303 results on '"William A. Knight"'
Search Results
2. Striatal oxidative damages and neuroinflammation correlate with progression and survival of Lewy body and Alzheimer diseases
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Huifangjie Li, William C Knight, and Jinbin Xu
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alzheimer disease ,disease progression ,lewy body diseases ,microglia ,neurodegeneration ,oxidative damage ,striatum ,survival ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Neurodegenerative diseases are a class of chronic and complex disorders featuring progressive loss of neurons in distinct brain areas. The mechanisms responsible for the disease progression in neurodegeneration are not fully illustrated. In this observational study, we have examined diverse biochemical parameters in the caudate and putamen of patients with Lewy body diseases (LBDs) and Alzheimer disease (AD), shedding some light on the involvement of oxidative damage and neuroinflammation in advanced neurodegeneration. We performed Spearman and Mantel-Cox analyses to investigate how oxidative stress and neuroinflammation exert comprehensive effects on disease progression and survival. Disease progression in LBDs correlated positively with poly (ADP-Ribose) and triggering receptors expressed on myeloid cell 2 levels in the striatum of LBD cohorts, indicating that potential parthanatos was a dominant feature of worsening disease progression and might contribute to switching microglial inflammatory phenotypes. Disease progression in AD corresponds negatively with 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) and myeloperoxidase concentrations in the striatum, suggesting that possible mitochondria dysfunction may be involved in the progression of AD via a mechanism of β-amyloid entering the mitochondria and subsequent free radicals generation. Patients with lower striatal 8-oxo-dG and myeloperoxidase levels had a survival advantage in AD. The age of onset also affected disease progression. Tissue requests for the postmortem biochemistry, genetics, and autoradiography studies were approved by the Washington University Alzheimer’s Disease Research Center (ADRC) Biospecimens Committee (ethics approval reference number: T1705, approval date: August 6, 2019). Recombinant DNA and Hazardous Research Materials were approved by the Washington University Environmental Health & Safety Biological Safety Committee (approval code: 3739, approval date: February 25, 2020). Radioactive Material Authorization was approved by the Washington University Environmental Health & Safety Radiation Safety Committee (approval code: 1056, approval date: September 18, 2019).
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- 2022
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3. Impact of Misting Systems on Local Particulate Matter (PM) Levels
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William L. Knight, Matthew P. Fraser, and Pierre Herckes
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Particulate matter ,Atmospheric aerosols ,Ion chromatography ,Misting systems ,Science - Abstract
Abstract In hot, arid environments, many outdoor spaces are cooled by misting systems. These systems spray a fine mist of water droplets that cool down the surrounding air through the endothermic evaporation process. As water sources often contain dissolved minerals, the evaporating droplet may leave an airborne particulate matter (PM) residue. Currently there is no information available on the impact of misting systems on localized PM concentrations. In this study, PM concentrations are found to increase by a factor of 8 from ambient levels in the vicinity of a residential misting system in controlled experiments. These experiments show PM concentrations decrease with increasing distance from misting systems. Chemical data reveal that chloride and magnesium ions may be used locally as tracers of particles from misting systems as chloride may be subject to atmospheric transformation. The average chloride concentration was 71 µg m−3 in samples collected while the misting system was operational and below the detection limit (< 8.2 µg m−3) in samples collected when the misting system was off. The average magnesium concentration was 11.7 µg m−3 in samples when misting system was on and 0.23 µg m−3 in samples when misting system was off. Ambient measurements of PM10 in public places cooled by misting ranged from 102 ± 10 µg m−3 to 1470 ± 150 µg m−3, and PM2.5 ranged from 95 ± 10 µg m−3 to 990 ± 100 µg m−3. Calculations suggest that misting systems could potentially emit PM quantities on the order of a gram per hour in the respirable particle size range.
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- 2021
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4. Human striatal glia differentially contribute to AD- and PD-specific neurodegeneration
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Jinbin Xu, Huifangjie L. Farsad, Yiran Hou, Kia Barclay, Ben Anthony Lopez, Shinnosuke Yamada, Ibrahim Olabayode Saliu, Yiming Shi, William C. Knight, Randall J. Bateman, Tammie L. S. Benzinger, Jason J. Yi, Qingyun Li, Ting Wang, Joel S. Perlmutter, John C. Morris, and Guoyan Zhao
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Aging ,Neuroscience (miscellaneous) ,Geriatrics and Gerontology ,Article - Abstract
The commonalities and differences in cell-type-specific pathways that lead to Alzheimer disease (AD) and Parkinson disease (PD) remain unknown. Here, we performed a single-nucleus transcriptome comparison of control, AD and PD striata. We describe three astrocyte subpopulations shared across different brain regions and evolutionarily conserved between humans and mice. We reveal common features between AD and PD astrocytes and regional differences that contribute toward amyloid pathology and neurodegeneration. In contrast, we found that transcriptomic changes in microglia are largely unique to each disorder. Our analysis identified a population of activated microglia that shared molecular signatures with murine disease-associated microglia (DAM) as well as disease-associated and regional differences in microglia transcriptomic changes linking microglia to disease-specific amyloid pathology, tauopathy and neuronal death. Finally, we delineate undescribed subpopulations of medium spiny neurons (MSNs) in the striatum and provide neuronal transcriptomic profiles suggesting disease-specific changes and selective neuronal vulnerability.
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- 2023
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5. The Poetical Works of William Wordsworth — Volume 5 (of 8)
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William Wordsworth, William Angus Knight
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- 2018
6. The Poetical Works of William Wordsworth — Volume 8 (of 8)
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William Wordsworth, William Angus Knight
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- 2016
7. Dopamine D1 + D3 receptor density may correlate with parkinson disease clinical features
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Pengfei Yang, Joel S. Perlmutter, Jinbin Xu, William C Knight, Huifangjie Li, John C. Morris, Yingqiu Guo, and Tammie L.S. Benzinger
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Male ,0301 basic medicine ,medicine.medical_specialty ,Substantia nigra ,Striatum ,03 medical and health sciences ,0302 clinical medicine ,Dopamine receptor D3 ,Dopamine ,Internal medicine ,Dopamine receptor D2 ,medicine ,Humans ,Dementia ,Research Articles ,Aged ,Aged, 80 and over ,Receptors, Dopamine D2 ,Dementia with Lewy bodies ,business.industry ,Receptors, Dopamine D1 ,General Neuroscience ,Receptors, Dopamine D3 ,Brain ,Parkinson Disease ,medicine.disease ,030104 developmental biology ,Endocrinology ,Dopamine receptor ,Autoradiography ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Research Article ,medicine.drug - Abstract
Objective Dopamine D2‐like receptors – mainly dopamine D2 receptors (D2R) and dopamine D3 receptors (D3R) – are believed to be greatly involved in the pathology of Parkinson disease (PD) progression. However, these receptors have not been precisely examined in PD patients. Our aim was to quantitatively calculate the exact densities of dopamine D1 receptors (D1R), D2R, and D3R in control, Alzheimer disease (AD), and Lewy body disease (LBD) patients (including PD, Dementia with Lewy bodies, and Parkinson disease dementia); and analyze the relationship between dopamine receptors and clinical PD manifestations. Methods We analyzed the densities of D1R, D2R, and D3R in the striatum and substantia nigra (SN) using a novel quantitative autoradiography procedure previously developed by our group. We also examined the expression of D2R and D3R mRNA in the striatum by in situ hybridization. Results The results showed that although no differences of striatal D1R were found among all groups; D2R was significantly decreased in the striatum of PD patients when compared with control and AD patients. Some clinical manifestations: age of onset, PD stage, dopamine responsiveness, and survival time after onset; showed a better correlation with striatal D1R + D3R densities combined compared to D1R or D3R alone. Interpretation There is a possibility that we may infer the results in diagnosis, treatment, and prognosis of PD by detecting D1R + D3R as opposed to using dopamine D1 or D3 receptors alone. This is especially true for elderly patients with low D2R expression as is common in this disease.
