sleep Stages/physiology
8.
Eur J Neurol ; 16(11): 1217-23, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19538221

ABSTRACT

BACKGROUND AND PURPOSE: Diabetes and the metabolic syndrome are known risk factors for ischaemic stroke. Our aim was to examine whether amongst patients with pre-existing atherothrombotic disease, increased insulin resistance is associated with incident cerebrovascular events. METHODS: Patients with stable coronary heart disease included in a secondary prevention trial were followed up for a mean of 6.2 years. Coronary heart disease was documented by a history of myocardial infarction > or =6 months and <5 years before enrollment and/or stable angina pectoris with evidence of ischaemia confirmed by ancillary diagnostic testing. Main exclusion criteria were insulin treated diabetes, hepatic or renal failure, and disabling stroke. Baseline insulin levels were measured in 2938 patients from stored frozen plasma samples and increased insulin resistance assessed using the homeostatic model assessment of insulin resistance (HOMA-IR), categorized into tertiles or quartiles. RESULTS: Crude rates of incident cerebrovascular events rose from 5.0% for HOMA-IR at the bottom tertile to 5.7% at the middle tertile, and 7.0% at the top tertile (P = 0.07). HOMA-IR at the top versus bottom tertile was associated with an unadjusted hazard ratio (HR) of 1.37 (95%CI, 0.94-1.98) and a 1-unit increase in the ln HOMA-IR was associated with a HR of 1.14 (95%CI, 0.97-1.35). In further analyses adjusting for potential confounders, or categorizing baseline HOMA-IR into quartiles, or excluding diabetic patients, we did not identify an increased risk for incident cerebrovascular events conferred by the top category. CONCLUSIONS: Increased insulin resistance did not predict incident cerebrovascular events amongst patients with pre-existing atherothrombotic disease.


Subject(s)
Coronary Artery Disease/complications , Insulin Resistance/physiology , Metabolic Syndrome/complications , Stroke/etiology , Aged , Blood Pressure/physiology , Chi-Square Distribution , Coronary Artery Disease/metabolism , Female , Follow-Up Studies , Humans , Insulin/blood , Male , Metabolic Syndrome/blood , Middle Aged , Patient Selection , Risk Assessment , Risk Factors , Stroke/blood
9.
Eur J Neurol ; 16(2): 218-25, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19138336

ABSTRACT

BACKGROUND AND PURPOSE: Cerebral leukoaraiosis is frequently observed in patients with acute stroke, but its clinical consequences on functional recovery remain incompletely defined. We evaluated the clinical correlates of leukoaraiosis, and its association with stroke-outcome in a cohort of consecutively hospitalized patients. METHODS: One-thousand twenty-four consecutive patients with acute stroke or transient ischemic attack (TIA) undergoing brain CT were included in this single-center study. Patients were systematically evaluated at hospitalization and followed-up for 1 year. Mortality, functional outcome, quality of life (QoL), psychological distress, community integration, and patient perception of recovery were evaluated by leukoaraiosis severity. Adjusted ORs (95%CI) were calculated. RESULTS: Moderate/severe leukoaraiosis was diagnosed in 177 patients (17.3%) and mild leukoaraiosis in 362 patients (35.3%). After 1 year, adjusted ORs for moderate/severe leukoaraiosis compared with no leukoaraiosis were 2.0 (95%CI 1.1-4.0) for Barthel Index

Subject(s)
Brain/pathology , Ischemic Attack, Transient/complications , Leukoaraiosis/complications , Stroke/complications , Aged , Cohort Studies , Female , Humans , Ischemic Attack, Transient/pathology , Leukoaraiosis/pathology , Male , Recovery of Function , Risk Factors , Stroke/pathology , Tomography, X-Ray Computed
10.
Eur J Neurol ; 15(4): 323-8, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18312408

