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July 24, 1997

RESEARCH NOTES

Johnstown prof receives grant

John D. Beuthin, an assistant professor of geology and planetary science at Pitt's Johnstown campus, has received an $1,800 grant from the West Virginia Geological and Economic Survey.

The grant will support Beuthin's research examining the rocks that form the boundary between the Mississippian and Pennsylvanian geological periods. Part of the project is to determine the paleoenvironments in which these rocks were deposited by correlating them with strata of a similar age in other parts of the world.

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Musculoskeletal researcher team is honored

The American Orthopaedic Society for Sports Medicine (AOSSM) has awarded its 1997 O'Donoghue Sports Injury Research Award to a team of researchers from the UPMC Musculoskeletal Research Center. The award is the highest and most prestigious given by AOSSM.

The award was given for the project, "Growth Factors Can Improve MCL (medial collateral ligament) Healing in Vivo." Pitt researchers participating in the project included Kevin Hildebrand, Savio Woo, David Smith, Christina Allen, Masataka Deie, Brian Taylor and Christopher Schmidt.

Their work showed that the presence of growth factors at the site of a complete MCL tear can reduce the size of the scar tissue mass and improve the histological and biomechanical quality of the healing tissue. IL-12 gene therapy reduces tumors in patients with advanced cancer, research shows Injecting cells genetically engineered with the genes of the hormone-like substance, inter-leukin-12 (IL-12), can significantly reduce tumors in some patients with advanced cancer, according to University of Pittsburgh Cancer Institute (UPCI) researchers.

The results were based on the first gene therapy trial using IL-12 for patients with breast cancer, melanoma, thyroid cancer or head and neck cancer.

"IL-12 gene therapy successfully reduced tumors in 28 percent of patients treated," said Michael Lotze, who is the study's principal investigator as well as co-director of UPCI's Biologic Therapeutics Program and professor of surgery and molecular genetics and biochemistry.

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Prozac may be first effective drug treatment for anorexia nervosa

Prozac may help people with anorexia nervosa maintain healthy body weight, according to results of a UPMC study.

The study is the first to suggest that an antidepressant may prevent a relapse into anorexia, said the study's principal investigator, Walter H. Kaye, professor of psychiatry at Western Psychiatric Institute and Clinic.

Anorexia nervosa is the most deadly psychiatric disorder. There is no medication approved to treat it. Patients starve themselves in pursuit of weight loss and have accompanying symptoms such as depression, anxiety, obsessions and compulsions. Research indicates these symptoms may be linked to disturbances in serotonin, a neurotransmitter that helps regulate mood and appetite. Prozac may work by stabilizing serotonin systems in the brain, correcting the changes in brain function responsible for many of the disorder's symptoms.

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Working memory may operate outside conscious awareness, UPMC and CMU researchers say

Research at UPMC and Carnegie Mellon University have identified regions of the brain that allow learning to take place without the person being consciously aware of it. The results could change the way researchers view learning and may affect treatment of certain disorders.

"Being able to learn and adapt to change subconsciously is an important function of the brain," said principal investigator Gregory S. Berns, resident in psychiatry at Western Psychiatric Institute and Clinic.

"People base their behavior on consistency, whether it's driving to work every day or investing in the stock market," Berns explained. "People who play the stock market, for example, often develop a hunch on how a stock is going to move, without being able to say exactly why they feel that way. They may do this because one part of their brain has formed expectations based on certain consistencies about the market while the other part is paying attention to what is actually happening moment to moment, both working on a subconscious level. These two parts of the brain share information and the investor forms a hunch." The area of the brain that researchers believe is responsible for learning consistencies and storing expectations is in the right prefrontal cortex, behind the forehead above the right eye.

Deep in the center of the brain, a part of the basal ganglia called the striatum seems to weigh what the cortex knows from experience against what is happening at that moment. If something in the environment changes, this system picks up on it and unconsciously alters behavior accordingly.

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Pitt study links auto crashes to long-term stress

Victims of serious motor vehicle accidents who were not responsible for the crash suffer more long-term distress than drivers who were responsible, a Pitt study shows. Drivers responsible for a crash seemed to cope more easily with the memories, while those not responsible suffered long-lasting fear of being unable to control future driving experiences.

Andrew Baum, professor of psychiatry and psychology who was the study's senior author, interviewed 130 victims of serous car crashes at two weeks, three months, six months and one year after the accidents. A control group of 43 people was included for comparison.