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- 2020
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8. Endovascular Therapy for Patients With Acute Ischemic Stroke During the COVID-19 Pandemic: A Proposed Algorithm
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Opeolu Adeoye, Achala Vagal, Pooja Khatri, Anne Housholder, Joseph P. Broderick, Jordan Bonomo, Christopher T Richards, Evan Ramser, Peyman Shirani, Aaron W. Grossman, Charles J. Prestigiacomo, Dawn Kleindorfer, William A. Knight, Matthew S. Smith, Carl J. Fichtenbaum, and Stuart Bertsch
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Advanced and Specialized Nursing ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,medicine.disease ,Endovascular therapy ,Brain ischemia ,Pneumonia ,Internal medicine ,Pandemic ,Cardiology ,Medicine ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,Acute ischemic stroke - Published
- 2020
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9. The Poetical Works of William Wordsworth — Volume 6 (of 8)
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William Wordsworth, William Angus Knight
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- 2014
10. The Poetical Works of William Wordsworth — Volume 7 (of 8)
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William Wordsworth, William Angus Knight
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- 2014
11. Journals of Dorothy Wordsworth, Vol. 2 (of 2)
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Dorothy Wordsworth, William Angus Knight
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- 2013
12. Journals of Dorothy Wordsworth, Vol. 1 (of 2)
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Dorothy Wordsworth, William Angus Knight
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- 2013
13. The Poetical Works of William Wordsworth — Volume 4 (of 8)
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William Wordsworth, William Angus Knight
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- 2010
14. The interactions of dopamine and oxidative damage in the striatum of patients with neurodegenerative diseases
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Jinbin Xu, Joel S. Perlmutter, Yingqiu Guo, William C Knight, Pengfei Yang, John C. Morris, Tammie L.S. Benzinger, and Huifangjie Li
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0301 basic medicine ,Male ,medicine.medical_specialty ,striatum ,Dopamine ,Substantia nigra ,Striatum ,oxidative damage ,Vesicular monoamine transporter 2 ,Biochemistry ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Dopamine receptor D1 ,Internal medicine ,medicine ,Humans ,Aged ,Aged, 80 and over ,biology ,Chemistry ,Dementia with Lewy bodies ,Putamen ,Neurodegeneration ,Neurodegenerative Diseases ,DNA ,Clinical Studies, Biomarkers & Imaging ,Alzheimer's disease ,Lewy body diseases ,Middle Aged ,medicine.disease ,Corpus Striatum ,3. Good health ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,biology.protein ,RNA ,Original Article ,Female ,ORIGINAL ARTICLES ,030217 neurology & neurosurgery ,medicine.drug ,Protein Binding - Abstract
The striatum with a number of dopamine containing neurons, receiving projections from the substantia nigra and ventral tegmental area; plays a critical role in neurodegenerative diseases of motor and memory function. Additionally, oxidative damage to nucleic acid may be vital in the development of age‐associated neurodegeneration. The metabolism of dopamine is recognized as one of the sources of reactive oxygen species through the Fenton mechanism. The proposed interactions of oxidative insults and dopamine in the striatum during the progression of diseases are the hypotheses of most interest to our study. This study investigated the possibility of significant interactions between these molecules that are involved in the late‐stage of Alzheimer's disease (AD), Parkinson disease (PD), Parkinson disease dementia, dementia with Lewy bodies, and controls using ELISA assays, autoradiography, and mRNA in situ hybridization assay. Interestingly, lower DNA/RNA oxidative adducts levels in the caudate and putamen of diseased brains were observed with the exception of an increased DNA oxidative product in the caudate of AD brains. Similar changes were found for dopamine concentration and vesicular monoamine transporter 2 densities. We also found that downstream pre‐synaptic dopamine D1 Receptor binding correlated with dopamine loss in Lewy body disease groups, and RNA damage and β‐site APP cleaving enzyme 1 in the caudate of AD. This is the first demonstration of region‐specific alterations of DNA/RNA oxidative damage which cannot be viewed in isolation, but rather in connection with the interrelationship between different neuronal events; chiefly DNA oxidative adducts and density of vesicular monoamine transporter 2 densities in AD and PD patients., We hypothesized the following interactions between oxidative damage and dopaminergic biological molecules. One, metabolism of dopamine yields ·OH through the Fenton Reaction and leads to oxidative damage of DNA and RNA molecules. Two, VMAT2 plays a vital anti‐oxidation role. Three, D1R plays a compensatory role against dopamine loss and takes on damage effects in the regulation of BACE1 during these biochemical events. We believe these interactions are involved in the late‐stages of neurodegenerative diseases – resulting in striatal neuron dysfunction.
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- 2019
15. Gastric tumours
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William R. Knight and William H. Allum
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General Medicine - Published
- 2019
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16. Lower Extremity Strength Is A Predictor Of Function Prior To Total Joint Arthroplasty In Veterans
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Jared M. Gollie, Erin A. Dennis, Arsalan F. Khan, William J. Knight, Obioma Ogbuawa, Melanie L. Millstein, and Latasha N. Thomas
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Physical Therapy, Sports Therapy and Rehabilitation ,Orthopedics and Sports Medicine - Published
- 2022
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17. The Song of our Syrian Guest
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William Allen Knight
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- 2004
18. The Poetical Works of William Wordsworth — Volume 3 (of 8)
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William Wordsworth, William Angus Knight
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- 2004
19. Diary of a Pedestrian in Cashmere and Thibet
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W. H. (William Henry) Knight
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- 2003
20. The Poetical Works of William Wordsworth — Volume 1 (of 8)
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William Wordsworth, William Angus Knight
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- 2003
21. Microglia Implicated in Tauopathy in the Striatum of Neurodegenerative Disease Patients from Genotype to Phenotype
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John C. Morris, Randall J. Bateman, Pengfei Yang, Huifangjie Li, Jinbin Xu, Yingqiu Guo, Tammie L.S. Benzinger, Joel S. Perlmutter, and William C Knight
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Male ,Poly Adenosine Diphosphate Ribose ,striatum ,microglia ,Striatum ,oxidative damage ,lcsh:Chemistry ,Receptors, Immunologic ,lcsh:QH301-705.5 ,Spectroscopy ,Aged, 80 and over ,Membrane Glycoproteins ,Microglia ,biology ,Putamen ,Neurodegeneration ,Nuclear Proteins ,Neurodegenerative Diseases ,Parkinson Disease ,General Medicine ,Middle Aged ,Computer Science Applications ,medicine.anatomical_structure ,Tauopathies ,Female ,Tauopathy ,Lewy Body Disease ,medicine.medical_specialty ,Genotype ,tau Proteins ,Polymorphism, Single Nucleotide ,Catalysis ,Article ,Inorganic Chemistry ,Receptors, GABA ,Alzheimer Disease ,Internal medicine ,medicine ,Translocator protein ,lewy body diseases ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,Genetic Association Studies ,Adaptor Proteins, Signal Transducing ,Aged ,Peroxidase ,Lewy body ,TREM2 ,Tumor Suppressor Proteins ,Organic Chemistry ,tauopathy ,medicine.disease ,Corpus Striatum ,Endocrinology ,lcsh:Biology (General) ,lcsh:QD1-999 ,nervous system ,Case-Control Studies ,biology.protein - Abstract
We found interactions between dopamine and oxidative damage in the striatum involved in advanced neurodegeneration, which probably change the microglial phenotype. We observed possible microglia dystrophy in the striatum of neurodegenerative brains. To investigate the interactions between oxidative damage and microglial phenotype, we quantified myeloperoxidase (MPO), poly (ADP-Ribose) (PAR), and triggering receptors expressed on myeloid cell 2 (TREM2) using enzyme-linked immunosorbent assay (ELISA). To test the correlations of microglia dystrophy and tauopathy, we quantified translocator protein (TSPO) and tau fibrils using autoradiography. We chose the caudate and putamen of Lewy body diseases (LBDs) (Parkinson&rsquo, s disease, Parkinson&rsquo, s disease dementia, and Dementia with Lewy body), Alzheimer&rsquo, s disease (AD), and control brains and genotyped for TSPO, TREM2, and bridging integrator 1 (BIN1) genes using single nucleotide polymorphisms (SNP) assays. TREM2 gene variants were absent across all samples. However, associations between TSPO and BIN1 gene polymorphisms and TSPO, MPO, TREM2, and PAR level variations were found. PAR levels reduced significantly in the caudate of LBDs. TSPO density and tau fibrils decreased remarkably in the striatum of LBDs but increased in AD. Oxidative damage, induced by misfolded tau proteins and dopamine metabolism, causes microglia dystrophy or senescence during the late stage of LBDs. Consequently, microglia dysfunction conversely reduces tau propagation. The G allele of the BIN1 gene is a potential risk factor for tauopathy.
