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79 results on '"Burke, Robert E."'

1. Postacute care outcomes in home health or skilled nursing facilities in patients with a diagnosis of dementia

Author

Burke, Robert E., Xu, Yao, Ritter, Ashley Z., and Werner, Rachel M.

Subjects
Care and treatment, Comparative analysis, Patient outcomes, Forecasts and trends, Market trend/market analysis, Home care -- Patient outcomes -- Comparative analysis, Nursing homes -- Patient outcomes -- Comparative analysis, Medicare -- Forecasts and trends, Dementia -- Care and treatment
Abstract

1 | INTRODUCTION Currently, more than 40% of Medicare beneficiaries receive postacute care in a skilled nursing facility (SNF) or from a home health (HH) agency after hospital discharge, for [...], Objective: To compare the outcomes of postacute care between home health (HH) and skilled nursing facilities (SNFs) following hospitalization among Medicare beneficiaries with a diagnosis of dementia. Data Sources: 100% MedPAR data, Minimum Data Set, and Outcome and Assessment Information Set assessment data from January 1, 2015 to December 31, 2016. Study Design: Retrospective cohort analysis using an instrumental variable design to compare outcomes (30-day readmission and mortality, 100-day mortality) of HH versus SNF following acute hospitalization. We used the differential distance between patients' home and the closest HH agency and SNF to instrument for nonrandom allocation of patients. Data Collection/Extraction Methods: We identified hospital discharges followed by SNF and HH stays for Medicare fee-for-service beneficiaries with dementia. We excluded beneficiaries younger than age 65, admitted to the hospital from a nursing home, or enrolled in hospice. We identified dementia using validated diagnostic codes with a 3-year look-back. Principal Findings: Our sample included 977,946 beneficiaries with a diagnosis of dementia; 297,732 (30.4%) received HH, while 680,214 (69.6%) went to SNF. Overall, 16.8% were readmitted to the hospital and 6.1% died within 30 days, while 15.4% died within 100 days of hospital discharge. In the instrumental variable analysis, there were no differences in any outcome between the two postacute care settings. Conclusions: Medicare beneficiaries with a diagnosis of dementia receiving postacute care in HH or SNF experienced similar rates of readmission and mortality across settings. This finding raises important questions about current postacute care referral patterns, given 7 in 10 patients with a diagnosis of dementia in our sample were discharged to SNF. KEYWORDS dementia, health policy, home health, postacute care, skilled nursing facility What is known on this topic * The prevalence of dementia and of postacute care use is rising in the United States. * No studies have compared outcomes of different postacute care settings for patients with dementia even though they vary significantly on cost and services provided. What this study adds * Medicare beneficiaries with a diagnosis of dementia receiving HH care had similar rates of hospital readmission and mortality to those receiving care in a SNF. * This finding raises questions about the appropriateness of postacute care referral patterns in beneficiaries without a diagnosis of dementia (where 50% of postacute care use is in SNF) and in beneficiaries with a diagnosis of dementia (where 70% of postacute care use in this sample is in SNF).

Published
2022
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2. Impaired Physical Performance Predicts Hospitalization Risk for Participants in the Program of All-inclusive Care for the Elderly

Author

Falvey, Jason R., Burke, Robert E., Levy, Cari R., Gustavson, Allison M., Price, Lisa, Forster, Jeri E., and Stevens-Lapsley, Jennifer E.

Subjects
Medical examination, Prognosis, Methods, Risk factors, Elderly patients -- Medical examination -- Prognosis, Geriatric assessment -- Methods, Hospitalization -- Risk factors, Elderly, Medicaid, Batteries
Abstract

Background. Medicaid spending on the Program of All-inclusive Care for the Elderly (PACE) has grown rapidly over the last 5 years. Reducing hospitalization rates is a major goal for PACE. [...]

Published
2019
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3. Characteristics associated with home health care referrals at hospital discharge: Results from the 2012 national inpatient sample

Author

Jones, Christine D., Wald, Heidi L., Boxer, Rebecca S., Masoudi, Frederick A., Burke, Robert E., Capp, Roberta, Coleman, Eric A., and Ginde, Adit A.

Subjects
Analysis, Home care -- Analysis, Hospitalization -- Analysis, Hospital admission and discharge -- Analysis
Abstract

Objective. To assess patient- and hospital-level factors associated with home health care (HHC) referrals following nonelective U.S. patient hospitalizations in 2012. Data Source. The 2012 National Inpatient Sample (NIS). Study [...]

Published
2017
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4. Role of physical therapists in reducing hospital readmissions: optimizing outcomes for older adults during care transitions from hospital to community

Author

Falvey, Jason R., Burke, Robert E., Malone, Daniel, Ridgeway, Kyle J., McManus, Beth M., and Stevens-Lapsley, Jennifer E.

Subjects
Practice, Methods, Forecasts and trends, Market trend/market analysis, Hospitalization -- Forecasts and trends, Preventive medicine -- Methods, Physical therapists -- Practice, Transitional care -- Forecasts and trends, Medicine, Preventive -- Methods, Hospital care -- Forecasts and trends, Preventive health services -- Methods
Abstract

Nearly 1 in 5 Medicare beneficiaries are readmitted to the hospital within 30 days after an acute hospitalization. (1) Reduction of 30-day hospital readmissions is a major quality improvement goal [...], Hospital readmissions in older adult populations are an emerging quality indicator for acute care hospitals. Recent evidence has linked functional decline during and after hospitalization with an elevated risk of hospital readmission. However, models of care that have been developed to reduce hospital readmission rates do not adequately address functional deficits. Physical therapists, as experts in optimizing physical function, have a strong opportunity to contribute meaningfully to care transition models and demonstrate the value of physical therapy interventions in reducing readmissions. Thus, the purposes of this perspective article are: (1) to describe the need for physical therapist input during care transitions for older adults and (2) to outline strategies for expanding physical therapy participation in care transitions for older adults, with an overall goal of reducing avoidable 30-day hospital readmissions.

Published
2016
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7. Identifying Major Barriers to Home Dialysis (The IM-HOME Study): Findings From a National Survey of Patients, Care Partners, and Providers

Author

Reddy, Yuvaram N.V., Kearney, Matthew D., Ward, Michaela, Burke, Robert E., O’Hare, Ann M., Reese, Peter P., Lane-Fall, Meghan B., Jones, Jennifer, Liu, Frank, Martin, Ashley, McGraw, April, Neumann, Joanna, Pettis, Amber, and Salenger, Page

Abstract

Developing strategies to improve home dialysis use requires a comprehensive understanding of barriers. We sought to identify the most important barriers to home dialysis use from the perspective of patients, care partners, and providers.

