Showing papers by "University of Kansas published in 2001"

Wechsler Adult Intelligence Scale-III

Abstract: The Wechsler Adult Intelligence Scale-III (wais-iii) comes from a tradition of mental ability testing that began in 1939 with the publication of the Wechsler-Bellevue Intelligence Scale, Form I (W-B I). The W-B I, which was named after David Wechsler and the Bellevue Hospital where he was employed as chief psychologist, was considered a unique clinical instrument because it possessed good face validity with adolescents and adults, grouped items into subtests, and provided extensive assessment of both verbal and nonverbal abilities. The scale also utilized standard scores and deviation IQs instead of the mental age values and ratio IQs provided by contemporary tests such as the Stanford-Binet Intelligence Scale, Forms L and M.

Unified huntington’s disease rating scale: Reliability and consistency

Abstract: The Unified Huntington's disease Rating Scale (UHDRS) was developed as a clinical rating scale to assess four domains of clinical performance and capacity in HD: motor function, cognitive function, behavioral abnormalities, and functional capacity. We assessed the internal consistency and the intercorrelations for the four domains and examined changes in ratings over time. We also performed an interrater reliability study of the motor assessment. We found there was a high degree of internal consistency within each of the domains of the UHDRS and that there were significant intercorrelations between the domains of the UHDRS, with the exception of the total behavioral score. There was an excellent degree of interrater reliability for the motor scores. Our limited longitudinal database indicates that the UHDRS may be useful for tracking changes in the clinical features of HD over time. The UHDRS assesses relevant clinical features of HD and appears to be appropriate for repeated administration during clinical studies.

High-Involvement Work Practices, Turnover, and Productivity: Evidence from New Zealand

Abstract: Study results indicate a positive association between use of high-involvement work practices and employee retention and firm productivity. A disordinal interaction was indicated: employee turnover was associated with decreased productivity when use of high-involvement work practices was high and with increased productivity when use of these practices was low.

Practice parameter: Diagnosis of dementia (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology

Abstract: Article abstract—Objective: To update the 1994 practice parameter for the diagnosis of dementia in the elderly. Background: The AAN previously published a practice parameter on dementia in 1994. New research and clinical developments warrant an update of some aspects of diagnosis. Methods: Studies published in English from 1985 through 1999 were identified that addressed four questions: 1) Are the current criteria for the diagnosis of dementia reliable? 2) Are the current diagnostic criteria able to establish a diagnosis for the prevalent dementias in the elderly? 3) Do laboratory tests improve the accuracy of the clinical diagnosis of dementing illness? 4) What comorbidities should be evaluated in elderly patients undergoing an initial assessment for dementia? Recommendations: Based on evidence in the literature, the following recommendations are made. 1) The DSM-III-R definition of dementia is reliable and should be used (Guideline). 2) The National Institute of Neurologic, Communicative Disorders and Stroke‐AD and Related Disorders Association (NINCDS-ADRDA) or the Diagnostic and Statistical Manual, 3rd edition, revised (DSM-IIIR) diagnostic criteria for AD and clinical criteria for Creutzfeldt‐Jakob disease (CJD) have sufficient reliability and validity and should be used (Guideline). Diagnostic criteria for vascular dementia, dementia with Lewy bodies, and frontotemporal dementia may be of use in clinical practice (Option) but have imperfect reliability and validity. 3) Structural neuroimaging with either a noncontrast CT or MR scan in the initial evaluation of patients with dementia is appropriate. Because of insufficient data on validity, no other imaging procedure is recommended (Guideline). There are currently no genetic markers recommended for routine diagnostic purposes (Guideline). The CSF 14-3-3 protein is useful for confirming or rejecting the diagnosis of CJD (Guideline). 4) Screening for depression, B12 deficiency, and hypothyroidism should be performed (Guideline). Screening for syphilis in patients with dementia is not justified unless clinical suspicion for neurosyphilis is present (Guideline). Conclusions: Diagnostic criteria for dementia have improved since the 1994 practice parameter. Further research is needed to improve clinical definitions of dementia and its subtypes, as well as to determine the utility of various instruments of neuroimaging, biomarkers, and genetic testing in increasing diagnostic accuracy.

