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November 22, 2006

RESEARCH NOTES

Walking may prevent seniors’ disability

Regular structured exercise may allow previously sedentary elderly people to improve their physical functioning and reduce the likelihood they will become disabled in the future, according to findings from a multi-center pilot study presented Nov. 17 at the Gerontological Society of America’s annual meeting. The results of the study, known as the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study, also appeared in the November issue of the Journal of Gerontology: Medical Sciences.

The pilot study, which included researchers from Pitt’s Graduate School of Public Health, had a group of sedentary people ages 70-89 walk at a moderate intensity for at least 150 minutes a week and do leg stretches, balance exercises and leg-strengthening exercises. A control group was given only instructions on successful aging, which included information on good nutrition and the proper use of medications, foot care and preventive services. Both groups’ physical functioning was tested before the interventions and twice during the one-year study.

Participants in the physical activity group increased their performance score on a test known as the Short Physical Performance Battery, or SPPB, from a baseline average of about 7.5 to about 8.5, whereas the scores of many participants in the successful aging group declined. In addition, the physical activity group improved their performance on a 400-meter walking test and had a lower incidence of a major mobility disability (defined as an inability to walk a quarter-mile) than did those in the control group.

The study looked at people with SPPB scores from 4 to 9 to see if exercise could improve or prevent a decline in their scores. Even a half-point improvement on the 0-12 scale may represent major improvement in an elder person’s ability to perform activities of daily living, researchers said. A low score, 0-4, is a strong risk factor for disability and death.

Anne B. Newman, professor of epidemiology and medicine, director of the Center for Aging and Population Health at GSPH and principal investigator for the Pitt field center, said these findings confirm that even sedentary elderly can be brought back from the brink of disability by moderate, structured exercise.

Previous research has demonstrated that scores on the SPPB are highly predictive of future health problems. People with lower scores are more likely than others to die earlier, have health problems, be institutionalized and become unable to get around.

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Support improves quality of life for caregivers

A follow-up to the Resources for Enhancing Alzheimer’s Caregiver Health (REACH) I study has found that helping caregivers develop coping skills can improve quality of life for those caring for a family member with dementia. Results of the Pitt-coordinated study were published in the Nov. 21 issue of Annals of Internal Medicine.

The REACH II study found that an intervention tailored to meet individual needs can significantly ease the burden, improve quality of life and reduce the likelihood of clinical depression in the caregiver. The study intervention used strategies such as role playing, problem solving, skills training, stress management and telephone support groups to address five areas in which caregivers commonly experience problems: depression, caregiver burden and stress, attention to personal health needs, social support and problem behaviors exhibited by the care recipient, such as aggressive outbursts or feelings of hopelessness.

At a six-month follow-up, the rate of clinical depression was significantly lower among the participants who received the intervention than those in the control group. Caregivers also reported that the intervention helped them feel more confident and able to deal with caring for their loved one, improved the care-recipient’s quality of life and helped them keep the recipient at home.

Researchers found that, overall, the intervention was effective across racial and ethnic groups, with the most significant improvements among Hispanic and white caregivers. In African Americans, the intervention was effective among spouse-caregivers, but relatively ineffective among caregivers who were caring for a relative other than their husband or wife.

Richard Schulz, professor of psychiatry and the study’s corresponding author, said, “For the millions of Americans who care for a loved one at home, an intervention that can improve their quality of life and lessen the burden of care-giving can make meaningful differences in their ability to better care both for themselves and their loved ones.”

Other Pitt co-authors were Steven H. Belle and Song Zhang of epidemiology and Julie Klinger of the University Center for Social and Urban Research.

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State funds more of MWRI expansion

The Magee-Womens Research Institute & Foundation has received $500,000 toward its $31 million building expansion from the state House and Senate Republican Caucus. Added to earlier funding from the governor’s office and the Democratic and Republican caucuses, the donation brings the total state contribution to $5 million.

Occupancy of the 70,000-square-foot. expansion of the MWRI building at Forbes and Craft avenues is expected in early 2007.

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UPMC gains MDS center of excellence designation

The Myelodysplastic Syndromes Foundation has recognized UPMC Cancer Centers as a Center of Excellence in the research, diagnosis and treatment of myelodysplastic syndrome (MDS).

MDS, a precursor to leukemia, is a group of disorders in which the bone marrow does not produce enough blood cells, which can lead to anemia, increased risk of infection and risk of severe bleeding. It is most common in people over the age of 60.

The designation will allow UPMC Cancer Centers to conduct multi-site clinical trials on MDS and to use the foundation’s international patient registry as a central database to identify characteristics of the disease.

