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Biomedical subjects

Eric E Smith

Publications and source records attributed to Eric E Smith.

At least 19 recordsLinked to original sources
PubMed2006

White matter alterations in cerebral amyloid angiopathy measured by diffusion tensor imaging.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) represents beta-amyloid deposition in the small- and medium-sized vessels of the brain and meninges. CAA contributes to altered vessel function and is associated with white matter damage, cognitive impairment, and most salient, hemorrhagic stroke. We used diffusion tensor imaging to evaluate the anatomic distribution of white matter degeneration in participants diagnosed with advanced CAA. METHODS: Diffusion tensor imaging was obtained from 11 participants diagnosed with CAA-related intracerebral hemorrhage and 13 matched healthy control participants. Fractional anisotropy (FA) and diffusivity maps were compared using voxel based t test and region-of-interest analyses. RESULTS: FA was reduced in CAA in temporal white matter and in the splenium of the corpus callosum (P<0.001 with approximately 17% reduction in temporal white matter and 15% reduction in the splenium). FA was marginally increased in CAA in the posterior limb of the internal capsule and subthalamic gray matter regions (approximately 7% increase in subthalamic gray). FA changes were bilateral, remained significant in cluster analysis controlling for multiple comparisons, and did not depend on the hemisphere of the cerebral hemorrhage. Diffusivity was not substantially altered. CONCLUSIONS: These findings suggest that a pattern of regional brain tissue degeneration is a characteristic feature of advanced CAA.

Aged↗
PubMed2006

Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients.

In many human infections, hosts and pathogens coexist for years or decades. Important examples include HIV, herpes viruses, tuberculosis, leprosy, and malaria. With the exception of intensively studied viral infections such as HIV/AIDs, little is known about the extent to which the clonal expansion that occurs during long-term infection by pathogens involves important genetic adaptations. We report here a detailed, whole-genome analysis of one such infection, that of a cystic fibrosis (CF) patient by the opportunistic bacterial pathogen Pseudomonas aeruginosa. The bacteria underwent numerous genetic adaptations during 8 years of infection, as evidenced by a positive-selection signal across the genome and an overwhelming signal in specific genes, several of which are mutated during the course of most CF infections. Of particular interest is our finding that virulence factors that are required for the initiation of acute infections are often selected against during chronic infections. It is apparent that the genotypes of the P. aeruginosa strains present in advanced CF infections differ systematically from those of "wild-type" P. aeruginosa and that these differences may offer new opportunities for treatment of this chronic disease.

Adaptation, Physiological↗
PubMed2006

Risk factors for stroke after acute coronary syndromes in the Orbofiban in Patients with Unstable Coronary Syndromes--Thrombolysis In Myocardial Infarction (OPUS-TIMI) 16 study.

BACKGROUND: Previous reports have associated acute coronary syndromes (ACSs) with cerebrovascular disease but in general have not included long-term patient follow-up or have not analyzed ischemic and hemorrhagic cerebrovascular events separately. METHODS: We analyzed stroke outcomes from the OPUS-TIMI 16 study, a multicenter, randomized, placebo-controlled trial. Patients were randomized to aspirin plus either orbofiban or placebo and followed for up to 1 year. Cerebrovascular events were prospectively identified and classified by a committee of cardiologists and neurologists blinded to treatment assignment. RESULTS: During 10 months of follow-up, there were 150 (1.5%) patients with cerebrovascular events. Risk factors for ischemic stroke (n = 67) and transient ischemic attack (TIA) (n = 44) were age, prior ischemic stroke, history of hypertension, and increased heart rate. Prior ischemic stroke and history of hypertension were not risk factors for 30-day ischemic stroke or TIA. Risk factors for intracranial hemorrhage (ICH) (n = 14) were age, history of hypertension, history of TIA, and coronary angiography with evidence of coronary artery disease. Compared with placebo, treatment with orbofiban was associated with a nonsignificant increased risk of ischemic stroke or TIA (HR 1.15, 95% CI 0.76-1.74, P = .51) and ICH (HR 1.25, 95% CI 0.39-4.00, P = .70). CONCLUSIONS: The overall incidence of cerebrovascular events after ACS was highest in the first 30 days then declined; risk factors for cerebrovascular events may be different in the different periods. Orbofiban, despite no significant excess risk of ICH, was not effective in preventing ischemic stroke or TIA.

