Biomedical subjects

Robert D Brown

Publications and source records attributed to Robert D Brown.

At least 19 recordsLinked to original sources

PubMed2006

Incidence and outcome of cervical artery dissection: a population-based study.

BACKGROUND: Incidence rates for internal carotid artery dissection (ICAD) have been reported to be 2.6 to 2.9 per 100,000, but reliable epidemiologic data for vertebral artery dissection (VAD) are not available. OBJECTIVE: To determine the incidence rate of cervical artery dissection (CAD) in a defined population. METHODS: With IRB approval, we used the medical record linkage system of the Rochester Epidemiology Project to identify all patients diagnosed with spontaneous ICAD and VAD for the period of 1987-2003 in Olmsted County, MN. RESULTS: Of 48 patients with CAD, there were 32 patients with ICAD and 18 patients with VAD. In Olmsted County, the average annual incidence rate for ICAD was 1.72 per 100,000 population (95% CI, 1.13 to 2.32) and for VAD 0.97 per 100,000 population (95% CI, 0.52 to 1.4). The average annual incidence rate for CAD was 2.6 per 100,000 population (95% CI, 1.86 to 3.33). The most frequently encountered symptoms in CAD were head or neck pain (80%), cerebral ischemia (TIA or infarct) (56%), and Horner syndrome (25%). Good outcome (defined as modified Rankin score of 0 to 2) was seen in 92% of patients. No recurrence of dissection was observed during a mean 7.8 years of follow-up. CONCLUSIONS: Internal carotid artery dissection was detected approximately twice as frequently as vertebral artery dissection in the overall study, but in the latter half of the study period, vertebral artery and internal carotid artery dissection incidence rates were equivalent. The majority of cervical artery dissection patients in the community have excellent outcome, and contrary to many tertiary referral series, re-dissection is rare.

Adult↗

PubMed2006

Use of the Modified Rankin Scale to assess outcome after arteriovenous malformation radiosurgery.

OBJECTIVE: To present the results of arteriovenous malformation (AVM) radiosurgery using the Modified Rankin Scale (MRS) as the primary outcome measure and to analyze whether previous AVM rupture or other factors have an effect on outcomes after AVM radiosurgery. METHODS: We reviewed outcomes after AVM radiosurgery for 243 patients from 1990 and 2001. The mean follow-up after radiosurgery was 65 months. RESULTS: Forty-one patients (17%) sustained a decline in MRS (median -2) after AVM radiosurgery. We noted a decline in MRS in 4% of patients 1 year after radiosurgery, 8% of patients at 3 years after radiosurgery, and 15% of patients at 7 years after radiosurgery. The radiosurgery-based AVM score correlated with a decline in MRS after AVM radiosurgery in multivariate testing (odds ratio 2.1; 95% CI 1.2 to 3.6; p < 0.01). CONCLUSIONS: Previous AVM rupture did not influence neurologic deterioration after AVM radiosurgery. The radiosurgery-based AVM score predicted the chance of a worse MRS after radiosurgery.

Activities of Daily Living↗

PubMed2006

Cheminformatics analysis and learning in a data pipelining environment.

Workflow technology is being increasingly applied in discovery information to organize and analyze data. SciTegic's Pipeline Pilot is a chemically intelligent implementation of a workflow technology known as data pipelining. It allows scientists to construct and execute workflows using components that encapsulate many cheminformatics based algorithms. In this paper we review SciTegic's methodology for molecular fingerprints, molecular similarity, molecular clustering, maximal common subgraph search and Bayesian learning. Case studies are described showing the application of these methods to the analysis of discovery data such as chemical series and high throughput screening results. The paper demonstrates that the methods are well suited to a wide variety of tasks such as building and applying predictive models of screening data, identifying molecules for lead optimization and the organization of molecules into families with structural commonality.

Anti-Infective Agents↗

PubMed2006

National Stroke Association guidelines for the management of transient ischemic attacks.