Published
2024
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13. Using the Practical, Robust Implementation and Sustainability Model (PRISM) to qualitatively assess multilevel contextual factors to help plan, implement, evaluate, and disseminate health services programs

Author

McCreight, Marina S, Rabin, Borsika A, Glasgow, Russell E, Ayele, Roman A, Leonard, Chelsea A, Gilmartin, Heather M, Frank, Joseph W, Hess, Paul L, Burke, Robert E, and Battaglia, Catherine T

Abstract

PRISM is useful to identify contextual factors that influence implementation, modification, uptake, and evaluation of health services programs.There is consensus in dissemination and implementation (D&I) science that addressing contextual factors is critically important for understanding translation of health care delivery interventions but little agreement on which contextual factors are key determinants of implementation outcomes. We describe the application of the Practical Robust Implementation and Sustainability Model (PRISM), which expands the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework to identify contextual factors across four diverse programs. Multiple qualitative methods were used to collect multilevel, multistakeholder perspectives from the adopting organizations and staff. We identified measures for evaluating context through the various domains of PRISM to guide health services research across the phases of program implementation. The PRISM domains of Recipients, Implementation and Sustainability Infrastructure, and External Environment identified important multilevel contextual factors, including variability in operational processes and available resources. These domains helped to facilitate planning and implementation phases of the four interventions and guide purposeful adaptations. We found assessments of PRISM domains useful to systematically assess multilevel contextual factors across various content areas as well as phases of program implementation. Additionally, these contextual factors were found to be relevant to RE-AIM outcomes. Lessons learned can be applied to future research as there is a need to investigate the measurement properties of PRISM and continue to test which contextual factors are most important to successful implementation and for which outcomes.

Published
2019
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15. Brainwriting Premortem

Author

Gilmartin, Heather, Lawrence, Emily, Leonard, Chelsea, McCreight, Marina, Kelley, Lynette, Lippmann, Brandi, Coy, Andrew, and Burke, Robert E.

Abstract

Supplemental Digital Content is Available in the Text.

Published
2019
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17. Combining Constitutively Active Rheb Expression and Chondroitinase Promotes Functional Axonal Regeneration after Cervical Spinal Cord Injury

Author

Wu, Di, Klaw, Michelle C., Connors, Theresa, Kholodilov, Nikolai, Burke, Robert E., Côté, Marie-Pascale, and Tom, Veronica J.

Abstract

After spinal cord injury (SCI), severed axons in the adult mammalian CNS are unable to mount a robust regenerative response. In addition, the glial scar at the lesion site further restricts the regenerative potential of axons. We hypothesized that a combinatorial approach coincidentally targeting these obstacles would promote axonal regeneration. We combined (1) transplantation of a growth-permissive peripheral nerve graft (PNG) into an incomplete, cervical lesion cavity; (2) transduction of neurons rostral to the SCI site to express constitutively active Rheb (caRheb; a Ras homolog enriched in brain), a GTPase that directly activates the growth-promoting pathway mammalian target of rapamycin (mTOR) via AAV-caRheb injection; and (3) digestion of growth-inhibitory chondroitin sulfate proteoglycans within the glial scar at the distal PNG interface using the bacterial enzyme chondroitinase ABC (ChABC). We found that expressing caRheb in neurons post-SCI results in modestly yet significantly more axons regenerating across a ChABC-treated distal graft interface into caudal spinal cord than either treatment alone. Excitingly, we found that caRheb+ChABC treatment significantly potentiates the formation of synapses in the host spinal cord and improves the animals’ ability to use the affected forelimb. Thus, this combination strategy enhances functional axonal regeneration following a cervical SCI.

Published
2017
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18. Nurses' Role in Managing “The Fit” of Older Adults in Skilled Nursing Facilities

Author

Jones, Jacqueline, Lawrence, Emily, Ladebue, Amy, Leonard, Chelsea, Ayele, Roman, and Burke, Robert E.

Abstract

Post-acute care for older adults often involves transfer to a skilled nursing facility (SNF) following hospital discharge. This transition is often poorly coordinated and leaves older adults at risk for poor health outcomes, but new payment models offer opportunities to align improved care practices with payments. There is a dearth of evidence regarding the role of nursing and its potential to improve hospital to SNF care transitions. Ninety-nine semi-structured interviews were conducted with clinicians, patients, and caregivers from three hospitals and three SNFs. Results indicate a sharp contrast in the roles of hospital nurses—who are often silent partners in post-acute care decision making—and SNF nurses, who take a primary role as managing “the fit” for patients transitioning to a SNF. Nurses are uniquely positioned to make needed changes to culture to adapt to new payment models and improve patient outcomes. [Post-acute care for older adults often involves transfer to a skilled nursing facility (SNF) following hospital discharge. This transition is often poorly coordinated and leaves older adults at risk for poor health outcomes, but new payment models offer opportunities to align improved care practices with payments. There is a dearth of evidence regarding the role of nursing and its potential to improve hospital to SNF care transitions. Ninety-nine semi-structured interviews were conducted with clinicians, patients, and caregivers from three hospitals and three SNFs. Results indicate a sharp contrast in the roles of hospital nurses—who are often silent partners in post-acute care decision making—and SNF nurses, who take a primary role as managing “the fit” for patients transitioning to a SNF. Nurses are uniquely positioned to make needed changes to culture to adapt to new payment models and improve patient outcomes. [Journal of Gerontological Nursing, 43(12), 11–20.]

Published
2017
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19. Residents' Exposure to Educational Experiences in Facilitating Hospital Discharges

Author

Young, Eric, Stickrath, Chad, McNulty, Monica, Calderon, Aaron J., Chapman, Elizabeth, Gonzalo, Jed D., Kuperman, Ethan F., Lopez, Max, Smith, Christopher J., Sweigart, Joseph R., Theobald, Cecelia N., and Burke, Robert E.

Abstract

ABSTRACTBackground There is an incomplete understanding of the most effective approaches for motivating residents to adopt guideline-recommended practices for hospital discharges.Objective We evaluated internal medicine (IM) residents' exposure to educational experiences focused on facilitating hospital discharges and compared those experiences based on correlations with residents' perceived responsibility for safely transitioning patients from the hospital.Methods A cross-sectional, multi-center survey of IM residents at 9 US university- and community-based training programs in 2014–2015 measured exposure to 8 transitional care experiences, their perceived impact on care transitions attitudes, and the correlation between experiences and residents' perceptions of postdischarge responsibility.Results Of 817 residents surveyed, 469 (57) responded. Teaching about care transitions on rounds was the most common educational experience reported by residents (74, 327 of 439). Learning opportunities with postdischarge patient contact were less common (clinic visits: 32, 142 of 439; telephone calls: 12, 53 of 439; and home visits: 4, 18 of 439). On a 1–10 scale (10 highest impact), residents rated postdischarge clinic as having the highest impact on their motivation to ensure safe transitions of care (mean 7.61). Prior experiences with a postdischarge clinic visit, home visit, or telephone call were each correlated with increased perceived responsibility for transitional care tasks (correlation coefficients 0.12 P  .004, 0.1 P  .012, and 0.13 P  001, respectively).Conclusions IM residents learn to facilitate hospital discharges most often through direct patient care. Opportunities to interact with patients across the postdischarge continuum are uncommon, despite correlating with increased perceived responsibility for ensuring safe transitions of care.

