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Biomedical subjects

Alison E Baird

Publications and source records attributed to Alison E Baird.

16 recordsLinked to original sources
PubMed2006

Effects of conjugated equine estrogen on stroke in the Women's Health Initiative.

BACKGROUND: The Women's Health Initiative (WHI) Estrogen Alone trial assessed the balance of benefits and risks of hormone use in healthy postmenopausal women. The trial was stopped prematurely because there was no benefit for coronary heart disease and an increased risk of stroke. This report provides a thorough analysis of the stroke finding using the final results from the completed trial database. METHODS AND RESULTS: The WHI Estrogen Alone hormone trial is a multicenter, double-blind, placebo-controlled, randomized clinical trial in 10,739 women aged 50 to 79 years who were given daily conjugated equine estrogen (CEE; 0.625 mg; n=5310) or placebo (n=5429). During an average follow-up of 7.1 years, there were 168 strokes in the CEE group and 127 in the placebo group; 80.3% of strokes were ischemic. For all stroke the intention-to-treat hazard ratio [HR] (95% CI) for CEE versus placebo was 1.37 (1.09 to 1.73). The HR (95% CI) was 1.55 (1.19 to 2.01) for ischemic stroke and 0.64 (0.35, 1.18) for hemorrhagic stroke. The HRs indicate excess risk of ischemic stroke was apparent in all categories of baseline stroke risk, including younger and more recently menopausal women and in women with prior or current use of statins or aspirin. CONCLUSIONS: CEE increases the risk of ischemic stroke in generally healthy postmenopausal women. The excess risk appeared to be present in all subgroups of women examined, including younger and more recently menopausal women. There was no convincing evidence to suggest that CEE had an effect on the risk of hemorrhagic stroke.

Aged↗
PubMed2006

Blood biologic markers of stroke: improved management, reduced cost?

Identifying blood biomarkers may be of particular value in neurologic disorders such as stroke because of the difficulty in directly studying the brain and its blood vessels. Markers of brain injury, inflammation, excitotoxicity, and oxidative damage have been evaluated for their value in stroke diagnosis, treatment, and management, but none have proved to be sensitive or specific enough for routine clinical use. However, new cellular and molecular profiling approaches using the peripheral blood offer the potential for identifying panels of genes and proteins by increasing specificity while maintaining sensitivity. Furthermore, the first biomarker for predicting stroke risk associated with atherosclerosis (lipoprotein-associated phospholipase A2) was recently approved by the United States Food and Drug Administration. The ultimate aim for stroke biomarkers is to develop rapid, easy to use, widely available, and inexpensive diagnostic tests that can be used in the clinic and in clinical trials.

Biomarkers↗
PubMed2006

Vascular biology: cellular and molecular profiling.

Our understanding of the mechanisms underlying cerebrovascular atherosclerosis has improved in recent years, but significant gaps remain. New insights into the vascular biological processes that result in ischemic stroke may come from cellular and molecular profiling studies of the peripheral blood. In recent cellular profiling studies, increased levels of a proinflammatory T-cell subset (CD4 (+)CD28 (-)) have been associated with stroke recurrence and death. Expansion of this T-cell subset may occur after ischemic stroke and be a pathogenic mechanism leading to recurrent stroke and death. Increases in certain phenotypes of endothelial cell microparticles have been found in stroke patients relative to controls, possibly indicating a state of increased vascular risk. Molecular profiling approaches include gene expression profiling and proteomic methods that permit large-scale analyses of the transcriptome and the proteome, respectively. Ultimately panels of genes and proteins may be identified that are predictive of stroke risk. Cellular and molecular profiling studies of the peripheral blood and of atherosclerotic plaques may also pave the way for the development of therapeutic agents for primary and secondary stroke prevention.

Atherosclerosis↗
PubMed2006

The blood option: transcriptional profiling in clinical trials.

Transcriptional profiling of peripheral blood shows considerable promise, with the number of clinical studies increasing rapidly over the past 2-3 years. Peripheral blood is in contact with almost every tissue of the body, is the most readily accessible source of RNA in the clinical setting, and allows for repeated measurements. Studies have already been performed across multiple clinical disciplines and before and after therapeutic intervention. However, blood transcriptional profiling is not yet ready to be applied in clinical practice. A number of methodological issues and hurdles need to be overcome, with issues of standardizing blood sample collection and processing of paramount importance. The specificity of gene expression signatures for individual disease states also needs to be established. Large-scale, well-planned and integrated approaches across multiple medical disciplines could accelerate the pace of research, by resolving these methodological issues and by determining the clinical applications of blood transcriptional profiling, particularly in relation to clinical trials.

