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1. SYNTAX Score and Long-Term Outcomes

Author

Fumiaki Ikeno, Maria Mori Brooks, Kaori Nakagawa, Min-Kyu Kim, Hideaki Kaneda, Yoshiaki Mitsutake, Helen A. Vlachos, Leonard Schwartz, Robert L. Frye, Sheryl F. Kelsey, Katsuhisa Waseda, Mark A. Hlatky, Katherine M. Detre, Trevor J. Orchard, Stephen B. Thomas, Kim Sutton Tyrrell, Jamal S. Rana, Frani Averbach, Joan M. MacGregor, Scott M. O’Neal, Kathleen Pitluga, Veronica Sansing, Mary Tranchine, Sharon W. Crow, Marianne (Marnie) Bertolet, Regina Hardison, Kevin Kip, Manuel Lombardero, Jiang Lu, Sue Janiszewski, Darina Protivnak, Sarah Reiser, Stephen Barton, Ping Guo, Yulia Kushner, Owen Michael, Jeffrey P. Martin, Christopher Kania, Michael Kania, Jeffrey O’Donnell, Rae Ann Maxwell, Suzanne Goldberg, Yves Rosenberg, Patrice Desvigne-Nickens, Abby Ershow, David Gordon, Dina Paltoo, Teresa L.Z. Jones, Whady Hueb, José Ramires, Neuza Lopes, Bernardo Léo Wajchenberg, Eulogio E. Martinez, Sergio A. Oliveira, Expedito E. Ribeiro, Marcos Perin, Roberto Betti, George Steiner, Alan Barolet, Yolanda Groenewoud, Lisa Mighton, Kathy Camelon, Robert O’Rourke, Janet Blodgett, Edward Sako, Judith Nicastro, Robin Prescott, Charanjit Rihal, Frank Kennedy, Gregory Barsness, Amanda Basu, Alfredo Clavell, Robert Frye, David R. Holmes, Amir Lerman, Charles Mullaney, Guy Reeder, Robert Rizza, Hartzell Schaff, Steven Smith, Virend Somers, Thoralf Sundt, Henry Ting, R. Scott Wright, Pam Helgemoe, Diane Lesmeister, Deborah Rolbiecki, Luis Lepe-Montoya, Jorge Escobedo, Rafael Barraza, Rubén Baleón, Arturo Campos, Paula García, Carlos Lezama, Carlos Miramontes, Salvador Ocampo, Joaquín V. Peñafiel, Aquiles Valdespino, Raúl Verdín, Héctor Albarrán, Fernando Ayala, Eduardo Chávez, Héctor Murillo, Luisa Virginia Buitrón, Beatriz Rico-Verdin, Fabiola Angulo, Dale Adler, Austin Arthur Halle, Faramarz Ismail-Beigi, Suvinay Paranjape, Stacey Mazzurco, Karen Ridley, Kodangudi Ramanathan, Solomon Solomon, Barry Wall, Darryl Weinman, Tammy Touchstone, Lillie Douglas, Martial Bourassa, Jean-Claude Tardif, Jean-Louis Chiasson, Marc Andre Lavoie, Rémi Rabasa-Lhoret, Hélène Langelier, Suzy Foucher, Johanne Trudel, Scott Monrad, Vankeepuram Srinivas, Joel Zonszein, Jill Crandall, Helena Duffy, Eugen Vartolomei, Spencer King, Carl Jacobs, David Robertson, Marty Porter, Melanie Eley, Emmalee Nichols, Jennifer LaCorte, Melinda Mock, William Rogers, Fernando Ovalle, David Bell, Vijay K. Misra, William B. Hillegass, Raed Aqel, Penny Pierce, Melanie Smith, Leah Saag, Ashley Vaughn, Dwight Smith, Tiffany Grimes, Susan Rolli, Roberta Hill, Beth Dean Barrett, Clarinda Morehead, Ken Doss, Charles J. Davidson, Mark Molitch, Nirat Beohar, Elaine Massaro, Lynne Goodreau, Fabiola Arroyo, Petr Neužil, Lenka Pavlickova, Štĕpánka Stehlíková, Jaroslav Benedik, Liz Coling, Richard Davies, Christopher Glover, Michel LeMay, Thierry Mesana, Teik Chye Ooi, Mark Silverman, Alexander Sorisky, Colette Favreau, Susan McClinton, Melvin Weiss, Irene Weiss, Leo Saulle, Harichandra Kannam, Joanne C. Kurylas, Lorraine Vasi, John Douglas, Ziyad Ghazzal, Laurence Sperling, Priya Dayamani, Suzanne Gebhart, Sabreena Basu, Tarek Helmy, Vin Tangpricha, Pamela Hyde, Margaret Jenkins, Barbara P. Grant, Kenneth Kent, William Suddath, Michelle Magee, Patricia Julien-Williams, Vida Reed, Carine Nassar, Gilles Dagenais, Claude Garceau, Dominique Auger, Christopher Buller, Tom