OBJECTIVE: Transient ischemic attacks are common and important harbingers of subsequent stroke. Management varies widely, and most published guidelines have not been updated in several years. We sought to create comprehensive, unbiased, evidence-based guidelines for the management of patients with transient ischemic attacks. METHODS: Fifteen expert panelists were selected based on objective criteria, using publication metrics that predicted nomination by practitioners in the field. Prior published guidelines were identified through systematic review, and recommendations derived from them were rated independently for quality by the experts. Highest quality recommendations were selected and subsequently edited by the panelists using a modified Delphi approach with multiple iterations of questionnaires to reach consensus on new changes. Experts were provided systematic reviews of recent clinical studies and were asked to justify wording changes based on new evidence and to rate the final recommendations based on level of evidence and quality. No expert was allowed to contribute to recommendations on a topic for which there could be any perception of a conflict of interest. RESULTS: Of 257 guidelines documents identified by systematic review, 13 documents containing 137 recommendations met all entry criteria. Six iterations of questionnaires were required to reach consensus on wording of 53 final recommendations. Final recommendations covered initial management, evaluation, medical treatment, surgical treatment, and risk factor management. INTERPRETATION: The final recommendations on the care of patients with transient ischemic attacks emphasize the importance of urgent evaluation and treatment. The novel approach used to develop these guidelines is feasible, allows for rapid updating, and may reduce bias.

Health Planning Guidelines↗

PubMed2006

Ischemic stroke after heart failure: a community-based study.

BACKGROUND: Although studies have examined the incidence of stroke in heart failure (HF), their findings are inconsistent and difficult to interpret because of heterogeneity in study design and population. Although HF remains a highly fatal disease, the excess mortality imparted from stroke is unknown. METHODS: A random sample of cases of HF from 1979 to 1999 was identified and validated according to Framingham criteria. Strokes were identified by screening medical diagnoses and subsequent physician validation. Stroke risk in HF was compared with the risk in the general population with standardized morbidity ratios. Associations between selected characteristics and stroke were examined using proportional hazards regression. RESULTS: The study cohort included 630 persons with incident HF. During a median of 4.3 years of follow-up, 102 (16%) experienced an ischemic stroke. Heart failure was associated with a 17.4-fold increased risk for stroke compared with the general population in the first 30 days after HF diagnosis and remained elevated during 5 years of follow-up. Older persons with prior stroke or diabetes were more likely to experience stroke after HF diagnosis. Persons with stroke after HF were 2.31 times more likely to die compared with persons without stroke. CONCLUSIONS: In the community, persons with HF have a large increase in the risk for ischemic stroke compared with the general population. Stroke results in a >2-fold increase in mortality. Thus, prevention of stroke has the potential to improve survival among patients with HF, particularly among the elderly and those with diabetes or prior stroke.

Age Factors↗

PubMed2006

The incidence of stroke after myocardial infarction: a meta-analysis.

PURPOSE: While the risk of stroke after myocardial infarction (MI) is increased compared with the risk among those without MI, the magnitude of this risk remains unclear. Although numerous clinical trials have reported the incidence of stroke following MI, these are among selected populations. We reviewed cohort studies reporting the incidence of stroke after MI to better define the risk of ischemic stroke in an unselected population. METHODS: A computerized literature search (MEDLINE and PubMed) and manual review of reference lists of identified articles were conducted. Population-based studies published from 1978-2004 with at least 100 subjects that reported number or percent of ischemic strokes experienced by MI survivors were identified. Data were extracted using standardized forms, and study quality was assessed by 2 independent reviewers. Ischemic stroke rates were reported as number of events per 1000 MI with 95% confidence intervals (CI) calculated by Poisson distribution. A combined stroke rate was calculated for in-hospital, 30 days, and 1-year post-MI using weights of 1/variance. A random-effects model also was created to estimate in-hospital stroke rate. Variability in study designs and outcome definitions limit synthesis of available data. RESULTS: During hospitalization for the index MI, 11.1 ischemic strokes occurred per 1000 MI compared with 12.2 at 30 days and 21.4 at 1 year. Using a random-effects model, 14.5 strokes occurred per 1000 MI. Positive predictors of stroke after MI included: advanced age, diabetes, hypertension, history of prior stroke, anterior location of index MI, prior MI, atrial fibrillation, heart failure, and nonwhite race. CONCLUSIONS: The public health implications of stroke among MI survivors, as well as the large number of MI survivors, underscore the need to be aware of this devastating complication. Further research is needed to determine the optimal stroke prevention strategies for MI survivors.

