Hugh Markus

..We have therefore sought to address this issue in a large, well-phenotyped community population to assess the effect of a number of polymorphisms in both MMP and TIMP genes on carotid artery intima-media thickness (IMT)...

..This technique was applied to patients with ischaemic leukoaraiosis to determine whether reduced white matter CBF in this patient group could be demonstrated...

..A central concept in treating patients with acute ischaemic stroke is the existence of an ischaemic penumbra of potentially salvageable tissue, and the evidence for its existence in humans is reviewed...

..The evidence for each of these approaches is reviewed. Organization of stroke services, and particularly the use of stroke units, have been shown to significantly improve stroke outcome and these data are presented...

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..Small studies have demonstrated that they predict the combined endpoint of stroke and transient ischemic attack (TIA), but no studies have shown that they predict the more important endpoint of stroke alone...

..They offer a surrogate marker to evaluate antiplatelet therapy, but no multicenter study has evaluated the feasibility of this approach...

..In a prospective study, we determined whether circulating markers of endothelial activation predicted progression of WMH...

..We aimed to investigate whether detection of asymptomatic embolic signals by use of transcranial doppler (TCD) could predict stroke risk in patients with asymptomatic carotid stenosis...

..A lower frequency transducer of 1 MHz or possibly 1.5 MHz with transcranial Doppler ultrasound may improve the application of embolic signal detection but may not improve the signal for routine measurement of flow velocities...

..Particularly in the former group, a study is required to determine whether revascularization reduces the risk of stroke in patients with exhausted reactivity...

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..ES detection is time-consuming, and whether similar predictive information could be obtained from simpler recording protocols is unknown...

..We explored the predictive value of a score based on these 2 measures in the prospective, observational, international multicenter Asymptomatic Carotid Emboli Study...

..Using Asymptomatic Carotid Emboli Study (ACES) prospective data, the effect of current treatment and risk factors on future stroke and transient ischemic attack risk were determined...

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..In a randomized trial (ISRCTN68019845) with blinded end point evaluation, we determined whether treatment with dipyridamole or clopidogrel, in addition to aspirin, was more effective at reducing embolization...

..We aimed to investigate the long-term risks of restenosis in patients included in CAVATAS...

..The Carotid and Vertebral Artery Transluminal Angioplasty study contained a trial comparing medical and endovascular treatment in patients not suitable for surgery...

..We therefore report the long-term results of the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS)...

..Carotid intima-media thickness (IMT) is an independent predictor of vascular events in age groups >45 years. However, there is little information about the predictive value of IMT in younger individuals...

..84; P<0.001). CONCLUSIONS: Multicenter studies using MES as outcome parameter are feasible. However, primary and secondary quality control procedures are important...

..We replicated this finding in a second large population and extended the analysis by inclusion of other inflammatory conditions (chronic infection and obesity/abnormal glucose tolerance)...

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..If atherosclerosis were important in SVD as a whole or in one particular subtype, one would expect the risk factor profile to be similar to that of cerebral large vessel disease (LVD)...

..Its use relies on its ability to predict future clinical cardiovascular end points. We performed a systematic review and meta-analysis of data to examine this association...

..We determined the association between homocysteine and stroke subtypes, especially SVD, in a well-phenotyped UK cohort of black stroke patients compared to community controls...

..Meta-analysis provides a method to combine this data and determine in a larger sample size whether the association with PDE4D can be replicated...

..Using a case control replication methodology, all members of the leukotriene synthesis pathway and their receptors were examined for genetic variants, which may act as risk factors for all ischemic stroke and stroke subtypes...

..457, controls -0.317). NAA is a marker of axonal loss/dysfunction. These findings are consistent with axonal loss/dysfunction being the principal process causing the DTI changes found in cerebral SVD and ageing...

..Determining whether the distribution of stroke subtypes differs between ethnic groups is important in understanding the mechanisms of the increased stroke incidence in black patients...

..It is unclear whether elevated serum C-reactive protein (CRP) is causal to the initiation and progression of atherosclerosis. We undertook a prospective longitudinal cohort study to address this question...

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..A large number of candidate gene association studies have attempted to identify genes implicated in stroke, but there have been few replicable and robust associations reported...