Elliott, Krishnan Ramanathan, Donald Ricci, Rebecca Fox, Daniela Kolesniak, Michael Attubato, Frederick Feit, Stephen Richardson, Ivan Pena Sing, James Slater, Angela Amendola, Bernardo Vargas, Nicholas Tsapatsaris, Bartholomew Woods, Gary Cushing, Martin Rutter, Premranjan Singh, Gail DesRochers, Gail Woodhead, Deborah Gannon, Nancy Shinopulos Campbell, Michael Ragosta, Ian Sarembock, Eric Powers, Eugene Barrett, Linda Jahn, Karen Murie, Gladwin Das, Gardar Sigurdsson, Carl White, John Bantle, J. Bruce Redmon, Christine Kwong, Jacqueline Tamis-Holland, Jeanine Albu, Judith S. Hochman, James Wilentz, Sylvaine Frances, Deborah Tormey, Carl Pepine, Karen Smith, Laurence Kennedy, Karen Brezner, Tempa Curry, Frank Bleyer, Stewart Albert, Arshag Mooradian, Sharon Plummer, Francisco Fuentes, Roberto Robles, Victor Lavis, Jaime Gomez, Cesar Iliescu, Carol Underwood, Maria Selin Fulton, Julie Gomez Ramirez, Jennifer Merta, Glenna Scott, Ashok Krishnaswami, Lynn Dowdell, Sarah Berkheimer, Adam Greenbaum, Fred Whitehouse, Raquel Pangilinan, Kelly Mann, Alice K. Jacobs, Elliot Sternthal, Susana Ebner, Zoran Nedeljkovic, Paula Beardsley, David Schneider, Richard Pratley, William Cefalu, Joel Schnure, Michaelanne Rowen, Linda Tilton, Alan Niederman, Cristina Mata, Terri Kellerman, John Farmer, Alan J. Garber, Neal Kleiman, Nancy Howard, Debra Nichols, Madonna Pool, Christopher Granger, Mark Feinglos, George Adams, Jennifer Green, Bernadette Druken, Dani Underwood, J. Lawrence Stafford, Thomas Donner, Warren Laskey, Dana Beach, John Lopez, Andrew Davis, David Faxon, Sirimon Reutrakul, Emily Bayer, Oscar Marroquin, Howard Cohen, Mary Korytkowski, Glory Koerbel, Lisa Baxendell, Debbie Rosenfelder, Louise DeRiso, Carole Farrell, Tina Vita, Janet McGill, Ronald Krone, Richard Bach, Carol Recklein, Kristin M. Luepke, Mary Jane Clifton, Michael E. Farkouh, Michael C. Kim, Donald A. Smith, Ida Guzman, Arlene Travis, James O’Keefe, Alan Forker, William Isley, Richard Moe, Paul Kennedy, Margaret Rosson, Aimee Long, Eric Bates, William Herman, Rodica Pop-Busui, Claire Duvernoy, Martin Stevens, Ann Luciano, Cheryl Majors, Sheldon H. Gottlieb, Annabelle Rodriguez, Melanie Herr, David Williams, Robert J. Smith, J. Dawn Abbott, Marc J. Laufgraben, Mary Grogan, Janice Muratori, Gabriel Habib, Marco Marcelli, Issam Mikati, Emilia Cordero, Gina Caldwell, David Schechter, Daniel Lorber, Phyllis August, Maisie Brown, Patricia Depree, Kurt Huber, Ursula Hanusch-Enserer, Nelly Jordanova, Dilek Cilesiz, Birgit Vogel, Ben McCallister, Michael Kleerekoper, Kelly Mandagere, Robert Urbanic, James Bengston, Bobby K. Kong, Andrew Pruitt, Jeffrey Sanfield, Carol Carulli, Ruth Churley-Strom, Raymond Magorien, Kwame Osei, Cecilia Casey Boyer, Richard Lee, Pasquale Palumbo, Joyce Wisbey, Edwin Alderman, Anne Schwarzkopf Michael Steffes, Maren Nowicki, Jean Bucksa, Bernard Chaitman, Jane Eckstein, Karen Stocke, Derek B. Boothroyd, Kathryn A. Melsop, Burton E. Sobel, Dagnija Neimane, Ami E. Iskandrian, Mary Beth Schaaf, Saul Genuth, Theresa Bongarno, Richard Nesto, Karen Hultberg, Helene Rosenhouse-Romeo, Georgia Pambianco, Michael Mock, Sheryl Kelsey, Trevor Orchard, Thomas Ryan, Harold Lebovitz, Robert Brown, Gottlieb Friesinger, Edward Horton, Jay Mason, Renu Virmani, Lawrence Wechsler, C. Noel Bairey-Merz, J. Ward Kennedy, Elliott Antman, John Colwell, Sarah Fowler, Curt Furberg, Lee Goldman, Bruce Jennings, and Scott Rankin

