Showing papers by "Icahn School of Medicine at Mount Sinai published in 2002"

Results of a Prospective Study of Acute Liver Failure at 17 Tertiary Care Centers in the United States

Abstract: Acetaminophen overdose and idiosyncratic drug reactions have replaced viral hepatitis as the most frequent causes of acute liver failure. The cause of liver failure and coma grade at admission were...

Is volume related to outcome in health care? A systematic review and methodologic critique of the literature

Abstract: High volume is associated with better outcomes across a wide range of procedures and conditions, but the magnitude of the association varies greatly. The clinical and policy significance of these f...

The contextual effect of the local food environment on residents' diets: The atherosclerosis risk in communities study

Abstract: Objectives. We studied the association between the local food environment and residents’ report of recommended dietary intake. Methods. Recommended intakes of foods and nutrients for 10 623 Atherosclerosis Risk in Communities participants were estimated from food frequency questionnaires. Supermarkets, grocery stores, and full-service and fast-food restaurants were geocoded to census tracts. Results. Black Americans’ fruit and vegetable intake increased by 32% for each additional supermarket in the census tract (relative risk [RR] = 1.32; 95% confidence interval [CI] = 1.08, 1.60). White Americans’ fruit and vegetable intake increased by 11% with the presence of 1 or more supermarket (RR = 1.11; 95% CI = 0.93, 1.32). Conclusions. These findings suggest the local food environment is associated with residents’ recommended diets.

A Road Map for Those Who Don't Know JAK-STAT

Abstract: The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway transmits information received from extracellular polypeptide signals, through transmembrane receptors, directly to target gene promoters in the nucleus, providing a mechanism for transcriptional regulation without second messengers. Evolutionarily conserved in eukaryotic organisms from slime molds to humans, JAK-STAT signaling appears to be an early adaptation to facilitate intercellular communication that has co-evolved with myriad cellular signaling events. This co-evolution has given rise to highly adapted, ligand-specific signaling pathways that control gene expression. In addition, the JAK-STAT signaling pathways are regulated by a vast array of intrinsic and environmental stimuli, which can add plasticity to the response of a cell or tissue.

G Protein Pathways

Abstract: The heterotrimeric guanine nucleotide-binding proteins (G proteins) are signal transducers that communicate signals from many hormones, neurotransmitters, chemokines, and autocrine and paracrine factors. The extracellular signals are received by members of a large superfamily of receptors with seven membrane-spanning regions that activate the G proteins, which route the signals to several distinct intracellular signaling pathways. These pathways interact with one another to form a network that regulates metabolic enzymes, ion channels, transporters, and other components of the cellular machinery controlling a broad range of cellular processes, including transcription, motility, contractility, and secretion. These cellular processes in turn regulate systemic functions such as embryonic development, gonadal development, learning and memory, and organismal homeostasis.

Neck Dissection Classification Update: Revisions Proposed by the American Head and Neck Society and the American Academy of Otolaryngology–Head and Neck Surgery

Abstract: Since the first description of the radical neck dissection by George Crile almost a century ago, many variations and modifications of the procedure have been added. These include the functional neck dissection, the modified radical neck dissection, and various selective neck dissections. In response to the need for an organized approach in describing these operations, the Committee for Head and Neck Surgery and Oncology of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) in 1988 initiated an effort to develop a standardized classification system for neck dissection (Table 1). During this process, input was obtained from the Education Committee of the American Society for Head and Neck Surgery (ASHNS) and its Council. The final product, endorsed by the ASHNS and the AAO-HNS, was published in the ARCHIVES 1 and as a monograph 2 by the AAO-HNS in 1991.

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision

Abstract: SummaryIn this report, recommendations for the pharmacological treatment of anxiety and obsessive-compulsive disorders are presented, based on available randomized, placebo-or comparator-controlled

Working Group on Blood Pressure Monitoring of the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults

Abstract: Working Group on Blood Pressure Monitoring of the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults Eoin O’Brien,Thomas Pickering, Roland Asmar, Martin Myers, Gianfranco Parati, Jan Staessen, Thomas Mengden, Yutaka Imai, Bernard Waeber and Paolo Palatini and with the statistical assistance of Neil Atkins and William Gerin, on behalf of the Working Group on Blood Pressure Monitoring of the European Society of Hypertension

A presenilin‐1/γ‐secretase cleavage releases the E‐cadherin intracellular domain and regulates disassembly of adherens junctions