The point of triangulation.

Abstract: Purpose: To explore various types of triangulation strategies and to indicate when different types of triangulation should be used in research. Methods: Reviews included literature on triangulation and multimethod strategies published since 1960 and research books specifically focusing on triangulation. Findings: Triangulation is the combination of at least two or more theoretical perspectives, methodological approaches, data sources, investigators, or data analysis methods. The intent of using triangulation is to decrease, negate, or counterbalance the deficiency of a single strategy, thereby increasing the ability to interpret the findings. Conclusions: The use of triangulation strategies does not strengthen a flawed study. Researchers should use triangulation if it can contribute to understanding the phenomenon; however, they must be able to articulate why the strategy is being used and how it might enhance the study.

The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity

Abstract: The pregnane X receptor (PXR) is the molecular target for catatoxic steroids such as pregnenolone 16α-carbonitrile (PCN), which induce cytochrome P450 3A (CYP3A) expression and protect the body from harmful chemicals. In this study, we demonstrate that PXR is activated by the toxic bile acid lithocholic acid (LCA) and its 3-keto metabolite. Furthermore, we show that PXR regulates the expression of genes involved in the biosynthesis, transport, and metabolism of bile acids including cholesterol 7α-hydroxylase (Cyp7a1) and the Na+-independent organic anion transporter 2 (Oatp2). Finally, we demonstrate that activation of PXR protects against severe liver damage induced by LCA. Based on these data, we propose that PXR serves as a physiological sensor of LCA, and coordinately regulates gene expression to reduce the concentrations of this toxic bile acid. These findings suggest that PXR agonists may prove useful in the treatment of human cholestatic liver disease.

Predicting species invasions using ecological niche modeling: New approaches from bioinformatics attack a pressing problem

Abstract: O 3 February 1999, President Clinton signed an executive order dealing with invasive species in the United States. The order was designed to lay the foundation for a program “to prevent the introduction of invasive species and provide for their control and to minimize the economic, ecological, and human health impacts that invasive species cause” (Clinton 1999). This program includes far-reaching plans to prevent, plan, monitor, and study species’ invasions. Such high-level attention emphasizes the enormity of the problem facing the United States, and in fact the entire world: With ever-growing international commerce, reduced barriers to trade, and increasing human influence, species are moving around, and natural systems are suffering drastic changes. The dimensions of the problem are indeed impressive. Alien plants, animals, and microbes have poured into the United States from all directions. Natural systems have been disrupted, species extinguished, transportation and agriculture compromised, and resources damaged (Carlton 1997–1998, Ogutu-Ohwayo 1997–1998, Richardson 1997–1998, Shiva 1997–1998). In fact, most modern agriculture is based on nonnative organisms; problems arise because questions of when and why some escape and become nuisances remain unanswered. More generally, no proactive approach to combating such species is available—invasive species are dealt with one at a time, as they become problematic. Scientific approaches to a synthetic, and ultimately proactive, understanding of species invasions have developed along several lines, but most have been frustrated by the complex and unpredictable nature of such invasions—which species will invade and which invaders will become serious problems? For example, considerable effort has gone into identifying characteristics of species likely to invade, or of invaders likely to become pests (e.g., Lawton and Brown 1986, Smallwood and Salmon 1992, Carlton 1996). Another line of inquiry and effort has focused on modeling spatial patterns of range expansion after initial invasion (e.g., Mollison 1986, Williamson and Brown 1986, Reeves and Usher 1989, Hastings 1996, Shigesada and Kawasaki 1997, Holway 1998). All in all, though, a general, synthetic, predictive, proactive approach to species invasions is lacking (Mack 1996) but is desperately needed (Hobbs and Mooney 1998).