Published
2017
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21. Is Axonal Degeneration a Key Early Event in Parkinson’s Disease?

Author

Kurowska, Zuzanna, Kordower, Jeffrey H., Stoessl, A. Jon, Burke, Robert E., Brundin, Patrik, Yue, Zhenyu, Brady, Scott T., Milbrandt, Jeffrey, Trapp, Bruce D., Sherer, Todd B., and Medicetty, Satish

Abstract

Recent research suggests that in Parkinson’s disease the long, thin and unmyelinated axons of dopaminergic neurons degenerate early in the disease process. We organized a workshop entitled ‘Axonal Pathology in Parkinson’s disease’, on March 23rd, 2016, in Cleveland, Ohio with the goals of summarizing the state-of-the-art and defining key gaps in knowledge. A group of eight research leaders discussed new developments in clinical pathology, functional imaging, animal models, and mechanisms of degeneration including neuroinflammation, autophagy and axonal transport deficits. While the workshop focused on PD, comparisons were made to other neurological conditions where axonal degeneration is well recognized.

Published
2016
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22. Retrograde Axonal Degeneration in Parkinson Disease

Author

Tagliaferro, Patricia and Burke, Robert E.

Abstract

In spite of tremendous research efforts we have not yet achieved two of our principal therapeutic goals in the treatment of Parkinson’s disease (PD), to prevent its onward progression and to provide restoration of systems that have already been damaged by the time of diagnosis. There are many possible reasons for our inability to make progress. One possibility is that our efforts thus far may not have been directed towards the appropriate cellular compartments. Up until now research has been largely focused on the loss of neurons in the disease. Thus, neuroprotection approaches have been largely aimed at blocking mechanisms that lead to destruction of the neuronal cell body. Attempts to provide neurorestoration have been almost entirely focused on replacement of neurons. We herein review the evidence that the axonal component of diseased neuronal systems merit more of our attention. Evidence from imaging studies, from postmortem neurochemical studies, and from genetic animal models suggests that the axons of the dopaminergic system are involved predominantly and early in PD. Since the mechanisms of axonal destruction are distinct from those of neuron cell body degeneration, a focus on axonal neurobiology will offer new opportunities for preventing their degeneration. At present these mechanisms remain largely obscure. However, defining them is likely to offer new opportunities for neuroprotection. In relation to neurorestoration, while it has been classically believed that neurons of the adult central nervous system are incapable of new axon growth, recent evidence shows that this is not true for the dopaminergic projection. In conclusion, the neurobiology of axons is likely to offer many new approaches to protective and restorative therapeutics.

Published
2016
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23. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Author

