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| ### *GRECC Annual Report: Fiscal Year [2005]{.underline}*             |
|                                                                       |
| ######## Part II: Accomplishments                                     |
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| This GRECC Annual Report covers [October 1, 2004-September 30,        |
| 2005]{.underline}: **the "Report Year"**.                             |
|                                                                       |
| This GRECC Annual Report reflects status and accomplishments of       |
| [**GRECC Core Staff \***only]{.underline}.                            |
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| **\*[GRECC Core Staff ]{.underline}**is limited to either **Primary   |
| Core**, **Affiliate Core**, or **Research Core**:                     |
|                                                                       |
| -   **Primary Core =** positions authorized by the original GRECC     |
|     allocation plus any addition in ceiling from VA Central Office    |
|     specifically designated for GRECC.                                |
|                                                                       |
| -   **Affiliated Core** = Staff who work full- or part-time in        |
|     [direct support]{.underline} of the GRECC's research, education   |
|     or clinical activity.                                             |
|                                                                       |
|     -   May be either "contributed" by the VA Medical Center or       |
|                                                                       |
|     -   May have been acquired through centralized                    |
|         enhancements/awards for programs\                             |
|         (e.g., Home-Based Primary Care, Geriatric Evaluation and      |
|         Management Program, etc.)                                     |
|                                                                       |
|     -   To be considered Affiliated Core, staff must be               |
|         organizationally aligned under the GRECC or specifically      |
|         identified by the Medical Center as **"GRECC-affiliated       |
|         staff."**                                                     |
|                                                                       |
| -   **Research Core** = Full-or part-time staff who devote 51% or     |
|     more of their total time to GRECC research and whose salaries are |
|     supported by research funds (either VA or non-VA). Includes all   |
|     GRECC staff whose salaries are paid from research funds, e.g.:    |
|                                                                       |
|     -   Associate Investigator                                        |
|                                                                       |
|     -   Assistant Research Scientist                                  |
|                                                                       |
|     -   Senior Research Career Scientist                              |
|                                                                       |
|     -   Research Career Scientist                                     |
|                                                                       |
|     -   Advanced Research Career Scientist.                           |
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| **1. GRECC NAME/LOCATION**                                            |
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| a.  **GRECC Name:** Baltimore GRECC                                   |
|                                                                       |
| b.  **Location** *(facility, VISN)*: *(facility, VISN)*: Baltimore VA |
|     Medical Center, VA Maryland Health Care System, VISN 5            |
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| **2. CONTACT PERSON (if there are questions about this report)**      |
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| a.  **Name:** Andrew P. Goldberg, M.D.                                |
|                                                                       |
| b.  **Position:** Director, Baltimore GRECC                           |
|                                                                       |
| c.  **Phone, e-mail:** (410) 605-7183, agoldber@grecc.umaryland.edu   |
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| **3. GRECC FOCUS AREA(S)**                                            |
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| GRECCs are required to conduct research in a basic biomedical area,   |
| an applied clinical area, and either a health services or             |
| rehabilitation topic. The number of specific research foci in each    |
| perspective should be limited to two or fewer.                        |
|                                                                       |
| Please enter a succinct phrase that best characterizes the focus      |
| area(s) recognized for your GRECC in the first two and either the     |
| third or fourth (or both) category below:                             |
|                                                                       |
| > **a. Basic Biomedical**:                                            |
|                                                                       |
| -   Exercise, weight loss, lipid and glucose metabolism in obese      |
|     veterans                                                          |
|                                                                       |
| -   Functional genomics, genetics and metabolism in aging veterans    |
|                                                                       |
| -   Exercise rehabilitation and brain plasticity after stroke         |
|                                                                       |
| -   Muscle and adipocyte biology in aging, obesity and CVD            |
|                                                                       |
| **b. Applied Clinical**:                                              |
|                                                                       |
| -   Exercise, weight loss, and CVD risk factor modification           |
|                                                                       |
| ```{=html}                                                            |
| <!-- -->                                                              |
| ```                                                                   |
| -   Treadmill exercise, neuromuscular function and metabolism in      |
|     stroke                                                            |
|                                                                       |
| -   Genes, lifestyle and CVD risk factors with aging                  |
|                                                                       |
| **c. Health Services**:                                               |
|                                                                       |
| -   Exercise rehabilitation, quality of life and health outcomes in   |
|     chronic stroke                                                    |
|                                                                       |