Aged↗
PubMed2006

Imaging of hemorrhagic stroke.

Neuroimaging by CT or MR is necessary for the detection of hemorrhagic stroke and provides important data regarding the cause of stroke. Serial changes in the CT and MR appearance of hematoma attributable to temporal evolution must be assessed to assure accurate diagnosis. Emerging evidence suggests that the use of MR imaging alone may be adequate for identifying hemorrhage in acute stroke patients and that GRE MR imaging is superior to both CT and conventional spin-echo MR imaging sequences for the detection of chronic microbleeds and hemorrhagic conversion of infarction.

Journal Article↗
PubMed2006

Thrombolytic therapy in acute cerebral infarction complicating diagnostic cardiac catheterization.

Diagnostic and interventional percutaneous coronary catheterization is associated with stroke. Many of such strokes are asymptomatic, but some are devastating. Once the diagnosis of acute cerebral infarction is confirmed, thrombolytic therapy should be administrated within the time window of 3 hours. We report a 61-year-old woman who suffered from an acute cerebral infarction during diagnostic cardiac catheterization for unstable angina, which manifested as sudden onset of global aphasia, right hemiplegia and gaze preponderance to the left side. Computed tomography of the head performed immediately after recognition of the symptoms showed a hyperdense middle cerebral artery (MCA) sign. Following prompt recognition and diagnosis, intravenous thrombolytic therapy was administered 2 hours after symptom onset. The patient had a favorable outcome. Initially, National Institutes of Health Stroke Scale score was 21, and 24 hours later it improved to 9. The hyperdense MCA lesion had resolved on the 24-hour follow-up scan. This case illustrates the clinical benefit of thrombolytic therapy in the setting of acute stroke associated with cardiac catheterization.

Angina, Unstable↗
PubMed2005

Timing of fresh frozen plasma administration and rapid correction of coagulopathy in warfarin-related intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Anticoagulation-related intracerebral hemorrhage (ICH) is often fatal, and rapid reversal of anticoagulation is the most appealing strategy currently available for treatment. We sought to determine whether particular emergency department (ED) interventions are effective in reversing coagulopathy and improving outcome. METHODS: Consecutive patients with warfarin-related ICH presenting to an urban tertiary care hospital from 1998 to 2004 were prospectively captured in a database. ED records were retrospectively reviewed for dose and timing of fresh-frozen plasma (FFP) and vitamin K, as well as serial coagulation measures. After excluding patients with incomplete ED records, do-not-resuscitate orders established in the ED, initial international normalized ratio (INR) < or =1.4, and for whom no repeat INR was performed, 69 patients were available for analysis. The primary outcome was a documented INR < or =1.4 within 24 hours of ED presentation. RESULTS: Patients whose INR was successfully reversed within 24 hours had a shorter median time from diagnosis to first dose of FFP (90 minutes versus 210 minutes; P=0.02). In multivariable analysis, shorter time to vitamin K, as well as FFP, predicted INR correction. Every 30 minutes of delay in the first dose of FFP was associated with a 20% decreased odds of INR reversal within 24 hours (odds ratio, 0.8; 95% CI, 0.63 to 0.99). Dosing of FFP and vitamin K had no effect. No ED intervention was associated with improved clinical outcome. CONCLUSIONS: Time to treatment is the most important determinant of 24-hour anticoagulation reversal. Although additional study is required to determine the clinical benefit of rapid reversal of anticoagulation, minimizing delays in FFP administration is a prudent first step in emergency management of warfarin-related ICH.

Aged↗
PubMed2005

Poor outcomes in patients who do not receive intravenous tissue plasminogen activator because of mild or improving ischemic stroke.