Predicting species’ geographic distributions based on ecological niche modeling

Abstract: Recent developments in geographic information systems and their application to conservation biology open doors to exciting new synthetic analyses. Exploration of these possibilities, however, is limited by the quality of information available: most biodiversity data are incomplete and characterized by biased sampling. Inferential procedures that provide robust and reliable predictions of species' geographic distributions thus become critical to biodiversity analyses. In this contribution, models of species' ecological niches are developed using an artificial-intelligence algorithm, and projected onto geography to predict species' distributions. To test the validity of this approach, I used North American Breeding Bird Survey data, with large sample sizes for many species. I omitted randomly selected states from model building, and tested models using the omitted states. For the 34 species tested, all predictions were highly statistically significant (all P < 0.001), indicating excellent predictiv...

Periaqueductal gray matter dysfunction in migraine: cause or the burden of illness?

Abstract: Objective.—The periaqueductal gray matter (PAG) is at the center of a powerful descending antinociceptive neuronal network. We studied iron homeostasis in the PAG as an indicator of function in patients with episodic migraine (EM) between attacks and patients with chronic daily headache (CDH) during headache. High-resolution magnetic resonance techniques were used to map the transverse relaxation rates R2, R2*, and R2′ in the PAG, red nucleus (RN), and substantia nigra (SN). R2′ is a measure of non-heme iron in tissues. Methods.—Seventeen patients diagnosed with EM with and without aura, 17 patients diagnosed with CDH and medication overuse, and 17 normal adults (N) were imaged with a 3.0-tesla magnetic resonance imaging system. For each subject, mean values of the relaxation rates, R2 (1/T2), R2* (1/T2*), and R2′ (R2* − R2) were obtained for the PAG, RN, and SN. R2, R2*, and R2′ values of the EM, CDH, and N groups were compared using analysis of variance, Student t test, and correlation analysis. Results.—In the PAG, there was a significant increase in mean R2′ and R2* values in both the EM and CDH groups (P<.05) compared with the N group, but no significant difference in these values was demonstrated between the EM and CDH groups, or between those with migraine with or without aura in the EM group. Positive correlations were found for duration of illness with R2′ in the EM and CDH groups. A decrease in mean R2′ and R2* values also was observed in the RN and SN of the CDH group compared with the N and EM groups (P<.05), explained best by flow activation due to head pain. Conclusions.—Iron homeostasis in the PAG was selectively, persistently, and progressively impaired in the EM and CDH groups, possibly caused by repeated migraine attacks. These results support and emphasize the role of the PAG as a possible “generator” of migraine attacks, potentially by dysfunctional control of the trigeminovascular nociceptive system.

The Development of Visual Attention in Infancy

Abstract: ▪ Abstract Over the past decade, the study of attention in infancy has seen dramatic progress. This review delineates four attentional functions (alertness, spatial orienting, attention to object features, and endogenous attention) that are relevant to infancy and uses these functions as a framework for summarizing the developmental course of attention in infancy. Rudimentary forms of various attentional functions are present at birth, but each of the functions exhibits different and apparently dissociable periods of postnatal change during the first years of life. The role of attention in development should therefore be considered in the context of interaction among different systems at different levels of maturity during the first years of life.

Role of adaptive plasticity in recovery of function after damage to motor cortex

Abstract: Based upon neurophysiologic, neuroanatomic, and neuroimaging studies conducted over the past two decades, the cerebral cortex can now be viewed as functionally and structurally dynamic. More specifically, the functional topography of the motor cortex (commonly called the motor homunculus or motor map), can be modified by a variety of experimental manipulations, including peripheral or central injury, electrical stimulation, pharmacologic treatment, and behavioral experience. The specific types of behavioral experiences that induce long-term plasticity in motor maps appear to be limited to those that entail the development of new motor skills. Moreover, recent evidence demonstrates that functional alterations in motor cortex organization are accompanied by changes in dendritic and synaptic structure, as well as alterations in the regulation of cortical neurotransmitter systems. These findings have strong clinical relevance as it has recently been shown that after injury to the motor cortex, as might occur in stroke, post-injury behavioral experience may play an adaptive role in modifying the functional organization of the remaining, intact cortical tissue.