Researchers found that a year after an accident, 41 percent of non-responsible drivers continued to show symptoms of post-traumatic stress disorder (PTSD). However, drivers who actually caused crashes dealt with their trauma through a mental process called "self-blame coping. A year later, only 13.6 percent showed PTSD symptoms.

Baum said, "Victims who did not do anything wrong to cause the accident may have not seen any behaviors they could change, and thereby lost some confidence in their ability to avoid future driving accidents. But the responsible group used self-blame as a way to gain a sense of control over present and future accidents."

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UPMC study shows immune globulin improves heart function in adult cardiomyopathy patients

Cardiac researchers at the University of Pittsburgh Medical Center (UPMC) have found that patients with acute cardiomyopathy who were treated with high doses of intravenous immune globulin, human antibodies, showed a significant improvement in heart function to the extent that they were removed from the heart transplant waiting list.

Dennis McNamara, assistant professor of medicine and director of UPMC's cardiomyopathy clinic, led the study.

"Immune globulin is frequently used to treat other autoimmune diseases but has never been looked at in adults with inflammatory heart disease," McNamara said. "We wanted to determine if patients with recent onset acute primary dilated cardiomyopathy, who were sick enough to need a heart transplant, might improve with therapy sufficiently to delay or prevent the need for heart transplantation." The study followed 10 patients, one of whom died before the therapy could be completed. The remaining nine patients received intravenous immune globulin for up to four days and discharged from the hospital. Patients ranged in age from 18 to 60. All were awaiting heart transplants. After one year, all nine showed an improved left ventricular ejection fraction, the percentage of blood ejected from the heart during each beat.

"The immune globulin essentially reset the body's immune system and allowed the body to heal itself," McNamara said. "The average increase in ejection fractions was twice what had been reported using other treatments. All had a marked improvement in their exercise capacity and quality of life. All were working and none of them, two years after treatment, have been readmitted to the hospital with heart failure." In contrast, during the same study period, 72 other patients were treated conventionally; 31 percent had died or received transplants after one year.

"We are now in the middle of a multi-center trial which will include 60 patients nationwide," McNamara said. "We are excited by the results of this initial study, but we need a controlled trial in a large group before we know what role immune globulin will play in the treatment of this illness." Heart failure due to dilated cardiomyopathy affects more than 100,000 Americans and is a major reason for heart transplants in young adults. Studies suggest that the condition results from a common viral infection which, in some patients, causes an autoimmune response in which the body attacks itself.

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UPJ professor gets grant

Stephen Kilpatrick, assistant professor of biology at the Johnstown campus, has received a $10,429 University of Pittsburgh Research Council grant to research his proposed project, "Molecular Population Genetics of Drosophila melanogaster.

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Energy department awards Pitt $5 million for radiation science training center

The U.S. Department of Energy (DOE) has awarded Pitt $5 million to establish the first comprehensive training program for post-doctoral fellows in radiation research.

Designated a University Center for Excellence for Training in Radiation Science by the DOE, Pitt will recruit highly qualified candidates with scientific or medical doctoral degrees for an intensive education program, which will include in-depth coursework and independent research in health physics, radiobiology, radiation epidemiology, toxicology of radiation, occupational and environmental medicine and health risk assessment. The program is devised to be flexible and individualized and offers a competitive stipend.

Pitt's program will be based in the Department of Environmental and Occupational Health in the Graduate School of Public Health. Program leaders say they hope to train 30 fellows over five years.

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Storm forecasting wins award

A storm forecasting system developed by University of Oklahoma researchers using resources at the Pittsburgh Supercomputing Center won the 1997 Discover Magazine Award for Technological Innovation in Computer Software.

The system, called the Advanced Regional Prediction System (ARPS), could save billions of dollars annually in U.S. business and property loss as well as innumerable lives. Current methods give about 30 minutes' warning of severe storms, with fairly imprecise information about extent and severity. In 1996 tests at the Pittsburgh Supercomputing Center, ARPS predicted storms seven hours in advance with a high degree of accuracy.

The Pittsburgh Supercomputing Center is a joint effort of Pitt and Carnegie Mellon University, together with Westinghouse Electric Corp.

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New treatment improves survival for non-small cell lung cancer

A novel treatment using combination chemoradiation for regionally advanced, surgically unremovable non-small cell lung cancer (NSCLC) appears to be promising and could lead to a new standard of care for the disease, according to a Pitt researcher.