Subjects
medicine.medical_specialty, business.industry, medicine.medical_treatment, Hazard ratio, Percutaneous coronary intervention, 030204 cardiovascular system & hematology, medicine.disease, Revascularization, humanities, Cardiac surgery, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Angioplasty, Conventional PCI, medicine, Cardiology, 030212 general & internal medicine, Myocardial infarction, Cardiology and Cardiovascular Medicine, business, Stroke
Abstract

Background The extent of coronary disease affects clinical outcomes and may predict the effectiveness of coronary revascularization with either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score quantifies the extent of coronary disease. Objectives This study sought to determine whether SYNTAX scores predicted outcomes and the effectiveness of coronary revascularization compared with medical therapy in the BARI-2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. Methods Baseline SYNTAX scores were retrospectively calculated for BARI-2D patients without prior revascularization (N = 1,550) by angiographic laboratory investigators masked to patient characteristics and outcomes. The primary outcome was major cardiovascular events (a composite of death, myocardial infarction, and stroke) over 5 years. Results A mid/high SYNTAX score (≥23) was associated with a higher risk of major cardiovascular events (hazard ratio: 1.36, confidence interval: 1.07 to 1.75, p = 0.01). Patients in the CABG stratum had significantly higher SYNTAX scores: 36% had mid/high SYNTAX scores compared with 13% in the PCI stratum (p Conclusions Among patients with diabetes and stable ischemic heart disease, higher SYNTAX scores predict higher rates of major cardiovascular events and were associated with more favorable outcomes of revascularization compared with medical therapy among patients suitable for CABG. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes; NCT00006305)

Published
2017

2. Sex, Prescribing Practices and Guideline Recommended, Blood Pressure, and LDL Cholesterol Targets at Baseline in the BARI 2D Trial