| **d. Rehabilitation**:                                                |
|                                                                       |
| -   Rehabilitation and tertiary prevention in chronic stroke and      |
|     cardiovascular disease                                            |
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| **4. ADMINISTRATION**                                                 |
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| a.  **GRECC Impact on Host VAMC in Report Year**\                     |
|     *(list the most important ways in which the GRECC has had         |
|     positive impact on the host VAMc\--i.e., how the GRECC has "made  |
|     a difference"locally. **Please limit your response to five ways   |
|     or fewer.** Please be as succinct as possible but specify the     |
|     GRECC contribution, what the impact was and whom it benefited,    |
|     where it occurred, and why it was important. **Please limit the   |
|     description of each bullet item to 5 lines or fewer**)*           |
|                                                                       |
| -   Faculty provide clinical and educational training in geriatrics   |
|     to VA health professionals, faculty, GRECC MD fellows, students   |
|     and trainees in weekly conferences, on the Geriatric Evaluation   |
|     and Management Unit, Geriatrics/Dementia Clinic, Geriatric        |
|     Pulmonary Care Clinic, Home Based Primary Care the Baltimore      |
|     Rehabilitation and Extended Care Center (BRECC),and in geriatric  |
|     medicine outpatient clinics. GRECC MDs supervise one general      |
|     medical ward team to enhance Geriatric Medical education for the  |
|     housestaff and students.                                          |
|                                                                       |
| ```{=html}                                                            |
| <!-- -->                                                              |
| ```                                                                   |
| -   Dr. Shaughnessy chairs the VAMHCS Nursing Practice Council, which |
|     ensures that standards of nursing practice are consistent with    |
|     the professional and community standards and current research     |
|     findings. She participated in the 2004 Evidence-Based Practice    |
|     Conference co-sponsored with the University of Maryland School of |
|     Nursing, and served on the Planning Committee for the 2005 and    |
|     2006 conferences.                                                 |
|                                                                       |
| -   GRECC exercise and nutrition research programs impact older       |
|     veterans at high risk for CVD through prudent changes in          |
|     nutrition and physical activity to prevent complications of CVD   |
|     and disability. These programs translated into clinical practice  |
|     in a GRECC-CVD risk assessment clinic and the national VA         |
|     sponsored pilot MOVE! Program that enrolled 42 veterans at        |
|     Baltimore. The first cohort lost an average of 11 pounds or       |
|     \~5.3% of their initial body weight in 6-mo. MOVE! will be        |
|     incorporated into a newly developed GRECC-Cardiology Service      |
|     cardiac rehabilitation program that will begin in spring FY2006.  |
|                                                                       |
| -   GRECC investigators receive Center grants: A/D Research Richard   |
|     Macko, M.D. received a 5-year, \$4.2 million VA Rehabilitation    |
|     Research and Development Center of Excellence in "Exercise and    |
|     Robotics in Neurological Disease"; Susan K. Fried, Ph.D. received |
|     5-year \$3.7 million NIDDK Clinical Nutrition Research Unit; and  |
|     Alan Shuldiner, M.D. received 5-year \$13.8 million NIH-K12 for   |
|     multidisciplinary clinician scientist career development training |
|     and a NIH grant to study the pharmacogenetics of clopidogrel      |
|     (Plavix).                                                         |
|                                                                       |
| -   GRECC investigators received basic science grants: Charlene       |
|     Hafer-Macko, M.D. received 3 year \$645,000 VA Merit to study     |
|     effects of exercise on inflammatory abnormalities in muscle after |
|     stroke; Jacob Blumenthal, MD received 3 year \$360,000 VA ACDA to |
|     study the effects of central obesity and aging on fat metabolism  |
|     and cytokines; Ronald Prigeon, MD received 3 year \$393,300 VA    |
|     Merit to study effects of aging on beta cell function; and Carole |
|     Sztalryd Woodle, Ph.D., received a 5 year \$1 million ADA Career  |
|     Development Award to study the regulation of lipolysis and the    |
|     lipid droplet by perilipin.                                       |
|                                                                       |
| -   GRECC investigators collaborated with the VISN 5 Mental Illness   |
|     Research, Education and Clinical Center (Richard Goldberg, Ph.D., |
|     PI) on a HSR VA Merit grant to implement a more intense,          |
|     behavioral MOVE! Program in veterans with serious mental illness  |
|     (priority score: 16.29; percentile 7.06).                         |
|                                                                       |
| -   The GRECC sponsors a 2 hr daily employee wellness program at the  |
|     Baltimore VAMC Senior Exercise Rehabilitation Center (SERC).      |
|     Attendance ranges from 40-70 employees/week, despite an initial   |
|     interest and enrollment of 467 employees.                         |
|                                                                       |
| -   Dr. Goldberg, Kelly Barton, R.D., and Mr. Woodcock worked with of |
|     the VA Canteen Service representatives to provide healthier food  |
|     choices in the Baltimore VAMHC Canteen. A salad bar will be       |
|     installed in FY06.                                                |
|                                                                       |
| -   GRECC faculty serve on VAMHCS committees: Drs. Goldberg and       |
|     Katzel on the Executive Committee of the Medical Center; Drs.     |
|     Sorkin and Ryan on the VA R&D committee; and Dr. Sorkin on the VA |
|     Information Security Committee. Dr. Shaughnessy chairs the VAMHCS |
|     Nursing Practice Council, and has been on the Nursing Policy and  |
|     Procedure Action Team, a committee charged with the coordination  |
|     and consolidation of nursing policies and procedures as we        |
|     reorganize from decentralized into a centralized reporting        |
|     structure.                                                        |
|                                                                       |
| []{.mark}                                                             |
|                                                                       |
| > []{.mark}                                                           |
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| b.  **GRECC Impact on VISN in Report Year** *\                        |
|     (list the most important ways in which the GRECC has had positive |
|     impact on the host VISN\-- i.e., how the GRECC has "made a        |