ABSTRACT

Inflammation plays a critical role in the pathogenesis of atherothrombosis. Our aim was to examine the association between plasma concentrations of inflammatory biomarkers and severity and outcome of acute brain ischaemia. Plasma samples were collected within 36 h of symptom onset in patients with acute brain ischaemia, and assessed by conventional ELISA kits for concentration of interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1). Patients were assessed serially for stroke severity (National Institute of Health stroke scale) and outcome during follow-up (modified Rankin Scale, mRS; and Stroke Impact Scale-16, SIS). Patients (n = 113, 65% men, mean age 64 +/- 12 years) had a mean IL-6 concentrations of 5.1 +/- 5.0 pg/ml and sICAM-1 of 377 +/- 145 ng/ml. IL-6, but not sICAM-1, concentrations were strongly associated with stroke severity (P < 0.01 at all serial assessments). Ln-transformed IL-6 levels (per 1 SD) were associated with disability (mRS > or = 2, OR = 1.7; 95% CI 1.1-3.0) and poor physical function (SIS < or = 85, OR = 1.7; 95% CI 1.0-2.8). Further adjustment for baseline stroke severity, however, eliminated these associations. Our results suggest that high plasma concentrations of the inflammatory biomarker IL-6 but not sICAM-1 are associated with stroke severity and poorer functional outcome. IL-6 does not add, however, additional prognostic information for stroke outcome beyond that conveyed by the stroke severity.


Subject(s)
Brain Ischemia/blood , Intercellular Adhesion Molecule-1/blood , Interleukin-6/blood , Acute Disease , Adult , Aged , Aged, 80 and over , Analysis of Variance , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Male , Middle Aged , Severity of Illness Index
11.
Cerebrovasc Dis ; 25(4): 355-61, 2008.
Article in English | MEDLINE | ID: mdl-18305387

ABSTRACT

PURPOSE: Platelets play a critical role in the pathogenesis of acute brain ischaemia. We studied the association between the degree of inhibition of platelet function by aspirin (ASA) and the severity and outcome of acute brain ischaemia. METHODS: Platelet responsiveness to ASA was assessed in patients with acute brain ischaemia, treated with ASA since hospital admission. The degree of ASA responsiveness was assessed by optical aggregometry and categorized into patients with good response, partial response and complete unresponsiveness to ASA (good responders, partial responders and non-responders, respectively). An additional evaluation of responsiveness to ASA was performed by Impact-R (cone and platelet analyzer). Patients underwent serial clinical assessment during hospitalization, at discharge and during follow-up. RESULTS: Among 105 patients (mean age 63 +/- 12 years; 66% men), impaired ASA responsiveness at baseline as assessed by aggregometry was associated with increased stroke severity at baseline, unfavourable clinical course, and poor functional outcome during follow-up (p < 0.05 for all). Age-adjusted odds ratios in non-responders compared to good responders were 9.8 for severe stroke on admission (95% CI 2.8-34.9), 3.1 for lack of early clinical improvement (95% CI 1.1-8.8) and 8.6 for poor functional outcome during follow-up (95% CI 2.4-30.4). Less robust trends were observed with the Impact-R. CONCLUSIONS: Impaired responsiveness to ASA in acute brain ischaemia is common and is associated with worse neurological deficits at stroke onset, early clinical deterioration and poorer functional outcome. The clinical significance of these findings requires further evaluation in larger longitudinal studies.


Subject(s)
Aspirin/therapeutic use , Brain Ischemia/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Stroke/prevention & control , Acute Disease , Adult , Aged , Aged, 80 and over , Aspirin/pharmacology , Blood Platelets/drug effects , Blood Platelets/physiology , Brain Ischemia/complications , Brain Ischemia/physiopathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Severity of Illness Index , Stroke/etiology , Stroke/physiopathology , Treatment Outcome
12.
Cardiology ; 107(4): 345-53, 2007.
Article in English | MEDLINE | ID: mdl-17283424