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- 2020
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22. KEY Careers: Increasing Retention and Graduation Rates With Career Interventions
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William E. Knight, Jim McAtee, Karley Clayton, and Roger D. Wessel
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Organizational Behavior and Human Resource Management ,Medical education ,Intervention program ,education ,05 social sciences ,Psychological intervention ,050301 education ,Education ,050106 general psychology & cognitive sciences ,Intervention (counseling) ,Key (cryptography) ,0501 psychology and cognitive sciences ,Psychology ,0503 education ,General Psychology ,Applied Psychology ,Graduation ,Career development - Abstract
The purpose of the study was to investigate how promoting participation in KEY Careers, a career intervention program available to all incoming matriculates, influenced 1-year retention and 4-year graduation rates compared to nonparticipants at a singular institution. Archival data of 14,099 matriculates from the 2011–2014 freshman fall cohorts were utilized to examine the significance of a career intervention program on 1-year retention and 4-year graduation rates for various student demographics through an analysis of covariance. The results of this study suggest student participation in a career intervention program causes a statistically significant increase in 1-year retention and 4-year graduation rates regardless of gender or race. The discussion of this study is focused on why vocational identity development is significant at the beginning of the college experience and includes suggestions for how university administration can proactively infuse career development into their practices to benefit students of all backgrounds.
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- 2018
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23. A Primer on Employment and Intellectual Property Law: Legal Guidance for Supervisors of Assessment and Institutional Research Staff
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William E. Knight and Elizabeth Timmerman Lugg
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ComputingMilieux_THECOMPUTINGPROFESSION ,Higher education ,business.industry ,media_common.quotation_subject ,05 social sciences ,050301 education ,Intellectual property ,Public relations ,Institutional research ,Political science ,0502 economics and business ,Institution ,050207 economics ,business ,0503 education ,media_common - Abstract
Institutional research (IR) leaders rely on staff members to accomplish office missions and support institutional decisions. Like any supervisors in higher education, IR leaders must be familiar with a host of employment and intellectual property laws that guide the institution/employee relationship. This chapter offers insights into specific issues IR supervisors and staff members should heed.
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- 2017
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24. Abstract WMP102: Pilot Study of a Non-invasive Radiofrequency Method to Monitor Intracranial Hemorrhage: A First-in-Human Study
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George J. Shaw, William A. Knight, Opeolu Adeoye, Matthew L. Flaherty, and Joseph J. Korfhagen
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Advanced and Specialized Nursing ,medicine.medical_specialty ,business.industry ,Non invasive ,Medicine ,cardiovascular diseases ,Neurology (clinical) ,Radiology ,First in human ,Cardiology and Cardiovascular Medicine ,business - Abstract
Introduction: Intracerebral hemorrhage (ICH) is a devastating form of stroke. Hemorrhage expansion after ICH occurs in ~40% of patients and leads to worse outcomes. Currently, ICH patients are monitored for hemorrhage expansion by neurologic exam and head CT. CT studies are a source of radiation exposure and can require transporting the patient out of the ICU. There is a clinical need for a non-invasive bedside monitor of ICH. Methods: A radiofrequency based monitor (RFM) was developed as a non-invasive method to monitor ICH at the bedside. The RFM consists of a 9-antenna array mounted around the head, cables, and driving electronics. A 913 MHz signal is transmitted from a given antenna, crosses the brain, and is received by the remaining 8 antennae. A complete measurement consists of one cycle with all antenna serving as the transmitting antenna. As the signal traverses the brain, it is partially scattered and absorbed by the ICH, thus changing the signal at the receiving antennae. The altered signal can be compared to signals at earlier times to detect changes induced by ICH expansion. Based upon pre-clinical work it was hypothesized that ICH expansion of ≥3 ml would be detected by the RFM. The RFM device was approved for human study under an IDE from the FDA. The device was tested on 10 ICH subjects admitted within 24 hours of stroke onset. All subjects received a baseline head CT and a repeat head CT at 12 (+/- 6) hours. ICH volumes were determined by a blinded neuroradiologist. Subjects were scanned with the device every 10 minutes. Results: Data from one subject was lost due to user error. Among the remaining nine, two experienced hemorrhage expansion of ≥ 3ml (3 and 8.2 ml respectively). The RFM readings were 100% concordant with CT scans in identifying presence and absence of hemorrhage expansion. The figure shows monitor readings from a subject with expansion. Conclusion: The RFM may be useful in detection of real-time hemorrhage expansion in ICH patients. A pivotal clinical study is planned.
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- 2020
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25. The ED-SED Study: a multicenter, prospective cohort study of practice patterns and clinical outcomes associated with Emergency Department SEDation for mechanically ventilated patients
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Matthew Dettmer, Catherine L. Hough, Michael S. Avidan, Chris Carpenter, Carrie E. Harvey, Zaffer Qasim, Sharukh Lokhandwala, Marin H. Kollef, Nicholas M. Mohr, Colin Gibson, Joseph E. Tonna, Benjamin S. Bassin, Opeolu Adeoye, Robert J. Stephens, Frederick Lin, Stacy Marshall, Brian W. Roberts, Yan Yan, Jarrod Mosier, William A. Knight, Brian J. Levine, Jayna Gardner-Gray, James Dargin, Munish Goyal, Ryan D Pappal, Nicholas J. Johnson, Robert Alunday, Rachel E. Tsolinas, Fraser Mackay, and Brian M. Fuller
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Male ,medicine.medical_specialty ,Sedation ,Hospital mortality ,Critical Care and Intensive Care Medicine ,Severity of Illness Index ,Article ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Severity of illness ,medicine ,Humans ,Hypnotics and Sedatives ,Hospital Mortality ,Coma ,Prospective cohort study ,Practice patterns ,business.industry ,Delirium ,030208 emergency & critical care medicine ,Emergency department ,Middle Aged ,Respiration, Artificial ,humanities ,United States ,Intensive Care Units ,030228 respiratory system ,Multicenter study ,Emergency medicine ,Female ,medicine.symptom ,Deep Sedation ,business ,Emergency Service, Hospital ,Cohort study - Abstract
To characterize emergency department sedation practices in mechanically ventilated patients, and test the hypothesis that deep sedation in the emergency department is associated with worse outcomes.Multicenter, prospective cohort study.The emergency department and ICUs of 15 medical centers.Mechanically ventilated adult emergency department patients.None.All data involving sedation (medications, monitoring) were recorded. Deep sedation was defined as Richmond Agitation-Sedation Scale of -3 to -5 or Sedation-Agitation Scale of 2 or 1. A total of 324 patients were studied. Emergency department deep sedation was observed in 171 patients (52.8%), and was associated with a higher frequency of deep sedation in the ICU on day 1 (53.8% vs 20.3%; p0.001) and day 2 (33.3% vs 16.9%; p = 0.001), when compared to light sedation. Mean (SD) ventilator-free days were 18.1 (10.8) in the emergency department deep sedation group compared to 20.0 (9.8) in the light sedation group (mean difference, 1.9; 95% CI, -0.40 to 4.13). Similar results according to emergency department sedation depth existed for ICU-free days (mean difference, 1.6; 95% CI, -0.54 to 3.83) and hospital-free days (mean difference, 2.3; 95% CI, 0.26-4.32). Mortality was 21.1% in the deep sedation group and 17.0% in the light sedation group (between-group difference, 4.1%; odds ratio, 1.30; 0.74-2.28). The occurrence rate of acute brain dysfunction (delirium and coma) was 68.4% in the deep sedation group and 55.6% in the light sedation group (between-group difference, 12.8%; odds ratio, 1.73; 1.10-2.73).Early deep sedation in the emergency department is common, carries over into the ICU, and may be associated with worse outcomes. Sedation practice in the emergency department and its association with clinical outcomes is in need of further investigation.
