Search PubMed⌕ Search

Biomedical subjects

James F Meschia

Publications and source records attributed to James F Meschia.

At least 19 recordsLinked to original sources
PubMed2006

High prevalence of stroke symptoms among persons without a diagnosis of stroke or transient ischemic attack in a general population: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

BACKGROUND: A substantial portion of the general population has clinically silent stroke on brain imaging. These lesions may cause symptoms. This study assessed the prevalence of stroke symptoms in a stroke- and transient ischemic attack (TIA)-free population and the association of symptoms with risk factors indexed by the Framingham Stroke Risk Score. METHODS: We performed a cross-sectional analysis from a randomly sampled national cohort enrolled from January 25, 2003, through November 30, 2005, with oversampling from the southeastern stroke belt and African American populations. The main outcome measure was stroke symptoms assessed by validated questionnaire. RESULTS: The study included 18 462 (41% African American; 51% female; mean age, 65.8 years) participants who reported no stroke or TIA. The prevalence of stroke symptoms was 5.8% for sudden painless hemibody weakness, 8.5% for sudden hemibody numbness, 4.6% for sudden painless loss of vision in one or both eyes, 3.1% for sudden hemifield visual loss, 2.7% for sudden inability to understand speech, and 3.8% for sudden inability of linguistic expression. The prevalence of 1 or more symptoms was 17.8%. Relative to the first quartile of the Framingham Stroke Risk Score, the adjusted odds ratio for 1 or more stroke symptoms increased from 1.0 (95% confidence interval [CI], 0.90-1.2) in the second quartile to 1.2 (95% CI, 1.1-1.5) and 1.5 (95% CI, 1.3-1.6) in successive quartiles. Symptoms were more prevalent among African American compared with white participants and among those with lower income, lower educational level, and fair to poor perceived health status. CONCLUSIONS: The general population without prior diagnosed stroke or TIA has a high prevalence of stroke symptoms. The relationship between symptoms and risk factors suggests that some symptomatic individuals may have had clinically undetected cerebrovascular events and may benefit from aggressive stroke prophylaxis.

Aged↗
PubMed2006

Choice of neuroimaging in perioperative acute stroke management.

At the time of this publication, the fast examination time, wide availability, lack of contraindications, and high accuracy for detecting hemorrhage make NCCT the diagnostic study of choice for initial evaluation of patients who have preoperative stroke. NCCT also has a role in excluding patients who will not benefit from IV thrombolysis, including those who have ICH and patients who have ASPECTS less than 7 or ischemic signs exceeding one third of the MCA territory. Because optimal selection of inpatients who have acute stroke mandates not just brain tissue data but also information about the aortic arch, cervical and intracranial vasculature, and cerebral hemodynamics, additional imaging with multimodal CT technology can, in one scanning session, depicts early ischemic changes, demonstrates hypoperfusion/ischemic penumbra, and locates the vascular lesion. When combined with the clinical scenario, the information provided by CT often is sufficient to help clinicians decide on the appropriate treatment, especially determining eligibility for thrombolysis. The rapidly evolving field of neuroradiology will provide a newer armamentarium in the near future. Although MRI can provide more precise information, it is more time consuming and currently should be considered the method of choice for follow-up imaging, rather than initial imaging, in patients who have perioperative stroke.

Brain↗
PubMed2006

Lessons from adult stroke trials.

Before designing epidemiologic, genetic, or treatment trials in pediatric stroke, we should learn from adult trials which preceded. Adult trialists state that there is a need for improved animal models to mimic human disease. Dose-response curves with blinded outcome measures would improve preclinical data. Functional and histologic outcome measures would improve the animal model. In regard to human Phase 2 medication trials, safety, delivery, end points, and surrogate markers are necessary. The detection of biologic activity can be defined in Phase 2B trials. For Phase 3 trials, the experiment needs to be simple with global outcome measures as end points. New statistical designs such as futility analysis may improve and streamline trials in both adults and children. Clinical trials are a long process, and care needs to be incorporated at every step. Why is there a propensity of failed studies for acute ischemic stroke in adults? The reasons include (a) the animal model fails us, (b) the Phase 2 trials are ineffective in defining dose, and (c) the Phase 3 trials are poorly done. Because clinical trials, more often than not, fail to give positive (effective treatment) results, it seems reasonable to attempt to learn from others' past experiences before initiating pediatric stroke trials.