Confidence Intervals↗

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

Tako-tsubo cardiomyopathy in aneurysmal subarachnoid hemorrhage: an underappreciated ventricular dysfunction.

OBJECT: Neurogenic stunned myocardium in aneurysmal subarachnoid hemorrhage (SAH) is associated with a wide spectrum of reversible left ventricular wall motion abnormalities and includes a subset of patients with a pattern of apical akinesia and concomitant sparing of basal segments called "tako-tsubo cardiomyopathy". METHODS: After obtaining institutional review board approval, the authors retrospectively identified among all patients admitted to the Mayo Clinic's Neurological Intensive Care Unit between January 1990 and January 2005 those with aneurysmal SAH who had met the echocardiographic criteria for tako-tsubo cardiomyopathy. Among 24 patients with SAH-induced reversible cardiac dysfunction, the authors identified eight with SAH-induced tako-tsubo cardiomyopathy. All eight patients were women with a mean age of 55.5 years (range 38.6-71.1). Seven patients presented with a poor-grade SAH, reflected by a Hunt and Hess grade of III or IV. Four patients underwent aneurysm clip application, and four underwent endovascular coil occlusion. The initial mean ejection fraction (EF) was 38% (range 25-55%), and the mean EF at recovery was 55% (range 40-68%). Cerebral vasospasm developed in six patients, but cerebral infarction developed in only three patients. CONCLUSIONS: The authors describe the largest cohort with aneurysmal SAH-induced tako-tsubo cardiomyopathy. In the SAH population, tako-tsubo cardiomyopathy predominates in postmenopausal women and is often associated with pulmonary edema, prolonged intubation, and cerebral vasospasm. Additional studies are warranted to understand the complex mechanism involved in tako-tsubo cardiomyopathy and its intriguing relationship to neurogenic stunned myocardium.

Adult↗

PubMed2005

A community-based study of stroke incidence after myocardial infarction.

BACKGROUND: The rate of stroke after myocardial infarction (MI) remains unclear. OBJECTIVES: To examine the rate of stroke after incident MI; compare it with that observed in the population of Rochester, Minnesota; determine how the rate of stroke after MI has changed over time; and examine the impact of stroke on survival after incident MI. DESIGN: Community-based cohort. SETTING: Olmsted County, Minnesota. PARTICIPANTS: Persons with incident (first-ever) MI between 1979 and 1998. MEASUREMENTS: Ischemic or hemorrhagic stroke in hospitalized and nonhospitalized patients that was identified by screening of the medical record for stroke diagnostic codes and subsequent stroke confirmation by physician review of the recorded event. Medical record review was used to ascertain baseline characteristics and death. RESULTS: A total of 2160 persons with incident MI were hospitalized between 1979 and 1998 and followed for a median of 5.6 years (range, 0 to 22.2 years). The rate of stroke was 22.6 per 1000 person-months (95% CI, 16.3 to 30.6 per 1000 person-months) during the first 30 days after MI, corresponding to a 44-fold increase (standardized morbidity ratio, 44 [95% CI, 32 to 59]) risk for stroke in the population of Rochester, Minnesota. The risk for stroke remained 2 to 3 times higher than expected during the first 3 years after MI. Older age, previous stroke, and diabetes increased the risk for stroke, which did not decline over the study period. Strokes were associated with a large increase in the risk for death after MI (hazard ratio, 2.89 [CI, 2.44 to 3.43]). LIMITATIONS: Findings may not be generalizable to different populations. The authors measured outcomes by reviewing medical records. CONCLUSIONS: In the community, the risk for stroke is markedly increased after MI, particularly early after MI, compared with the expected risk in population without MI. Stroke is associated with a large increase in the risk for death after MI.