- Published
- 2019
26. Microglia implicated in tau proteostasis disturbances in the striatum of neurodegenerative disease patients from genotype to phenotype
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William C Knight, H. Li, P. Yang, and J. Xu
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medicine.anatomical_structure ,Proteostasis ,Neurology ,Microglia ,Immunology ,medicine ,Neurology (clinical) ,Disease ,Striatum ,Geriatrics and Gerontology ,Biology ,Genotype to phenotype - Published
- 2020
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27. Mfn2 agonists reverse mitochondrial defects in preclinical models of Charcot Marie Tooth disease type 2A
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Nikolaos Biris, Agostinho G. Rocha, James W. Janetka, Justin M. Alberti, Andrzej M. Krezel, Jeanne M. Rumsey, Evripidis Gavathiotis, Richard N. Kitsis, Antonietta Franco, Emmanouil Zacharioudakis, Daria Mochly-Rosen, Robert H. Baloh, Raymond R. Townsend, William C Knight, and Gerald W. Dorn
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0301 basic medicine ,Agonist ,Threonine ,Mitochondrial Diseases ,medicine.drug_class ,Glutamine ,Mutant ,MFN2 ,PINK1 ,Arginine ,Article ,GTP Phosphohydrolases ,Mitochondrial Proteins ,Small Molecule Libraries ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Methionine ,Charcot-Marie-Tooth Disease ,medicine ,Animals ,Humans ,Fragmentation (cell biology) ,Phosphorylation ,Multidisciplinary ,Chemistry ,Depolarization ,Sciatic Nerve ,Axons ,Cell biology ,Mitochondria ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,mitochondrial fusion ,Amino Acid Substitution ,Drug Design ,Oligopeptides ,Protein Kinases ,030217 neurology & neurosurgery - Abstract
An innovative approach for a rare disease Charcot-Marie-Tooth disease type 2A (CMT2A) is a rare, inherited neurodegenerative condition. Affected individuals develop severe progressive muscle weakness, motor deficits, and peripheral neuropathy. Although defects in the gene encoding mitofusin 2 (MFN2) are known to cause CMT2A, the disease remains incurable. Rocha et al. identified specific MFN2 residues contributing to the disease and developed a class of MFN2-agonist drugs. The small molecules restored mitochondrial fusion and activity in the sciatic nerves of mice; they may also help in other diseases linked to mitochondrial trafficking. Science , this issue p. 336
- Published
- 2018
28. Persistence to Graduation for Students With Disabilities: Implications for Performance-Based Outcomes
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William E. Knight, Larry Markle, and Roger D. Wessel
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Persistence (psychology) ,030506 rehabilitation ,Medical education ,education ,05 social sciences ,050301 education ,Education ,Disadvantaged ,03 medical and health sciences ,Incentive ,State policy ,Pedagogy ,Statistical analysis ,0305 other medical science ,Psychology ,0503 education ,Graduation - Abstract
The study sought to determine whether students with disabilities are disadvantaged because of state and institutional performance-based policies providing incentives for 4-year graduation. In a longitudinal study of 32,187 students at a Midwestern Research University, the retention and graduation rates, and mean years to graduation, of students with disabilities were compared with students without disabilities. This study demonstrated that the presence of a disability does not negatively influence eventual graduation, but that it does influence the amount of time to degree completion. However, as the transition to college for students with disabilities can be more difficult, it is important that the institution has interventions in place to assist students with disabilities to assimilate into college. The discussion focuses on policy and practice implications linked to performance-based outcomes related to students with disabilities.
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- 2016
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29. Institutional Research and Planning in Higher Education: Global Contexts and Themes by Karen L. Webber and Angel J. Calderon
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William E. Knight
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Institutional research ,Higher education ,business.industry ,Sociology ,Social science ,business ,Education - Published
- 2016
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30. Emergency Neurological Life Support: Traumatic Spine Injury
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Deborah M. Stein, Jose A. Pineda, Vincent Roddy, and William A. Knight
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Life Support Care ,Neurology ,Spinal Injuries ,Humans ,Neurology (clinical) ,Critical Care and Intensive Care Medicine ,Emergency Treatment ,Spinal Cord Injuries - Abstract
Traumatic spine injuries (TSIs) carry significantly high risks of morbidity, mortality, and exorbitant health care costs from associated medical needs following injury. For these reasons, TSI was chosen as an ENLS protocol. This article offers a comprehensive review on the management of spinal column injuries using the best available evidence. Alhough the review focuses primarily on cervical spinal column injuries, thoracolumbar injuries are briefly discussed as well. The initial emergency department clinical evaluation of possible spinal fractures and cord injuries, along with the definitive early management of confirmed injuries, is also covered.
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- 2015
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31. Electroencephalography findings in patients presenting to the ED for evaluation of seizures
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Opeolu Adeoye, Christopher J. Lindsell, Kimberly W. Hart, William A. Knight, and Pooja Kadambi
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Male ,medicine.medical_specialty ,Time Factors ,animal diseases ,Status epilepticus ,Electroencephalography ,Article ,Diagnosis, Differential ,Status Epilepticus ,Seizures ,medicine ,Humans ,heterocyclic compounds ,In patient ,Retrospective Studies ,medicine.diagnostic_test ,Extramural ,business.industry ,Retrospective cohort study ,General Medicine ,Emergency department ,Middle Aged ,nervous system diseases ,nervous system ,Anesthesia ,Emergency medicine ,Emergency Medicine ,Female ,medicine.symptom ,Emergency Service, Hospital ,business - Abstract
Status epilepticus is a life-threatening, time-sensitive emergency. Acquiring an electroencephalogram (EEG) in the emergency department (ED) could impact therapeutic and disposition decisions for patients with suspected status epilepticus.The objective of this study is to estimate the proportion of EEGs diagnostic for seizures in patients presenting to an ED with a complaint of seizures.This retrospective chart review included adults presenting to the ED of an urban, academic, tertiary care hospital with suspected seizures or status epilepticus, who received an EEG within 24 hours of hospital admission. Data abstraction was performed by a single, trained, nonblinded abstractor. Seizures were defined as an epileptologist's diagnosis of either seizures or status epilepticus on EEG. The proportion of patients with seizures is given with confidence interval95 (CI95).Of 120 included patients, 67 (56%) had a history of epilepsy. Mean age was 52 years (SD, 16), 58% were White, and 61% were male. Within 24 hours, 3% had an EEG diagnostic for seizures. Electroencephalogram was obtained in the ED in 32 (27%) of 120 (CI95, 19%-35%), and 2 (6%) of 32 (CI95, 1%-19%) had seizures. Electroencephalogram was performed inpatient for 88 (73%) of 120 (CI95, 65%-81%), and 2 (2%) of 88 (CI95, 0.5%-7.1%) had seizures.Only 3% of ED patients with suspected seizures or status epilepticus had EEG confirmation of seizures within 24 hours. Early EEG acquisition in the ED may identify a group of patients amenable to ED observation and subsequent discharge from the hospital.