Adult↗
PubMed2006

Ischemic stroke as a complex genetic disorder.

Ischemic stroke is a complex genetic disorder, diverse in pathophysiology and clinical presentation. This phenotypic diversity may reflect genotypic diversity. One approach to discovering genetic risk factors has been to study intermediate phenotypes as in carotid intima-media thickness and leukoaraiosis. Intermediate phenotypes can be highly heritable, assessed in stroke-affected and unaffected individuals, and analyzed as quantitative traits. Because there is not a one-to-one relationship between intermediate phenotypes and ischemic stroke, polymorphisms or haplotypes associated with an intermediate phenotype should be validated as risk factors for stroke itself. A complementary approach to gene discovery has been to fractionate the ischemic stroke phenotype into more homogeneous subphenotypes. Family history studies suggest that some subphenotypes like cardioembolic stroke may be less heritable than others.

Brain Ischemia↗
PubMed2006

Aging is neuroprotective during global ischemia but leads to increased caspase-3 and apoptotic activity in hippocampal neurons.

Previously, we found a significantly greater number of surviving CA1 neurons to global ischemia in the aged (24-month-old) F344 rats than in young (4-month-old) rats. The present study tests the hypothesis that aging retards neuronal death in the hippocampal CA1 region following cerebral ischemia. The CA1 "living cell ratio" was significantly greater in aged than in young rats at three days (62+/-8% vs. 30+/-8%) and at eight days (36+/-6% vs. 17+/-5%), but not at 14 days (15+/-12% vs. 18+/-12%) following ischemia. The number of the CA1 cells exhibiting co-localized TdT-mediated X-dUTP nick end labeling reaction and caspase-3 active peptide (C3AP) immunoreactivity was greater in aged than young animals at three and eight days following ischemia (36+/-8/mm vs. 3+/-1/mm and 36+/-14 vs. 0+/-0, p<0.05 respectively). Also, the total number of C3AP-positive cells in the CA1 region in the aged group was significantly greater than in the young group at three and eight days post-ischemia (p<0.05). Aging appears to delay caspase-3-dependent apoptotic cell death induced by global ischemia in the CA1 region of the hippocampus, consistent with an age-induced neuroprotective process.

Aging↗
PubMed2006

The Siblings With Ischemic Stroke Study (SWISS): a progress report.

There is increasing evidence that genetic factors are associated with ischemic stroke, including multiple recent reports of association with the gene PDE4D, encoding phosphodiesterase 4D, on chromosome 5q12. Genetic studies of stroke are important but can be logistically difficult to perform. This article reviews the design of the Siblings With Ischemic Stroke Study (SWISS) and discusses problems in performing a sibling-based pedigree study where proband-initiated consent is used to enroll pedigree members. Proband-initiated enrollment optimizes privacy protections for family members, but it is associated with a substantial pedigree non-completion rate such that 3 to 4 probands must be identified to obtain one completed sibling pedigree. This report updates the progress of enrollment in the SWISS protocol, discusses barriers to pedigree completion and describes innovative approaches used by the SWISS investigators to enhance enrollment.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2006

Spanish cross-cultural adaptation and validation of the National Institutes of Health Stroke Scale.

