Institution
Eli Lilly and Company
Company•Indianapolis, Indiana, United States•
About: Eli Lilly and Company is a company organization based out in Indianapolis, Indiana, United States. It is known for research contribution in the topics: Population & Agonist. The organization has 17826 authors who have published 22835 publications receiving 946714 citations. The organization is also known as: Eli Lily.
Topics: Population, Agonist, Insulin, Placebo, Olanzapine
Papers published on a yearly basis
Papers
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TL;DR: Improved mechanical synchrony and function do not require electrical synchrony, and mechanical coordination plays the dominant role in global systolic improvement with either pacing approach.
Abstract: Background— Biventricular (BiV) and left ventricular (LV) pacing similarly augment systolic function in left bundle-branch block (LBBB)-failing hearts despite different electrical activation. We tested whether electrical synchrony is required to achieve mechanical synchronization and functional benefit from pacing. Methods and Results— Epicardial mapping, tagged MRI, and hemodynamics were obtained in dogs with LBBB-failing hearts during right atrial, LV, and BiV stimulation. BiV and LV both significantly improved chamber hemodynamics (eg, 25% increase in dP/dtmax and aortic pulse pressure) compared with atrial pacing-LBBB, and this improvement correlated with mechanical resynchronization. Electrical dispersion, however, decreased 13% with BiV but increased 23% with LV pacing (P<0.01). Conclusion— Improved mechanical synchrony and function do not require electrical synchrony. Mechanical coordination plays the dominant role in global systolic improvement with either pacing approach.
477 citations
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TL;DR: Olanzapine has some superior cognitive benefits relative to haloperidol and risperidone, and a larger sample replication study is necessary to confirm and generalize the observations of this study.
Abstract: Background The purpose of this investigation was to test the efficacy of novel antipsychotic medications in the treatment of cognitive impairment in early phase schizophrenia. Methods Sixty-five patients in this multicenter double-blind study were randomly assigned to olanzapine (5-20 mg), risperidone (4-10 mg), or haloperidol (5-20 mg). Standard measures of clinical and motor syndromes were administered, as well as a comprehensive battery of tests to assess (1) motor skills, (2) attention span, (3) verbal fluency and reasoning, (4) nonverbal fluency and construction, (5) executive skills, and (6) immediate recall at baseline and after 6, 30, and 54 weeks of treatment. Results The general cognitive index derived from the 6 domain scores revealed a significantly greater benefit from treatment with olanzapine relative to haloperidol and olanzapine relative to risperidone, but no significant difference was shown between risperidone and haloperidol. The improvement related to olanzapine was apparent after 6 weeks and enhanced after 30 and 54 weeks of treatment. Exploratory within-group analyses of the 6 cognitive domains after a conservative Bonferroni adjustment revealed a significant improvement with olanzapine only on the immediate recall domain, and similar analyses of the 17 individual tests revealed a significant improvement with olanzapine only on the Hooper Visual Organization Test. Conclusions These data suggest that olanzapine has some superior cognitive benefits relative to haloperidol and risperidone. A larger sample replication study is necessary to confirm and generalize the observations of this study and begin evaluation of the implications of this change to cerebral function and quality of life for people with schizophrenia.
476 citations
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Broad Institute1, Eli Lilly and Company2, University of Victoria3, Institute for Systems Biology4, University of Washington5, University of California, San Francisco6, ETH Zurich7, University of South Florida8, Vanderbilt University9, Pacific Northwest National Laboratory10, Food and Drug Administration11, Pfizer12, Fred Hutchinson Cancer Research Center13, Purdue University14, National Institutes of Health15, Centers for Disease Control and Prevention16, Johns Hopkins University17, Korea University18, Harvard University19, Emory University20, Washington University in St. Louis21, Leidos22, University of Texas Health Science Center at San Antonio23
TL;DR: A workshop was held at the National Institutes of Health with representatives from the multiple communities developing and employing targeted MS assays and defined three tiers of assays distinguished by their performance and extent of analytical characterization.
476 citations
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TL;DR: It is postulated that apoE promotes both the deposition and fibrillization of Abeta, ultimately affecting clearance of protease-resistant Abeta/apoE aggregates.