|     difference "regionally. **Please limit your response to five ways |
|     or fewer.** Please be as succinct as possible but specify the     |
|     GRECC contribution, what the impact was and whom it benefited,    |
|     where it occurred, and why it was important. **Please limit the   |
|     description of each bullet item to 5 lines or fewer**)*           |
|                                                                       |
| -   GRECC exercise and nutrition research programs impact older       |
|     veterans at high risk for CVD through prudent changes in          |
|     nutrition and physical activity to prevent complications of CVD   |
|     and disability. These programs translated into clinical practice  |
|     in the national VA sponsored MOVE! pilot program that enrolled 42 |
|     veterans in Baltimore. GRECC faculty are working with staff from  |
|     Washington, Martinsburg, Perry Point to plan the VISN5 MOVE!      |
|     initiative.                                                       |
|                                                                       |
| -   Baltimore VA RR&D Center of Excellence in Exercise and Robotics   |
|     in Neurological Disease (funded 2005-2010) builds on exercise     |
|     models developed in GRECC Demonstration Projects to optimize      |
|     exercise prescriptions to improve cardiovascular health and brain |
|     plasticity, use robotics assisted exercise, and                   |
|     Behavioral-Education Interventions for aging stroke patients.     |
|     Plans are being made to extend this research to the BRECC, with a |
|     proposal to construct a building at the BRECC for this purpose in |
|     development.                                                      |
|                                                                       |
| -   GRECC interdisciplinary clinical teams led by Drs. May and Katzel |
|     at Baltimore and Drs. Colvin (BRECC Director), and Dr. Heuser     |
|     (G/LTC Service Line Manager) provide clinical, hospice and        |
|     palliative care to older veterans in VAMHCS. GRECC faculty        |
|     provide geriatric medicine training in long-term care,            |
|     end-of-life care, geriatric psychiatry, and acute rehabilitation  |
|     to VA and UMB: fellows, residents, physicians' assistants, nurses |
|     nurse practitioners, health professional students, physical       |
|     therapists, and social work, exercise physiology and psychology   |
|     interns from local Universities (Delaware, Towson, UMB) and       |
|     community colleges at VISN 5 facilities.                          |
|                                                                       |
| -   Dr. Heuser is the GRECC representative on the Geriatric Long Term |
|     Care Service Line Steering Committee, assists the managers of     |
|     programs at Washington and Martinsburg with systems, environment  |
|     of care, and program development. Dr. Shaughnessy reviewed        |
|     patient care programs at the BRECC as a member of the VISN        |
|     organized external task force.                                    |
|                                                                       |
| []{.mark}                                                             |
|                                                                       |
| []{.mark}                                                             |
|                                                                       |
| -   The GRECC and the Geriatrics-LTC Service lines implemented a      |
|     monthly journal club/education meeting for physicians and nurse   |
|     practitioners at Loch Raven and Perry Point to educate staff on   |
|     new research and developments in the care of the elderly.         |
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| c.  **GRECC Trend-Setting Innovations since October 1,                |
|     [2000]{.underline}**\                                             |
|     *(list the most significant research, education or clinical       |
|     innovations originating in your GRECC in the past five years.     |
|     Please limit your response to five innovations or fewer. For each |
|     item, succinctly describe the innovation, specify the time frame  |
|     of its earliest impact, whom it benefited, where it occurred, and |
|     why it was important. **Please limit the comments concerning each |
|     innovation to 5 lines or fewer**)*:                               |
|                                                                       |
| -   We developed treadmill training (T-AEX) to promote motor          |
|     re-learning improve fitness and reduce chronic ambulatory and     |
|     functional disabilities in stroke patients. This program improves |
|     ambulation, fitness, and gait, and reduces hamstring spasticity   |
|     and energy cost of hemiparetic gait. This suggests T-AEX may      |
|     improve free-living daily activity and function, reduce           |
|     disability and maintain independent living in chronic stroke      |
|     patients. More specific training prescriptions are being tested   |
|     to target functional deficits. 1997-2005. Drs. Macko, Goldberg,   |
|     Hafer-Macko, Ryan, Shaughnessy, Sorkin, Katzel, Hanley, Ivey.     |
|                                                                       |
| -   Rehabilitation using bilateral arm training with rhythmic         |
|     auditory cueing (BATRAC) and Saeboflex (a new hand device to aid  |
|     grasp) in chronic stroke patients with upper extremity            |
|     hemiparesis show potential for improved motor function and brain  |
|     plasticity measured by functional magnetic resonance imaging.     |
|     More progressive and intensive programs are being implemented     |
|     using these methods to improve hand function. 2000-2005, Drs.     |
|     Whitall, McCombe-Waller, Luft, Hanley, Macko.                     |
|                                                                       |
| -   A number of improvements have been made to GERI, the informatics  |
|     system that is used to collect and store data from GRECC research |
|     studies for analysis. Modules have been added that help track (1) |
|     subject medications; (2) the status of research subjects in       |
|     protocols, and (3) facilitate reporting unexpected and adverse    |
|     events that may take place during research studies. The modules   |
|     assist GRECC investigators in the collection and analysis of data |
|     in GRECC research studies. 2000-2005. Drs Sorkin, Prigeon.        |
|                                                                       |
| []{.mark}                                                             |
|                                                                       |
| []{.mark}                                                             |
|                                                                       |
| -   We use high throughput genotyping, SNP identification and genome  |
|     wide scans to identify candidate genes in key regions that may    |
|     provide insights into the molecular mechanisms underlying the     |
|     etiology of type 2 diabetes, obesity, hypertension, stroke and    |
|     osteoporosis. These findings are being tested in pharmacogenetic  |