Clinical Trials as Topic↗
PubMed2005

Actual diagnostic approach to the acute stroke patient.

Since acute stroke is now considered a potentially treatable medical emergency, a rapid and correct diagnosis must be made. The first step is to exclude hemorrhage, then to visualize any early ischemic changes, demonstrate the presence of hypoperfusion and locate the presence of a vascular underlying pathology as well as elucidate the presence of a potential penumbra (tissue at risk). Thanks to improvements and advances in both MR and CT technology, this can now be done in a number of ways. At the moment, CT is the most widely available and fast method for obtaining imaging of the brain and neck vessels of patients presenting with acute stroke. MRI can provide more precise information, although it remains slightly more time-consuming, but is, however, the method of choice for follow-up imaging. The main point is to take the one-stop-shopping approach where imaging of the vessels and brain is done from the aortic arch to the circle of Willis in one single session in order to have all the necessary information in the acute phase.

Brain Ischemia↗
PubMed2005

Using peripheral blood mononuclear cells to determine a gene expression profile of acute ischemic stroke: a pilot investigation.

BACKGROUND: Direct brain biopsy is rarely indicated during acute stroke. This study uses peripheral blood mononuclear cells (PBMCs) to determine whether a systemic gene expression profile could be demonstrated in patients with acute ischemic stroke. METHODS AND RESULTS: Using oligonucleotide microarrays, we compared the gene expression profile of an index cohort of 20 patients with confirmed ischemic stroke on neuroimaging studies with that of 20 referent subjects. Validation studies used quantitative real-time polymerase chain reaction to measure the levels of 9 upregulated genes in the index cohort, and an independent cohort of 9 patients and 10 referent subjects was prospectively studied to determine the accuracy of the Prediction Analysis for Microarrays list to classify stroke. After correction for multiple comparisons with the Bonferroni technique, 190 genes were significantly different between the stroke and referent groups. Broad classes of genes included white blood cell activation and differentiation (approximately 60%), genes associated with hypoxia and vascular repair, and genes potentially associated with an altered cerebral microenvironment. Real-time polymerase chain reaction confirmed increased mRNA expression in 9 of 9 upregulated stroke-associated genes in the index cohort. A panel of 22 genes derived from the Prediction Analysis for Microarrays algorithm in the index cohort classified stroke in the validation cohort with a sensitivity of 78% and a specificity of 80%. Control for the Framingham stroke risk score revealed only a partial dependence of the stroke gene expression profile in PBMCs on vascular risk. CONCLUSIONS: This study demonstrated an altered gene expression profile in PBMCs during acute ischemic stroke. Some genes with altered expression were consistent with an adaptive response to central nervous system ischemia.

Acute Disease↗
PubMed2004

Comparison of MRI and CT for detection of acute intracerebral hemorrhage.

CONTEXT: Noncontrast computed tomography (CT) is the standard brain imaging study for the initial evaluation of patients with acute stroke symptoms. Multimodal magnetic resonance imaging (MRI) has been proposed as an alternative to CT in the emergency stroke setting. However, the accuracy of MRI relative to CT for the detection of hyperacute intracerebral hemorrhage has not been demonstrated. OBJECTIVE: To compare the accuracy of MRI and CT for detection of acute intracerebral hemorrhage in patients presenting with acute focal stroke symptoms. DESIGN, SETTING, AND PATIENTS: A prospective, multicenter study was performed at 2 stroke centers (UCLA Medical Center and Suburban Hospital, Bethesda, Md), between October 2000 and February 2003. Patients presenting with focal stroke symptoms within 6 hours of onset underwent brain MRI followed by noncontrast CT. MAIN OUTCOME MEASURES: Acute intracerebral hemorrhage and any intracerebral hemorrhage diagnosed on gradient recalled echo (GRE) MRI and CT scans by a consensus of 4 blinded readers. RESULTS: The study was stopped early, after 200 patients were enrolled, when it became apparent at the time of an unplanned interim analysis that MRI was detecting cases of hemorrhagic transformation not detected by CT. For the diagnosis of any hemorrhage, MRI was positive in 71 patients with CT positive in 29 (P<.001). For the diagnosis of acute hemorrhage, MRI and CT were equivalent (96% concordance). Acute hemorrhage was diagnosed in 25 patients on both MRI and CT. In 4 other patients, acute hemorrhage was present on MRI but not on the corresponding CT--each of these 4 cases was interpreted as hemorrhagic transformation of an ischemic infarct. In 3 patients, regions interpreted as acute hemorrhage on CT were interpreted as chronic hemorrhage on MRI. In 1 patient, subarachnoid hemorrhage was diagnosed on CT but not on MRI. In 49 patients, chronic hemorrhage, most often microbleeds, was visualized on MRI but not on CT. CONCLUSION: MRI may be as accurate as CT for the detection of acute hemorrhage in patients presenting with acute focal stroke symptoms and is more accurate than CT for the detection of chronic intracerebral hemorrhage.