Abstract: We quantified the amount of amyloid beta-peptide (Abeta) immunoreactivity as well as amyloid deposits in a large cohort of transgenic mice overexpressing the V717F human amyloid precursor protein (APP(V717F+/-) TG mice) with no, one, or two mouse apolipoprotein E (Apoe) alleles at various ages. Remarkably, no amyloid deposits were found in any brain region of APP(V717F+/-) Apoe(-/-) TG mice as old as 22 mo of age, whereas age-matched APP(V717F +/-) Apoe(+/-) and Apoe(+/+) TG mice display abundant amyloid deposition. The amount of Abeta immunoreactivity in the hippocampus was also markedly reduced in an Apoe gene dose-dependent manner (Apoe(+/+) > Apoe(+/-) >> Apoe(-/-)), and no Abeta immunoreactivity was detected in the cerebral cortex of APP(V717F+/-) Apoe(-/-) TG mice at any of the time points examined. The absence of apolipoprotein E protein (apoE) dramatically reduced the amount of both Abeta(1-40) and Abeta(1-42) immunoreactive deposits as well as the resulting astrogliosis and microgliosis normally observed in APP(V717F) TG mice. ApoE immunoreactivity was detected in a subset of Abeta immunoreactive deposits and in virtually all thioflavine-S-fluorescent amyloid deposits. Because the absence of apoE alters neither the transcription or translation of the APP(V717F) transgene nor its processing to Abeta peptide(s), we postulate that apoE promotes both the deposition and fibrillization of Abeta, ultimately affecting clearance of protease-resistant Abeta/apoE aggregates. ApoE appears to play an essential role in amyloid deposition in brain, one of the neuropathological hallmarks of Alzheimer's disease.
475 citations
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TL;DR: LY2439821 added to oral DMARDs improved signs and symptoms of RA, with no strong adverse safety signal noted, and supports neutralization of IL-17 as a potential novel goal for the treatment of RA.
Abstract: Objective
We undertook this study to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of LY2439821, a humanized anti–interleukin-17 (anti–IL-17) monoclonal antibody, in a first in-human trial in rheumatoid arthritis (RA) patients taking oral disease-modifying antirheumatic drugs (DMARDs).
Methods
This randomized, double-blind, placebo-controlled study consisted of 2 parts. In part A, 20 patients received 1 intravenous (IV) dose of LY2439821 (0.06, 0.2, 0.6, or 2.0 mg/kg, escalating) or placebo followed by 8 weeks of evaluation. End points included safety, tolerability, and pharmacokinetics. In part B, 77 patients received 1 IV dose of LY2439821 (0.2, 0.6, or 2.0 mg/kg) or placebo every 2 weeks for a total of 5 doses, with a total evaluation period of 16 weeks. End points included safety, tolerability, pharmacokinetics/pharmacodynamics, and efficacy (Disease Activity Score in 28 joints [DAS28] and percentages of patients meeting American College of Rheumatology 20%, 50%, or 70% improvement criteria [achieving an ACR20, ACR50, or ACR70 response]). The primary efficacy end point was the DAS28 at week 10.
Results
Baseline characteristics were similar across all groups. Changes in the DAS28 were significantly greater in the 0.2 mg/kg, 2.0 mg/kg, and all-LY2439821–combined groups (−2.3, −2.4, and −2.3, respectively) than in the placebo group (−1.7) at week 10 (P ≤ 0.05), and these differences were significant as early as week 1. Percentages of ACR20, ACR50, and ACR70 responses as well as improvements in the ACR core set of measures were greater in LY2439821-treated patients than in placebo-treated patients at multiple time points. There was no apparent dose-response relationship in treatment-emergent adverse events.
Conclusion
LY2439821 added to oral DMARDs improved signs and symptoms of RA, with no strong adverse safety signal noted. This first evaluation of LY2439821 supports neutralization of IL-17 as a potential novel goal for the treatment of RA.
474 citations
Authors
Showing all 17866 results
Name | H-index | Papers | Citations |
---|---|---|---|
Mark J. Daly | 204 | 763 | 304452 |
Irving L. Weissman | 201 | 1141 | 172504 |
Eric J. Topol | 193 | 1373 | 151025 |
Tony Hunter | 175 | 593 | 124726 |
Xiang Zhang | 154 | 1733 | 117576 |
Jerrold M. Olefsky | 143 | 595 | 77356 |
Stephen F. Badylak | 133 | 530 | 57083 |
George A. Bray | 131 | 896 | 100975 |
Lloyd Paul Aiello | 131 | 506 | 85550 |
Levi A. Garraway | 129 | 366 | 99989 |
Mark Sullivan | 126 | 802 | 63916 |
James A. Russell | 124 | 1024 | 87929 |
Tony L. Yaksh | 123 | 806 | 60898 |
Elisabetta Dejana | 122 | 430 | 48254 |
Hagop S. Akiskal | 118 | 565 | 50869 |