Aged↗

PubMed2005

Initial emergency department blood pressure as predictor of survival after acute ischemic stroke.

OBJECTIVE: To evaluate the association of diastolic blood pressure (dBP), systolic blood pressure (sBP), and mean arterial pressure (MAP) in the emergency department (ED) with mortality within 90 days in patients with acute ischemic stroke (AIS). METHODS: This observational study was conducted at an ED with an annual census of 70,000 visits, with approximately 500 for AIS. The cohort consisted of 357 patients who presented to the ED within 24 hours of stroke symptom onset. sBP and dBP were measured at triage by a nurse blinded to the study. The duration of follow-up was limited to the first 90 days following ED presentation. BP levels were categorized as low, normotensive, and high after examining scatter plots of a patient's risk of death adjusted for duration of follow-up vs dBP, sBP, and MAP. These BP categories were evaluated using indicator variables in Cox proportional hazards models, after adjusting for age, sex, and the National Institute of Health Stroke Scale (NIHSS) score. RESULTS: Patients with low BP (dBP <70, sBP <155, or MAP <100 mm Hg) were significantly more likely to die within 90 days than those with BP in the normotensive range (dBP 70 to 105, sBP 155 to 220, MAP 100 to 140 mm Hg). These associations were significant even after adjusting for age, gender, and NIHSS score. CONCLUSIONS: There appears to be an optimal acute BP range below which early mortality is greater following AIS, suggesting avoidance of hypotension in the first 24 hours.

Acute Disease↗

PubMed2005

Using extended-connectivity fingerprints with Laplacian-modified Bayesian analysis in high-throughput screening follow-up.

This article describes the use of a combination of extended-connectivity fingerprints (ECFPs) and Laplacian-modified Bayesian analysis in a study of the inhibition of Escherichia coli dihydrofolate reductase. The McMaster High-Throughput Screening Lab at McMaster University proposed a competition to predict the hits in a separate test set of 50,000 compounds. Although the problem seemed best approached with 3D methods, the authors show that 2D methods offer surprisingly competitive results with a low computational cost.

Algorithms↗

PubMed2005

Left atrial volume predicts cardiovascular events in patients originally diagnosed with lone atrial fibrillation: three-decade follow-up.

AIMS: The objectives of this study were to determine the long-term outcome and the predictors of adverse events in patients originally diagnosed with lone atrial fibrillation (AF). METHODS AND RESULTS: This population-based historical cohort study comprised 46 residents of Olmsted County, MN, USA, with well-documented, clinically defined lone AF and a complete two-dimensional echocardiographic examination. The original echocardiographic videotape recordings were analysed in a blinded fashion for left atrial volume (LAV) and left ventricular ejection fraction. With 1296 person-years of follow-up, the median duration of AF was 27 (first quartile=24, third quartile=33) years. Twenty-three (50%) patients developed events. Cerebral infarction occurred in seven patients, myocardial infarction in 11, and congestive heart failure in 16. In a multivariable analysis, patients with indexed LAV >or=32 mL/m(2) had a significantly worse event-free survival (adjusted HR, 4.46; 95% CI, 1.56-12.74; P=0.005). All cerebral infarctions occurred in patients with an indexed LAV >32 mL/m(2). CONCLUSION: Patients originally diagnosed with benign lone AF follow divergent courses based on LAV. Those originally diagnosed with lone AF and normal sized atria had a benign clinical course throughout the long-term follow-up. Patients with increased LAV at diagnosis or later during the follow-up experienced adverse events.

Aged↗

PubMed2005

The natural history of radiographically defined vertebrobasilar nonsaccular intracranial aneurysms.