Klionsky, Daniel J, Abdelmohsen, Kotb, Abe, Akihisa, Abedin, Md Joynal, Abeliovich, Hagai, Acevedo Arozena, Abraham, Adachi, Hiroaki, Adams, Christopher M, Adams, Peter D, Adeli, Khosrow, Adhihetty, Peter J, Adler, Sharon G, Agam, Galila, Agarwal, Rajesh, Aghi, Manish K, Agnello, Maria, Agostinis, Patrizia, Aguilar, Patricia V, Aguirre-Ghiso, Julio, Airoldi, Edoardo M, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akporiaye, Emmanuel T, Al-Rubeai, Mohamed, Albaiceta, Guillermo M, Albanese, Chris, Albani, Diego, Albert, Matthew L, Aldudo, Jesus, Algül, Hana, Alirezaei, Mehrdad, Alloza, Iraide, Almasan, Alexandru, Almonte-Beceril, Maylin, Alnemri, Emad S, Alonso, Covadonga, Altan-Bonnet, Nihal, Altieri, Dario C, Alvarez, Silvia, Alvarez-Erviti, Lydia, Alves, Sandro, Amadoro, Giuseppina, Amano, Atsuo, Amantini, Consuelo, Ambrosio, Santiago, Amelio, Ivano, Amer, Amal O, Amessou, Mohamed, Amon, Angelika, An, Zhenyi, Anania, Frank A, Andersen, Stig U, Andley, Usha P, Andreadi, Catherine K, Andrieu-Abadie, Nathalie, Anel, Alberto, Ann, David K, Anoopkumar-Dukie, Shailendra, Antonioli, Manuela, Aoki, Hiroshi, Apostolova, Nadezda, Aquila, Saveria, Aquilano, Katia, Araki, Koichi, Arama, Eli, Aranda, Agustin, Araya, Jun, Arcaro, Alexandre, Arias, Esperanza, Arimoto, Hirokazu, Ariosa, Aileen R, Armstrong, Jane L, Arnould, Thierry, Arsov, Ivica, Asanuma, Katsuhiko, Askanas, Valerie, Asselin, Eric, Atarashi, Ryuichiro, Atherton, Sally S, Atkin, Julie D, Attardi, Laura D, Auberger, Patrick, Auburger, Georg, Aurelian, Laure, Autelli, Riccardo, Avagliano, Laura, Avantaggiati, Maria Laura, Avrahami, Limor, Awale, Suresh, Azad, Neelam, Bachetti, Tiziana, Backer, Jonathan M, Bae, Dong-Hun, Bae, Jae-sung, Bae, Ok-Nam, Bae, Soo Han, Baehrecke, Eric H, Baek, Seung-Hoon, Baghdiguian, Stephen, Bagniewska-Zadworna, Agnieszka, Bai, Hua, Bai, Jie, Bai, Xue-Yuan, Bailly, Yannick, Balaji, Kithiganahalli Narayanaswamy, Balduini, Walter, Ballabio, Andrea, Balzan, Rena, Banerjee, Rajkumar, Bánhegyi, Gábor, Bao, Haijun, Barbeau, Benoit, Barrachina, Maria D, Barreiro, Esther, Bartel, Bonnie, Bartolomé, Alberto, Bassham, Diane C, Bassi, Maria Teresa, Bast, Robert C, Basu, Alakananda, Batista, Maria Teresa, Batoko, Henri, Battino, Maurizio, Bauckman, Kyle, Baumgarner, Bradley L, Bayer, K Ulrich, Beale, Rupert, Beaulieu, Jean-François, Beck, George R., Becker, Christoph, Beckham, J David, Bédard, Pierre-André, Bednarski, Patrick J, Begley, Thomas J, Behl, Christian, Behrends, Christian, Behrens, Georg MN, Behrns, Kevin E, Bejarano, Eloy, Belaid, Amine, Belleudi, Francesca, Bénard, Giovanni, Berchem, Guy, Bergamaschi, Daniele, Bergami, Matteo, Berkhout, Ben, Berliocchi, Laura, Bernard, Amélie, Bernard, Monique, Bernassola, Francesca, Bertolotti, Anne, Bess, Amanda S, Besteiro, Sébastien, Bettuzzi, Saverio, Bhalla, Savita, Bhattacharyya, Shalmoli, Bhutia, Sujit K, Biagosch, Caroline, Bianchi, Michele Wolfe, Biard-Piechaczyk, Martine, Billes, Viktor, Bincoletto, Claudia, Bingol, Baris, Bird, Sara W, Bitoun, Marc, Bjedov, Ivana, Blackstone, Craig, Blanc, Lionel, Blanco, Guillermo A, Blomhoff, Heidi Kiil, Boada-Romero, Emilio, Böckler, Stefan, Boes, Marianne, Boesze-Battaglia, Kathleen, Boise, Lawrence H, Bolino, Alessandra, Boman, Andrea, Bonaldo, Paolo, Bordi, Matteo, Bosch, Jürgen, Botana, Luis M, Botti, Joelle, Bou, German, Bouché, Marina, Bouchecareilh, Marion, Boucher, Marie-Josée, Boulton, Michael E, Bouret, Sebastien G, Boya, Patricia, Boyer-Guittaut, Michaël, Bozhkov, Peter V, Brady, Nathan, Braga, Vania MM, Brancolini, Claudio, Braus, Gerhard H, Bravo-San Pedro, José M, Brennan, Lisa A, Bresnick, Emery H, Brest, Patrick, Bridges, Dave, Bringer, Marie-Agnès, Brini, Marisa, Brito, Glauber C, Brodin, Bertha, Brookes, Paul S, Brown, Eric J, Brown, Karen, Broxmeyer, Hal E, Bruhat, Alain, Brum, Patricia Chakur, Brumell, John H, Brunetti-Pierri, Nicola, Bryson-Richardson, Robert J, Buch, Shilpa, Buchan, Alastair M, Budak, Hikmet, Bulavin, Dmitry V, Bultman, Scott J, Bultynck, Geert, Bumbasirevic, Vladimir, Burelle, Yan, Burke, Robert E, Burmeister, Margit, Bütikofer, Peter, Caberlotto, Laura, Cadwell, Ken, Cahova, Monika, Cai, Dongsheng, Cai, Jingjing, Cai, Qian, Calatayud, Sara, Camougrand, Nadine, Campanella, Michelangelo, Campbell, Grant R, Campbell, Matthew, Campello, Silvia, Candau, Robin, Caniggia, Isabella, Cantoni, Lavinia, Cao, Lizhi, Caplan, Allan B, Caraglia, Michele, Cardinali, Claudio, Cardoso, Sandra Morais, Carew, Jennifer S, Carleton, Laura A, Carlin, Cathleen R, Carloni, Silvia, Carlsson, Sven R, Carmona-Gutierrez, Didac, Carneiro, Leticia AM, Carnevali, Oliana, Carra, Serena, Carrier, Alice, Carroll, Bernadette, Casas, Caty, Casas, Josefina, Cassinelli, Giuliana, Castets, Perrine, Castro-Obregon, Susana, Cavallini, Gabriella, Ceccherini, Isabella, Cecconi, Francesco, Cederbaum, Arthur I, Ceña, Valentín, Cenci, Simone, Cerella, Claudia, Cervia, Davide, Cetrullo, Silvia, Chaachouay, Hassan, Chae, Han-Jung, Chagin, Andrei S, Chai, Chee-Yin, Chakrabarti, Gopal, Chamilos, Georgios, Chan, Edmond YW, Chan, Matthew TV, Chandra, Dhyan, Chandra, Pallavi, Chang, Chih-Peng, Chang, Raymond Chuen-Chung, Chang, Ta Yuan, Chatham, John C, Chatterjee, Saurabh, Chauhan, Santosh, Che, Yongsheng, Cheetham, Michael E, Cheluvappa, Rajkumar, Chen, Chun-Jung, Chen, Gang, Chen, Guang-Chao, Chen, Guoqiang, Chen, Hongzhuan, Chen, Jeff W, Chen, Jian-Kang, Chen, Min, Chen, Mingzhou, Chen, Peiwen, Chen, Qi, Chen, Quan, Chen, Shang-Der, Chen, Si, Chen, Steve S-L, Chen, Wei, Chen, Wei-Jung, Chen, Wen Qiang, Chen, Wenli, Chen, Xiangmei, Chen, Yau-Hung, Chen, Ye-Guang, Chen, Yin, Chen, Yingyu, Chen, Yongshun, Chen, Yu-Jen, Chen, Yue-Qin, Chen, Yujie, Chen, Zhen, Chen, Zhong, Cheng, Alan, Cheng, Christopher HK, Cheng, Hua, Cheong, Heesun, Cherry, Sara, Chesney, Jason, Cheung, Chun Hei Antonio, Chevet, Eric, Chi, Hsiang Cheng, Chi, Sung-Gil, Chiacchiera, Fulvio, Chiang, Hui-Ling, Chiarelli, Roberto, Chiariello, Mario, Chieppa, Marcello, Chin, Lih-Shen, Chiong, Mario, Chiu, Gigi NC, Cho, Dong-Hyung, Cho, Ssang-Goo, Cho, William C, Cho, Yong-Yeon, Cho, Young-Seok, Choi, Augustine MK, Choi, Eui-Ju, Choi, Eun-Kyoung, Choi, Jayoung, Choi, Mary E, Choi, Seung-Il, Chou, Tsui-Fen, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chow, Kuan-Chih, Chowdhury, Kamal, Chu, Charleen T, Chuang, Tsung-Hsien, Chun, Taehoon, Chung, Hyewon, Chung, Taijoon, Chung, Yuen-Li, Chwae, Yong-Joon, Cianfanelli, Valentina, Ciarcia, Roberto, Ciechomska, Iwona A, Ciriolo, Maria Rosa, Cirone, Mara, Claerhout, Sofie, Clague, Michael J, Clària, Joan, Clarke, Peter GH, Clarke, Robert, Clementi, Emilio, Cleyrat, Cédric, Cnop, Miriam, Coccia, Eliana M, Cocco, Tiziana, Codogno, Patrice, Coers, Jörn, Cohen, Ezra EW, Colecchia, David, Coletto, Luisa, Coll, Núria S, Colucci-Guyon, Emma, Comincini, Sergio, Condello, Maria, Cook, Katherine L, Coombs, Graham H, Cooper, Cynthia D, Cooper, J Mark, Coppens, Isabelle, Corasaniti, Maria Tiziana, Corazzari, Marco, Corbalan, Ramon, Corcelle-Termeau, Elisabeth, Cordero, Mario D, Corral-Ramos, Cristina, Corti, Olga, Cossarizza, Andrea, Costelli, Paola, Costes, Safia, Cotman, Susan L, Coto-Montes, Ana, Cottet, Sandra, Couve, Eduardo, Covey, Lori R, Cowart, L Ashley, Cox, Jeffery S, Coxon, Fraser P, Coyne, Carolyn B, Cragg, Mark S, Craven, Rolf J, Crepaldi, Tiziana, Crespo, Jose L, Criollo, Alfredo, Crippa, Valeria, Cruz, Maria Teresa, Cuervo, Ana Maria, Cuezva, Jose M, Cui, Taixing, Cutillas, Pedro R, Czaja, Mark J, Czyzyk-Krzeska, Maria F, Dagda, Ruben K, Dahmen, Uta, Dai, Chunsun, Dai, Wenjie, Dai, Yun, Dalby, Kevin N, Dalla Valle, Luisa, Dalmasso, Guillaume, D'Amelio, Marcello, Damme, Markus, Darfeuille-Michaud, Arlette, Dargemont, Catherine, Darley-Usmar, Victor M, Dasarathy, Srinivasan, Dasgupta, Biplab, Dash, Srikanta, Dass, Crispin R, Davey, Hazel Marie, Davids, Lester M, Dávila, David, Davis, Roger J, Dawson, Ted M, Dawson, Valina L, Daza, Paula, de Belleroche, Jackie, de Figueiredo, Paul, de Figueiredo, Regina Celia Bressan Queiroz, de la Fuente, José, De Martino, Luisa, De Matteis, Antonella, De Meyer, Guido RY, De Milito, Angelo, De Santi, Mauro, de Souza, Wanderley, De Tata, Vincenzo, De Zio, Daniela, Debnath, Jayanta, Dechant, Reinhard, Decuypere, Jean-Paul, Deegan, Shane, Dehay, Benjamin, Del Bello, Barbara, Del Re, Dominic P, Delage-Mourroux, Régis, Delbridge, Lea MD, Deldicque, Louise, Delorme-Axford, Elizabeth, Deng, Yizhen, Dengjel, Joern, Denizot, Melanie, Dent, Paul, Der, Channing J, Deretic, Vojo, Derrien, Benoît, Deutsch, Eric, Devarenne, Timothy P, Devenish, Rodney J, Di Bartolomeo, Sabrina, Di Daniele, Nicola, Di Domenico, Fabio, Di Nardo, Alessia, Di Paola, Simone, Di Pietro, Antonio, Di Renzo, Livia, DiAntonio, Aaron, Díaz-Araya, Guillermo, Díaz-Laviada, Ines, Diaz-Meco, Maria T, Diaz-Nido, Javier, Dickey, Chad A, Dickson, Robert C, Diederich, Marc, Digard, Paul, Dikic, Ivan, Dinesh-Kumar, Savithrama P, Ding, Chan, Ding, Wen-Xing, Ding, Zufeng, Dini, Luciana, Distler, Jörg HW, Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dmytruk, Kostyantyn, Dobson, Renwick CJ, Doetsch, Volker, Dokladny, Karol, Dokudovskaya, Svetlana, Donadelli, Massimo, Dong, X Charlie, Dong, Xiaonan, Dong, Zheng, Donohue, Terrence M, Doran, Kelly S, D'Orazi, Gabriella, Dorn, Gerald W, Dosenko, Victor, Dridi, Sami, Drucker, Liat, Du, Jie, Du, Li-Lin, Du, Lihuan, du Toit, André, Dua, Priyamvada, Duan, Lei, Duann, Pu, Dubey, Vikash Kumar, Duchen, Michael R, Duchosal, Michel A, Duez, Helene, Dugail, Isabelle, Dumit, Verónica I, Duncan, Mara C, Dunlop, Elaine A, Dunn, William A, Dupont, Nicolas, Dupuis, Luc, Durán, Raúl V, Durcan, Thomas M, Duvezin-Caubet, Stéphane, Duvvuri, Umamaheswar, Eapen, Vinay, Ebrahimi-Fakhari, Darius, Echard, Arnaud, Eckhart, Leopold, Edelstein, Charles L, Edinger, Aimee L, Eichinger, Ludwig, Eisenberg, Tobias, Eisenberg-Lerner, Avital, Eissa, N Tony, El-Deiry, Wafik S, El-Khoury, Victoria, Elazar, Zvulun, Eldar-Finkelman, Hagit, Elliott, Chris 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Published
2016
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24. Patient and Hospitalization Characteristics Associated With Increased Postacute Care Facility Discharges From US Hospitals