OBJECTIVES: To adapt and validate a Spanish-language version (SV) of the National Institutes of Health Stroke Scale (NIHSS) to facilitate its use in Spanish-speaking contexts. PATIENTS AND METHODS: The methods recommended by the International Quality of Life Assessment Project were followed. Two forward translations and 1 back translation of the NIHSS were developed to ensure lingual and cultural equivalence. A final revised SV-NIHSS was administered by 8 physicians to patients with stroke in 3 clinics in Buenos Aires, Argentina, from September 2003 to December 2003. RESULTS: The study included 102 patients (mean +/- SD age, 73.3+/-6.5 years; 56% women) with stroke (86% ischemic). The SV-NIHSS mean baseline score was 9.78+/-7.04. Interrater reliability was Independently evaluated for 98 patients, showing a high agreement: kappa, 0.77 to 0.99 for the 15 items; interrater correlation coefficient, 0.991 (95% confidence Interval, 0.987-0.994). Intrarater reliability was excellent: kappa, 0.86 to 1.00 for the 15 items; mean intrarater correlation coefficient, 0.994 (95% confidence interval, 0.991-0.996). Construct validity was also adequate; the SV-NIHSS had a negative correlation with baseline Glasgow Coma Scale (Spearman coefficient = -0.574, P < .001) and with Barthel index at 3 months (Spearman coefficient = -0.658, P < .001). Patients with different Rankin scores at 3 months also had significantly different baseline SV-NIHSS scores, from a mean of 4.29+/-2.21 for Rankin score of 0 to a mean of 29.40+/-3.97 for Rankin score of 6 (P < .001). CONCLUSION: This study shows that a Spanish-language version of the NIHSS developed with internationally recommended methods is reliable and valid when applied in a Spanish-speaking setting.

Aged↗
PubMed2005

Genetics of vascular cognitive impairment: the opportunity and the challenges.

BACKGROUND AND PURPOSE: This review considers the current state of knowledge of genetic factors underlying vascular cognitive impairment (VCI). SUMMARY OF REVIEW: We argue here that genes conferring susceptibility to VCI must be of 2 nonmutually exclusive classes: (1) genes that confer susceptibility to cerebrovascular disease, and (2) genes that determine brain tissue responses to cerebrovascular disease (ie, render parenchymal tissue more or less susceptible to injury or able to repair itself after injury). Although some progress has been made in identifying genes of the first class, little has been done to explore genes of the second class. Evidence for the existence of such genes is presented. We discuss the advantages and disadvantages of different forms of cerebrovascular disease for studying these genes, and different study designs that might be used. CONCLUSIONS: The most critical challenge for genetic studies of VCI is to identify quantifiable phenotypes that can be reliably and effectively determined in large samples of subjects.

Brain↗
PubMed2005

Hippocampal progenitor cells express nestin following cerebral ischemia in rats.

This study addresses whether hippocampal progenitor cells express nestin following cerebral ischemia in rats. Cell counts within the hippocampal hilus were significantly greater following severe (eight-vessel occlusion) ischemia than following intermediate (four-vessel occlusion) ischemia (1527+/-87/mm2 vs. 918+/-71/mm2). Bromedeoxyuridine-positive cell counts were significantly higher with severe ischemia than with intermediate ischemia or in sham-operated animals, respectively (368+/-45, 43+/-14 and 7+/-1/mm2). In the eight-vessel occlusion group, 47+/-8/mm2 bromedeoxyuridine-labeled cells expressed nestin, significantly higher than in the four-vessel occlusion group and sham-operated animals (1+/-1 and 1+/-0/mm2, P<0.01 vs. eight-vessel occlusion, respectively). Confocal microscopy verified that a subset of the bromedeoxyuridine-positive cells expressed nestin. In conclusion, severe ischemia elicits nestin expression in hippocampal progenitor cells in rats.

Analysis of Variance↗
PubMed2005

A survey of the SWISS researchers on the impact of sibling privacy protections on pedigree recruitment.

To understand the perceptions and attitudes about privacy safeguards in research and investigate the impact of letter-based proband-initiated contact on recruitment, we surveyed researchers in the Siblings With Ischemic Stroke Study (SWISS). All 49 actively recruiting sites provided at least 1 response, and 61% reported that potential probands were enthusiastic. Although 66% of researchers valued proband-initiated contact, only 23% said that probands viewed this strategy as important to protecting the privacy of siblings. A substantial minority of researchers (37%) said the strategy impeded enrollment, and 44% said it was overly burdensome to probands.

Attitude of Health Personnel↗
PubMed2005

Phosphodiesterase 4D and 5-lipoxygenase activating protein in ischemic stroke.