Abstract: E‐cadherin controls a wide array of cellular behaviors including cell–cell adhesion, differentiation and tissue development. Here we show that presenilin‐1 (PS1), a protein involved in Alzheimer9s disease, controls a γ‐secretase‐like cleavage of E‐cadherin. This cleavage is stimulated by apoptosis or calcium influx and occurs between human E‐cadherin residues Leu731 and Arg732 at the membrane–cytoplasm interface. The PS1/γ‐secretase system cleaves both the full‐length E‐cadherin and a transmembrane C‐terminal fragment, derived from a metalloproteinase cleavage after the E‐cadherin ectodomain residue Pro700. The PS1/γ‐secretase cleavage dissociates E‐cadherins, β‐catenin and α‐catenin from the cytoskeleton, thus promoting disassembly of the E‐cadherin–catenin adhesion complex. Furthermore, this cleavage releases the cytoplasmic E‐cadherin to the cytosol and increases the levels of soluble β‐ and α‐catenins. Thus, the PS1/γ‐secretase system stimulates disassembly of the E‐cadherin– catenin complex and increases the cytosolic pool of β‐catenin, a key regulator of the Wnt signaling pathway.

PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity

Abstract: Noonan syndrome (NS) is a developmental disorder characterized by facial dysmorphia, short stature, cardiac defects, and skeletal malformations. We recently demonstrated that mutations in PTPN11, the gene encoding the non-receptor-type protein tyrosine phosphatase SHP-2 (src homology region 2-domain phosphatase-2), cause NS, accounting for approximately 50% of cases of this genetically heterogeneous disorder in a small cohort. All mutations were missense changes and clustered at the interacting portions of the amino-terminal src-homology 2 (N-SH2) and protein tyrosine phosphatase (PTP) domains. A gain of function was postulated as a mechanism for the disease. Here, we report the spectrum and distribution of PTPN11 mutations in a large, well-characterized cohort with NS. Mutations were found in 54 of 119 (45%) unrelated individuals with sporadic or familial NS. There was a significantly higher prevalence of mutations among familial cases than among sporadic ones. All defects were missense, and several were recurrent. The vast majority of mutations altered amino acid residues located in or around the interacting surfaces of the N-SH2 and PTP domains, but defects also affected residues in the C-SH2 domain, as well as in the peptide linking the N-SH2 and C-SH2 domains. Genotype-phenotype analysis revealed that pulmonic stenosis was more prevalent among the group of subjects with NS who had PTPN11 mutations than it was in the group without them (70.6% vs. 46.2%; P<.01), whereas hypertrophic cardiomyopathy was less prevalent among those with PTPN11 mutations (5.9% vs. 26.2%; P<.005). The prevalence of other congenital heart malformations, short stature, pectus deformity, cryptorchidism, and developmental delay did not differ between the two groups. A PTPN11 mutation was identified in a family inheriting Noonan-like/multiple giant-cell lesion syndrome, extending the phenotypic range of disease associated with this gene.

Diabetes and advanced glycation endproducts.

Abstract: Bio-reactive advanced glycation endproducts (AGE) alter the structure and function of molecules in biological systems and increase oxidative stress. These adverse effects of both exogenous and endogenously derived AGE have been implicated in the pathogenesis of diabetic complications and changes associated with ageing including atherosclerosis, renal, eye and neurological disease. Specific AGE receptors and nonreceptor mechanisms contribute to these processes but also assist in the removal and degradation of AGE. The final disposal of AGE depends on renal clearance. Promising pharmacologic strategies to prevent AGE formation, reduce AGE toxicity, and/or inactivate AGE are under investigation.

C-cadherin ectodomain structure and implications for cell adhesion mechanisms

Abstract: Cadherins are transmembrane proteins that mediate adhesion between cells in the solid tissues of animals. Here we present the 3.1 angstrom resolution crystal structure of the whole, functional extracellular domain from C-cadherin, a representative “classical” cadherin. The structure suggests a molecular mechanism for adhesion between cells by classical cadherins, and it provides a new framework for understanding both cis (same cell) and trans (juxtaposed cell) cadherin interactions. The trans adhesive interface is a twofold symmetric interaction defined by a conserved tryptophan side chain at the membrane-distal end of a cadherin molecule from one cell, which inserts into a hydrophobic pocket at the membrane-distal end of a cadherin molecule from the opposing cell.

Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy

Abstract: Diet is a major environmental source of proinflammatory AGEs (heat-generated advanced glycation end products); its impact in humans remains unclear. We explored the effects of two equivalent diets, one regular (high AGE, H-AGE) and the other with 5-fold lower AGE (L-AGE) content on inflammatory mediators of 24 diabetic subjects: 11 in a 2-week crossover and 13 in a 6-week study. After 2 weeks on H-AGE, serum AGEs increased by 64.5% (P = 0.02) and on L-AGE decreased by 30% (P = 0.02). The mononuclear cell tumor necrosis factor-alphabeta-actin mRNA ratio was 1.4 +/- 0.5 on H-AGE and 0.9 +/- 0.5 on L-AGE (P = 0.05), whereas serum vascular adhesion molecule-1 was 1,108 +/- 429 and 698 +/- 347 ngml (P = 0.01) on L- and H-AGE, respectively. After 6 weeks, peripheral blood mononuclear cell tumor necrosis factor-alpha rose by 86.3% (P = 0.006) and declined by 20% (P, not significant) on H- or L-AGE diet, respectively; C-reactive protein increased by 35% on H-AGE and decreased by 20% on L-AGE (P = 0.014), and vascular adhesion molecule-1 declined by 20% on L-AGE (P < 0.01) and increased by 4% on H-AGE. Serum AGEs were increased by 28.2% on H-AGE (P = 0.06) and reduced by 40% on L-AGE (P = 0.02), whereas AGE low density lipoprotein was increased by 32% on H-AGE and reduced by 33% on L-AGE diet (P < 0.05). Thus in diabetes, environmental (dietary) AGEs promote inflammatory mediators, leading to tissue injury. Restriction of dietary AGEs suppresses these effects.

MAP Kinase Phosphatase As a Locus of Flexibility in a Mitogen-Activated Protein Kinase Signaling Network

Abstract: Intracellular signaling networks receive and process information to control cellular machines. The mitogen-activated protein kinase (MAPK) 1,2/protein kinase C (PKC) system is one such network that regulates many cellular machines, including the cell cycle machinery and autocrine/paracrine factor synthesizing machinery. We used a combination of computational analysis and experiments in mouse NIH-3T3 fibroblasts to understand the design principles of this controller network. We find that the growth factor-stimulated signaling network containing MAPK 1, 2/PKC can operate with one (monostable) or two (bistable) stable states. At low concentrations of MAPK phosphatase, the system exhibits bistable behavior, such that brief stimulus results in sustained MAPK activation. The MAPK-induced increase in the amounts of MAPK phosphatase eliminates the prolonged response capability and moves the network to a monostable state, in which it behaves as a proportional response system responding acutely to stimulus. Thus, the MAPK 1, 2/PKC controller network is flexibly designed, and MAPK phosphatase may be critical for this flexible response.

Illness management and recovery: a review of the research.

Abstract: Illness management is a broad set of strategies designed to help individuals with serious mental illness collaborate with professionals, reduce their susceptibility to the illness, and cope effectively with their symptoms. Recovery occurs when people with mental illness discover, or rediscover, their strengths and abilities for pursuing personal goals and develop a sense of identity that allows them to grow beyond their mental illness. The authors discuss the concept of recovery from psychiatric disorders and then review research on professional-based programs for helping people manage their mental illness. Research on illness management for persons with severe mental illness, including 40 randomized controlled studies, indicates that psychoeducation improves people's knowledge of mental illness; that behavioral tailoring helps people take medication as prescribed; that relapse prevention programs reduce symptom relapses and rehospitalizations; and that coping skills training using cognitive-behavioral te...

Neurochemical correlates of dementia severity in Alzheimer's disease: relative importance of the cholinergic deficits.

Abstract: Cholinergic markers, neuropeptides, and amines and their metabolites were sampled from identical specimens across 10 neocortical regions in a large sample of Alzheimer's disease (AD) cases and controls. Levels of choline acetyltransferase, acetylcholinesterase, somatostatin, corticotropin-releasing factor, serotonin, and 5-hydroxyindoleacetic acid were significantly reduced in AD versus controls. After data reduction, the most descriptive neurochemical indices were used to examine the relationship of neurochemical measures and dementia severity within the AD sample, controlling for age effects. Dementia severity ratings were based on antemortem assessments (46.9% of AD sample) and postmortem chart review (53.1% of the AD sample). Choline acetyltransferase activity was highly correlated with clinical dementia ratings across the neocortex of the AD cases. Somatostatin and corticotropin-releasing factor levels were correlated with dementia severity only when control cases were included in the analyses. None of the amines, their metabolites, or the neuropeptides quantified related significantly to dementia severity in the AD cohort. These data (a) confirm the strong association of cholinergic deficits with functional impairment in AD and show that this association is independent of age and (b) suggest that of all the neurochemical species quantified, the cholinergic indices may be unique in their association with dementia severity.