Author

Sirimon Reutrakul, Penny Pierce, Sarah Berkheimer, J. Lawrence Stafford, Sue Janiszewski, Harold E. Lebovitz, Diane Lesmeister, Deborah Rolbiecki, Mark E. Molitch, William O. Suddath, Susan McClinton, Frank P. Kennedy, Helene Rosenhouse-Romeo, Vin Tangpricha, Karen Stocke, Sharon Plummer, Michael Ragosta, Jeffrey Sanfield, Stacey Mazzurco, Austin Arthur Halle, Marc J. Laufgraben, Terri Kellerman, Carlos Lezama, Expedito E. Ribeiro, Tempa Curry, Michael J. Attubato, David R. Holmes, Rafael Barraza, Paula García, Johanne Trudel, Michael B. Mock, Melvin B. Weiss, Jennifer LaCorte, Thomas J. Ryan, Mary Tranchine, Richard Moe, Saul Genuth, Linda Tilton, Lawrence Wechsler, Jean M. Bucksa, Hartzell V. Schaff, Barry M. Wall, Maria M. Brooks, Ida Guzman, Eric R. Bates, Nicholas P. Tsapatsaris, Robert Brown, Sheldon H. Gottlieb, Yves Rosenberg, William B. Hillegass, Fred W. Whitehouse, Jean Louis Chiasson, Ashok Krishnaswami, Claude Garceau, Laurence S. Sperling, L. Z Jones Teresa, Abby G. Ershow, Scott Monrad, Jean-Claude Tardif, Emilia Cordero, Scott M. O'Neal, Leah Saag, Thomas Donner, Marianne Bertolet, Scott Rankin, Irene Weiss, Elliot Sternthal, Dana Beach, Judith S. Hochman, Kevin E. Kip, Andrew L. Pruitt, Rebecca Fox, David S.H. Bell, Melanie Eley, Ian J. Sarembock, Vera Bittner, Derek B. Boothroyd, Richard E. Pratley, Annabelle Rodriguez, Robert A. O'Rourke, Michael Kleerekoper, Gail DesRochers, Trevor Orchard, Dilek Cilesiz, Thoralf M. Sundt, Cesar Iliescu, Lee Goldman, Eric R. Powers, Donald A. Smith, Jeffrey P. Martin, Carl J. Pepine, Gabriel B. Habib, Daniel L. Lorber, Marcos Perin, Paula Beardsley, Kathryn Melsop, Frank Bleyer, Melanie Herr, David Robertson, Gladwin S. Das, Phyllis August, Alan D. Forker, Alan J. Garber, Madonna Pool, Suzy Foucher, Joyce Wisbey, Susana Ebner, Eugene J. Barrett, Christopher Glover, Nancy Shinopulos Campbell, Veronica V. Sansing, Kim Sutton Tyrrell, Elliott M. Antman, Suvinay Paranjape, Katherine M. Detre, Jill P. Crandall, Michaelanne Rowen, Dwight Smith, Bernardo Léo Wajchenberg, Cecilia Casey Boyer, Roberta Hill, José Antonio Franchini Ramires, Hélène Langelier, Tina Vita, Renu Virmani, Lynne Goodreau, Jennifer Merta, David Gordon, Luis Lepe-Montoya, Angela Amendola, Jennifer B. Green, Cristina Mata, Edwin L. Alderman, Andrew M. Davis, Gary W. Cushing, Carol Underwood, Gottlieb Friesinger, Beatriz Rico-Verdin, Eulógio E. Martinez, Pam Helgemoe, Richard W. Lee, Hé Albarrán, Gail Woodhead, Melanie Smith, Victor Lavis, Harichandra Kannam, Gardar Sigurdsson, Sabreena Basu, Debbie Rosenfelder, Patricia Julien-Williams, Mark A. Hlatky, Raquel Pangilinan, Alan Barolet, Yolanda Groenewoud, Lisa Baxendell, Jeanine Albu, William H. Herman, Sharon Crow, Carole Farrell, Dawn J. Bbott, Vida Reed, Steven A. Smith, Solomon S. Solomon, Rae Ann Maxwell, Michel LeMay, Anne Schwarzkopf, Frani Averbach, Martial G. Bourassa, Lynn Dowdell, Adam Greenbaum, John P. Bantle, Edward Y. Sako, John Colwell, Paul Kennedy, Karen Brezner, David O. Williams, Clarinda Morehead, Louise DeRiso, Neal S. Kleiman, Linda A. Jahn, James Bengston, Vankeepuram S. Srinivas, Michael Kania, Petr Neužil, Ziyad M.B. Ghazzal, Zoran S. Nedeljkovic, Nirat Beohar, Whady Hueb, Thierry G. Mesana, Emmalee Nichols, Jamal S. Rana, Jaroslav Benedik, Roberto Robles, Curt D. Furberg, Joel Zonszein, Melinda Mock, Dagnija Neimane, Henry Ting, Michelle F. Magee, Birgit Vogel, Arlene Travis, Robert J. Smith, Spencer B. King, Cheryl Majors, Alfredo L. Clavell, Joel