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August 29, 2002

RESEARCH NOTES

Grants awarded to researchers

The National Institute on Aging has granted Kathryn M. Albers of the School of Medicine $349,302 to study "Mechanisms of Aging in the Somatosensory System." The goal of this research is to identify the cellular mechanisms that lead to degeneration of sensory neurons and their end organs and determine whether the level of trophic support provided by the skin can alleviate the onset and progression of age-related deficits in sensation.

German Barrionuevo, professor of neuroscience and psychiatry, has received a $100,000 Independent Investigator Award from the National Alliance for Research on Schizophrenia and Depression. Barrionuevo is studying the dynamics of synaptic transmission and calcium transients in the in vitro monkey prefrontal cortex during natural patterns of stimulation.

The Ford Foundation has awarded $300,000 to the music department's Nathan Davis to continue support of the International Institute of Jazz at Pitt.

The nursing school's Sandra Engberg has been granted $360,207 by the National Institute of Nursing Research to continue research on maintaining post-treatment continence in the homebound elderly.

The U.S. Department of Education has granted $463,023 to Renee Frazier of the University Challenge for Excellence Programs to continue funding of the Upward Bound project at Pitt. Upward Bound provides academic and personal support services to encourage low-income and/or first-generation college students to pursue post-secondary educations.

Mitchell Seligson of the political science department has been awarded $259,832 by ARD, Inc., for "A Study of the Impact on Democracy of Municipal Development in Ecuador." The study will conduct surveys of approximately 4,500 Ecuadorians in 15 municipalities.

The Air Force Office of Scientific Research has granted $350,000 to Judith Yang of the engineering school to acquire a portable hyperthermal atomic oxygen source for use in a multi-university study of fundamental mechanisms of degradation of materials in outer space.

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Institute gets $8.9 million for research into osteoarthritis

The University of Pittsburgh Arthritis Institute has received an $8.9 million grant from the National Institutes of Health's (NIH) National Institute of Arthritis and Musculoskeletal and Skin Diseases for a research study on early osteoarthritis (OA) in the knee, with the ultimate goal of speeding OA drug development.

Pittsburgh is one of four clinical centers nationally to participate in the Osteoarthritis Initiative, a public-private partnership that brings together new resources to help find biological and structural markers for progression of this degenerative joint disease, which is a major cause of disability in older people.

The seven-year project, which will recruit 5,000 people nationally at high risk of developing osteoarthritis in the knee, will collect information and define disease standards.

C. Kent Kwoh, professor of medicine and epidemiology, is the principal investigator for Pitt.

"The ultimate goal of the Osteoarthritis Initiative is to identify biomarkers of disease risk and/or progression," Kwoh said. "These biomarkers are critical to the development of new therapies to halt the progression of osteoarthritis. Our current treatments address only symptoms such as pain without changing the course of the disease."

Kwoh said that next spring the Arthritis Institute will begin recruiting between 1,250 and 1,500 participants over age 50 who will undergo periodic X-ray and magnetic resonance imaging examinations to reveal any physical changes in the knee joint along with blood draws to identify biomarkers. This information will go into a national database.

While recent advances have yielded highly effective therapies for rheumatoid arthritis, no such therapies exist for osteoarthritis, and most current treatments are designed only to relieve the pain and stall the disability caused by bone and joint degeneration.

Today, 35 million people — 13 percent of the U.S. population — are 65 or older and more than half of them show evidence of osteoarthritis in at least one joint. By 2030, 20 percent of Americans — about 70 million people — will have passed their 65th birthday and will be at increased risk for OA.

The Osteoarthritis Initiative's co-principal investigator at Pitt is Anne Newman, associate professor of geriatric medicine. Co-investigators include Bret Goodpastor, assistant professor of medicine and endrocrinology; Douglas Robertson Jr., associate professor of radiology and orthopaedic surgery; Said Ibrahim, assistant professor of medicine; Kathryn Wildy, instructor of medicine, and Fernando Boada, associate professor of radiology and bioengineering.

The initiative's consortium includes funding from NIH and the pharmaceutical companies GlaxoSmithKline, Merck, Novartis and Pfizer. Other centers involved in the research study are the University of Maryland School of Medicine, Baltimore; Ohio State University, and Memorial Hospital of Rhode Island, Pawtucket. The University of California at San Francisco is the data coordinating center.

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Botox used to treat spasticity in stroke patients

Researchers have found that intramuscular injections of botulinum toxin type A (BTX-A), commonly known as botox, effectively improve disability of the wrist and fingers after a stroke, according to an article in The New England Journal of Medicine.

The study assessed the effects of singular BTX-A injection sessions on measures of self-care, limb posture, pain and muscle tone. Sixty-two percent of the patients receiving the BTX-A injections reported improvement in their symptoms, with no serious adverse effects. The benefits lasted for at least 12 weeks.

"Seventy percent of patients survive stroke or, in other words, six out of 1,000 people in the United States are stroke survivors," said Ross Zafonte, professor and chair of the Pitt medical school's Department of Physical Medicine and Rehabilitation, who participated in the trial during his tenure at the Rehabilitation Institute of Michigan. "Many of these patients experience spasticity of the upper limbs, which limits their ability to participate in many activities of day-to-day life like dressing and washing. This study proves that botox injections can dramatically improve these patients' quality of life."

Spasticity — tight or stiff muscles that may be subject to spasms — can affect the arms and/or legs with stiffness, pain, long-term muscle shortening, fibrosis and loss of muscle tone. Spasticity is caused by injury to the brain, as in stroke, causing the brain to lose control of muscle function.