|     studies of responses lifestyle (diet, activity, stress) and       |
|     pharmacological interventions to determine clinical relevance and |
|     generalizability. We show that APOE, PPAR, 2-AR, 3-AR, and ACE    |
|     gene polymorphisms affect the lipid and glucose metabolic, body   |
|     composition and blood pressure responses to weight loss,          |
|     exercise, diet and AHA dietary interventions. 1999-2005.          |
|     Shuldiner, Mitchell, Kittner, Sorkin, Goldberg, Hagberg, Katzel,  |
|     Fried, Ryan, Prigeon, Macko.                                      |
|                                                                       |
| -   A novel study examines gene-environment interactions for          |
|     cardiovascular disease risk by assessing physiological responses  |
|     to cold pressor tests, high fat meals, high/low salt diets, and   |
|     aspirin in participants of the Amish Heredity and Phenotype       |
|     Intervention Heart Study. Genomewide linkage and association      |
|     analysis will evaluate genes that influence the responses to      |
|     these perturbations*.*2002-2005. Shuldiner, Mitchell, Sorkin.     |
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| **5. RESEARCH**                                                       |
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| a.  **Most Noteworthy Findings Published in Report Year by GRECC Core |
|     Staff as PI or CO-PI\                                             |
|     ***(Please list five or fewer. For each noteworthy finding,       |
|     include the GRECC Core Staff name(s), journal reference, and a    |
|     JARGON-FREE description of the finding and its clinical or other  |
|     significance. Please limit your description of each noteworthy    |
|     finding to five lines or fewer.)*                                 |
|                                                                       |
| -   **Charlene E. Hafer-Macko, M.D.,** Shuzhen Yu, M.D., **Alice S.   |
|     Ryan, Ph.D., Frederick M. Ivey, Ph.D., and Richard F. Macko,      |
|     M.D.** Elevated Tumor Necrosis Factor-alpha in Skeletal Muscle    |
|     After Stroke. Stroke. 2005; 36: 2021-2023.                        |
|                                                                       |
| There is muscular atrophy in the hemiparetic (partially paralyzed)    |
| leg and insulin resistance in chronic stroke patients. An             |
| inflammatory protein (cytokine), tumor necrosis factor - alpha (TNF)  |
| is implicated in both processes. We find that skeletal muscle TNF     |
| mRNA levels are 3.5-fold higher in the paretic and 2-fold higher in   |
| non-affected leg muscle after stroke compared with age-matched        |
| control muscles. The elevated muscle TNF in both legs suggests        |
| inflammatory pathways contribute to muscular atrophy and risk for     |
| diabetes after stroke. Treatments to lower muscle cytokine levels     |
| could restore muscle function and reduce risk for diabetes in stroke  |
| survivors.                                                            |
|                                                                       |
| -   **Richard F. Macko, M.D., Frederick M. Ivey, Ph.D., Larry W.      |
|     Forrester, Ph.D**., Daniel Hanley, M.D., **John D. Sorkin, M.D.,  |
|     Ph.D., Leslie I Katzel, M.D., Ph.D.,** Kenneth H. Silver, M.D.,   |
|     and **Andrew P. Goldberg, M.D.** Treadmill Exercise               |
|     Rehabilitation Improves Ambulatory Function and Cardiovascular    |
|     Fitness in Patients With Chronic Stroke; A Randomized, Controlled |
|     Trial. Stroke. 2005; 36:2206-2211.                                |
|                                                                       |
| Inactivity propagates disability while aging with disability from     |
| stroke. This randomized study is the 1^st^ to prove treadmill         |
| training more effective than conventional rehabilitation style        |
| exercises to improve walking function, ambulation and cardiovascular  |
| fitness in chronic stroke patients. Treadmill training improves both  |
| fitness and function even ten years post-stroke, with specific        |
| features of the exercise prescription predicting the nature of its    |
| benefits. This suggests T-AEX may improve free-living daily activity  |
| and function, reduce disability and maintain independent living in    |
| chronic stroke patients.                                              |
|                                                                       |
| -   Toni I. Pollin, Ph.D., Keith Tanner, Jeffrey R. O'Connell, Ph.D., |
|     Sandra H. Ott, Coleen M. Damcott, Ph.D., **Alan R. Shuldiner,     |
|     M.D.,** John McLenithan, Ph.D.**,** and **Braxton D. Mitchell,    |
|     Ph.D.** Linkage of Plasma Adiponectin Levels to 3q27 Explained by |
|     Association With Variation in the APM1 Gene. Diabetes 54:         |
|     268-274, 2005.                                                    |
|                                                                       |
| We found that adiponectin levels are linked to chromosome 3q27, which |
| encodes the adiponectin gene and specific SNPs within this gene       |
| appear to explain most or all of the linkage result. Elucidation of   |
| specific genes that increase susceptibility to diabetes and obesity   |
| will provide new molecular targets for the design of effective        |
| therapeutic and preventive strategies.                                |
|                                                                       |
| -   Maria E. Trujillo, Ph.D., Sean Sullivan, Ingrid Gharten,          |
|     Stephen H. Schneider, M.D., Andrew S. Greenberg, M.D., and        |
|     **Susan K. Fried, Ph.D.** Interleukin-6 Regulates Human Adipose   |
|     Tissue Lipid Metabolism and Leptin Production in Vitro. Journal   |
|     of Clinical Endocrinology and Metabolism 89: 5577-5582, 2004.     |
|                                                                       |
| Adipose (fat) tissue of obese individuals overproduces interleukin-6  |
| (IL-6). This study examines the effects of IL-6 on human fat cell     |
| function. We found that IL-6 promoted the breakdown of fat stored in  |
| fat cells and also decreased the activity of the enzyme lipoprotein   |
| lipase that normally promotes fat storage. When we add IL-6 and a     |
| glucocorticoid (a stress hormone) to fat cells, there is an increase  |
| in the production of leptin, a hormone that signals to the brain to   |
| decrease appetite. Thus, as the storage of fat increases in obesity,  |
| high local concentrations of IL-6 within the fat tissue of obese      |
| subjects limit fat storage. This could have implications for the      |
| treatment and prevention of obesity.                                  |
|                                                                       |
| -   **Marianne Shaughnessy, CRNP, Ph.D., Kathleen M. Michael, RN,     |
|     Ph.D., John D. Sorkin, M.D., Ph.D., and Richard F. Macko, M.D.**  |
|     Steps After Stroke: Capturing Ambulatory Recovery. Stroke. 2005;  |
|     36:1305-1307.                                                     |
|                                                                       |
| This study compared Step Activity Monitoring (SAM) with FIM mobility  |
| sub-scale, SAM-derived daily steps, Stroke Impact Scale (SIS)         |