J. Schnure, Sheryl F. Kelsey, Stewart G. Albert, Dominique Auger, Raúl Verdín, Suzanne Goldberg, Kwame Osei, Bruce Jennings, Ivan R. Pena Sing, Suzanne Gebhart, Carol Recklein, R. Scott Wright, Marty H. Porter, Carl W. White, Jay W. Mason, Patrice Desvigne-Nickens, Dina N. Paltoo, Marco Marcelli, Neuza Lopes, Elaine Massaro, Theresa Bongarno, William Isley, Robert Urbanic, Roberto T. B. Betti, Glory Koerbel, Judith Nicastro, Pamela Hyde, Christine A. Kwong, Darina Protivnak, Guy S. Reeder, George L. Adams, Tiffany Grimes, Carol Carulli, Salvador Ocampo, Sarah Fowler, Fumiaki Ikeno, Robert L. Frye, Bernard R. Chaitman, Stephen B. Richardson, Arshag D. Mooradian, Robin Prescott, Leonard Schwartz, Helena Duffy, Janet C. Blodgett, Issam Mikati, Ward J. Ennedy, Arturo Campos, Mary Jane Clifton, Mary Beth Schaaf, Debra Nichols, Christopher B. Granger, Maren Nowicki, Stephen Barton, George Steiner, Kelly Mandagere, Luisa Virginia Buitrón, Aimee Long, Janice Muratori, Joan M. MacGregor, Tammy Touchstone, Michael E. Farkouh, Ashley Vaughn, Pasquale Palumbo, John J. Lopez, Carlos Miramontes, Charanjit S. Rihal, C. Noel Bairey-Merz, Mark Silverman, Patricia Depree, Kathleen Pitluga, Martin J. Stevens, Bobby Kong, John S. Douglas, Eduardo Chávez, Yulia Kushner, Leo Saulle, Christopher Kania, Jacqueline E. Tamis-Holland, Donald R. Ricci, Amir Lerman, Emily Bayer, William J. Rogers, Charles Mullaney, Mary Grogan, Jiang Lu, Warren K. Laskey, James R. Wilentz, Karen Ridley, Laurence Kennedy, Dale Adler, Fabiola Arroyo, Eugen Vartolomei, Kristin M. Luepke, Dani Underwood, Lenka Pavlíɥková, Barbara P. Grant, Sylvaine Frances, Colette Favreau, Jane Eckstein, Rodica Pop-Busui, Georgia Pambianco, Kathy Camelon, Liz Coling, Virend K. Somers, Rémi Rabasa-Lhoret, Daniela Kolesniak, Darryl Weinman, Fernando Ayala, Christopher E. Buller, Charles J. Davidson, Martin K. Rutter, Tom Elliott, Susan Rolli, Jeffrey O'Donnell, Ann Luciano, James O'Keefe, Gregory W. Barsness, Regina M. Hardison, Maisie Brown, Kelly Mann, Krishnan Ramanathan, Kenneth M. Kent, David J. Schneider, Alice K. Jacobs, Bernadette Druken, Julie Gomez Ramirez, Gina Caldwell, David Chechter, Bartholomew O'b. Woods, Michael C. Kim, Howard A. Cohen, William T. Cefalu, Lisa Mighton, Michael W. Steffes, Trevor J. Orchard, Lorraine Vasi, Amanda Basu, Robert A. Rizza, Bruce Redmon, Glenna Scott, John A. Farmer, Lillie Douglas, Fernando Ovalle, Margaret Jenkins, Frederick Feit, Joaquí Peñafiel, Alexander Sorisky, Ronald J. Krone, Ken Doss, Oscar C. Marroquin, Janet B. McGill, Hé Murillo, Mary T. Korytkowski, David P. Faxon, Tarek Helmy, Manuel Lombardero, Fabiola Angulo, Ping Guo, Nelly Jordanova, Mark N. Feinglos, Sérgio Almeida de Oliveira, Burton E. Sobel, Ben D. McCallister, Premranjan P. Singh, Richard W. Nesto, Aquiles Valdespino, Teresa L.Z. Jones, Stephen B. Thomas, Francisco Fuentes, Marc Andre Lavoie, Karen Hultberg, Gilles R. Dagenais, Beth Dean Barrett, Ruth Churley-Strom, Karen Murie, Alan Niederman, Kodangudi B. Ramanathan, Nancy Howard, Raymond D. Magorien, Maria Selin Fulton, Priya Dayamani, Sarah Reiser, Edward Horton, Deborah Tormey, Karen M. Smith, Rubén Baleón, Joanne C. Kurylas, Jorge Escobedo, Bernardo Vargas, Richard G. Bach, Vijay K. Misra, Faramarz Ismail-Beigi, Kurt Huber, Ursula Hanusch-Enserer, Carine Nassar, Richard F. Davies, James Slater, Teik Chye Ooi, Claire S. Duvernoy, Štěpánka Stehlíková, Deborah Gannon, Margaret Rosson, Carl Jacobs, Jaime Gomez, Raed A. Aqel, and Ami E. Iskandrian