Estimating the Risk of Future Reading Difficulties in Kindergarten Children: A Research-Based Model and Its Clinical Implementation.

Abstract: Purpose: Speech-language pathologists have the skills and knowledge needed to play an important role in the early identification of children who are at risk for reading difficulties. Whereas resear...

The sensations of everyday life: empirical, theoretical, and pragmatic considerations.

Abstract: The experience of being human is embedded in sensory events of everyday life. This lecture reviews sensory processing literature, including neuroscience and social science perspectives. Introduced is Dunn’s Model of Sensory Processing, and the evidence supporting this model is summarized. Specifically, using Sensory Profile questionnaires (i.e., items describing responses to sensory events in daily life; persons mark the frequency of each behavior), persons birth to 90 years of age demonstrate four sensory processing patterns: sensory seeking, sensory avoiding, sensory sensitivity, and low registration. These patterns are based on a person’s neurological thresholds and self-regulation strategies. Psychophysiology studies verify these sensory processing patterns; persons with strong preferences in each pattern also have unique patterns of habituation and responsivity in skin conductance. Studies also indicate that persons with disabilities respond differently than peers on these questionnaires, suggesting underlying poor sensory processing in certain disorders, including autism, attention deficit hyperactivity disorder, developmental delays, and schizophrenia. The author proposes relationships between sensory processing and temperament and personality traits. The four categories of temperament share some consistency with the four sensory processing patterns described in Dunn’s model. As with temperament, each person has some level of responsiveness within each sensory processing preference (i.e., a certain amount of seeking, avoiding, etc., not one or the other). The author suggests that one’s sensory processing preferences simultaneously reflect his or her nervous system needs and form the basis for the manifestation of temperament and personality. The final section of this lecture outlines parameters for developing best practice that supports interventions based on this knowledge.

Degradation of p53 by adenovirus E4orf6 and E1B55K proteins occurs via a novel mechanism involving a Cullin-containing complex