- Published
- 2015
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32. Emergency Neurological Life Support: Traumatic Spine Injury
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Deborah M. Stein and William A. Knight
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Canada ,Emergency Medical Services ,Critical Care and Intensive Care Medicine ,Life Support Care ,03 medical and health sciences ,0302 clinical medicine ,Neurology ,Spinal Injuries ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Humans ,Neurology (clinical) ,030217 neurology & neurosurgery ,Algorithms ,Spinal Cord Injuries - Abstract
Traumatic spine injuries (TSIs) carry significantly high risks of morbidity, mortality, and exorbitant health care costs from associated medical needs following injury. For these reasons, TSI was chosen as an ENLS protocol. This article offers a comprehensive review on the management of spinal column injuries using the best available evidence. Though the review focuses primarily on cervical spinal column injuries, thoracolumbar injuries are briefly discussed as well. The initial emergency department (ED) clinical evaluation of possible spinal fractures and cord injuries, along with the definitive early management of confirmed injuries, are also covered.
- Published
- 2017
33. [P4–570]: A DOUBLE‐BLIND PLACEBO‐CONTROLLED CROSS‐OVER CLINICAL TRIAL OF DONEPEZIL IN POSTERIOR CORTICAL ATROPHY DUE TO UNDERLYING ALZHEIMER's DISEASE: DONIPAD STUDY
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Sebastian J. Crutch, Riitta Kukkastenvehmas, Dawn Cutler, Elizabeth K. Warrington, Suzie Barker, William D. Knight, Basil H. Ridha, Douglas Jane, Chris Frost, Martin N. Rossor, and Norah Epie
- Subjects
Cross over ,medicine.medical_specialty ,Epidemiology ,business.industry ,Health Policy ,Posterior cortical atrophy ,Disease ,Placebo ,Double blind ,Clinical trial ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Internal medicine ,Medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,business ,Donepezil ,Neuroscience ,medicine.drug - Published
- 2017
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34. DPP4 inhibition attenuates filtration barrier injury and oxidant stress in the zucker obese rat
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Thomas Klein, James R. Sowers, Javad Habibi, Ravi Nistala, Vincent G. DeMarco, Adam Whaley-Connell, Tamara S. Hancock, Melvin R. Hayden, Alex Meuth, William C Knight, and Annayya R. Aroor
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medicine.medical_specialty ,Kidney ,Nutrition and Dietetics ,Proteinuria ,biology ,Chemistry ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,medicine.disease ,Nephrin ,Endocrinology ,medicine.anatomical_structure ,Glomerulopathy ,Internal medicine ,medicine ,Glomerular Filtration Barrier ,biology.protein ,Endothelial dysfunction ,medicine.symptom ,Glomerular hyperfiltration ,Dipeptidyl peptidase-4 - Abstract
Objective Obesity-related glomerulopathy is characterized initially by glomerular hyperfiltration with hypertrophy and then development of proteinuria. Putative mechanisms include endothelial dysfunction and filtration barrier injury due to oxidant stress and immune activation. There has been recent interest in targeting dipeptidyl peptidase 4 (DPP4) enzyme due to increasing role in non-enzymatic cellular processes. Methods The Zucker obese (ZO) rat (aged 8 weeks) fed a normal chow or diet containing the DPP4 inhibitor linagliptin for 8 weeks (83 mg/kg rat chow) was utilized. Results Compared to lean controls, there were increases in plasma DPP4 activity along with proteinuria in ZO rats. ZO rats further displayed increases in glomerular size and podocyte foot process effacement. These findings occurred in parallel with decreased endothelial stromal-derived factor-1α (SDF-1α), increased oxidant markers, and tyrosine phosphorylation of nephrin and serine phosphorylation of the mammalian target of rapamycin (mTOR). DPP4 inhibition improved proteinuria along with filtration barrier remodeling, circulating and kidney tissue DPP4 activity, increased active glucagon like peptide-1 (GLP-1) as well as SDF-1α, and improved oxidant markers and the podocyte-specific protein nephrin. Conclusions These data support a role for DPP4 in glomerular filtration function and targeting DPP4 with inhibition improves oxidant stress-related glomerulopathy and associated proteinuria.
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- 2014
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35. The incidence of seizures in patients undergoing therapeutic hypothermia after resuscitation from cardiac arrest
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Opeolu Adeoye, Christopher J. Lindsell, Kimberly W. Hart, Jerzy P. Szaflarski, Michael Privitera, Jordan Bonomo, Shaun Keegan, David M. Ficker, and William A. Knight
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Adult ,Male ,Emergency Medical Services ,Resuscitation ,medicine.medical_treatment ,Conscious Sedation ,Status epilepticus ,Article ,law.invention ,Electrocardiography ,Epilepsy ,Trauma Centers ,Hypothermia, Induced ,Seizures ,law ,Confidence Intervals ,Humans ,Medicine ,Glasgow Coma Scale ,Cardiopulmonary resuscitation ,Coma ,Aged ,Aged, 80 and over ,business.industry ,Arrhythmias, Cardiac ,Electroencephalography ,Middle Aged ,Hypothermia ,medicine.disease ,Intensive care unit ,Cardiopulmonary Resuscitation ,Heart Arrest ,Treatment Outcome ,Neurology ,Data Interpretation, Statistical ,Anesthesia ,Female ,Neurology (clinical) ,medicine.symptom ,business - Abstract
Summary Study objective Non-convulsive seizures/status epilepticus occur in approximately 20% of comatose, non-cardiac arrest intensive care unit (ICU) patients, and are associated with increased mortality. The prevalence and clinical significance of seizures in comatose survivors of cardiac arrest undergoing therapeutic hypothermia is not well described. Methods At this urban level I trauma center, every patient undergoing therapeutic hypothermia is monitored with continuous video encephalography (cvEEG). We abstracted medical records for all cardiac arrest patients treated with therapeutic hypothermia during 2010. Clinical data were extracted in duplicate. cvEEGs were independently reviewed for seizures by two board-certified epileptologists. Results There were 33 patients treated with therapeutic hypothermia after cardiac arrest in 2010 who met inclusion criteria for this study. Median age was 58 (range 28–86 years), 63% were white, 55% were male, and 9% had a history of seizures or epilepsy. During cooling, seizures occurred in 5/33 patients (15%, 95%CI 6%–33%). 11/33 patients (33%, 95% CI 19%–52%) had seizures at some time during hospitalization. 13/33 (39%) survived to discharge and of these, 7/13 (54%) survived to 30 days. 9/11 patients with seizures died during hospitalization, compared with 11/22 patients without seizures (82% vs. 50%; difference 32%, CI 95 1%–63%). No patient with seizures was alive at 30 days. Conclusions Seizures are common in comatose patients treated with therapeutic hypothermia after cardiac arrest. All patients with seizures were deceased within 30 days of discharge. Routine use of EEG monitoring could assist in early detection of seizures in this patient population, providing an opportunity for intervention to potentially improve outcomes.