BACKGROUND AND PURPOSE: Some patients with mild or improving ischemic stroke symptoms do not receive intravenous tissue plasminogen activator (tPA) because they look "too good to treat" (TGT); however, some have poor outcomes. METHODS: We retrospectively analyzed data from a prospective single-center study between 2002 and 2004. TGT patients were those arriving within 3 hours of symptom onset and not treated with intravenous tPA solely because of mild or improving symptoms. RESULTS: Of 128 patients presenting within 3 hours, 41 (34%) were not given tPA because of mild or improving stroke. Of the TGT patients, 11 of 41 (27%) died or were not discharged home because of neurological worsening (n=6) or persistent "mild" neurological deficit (n=5). No single variable at presentation was associated with death or lack of home discharge. There were 10 of 41 TGT patients (24%) who had > or =4-point improvement in National Institutes of Health Stroke Scale score before tPA decision; these patients were more likely to have subsequent neurological worsening (relative risk, 4.1, 95% CI, 1.1 to 15.4; P=0.05). CONCLUSIONS: A substantial minority of patients deemed too good for intravenous tPA were unable to be discharged home. A re-evaluation of the stroke severity criteria for tPA eligibility may be indicated.

Aged↗
PubMed2005

Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is a common cause of symptomatic intracerebral hemorrhage (ICH), as well as small asymptomatic hemorrhage in the elderly. We used gradient-echo MRI to analyze spatial distribution of 321 hemorrhages in 59 patients with probable CAA-related ICH. Hemorrhagic lesions were found preferentially in the temporal (ratio of actual to expected hemorrhages = 1.37) and occipital lobes (ratio = 1.45, p < 0.0001). Within individuals, hemorrhages tended to cluster, regardless of lobe (p < 0.0001). Among subjects followed prospectively for recurrence, clustering of new symptomatic and asymptomatic hemorrhages was observed. These data suggest that regional differences within the brain play a role in the development of CAA-related hemorrhage.

Aged↗
PubMed2005

Hemorrhagic stroke.

Neuroimaging by CT or MR imaging is necessary for the identification of hemorrhagic stroke and provides information about its cause. The appearance of intracranial hematoma (ICH) on CT and MR imaging evolves over time and must be understood to facilitate accurate diagnosis. The cause of ICH varies by location. New evidence suggests that MR imaging alone may be adequate to identify hemorrhagic stroke in the acute setting, and that MR imaging is superior to CT for identification of chronic microbleeds and hemorrhagic conversion of infarction.

Cerebral Hemorrhage↗
PubMed2005

Relationship between hyperglycemia and symptomatic vasospasm after subarachnoid hemorrhage.

OBJECTIVE: To determine the relationship between blood glucose levels (mg/dL) and occurrence of symptomatic vasospasm (VSP) and clinical outcomes after aneurysmal subarachnoid hemorrhage. DESIGN: Retrospective observational study of 352 patients with subarachnoid hemorrhage admitted within 48 hrs of ictus between January 1995 and June 2002. SETTING: Neurointensive care unit. PATIENTS: Adult patients admitted after subarachnoid hemorrhage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Variables included age; Hunt-Hess classification score; Fisher group; insulin use; infectious disease status; history of diabetes mellitus; and blood glucose values. Poor clinical outcome was defined by a modified Rankin score > or =3, and hyperglycemia was defined by a blood glucose level >140 mg/dL. Mean daily blood glucose values were assessed from admission to development of VSP or day 14. Mean admission blood glucose value, mean inpatient blood glucose value, insulin use, infectious disease status, Hunt-Hess classification score, Fisher group, and history of diabetes mellitus were entered in a Cox proportional hazards model. VSP occurred in 103 (29.2%) of 352 patients. Mean admission blood glucose values (176.6 +/- 40.3 mg/dL vs. 162.3 +/- 47.8 mg/dL; p = .01) and mean inpatient blood glucose values (166.2 +/- 24.7 mg/dL vs. 155.8 +/- 29.7 mg/dL; p = .001) were significantly higher in patients with VSP. Mean inpatient blood glucose value (relative risk, 1.01; 95% confidence interval, 1.0-1.03; p = .04), Hunt-Hess classification score > or =3 (relative risk, 2.23; 95% confidence interval, 1.21-3.99; p = .02), and Fisher group score of 3 (relative risk, 1.28; 95% confidence interval, 1.15-3.1; p = .05) increased the risk for VSP. Hyperglycemia was associated with longer length of stay in the neurointensive care unit (14.5 +/- 7.1 days vs. 11.6 +/- 5.4 days; p < .001) and poor outcome at discharge (modified Rankin score > or =3: 58.9% vs. 18.8%; p < .001). CONCLUSIONS: Mean inpatient blood glucose value is associated with the development of VSP and may represent a target for therapy to prevent VSP and improve clinical outcomes.