Author

Burke, Robert E., Juarez-Colunga, Elizabeth, Levy, Cari, Prochazka, Allan V., Coleman, Eric A., and Ginde, Adit A.

Abstract

The number of patients discharged to postacute care (PAC) facilities after hospitalization increased by 50 nationally between 1996 and 2010. We sought to describe payors and patients most affected by this trend and to identify diagnoses for which PAC facility care may be substituting for continued hospital care.

Published
2015
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25. Interventions to Decrease Hospital Readmissions: Keys for Cost-effectiveness

Author

Burke, Robert E. and Coleman, Eric A.

Abstract

Hospitals began paying financial penalties for high-risk–adjusted 30-day readmission rates for certain diagnoses in October 2012. Physician leaders seeking to reduce readmission rates will find that proven interventions often require substantial up-front financial and organizational investment. To reduce readmissions while minimizing the investment, leaders need to develop new and creative strategies guided by the evidence. This article describes 5 proposed strategies or “best practices” derived from critical evaluation of prior interventions and experience in the field. These practices include matching the intensity of the intervention to the patient's risk of readmission, avoiding commonly used but unproven interventions, using interventions with a durable effect, creating an effective team before selecting an intervention, and focusing on previously unrecognized high-risk patient groups.

Published
2013
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26. Pediatric and Neonatal Staphylococcus aureusBacteremia Epidemiology, Risk Factors, and Outcome

Author

Burke, Robert E., Halpern, Meira S., Baron, Ellen Jo, and Gutierrez, Kathleen

Abstract

Objective.To evaluate the impact of methicillin-resistant Staphylococcus aureuson the prevalence of S. aureusbloodstream infection among children.Methods.Retrospective analysis of demographic data, risk factors for infection, and clinical outcomes for children (age, less than 18 years) with S. aureusbacteremia hospitalized at a children's hospital during 2001–2006.Results.We identified 164 episodes of S. aureusbacteremia among 151 children. The prevalence of bacteremia due to methicillin-susceptible S. aureusduring 2001–2003 was approximately the same as that during 2004–2006 (29 and 30 cases, respectively, per 10,000 hospitalized children [hereafter, “per 10,000 hospitalizations”]), but the prevalence of bacteremia due to methicillin-resistant S. aureusincreased from 4 to 11 cases, respectively, per 10,000 hospitalizations (P= .015). A total of 48% of infections involved children who had S. aureus-positive blood cultures less than 3 days after hospital admission. Seventy-four percent of these children had a preexisting comorbidity. When the prevalence of S. aureusbacteremia was stratified by race, sex, or age, neonates hospitalized at birth and Hispanic children had significantly reduced risks of infection. Children younger than 1 year of age (excluding neonates hospitalized at birth) had an increased prevalence of hospital-onset S. aureusbacteremia. There was a disproportionate increase in the risk of S. aureusbacteremia for each additional week of hospitalization among children with hospital-onset S. aureusbacteremia. Children with methicillin-resistant S. aureusbacteremia had a longer hospital stay, were transferred to another facility at a greater rate than they were discharged home, and had a greater mortality rate, compared with children with methicillin-susceptible S. aureusbacteremia.Conclusion.This study documents the prevalence of S. aureusbacteremia among children with a high risk for acquiring this infection, and it describes populations of children who are at higher risk for bacteremia due to either methicillin-susceptible or methicillin-resistant S. aureus. Methods to improve prevention of S. aureusbacteremia are needed for children with healthcare-associated risk factors for S. aureusbacteremia.