Subjects
medicine.medical_specialty, lcsh:RC648-665, Article Subject, Endocrine and Autonomic Systems, business.industry, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Guideline, Pharmacology, medicine.disease, lcsh:Diseases of the endocrine glands. Clinical endocrinology, 3. Good health, Metformin, Coronary artery disease, Endocrinology, Pharmacotherapy, Blood pressure, Internal medicine, Diabetes mellitus, Hyperlipidemia, Clinical Study, Medicine, business, medicine.drug
Abstract

Background.Research has shown less aggressive treatment and poorer control of cardiovascular disease (CVD) risk factors in women than men.Methods.We analyzed sex differences in pharmacotherapy strategies and attainment of goals for hemoglobin A1c (HbA1c), blood pressure (BP), and low density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes and established coronary artery disease enrolled into the BARI 2D trial.Results.Similar numbers of drugs were prescribed in both women and men. Women were less frequent on metformin or sulfonylurea and more likely to take insulin and to be on higher doses of hydroxymethylglutaryl-CoA reductase inhibitors (statins) than men. After adjusting for baseline differences and treatment prescribed, women were less likely to achieve goals for HbA1c (OR = 0.71, 95% CI 0.57, 0.88) and LDL-C (OR = 0.64, 95% CI 0.53, 0.78). More antihypertensives were prescribed to women, and yet BP ≤ 130/80 mmHg did not differ by sex.Conclusions.Women entering the BARI 2D trial were as aggressively treated with drugs as men. Despite equivalent treatment, women less frequently met targets for HbA1c and LDL-C. Our findings suggest that there may be sex differences in response to drug therapies used to treat diabetes, hypertension, and hyperlipidemia.

Published
2015

3. Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families

Author

Cheryl Horn, Tatiana Foroud, Ryan J. Uitti, Maureen A. Leehey, Rachel Saunders Pullman, Lisa Scollins, Sabrina Phipps, Alice Rudolph, Tanya Simuni, Lisa M. Shulman, Julie So, Barbara Shannon, Paul J. Tuite, Joan Young, Judith Dobson, Paul Atchison, John M. Bertoni, Karen Blindauer, William C. Nichols, Janet Mannetter, Anette Nieves, William J. Weiner, Jayaraman Rao, Kelly E. Lyons, Nathan Pankratz, Paul Gordon, P. Michael Conneally, Joanna Hamman, Andrew Feigin, Susan Rolli, Brian Wulbrecht, Robyn Schacherer, Todd Ajax, Laura Good, Francis O. Walker, James Sutton, Karyn Boyar, Brad A. Racette, Juliette Harris, Melinda Meacham, Annette Kaczmarek, Mandar Jog, Lisa Giffin, Roger Kurlan, Kelli Williamson, Jeannine Petit, An Tran, Joan Werner, Anthony E. Lang, Maureen Cook, Robert L. Rodnitzky, Mayank Pathak, William C. Koller, Sharon Evans, Bala V. Manyam, Donna Schwieterman, Carolyn Peterson, Cheryl Halter, Clifford W. Shults, Marguerite Wieler, Joseph Jankovic, Vincent Calabrese, Mark Forrest Gordon, Jill R. Murrell, Neal Hermanowicz, Stewart A. Factor, Miodrag Velickovic, Theresa Derian, W.R. Wayne Martin, Galit Kleimer-Fisman, Richard B. Dewey, Shari Niswonger, Hunter Homes, J. Carpenter, Victoria Hunt, Lewis Sudarsky, Mark Stacy, Debra Berry, Claire Corwin, Sean K. Uniacke, G. David Podskalny, David Simon, Christine Hunter, Daniel D. Truong, Peggy Roberge, Kelly Dustin, Kapil D. Sethi, Brad Hutchinson, Un Jang Kang, Karen Marder, and Margaret F. Turk