| mobility scores, and timed walks in 11 subjects in the sub-acute      |
| stroke rehabilitation phase. SAM was found to be a more sensitive     |
| indicator of ambulatory recovery than other conventional outcomes     |
| instruments. The SAM represents an accurate, reliable new generation  |
| of outcome measurement instruments in patients with hemiparetic       |
| stroke and other gait disorders.                                      |
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| b.  **Most Noteworthy Findings Published in Report Year -- GRECC Core |
|     Staff as Co-Investigators on Projects with Non-GRECC PI\          |
|     ***(Please list five or fewer. For each noteworthy finding,       |
|     include the GRECC Core Staff name(s), journal reference, and a    |
|     JARGON-FREE description of the finding and its clinical or other  |
|     significance. Please limit your description of each noteworthy    |
|     finding to five lines or fewer)*                                  |
|                                                                       |
| -   Andreas R. Luft, M.D., Sandy McCombe-Waller, PT, Ph.D., **Jill    |
|     Whitall, Ph.D., Larry W. Forrester, Ph.D.,** **Richard F. Macko,  |
|     M.D., John D. Sorkin, M.D., Ph.D.,** Jorg B. Schulz, M.D.,        |
|     **Andrew P. Goldberg, M.D.,** Daniel F. Hanley, M.D. Repetitive   |
|     Bilateral Arm Training and Motor Cortex Activation in Chronic     |
|     Stroke. JAMA. 2004; 292: 1853-1861.                               |
|                                                                       |
| We showed that chronic stroke patients re-organize the neural         |
| pathways for elbow movements of the affected arm after 6 weeks        |
| repetitive bilateral arm training with rhythmic auditory cueing       |
| (BATRAC) but not after dose matched, therapeutic exercises. The       |
| neural changes were in the unaffected hemisphere and accompanied by   |
| motor function change. This is the first functional magnetic          |
| resonance imaging (fMRI) study to demonstrate a correspondence        |
| between neural and motor changes in stroke patients with moderate to  |
| severe impairments. This suggests BATRAC is a useful training         |
| stimulus to change brain activation and improve arm function in       |
| chronic stroke patients.                                              |
|                                                                       |
| -   Andreas R. Luft, M.D., **Larry W. Forrester, Ph.D., Richard F.    |
|     Macko, M.D.,** Sandy McCombe Waller, PT, Ph.D., **Jill Whitall,   |
|     Ph.D.,** Federico Villagra, Ph.D., and Daniel F. Hanley, M.D.     |
|     Brain activation of lower extremity movement in chronically       |
|     impaired stroke survivors. Neuroimage 26 (2005) 184-194.          |
|                                                                       |
| Hemiparesis (half-paralysis) is a major sequelae of stroke, yet brain |
| networks controlling the paretic leg are unknown. We found            |
| differences in 10 brain activation regions between controls and       |
| stroke patients moving the paralyzed knee. Activation sites related   |
| to stroke locations. Better walking was associated with less cortex   |
| activation on the stroke side, but stronger recruitment on the        |
| opposite, un-injured side. This provides insight as to how the brain  |
| adapts to improve function after a stroke.                            |
|                                                                       |
| -   Amy Halverstadt, Dana A. Phares, Stephen Roth, Robert E. Ferrell, |
|     **Andrew P. Goldberg, M.D.,** and **James M. Hagberg, M.D.**      |
|     Interleukin-6 genotype is associated with high-density            |
|     lipoprotein cholesterol responses to exercise training.           |
|     Biochimica et Biophysica Acta 1734 (2005), 143-151.               |
|                                                                       |
| Inflammatory proteins secreted from fat (adipocytokines, IL-6, TNF-)  |
| produce changes in cholesterol (heart protective, HDL-C) metabolism   |
| that increase risk for heart disease. We find significant             |
| associations between endurance exercise training induced improvements |
| in HDL-C and the IL6-174G/C gene promoter polymorphism, but not LDL-C |
| or TG (heart damaging cholesterol or triglyceride) in 65 men and      |
| women mean ages 601 years (SEM). These suggest that genetic           |
| susceptibility could affect heart disease risk (atherosclerotic       |
| responses) to high blood fat (hyperlipidemia), and identify subjects  |
| likely to derive heart-protective benefits from exercise training.    |
|                                                                       |
| -   Tongjian You, **Alice S. Ryan, Ph.D.,** and Barbara J. Nicklas,   |
|     Ph.D. The Metabolic Syndrome in Obese Postmenopausal Women:       |
|     Relationship to Body Composition, Visceral Fat, and Inflammation. |
|     Journal of Clinical Endocrinology and Metabolism 89: 5517-5522,   |
|     2004.                                                             |
|                                                                       |
| The increase in total and central obesity which usually occurs in     |
| older women, especially following the menopause transition is linked  |
| with a number of metabolic complications. In 58 postmenopausal women, |
| lean mass, visceral fat, and inflammation (plasma soluble tumor       |
| necrosis factor receptor 1) were higher in women with the metabolic   |
| syndrome (n=27) compared to those without the metabolic syndrome      |
| (n=31). Thus, aerobic fitness, body composition, body fat             |
| distribution and inflammation differ in obese postmenopausal women    |
| with and without the metabolic syndrome; this suggests that           |
| treatments to modify these risk factors could reduce risk for         |
| coronary heart disease in obese older women with the metabolic        |
| syndrome.                                                             |
|                                                                       |
| -   Shari R. Waldstein, Ph.D., and **Leslie I. Katzel, M.D., Ph.D.**  |
|     Stress-induced blood pressure reactivity and cognitive function.  |
|     Neurology 2005; 64: 1746-1749.                                    |
|                                                                       |
| Increased blood pressure (BP) and increasing heart rate in response   |
| to stress (stress reactivity) may increase the risk for               |
| atherosclerosis and stroke. We examined whether greater BP reactivity |
| was related to impaired cognitive (mental) function in 94 older       |
| adults. Exaggerated blood pressure and heart rate responses to stress |
| were associated with diminished performance on tests of immediate and |
| delayed verbal memory, and impaired ability to rapidly perform        |
| complex planning tasks (executive function). Thus high blood pressure |
| and increased blood pressure responses to stress may require          |
| treatment for the preservation of cognitive function.                 |
+-----------------------------------------------------------------------+
| **6. EDUCATION**                                                      |