The treatment uses the drugs Taxol (paclitaxel) and Paraplatin (carboplatin for injection) in conjunction with thoracic radiotherapy.

An ongoing Pitt study of 38 NSCLC patients projects that 54 percent of them will remain alive after three years. That's compared with an average 19 percent survival rate at the three-year mark for patients receiving conventional chemotherapy and radiation treatment.

"The message here is that this early, aggressive, well tolerated treatment appears to save a significant number of lives," said study leader Chandra Belani, a Pitt associate professor of medicine and co-director of experimental therapeutics at the University of Pittsburgh Cancer Institute.

Lung cancer is the largest single cause of cancer death in the United States, according to the National Cancer Institute. Hard to detect and difficult to treat, it is responsible for one of every four cancer deaths in the nation. The five-year survival rate has remained low — 12 percent in 1973 and 13 percent in 1992.

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Study improves prognostic tools for AIDS and HIV-infected patients

The development of effective treatments for some AIDS patients within the last few years presents physicians with a new dilemma: When should they initiate therapy? A report in the June 15 issue of Annals of Internal Medicine showed for the first time that using two tests in combination — viral load measurement and CD4 T cell counts — more accurately determines the time for an HIV-infected person to develop AIDS.

The finds were reported by John Mellors, a Pitt associate professor of medicine and co-investigator of the Pittsburgh site of the Multicenter AIDS Cohort Study (MACS), and Alvaro Munoz of Johns Hopkins University.

"Rather than guessing about when a patient with HIV infection will develop AIDS, we can now look into the future with much greater accuracy," Mellors said. "These findings will enable physicians to assess the risk of AIDS for individual patients. This is especially crucial for deciding when to initiate antiretroviral therapy." Mellors and Munoz led the research in collaboration with colleagues from two other centers participating in the National Institute of Allergy and Infectious Diseases MACS project.

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UPMC using new heart drug

Cardiologists at the University of Pittsburgh Medical Center are using a new drug, recently approved by the U.S. Food and Drug Administration, for treating congestive heart failure.

The drug, Coreg (Carvedilol), is the first new drug for the treatment of heart failure in 14 years.

It is the first of its type to be available in the United States for heart failure. "Coreg reduces the heart rate by blocking beta receptors on the cells of the heart. This reduces the work the heart has to do to pump blood," said Srinivas Murali, a Pitt associate professor of medicine and director of transplant cardiology at UPMC.

"In the multi-center trials in which the UPMC participated, Coreg significantly reduced the combined risk of mortality and cardiovascular morbidity. In three other studies, it reduced death from congestive heart failure and total hospitalizations by up to 49 percent," Murali said.

An estimated 4.8 million Americans have congestive heart failure, in which the heart fails to maintain adequate circulation of the blood because of a dysfunction in the pumping action of the heart. Heart failure is the chief cause of about 40,000 deaths in the United States each year and is a major contributing factor in an additional 225,000 deaths. It also is the leading cause of hospitalization among Americans age 65 and older and, consequently, consumes a significant portion of the Medicare budget.

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Researchers study blood substitute in trauma patients

University of Pittsburgh Medical Center researchers are participating in a study to determine the effectiveness of a new blood substitute in treating trauma patients with severe blood loss. About 40 sites nationwide are participating in the study.

A patented, experimental blood substitute will be given to trauma patients to treat the harmful side effects of severe blood loss and possibly prevent death. The study is made possible by guidelines recently adopted by the U.S. Food and Drug Administration that allow consent to be waived in studies of emergency therapies for patients in life-threatening situations.

Due to the nature of this study, patient consent may not be possible. Obtaining advance consent from family members also will be difficult because the blood substitute must be given within one hour of hospital arrival. Patients or their families will be notified as soon as possible about the study and given the option of whether or not to continue.

About 20 patients will be enrolled in the study at UPMC. Half will receive the blood substitute and half will receive a saline solution. Patients also will be given all current standard treatments.

The blood substitute, developed by Baxter Healthcare Corp., is derived from human red blood cells. A specialized filtration and heating process makes the finished product safe from viruses. The solution carries oxygen and therefore has significant potential in trauma situations where large amounts of blood loss can result in a lack of oxygen to vital tissues. It is easily stored in emergency departments and can be immediately transfused in trauma patients.


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