ABSTRACT

BACKGROUND: C-reactive protein (CRP) elevated in inflammation is associated with atherosclerotic disease. We describe the distribution of CRP and its association with coronary heart disease (CHD) risk factors in a large CHD patient group. METHODS: This analysis comprises 2,723 male and 256 female CHD patients, included in the Bezafibrate Infarction Prevention (BIP) study. High sensitive CRP levels were determined in frozen plasma samples. RESULTS: CRP distribution, was normalized upon log transformation. Levels among women were higher than in men in the entire group (4.4 vs. 3.5 mg/l) and in each age group. Co-morbidities, smoking, lower education level, and use of cardiovascular drugs, were associated with elevated CRP levels in both sexes. The correlation between CRP and body mass index (BMI), insulin and glucose was stronger among women. The explained variability in CRP level was larger in women (20%) compared to men (13%). Among women, BMI explained 10% of CRP variability, whereas the contribution of each variable among men was significantly smaller. CONCLUSIONS: Among men and women with CHD, CRP level was correlated with traditional risk factors and to a lesser degree to manifestation of CHD. BMI is the main contributor to CRP variability, explained by these factors among women.


Subject(s)
C-Reactive Protein/analysis , Coronary Disease/blood , Aged , Biomarkers/blood , Chronic Disease , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Risk Factors , Sex Factors
13.
Curr Opin Neurobiol ; 4(2): 195-9, 1994 Apr.
Article in English | MEDLINE | ID: mdl-8038576

ABSTRACT

Perceptual learning in vision has been found to be highly specific for simple stimulus attributes, implying highly specific modifications in the nervous system. The type of specificity found (location, orientation, eye) implied plasticity at very early stages of visual processing, where processing modules were believed to be hard-wired and task independent. Recent studies show, however, that learning is task dependent. Studies examining the time course of learning indicate that at least two different learning processes are involved in perceptual learning, reflecting different levels of processing. Perceptual learning appears to be governed by associative rules and to be constrained by system architecture.


Subject(s)
Learning/physiology , Visual Perception/physiology , Electrophysiology , Humans , Time Factors
14.
Neuroscience ; 320: 93-104, 2016 Apr 21.
Article in English | MEDLINE | ID: mdl-26851772

ABSTRACT

Although thrombin has an important role in both central and peripheral nerve diseases, characterization of the anatomical distribution of its proteolytic activity has been limited by available methods. This study presents the development, challenges, validation and implementation of a novel histochemical method for visualization of thrombin activity in the nervous system. The method is based on the cleavage of the substrate, Boc-Asp(OBzl)-Pro-Arg-4MßNA by thrombin to liberate free 4-methoxy-2-naphthylamine (4MßNA). In the presence of 5-nitrosalicylaldehyde, free 4MßNA is captured, yielding an insoluble yellow fluorescent precipitate which marks the site of thrombin activity. The sensitivity of the method was determined in vitro using known concentrations of thrombin while the specificity was verified using a highly specific thrombin inhibitor. Using this method we determined the spatial distribution of thrombin activity in mouse brain following transient middle cerebral artery occlusion (tMCAo) and in mouse sciatic nerve following crush injury. Fluorescence microscopy revealed well-defined thrombin activity localized to the right ischemic hemisphere in cortical areas and in the striatum compared to negligible thrombin activity contralaterally. The histochemical localization of thrombin activity following tMCAo was in good correlation with the infarct areas per triphenyltetrazolium chloride staining and to thrombin activity measured biochemically in tissue punches (85 ± 35 and 20 ± 3 mU/ml, in the cortical and striatum areas respectively, compared to 7 ± 2 and 13 ± 2 mU/ml, in the corresponding contralateral areas; mean ± SEM; p<0.05). In addition, 24 h following crush injury, focal areas of highly elevated thrombin activity were detected in teased sciatic fibers. This observation was supported by the biochemical assay and western blot technique. The histochemical method developed in this study can serve as an important tool for studying the role of thrombin in physiological and pathological conditions.


Subject(s)
Brain/enzymology , Histocytochemistry/methods , Peripheral Nerves/enzymology , Thrombin/analysis , Animals , Disease Models, Animal , Mice , Peripheral Nerve Injuries/enzymology , Sensitivity and Specificity , Stroke/enzymology
15.
AJNR Am J Neuroradiol ; 42(7): E47, 2021 07.
Article in English | MEDLINE | ID: mdl-34016585
16.
Circulation ; 104(24): 2892-7, 2001 Dec 11.
Article in English | MEDLINE | ID: mdl-11739302