Environmental pollutants and disease in American children: estimates of morbidity, mortality, and costs for lead poisoning, asthma, cancer, and developmental disabilities.

Abstract: In this study, we aimed to estimate the contribution of environmental pollutants to the incidence, prevalence, mortality, and costs of pediatric disease in American children. We examined four categories of illness: lead poisoning, asthma, cancer, and neurobehavioral disorders. To estimate the proportion of each attributable to toxins in the environment, we used an environmentally attributable fraction (EAF) model. EAFs for lead poisoning, asthma, and cancer were developed by panels of experts through a Delphi process, whereas that for neurobehavioral disorders was based on data from the National Academy of Sciences. We define environmental pollutants as toxic chemicals of human origin in air, food, water, and communities. To develop estimates of costs, we relied on data from the U.S. Environmental Protection Agency, Centers for Disease Control and Prevention, National Center for Health Statistics, the Bureau of Labor Statistics, the Health Care Financing Agency, and the Practice Management Information Corporation. EAFs were judged to be 100% for lead poisoning, 30% for asthma (range, 10-35%), 5% for cancer (range, 2-10%), and 10% for neurobehavioral disorders (range, 5-20%). Total annual costs are estimated to be $54.9 billion (range $48.8-64.8 billion): $43.4 billion for lead poisoning, $2.0 billion for asthma, $0.3 billion for childhood cancer, and $9.2 billion for neurobehavioral disorders. This sum amounts to 2.8 percent of total U.S. health care costs. This estimate is likely low because it considers only four categories of illness, incorporates conservative assumptions, ignores costs of pain and suffering, and does not include late complications for which etiologic associations are poorly quantified. The costs of pediatric environmental disease are high, in contrast with the limited resources directed to research, tracking, and prevention.

A controlled trial of rasagiline in early Parkinson disease: The tempo study

Abstract: CONTEXT Monotherapy with rasagiline mesylate may be useful in early Parkinson disease (PD). OBJECTIVE To evaluate the safety and efficacy of the selective monoamine oxidase type B inhibitor rasagiline. DESIGN Multicenter, 26-week, parallel-group, randomized, double-blind, placebo-controlled clinical trial. SETTING Academically based movement disorders clinics. PATIENTS Patients with early PD not requiring dopaminergic therapy (n = 404). INTERVENTION Research participants were randomized to rasagiline mesylate at dosages of 1 mg or 2 mg per day or matching placebo. A 1-week escalation period was followed by a 25-week maintenance period. MAIN OUTCOME MEASURE The primary prespecified measure of efficacy was the change in the total Unified Parkinson's Disease Rating Scal score between baseline and 26 weeks of treatment, comparing each active treatment group with the placebo group. RESULTS Monotherapy with rasagiline was effective in this 26-week study. The adjusted effect size for the total Unified Parkinson's Disease Rating Scale was -4.20 units comparing 1 mg of rasagiline and placebo (95% confidence interval, -5.66 to -2.73 units; P<.001) and -3.56 units comparing a 2-mg dosage and placebo (95% confidence interval, -5.04 to -2.08 units; P<.001). There were no meaningful differences in the frequency of adverse events or premature withdrawals among the treatment groups. CONCLUSIONS Rasagiline is effective as monotherapy for patients with early PD. The 2 dosages in this trial were both effective relative to placebo. Further study is warranted to evaluate the longer-term effects of rasagiline in PD.