Abstract: The p53 cellular tumor suppressor induces cell cycle arrest and apoptosis by functioning as a transcriptional regulator (for review, see Woods and Vousden 2001). Intracellular levels of activated p53 are known to be regulated by a variety of mechanisms, including phosphorylation, acetylation, and targeted degradation. In most cells p53 is degraded, at least in part, through ubiquitin-dependent proteolysis involving MDM2 (for review, see Woods and Vousden 2001), which binds near the N terminus and functions as an E3 ubiquitin ligase for p53 (Honda et al. 1997). Nuclear export appears to be required for MDM2-dependent p53 degradation, which is blocked by both the drug leptomycin B (Roth et al. 1998; Lain et al. 1999) and the p53-binding protein ARF (for review, see Zhang and Xiong 2001). ARF binds MDM2, thus blocking MDM2-mediated ubiquitination and degradation. Although MDM2 is clearly a major regulator of p53 stability, MDM2-independent cellular pathways for p53 degradation exist, including the c-Jun N-terminal kinase (JNK), which binds to and destabilizes p53 (Fuchs et al. 1998), and calpain proteases (Gonen et al. 1997; Kubbutat and Vousden 1997; Zhang et al. 1997). Infection of cells by many viruses induces the stabilization and activation of p53 (for review, see Roulston et al. 1999). In the case of human adenoviruses, binding of the viral early region 1A (E1A) protein with either the retinoblastoma tumor suppressor family or p300/CBP/p400 histone acetyl transferases induces the activation, stabilization, and accumulation of p53 (Chiou and White 1997; Querido et al. 1997b; Samuelson and Lowe 1997). Increased levels of p53 could therefore result in the induction of cell cycle arrest and early apoptotic cell death, effects that would severely limit the yield of viral progeny. Adenoviruses and other small DNA tumor viruses have evolved various types of mechanisms to prevent the deleterious effects of p53. The large T antigen of simian virus 40 binds to the DNA-binding domain of p53 and prevents p53-mediated transcriptional effects (Sarnow et al. 1982; Bargonetti et al. 1992). This process leads to a large accumulation of p53, but it is nonfunctional. The E6 products of human papillomavirus types 16 and 18 bind p53 (Werness et al. 1990) and target it for degradation by the ubiquitin pathway. Targeting is mediated by a cellular E6-associated protein, E6AP-100K, that functions as a ubiquitin ligase, with E6 functioning as a bridge between the ligase and the p53 substrate (Scheffner et al. 1993). Although adenovirus E1A can induce a large accumulation of p53 when expressed alone, such increased p53 levels are not usually apparent in wild-type adenovirus-infected cells. Two products of early regions 1B and 4, E1B55K and E4orf6, bind p53 near the N and C termini, respectively, and inhibit transcriptional activation by the tumor suppressor (Sarnow et al. 1982; Yew and Berk 1992; Yew et al. 1994; Dobner et al. 1996; Teodoro and Branton 1997; E. Querido, S. Gurd, and P.E. Branton, unpubl.). In addition, several studies, including our own, have shown that E4orf6 and E1B55K function together to reduce the half-life of p53 and induce efficient p53 degradation (Moore et al. 1996; Querido et al. 1997a; Steegenga et al. 1998; Cathomen and Weitzman 2000; Nevels et al. 2000; Shen et al. 2001). Furthermore, the E1B55K/E4orf6 complex (Sarnow et al. 1984) can induce p53 turnover in cells lacking either MDM2 or ARF, indicating that neither is required for this process (Querido et al. 2001). E4orf6 is a nuclear protein containing both nuclear localization and nuclear retention signals that are believed to be responsible for targeting E4orf6 and E4orf6/E1B55K complexes to the nucleus (Goodrum et al. 1996; Orlando and Ornelles 1999; Nevels et al. 2000). In addition, both E4orf6 and E1B55K have nuclear export signals, and several groups have shown they can shuttle between the nucleus and the cytoplasm (Dobbelstein et al. 1997; Weigel and Dobbelstein 2000; Rabino et al. 2000; Dosch et al. 2001). In the present studies, we have determined the mechanism of adenovirus-induced p53 degradation through the identification of E4orf6-associated cellular proteins. Such proteins were found to be members of a novel Cullin-containing complex that is required for E4orf6–E1B55K-mediated p53 degradation and capable of inducing ubiquitination of p53 in vitro. These findings suggest that similar complexes could also function in the regulation of p53 levels in normal cells.

Interaction of the herbicide glyphosate with its target enzyme 5-enolpyruvylshikimate 3-phosphate synthase in atomic detail

Abstract: Biosynthesis of aromatic amino acids in plants, many bacteria, and microbes relies on the enzyme 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase, a prime target for drugs and herbicides. We have identified the interaction of EPSP synthase with one of its two substrates (shikimate 3-phosphate) and with the widely used herbicide glyphosate by x-ray crystallography. The two-domain enzyme closes on ligand binding, thereby forming the active site in the interdomain cleft. Glyphosate appears to occupy the binding site of the second substrate of EPSP synthase (phosphoenol pyruvate), mimicking an intermediate state of the ternary enzyme⋅substrates complex. The elucidation of the active site of EPSP synthase and especially of the binding pattern of glyphosate provides a valuable roadmap for engineering new herbicides and herbicide-resistant crops, as well as new antibiotic and antiparasitic drugs.