ABSTRACT

BACKGROUND: Despite unclear associations between blood lipids, including fractionated cholesterol and triglycerides, and stroke, recent evidence demonstrates that lipid-modifying agents decrease the risk of stroke in patients with coronary heart disease (CHD). METHODS AND RESULTS: Patients with documented CHD who were screened for but not included in the Bezafibrate Infarction Prevention study and had no history of stroke or transient ischemic attack (TIA) (n=11 177) were followed up. At baseline, medical histories were obtained and blood lipids assessed at a central study laboratory. During a 6- to 8-year follow-up period, 941 patients were identified as having nonhemorrhagic cerebrovascular disease, of whom 487 had verified ischemic stroke (per clinical findings and brain CT) or TIA. Patients experiencing an ischemic stroke/TIA had higher mean levels of triglycerides, lower levels of HDL cholesterol, and lower percentages of cholesterol contained in the HDL cholesterol moiety (%HDL; P<0.01 for all). In a logistic regression model, the adjusted ORs for developing an ischemic stroke/TIA were 1.27 (95% CI 1.01 to 1.60) associated with triglycerides >200 mg/dL and 0.87 (95% CI 0.78 to 0.97) associated with a 5% decrease in %HDL. The increased risk associated with high triglycerides was found across subgroups of age, sex, patient characteristics, and cholesterol fractions. CONCLUSIONS: High triglycerides constitute an independent risk factor for ischemic stroke/TIA across subgroups of age, sex, patient characteristics, and cholesterol fractions, whereas high %HDL was an independent protective factor among patients with CHD. These findings support the role of blood lipids, including triglycerides, as important modifiable stroke risk factors.


Subject(s)
Bezafibrate/therapeutic use , Coronary Disease/prevention & control , Hypolipidemic Agents/therapeutic use , Ischemic Attack, Transient/blood , Lipids/blood , Age Factors , Aged , Cerebrovascular Disorders/blood , Coronary Disease/blood , Female , Follow-Up Studies , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Myocardial Ischemia/blood , Randomized Controlled Trials as Topic , Registries , Risk Factors , Triglycerides/blood
17.
Stroke ; 36(7): 1366-71, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15933253

ABSTRACT

BACKGROUND AND PURPOSE: The combination of risk factors known as the metabolic syndrome is receiving increased attention, but prospective data on the syndrome's association with ischemic cerebrovascular events are scarce. We explored the relation of metabolic syndrome versus frank diabetes with first-ever ischemic stroke or transient ischemic attack (TIA) in a large cohort of patients with atherosclerotic cardiovascular disease. METHODS: Patients with coronary heart disease, screened for a clinical trial, underwent an extensive medical evaluation and follow-up for cerebrovascular disease over 4.8 to 8.1 years. National Cholesterol Education Program Adult Treatment Panel III criteria were used to define the metabolic syndrome, with body mass index substituted for waist circumference. Patients with previously diagnosed diabetes or with a fasting plasma glucose level >125 mg/dL (> or =7.0 mmol/L) were considered diabetic. RESULTS: The study sample comprised 14,284 patients, of which 3703 (26%) fulfilled the criteria for the metabolic syndrome without diabetes and 3500 others (25%) the criteria for diabetes. Adjusting for stroke risk factors, patients with the metabolic syndrome without diabetes exhibited a 1.49-fold increased odds for ischemic stroke or TIA (95% confidence interval [CI], 1.20 to 1.84), whereas those with frank diabetes had a 2.29-fold increased odds (95% CI, 1.88 to 2.78). The relative odds for ischemic stroke or TIA, associated with presence of the metabolic syndrome per se, were 1.39 (95% CI, 1.10 to 1.77) in men but 2.10 (95% CI, 1.26 to 3.51) in women. Although all components of the metabolic syndrome were associated with increased risk for ischemic stroke or TIA, impaired fasting glucose and hypertension were the strongest predictors of risk. CONCLUSIONS: The presence of the metabolic syndrome, even without diabetes, in patients with pre-existing atherosclerotic vascular disease identifies patients at increased risk for ischemic stroke or TIA. The suggestion of more pronounced risk associated with the metabolic syndrome in women deserves further assessment in other cohorts.


