University Times

Heart study receives 2-year grant

The Agency for Healthcare Research and Quality has awarded Pitt a two-year, $368,000 grant to study patients with acute heart failure. The goal of the project, "A Risk Stratification Rule for Heart Failure," is to derive a clinical guideline to help identify patients who are at low risk for short-term mortality and morbidity.

This guideline will assist in physician decision-making and limit variability in practice, especially the decision to admit. Donald Yealy, professor of emergency medicine and medicine, UPMC Presbyterian, and Thomas Auble, research assistant professor of emergency medicine, are the study's principal and co-principal investigators, respectively.

Other investigators are: William Gardner, professor of medicine and psychiatry; Steven Reis, associate professor of medicine; Margaret Hsieh, instructor of emergency medicine, and Arthur Feldman, professor of medicine.

Surgeons save limbs ravaged by diabetic complications and trauma

UPMC Health System surgeons have announced the opening of the Limb Salvage Center dedicated to saving limbs damaged by diabetic complications, trauma and peripheral vascular disease.

The program is a collaboration of vascular, orthopaedic, plastic and trauma surgeons and specialists in infectious disease.

"Although some patients may be told by their physician that they have no recourse but to have their foot or leg amputated, many limbs can be saved with aggressive medical management and surgery," said David Steed, professor in the Division of Vascular Surgery at Pitt's School of Medicine and director of the new program at UPMC Presbyterian. "Our center hopes to reduce the amputation rate for severely damaged limbs."

A recent study published in the journal Diabetes Care reported on the dramatic increase in the incidence of diabetes in the United States from 1990 to 1998. Diabetes can cause severe complications including difficult-to-treat foot ulcers, which can lead to foot or leg amputation. It is responsible for more than 40 percent of all non-traumatic amputations in the United States. Other causes for amputation are trauma and ischemic disease.

The UPMC program features a research component that gives patients access to clinical trials looking for new methods and treatments to prevent amputation.

"In the past several years alone, there have been a number of promising topical agents to treat chronic wounds such as diabetic skin wounds, pressure sores and wounds from poor circulation," said Steed, who is a national leader in performing clinical trials of new wound healing agents for difficult-to-treat wounds that can eventually result in amputation if not treated aggressively.

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Professors developing biological and chemical weapons detoxification coating

The Department of Defense, through The Defense Advanced Research Project Agency (DARPA) and The Army Research Office, has awarded a $5.6 million grant to Pitt and two partners to develop a thin polymer coating for vehicles to detect and deactivate chemical and biological agents.

The research project will be led by Pitt R.K. Mellon Professor of Chemistry John T. Yates Jr., and will be cooperatively carried out at Pitt, Kansas State University, and Texas A&M University, under the Defense Department's Multidisciplinary University Research Initiative (MURI). The grant is one of the largest under this year's MURI program.

"We are seeking novel ways to protect personnel from chemical and biological agent attack," said Yates, who holds a dual appointment in the chemistry and the physics and astronomy departments, and directs the Pittsburgh Surface Science Center. "A combination of biochemistry, solar-driven photochemistry, and surface chemistry will be employed to detect and destroy agent materials."

Yates will be joined by Pitt professors Alan J. Russell, chairperson of the chemical and petroleum engineering department, and Hrvoje Petek of the physics and astronomy department, along with professors from Kansas State and Texas A&M. The group will probe the details of biochemical and chemical processes using methods ranging from surface spectroscopies to genetic engineering to nano-science.

The project builds on expertise at Pitt and the other universities in surface chemistry and physics, biochemical engineering, and nanometer-sized materials.

"The research findings are expected to extend far beyond military applications, leading to thin film coatings that can be used on many commercial surfaces for chemical and bacterial decontamination," Yates said.

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Professor gets grant to study how materials degrade in orbit

Judith C. Yang, a Pitt assistant professor of materials science and engineering, will lead a team studying the degradation of materials in low Earth orbit through the Department of Defense's Multidisciplinary University Research Initiative (MURI) and the Air Force Office of Scientific Research.

The grant, for $250,000 per year, is for three years, with a possible two-year renewal, for a total of $1.25 million.