A Two-Dimensional, Two-Phase, Multicomponent, Transient Model for the Cathode of a Proton Exchange Membrane Fuel Cell Using Conventional Gas Distributors

Abstract: A two-dimensional, two-phase, multicomponent, transient model was developed for the cathode of the proton exchange membrane fuel cell. Gas transport was addressed by multicomponent diffusion equations while Darcy's law was adapted to account for the capillary flow of liquid water in the porous gas diffusion layer. The model was validated with experimental results and qualitative information on the effects of various operating conditions and design parameters and the transient phenomena upon imposing a cathodic overpotential were obtained. The performance of the cathode was found to be dominated by the dynamics of liquid water, especially in the high current density range. Conditions that promote faster liquid water removal such as temperature, dryness of the inlet gas stream, reduced diffusion layer thickness, and higher porosity improved the performance of the cathode. There seems to be an optimum in the diffusion layer thickness at the low current density range. The model results showed that for a fixed electrode width, a greater number of channels and shorter shoulder widths are preferred. The transient profiles clearly showed that liquid water transport is the slowest mass-transfer phenomenon in the cathode and is primarily responsible for mass-transfer restrictions especially over the shoulder.

Electrochemical biosensors: recommended definitions and classification*

Abstract: *A special report on the International Union of Pure and Applied Chemistry, Physical Chemistry Division, Commission I.7 (Biophysical Chemistry), Analytical Chemistry Division, Commission V.5 (Electroanalytical Chemistry).

Branching fraction and photon energy spectrum for b→sγ

Abstract: We have measured the branching fraction and photon energy spectrum for the radiative penguin process b-->s gamma. We find Beta(b-->s gamma) = (3.21+/-0.43+/-0.27(+0.18)(-0.10))x10(-4), where the errors are statistical, systematic, and from theory corrections. We obtain first and second moments of the photon energy spectrum above 2.0 GeV, = 2.346+/-0.032+/-0.011 GeV, and - (2) = 0.0226+/-0.0066+/-0.0020 GeV(2), where the errors are statistical and systematic. From the first moment, we obtain (in the modified minimal subtraction renormalization scheme, to order 1/M(3)(B) and beta(0)alpha(2)(s)) the heavy quark effective theory parameter Lambda = 0.35+/-0.08+/-0.10 GeV.

Rebels with a Cause: Group Identification as a Response to Perceived Discrimination from the Mainstream

Abstract: Two studies involving people with body piercings tested the hypothesis that perceived discrimination increases group identification. In Study 1, group identification mediated the positive relationship between perceived discrimination and attempts to differentiate the ingroup from the mainstream. In Study 2, perceived discrimination against people with body piercings was manipulated and was found to increase group identification. Support was found for the prediction that group identification mediates the relation-ship between perceptions of discrimination and collective self-esteem. Results demonstrate the importance of group identification for both the meaning of group membership and its consequences for well-being among members of disadvantaged groups.

Spatial patterns of NDVI in response to precipitation and temperature in the central Great Plains

Abstract: The Normalized DiVerence Vegetation Index (NDVI) has proven to bea robust indicator ofterrestrial vegetation productivity. Among climaticfactors, precipitation and temperature strongly ine uence both temporal and spatial pat- terns of NDVI. We examined spatial responses of NDVI to precipitation and temperature during a 9-year period (1989-1997) in Kansas. Biweekly climate maps (precipitation and temperature) were constructed by interpolation of weather station measurements. Maps of biweekly growing season (March to October) NDVI were constructed for Kansas using National Oceanic and Atmospheric Administration (NOAA) Advanced Very High Resolution Radio- meter (AVHRR) NDVI images. Average precipitation is a strong predictor of the major east-west NDVI gradient. Deviation from average precipitation explained most of the year-to-year variation in spatial patterns. NDVI and precipitation covaried in the same direction (both positive or both negative) for 60-95% of the total land area. Minimum and average temperatures were positively correlated with NDVI, but temperature deviation from average was generally not correlated with NDVI deviation from average. Our results demonstrate that precipitation is a strong predictor of regional spatial patterns of NDVI and, by inference, patterns of productivity.