Subjects
Male, Genotype, Genetic Linkage, Biology, Genome, Gene mapping, Gene interaction, Genetic linkage, Genetics, Humans, Family, Genetic Predisposition to Disease, Allele, Molecular Biology, Alleles, Genetics (clinical), X chromosome, Family Health, Chromosomes, Human, X, Chromosomes, Human, Pair 10, Genome, Human, Chromosome Mapping, Chromosome, Parkinson Disease, General Medicine, Chromosomes, Human, Pair 2, Mutation, Female, Human genome, Lod Score
Abstract

Parkinson disease (PD) is the second most common neurodegenerative disorder. We studied 754 affected individuals, comprising 425 sibling pairs, to identify PD susceptibility genes. Screening of the parkin gene was performed in a subset of the sample having earlier age of PD onset or a positive LOD score with a marker in the parkin gene. All subjects were evaluated using a rigorous neurological assessment. Two diagnostic models were considered for genome-wide, non-parametric linkage analyses. Model I included only those individuals with a more stringent diagnosis of verified PD (216 sibling pairs) and resulted in a maximum LOD score of 3.4 on chromosome 2. Model II included all affected individuals (425 sibling pairs) and yielded a LOD score of 3.1 on the X chromosome. Our large sample was then employed to test for gene-by-gene (epistatic) interactions. A genome screen using the 23 families with PD patients having a mutation in only one allele of the parkin gene detected evidence of linkage to chromosome 10 (LOD=2.3). The 85 families with a very strong family history of PD were employed in a genome screen and, in addition to strong evidence of linkage to chromosome 2 (LOD = 4.9), also produced a LOD of 2.4 on chromosome 14. A genome screen performed in the 277 families without a strong family history of PD detected linkage to chromosomes 10 (LOD = 2.4) and X (LOD = 3.2). These findings demonstrate consistent evidence of linkage to chromosomes 2 and X and also support the hypothesis that gene-by-gene interactions are important in PD susceptibility.