Accuracy and calibration of commercial oligonucleotide and custom cDNA microarrays

Abstract: We compared the accuracy of microarray measurements obtained with oligonucleotide arrays (GeneChip, Affymetrix) with a laboratory-developed cDNA array by assaying test RNA samples from an experiment using a paradigm known to regulate many genes measured on both arrays. We selected 47 genes represented on both arrays, including both known regulated and unregulated transcripts, and established reference relative expression measurements for these genes in the test RNA samples using quantitative reverse transcriptase real-time PCR (QRTPCR) assays. The validity of the reproducible (average coefficient of variation = 11.8%) QRTPCR measurements were established through application of a new mathematical model. The performance of both array platforms in identifying regulated and non-regulated genes was identical. With either platform, 16 of 17 definitely regulated genes were correctly identified, and no definitely unregulated transcript was falsely identified as regulated. Accuracy of the fold-change measurements obtained with each platform was assessed by determining measurement bias. Both platforms consistently underestimate the relative changes in mRNA expression between experimental and control samples. The bias observed with cDNA arrays was predictable for fold-changes <250-fold by QRTPCR and could be corrected by the calibration function F(c) = F(a(cDNA))(q), where F(a(cDNA)) is the microarray-determined fold-change comparing experimental with control samples, q is the correction factor and F(c) is the calibrated value. The bias observed with the commercial oligonucleotide arrays was less predictable and calibration was unfeasible. Following calibration, fold-change measurements generated by custom cDNA arrays were more accurate than those obtained by commercial oligonucleotide arrays. Our study demonstrates systematic bias of microarray measurements and identifies a calibration function that improves the accuracy of cDNA array data.

Drug use and the risk of major depressive disorder, alcohol dependence, and substance use disorders.

Abstract: Methods: Using data from a community-based sample of 736 adults (50% female) from upstate New York, the subjects were interviewed at the mean ages of 14, 16, 22, and 27 years. Psychiatric disorders, measured by ageappropriate versions of the University of Michigan Composite International Diagnostic Interview, and participant’s drug use were assessed. Results: Adolescent and young adult tobacco use was significantly associated with an increased risk of alcohol dependence and substance use disorders at a mean age of 27 years, but not with new episodes of major depressive disorder. Earlier alcohol use significantly predicted later major depressive disorder, alcohol dependence, and substance use disorders in the late 20s, as did early marijuana use and other illicit drug use. Except for the effect of tobacco use on major depressive disorder, early drug use was significantly related to later psychiatric disorders, even after statistically controlling for age, sex, parental educational level, family income, and prior episodes of major depressive disorder and substance use disorders. Conclusions: Our results suggest that early drug use is associated with and predicts later psychiatric disorders. Preventive implications stem from the importance of studying a range of psychiatric disorders in the context of substance use assessed over a wide age range. Arch Gen Psychiatry. 2002;59:1039-1044

Molecular characterization of lymphatic endothelial cells

Abstract: The lymphatic microvasculature is uniquely adapted for the continuous removal of interstitial fluid and proteins and is an important entry point for leukocytes and tumor cells. Specialized functions of lymphatics suggest differences in the molecular composition of the lymphatic and blood vascular endothelium. However, the extent to which the two cell types differ is still unclear, and few molecules that are truly specific to lymphatic endothelial cells have been identified to date. We have isolated primary lymphatic and blood microvascular endothelial cells from human skin by immunoselection with the lymphatic marker LYVE-1 and demonstrate that the two cell lineages express distinct sets of vascular markers and respond differently to growth factors and extracellular matrix. Comparative microarray analysis of gene-expression profiles revealed a number of unique molecular properties that distinguish lymphatic and blood vascular endothelium. The molecular profile of lymphatic endothelium seems to reflect characteristic functional and structural features of the lymphatic capillaries. Classification of the differentially expressed genes into functional groups revealed particularly high levels of genes implicated in protein sorting and trafficking, indicating a more active role of lymphatic endothelium in uptake and transport of molecules than previously anticipated. The identification of a large number of genes selectively expressed by lymphatic endothelium should facilitate the discovery of hitherto unknown lymphatic vessel markers and provide a basis for the analysis of the molecular mechanisms accounting for the characteristic functions of lymphatic capillaries.

Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging.