Subject(s)
Atherosclerosis/pathology , Brain Ischemia/complications , Ischemic Attack, Transient/complications , Metabolic Syndrome/complications , Age Factors , Aged , Atherosclerosis/diagnosis , Blood Glucose/metabolism , Body Mass Index , Clinical Trials as Topic , Cohort Studies , Diabetes Complications/pathology , Diabetes Mellitus/pathology , Female , Humans , Male , Middle Aged , Odds Ratio , Placebos , Prospective Studies , Risk Factors , Stroke/diagnosis , Time Factors
18.
J Am Coll Cardiol ; 30(6): 1484-90, 1997 Nov 15.
Article in English | MEDLINE | ID: mdl-9362406

ABSTRACT

OBJECTIVES: This study sought to compare the incidence of early cerebrovascular events and subsequent mortality in two cohorts of consecutive patients with acute myocardial infarction (AMI), admitted to coronary care units (CCUs) in Israel, in the prethrombolytic and thrombolytic eras. BACKGROUND: During the past decade, substantial changes have occurred in the medical treatment of AMI, and important new therapies have been introduced that could all affect stroke risk and type by diverse mechanisms. Yet the overall impact of these new therapeutic modalities on the incidence of stroke complicating AMI is not clear. METHODS: We compared the incidence and mortality rates of cerebrovascular events complicating AMI within CCUs among 5,839 consecutive patients admitted in the period 1981 to 1983 versus 2,012 patients from two prospective nationwide surveys conducted in all CCUs operating in Israel in 1992 and 1994. RESULTS: The demographic and clinical characteristics of patients with AMI in both periods were comparable. Patients admitted in the period 1981 to 1983 did not receive thrombolysis and reperfusion therapy; those admitted in 1992 and 1994 received thrombolysis (45%) and coronary angioplasty or coronary artery bypass graft surgery (14%), and antiplatelet and anticoagulant treatments were more frequently used. The incidence of early cerebrovascular events was 0.74% (43 of 5,839) in 1981 to 1983 versus 0.75% (15 of 2,012) in the 1992 to 1994 cohort. Patients with an AMI who experienced a cerebrovascular event were somewhat older in both groups and had a high rate of previous cerebrovascular events, congestive heart failure and atrial and ventricular arrhythmias during the hospital period. Mortality declined by one-third between the two periods. However, the mortality rate of patients with AMI who sustained a cerebrovascular event remained high (> or =40% for 30 days, 60% for 1 year). CONCLUSIONS: The overall incidence of early cerebrovascular events complicating AMI remained similar (0.75%) in the prethrombolytic and thrombolytic eras. Mortality rates of patients with an AMI but no cerebrovascular events decreased substantially over the past decade but not in patients with AMI with a cerebrovascular event.


Subject(s)
Cerebrovascular Disorders/mortality , Myocardial Infarction/complications , Thrombolytic Therapy , Aged , Angioplasty, Balloon, Coronary , Cerebrovascular Disorders/epidemiology , Cerebrovascular Disorders/etiology , Cohort Studies , Coronary Artery Bypass , Female , Humans , Incidence , Male , Middle Aged , Myocardial Infarction/therapy , Treatment Outcome
19.
Arch Intern Med ; 158(6): 601-6, 1998 Mar 23.
Article in English | MEDLINE | ID: mdl-9521224