+-----------------------------------------------------------------------+
| a.  **Innovations in Educational Activities Implemented During Report |
|     Year**\                                                           |
|     (*Please list up to five. For each, describe the innovation and   |
|     the context in which it was innovative. Please limit your         |
|     description of each innovation to five lines or fewer):*          |
|                                                                       |
| -   Dr. Shaughnessy has continued to work on the training module for  |
|     the Geriatric Extended Care (GEC) Referral Form, which has not    |
|     yet been rolled out nationally. However, training on completing   |
|     this new instrument started this year. This new form creates an   |
|     assessment and tracking mechanism that will eventually facilitate |
|     the planning of extended care needs for veterans nationwide.      |
|                                                                       |
| -   The interactive web-based module "Early Recognition of Acute      |
|     Illness in Older Adults" was completed and rolled out this year   |
|     to staff at the BRECC. This module educates bedside staff         |
|     regarding observations of behavioral, functional or cognitive     |
|     changes in vulnerable veterans and has a built in CPRS-based      |
|     evaluation mechanism that triggers notification reports to        |
|     nursing administration and medical providers, and tracks          |
|     outcomes. Orientation of all staff at BRECC and Perry Point       |
|     should be completed by FY 2006.                                   |
|                                                                       |
| -   GRECC investigators, in partnership with the GLTC service line    |
|     under Dr. Heuser, established a VISN 5 wide, integrated monthly   |
|     Geriatric Medicine Grand Rounds at BVAMC as an educational forum  |
|     for Geriatric faculty to present research and clinical topics,    |
|     and current advances in the care of the elderly. Conferences are  |
|     attended by medical students and housestaff from the UM-School of |
|     Medicine and simultaneously transmitted via two-way               |
|     videoconferencing to extended care staff at Martinsburg, West     |
|     Virginia, Washington DC, the BRECC and Perry Point VAMCs.         |
|                                                                       |
| -   Dr. Shaughnessy is part of a VA Geriatrics and Long Term Care     |
|     Delirium Special Interest Group comprised of investigators,       |
|     information management and educators in VAMCs nationwide that     |
|     meets via conference call monthly to design and implement plans   |
|     to study effective ways to identify and treat delirium in the     |
|     frail veteran population across settings.                         |
|                                                                       |
| -   Drs. Katzel and Sorkin are mentors and educators on a K30 grant   |
|     awarded to the University of Maryland to train new researchers in |
|     clinical investigation.                                           |
+-----------------------------------------------------------------------+
| b.  **Exportable Educational Products First Available for             |
|     Distribution in Report Year**\                                    |
|     *(Please list your most important products. Please limit to five. |
|     Your description of each item should succinctly summarize the     |
|     content, target audience, format, and product evaluation results  |
|     if any. You may include products developed in prior years ONLY IF |
|     THIS IS THE FIRST YEAR they have been available for distribution. |
|     Please limit each description to five lines or fewer)*:           |
|                                                                       |
| -   Dr. Shaughnessy was the author of the training module for the     |
|     Geriatric Extended Care (GEC) Referral Form, a new referral       |
|     instrument designed to assist with national planning for          |
|     long-term care needs. The GEC Referral Form has not yet rolled    |
|     out nationally, but the training module went into use this year,  |
|     as staff nationwide prepare for the rollout.                      |
|                                                                       |
| -   PRAISED (People Reducing Risk and Improving Strength through      |
|     Exercise and Diet) is a GRECC sponsored translational research    |
|     project that exported our successful GRECC exercise and weight    |
|     loss programs to a high-risk West Baltimore Faith Community. Dr.  |
|     Shaughnessy and an exercise physiologist conducted a 6-month      |
|     exercise and nutrition program in the participants' church, and   |
|     utilized prayer and social support to maintain motivation and     |
|     achieve weight loss goals.                                        |
|                                                                       |
| -   Dr. Macko and Dr. Whitall's work in exercise in stroke            |
|     rehabilitation will be highlighted in an upcoming episode of      |
|     Veterans HealthWatch, a cable show distributed to local cable     |
|     access stations in and around Baltimore and sponsored by the      |
|     VAMHCS Public Affairs Office. Taped copies of the show will be    |
|     available for distribution to VA's nationwide shortly.            |
|                                                                       |
| -   The Baltimore GRECC website,                                      |
|                                                                       |
|    [http://www.grecc.umaryland.edu](http://www.grecc.umaryland.edu/), |
|     was activated during FY05.                                        |
+-----------------------------------------------------------------------+
| **7. CLINICAL INNOVATIONS**                                           |
+-----------------------------------------------------------------------+
| **NEW DEFINITION:** A "Clinical Innovation" is an untested,           |
| GRECC-initiated clinical effort that ideally is related to one of the |
| GRECC's research foci. A Clinical Innovation may be a wholly original |
| clinical program or an original aspect of or variation on an          |
| established program. A Clinical Innovation must incorporate an        |
| evaluation plan for assessing the innovation's efficacy so that, if   |
| the innovation is demonstrated to be an improvement over an existing  |
| approach to care, there is a basis on which it can be exported for    |
| implementation elsewhere.                                             |
+-----------------------------------------------------------------------+
| a.  **Clinical Innovations Underway in Report Year**\                 |
|     *(list all Clinical Innovations underway during the report year.  |
|     For each, indicate whether the innovation is [N]{.underline}ew or |
|     [O]{.underline}ngoing in the report year. Please describe each    |
|     innovation in five lines or fewer)*:                              |
|                                                                       |
| -   MOVE! (Managing Overweight and Obesity for Veterans Everywhere)   |