Abstract: Objective: To investigate whether plasma interleukin-6 (IL-6) is cross-sectionally related to poorer cognitive function and whether a baseline plasma IL-6 measurement can predict risk for decline in cognitive function in longitudinal follow-up of a population-based sample of nondisabled elderly people. Methods: A prospective cohort study of 779 high-functioning men and women aged 70 to 79 from the MacArthur Study of Successful Aging was conducted. Regression modeling was used to investigate whether baseline IL-6 levels (classified by tertiles) were associated with initial cognitive function and whether IL-6 levels predicted subsequent declines in cognitive function from 1988 to 1991 (2.5-year follow-up) and from 1988 to 1995 (7-year follow-up). Results: Subjects in the highest tertile for plasma IL-6 were marginally more likely to exhibit poorer baseline cognitive function (i.e., scores below the median), independent of demographic status, social status, health and health behaviors, and other physiologic variables (odds ratio [OR] = 1.46; 95% CI: 0.97, 2.20). At 2.5 years, those in both the second tertile of IL-6 (OR = 2.21; 95% CI: 1.44, 3.42) and the third tertile (OR = 2.03; 95% CI: 1.30, 3.19) were at increased risk of cognitive decline even after adjusting for all confounders. At 7 years of follow-up, only those in the highest IL-6 tertile were significantly more likely to exhibit declines in cognition (OR = 1.90; 95% CI: 1.14, 3.18) after adjustment for all confounders. Conclusions: The results suggest a relationship between elevated baseline plasma IL-6 and risk for subsequent decline in cognitive function. These findings are consistent with the hypothesized relationship between brain inflammation, as measured here by elevated plasma IL-6, and neuropathologic disorders.

Position of the American Dietetic Association: weight management.

Abstract: It is the position of the American Dietetic Association that successful weight management to improve overall health for adults requires a lifelong commitment to healthful lifestyle behaviors emphasizing sustainable and enjoyable eating practices and daily physical activity. Americans are increasing in body fat as they become more sedentary. Obesity has reached epidemic proportions and health care costs associated with weight-related illnesses have escalated. Although our knowledge base has greatly expanded regarding the complex causation of increased body fat, little progress has been made in long-term maintenance interventions with the exception of surgery. Lifestyle modifications in food intake and exercise remain the hallmarks of effective treatment, but are difficult to initiate and sustain over the long term. The dietitian can play a pivotal role in modifying weight status by helping to formulate reasonable goals which can be met and sustained with a healthy eating approach as outlined in the Dietary Guidelines for 2000. Any changes in dietary intake and exercise patterns which decrease caloric intake below energy expenditure will result in weight loss, but it is the responsibility of the dietitian to make sure the changes recommended are directed toward improved physiological and psychological health. A thorough clinical assessment should help define possible genetic, environmental, and behavioral factors contributing to weight status and is important to the formulation of an individualized intervention. The activation of treatment strategies is often limited by available resources and cost. Reimbursement by third party payers for services is limited. Health care dollars are consumed for treatment of weight-related diseases. Public policy must change if the obesity epidemic is to be stopped and appropriate weight management techniques activated.

Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial.

Abstract: Background: Hyperglycemia during acute ischemic stroke may augment brain injury, predispose to intracerebral hemorrhage (ICH), or both. Method: To analyze the relationship between admission glucose level and clinical outcomes from acute ischemic stroke, the authors performed multivariate regression analysis with the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator (rt-PA) Stroke Trial data. Neurologic improvement was defined as improvement on the NIH Stroke Scale by 4 or more points from baseline to 3 months, or a final score of zero. Favorable outcome was defined as both Glasgow Outcome score of 1 and Barthel Index 95 to 100 at 3 months. Symptomatic ICH was defined as CT-documented hemorrhage temporally related to clinical deterioration within 36 hours of treatment. Potential confounding factors were controlled, including acute treatment (rt-PA or placebo), age, baseline NIH Stroke Scale score, history of diabetes mellitus, stroke subtype, and admission blood pressure. Results: There were 624 patients enrolled within 3 hours after stroke onset. As admission glucose increased, the odds for neurologic improvement decreased (odds ratio [OR] = 0.76 per 100 mg/dL increase in admission glucose, 95% CI 0.61 to 0.95, p = 0.01). The relation between admission glucose and favorable outcome depended on admission mean blood pressure (MBP): as admission MBP increased, the odds for favorable outcome related to increasing admission glucose levels progressively decreased ( p = 0.02). As admission glucose increased, the odds for symptomatic ICH also increased (OR = 1.75 per 100 mg/dL increase in admission glucose, 95% CI 1.11 to 2.78, p = 0.02). Admission glucose level was not associated with altered effectiveness of rt-PA. Conclusions: In patients with acute ischemic stroke, higher admission glucose levels are associated with significantly lower odds for desirable clinical outcomes and significantly higher odds for symptomatic ICH, regardless of rt-PA treatment. Whether this represents a cause and effect relationship remains to be determined.