Published
2009
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27. Targeting the JNK Signaling Pathway for Stroke and Parkinson's Diseases Therapy

Author

Kuan, Chia-Yi and Burke, Robert E.

Abstract

The c-Jun NH2-terminal Kinase (JNK) signaling pathway is frequently induced by cellular stress and correlated with neuronal death. This unique property makes JNK signaling a promising target for developing pharmacological intervention. Among several neurological disorders, JNK signaling is particularly implicated in ischemic stroke and Parkinson's disease. The inhibitors of the JNK signaling pathway include upstream kinase inhibitors (for example, CEP-1347), small chemical inhibitors of JNK (SP600125 and AS601245), and peptide inhibitors of the interaction between JNK and its substrates (D-JNKI and I-JIP). The mechanisms by which JNK signaling induces apoptosis and evidence of cytoprotective effects of these JNK inhibitors are summarized in the present review.

Published
2005

28. Postnatal Developmental Programmed Cell Death in Dopamine Neurons

Author

BURKE, ROBERT E.

Abstract

The prenatal development of dopamine (DA) neurons of the substantia nigra (SN) is characterized by their birth, specification, and migration to their final positions. Their postnatal development is characterized by the establishment of contact and interactions between the SN and other neural nuclei, particularly the striatal target, by extension of axons, terminal differentiation, and synapse formation. In this postnatal context there is a natural cell death event, which is apoptotic in nature and biphasic in time course, with an initial peak on postnatal day (PND) 2, and a second on PND14. By PND20 the event has largely subsided. This natural cell death event is regulated in vivoby interaction with striatal target: it is augmented by axon-sparing target lesion, DA terminal destruction, and medial forebrain bundle axotomy. This target dependence is present largely within only the first two postnatal weeks. The striatal target-derived neurotrophic factor(s) that regulate this death event are unknown. We have shown, in a postnatal primary culture model of mesencephalic DA neurons, that glia-derived neurotrophic factor (GDNF) is unique in its ability to support their viability by suppressing apoptosis. We have also recently found that intrastriatal injection of GDNF in vivosuppresses apoptosis, and injection of neutralizing antibodies augments it. Thus, GDNF is a leading candidate for a striatum-derived neurotrophic factor for DA neurons during development.

Published
2003
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30. Medial forebrain bundle axotomy during development induces apoptosis in dopamine neurons of the substantia nigra and activation of caspases in their degenerating axons

Author

El‐Khodor, Bassem F. and Burke, Robert E.

Abstract

There is growing evidence that programmed cell death may play a role in degenerative neurologic disease. The caspases are a family of cell death proteins that mediate proteolytic cascades in the death process. Although there is clear evidence that caspases play a role in the destruction of the components of the neuronal soma, it has been controversial whether they play a role in the degeneration of axons that accompanies the death of the cell body. It is important to define the molecular mechanisms of axonal degeneration, because terminal degeneration may occur early in neurodegenerative disease. We have therefore investigated whether caspases play a role in axonal degeneration in the dopaminergic nigrostriatal system following axotomy of the median forebrain bundle during development. We find that this lesion induces apoptosis in midbrain dopaminergic neurons at the level of the cell soma. Concomitantly with this induction of apoptosis, degeneration of dopaminergic axons occurs and is characterized by the formation of axonal swellings and spheroids. Immunohistochemical analysis reveals that the activated form of caspase‐3 and a caspase cleavage product of β‐actin are abundantly expressed in these degenerating fibers. We conclude that caspases are activated in degenerating dopaminergic axons as the somata undergo programmed cell death in this model. These results raise the possibility that caspase activation may occur in other programmed cell death contexts for these neurons, and, if this is so, then their inhibition may be a useful therapeutic target. J. Comp. Neurol. 452:65–79, 2002. © 2002 Wiley‐Liss, Inc.

Published
2002
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31. Developmental cell death in dopaminergic neurons of the substantia nigra of mice

Author

Jackson‐Lewis, Vernice, Vila, Miquel, Djaldetti, Ruth, Guegan, Christelle, Liberatore, Gabriel, Liu, Jian, O'Malley, Karen L., Burke, Robert E., and Przedborski, Serge

Abstract

Dopaminergic neurons in the substantia nigra pars compacta (SNpc) undergo natural cell death during development in rats. Controversy exists as to the occurrence of this phenomenon in SNpc dopaminergic neurons in the developing mouse. Herein, by using an array of morphologic techniques, we show that many SNpc neurons fulfill the criteria for apoptosis and that the number of apoptotic neurons in the SNpc vary in a time‐dependent manner from postnatal day 2 to 32. These dying neurons also show evidence of DNA fragmentation, of activated caspase‐3, and of cleavage of β‐actin. Some, but not all of the SNpc apoptotic neurons still express their phenotypic marker tyrosine hydroxylase, confirming their dopaminergic nature. Consistent with the importance of target‐derived trophic support in modulating developmental cell death, we demonstrate that destruction of intrinsic striatal neurons by a local injection of quinolinic acid (QA) dramatically enhances the magnitude of SNpc apoptosis and results in a lower number of adult SNpc dopaminergic neurons. Strengthening the apoptotic nature of the observed SNpc developmental cell death, we demonstrate that overexpression of the anti‐apoptotic protein Bcl‐2 attenuates both natural and QA‐induced SNpc apoptosis. The present study provides compelling evidence that developmental neuronal death with a morphology of apoptosis does occur in the SNpc of mice and that this process plays a critical role in regulating the adult number of dopaminergic neurons in the SNpc. J. Comp. Neurol. 424:476–488, 2000. © 2000 Wiley‐Liss, Inc.

Published
2000
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32. US slows dumping reform

Author

Burke, Robert E.

Subjects
International trade -- Negotiation, mediation and arbitration, Dumping (International trade) -- Laws, regulations and rules, Business, Business, general, General Agreement on Tariffs and Trade
Published
1990

33. Synuclein expression is decreased in rat substantia nigra following induction of apoptosis by intrastriatal 6-hydroxydopamine

Author

Kholodilov, Nikolai G., Oo, Tinmarla F., and Burke, Robert E.

