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James F Meschia

Publications and source records attributed to James F Meschia.

16 recordsLinked to original sources
PubMed2003

The Ischemic Stroke Genetics Study (ISGS) Protocol.

BACKGROUND: The molecular basis for the genetic risk of ischemic stroke is likely to be multigenic and influenced by environmental factors. Several small case-control studies have suggested associations between ischemic stroke and polymorphisms of genes that code for coagulation cascade proteins and platelet receptors. Our aim is to investigate potential associations between hemostatic gene polymorphisms and ischemic stroke, with particular emphasis on detailed characterization of the phenotype. METHODS/DESIGN: The Ischemic Stroke Genetic Study is a prospective, multicenter genetic association study in adults with recent first-ever ischemic stroke confirmed with computed tomography or magnetic resonance imaging. Patients are evaluated at academic medical centers in the United States and compared with sex- and age-matched controls. Stroke subtypes are determined by central blinded adjudication using standardized, validated mechanistic and syndromic classification systems. The panel of genes to be tested for polymorphisms includes beta-fibrinogen and platelet glycoprotein Ia, Iba, and IIb/IIIa. Immortalized cell lines are created to allow for time- and cost-efficient testing of additional candidate genes in the future. DISCUSSION: The study is designed to minimize survival bias and to allow for exploring associations between specific polymorphisms and individual subtypes of ischemic stroke. The data set will also permit the study of genetic determinants of stroke outcome. Having cell lines will permit testing of future candidate risk factor genes.

Academic Medical Centers↗
PubMed2003

Familial clustering of stroke according to proband age at onset of presenting ischemic stroke.

BACKGROUND AND PURPOSE: The magnitude of inherited risk of stroke may lessen with age, and this would have implications for optimizing genomic approaches to identifying genetic risk factors for stroke. We investigated the relationship between age and inherited risk of stroke. METHODS: Family histories of stroke were obtained in systematic interviews with 310 adult men and women with recent CT- or MR-confirmed ischemic stroke. Probability of stroke in first-degree relatives was analyzed by logistic regression, adjusting for sibship size. RESULTS: The probability of having a sibling with stroke increased as proband age at stroke presentation increased. Per decade increase in proband age, the odds ratio was 1.65 (95% confidence interval [CI], 1.20 to 2.28; P=0.002) for a concordant sibling and 1.69 (95% CI, 1.15 to 2.49; P=0.008) for >or=2 first-degree relatives with a history of stroke. CONCLUSIONS: Clustering of stroke was not greater in families with probands manifesting symptoms of stroke in earlier than later adulthood. The relationship between proband age and positive family history of stroke does not suggest an upper age-limit cutoff for genomewide linkage studies.

Adult↗
PubMed2003

New advances in identifying genetic anomalies in stroke-prone probands.

The past several years have been marked by significant progress in identifying genetic anomalies in stroke-prone probands. These advances have occurred in both highly penetrant single-gene disorders and in common stroke, which is influenced by risk/susceptibility genes. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can be challenging to diagnose because of the wide range of notch 3 mutations that can cause disease, but a new immunohistochemical technique using a skin biopsy sample appears to be highly sensitive and specific. In a landmark Icelandic study, linkage was established between stroke and a locus on chromosome 5q12 designated STRK1. Association studies continue to identify polymorphisms that predispose to stroke and to markers for cerebrovascular atherosclerosis, such as intima-media thickness. Intense interest now surrounds genes involved in inflammation, including genes that encode for the interleukin-1 receptor antagonist and paraoxonase-1. In the foreseeable future, prevention, diagnosis, and treatment will incorporate genetic data to refine and individualize management of cerebrovascular disease.

Genetic Predisposition to Disease↗
PubMed2002

The Siblings With Ischemic Stroke Study (SWISS) protocol.

BACKGROUND: Family history and twins studies suggest an inherited component to ischemic stroke risk. Candidate gene association studies have been performed but have limited capacity to identify novel risk factor genes. The Siblings With Ischemic Stroke Study (SWISS) aims to conduct a genome-wide scan in sibling pairs concordant or discordant for ischemic stroke to identify novel genetic risk factors through linkage analysis. METHODS: Screening at multiple clinical centers identifies patients (probands) with radiographically confirmed ischemic stroke and a family history of at least 1 living full sibling with stroke. After giving informed consent, without violating privacy among other family members, the proband invites siblings concordant and discordant for stroke to participate. Siblings then contact the study coordinating center. The diagnosis of ischemic stroke in potentially concordant siblings is confirmed by systematic centralized review of medical records. The stroke-free status of potentially discordant siblings is confirmed by validated structured telephone interview. Blood samples for DNA analysis are taken from concordant sibling pairs and, if applicable, from 1 discordant sibling. Epstein-Barr virus-transformed lymphoblastoid cell lines are created, and a scan of the human genome is planned. DISCUSSION: Conducting adequately powered genomics studies of stroke in humans is challenging because of the heterogeneity of the stroke phenotype and the difficulty of obtaining DNA samples from clinically well-characterized members of a cohort of stroke pedigrees. The multicentered design of this study is intended to efficiently assemble a cohort of ischemic stroke pedigrees without invoking community consent or using cold-calling of pedigree members.

Journal Article↗
PubMed2002

Paraneoplastic chorea associated with CRMP-5 neuronal antibody and lung carcinoma.