Blood Glucose↗
PubMed2005

Evidence for diversifying selection at the pyoverdine locus of Pseudomonas aeruginosa.

Pyoverdine is the primary siderophore of the gram-negative bacterium Pseudomonas aeruginosa. The pyoverdine region was recently identified as the most divergent locus alignable between strains in the P. aeruginosa genome. Here we report the nucleotide sequence and analysis of more than 50 kb in the pyoverdine region from nine strains of P. aeruginosa. There are three divergent sequence types in the pyoverdine region, which correspond to the three structural types of pyoverdine. The pyoverdine outer membrane receptor fpvA may be driving diversity at the locus: it is the most divergent alignable gene in the region, is the only gene that showed substantial intratype variation that did not appear to be generated by recombination, and shows evidence of positive selection. The hypothetical membrane protein PA2403 also shows evidence of positive selection; residues on one side of the membrane after protein folding are under positive selection. R', previously identified as a type IV strain, is clearly derived from a type III strain via a 3.4-kb deletion which removes one amino acid from the pyoverdine side chain peptide. This deletion represents a natural modification of the product of a nonribosomal peptide synthetase enzyme, whose consequences are predictive from the DNA sequence. There is also linkage disequilibrium between the pyoverdine region and pvdY, a pyoverdine gene separated by 30 kb from the pyoverdine region. The pyoverdine region shows evidence of horizontal transfer; we propose that some alleles in the region were introduced from other soil bacteria and have been subsequently maintained by diversifying selection.

Bacterial Outer Membrane Proteins↗
PubMed2005

Arterial occlusion revealed by CT angiography predicts NIH stroke score and acute outcomes after IV tPA treatment.

BACKGROUND AND PURPOSE: The relationship between location of occlusion and clinical outcome is poorly understood in patients receiving intravenous tissue-type plasminogen activator (IV tPA). We postulated that acute stroke patients receiving IV tPA with patent vasculature or occult arterial occlusion by CT angiography (CTA) would have better outcomes and decreased hemorrhagic risk. METHODS: We identified 47 patients from our prospective stroke database who underwent CTA before treatment with IV tPA. Site of occlusion was categorized as M1 segment of the middle cerebral artery, M2 segment, multiple (either carotid, basilar, or both middle and anterior cerebral arteries), or absent (no occlusion proximal to M3). The effect of site of occlusion on National Institutes of Health Stroke Scale (NIHSS), early improvement (> or = 4-point improvement in NIHSS at 24 hours after treatment), intracranial hemorrhages, and modified Rankin scale (mRS) at 7 days was tested in a multivariate analysis. RESULTS: The location of occlusion correlated with initial NIHSS for multiple, M1, M2 and absent occlusions (median NIHSS scores were 18, 18, 15, 10, respectively) (P < .02, rank sum). Following adjustment for initial NIHSS, age, and time to treatment, the absence of occlusion remained associated with early improvement (OR 5.0, 95% CI 1.1-23.3; P = .04) and independence at day 7 (mRS < or = 2) (OR 6.8, 95% CI 1.3-34.6; P = .02). Overall prevalence of symptomatic hemorrhages was 6.4%. Patients without occlusion had no hemorrhages (0% versus 23.3%; P < .04). CONCLUSION: Among patients treated with tPA, those with patent vasculature or occult distal occlusion on CTA before treatment have lower NIHSS, better chances of early improvement and early independence with fewer hemorrhages.