ABSTRACT

BACKGROUND: Patients with a history of stroke presenting with acute myocardial infarction (MI) are often excluded from thrombolytic therapy owing to fear of intracranial hemorrhage. Few data, however, are available on the risks vs the benefits of thrombolysis in patients with an acute MI and a prior cerebrovascular event (PCE). METHODS: Data were derived from 2 nationwide surveys of 2012 consecutive patients with acute MI admitted to all 25 coronary care units in Israel during 1992 and 1994. Thrombolytic therapy was given to patients with a PCE at the discretion of the treating physicians. Outcomes were compared between patients with an acute MI with and without a PCE and between patients with a PCE treated with or excluded from thrombolysis. RESULTS: Patients with a PCE (n = 115 [6%]) were older, with higher rates of atherosclerotic risk factors and in-hospital complications than their counterparts without a prior event (n = 1897). They were treated less often with thrombolysis or mechanical reperfusion. The 1-year mortality rates were higher among patients with a PCE (28% vs 19%, P<.01), but not after multivariate adjustments for clinical characteristics (adjusted hazard ratio, 1.08; 95% confidence interval, 0.75-1.55). Patients with an acute MI and a PCE who were treated with thrombolysis (n = 29 [25%]) were compared with 46 patients found ineligible for thrombolysis primarily because of their PCE. The timing of the PCE was comparable in both groups (one fifth in the preceding year), while prior transient ischemic attacks were more prevalent among patients who had undergone thrombolysis. The patients who were treated with thrombolysis (n = 29) were older, had a higher rate of anterior infarction, and, while in the hospital, received aspirin, anticoagulants, and beta-blockers more often than their counterparts (n= 46). In-hospital intracranial hemorrhage did not occur in either group. The 1-year mortality rates were 2-fold higher among patients who had not undergone thrombolysis compared with those who had (33% vs 18%; adjusted hazard ratio, 2.44; 95% confidence interval, 0.78-7.64). CONCLUSIONS: These findings, derived from 2 nationwide surveys of consecutive patients with acute MI, suggest that patients with PCEs have an adverse outcome attributed to their older age and less favorable risk profile. Thrombolytic therapy, however, based on our preliminary data, may be beneficial in selected patients with an acute MI with a nonrecent PCE.


Subject(s)
Cerebrovascular Disorders/complications , Myocardial Infarction/complications , Myocardial Infarction/drug therapy , Thrombolytic Therapy , Aged , Cerebral Hemorrhage/prevention & control , Female , Humans , Israel , Male , Middle Aged , Multivariate Analysis , Myocardial Infarction/mortality , Risk , Survival Analysis , Thrombolytic Therapy/adverse effects , Treatment Outcome
20.
Neurology ; 51(5): 1376-80, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9818863

ABSTRACT

BACKGROUND AND PURPOSE: There is an association between anticardiolipin antibodies (aCL) and ischemic stroke. There are, however, also occasional reports linking aCL with other CNS diseases (OND), particularly with multiple sclerosis (MS). Hence, we studied the specificity of aCL for ischemic stroke. METHODS: Prospective, consecutively identified patients evaluated for aCL (immunoglobulin G [IgG] and immunoglobulin M [IgM] isotypes) were divided into two groups: ischemic stroke (first ever) and OND (stroke-free subjects affected by OND). RESULTS: The ischemic stroke group (n = 300) and the OND (n = 149) differed in the following risk factors: age (64 +/- 14 versus 58 +/- 15 years; p < 0.001) and proportions of African Americans (67% versus 29%; p < 0.001); current cigarette smoker (26% versus 17%; p = 0.028); hypertensive (69% versus 34%; p < 0.001); diabetic (18% versus 7%; p = 0.001); history of angina (16% versus 8%; p = 0.015) or myocardial infarction (15% versus 3%; p < 0.001). There were higher rates of aCL positivity (26% versus 17%; p = 0.050), IgG-aCL > 10 GPL (23% versus 11%; p = 0.003) or IgG aCL > 20 GPL (12% versus 4%; p = 0.012) among the stroke group than among the OND group. No differences in IgG-aCL positivity were found between the MS group and the rest of the OND group but the MS patients had a higher rate of IgM-aCL positivity than the other OND patients. CONCLUSION: IgG-aCL positivity does not appear to be a marker for CNS disease generally but of ischemic stroke.


Subject(s)
Antibodies, Anticardiolipin/blood , Central Nervous System Diseases/immunology , Cerebrovascular Disorders/immunology , Immunoglobulin Isotypes/blood , Antibodies, Antiphospholipid/blood , Antibody Specificity , Black People , Brain Ischemia/blood , Brain Ischemia/immunology , Central Nervous System Diseases/blood , Cerebrovascular Disorders/blood , Female , Humans , Immunoenzyme Techniques , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Michigan , Middle Aged , Odds Ratio , Patient Selection , Reference Values , Risk Factors
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