BACKGROUND: Vertebrobasilar nonsaccular intracranial aneurysms (VBNIA) are characterized by dilatation, elongation, and tortuosity of the vertebrobasilar system. METHODS: The medical records and imaging of patients with vertebrobasilar fusiform aneurysms or dolichoectasia between 1989 and 2001 were reviewed. Prospective follow-up was obtained. RESULTS: One hundred and fifty-nine patients were identified (74% male) with 719 patient years of follow-up. Presenting events included: hemorrhage (3%), ischemia (28%), and compression (22%). The remainder were incidental. The 1-, 5-, and 10-year risk of cerebral infarction (CI) due toVBNIA is 2.7, 11.3, and 15.9% respectively. The risk of recurrent CI is 6.7% per patient year. Median survival was 7.8 years and death was most commonly due to ischemia. CONCLUSIONS: VBNIA are more common in men and typically present in the 6-7th decade. Recurrent CI is more common than hemorrhage risk.

Adult↗

PubMed2005

The Familial Intracranial Aneurysm (FIA) study protocol.

BACKGROUND: Subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms (IAs) occurs in about 20,000 people per year in the U.S. annually and nearly half of the affected persons are dead within the first 30 days. Survivors of ruptured IAs are often left with substantial disability. Thus, primary prevention of aneurysm formation and rupture is of paramount importance. Prior studies indicate that genetic factors are important in the formation and rupture of IAs. The long-term goal of the Familial Intracranial Aneurysm (FIA) Study is to identify genes that underlie the development and rupture of intracranial aneurysms (IA). METHODS/DESIGN: The FIA Study includes 26 clinical centers which have extensive experience in the clinical management and imaging of intracerebral aneurysms. 475 families with affected sib pairs or with multiple affected relatives will be enrolled through retrospective and prospective screening of potential subjects with an IA. After giving informed consent, the proband or their spokesperson invites other family members to participate. Each participant is interviewed using a standardized questionnaire which covers medical history, social history and demographic information. In addition blood is drawn from each participant for DNA isolation and immortalization of lymphocytes. High- risk family members without a previously diagnosed IA undergo magnetic resonance angiography (MRA) to identify asymptomatic unruptured aneurysms. A 10 cM genome screen will be performed to identify FIA susceptibility loci. Due to the significant mortality of affected individuals, novel approaches are employed to reconstruct the genotype of critical deceased individuals. These include the intensive recruitment of the spouse and children of deceased, affected individuals. DISCUSSION: A successful, adequately-powered genetic linkage study of IA is challenging given the very high, early mortality of ruptured IA. Design features in the FIA Study that address this challenge include recruitment at a large number of highly active clinical centers, comprehensive screening and recruitment techniques, non-invasive vascular imaging of high-risk subjects, genome reconstruction of dead affected individuals using marker data from closely related family members, and inclusion of environmental covariates in the statistical analysis.

Clinical Protocols↗

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

3.0-Tesla MR angiography of intracranial aneurysms: comparison of time-of-flight and contrast-enhanced techniques.

PURPOSE: To determine whether 3.0-T elliptical-centric contrast-enhanced (CE) magnetic resonance (MR) angiography is superior to 3.0-T elliptical-centric time-of-flight (TOF) MR angiography in the detection and characterization of intracranial aneurysms, and to determine whether increasing the acquisition matrix size in 3.0-T CE MR angiography improves image quality. MATERIALS AND METHODS: A total of 50 consecutive patients referred for MR angiographic evaluation of a known or suspected intracranial aneurysm underwent MR angiography, including three-dimensional TOF and elliptical-centric CE techniques at 3.0 T. The 3.0-T three-dimensional TOF and 3.0-T CE examinations were graded for image quality. A blind review identified the presence and location of aneurysms. RESULTS: A total of 28 aneurysms were identified in 23 of the 50 patients. The 3.0-T TOF MR angiography had a higher mean score for image quality than the 3.0-T elliptical-centric CE MR angiography (P < 0.0001). A total of 14 patients with aneurysms had conventional angiography for comparison. The 3.0-T TOF showed all the aneurysms, whereas 3.0-T CE MR angiography did not show 1 of 19 aneurysms when conventional angiography was the reference standard. CONCLUSION: For imaging intracranial aneurysms, 3.0-T TOF MR angiography offers better image quality than 3.0-T CE MR angiography using the elliptical-centric technique.

Adult↗

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↗