Aged↗
PubMed2004

Amyloid angiopathy-related vascular cognitive impairment.

We review accumulating evidence that cerebrovascular amyloid deposition (cerebral amyloid angiopathy [CAA]) is an independent risk factor for cognitive dysfunction. The two population-based autopsy studies that have analyzed cognitive status during life as a function of CAA have each suggested deleterious effects of CAA on cognition even after controlling for age and Alzheimer disease pathology. We also review data from patients with CAA-related intracerebral hemorrhage (the one form of CAA that can be noninvasively recognized) suggesting associations of CAA with radiographic white matter abnormalities and cognitive impairment. These data highlight the importance of elucidating the effects of vascular amyloid on cerebrovascular function and of developing therapeutic strategies for this potentially widespread form of microvascular cognitive impairment.

Cerebral Amyloid Angiopathy↗
PubMed2004

Hemorrhage burden predicts recurrent intracerebral hemorrhage after lobar hemorrhage.

BACKGROUND AND PURPOSE: Small asymptomatic cerebral hemorrhages detectable by gradient-echo MRI are common in patients with intracerebral hemorrhage (ICH), particularly lobar ICH related to cerebral amyloid angiopathy (CAA). We sought to determine whether hemorrhages detected at the time of lobar ICH predict the major clinical complications of CAA: recurrent ICH or decline in cognition and function. METHODS: Ninety-four consecutive survivors of primary lobar ICH (age > or =55) with gradient-echo MRI at presentation were followed in a prospective cohort study for 32.9+/-24.0 months. A subset of 34 subjects underwent a second MRI after a stroke-free interval of 15.8+/-6.5 months. Study endpoints were recurrent symptomatic ICH or clinical decline, defined as onset of cognitive impairment, loss of independent functioning, or death. RESULTS: The total number of hemorrhages at baseline predicted risk of future symptomatic ICH (3-year cumulative risks 14%, 17%, 38%, and 51% for subjects with 1, 2, 3 to 5, or > or =6 baseline hemorrhages, P=0.003). Higher numbers of hemorrhages at baseline also predicted increased risk for subsequent cognitive impairment, loss of independence, or death (P=0.002) among subjects not previously demented or dependent. For subjects followed after a second MRI, new microhemorrhages appeared in 17 of 34 and predicted increased risk of subsequent symptomatic ICH (3-year cumulative risks 19%, 42%, and 67% for subjects with 0, 1 to 3, or > or =4 new microhemorrhages, P=0.02), but not subsequent clinical decline. CONCLUSIONS: Hemorrhages identified by MRI predict clinically important events in survivors of lobar ICH. Detection of microhemorrhages may be useful for assessing risk in ICH patients and as a surrogate marker for clinical studies.

Aged↗
PubMed2004

Spontaneous hyperacute postischemic hemorrhage leading to death.

Hyperacute, spontaneous, and severe parenchymal postischemic hemorrhage is considered rare but might be frequently misdiagnosed as primary intracerebral hemorrhage. The authors report 2 patients with catastrophic postischemic hemorrhage unrelated to anticoagulation, thrombolytics, or coagulopathy. Patient 1 was a 73-year-old woman with left posterior frontal lobe infarction, followed at 5.5 hours by massive postischemic hemorrhage leading to death. Patient 2 was a 52-year-old man with recent brain irradiation who developed left middle cerebral artery occlusion and basal ganglia infarction. Initial gradient-echo magnetic resonance imaging (MRI) showed petechial hemorrhage within areas of infarction and widespread old microbleeds. He developed massive postischemic hemorrhage at 12 hours, leading to death. The authors conclude that early brain imaging is essential to distinguish postischemic from primary brain hemorrhage. In patients with ischemic stroke, MRI findings such as hyperacute petechial hemorrhage or chronic cerebral microbleeds might predict subsequent parenchymal hemorrhage and thus have implications for tissue plasminogen activator use.

Acute Disease↗