..An initial study with a small sample size suggested it provided excellent discrimination. We performed a validation study in subjects with embolic signals of known nature...

..The frequency of new lesions suggests that this approach has a potential role as a surrogate marker in therapeutic trials that warrants further investigation...

..Refinement of the algorithm is required to improve its sensitivity for AF data...

..No cerebrovascular events occurred in the GSNO group. CONCLUSIONS: S-nitrosoglutathione was highly effective in rapidly reducing the frequency of embolic signals after endovascular treatment for symptomatic high-grade carotid stenosis...

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..Homocysteine-lowering therapy may be particularly effective in this subgroup...

..Atypical phenotypes have been recognized, and the disease is probably underdiagnosed in the wider stroke population. Therefore, we determined the yield of screening for Notch3 mutations in lacunar stroke with or without leukoaraiosis...

..This study estimated ethnic-specific reference ranges in a community population to determine the prevalence of thrombophilic states in a multiethnic stroke population...

..We determined the familial aggregation of stroke risk in different stroke phenotypes and used the results to model estimated sample size requirements for case-control studies...

..Local anatomic and hemodynamic factors may also influence the initiation of the atherosclerotic process. We determined whether the angle of internal carotid artery (ICA) origin is a risk factor for early atherosclerosis...

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..In a community population (n=5400), we determined whether a parental history of myocardial infarction (MI) or stroke is associated with increased IMT and whether associations differ at specific sites in the carotid arterial tree...

..If inflammation were on the intermediate causal pathway between alcohol intake and atherosclerosis, then genetic determinants of enhanced inflammation would be expected to modify this relationship...

..01). CONCLUSIONS: Rosiglitazone reduces common carotid IMT progression in nondiabetic CAD patients, and insulin-sensitization may be one contributory mechanism...

..It may be particularly good for detecting short-duration low-energy signals, although a frequency filtering-based approach currently offers a higher sensitivity on an unselected data set...

..We determined whether genetic variants in components of the ET system are a risk factor for cerebral SVD...

..GSNO was highly effective in rapidly reducing the frequency of embolic signals in this patient group. Despite its short administration time and its short half-life, it resulted in therapeutic effects lasting 24 hours...

..B = 0.0194, 95% CI -0.004-0.042, P = 0.098). CONCLUSIONS: H. pylori and the CagA strain are not major risk factors for early arteriosclerosis as assessed by carotid artery intima-media thickness...

..The information from such studies should aid identification of those stroke patients who might be most likely to benefit from observation to imitate and therefore guide phase I clinical studies...

..This study examined the impact of inflammatory gene polymorphisms and gene-smoking interactions on common carotid artery intima-media thickness (IMT), a measure of early atherosclerosis...

..Nevertheless, the question whether serum CRP itself is an independent indicator of the atherosclerotic process remains unanswered...

..S-TDT approaches appear more practical. These estimates will aid in planning of such studies...

..Linkage-based approaches have been used less although current studies are implementing the affected-sibling-pair method. In the future genome-wide association studies are likely to become more widely used...

..Further large prospective studies are required to determine whether ES predict stroke risk in this patient group...

..Prospective data on IMT progression and incident vascular events are required to establish the true value of progression data as a surrogate measure of vascular risk...

..This implies that modulating factors influence phenotype. Smoking appears to increase the risk of stroke, while high homocysteine levels are associated with an increased risk of migraine...

..Therapies which help to stabilize the endothelium may have a role in this group of patients...

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..In patients with symptomatic sporadic small vessel disease, we determined which MRI parameters best correlated with cognitive function on cross-sectional analysis and which changed over a period of 1 year...

..TCD is unlikely to be useful for disease monitoring in patients without advanced disease...

..MR imaging lesion load correlated with some clinical features including stroke and dementia, whereas depression is more common in individuals with deep white matter changes...

..It provides evidence that DTI identifies axonal disruption in white matter tracts...

..Cardiopulmonary bypass, in particular, cerebral emboli, has been implicated. We compared neurocognitive function and cerebral emboli in patients undergoing on-pump and off-pump CABG...

..Our results also demonstrate clustering of embolic signals. Our study provides baseline data to allow studies in both asymptomatic and symptomatic carotid stenosis to be planned...