Acute Disease↗
PubMed2004

Rising statin use and effect on ischemic stroke outcome.

BACKGROUND: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have neuroprotective effects in experimental stroke models and are commonly prescribed in clinical practice. The aim of this study was to determine if patients taking statins before hospital admission for stroke had an improved clinical outcome. METHODS: This was an observational study of 436 patients admitted to the National Institutes of Health Suburban Hospital Stroke Program between July 2000 and December 2002. Self-reported risk factors for stroke were obtained on admission. Stroke severity was determined by the admission National Institutes of Health Stroke Scale score. Good outcome was defined as a Rankin score < 2 at discharge. Statistical analyses used univariate and multivariate logistic regression models. RESULTS: There were 436 patients with a final diagnosis of ischemic stroke; statin data were available for 433 of them. A total of 95/433 (22%) of patients were taking a statin when they were admitted, rising from 16% in 2000 to 26% in 2002. Fifty-one percent of patients taking statins had a good outcome compared to 38% of patients not taking statins (p = 0.03). After adjustment for confounding factors, statin pretreatment was associated with a 2.9 odds (95% CI: 1.2-6.7) of a good outcome at the time of hospital discharge. CONCLUSIONS: The proportion of patients taking statins when they are admitted with stroke is rising rapidly. Statin pretreatment was significantly associated with an improved functional outcome at discharge. This finding could support the early initiation of statin therapy after stroke.

Aged↗
PubMed2004

Asymptotic dental score and prevalent coronary heart disease.

BACKGROUND: Oral infections have been postulated to produce cytokines that may contribute to the pathogenesis of coronary heart disease (CHD). We hypothesized that by estimating the combined production of inflammatory mediators attributable to several oral pathologies, we might be able to explain CHD with better precision. METHODS AND RESULTS: A total of 256 consecutive Finnish cardiac patients from Kuopio University Hospital with angiographically confirmed CHD and 250 age-, gender-, and residence-matched noncardiac patients (controls) were recruited. All dental factors expected to generate inflammatory mediators, including pericoronitis, dental caries, dentate status, root remnants, and gingivitis, were examined, and an asymptotic dental score (ADS) was developed by logistic regression analyses with an appropriate weighting scheme according to the likelihood ratio. We validated the explanatory ability of ADS by comparing it to that of the Total Dental Index and examining whether the ADS was associated with known predictors of CHD. A model that included ADS, C-reactive protein, HDL, and fibrinogen offered an explanatory ability that equaled or exceeded that of the Framingham heart score (C statistic=0.82 versus 0.80). When ADS was removed from this model, the C-statistic decreased to 0.77, which indicates that the ADS was a significant contributor to the explanatory ability of a logistic model. CONCLUSIONS: ADS may be useful as a prescreening tool to promote proactive cardiac evaluation among individuals without overt symptoms of CHD. However, additional prospective study is needed to validate the use of an oral health score as a predictor of incident CHD.

Coronary Disease↗
PubMed2003

Magnetic resonance imaging of the ischaemic penumbra.

Acute cerebral ischaemia should no longer be considered a tragic untreatable event but a medical emergency. To be able to start therapy, imaging is needed to assess the presence of a potential penumbra, i.e. an area of the brain which is hypoperfused but not yet definitively infarcted. With the development of diffusion and perfusion MR techniques, the concept of a penumbra model has been developed in which it corresponds to the acute mismatch between diffusion and perfusion volumes. This penumbra should constitute the target for potential therapies.

Brain Ischemia↗
PubMed2003

Impact of establishing a primary stroke center at a community hospital on the use of thrombolytic therapy: the NINDS Suburban Hospital Stroke Center experience.