|     (Ongoing). This program, developed by the VA National Center for  |
|     Health Promotion and Disease Prevention (NCP), is being pilot     |
|     tested at the Baltimore GRECC and other VA sites. A VA HSRD MERIT |
|     review for an optimized, more behaviorally intensive MOVE! in     |
|     collaboration with MIRECC (PI, Richard Goldberg, Ph.D.) for       |
|     treatment of veterans with serious mental illness received a      |
|     fundable priority score, and will begin in FY2006.                |
|                                                                       |
| -   PRAISED. (Ongoing) A GRECC translational research project         |
|     exported successful GRECC exercise and weight loss clinical       |
|     demonstration projects to a high-risk West Baltimore African      |
|     American faith community with funding support from the Maryland   |
|     Tobacco settlement. This collaboration with the church leadership |
|     examined the feasibility of church based lifestyle interventions  |
|     to decrease obesity, increase physical activity and reduce        |
|     cardiac risk factors.                                             |
|                                                                       |
| -   GETFIT (Ongoing): A cross-sectional examination indicates that    |
|     physical functional performance as indexed by the peak aerobic    |
|     capacity is markedly reduced (18 ml/kg/min versus 30 ml/kg/min    |
|     for age-matched non-infected) in the older HIV infected veterans. |
|     This could affect their dyslipidemia, body composition            |
|     (lipodystrohy syndrome), inflammation and muscle wasting. We are  |
|     currently enrolling the first cohort into an exercise             |
|     intervention to improve functional performance, strength and      |
|     quality of life in older veterans with HIV.                       |
|                                                                       |
| -   Stroke - Lipid Clinic (Ongoing) has expanded as a joint VA GRECC, |
|     Cardiology and Pharmacy Service intervention to include high risk |
|     Veterans with all types of cardiovascular disease complications.  |
|     It employs computerized lipid screening algorithms and            |
|     evidence-based treatments to treat dyslipidemia, hypertension and |
|     diabetes in veterans with stroke and cardiovascular disease. The  |
|     program will expand to include veterans hospitalized with acute   |
|     coronary syndrome and offer cardiac rehabilitation.               |
|                                                                       |
| -   Progressive BATRAC (New) We are examining Progressive BATRAC, a   |
|     modification of the original non-progressive BATRAC that uses the |
|     conditioning principles of intensity and duration to increase the |
|     upper extremity workload. Intensity is systematically increased   |
|     by either changing the frequency of arm movement or by inclining  |
|     the plane of movement against gravity to resistance. The training |
|     program will be extended from 6 to 12 weeks to attempt to         |
|     increase strength and motor control.                              |
|                                                                       |
| -   Saeboflex (New) Given that the success of non-progressive and     |
|     progressive BATRAC is largely limited to proximal movements in    |
|     those with no residual distal arm function, we are also exploring |
|     the use of a new dynamic hand assist "Saeboflex" that is used     |
|     with a custom-designed unilateral training program based on motor |
|     learning principles designed to promote hand use in those who     |
|     have no residual hand function.                                   |
|                                                                       |
| -   ISS collaboration (New) Collaboration has been established        |
|     between Dr. Macko and the Istituto Superiore di Sanita            |
|     (ISS\--Public Health Agency of Italy) to develop and test a       |
|     community- based exercise model for chronic stroke patients.      |
|     Population-based studies within the Italian "regionalized health  |
|     care system" are planned to test the impact of exercise on health |
|     outcomes and utilization in the chronic stroke population         |
|                                                                       |
| -   Spinal Cord Injury (New) Drs. Peter Gorman and Richard Macko are  |
|     funded on a VA Merit Review to study Lokomat Robotics assisted    |
|     aerobic exercise training in individuals with incomplete spinal   |
|     cord injury. This new Merit Review is linked to the VA Center of  |
|     Excellence in Exercise and Robotics.                              |
+-----------------------------------------------------------------------+
| b.  **Evaluation Results of Clinical Innovations listed in the        |
|     preceding box\                                                    |
|     ***(for each clinical innovation listed in 7-a above, summarize   |
|     evaluation outcome(s) identified in the report year, in five      |
|     lines or fewer. Please specify "no evaluation results" for any    |
|     innovation for which that is the case)*                           |
|                                                                       |
| -   GRECC exercise and nutrition research programs impact older       |
|     veterans at high risk for CVD through prudent changes in          |
|     nutrition and physical activity to prevent complications of CVD   |
|     and disability. We enrolled 42 veterans in the national MOVE!     |
|     Pilot study. The final subjects are returning during the next 2   |
|     months for 6-month follow-up. The first cohort lost an average of |
|     11 pounds or \~5.3% of their initial body weight. These programs  |
|     may be translated into clinical practice as part of the national  |
|     VA sponsored MOVE! Program.                                       |
|                                                                       |
| -   PRAISED The prevalence of obesity and other risk factors for      |
|     heart disease and diabetes is very high in this Black population. |
|     Thirty-four patients were initially enrolled in this pilot        |
|     program. Attendance and compliance to the intervention started    |
|     strong but fell with time. Total attrition was approximately 50%. |
|     However, those who completed the program lost an average of 7     |
|     lbs, and significantly lowered their blood pressure and increased |
|     their HDL cholesterol. Significant improvements were also seen in |
|     functional tests such as the 6-minute walk, which demonstrated    |
|     benefit from increased activity.                                  |
|                                                                       |
| -   Cardiovascular disease risk lipid clinic Examination of adherence |
|     to evidence-based guidelines indicates that LDL-C was assessed    |
|     acutely in \<50%of the patients with acute stroke. During the     |
|     6-month follow-up post-stroke, when stroke recurrence is highest, |
|     \<38% of patients are evaluated. Of these, only 42% were at       |
|     target with LDL-C\< 100mg/dl. A nurse practitioner is being       |