- Published
- 2013
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36. Overweight female rats selectively breed for low aerobic capacity exhibit increased myocardial fibrosis and diastolic dysfunction
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Irina Mugerfeld, Steven L. Britton, Mona Garro, Vincent G. DeMarco, James R. Sowers, Megan S. Johnson, William C Knight, Lauren G. Koch, Lakshmi Pulakat, Melvin R. Hayden, and Lixin Ma
- Subjects
Male ,Cardiac Catheterization ,medicine.medical_specialty ,Physiology ,Blotting, Western ,Blood Pressure ,Citrate (si)-Synthase ,AMP-Activated Protein Kinases ,Overweight ,Biology ,Running ,Oxygen Consumption ,Integrative Cardiovascular Physiology and Pathophysiology ,Microscopy, Electron, Transmission ,Diastole ,Fibrosis ,Endurance training ,Physical Conditioning, Animal ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Telemetry ,Ventricular remodeling ,Aerobic capacity ,Ventricular Remodeling ,Myocardium ,Hemodynamics ,Baroreflex ,medicine.disease ,Immunohistochemistry ,Magnetic Resonance Imaging ,Obesity ,Aerobiosis ,Rats ,Blood pressure ,Endocrinology ,Heart Function Tests ,Physical Endurance ,Female ,Hydroxymethylglutaryl CoA Reductases ,Myocardial fibrosis ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,human activities - Abstract
The statistical association between endurance exercise capacity and cardiovascular disease suggests that impaired aerobic metabolism underlies the cardiovascular disease risk in men and women. To explore this connection, we applied divergent artificial selection in rats to develop low-capacity runner (LCR) and high-capacity runner (HCR) rats and found that disease risks segregated strongly with low running capacity. Here, we tested if inborn low aerobic capacity promotes differential sex-related cardiovascular effects. Compared with HCR males (HCR-M), LCR males (LCR-M) were overweight by 34% and had heavier retroperitoneal, epididymal, and omental fat pads; LCR females (LCR-F) were 20% heavier than HCR females (HCR-F), and their retroperitoneal, but not perireproductive or omental, fat pads were heavier as well. Unlike HCR-M, blood pressure was elevated in LCR-M, and this was accompanied by left ventricular (LV) hypertrophy. Like HCR-F, LCR-F exhibited normal blood pressure and LV weight as well as increased spontaneous cage activity compared with males. Despite normal blood pressures, LCR-F exhibited increased myocardial interstitial fibrosis and diastolic dysfunction, as indicated by increased LV stiffness, a decrease in the initial filling rate, and an increase in diastolic relaxation time. Although females exhibited increased arterial stiffness, ejection fraction was normal. Increased interstitial fibrosis and diastolic dysfunction in LCR-F was accompanied by the lowest protein levels of phosphorylated AMP-actived protein kinase [phospho-AMPK (Thr172)] and silent information regulator 1. Thus, the combination of risk factors, including female sex, intrinsic low aerobic capacity, and overweightness, promote myocardial stiffness/fibrosis sufficient to induce diastolic dysfunction in the absence of hypertension and LV hypertrophy.
- Published
- 2012
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37. Ground Emergency Medical Services Requests for Helicopter Transfer of ST-segment Elevation Myocardial Infarction Patients Decrease Medical Contact to Balloon Times in Rural and Suburban Settings
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April Shackleford, Matthew Gunderman, Kimberly W. Hart, Christopher J. Lindsell, William A. Knight, Jared C. Bentley, Christopher N. Miller, Jason T. McMullan, William R. Hinckley, Gregory J. Fermann, Todd Davis, and W. Brian Gibler
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Percutaneous coronary intervention ,Retrospective cohort study ,General Medicine ,medicine.disease ,Confidence interval ,Emergency medicine ,Conventional PCI ,Emergency Medicine ,medicine ,Emergency medical services ,ST segment ,Myocardial infarction ,Medical emergency ,business ,Patient transfer - Abstract
ACADEMIC EMERGENCY MEDICINE 2012; 19:153–160 © 2012 by the Society for Academic Emergency Medicine Abstract Objectives: ST-segment elevation myocardial infarction (STEMI) care is time-dependent. Many STEMI patients require interhospital helicopter transfer for percutaneous coronary intervention (PCI) if ground emergency medical services (EMS) initially transport the patient to a non-PCI center. This investigation models potential time savings of ground EMS requests for helicopter EMS (HEMS) transport of a STEMI patient directly to a PCI center, rather than usual transport to a local hospital with subsequent transfer. Methods: Data from a multicenter retrospective chart review of STEMI patients transferred for primary PCI by a single HEMS agency over 12 months were used to model medical contact to balloon times (MCTB) for two scenarios: a direct-to-scene HEMS response and hospital rendezvous after ground EMS initiation of transfer. Results: Actual MCTB median time for 36 hospital-initiated transfers was 160 minutes (range = 116 to 321 minutes). Scene response MCTB median time was estimated as 112 minutes (range = 69 to 187 minutes). The difference in medians was 48 minutes (95% confidence interval [CI] = 33 to 62 minutes). Hospital rendezvous MCTB median time was estimated as 113 minutes (range = 74 to 187 minutes). The difference in medians was 47 minutes (95% CI = 32 to 62 minutes). No patient had an actual MCTB time of less than 90 minutes; in the scene response and hospital rendezvous scenarios, 2 of 36 (6%) and 3 of 36 (8%), respectively, would have had MCTB times under 90 minutes. Conclusions: In this setting, ground EMS initiation of HEMS transfers for STEMI patients has the potential to reduce MCTB time, but most patients will still not achieve MCTB time of less than 90 minutes.
- Published
- 2012
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38. Genetic encoding of the post-translational modification 2-hydroxyisobutyryl-lysine
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William A. Knight and T. Ashton Cropp
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Lysine-tRNA Ligase ,Green Fluorescent Proteins ,Molecular Sequence Data ,Lysine ,Lysine—tRNA ligase ,medicine.disease_cause ,Bioinformatics ,Biochemistry ,Article ,Substrate Specificity ,Amino Acyl-tRNA Synthetases ,Escherichia coli ,medicine ,Amino Acid Sequence ,Physical and Theoretical Chemistry ,Peptide sequence ,chemistry.chemical_classification ,Escherichia coli Proteins ,Organic Chemistry ,Genetic code ,Amino acid ,chemistry ,Methanosarcina ,Posttranslational modification ,Protein Processing, Post-Translational - Abstract
We report the synthesis and genetic encoding of a recently discovered post-translational modification, 2-hydroxyisobutyryl-lysine, to the genetic code of E. coli. The production of homogeneous proteins containing this amino acid will facilitate the study of modification in full-length proteins.
- Published
- 2015
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39. Helicopter Scene Response for a STEMI Patient Transported Directly to the Cardiac Catheterization Laboratory
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Jason T. McMullan, William A. Knight, Christopher Palmer, Matt Gunderman, and William R. Hinckley
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Adult ,Cardiac Catheterization ,Chest Pain ,Vasodilator Agents ,medicine.medical_treatment ,Myocardial Infarction ,Emergency Nursing ,Electrocardiography ,Nitroglycerin ,Emergency medical services ,medicine ,Humans ,Medical history ,cardiovascular diseases ,Crushing chest pain ,Myocardial infarction ,Ohio ,Cardiac catheterization ,Aspirin ,Morphine ,business.industry ,Percutaneous coronary intervention ,Thrombosis ,Air Ambulances ,medicine.disease ,Coronary Vessels ,Ondansetron ,Stemi patient ,Analgesics, Opioid ,Oxygen ,Treatment Outcome ,Anti-Anxiety Agents ,Conventional PCI ,Emergency Medicine ,Female ,Stents ,Medical emergency ,business - Abstract
At 2:10 pm, a 40-year-old Caucasian woman with no known medical history called 911 complaining of substernal, crushing chest pain that had started 2 to 3 hours before she called emergency medical services (EMS). EMS arrived at 2:24 pm and obtained a 12-lead electrocardiogram (ECG) diagnostic of ST-segment elevation myocardial infarction (STEMI) at 2:36 pm. University Air Care was requested by local EMS at 2:42 pm to respond directly to the cardiac scene in rural Ohio for rapid transport to a facility capable of performing percutaneous coronary intervention (PCI). The closest PCI-capable facility was approximately 35 minutes away by ground or 13 minutes by air. The closest non-PCI hospital was approximately 20 minutes away by ground (Fig. 1).