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Black women left behind in breast cancer decline

Despite an overall decline in invasive breast cancer in the United States in recent years, African-American women, particularly younger ones, have not seen a significant decline in their rates, according to Pitt researchers. These findings, presented at the American Pubic Health Association annual meeting this month, strongly suggest the need for additional research to understand why these differences persist and to determine whether avoidable or preventable factors account for these patterns, the investigators said.

Breast cancer affects more than 2 million women in the United States each year and accounts for almost one in three cancer diagnoses in women. About 40,000 U.S. women die of the disease each year. Although white women have the highest overall breast cancer incidence rates, African-American women under age 40 have a significantly higher incidence of breast cancer as well as a higher rate of death from breast cancer than do white women. Furthermore, African Americans with breast cancer die at a younger age than women in other groups.

Researchers from the Graduate School of Public Health (GSPH) and the UPCI Center for Environmental Oncology analyzed breast cancer incidence among African-American and white women in the United States from 1975 to 2002. This study found that the chances of getting breast cancer in newer generations are about 21 percent higher in whites and 41 percent higher in African Americans than in previous generations of women.

The researchers attributed much of the increased incidence among white women to better detection and to the use of hormone replacement therapy. However, because mammographic screening is not typically recommended for younger African-American women, increased detection or changes in medical practice cannot explain the patterns of breast cancer seen in this ethnic group.

Among the many factors that could contribute to the difference, environmental factors are strong candidates, said lead investigator Devra L. Davis, director of the UPCI Center for Environmental Oncology and professor of epidemiology at GSPH. In particular, certain hormone-mimicking compounds, such as bisphenol A, a widely used plasticizer, and preservatives, called parabens, that are frequently used in personal care products, including deodorants, antiperspirants and many cosmetic, food and pharmaceutical products, have been shown to accelerate breast cancer cell growth in cell cultures.

In an upcoming paper in the journal Medical Hypotheses, Davis, along with Maryann Donovan, scientific director of the UPCI Center for Environmental Oncology, and their colleagues suggest that the use of estrogen and other hormone-containing personal care products by younger African-American women may account, in part, for their increased risk of breast cancer prior to menopause when developing breasts are subjected to elevated estrogen exposure during critical windows of vulnerability. The paper calls for public disclosure by manufacturers of personal care products of proprietary hormonally active ingredients in their products.

Other Pitt researchers involved in the study were Ji Young Song of the UPCI Center for Environmental Oncology and Yueh Ying Han and Joel L. Wessfield of GSPH.

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Visual stability circuit found

Although human eyes constantly are making small jumps, the world appears as a smooth whole because the brain’s visual system adjusts for the movement. In a paper recently published online in Nature, researchers at Pitt and the National Eye Institute (NEI) for the first time provide a circuit-level explanation as to why.

“This is a classic problem in neuroscience,” said Marc Sommer, assistant professor of neuroscience at Pitt who co-authored the paper with Robert Wurtz, senior investigator at NEI. “People have been searching for a circuit to accomplish this stability for the last 50 years, and we think we’ve made good progress with this study.”

In 1950, Nobel Laureate Roger Sperry hypothesized that when the brain commands the eyes to move, it also sends a corollary discharge, or internal copy, of that command to the visual system. Sommer and Wurtz showed in a 2002 Science paper that a pathway from brainstem to frontal cortex conveys a corollary discharge signal in the brains of monkeys. They suggested that this pathway might cause visual neurons of the cortex suddenly to shift their receptive field — their window on the world — just before a saccade, or jump.

In their current paper, which appeared in the Nov. 16 print edition of Nature, Sommer and Wurtz completed the circuit. They showed that the receptive fields in cortex are shifted because of the corollary discharge from the brainstem. To do this, they exploited the fact that the signals are relayed via the thalamus, a crucial intermediary. By knocking out the relay neurons, they interrupted the pathway. They found that receptive field shifts were curtailed by more than half.

A similar circuit is likely to exist in human brains, the researchers say. With this study, Sommer and Wurtz also provide a framework for studying corollary discharge in other sensory systems, such as hearing: When one moves one’s head around, sounds are still perceived as coming from the same place.

In future studies, Sommer and his graduate students will perform the first direct test of the visual stability hypothesis. To determine whether shifting receptive fields are responsible for visual stability, the shifts will be disrupted in monkeys trained to detect visual motion and indicate whether their world appears to be moving around abnormally as eye movements are made.

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Radiation oncology research presented

Radiation oncologists from Pitt’s School of Medicine recently presented research findings at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

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IMRT cuts side effects for cervical cancer patients

Preliminary results from an evaluation of extended-field intensity-modulated radiation therapy (IMRT) for cervical cancer found that it resulted in significantly reduced side effects and outcomes comparable to standard radiotherapy. Unlike standard radiation therapy, IMRT administers a radiation field that consists of several hundred small beams of varying intensities that pass through normal tissue without doing significant damage but converge to give a precise dose of radiation at the tumor site.