"As the air and space forces evolve in the 21st century, the need for increased numbers of spacecraft, including manned vehicles and satellites, with continually improving capabilities and durability, becomes imperative," Yang said. "Our aim is to predict materials and surface degradation in the low Earth orbit environment through a unified effort combining theory directly with experiments where primary degradation mechanisms are investigated in situ."

The team will study atomic oxygen surface reactions with ultra-high vacuum transmission electron microscopy and X-ray diffraction at the Advanced Photon Source at Argonne National Lab, and surface science techniques at Pitt's Surface Science Center. These experiments will be correlated with theoretical modeling and simulations of these interactions to provide a unique opportunity to advance substantially the knowledge base of the fundamental mechanisms of degradation in space environments.

The program represents a unified effort by Yang and John T. Yates Jr., the R.K. Mellon Professor at Pitt, and researchers from Carnegie Mellon University, the University of Illinois at Urbana Champaign and North Carolina State University. In addition, research will be conducted at national laboratories including Wright Patterson Air Force Base and NASA.

Yang is one of the few junior faculty named principal investigator in the MURI program. She joined Pitt's faculty in January 1999. Her research interests include gas-metal reactions, oxidation, high temperature corrosion, surface chemistry and physics, interfaces, catalysis, nano-particles, and nano-structured materials, as well as the use and development of advanced electron microscopy techniques.

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Kaposi's sarcoma associated herpesvirus causes no ill effects in HIV-negative people

New research at Pitt shows that a recently discovered herpesvirus, which often leads to Kaposi's sarcoma in HIV-positive people, has no negative effect on healthy HIV-negative adults. The study is published in the April 15 issue of Blood, a journal of the American Society of Hematology.

Researchers at the Graduate School of Public Health found that human herpesvirus 8 (HHV8), often a precursor to the blood vessel cancer Kaposi's sarcoma (KS) in HIV-positive adults, causes no symptoms or only a mild flu-like illness in healthy adults without HIV, and has no negative effects on their immune systems.

"This is the first study to unravel the natural history of primary HHV8 infection in the absence of underlying HIV infection or organ transplantation," said lead author Charles Rinaldo, professor of pathology and infectious diseases and microbiology. "Knowing how HIV-negative, otherwise healthy individuals respond to this virus in terms of symptoms and immune responses is important in preventing related diseases."

In a previous study, Rinaldo showed that HIV-infected people have a poor immune response to HHV8, which he says is likely the reason they are at high risk of contracting KS. This type of cancer can be very aggressive in HIV-infected individuals and in organ transplant recipients; a milder, rare form of KS occurs in some older men.

"Our current study shows that healthy adults produce T cells and antibodies that we believe control the first-time HHV8 infection," said Rinaldo. "The only signs of disease that we see, if any, are transient, flu-like symptoms." Like all herpesviruses, HHV8 remains, but in a latent form, after the initial infection.

In addition, the study demonstrates that HHV8 infection causes no negative changes in a patient's immune system, which is not the case with other, similar herpesviruses such as Epstein-Barr virus, the cause of infectious mononucleosis.

Rinaldo and his research team screened blood specimens taken over the past 15 years from 108 men participating in the Pitt Men's Study. They found five HIV-negative men who became infected with HHV8 during that period.

A review of these patients' clinical records showed that around the time of infection they experienced fatigue, enlarged lymph nodes, mild fever, diarrhea and/or mild skin rash. All symptoms were temporary, and the five men had no lingering changes in their health.

Moreover, the men had a strong immune response to the virus during the first few years of HHV8 infection that eventually subsided as the virus was controlled. This included formation of killer T cells and antibodies directed against different proteins made by the virus.

The flu-like symptoms and anti-HHV8 immune responses were not found in HIV-negative men who did not have primary HHV8 infection and who were examined at the same time by clinicians.

"While our study showed that first-time HHV8 infection is either asymptomatic or associated with several different mild, flu-like symptoms, many more cases of HHV8 infection must be analyzed before we can say definitively what specific clinical syndrome the virus causes in healthy adults," Rinaldo said.

To follow up on the current study, he and his research team have begun looking at how an HIV-positive patient's impaired immunity can lead to KS, and they are developing ways of boosting immunity to impede that progression.