Published
2003

4. Long-term outcome of early versus delayed rasagiline treatment in early Parkinson's disease

Author

Micki McCollister, Julie Hevezi, Naomi Santoni, Tracey Tam, Rajesh Pahwa, Cynthia Alcorn-Costa, Barbara Fussell, Xiaoming Lu, Cheryl Armstrong, Peggy Gray, Patricia Dyches, Jovianna N. Wellinghoff, Shaunna Caouette, James B. Osborne, William C. Koller, Tilak Mendis, Shantelle Coe, Jacqueline Nash, Shirley Uy, Howard I. Hurtig, Susan Rolli, Tracy Stewart, Judy Richman, Susan Rolandelli, William G. Ondo, Cathi A. Thomas, Melodie Moterson, Maryan DeAngelis, Sheila Everett, Mary Mathews, Linda L. Mann, Eric Molho, Lorette J. Jenkins, Jessie Roth, Sandra K. Kostyk, Deborah L. Caputo, Ali H. Rajput, Jean Ayan, Un Jung Kang, Paul Atchison, Jo Belden, Julie So, Andew Feigin, Lisa Johnston, Lawrence I. Golb, Howard H. Hurtig, Larisa I. Skrypnik, Michael J. Aminoff, J. Carpenter, Patricia Seuffert, Carlos Singer, Amy Parsons, Kapil D. Sethi, Mark Forrest Gordon, Pam King, Mary Lloyd, Katherine B. Hawthorne, Linda Klassen, Shoba Narayan, Cathy R. Anderson, Patricia Kaminski, Karen Caplan, Robert A. Hauser, Dinorah Bateman, Erica Barnabei, Cheryl Fitzer-Attas, Kellie Gelles, Tamara Gales, Joanne Wojcieszek, Robert Hauser, Teri Radam, Karen Stavris, Carolyn C. Weeks, Marlene Gerow, Connie Kawai, Tracey Borst, Caroline M. Tanner, Charles H. Adler, Mickie Welsh, Nancy Pearson, Anita Lopez, Georgia Germain, Cathy W. Allen, Marianne Ewasnishin, Lisa Tagg, Brenda Ebbitt, Myrna Schear, Jean A. Jaglin, Roberta Winnick, Dawn Miller, Nancy Saton, Suzanne W. Schuman, Davoud Mohtat, Barbara Shannon, Vincent Calabrese, Mark F. Lew, Janis M. Miyasaki, William J. Weiner, Jody Lowery, Christine Hunter, Diane Brown, Keely Haas, Paul J. Tuite, Peter A. LeWitt, Mirann DiMinno, Cheryl Cooper, Peter Novak, Robert G. Feldman, Joanne Hamann, Sharon Evans, W.R. Wayne Martin, Mark Stacy, Debra Berry, Sharon Wortzel, John M. Bertoni, Kenneth Marek, Kelli Williamson, Lisa Gauger, Cheryl Newcomb, Carolyn Peterson, K. Ligon, Stephanie Newman, Vanessa Patterson, Peggy Roberge, Arif Dalvi, Laura Sutherland, Frederick J. Marshall, Scott Cradr, Karen Betcher, Carolyn Deloa, Jean P. Hubble, Kathleen M. Shannon, Sharyn Parness, Neila Mendis, Germanine McInnes, Adrienne Baranauskas, and Irenita Gardiner

Subjects
Adult, Male, medicine.medical_specialty, Parkinson's disease, Monoamine Oxidase Inhibitors, Time Factors, Placebo, Severity of Illness Index, Drug Administration Schedule, law.invention, Central nervous system disease, Antiparkinson Agents, Levodopa, chemistry.chemical_compound, Randomized controlled trial, Double-Blind Method, law, Internal medicine, Severity of illness, medicine, Humans, Longitudinal Studies, Aged, Retrospective Studies, Rasagiline, Dose-Response Relationship, Drug, Reproducibility of Results, Retrospective cohort study, Parkinson Disease, Middle Aged, medicine.disease, Surgery, Clinical trial, Treatment Outcome, Neurology, chemistry, Indans, Quality of Life, Female, Neurology (clinical), Psychology
Abstract

The purpose of this study to compare the long-term clinical outcome of early versus delayed rasagiline treatment in early Parkinson's disease (PD). Subjects (N = 404) were randomly assigned to initial treatment with rasagiline (early-start group) or placebo for 6 months followed by rasagiline (delayed-start group) in the TEMPO study. Subjects who chose to participate in an open-label extension (N = 306) continued to receive rasagiline as well as other PD medications as needed. Average (+/-SD) duration in the study was 3.6 +/- 2.1 years; 177 subjects received rasagiline for > or =5.0 years. Over the entire 6.5-year follow-up period, the adjusted mean difference in change from baseline in total UPDRS scores was 2.5 units (SE 1.1; P = 0.021) or 16% (SE 5.7; P = 0.006) in favor of the early-start versus delayed-start rasagiline group. Although the interaction between treatment and time was significant, values for the early-start group were better than the delayed-start group across all time points. Significantly less worsening (percent change) in total UPDRS scores was observed in the early-start group at the time points 0.5, 1.5, 2.0, 3.0, 4.5, 5.0, and 5.5 years (P < 0.05). Compared to delayed start, early initiation of rasagiline provided long-term clinical benefit, even in the face of treatment with other dopaminergic agents. This might reflect enduring benefits due to neuroprotection or effects on compensatory mechanisms in early PD.

Published
2008

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