|     recruited to assist the Pharmacists in the clinic and develop a   |
|     cardiac rehab/MOVE! Program for cardiac patients.                 |
|                                                                       |
| -   GETFIT: There are no research outcomes on the effect of the       |
|     intervention on functional performance to report at this time.    |
|                                                                       |
| -   Progressive BATRAC: In 5 stroke subjects who completed the        |
|     progressive BATRAC pilot study, the quantitative effects on the   |
|     ability to coordinate and control the paretic arm are uniformly   |
|     positive. All patients reach further, faster, more smoothly and   |
|     more consistently after training. Patients also report increased  |
|     use of this arm in daily life usually in supportive roles such as |
|     carrying. Effects measured via standardized tests (i.e., Fugl     |
|     Meyer Test of Motor Impairment and Wolf Motor Function Test) are  |
|     more modest or mixed.                                             |
|                                                                       |
| -   Saeboflex: Since pilot work indicates that patients with little   |
|     initial proximal arm use do not benefit substantially from        |
|     BATRAC, we combined 6 weeks of the distal (Saeboflex) training    |
|     program with 6 prior weeks of progressive BATRAC. Data from one   |
|     subject who has completed this combination shows a huge gain      |
|     (80%) in a questionnaire on activities of daily living as well as |
|     reasonable gains on the standardized tests (Fugl Meyer = 28.5%    |
|     and Wolf = 11%).                                                  |
|                                                                       |
| -   ISS Collaboration: A hospital-based pilot study of 2 months of    |
|     adaptive physical activity in secondary chronic high-risk stroke  |
|     patients significantly improved balance function, floor walking,  |
|     and Geriatric Repression Scale scores. These promising findings   |
|     suggest that structured exercise can improve function and quality |
|     of life in older, chronically disabled stroke patients, which is  |
|     now being tested in a community-based intervention.               |
|                                                                       |
| -   Spinal Cord Injury: The Lokomat robot is adjustable to provide    |
|     varying levels of assistance to patients; however, there is no    |
|     pilot data to report at this time.                                |
+-----------------------------------------------------------------------+
| c.  **Clinical Innovation Exported in Report Year** Les please        |
|     answer\                                                           |
|     *(Please list up to five examples. In three lines or less for     |
|     each example, name or describe the innovation, identify the name  |
|     of the VA or non-VA facility to which it was exported, and the    |
|     method of export)*:                                               |
|                                                                       |
| -   PRAISED. The GRECC nutrition and exercise programs implemented a  |
|     pilot weight loss and exercise intervention at a large,           |
|     predominantly African American church in West Baltimore. The      |
|     GRECC will partner with the University of Maryland Center for     |
|     Health Policy & Health Services Research to submit an RO1 grant   |
|     to fund a larger intervention trial in this population.           |
|                                                                       |
| -   The treadmill exercise rehabilitation program for chronic stroke  |
|     patients was exported to the Ruxton Nursing Home and              |
|     Rehabilitation Center as a demonstration project to test the      |
|     translation of this effective laboratory based exercise           |
|     intervention to a community-based setting. The GRECC staff have   |
|     provided initial consultation, safety protocols and ongoing       |
|     collaboration to this effort which started at the end of FY 2005. |
|                                                                       |
| ```{=html}                                                            |
| <!-- -->                                                              |
| ```                                                                   |
| -   Drs. Macko and Goldberg have developed a collaboration with       |
|     Morehouse School of Medicine and SouthFulton Hospitals in Atlanta |
|     to implement and test treadmill aerobic training as a means to    |
|     improve outcomes and reduce recurrent stroke risk in this "stroke |
|     belt" region of the United States.                                |
|                                                                       |
| -   Collaborations between Dr. Macko and the Istituto Superiore di    |
|     Sanita (Public Health Agency of Italy) are now testing exercise   |
|     models at 5 community sites to improve health and function        |
|     outcomes in chronic stroke patients. These are based on models of |
|     motor learning --exercise for chronic stroke patients that were   |
|     developed at Baltimore VA as a GRECC demonstration project, and   |
|     provide a public health rationale based on improving insulin      |
|     sensitivity, to reduce CVD risk in this high- risk population.    |
+-----------------------------------------------------------------------+
| **8. CONSULTATION AND OUTREACH**                                      |
+-----------------------------------------------------------------------+
| **DEFINITIONS:**                                                      |
|                                                                       |
| **"Consultation"** for this section of the report has occurred when   |
| GRECC staff has materially assisted in the development of a non-GRECC |
| research, education or clinical program **[within the host            |
| VAMC.]{.underline}**                                                  |
|                                                                       |
| **"Outreach"** for this section of the report has occurred when GRECC |
| staff has materially assisted in the development of a non-GRECC       |
| research, education or clinical program **[at a facility other than   |
| the host VAMC.]{.underline}**                                         |
+-----------------------------------------------------------------------+
| **Note:**                                                             |
|                                                                       |
| **for the 2005 Annual Report,**                                       |
|                                                                       |
| **Consultation and Outreach activity**                                |
|                                                                       |
| **will NOT be reported here.**                                        |
|                                                                       |
| **It will be reported via the Electronic Annual report Data Base.**   |
+-----------------------------------------------------------------------+