- Published
- 2011
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40. Administrators' decisions about resource allocation
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Richard P. Kennell, Milton D. Hakel, William E. Knight, and John W. Folkins
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College English ,Public Administration ,Higher education ,business.industry ,Context effect ,Primary education ,Public relations ,Teacher education ,Education ,Resource allocation ,Academic administration ,Social science ,business ,Discipline - Abstract
Do academic administrators make decisions about resource allocation differently depending on the discipline receiving the funding? Does an administrator's academic identity influence these decisions? This study explored those questions with a sample of 1,690 academic administrators at doctoral-research universities. Participants used fictional summaries of academic program reviews. The summaries had scenarios of increased-resources and shrinking-resources involving hard versus soft and pure versus applied disciplines. Administrators were forced to choose among them for funding decisions. Results showed that a hard-applied discipline, mechanical engineering, was evaluated as significantly more likely to receive additional resources and to be exempted from cuts than examples from other disciplinary groups: physics, English, and elementary education. Decisions varied significantly with participants' home disciplines, but not their longevity in academe or in administration.
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- 2011
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41. A Matched Comparison of Eptifibatide Plus rt-PA Versus rt-PA Alone in Acute Ischemic Stroke
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Arthur M. Pancioli, William A. Knight, Opeolu Adeoye, Heidi Sucharew, Clear-Er Investigators, Jane C. Khoury, Joseph P. Broderick, and Pamela Schmit
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Male ,medicine.medical_specialty ,Time Factors ,Eptifibatide ,Severity of Illness Index ,Article ,Brain Ischemia ,law.invention ,Disability Evaluation ,Bolus (medicine) ,Double-Blind Method ,Fibrinolytic Agents ,Randomized controlled trial ,Risk Factors ,Modified Rankin Scale ,law ,Internal medicine ,medicine ,Humans ,Thrombolytic Therapy ,Infusions, Intravenous ,Aged ,business.industry ,Rehabilitation ,Odds ratio ,Middle Aged ,Recombinant Proteins ,United States ,Confidence interval ,Surgery ,Stroke ,Clinical trial ,Regimen ,Treatment Outcome ,Tissue Plasminogen Activator ,Drug Therapy, Combination ,Female ,Neurology (clinical) ,Peptides ,Cardiology and Cardiovascular Medicine ,business ,Intracranial Hemorrhages ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
Background The Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue Plasminogen Activator (rt-PA) in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER) trial found that intravenous rt-PA plus eptifibatide (combination arm) in acute ischemic stroke (AIS) was safe and had a direction of effect that would justify a phase III trial. CLEAR-ER had unanticipated imbalances between treatment groups. We compared the rates of symptomatic intracranial hemorrhage (sICH) and good outcomes for combination therapy patients in the CLEAR-ER trial to a matched cohort of rt-PA patients from the National Institute of Neurological Disorders and Stroke (NINDS) trial. Methods CLEAR-ER was a multicenter, double-blind, randomized study; rt-PA–eligible AIS patients were randomized to .6 mg/kg rt-PA plus eptifibatide (135 mcg/kg bolus and .75mcg/kg/min two-hour infusion) versus standard rt-PA (.9 mg/kg). For this analysis, we matched 1:1 CLEAR-ER combination therapy patients with rt-PA arm NINDS trial patients. Patients were matched by age, gender, race, baseline modified Rankin Scale score, baseline National Institutes of Health Stroke Scale (NIHSS) score, and stroke onset to rt-PA time. Results Fifty-four matches were made. One (1.8%) sICH occurred in each group (odds ratio [OR] 1.00, 95% confidence interval [CI] .01-78.50). At 90 days, 51.8% of the CLEAR-ER group had good outcomes versus 46.3% in the NINDS rt-PA group (OR 1.30, 95% CI .57-2.96). For subjects with baseline NIHSS score > 12 (CLEAR-ER median NIHSS score), 38.5% of the CLEAR-ER group had good outcomes versus 23.1% in the NINDS group (OR 2.33, 95% CI .60-9.02). Conclusions The safety and direction of effect of eptifibatide plus rt-PA were confirmed. A phase III trial is needed to determine the efficacy of eptifibatide plus rt-PA for improving long-term outcomes after AIS.
- Published
- 2014
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42. Time-critical neurological emergencies: the unfulfilled role for point-of-care testing
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Jason T. McMullan, Arthur M. Pancioli, William A. Knight, Fred R. Beyette, and Joseph F. Clark
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medicine.medical_specialty ,Neurology ,Subarachnoid hemorrhage ,Traumatic brain injury ,Point-of-care testing ,Review Article ,Disease ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Intervention (counseling) ,Diagnostic techniques, neurological ,medicine ,Intensive care medicine ,Spinal cord injury ,business.industry ,Brain ,medicine.disease ,3. Good health ,Critical care ,Emergency medicine ,Emergency Medicine ,Point-of-care systems ,business ,Meningitis ,030217 neurology & neurosurgery - Abstract
Background Neurological emergencies are common and frequently devastating. Every year, millions of Americans suffer an acute stroke, severe traumatic brain injury, subarachnoid hemorrhage, status epilepticus, or spinal cord injury severe enough to require medical intervention. Aims Full evaluation of the diseases in the acute setting often requires advanced diagnostics, and treatment frequently necessitates transfer to specialized centers. Delays in diagnosis and/or treatment may result in worsened outcomes; therefore, optimization of diagnostics is critical. Methods Point-of-care (POC) testing brings advanced diagnostics to the patient’s bedside in an effort to assist medical providers with real-time decisions based on real-time information. POC testing is usually associated with blood tests (blood glucose, troponin, etc.), but can involve imaging, medical devices, or adapting existing technologies for use outside of the hospital. Noticeably missing from the list of current point-of-care technologies are real-time bedside capabilities that address neurological emergencies. Results Unfortunately, the lack of these technologies may result in delayed identification of patients of these devastating conditions and contribute to less aggressive therapies than is seen with other disease processes. Development of time-dependent technologies appropriate for use with the neurologically ill patient are needed to improve therapies and outcomes. Conclusion POC-CENT is designed to support the development of novel ideas focused on improving diagnostic or prognostic capabilities for acute neurological emergencies. Eligible examples include biomarkers of traumatic brain injury, non-invasive measurements of intracranial pressure or cerebral vasospasm, and improved detection of pathological bacteria in suspected meningitis.
- Published
- 2010
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43. Critical Burn Patient with an Unknown Neuromuscular Disease: Conclusion
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Matthew Gunderman, William A. Knight, and William R. Hinckley
- Subjects
Adult ,Male ,Emergency Medical Services ,Neuromuscular disease ,Critical Care ,business.industry ,Crew ,Glasgow Coma Scale ,Air Ambulances ,Neuromuscular Diseases ,Emergency Nursing ,medicine.disease ,Fatal Outcome ,Anesthesia ,Intubation, Intratracheal ,Emergency Medicine ,Morphine ,Humans ,Spinocerebellar Ataxias ,Medicine ,Burns ,business ,Diazepam ,medicine.drug - Abstract
A 37-year-old man was severely burned while trying to fill a lighter with fuel while smoking. He sustained full-thickness (third-degree) burns over 60% to 70% of his body, including the oropharynx. A ground-based paramedic was unable to orotracheally intubate the patient after the administration of morphine and diazepam. The flight crew's assessment found an awake, alert man who was unable to speak because of his oral injuries. The Glasgow Coma Scale was estimated to be 10. In addition, the patient was wheelchair-bound from an undefined neuromuscular disease. The patient was successfully intubated by the flight team as in the following description.