Examining the shareholder wealth effects of announcements of newly created CIO positions

Abstract: While information technology (IT) has been transforming the business landscape for a long time now, it is only recently that empirical evidence demonstrating the positive impact of IT on firm performance has begun to accumulate The strategic importance of a firm's IT capabilities is prompting an increasing number of companies to appoint chief information officers (CIOs) to effectively manage these assets Such moves are reflective of changes in top management thinking and policy regarding the role of IT and firms' approaches to IT governance This paper uses the event study methodology to examine market reactions to announcements of new CIO positions Findings strongly support the notion that, for firms competing in industries undergoing IT-driven transformation, announcements of newly created CIO positions do indeed provoke positive reactions from the marketplace

Clinical spectrum of chronic acquired demyelinating polyneuropathies.

Abstract: A number of presentations of chronic demyelinating polyneuropathy have been identified, each distinguished by its phenotypic pattern. In addition to classic chronic inflammatory demyelinating polyneuropathy (CIDP), which is characterized clinically by symmetric proximal and distal weakness and sensory loss, several regional variants can be recognized: multifocal motor neuropathy (MMN: asymmetric and pure motor), multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy (asymmetric, sensory, and motor), and distal acquired demyelinating symmetric (DADS) neuropathy (symmetric, distal, sensory, and motor). There are also temporal, pathological, and disease-associated variants. This review describes a clinical scheme for approaching the chronic acquired demyelinating polyneuropathies that leads to a rational use of supportive laboratory studies and treatment options. In addition, we propose new diagnostic criteria for CIDP that more accurately reflect current clinical practice.

Lack of Clinical Significance of Early Ischemic Changes on Computed Tomography in Acute Stroke

Abstract: ContextThe prevalence and clinical significance of early ischemic changes (EICs) on baseline computed tomography (CT) scan of the head obtained within 3 hours of ischemic stroke are not established.ObjectiveTo determine the frequency and significance of EIC on baseline head CT scans in the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA (recombinant tissue plasminogen activator) Stroke Trial.Design and SettingThe original study, a randomized controlled trial, took place from January 1991 through October 1994 at 43 sites, during which CT images were obtained within 3 hours of symptom onset and prior to the initiation of rt-PA or placebo. For the current analysis, detailed reevaluation was undertaken after October 1994 of all baseline head CT scans with clinical data available pretreatment (blinded to treatment arm).PatientsOf 624 patients enrolled in the trial, baseline CT scans were retrieved and reviewed for 616 (99%).Main Outcome MeasuresFrequency of EICs on baseline CT scans; association of EIC with other baseline variables; effect of EICs on deterioration at 24 hours (≥4 points increase from the baseline National Institutes of Health Stroke Scale [NIHSS] score); clinical outcome (measured by 4 clinical scales) at 3 months, CT lesion volume at 3 months, death at 90 days; and symptomatic intracranial hemorrhage (ICH) within 36 hours of treatment.ResultsThe prevalence of EIC on baseline CT in the combined rt-PA and placebo groups was 31% (n = 194). The EIC was significantly associated with baseline NIHSS score (ρ = 0.23; P<.001) and time from stroke onset to baseline CT scan (ρ = 0.11; P = .007). After adjusting for baseline variables, there was no EIC × treatment interaction detected for any clinical outcome, including deterioration at 24 hours, 4 clinical scales, lesion volume, and death at 90 days (P≥.25), implying that EIC is unlikely to affect response to rt-PA treatment. After adjusting for NIHSS score (an independent predictor of ICH), no EIC association with symptomatic ICH at 36 hours was detected in the group treated with rt-PA (P≥.22).ConclusionsOur analysis suggests that EICs are prevalent within 3 hours of stroke onset and correlate with stroke severity. However, EICs are not independently associated with increased risk of adverse outcome after rt-PA treatment. Patients treated with rt-PA did better whether or not they had EICs, suggesting that EICs on CT scan are not critical to the decision to treat otherwise eligible patients with rt-PA within 3 hours of stroke onset.