Risk for ischemic stroke is mediated by both environmental and genetic factors. Although several environmental exposures have been implicated, relatively little is known about the genetic basis of predisposition to this disease. Recent studies in Iceland identified risk polymorphisms in two putative candidate genes for ischemic stroke: phosphodiesterase 4D (PDE4D) and 5-lipoxygenase activating protein (ALOX5AP). A collection of North American sibling pairs concordant for ischemic stroke and two cohorts of prospectively ascertained North American ischemic stroke cases and control subjects were used for evaluation of PDE4D and ALOX5AP. Although no evidence supported linkage of ischemic stroke with either of the two candidate genes, single-nucleotide polymorphisms and haplotypic associations were observed between PDE4D and ischemic stroke. There was no evidence of association between variants of ALOX5AP and ischemic stroke. These data suggest that common variants in PDE4D may contribute to the genetic risk for ischemic stroke in multiple populations.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2005

Genetics of cerebrovascular disorders.

Physicians must be able to recognize stroke caused by a mendelian or mitochondrial disorder. Some genetic disorders such as sickle cell anemia and Fabry disease have proven disease-specific treatments, whereas others have no effective treatment, including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Proper diagnosis of a genetic disorder has prognostic value and prevents patient exposure to unnecessary and potentially harmful therapeutic agents and diagnostic tests. This article reviews the clinical and genetic features of some mendellan and mitochondrial disorders associated with ischemic stroke, hemorrhagic stroke, and cerebrovascular malformations.

Acidosis, Lactic↗
PubMed2005

Aging blunts ischemic-preconditioning-induced neuroprotection following transient global ischemia in rats.

The present study examines the hypothesis that aging defined by the 50% survival age compromises neuroprotection afforded by ischemic preconditioning (IPC). Sixty-four male F344 rats aged 4- and 24-months, respectively, were subjected to IPC, (3-min ischemia) or sham-surgery followed by 10-min (full) ischemia or sham-surgery 2 days later. There were 4 groups at each age: sham-surgery-sham-surgery (SS), preconditioning-sham-surgery (PS), preconditioning-ischemia (PI) and sham-surgery-ischemia (SI) groups. Assessments of histology and immunoreactivities of N-methyl-D-aspartic acid receptor 1 (NMDAr1) and caspase-3 active peptide (C3AP) in the hippocampal CA1 region were performed 8 days after full ischemia. The CA1 "living cell ratio" was greater in the aged SI group than in the young SI group (32+/-6% vs. 17+/-5%, p<0.05), whereas the degree of protection against full ischemia afforded by IPC was reduced in the aged compared with the young (53+/-17% vs. 241+/-25%, P<0.0001). The basal level of NMDAr1 immunofluorescence was significantly higher in young animals, while the numbers of C3AP-positive cells were greater in all three aged ischemic groups as compared to respective young groups (p<0.01, p=0.055 and p<0.05). A fourth method of assessing cell damage using Fluoro Jade C labeled degenerating neurons that were also intensively eosinophilic. Counts of Fluoro Jade C-positive cells were higher in the young SI group than in the aged SI group (P<0.05), suggesting that mechanisms of ischemic cell death may change with aging. In conclusion, aging alters mechanisms of ischemic cell death in CA1 neurons and ischemic tolerance mechanisms are blunted by aging.

Aging↗
PubMed2004

Clinically translated ischemic stroke genomics.

Cohort studies show that having a positive family history of stroke increases the odds of having a stroke by approximately 30%. The heritability of stroke appears to be heterogeneous across ischemic stroke subtypes, with cardioembolic stroke being least heritable. The relative influence of stroke risk attenuates with age, but genetics does not cease to be relevant in later adulthood. Recent family history and twin studies suggest that genetic factors remain relevant even beyond the seventh decade of life. One of the challenges of gene discovery in stroke relates to the complexities of phenotype. The complexities of phenotype can be addressed by focusing on individual ischemic stroke subtypes or by studying intermediate phenotypes like leukaraiosis, which has a heritability of approximately 70%. Although most stroke genetics research has focused on the identification of risk factor genes, an independent set of genes likely influences poststroke outcomes (for example, apolipoprotein E) and response to drug therapies (example, alpha-adducin and diuretic therapy).

Humans↗