"This study confirms the efficacy of a treatment that doctors across the country have been offering to their patients at centers like the UPMC Spasticity Center for some time now," said Michael C. Munin, director of the UPMC Spasticity Treatment and Evaluation Center. "Most importantly, the study proves not only that the treatment works by reducing muscle tone, but it also shows the positive rehabilitative effects — and that is what matters most to our patients."

The UPMC Spasticity Evaluation and Treatment Center offers botox injections and other treatments for patients with spasticity due to stroke, brain injury, spinal cord injury, neuro-degenerative disease or multiple sclerosis.

"More than 500,000 Americans suffer from spasticity, for a variety of reasons, including stroke," said Munin, who also is an associate professor of physical medicine and rehabilitation here.

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GSPH prof leads study of brain cancer cluster

Gary M. Marsh, professor of biostatistics at Pitt's Graduate School of Public Health (GSPH), has received a $4 million grant to investigate a cluster of brain cancer cases at the Pratt & Whitney jet engine manufacturing plant near New Haven, Conn. The study is funded by Pratt & Whitney.

The cluster of brain cancer cases was first noted more than two years ago and has been investigated by the National Institute of Occupational Safety and Health (NIOSH) and the Connecticut Department of Health. After a feasibility study was conducted by Marsh and Nurt Esmen of the University of Oklahoma, Pratt & Whitney funded the larger study with the recommendation of both NIOSH and the state of Connecticut.

Marsh will perform a series of epidemiological studies in the company's index and control plants. Esmen, a former GSPH faculty member, has separate funding of a similar amount to assess the extent of exposure to various chemicals at the plant. The investigation is expected to take six years.

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Surgery prof's research team gets grant

A research team led by Pitt surgery professor Rakesh Sindhi was among 11 research groups worldwide to be awarded a total of $1 million from the Roche Organ Transplantation Research Foundation (ROTRF). The grants will support research on solid organ transplantation.

The research by Sindhi's team is entitled, "Designing Biomarker-Assisted Clinical Trials for Immunosuppressants." Their proposal was among 11 worldwide to be awarded ROTRF grants, from among 124 applicants.

ROTRF is a non-profit, independent and autonomous registered medical charity dedicated to advancing organ transplantation by supporting research with operating grants.

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Pregnancy hormone induces healthy blood vessels

The pregnancy hormone relaxin induces a healthy physiological response in blood vessels, increasing dilation and benefiting blood pressure and kidney function, scientists at Magee-Womens Research Institute report in the August issue of the American Journal of Physiology.

Specifically, relaxin affects kidney arteries by revving up production of nitric oxide in a layer of cells lining the inside of blood vessels called the endothelium. Finding the key to this physiologic response could have significant implications for the treatment of hypertension and other cardiovascular diseases.

"This study, which mainly targeted small renal arteries isolated from rats, is consistent with our earlier work showing that relaxin increases renal blood flow and kidney filtration by as much as 40 percent in non-pregnant rats," said senior study author Kirk P. Conrad, an investigator at the Magee-Womens Research Institute and a professor of obstetrics, gynecology and reproductive sciences and of cell biology and physiology at Pitt's School of Medicine. The hormone causes similar increases in kidney function during pregnancy.

"Linking relaxin with nitric oxide is another peptide hormone called endothelin which has a receptor on endothelial cells that increases nitric oxide," Conrad added. It is the action of endothelin and nitric oxide that increases dilation in the blood vessels, improving blood flow.

"What happens to the cardiovascular and renal systems during pregnancy is in many respects the antithesis of changes associated with aging," said Conrad. "If we can discover the hormones responsible for these pregnancy changes and how they work, they might be useful for fighting high blood pressure and other cardiovascular diseases such as heart attack and stroke."

Cardiovascular disease remains the No. 1 killer of Americans.

"Relaxin is an ovarian hormone that was discovered in 1926," said Jacqueline Novak, primary study author and a Pitt assistant professor of obstetrics, gynecology and reproductive sciences. "When a woman becomes pregnant, relaxin rapidly increases in the blood. Changes in the renal circulation are nearly at their highest by the end of the first trimester of pregnancy."

Experiments have shown relaxin to be "a potent renal vasodilator even in male rats," Novak said.

Conrad added: "Our studies on relaxin suggest that it may be time to evaluate other female hormones besides estrogen for affects on cardiovascular health — particularly in light of the newest findings on hormone-replacement therapy."

Funding was provided by the National Institutes of Health.

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More specialist care means fewer health problems for diabetics

People with type 1 diabetes who are treated by specialists — rather than general practitioners — are less likely to develop diabetes-related complications, according to a study by Pitt researchers.

Using data from 429 subjects in the Pittsburgh Epidemiology of Diabetes Complications Study, researchers found people who were treated primarily by general practitioners developed a higher incidence of coronary artery disease, kidney disease and problems with their nerves. Those who spent two-thirds of their years of diabetes under the care of a specialist — such as an endocrinologist, diabetologist or doctor at a diabetes clinic — were one-third to one-half as likely to develop these complications.

The researchers concluded that specialist care, or coordinated care between generalist and specialist providers, should be made more broadly available to all people with type 1 diabetes. The current lack of access to specialist care by some populations may be due to lack of coverage by some health insurance plans and a lack of patient knowledge about available resources.

Janice Zgibor of the Graduate School of Public Health's epidemiology department, was the study's lead researcher.

Study results appear in the September issue of Diabetes Care, a peer-reviewed journal published by the American Diabetes Association.


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