BACKGROUND AND PURPOSE: To increase the proportion of ischemic stroke patients treated with thrombolytic therapy, the establishment of primary stroke centers in community hospitals has been advocated. We evaluated the use of thrombolytic therapy before and after institution of a primary stroke center in a community hospital. METHODS: The availability of an on-call stroke emergency response team was the only significant additional resource required for this hospital. All eligible patients were treated with intravenous tissue plasminogen activator (tPA). The number of patients with cerebrovascular disease, number and proportion of patients treated with tPA, times to treatment, and patient outcomes were recorded during the first 2 years of the stroke center. RESULTS: During the 12 months before institution of the stroke center, 3 ischemic stroke patients (1.5%) were treated with tPA. During the 2-year period of around-the-clock coverage, 44 of 420 ischemic stroke patients (10.5%) were treated with intravenous tPA, a significant increase in tPA use (P<0.0001). CONCLUSIONS: Establishment of a primary stroke center at a community hospital resulted in a substantial increase in the proportion of patients receiving thrombolytic therapy for ischemic stroke. If this experience is generalized, the beneficial impact of primary stroke centers on stroke outcomes and costs to the healthcare system may be substantial.

Adult↗
PubMed2003

Meta-analysis of periodontal disease and risk of coronary heart disease and stroke.

OBJECTIVE: The purpose of this study was to analyze published studies and abstracts in order to provide a quantitative summary of periodontal disease as a risk factor for cardiovascular disease and to explore the possible causes for conflicting results in the literature. STUDY DESIGN: We searched all published literature on the Medline literature search engine since 1980. An additional search was performed with bibliographic citations from each article. Nine cohort studies (8 prospective and 1 retrospective), in which relative risks (RRs), CIs, and P values were reported or could be calculated were included. Four researchers independently extracted RRs, CIs, and P values from each study and evaluated the degree of confounding adjustment. The combined result was calculated with weighted average, and sources of disparity were tested with regression analyses. RESULTS: The summary RR was 1.19 (95% CI, 1.08 1.32), indicating a higher risk of future cardiovascular events in individuals with periodontal disease compared with those without. In an analysis stratified to individuals of </=65 years of age, the RR was 1.44 (95% CI, 1.20 to 1.73). When the outcome was restricted to stroke only, the RR was 2.85 (95% CI, 1.78 to 4.56). In the metaregression analysis, the effects of residual confounding caused an overestimate of the results by 12.9% and, with a proxy for periodontal disease, caused an underestimate of 29.7%. CONCLUSIONS: Periodontal disease appears to be associated with a 19% increase in risk of future cardiovascular disease. This increase in RR is more prominent (44%) in persons aged </=65 years. Although the increment of risk between subjects with or without periodontal disease in the general population is modest, at around 20% because nearly 40% of population has periodontal disease, this modest increase may have a profound public health impact.

Adult↗
PubMed2002

Significance of early CT signs in acute stroke. A CT scan-diffusion MRI study.

OBJECTIVE: To study the pathophysiology of early CT signs. BACKGROUND: Early CT signs, due to an increase in tissue water content, are commonly attributed to cytotoxic edema and development of irreversible injury. This may have important implications for thrombolysis. METHODS: In patients with acute ischemic stroke in the middle cerebral artery territory, the areas of early CT signs and diffusion weighted imaging (DWI) hypersignal were independently assessed and drawn on a standardized atlas. Then, patients were classified into three groups (early CT signs larger than, similar to or smaller than DWI hypersignal) and compared with perfusion weighted imaging (PWI). RESULTS: Of 16 patients, CT scanning was performed with a median time of 3 h after onset and early CT scan signs were recorded in 10/16 patients (62.5%). DWI signal hyperintensity was present in 15/16 (94%) patients. In 7/16 (43%) patients, the area with early CT scan signs was larger than the DWI lesion ('CT-larger group'). Only in 2/16 (12%) patients were the areas matching ('matching group'). In 7/16 (43%) the DWI lesion was larger than the early CT scan signs area ('DWI-larger group'). When compared with PWI, the areas of early CT signs were larger than DWI hypersignal and were matching with PWI abnormalities (rMTT) in 2 cases, suggesting that they may represent a reversible process. CONCLUSIONS: Early CT signs might have a potential dual fate: infarction or reversibility. Other techniques of recognizing reversible ischemic damage, such as DWI-PWI, are needed to improve acute stroke diagnosis and management.

Acute Disease↗