- Published
- 2008
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44. The Tsunami of 26 December, 2004: Numerical Modeling and Energy Considerations
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Tom Logan, William R. Knight, Zygmunt Kowalik, and P. Whitmore
- Subjects
Source function ,Shore ,geography ,geography.geographical_feature_category ,Energy flux ,Deep sea ,Geophysics ,Oceanography ,Geochemistry and Petrology ,Climatology ,Energy flow ,BENGAL ,Bathymetry ,Geology ,Energy (signal processing) - Abstract
A numerical model for the global tsunamis computation constructed by Kowalik et al. (2005), is applied to the tsunami of 26 December, 2004 in the World Ocean from 80°S to 69°N with spatial resolution of one minute. Because the computational domain includes close to 200 million grid points, a parallel version of the code was developed and run on a Cray X1 supercomputer. An energy flux function is used to investigate energy transfer from the tsunami source to the Atlantic and Pacific Oceans. Although the first energy input into the Pacific Ocean was the primary (direct) wave, reflections from the Sri Lankan and eastern shores of Maldives were a larger source. The tsunami traveled from Indonesia, around New Zealand, and into the Pacific Ocean by various routes. The direct path through the deep ocean to North America carried miniscule energy, while the stronger signal traveled a considerably longer distance via South Pacific ridges as these bathymetric features amplified the energy flux vectors. Travel times for these amplified energy fluxes are much longer than the arrival of the first wave. These large fluxes are organized in the wave-like form when propagating between Australia and Antarctica. The sources for the larger fluxes are multiple reflections from the Seychelles, Maldives and a slower direct signal from the Bay of Bengal. The energy flux into the Atlantic Ocean shows a different pattern since the energy is pumped into this domain through the directional properties of the source function. The energy flow into the Pacific Ocean is approximately 75% of the total flow to the Atlantic Ocean. In many locations along the Pacific and Atlantic coasts, the first arriving signal, or forerunner, has lower amplitude than the main signal which often is much delayed. Understanding this temporal distribution is important for an application to tsunami warning and prediction.
- Published
- 2007
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45. Research and Learning Intensive: Bowling Green State University Commits to Both
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Mark H. Gromko, William E. Knight, and Milton D. Hakel
- Subjects
business.industry ,media_common.quotation_subject ,Learning community ,General education ,General Medicine ,Academic achievement ,Public relations ,Learning experience ,Bowling green ,State (polity) ,Institution ,Operations management ,Sociology ,business ,media_common - Abstract
Ten years ago, BGSU pledged to become the premier learning community in Ohio and one of the best in the nation. With campuswide agreement and widespread assessment, the institution has made gains and has a clear sense of what it needs to do next.
- Published
- 2006
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46. Influences on Participation in a University Faculty and Staff Annual Giving Campaign
- Author
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William E. Knight
- Subjects
Strategic planning ,Private equity fund ,business.industry ,Organization development ,University faculty ,Communication methods ,Revenue ,Sample (statistics) ,Business ,Public relations ,Human resources ,Education - Abstract
As tuition and state support become increasingly constrained, private fund raising is becoming an ever more important source of institutional revenue. Internal faculty and staff giving campaigns are a key part of fund-raising efforts. This study, carried out at a mid-sized, state-assisted, Midwestern university, provided critical information about which types of employees are more likely to contribute and about faculty perceptions of the giving process. Human resources and development records were merged into a database for statistical analysis. Also, a sample of fulltime faculty was interviewed concerning motivation for giving, barriers or situations that prevent faculty from giving, best communication methods, and other relevant factors. Administrative staff, fulltime employees, blacks and whites, employees who were alumni, those who lived in the university's home city, employees who had ever given previously to the university, those with higher previous giving totals, employees with higher salaries, and those employed for a greater number of years were significantly more likely to give. Faculty generally understood the purpose of employee giving campaigns and agreed that departmental representatives were a good means of communication about the campaign. They felt that direct appeals to support needs at the individual department level might cause more faculty to participate than does a broad-based generic campaign approach. They would also like to be able to detail very speci.cally how their donations are used. Implications are included for which employees should be solicited and how the employee annual giving campaign should be marketed to various groups, particularly faculty.
- Published
- 2003
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47. Search in an Ordered Array Having Variable Probe Cost.
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William J. Knight
- Published
- 1988
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48. Ultrastructural Analysis of Neurosecretory Cells in the Antennae of the Mosquito, Culex Salinarius (Diptera: Culicidae)
- Author
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Roger W. Meola, Helga Sittertz-Bhatkar, William P. Knight, Michael W. Pendleton, Jimmy K. Olson, and Shirlee M. Meola
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Male ,media_common.quotation_subject ,Sensory system ,Insect ,Biology ,Cellular and Molecular Neuroscience ,medicine ,Animals ,Receptor ,media_common ,fungi ,General Medicine ,Anatomy ,Immunohistochemistry ,Neurosecretory Systems ,Culex salinarius ,Cell biology ,Culex ,Microscopy, Electron ,medicine.anatomical_structure ,Insect Hormones ,Microscopy, Electron, Scanning ,Ultrastructure ,Female ,Antennal lobe ,Neurohormones ,Mechanoreceptors ,Oligopeptides ,Neurosecretory granules - Abstract
An antiserum raised against the peptide, culetachykinin II, immunocytochemically detected a group of neurosecretory cells in the first flagellar segment of the antennae of both males and females of the mosquito, Culex salinarius. This is the first insect species in which neurosecretory cells have been found in the antennae. The ultrastructure of these antennal neurosecretory cells (ANC) is described, as well as their relationship to other neurons in the antennae and antennal lobe of the mosquito. These tachykinin-reactive cells contain relatively small (140-220 nm) elementary neurosecretory granules. Not only do the ANC have axons that terminate on specific glomeruli of the deutocerebrum, but these neurons also have collaterals that form neurohemal terminals in the receptor lymph channels of the dendrites of the sensory neurons. Thus, the ANC not only influence higher centers of the brain that interpret signals from the antennal sensillae, but also modulate the response of the sensory receptors. To our knowledge, this is the first report of neurosecretory cells directly affecting the signal reception of sensory neurons.
- Published
- 2000
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49. Lead-Induced Tricuspid Stenosis-Successful Management by Balloon Angioplasty
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Tarique Hussain, William Brodie Knight, and Karen McLeod
- Subjects
Pacemaker, Artificial ,medicine.medical_specialty ,Ventricular lead ,medicine.medical_treatment ,Perforation (oil well) ,Tricuspid stenosis ,Wounds, Penetrating ,Balloon ,Prosthesis Implantation ,Angioplasty ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,Angioplasty, Balloon, Coronary ,Child ,Lead (electronics) ,business.industry ,Infant ,General Medicine ,medicine.disease ,Electrodes, Implanted ,Surgery ,Stenosis ,Treatment Outcome ,Tricuspid valve stenosis ,cardiovascular system ,Cardiology ,Female ,Tricuspid Valve Stenosis ,Cardiology and Cardiovascular Medicine ,business - Abstract
We describe a case of tricuspid stenosis in a young woman 11 years after endocardial ventricular lead implantation. The cause of the stenosis appears to have been perforation of the septal leaflet by the lead at the time of insertion. We further describe successful management with percutaneous balloon valvuloplasty without the need for lead removal.
- Published
- 2009
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50. The cultural context of visual hallucinations
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Nick C. Fox, Jason D. Warren, Martin N. Rossor, William D. Knight, Neurology, and Neuroscience Campus Amsterdam 2008
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Male ,medicine.medical_specialty ,Medical consultation ,Hallucinations ,business.industry ,Interpretation (philosophy) ,Culture ,Cultural context ,General Medicine ,Middle Aged ,Article ,Visual Hallucination ,Religion ,medicine ,Humans ,Female ,Psychiatry ,business ,Aged ,Clinical psychology - Abstract
Visual hallucinations (VH) are a cardinal neuropsychiatric symptom and often have important diagnostic implications. The interpretation of VH is influenced by the patient's social and cultural milieu, but the impact of socio-cultural factors on the interpretation, presentation and detection of VH has been little studied. When patients exhibit VH and other neuropsychiatric phenomena, appropriate sensitivity to the role of cultural factors is an important determinant of the success of the medical consultation. We discuss this issue using three illustrative cases.
- Published
- 2008
- Full Text
- View/download PDF
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