Abstract

We have previously shown that synuclein is upregulated in the substantia nigra following developmental lesion of the target striatum. In this model, synuclein is preferentially expressed in normal-appearing neurons, rather than those which undergo apoptosis. It has been proposed, however, that synuclein may mediate apoptosis in other contexts, such as that induced by neurotoxins. To examine this possibility, we have studied a model in which apoptosis is induced in dopamine neurons by intrastriatal injection of 6-hydroxydopamine. In this model synuclein mRNA and protein expression are not upregulated at any time point, but instead diminish as dopamine neurons die. We observe a complete dissociation between apoptotic morphology and synuclein protein expression. We conclude that synuclein is unlikely to play a direct role in apoptotic death in dopamine neurons and is more likely, in the target injury model, to play a role in protection or restoration of neurons which survive.

Published
1999
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34. α‐Synuclein expression in substantia nigra and cortex in Parkinson's disease

Author

Neystat, Michael, Lynch, Timothy, Przedborski, Serge, Kholodilov, Nikolai, Rzhetskaya, Margarita, and Burke, Robert E.

Abstract

Mutations in the human α‐synuclein gene have been identified in several families of European descent with early‐onset Parkinson's disease (PD). We sequenced the complete α‐synuclein cDNA from substantia nigra and cortex from nine patients with PD and eight control subjects. No mutations were found. We then analyzed α‐synuclein mRNA levels using a ribonuclease protection assay. Two major protected bands of α‐synuclein mRNA, possibly representing two splice variants of the gene, were observed. α‐synuclein mRNA was significantly diminished in the substantia nigra of patients with PD compared with control subjects but not in the cortex. Our findings suggest that decreased synuclein mRNA may be an early alteration in the SN in PD, and imply that decreased levels of the protein may play a role in the pathogenesis of sporadic cases of the disease.

Published
1999
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36. Tardive dystonia

Author

Burke, Robert E., Fahn, Stanley, Jankovic, Joseph, Marsden, C. D., Lang, Anthony E., Gollomp, Stephen, and Ilson, Joyce

Abstract

It is not widely recognized that antipsychotic drugs can cause late-onset and persistent dystonia. This dystonia, which we call tardive dystonia, is to be distinguished from acute dystonic reactions, which are transient, and from classic tardive dyskinesia, which is a choreic disorder that predominantly affects the oral region. We present 42 patients with tardive dystonia. The age of onset of dystonia was 13 to 60 years. Symptoms began after 3 days to 11 years of antipsychotic therapy. Younger patients tended to have more generalized dystonia. In a few patients, spontaneous remission occurred, but dystonia persisted for years in most. Therapy was rarely a complete success. The most frequently helpful medications were tetrabenazine (68 of patients improved) and anticholinergics (39 improved).

Published
1982

37. Torsion dystonia

Author

Burke, Robert E., Fahn, Stanley, and Marsden, C. David

Abstract

We studied trihexyphenidyl in the treatment of torsion dystonia in a prospective, double-blind crossover protocol. Thirty-one patients completed the protocol. Twenty-two (71) had a clinically significant response. After a mean follow-up of 2.4 years, 68 of patients continued to take trihexyphenidyl, and 42 continued to show a considerable or dramatic benefit. The 30-mg dose used was generally well tolerated. High-dosage trihexyphenidyl therapy is effective in the management of torsion dystonia.

Published
1986

38. Programmed cell death: Does it play a role in parkinson's disease?

Author

Burke, Robert E. and Kholodilov, Nikolai G.

Abstract

In recent years, the possibility that programmed cell death (PCD), which is mediated by genetic programs intrinsic to the cell, may underlie the degeneration of neurons that occurs in Parkinson's disease (PD) and allied disorders has become an important hypothesis. Although PCD was originally identified in tissues as a normal developmental phenomenon, there is no question that it can also occur in neurologic disease and models thereof. The possibility that PCD could occur in dopamine neurons in degenerative disease is made plausible by the observations that natural cell death, with the morphology of apoptosis, does occur in these neurons and that this event is regulated by developmental target interactions. In addition, it has been shown that apoptotic death can be induced in these neurons in some animal models of parkinsonism. We have shown, for example, that apoptosis can be induced during development by intrastriatal injection of the neurotoxin 6‐hydroxydopamine. Other investigators have shown that apoptosis can be induced in a chronic model of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyride toxicity. However, investigations in human PD brains have yielded mixed results thus far, with some investigators identifying evidence of apoptotic death but others not. Further investigation of human postmortem tissue will benefit from a more complete understanding of the molecular basis of PCD in dopamine neurons, such that its molecular features can be investigated, rather than strictly relying on the morphologic markers presently available.

Published
1998
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39. Neuroleptic Malignant syndrome caused by dopaminedepleting drugs in a patient with Huntington disease

Author

Burke, Robert E., Fahn, Stanley, Mayeux, Richard, Weinberg, Harold, Louis, Kenneth, and Willner, Joseph H.

Abstract

Prior reports of neuroleptic malignant syndrome (NMS) concerned patients with psychiatric disorders, usually schizophrenia, who were taking dopamine receptor blocking agents. We report the syndrome in a patient with Huntington disease who was treated with dopamine-depleting agents. He had a negative evaluation for malignant hyperthermia (MH), and we suggest that NMS differs from MH. The occurrence of NMS caused by dopamine-depleting agents suggests that anticholinergic properties of phenotiazines are not the only cause. Central dopaminergic systems probably participate in thermo-regulation, and dopamine depletion probably plays a pathogenetic role in this syndrome.

Published
1981

40. Serum trihexyphenidyl levels in the treatment of torsion dystonia

Author

Burke, Robert E. and Fahn, Stanley

Abstract

Using a radioreceptor technique, we assayed serum trihexyphenidyl levels in patients with dystonia being treated chronically with high dosage. We found a significant correlation between total daily dose and the daily lowest (trough) serum levels. There was no relationship between serum levels and therapeutic response or toxicity. Toxicity was more closely related to patient age than to serum level. Although levels may be useful to monitor patient compliance, they cannot be used to judge adequacy of therapy.

Published
1985

41. Validity and reliability of a rating scale for the primary torsion dystonias

Author

Burke, Robert E., Fahn, Stanley, Marsden, C. David, Bressman, Susan B., Moskowitz, Carol, and Friedman, Joseph

Abstract

For quantitative assessment of the primary torsion dystonias, a rating scale is proposed that has two sections—a Movement Scale, based on examination, and a Disability Scale, based on the patient's statements about seven activities of daily living. We assessed the validity of the Movement Scale by comparing scores with a ranking of patients according to dystonia severity and with ratings of the patients on the Disability Scale. In addition, we assessed the inter-and intra-rater reliability of the scale by comparing independent scorings of patients by four examiners and by comparing scorings by the same examiners performed at different times. We found that the Movement Scale was a valid and reliable indicator of the severity of primary torsion dystonia.

Published
1985

42. Tardive dyskinesia

Author

Burke, Robert E.