Dwight E. Heron, study co-author and associate professor of radiation oncology at the School of Medicine and director of radiation oncology at UPMC, said: “Our study demonstrates that with IMRT, we can target high-energy beams directly to the tumor site and the areas of concern where the cancer cells may travel, resulting in less side effects and enabling us to give a full therapeutic dose.”

Heron said standard extended-field radiotherapy causes serious side effects including frequent urination and pain, diarrhea and bowel obstruction in as many as 40 percent of patients.

In the current study, 36 patients with cervical cancer were treated with extended-field IMRT and chemotherapy. Thirty-four had a complete response to treatment. Only two patients developed higher-grade gastrointestinal and urinary side effects and 10 developed myelotoxicity, a slowdown of blood cell production that is common with chemotherapy. The overall survival rate at two years was 54 percent.

“By using extended-field IMRT and chemotherapy, we were able to effectively reduce the toxic effects of treatment,” said Sushil Beriwal, principal investigator and assistant professor at the School of Medicine and medical director of radiation oncology at Magee-Womens Hospital. “This is important because it means there are less treatment interruptions and more patients are able to complete the treatment within the prescribed time period. This, in turn, increases the efficacy of treatment.”

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Integrated approach to IMRT provides quality cancer care

A Pitt study has demonstrated that intensity-modulated radiation therapy (IMRT) can be delivered uniformly in a large health care system of academic and community cancer centers through a centralized planning and treatment process, showing that patients can receive consistent quality of care despite geographic distances.

“Our study demonstrates that it is feasible for patients to receive IMRT in their own communities without sacrificing high-quality care,” said Ajay Bhatnagar, principal investigator of the study and chief resident in the Department of Radiation Oncology at the School of Medicine. “This is possible through an integrated network in which treatment is standardized across all cancer centers.”

The study found no significant differences in toxicity profiles and recommended radiation dose prescriptions in 758 prostate cancer patients treated with IMRT at 12 separate community cancer centers and one academic flagship facility. All 13 centers, connected through a telemedicine network, followed the same clinical pathway guidelines for the radiotherapy management of prostate cancer, which included specifics on volumes for radiation treatment planning and doses of IMRT.

“By standardizing planning and treatment for IMRT, patients who live in remote locations can benefit from the same quality of care available at a large academic medical center,” said Dwight E. Heron, study co-author and associate professor of radiation oncology at the School of Medicine and director of radiation oncology at UPMC.

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CMU, UPMC partner in health care info research

Carnegie Mellon University and the University of Pittsburgh Medical Center have signed a five-year, $10 million agreement for sponsored research in computer science, engineering, robotics and other advanced technology areas related to health care.

Among their plans is examining ways to make more reliable and efficient use of health care information. UPMC will serve as a setting to test emerging technologies developed at CMU.

Other planned projects include technology-enhanced training and simulation; secure, ubiquitous communication and access to health care information; business process management and optimization; medical robotics; medical-image processing, and other related research areas. Specific projects will be identified once the partnership takes effect in January.

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Ideal body image may shift following weight loss surgeries

Some people who undergo bariatric surgery and subsequent body contouring find themselves pleased with their significant weight loss but, over time, desire to be even thinner, according to a study published by UPMC researchers in the current issue of Obesity.

Using a rating scale specifically designed to measure quality of life in the post-bariatric population, researchers asked study participants to rate their body image, their desired silhouette, mood and quality of life at three months and again at six months following body contouring. While overall quality of life scores improved and mood remained stable over the six-month study period, study participants tended to view thinner silhouettes as the “ideal” body.

“While body contouring improves body image, often it also produces dissatisfaction with other parts of the body, suggesting that as patients become closer to their ideals, these ideals may shift,” said study author Madelyn Fernstrom, director of the UPMC Weight Management Center and associate professor of psychiatry, epidemiology and surgery at Pitt. “If we understand the issues that affect this unique group and know how to address their specific concerns, then we can help them to achieve lasting satisfaction with their weight loss and body images.”

This information, the authors suggest, may help to answer the debate about whether body contouring is a vanity operation or the second step in the surgical treatment of severe obesity. Body contouring after massive weight loss can alleviate common weight-loss deformities that tend to cause patients distress regarding their appearances, including excess skin, rash and hygiene problems and difficulties with mobility.

“In a patient who has undergone a striking transformation from massive weight loss, everything changes — from self-image to quality of life to mood,” said Angela Song, a plastic surgery resident at the School of Medicine. “Body contouring offers added benefits, but it also is possible that those who take this additional step cannot fully reap the psychological rewards of massive weight loss due perhaps to residual feelings of unattractiveness or self-consciousness.”


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