Paraneoplastic chorea is described in 16 patients: 11 with limited small-cell carcinoma, 2 with lung cancer revealed by imaging, 1 with renal cell carcinoma, and 1 with lymphoma. All had CRMP-5-IgG; 6 also had ANNA-1 (anti-Hu), including 1 without evident cancer. Chorea was the initial and most prominent symptom in 11 patients, asymmetric or unilateral in 5 patients, and part of a multifocal syndrome in 14 patients. Basal ganglia abnormalities were revealed by magnetic resonance imaging and at autopsy (as perivascular inflammation and microglial activation). Four patients improved with chemotherapy, and 2 improved with intravenous methylprednisolone.

Aged↗
PubMed2002

Addressing the heterogeneity of the ischemic stroke phenotype in human genetics research.

BACKGROUND AND PURPOSE: Many investigators have approached ischemic stroke as a complex phenotype by dividing the ischemic stroke population into distinct subtypes. The purpose of this study was to review systematically the methods used to subtype ischemic stroke in recent genetic studies. METHODS: The MEDLINE database was searched for articles pertaining to research on the genetics of human ischemic stroke published from January 2000 through January 2002. Abstracts and full-length reports were then sequentially screened to select articles pertaining to original case-control or cohort studies. RESULTS: The initial search yielded 153 publications. Of 41 relevant articles, ischemic stroke was subtyped in 25 (61%). The most common standard subtyping system was the Cerebrovascular Classification of Diseases III system (9 articles). Of the subtyping systems used, 3 had previously published interrater reliability. The subtyping system was reported to have been prespecified in 1 study. Four articles reported using central adjudication. Two articles reported that the person doing the subtyping was blinded to genotype, and 2 reported that the person doing the genotyping was blinded to the patient's subtype status. CONCLUSIONS: When investigators subtyped ischemic stroke, they typically used either nonstandard classification systems or systems of undetermined reliability. Important methodological issues, including blinding and prespecification of the classification system, were rarely reported. Advances in methodology and scientific reporting standards would foster identification of subtype-specific genetic risk factors.

Adolescent↗
PubMed2002

Contrasting the neurologic complications of cardiac transplantation in adults and children.

The objective of this study was to evaluate neurologic complications associated with cardiac transplantation and compare the neurologic complications seen in adults and children. As advances in immunology have led to longer survival times for cardiac transplant recipients (1- and 5-year survival rates have improved to 86% and 65%, respectively), a number of neurologic complications have emerged. We performed a 14-year retrospective review of all adults and children (<18 years old) who had orthotopic cardiac transplantation at either Indiana University Hospital or James Whitcomb Riley Hospital for Children. The rates of neurologic complications involving the central and peripheral nervous systems in adults and children were assessed for differences using the chi-square test and Fisher's exact test where appropriate. A total of 191 orthotopic cardiac transplants were performed from 1986 to 2000, with follow-up available for 184, including 107 adults and 77 children. Thirty-two of 107 (30%) adults experienced a total of 47 complications, with peripheral neuropathies being the most frequent complication. Eighteen of 77 (23%) children experienced a total of 22 complications, with seizures being the most frequent complication. Other complications occurring in both groups were cerebrovascular, infectious, encephalopathies, neoplasms, and "other." Neurologic complications in children and adults after orthotopic cardiac transplantation are similar in both incidence and type. However, peripheral neuropathies tend to occur more frequently in adults than in children (P = .04), and the types of complications in the immediate post-transplant period seem to differ.

Adolescent↗
PubMed2002

Thrombolytic treatment of acute ischemic stroke.

Intravenous recombinant tissue-type plasminogen activator is approved by the US Food and Drug Administration for treating acute ischemic stroke within 3 hours of onset of symptoms. Initiation of thrombolysis within 90 minutes of onset of symptoms is a treatment goal supported by current studies. Postmarketing data suggest that the risk of intracranial hemorrhage may be unacceptably high when recombinant tissue-type plasminogen activator is given to patients who would not have been eligible for enrollment in the pivotal phase 3 clinical trials. Further studies of local intra-arterial thrombolysis and improved selection of patients with advanced brain imaging are expected in the future, but the emphasis at present should be on rapid identification, evaluation, and treatment of appropriate patients with intravenous therapy.

Acute Disease↗
PubMedDate not supplied

Spouses and unrelated friends of probands as controls for stroke genetics studies.

To plan a multisite, ischemic stroke genetic study, stroke patients were surveyed about the availability and characteristics of a convenience sample of spouse/friend controls. 65% of all stroke-affected probands reported a living spouse. A more detailed survey was conducted at the University of Virginia, Charlottesville, Va., USA: 51% of stroke patients reported a living, stroke-free spouse who would be willing to serve as a control, and 49% reported having a stroke-free friend who would be willing to serve as a control. Overall, 75% of stroke patients reported at least 1 individual willing to participate as a control. Cases without an identified control were more likely to be non-white (48%) than were cases with a control (13%; p = 0.00004). Cases were older than controls (67.3 vs. 59.2 years; p = 0.000002), and a greater proportion of cases than controls were male (57 vs. 33%; p = 0.0002). Without proper attention to matching, the use of a spouse/friend convenience sample would result in imbalances in basic demographic characteristics.

Adult↗