Abstract

Tardive dyskinesia (TD) consists of persistent involuntary movements that are due to antipsychotic drug treatment. Prevention depends on accurate psychiatric diagnosis and use of antipsychotics only for specific indications. Little is known about what antipsychotic drug regimens affect the risk of TD. Clinical subtypes of TD may exist. Tardive dystonia differs from oral choreic TD in its clinical phenomenology, epidemiology, and clinical pharmacology. Another possible subtype, persistent motor restlessness, seems also distinguishable in its phenomenology and epidemiology. Both of these forms of TD can be disabling, whereas typical oral TD often is not. Although TD may spontaneously remit more often than was once believed, it nevertheless is often persistent. No current therapy is universally effective.

Published
1984

43. Dopamine beta-hydroxylase gene excluded in four subtypes of hereditary dystonia

Author

Schuback, Deborah, Kramer, Patricia, Ozelius, Laurie, Holmgren, Gösta, Forsgren, Lars, Kyllerman, Marten, Wahlström, Jan, Craft, Cheryl M., Nygaard, Torbjoern, Brin, Mitchell, Leon, Deborah, Bressman, Susan, Moskowitz, Carol B., Burke, Robert E., Sanner, G., Drugge, U., Gusella, James F., Fahn, Stanley, and Breakefield, Xandra O.

Abstract

The hereditary dystonias include a clinically heterogeneous group of movement disorders varying in symptoms, age of onset, and drug responsiveness. Dopamine beta-hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine, has been implicated in dystonia because of increased serum levels of DBH in some patients, the influence of catecholaminergic drugs on the human phenotypes, and altered norepinephrine levels in several brain regions in dystonia patients and in genetically dystonic rodents. In addition, markers linked to the dystonia gene in two ethnic groups map close to the DBH locus on human chromosome 9q34. Here we evaluate the inheritance of restriction fragment length polymorphisms near the DBH gene in families with four subtypes of hereditary dystonia: Jewish and non-Jewish, early onset, generalized idiopathic torsion dystonia (ITD); dopa-responsive dystonia; and myoclonic dystonia. In all families, obligate recombination events were observed between the DBH and dystonia genes, thus excluding the DBH gene as the primary defect.

Published
1991
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44. Apoptosis in neurodegenerative disorders

Author

Stefanis, Leonidas, Burke, Robert E., and Greene, Lloyd A.

Abstract

We review here recent reports pertaining to the issue of apoptosis in neurodegenerative diseases. Tissue culture models, animal models and human pathological studies are discussed. At present, there is supportive, but not definitive, evidence for apoptosis in a number of neurodegenerative disorders.

Published
1997

45. Apoptosis in Degenerative Diseases of the Basal Ganglia

Author

Burke, Robert E.

Abstract

Degenerative disorders of the basal ganglia are characterized by disturbances of motor control. Prototypic examples are Parkinson's disease, which is caused by degeneration of dopamine neurons of the substantia nigra, and Huntington's disease, which is caused by degeneration of neurons of the striatum. In recent years, it has been postulated that some of these disorders may be caused by programmed cell death or apoptosis, a genetically regulated form of cell death. There is clear evidence that apoptosis occurs in neurons of the basal ganglia during normal development, that it can be regulated, and that it can be induced in some animal models of these disorders. Although there is some suggestive direct evidence that apoptosis may occur in the human brain in these disorders, the evidence to date is partial and not yet compelling. Nevertheless, programmed cell death is an important new hypothesis for the pathogenesis of these disorders and warrants vigorous further investigation, particularly with molecular markers in addition to classic morphological markers. The concept of programmed cell death is relevant not only to the pathogenesis of these diseases but also to therapeutic issues, such as transplantation approaches.

Published
1998
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47. Augmented pharmacologic stimulation of striatal acetylcholine release following developmental hypoxic-ischemic injury

Author

Oo, Tinmarlar Frances, Naini, Ali, and Burke, Robert E.

Abstract

We have previously shown that developmental hypoxic-ischemic injury in a unilateral rodent model leads to an increase in both morphologic and biochemical indices of striatal cholinergic neurons. To investigate the functional significance these changes, we have used the in vivo microdialysis technique to examine the regulation of striatal acetylcholine release in awake, adult rats following postnatal hypoxic-ischemic injury. We have found that injury does not alter basal release of acetylcholine, but it results in a marked augmentation in the increase of acetylcholine release normally observed after infusion of atropine or pirenzepine.

Published
1996
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48. Naturally Occurring Cell Death during Postnatal Development of the Substantia Nigra Pars Compacta of Rat

Author

Janec, Eileen and Burke, Robert E.

Abstract

We have quantified degenerating cells during the postnatal development of the substantia nigra pars compacta (SNpc) of normal rat. The cells are identified at the light microscope level by the characteristic morphologic appearance of large, rounded clumps of chromatin, stained intensely with both Nissl and silver stains. These cells were most numerous on Postnatal Day (PND) 2 and rapidly declined in number by PND 12. However, on PND 14, there was a second peak in the number of pyknotic cells. Their number again rapidly diminished to very few by PND 28. Many of these cells appear neuronal in origin. We conclude that naturally occurring cell death is a prominent feature of normal nigra development, and we hypothesize that the magnitude of this regressive event may be regulated by target (striatal)-derived trophic support. Copyright 1993, 1999 Academic Press

Published
1993
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49. 6-Hydroxydopamine Lesion of the Rat Substantia Nigra: Time Course and Morphology of Cell Death

Author

Jeon, Beom S., Jackson-Lewis, Vernice, and Burke, Robert E.

Abstract

The 6-hydroxydopamine (6-OHDA) model of nigral injury in rats has been in use as a standard animal model of parkinsonism for many years. While earlier studies established the time course for loss of catecholamine histofluorescence or tyrosine hydroxylase immunostaining in the cell bodies and terminals, these alterations in phenotypic expression do not define the time course of morphologic degeneration. We have therefore used a silver impregnation method to characterize the time course and morphology of the degeneration of neurons in the nigrostriatal system. Abundant neuronal death was observed in substantia nigra pars compacta (SNpc) as early as 12 hours after nigral 6-OHDA injection, and prior to any evidence of striatal terminal degeneration. From 1 to 7 days neuron death was accompanied by striatal fibre degeneration. After 7 days, fibre degeneration was no longer seen, but identifiable neuron death continued at low levels for as long as 31 days, and stained amorphous material was present at 60 days. The morphologic pattern of cell death in the early phase was similar to that in the late phase, and included cytoplasmic silver deposits and dark staining of the nucleolus. At no time was the morphology of apoptosis observed. We conclude that neuron death is a progressive process following 6-OHDA lesion, with similar morphology throughout the course of degeneration.

Published
1995
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50. Motor unit types of cat triceps surae muscle

Author

Burke, Robert E.

Abstract

1. Motor units, defined as including a motoneurone (cell body, dendrites and axon) plus the muscle unit innervated, have been examined in the triceps surae motor pool of pentobarbital anaesthetized cats.

Published
1967
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