"We hope that this research will eventually lead to a vaccine for prevention of HHV8," he said. This project, too, is part of the Pitt Men's Study. Directed by Rinaldo, the Pitt Men's Study is the Pittsburgh site of the Multicenter AIDS Cohort Study (MACS), one of the longest-running studies of the natural history of AIDS and associated diseases.

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UPCI tackles head & neck cancer

Survival rates for patients with head and neck cancer are low and have remained relatively unchanged over the past 30 years. Treatment options are limited, and often leave the patient disabled and disfigured, unable to speak or swallow properly.

A patient's best hope for survival, and an adequate quality of life, is through early detection and treatment of head and neck cancer. In an effort to improve the quality of patients' lives and increase survival rates, the University of Pittsburgh Cancer Institute's Head and Neck Cancer Program announced a new initiative April 10 for preventing and treating this disease.

Heading these efforts will be the newly recruited Dong Moon Shin. As co-director of the Head and Neck Cancer Program, he will coordinate new and ongoing efforts in developing methods to prevent new and recurrent cancers such as vaccines, gene therapy and immunotherapy.

Shin is one of the few medical oncologists in the world who has dedicated his career exclusively to the study of head and neck cancer. UPCI is one of the few comprehensive cancer centers to provide a program with a focus on head and neck oncology.

The University of Pittsburgh Medical Center (UPMC) has received worldwide recognition for its work in the surgical treatment of head and neck cancers and for research studies identifying biological markers, which allow for targeted therapies for head and neck cancer. New interdisciplinary interventions will incorporate basic and translational research, gene therapy and medical oncology with traditional surgical and radiation treatments maximizing the potential for new discoveries. These therapies, along with treatment and rehabilitation services provided by Pitt's Voice Center and Swallowing Disorders Center will maximize the potential for new discoveries, improving patient care and patient quality of life.

Shin joins Jennifer Rubin Grandis as UPCI Head and Neck Cancer Program co-director.

Shin said: "We are in a very exciting time in the treatment of head and neck cancer. If we think of fighting cancer as a war, for years we only had one option, one 'Army' to fight head and neck cancer. That was surgical resection of the tumor and radiation therapy. Now we can utilize a variety of therapeutic strategies: surgery, radiation, gene therapy, molecular targeted therapy and chemoprevention. We now have the Army, the Navy, the Air Force and the Marines."

Shin will hold an academic appointment as a professor in both the Department of Medicine's hematology/oncology division and i n the Department of Otolaryngology. He comes from the University of Texas M.D. Anderson Cancer Center, one of the nation's leading cancer centers.

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Pitt surgeons first in country to use ZEUS robot during cardiac bypass on a beating heart

UPMC is the first center in the United States to use the ZEUS Robotic Surgical System during a beating-heart cardiac bypass operation. Surgeons used the three-armed robot during the most important part of the operation — when the artery being used as the bypass graft is connected to the heart's main coronary artery.

The 63-year-old male patient underwent multivessel off-pump coronary artery bypass surgery at UPMC Presbyterian Hospital on April 5 as part of a national, multi-center trial seeking to evaluate whether the robotic system can be helpful to surgeons and be safely used for surgical connection of the left internal mammary artery graft to the left anterior descending artery.

The ZEUS had been used in 32 patients at three centers as part of a phase one trial, but in all of these cases, the operation involved the use of a heart/lung machine while surgeons operated on a stopped heart.

Marco A. Zenati, assistant professor of surgery and principal investigator at the Pittsburgh site, operated the robot while seated at a console about 10 feet from the patient. One arm of the robot, which responded to his voice commands, positioned the endoscope, an instrument with a tiny camera that magnifies the operative site up to 10 to 15 times. While viewing the magnified image of the heart and vessels on a high-resolution monitor, Zenati controlled the action of surgical instruments attached to the two other robotic arms by operating handles that resemble conventional surgical instruments, in much the way joysticks are used to control the action of a video game.

"ZEUS is designed to give a surgeon greater precision while performing microsurgical tasks, and to be able to use it during a beating heart operation is quite significant. Essentially, it may allow surgeons to perform superhuman tasks, because the robot overcomes our dexterity and precision limitations," Zenati said.

Hand movements of the surgeon are scaled. For instance, one inch of movement by the surgeon results in a 1/4 inch movement by the robotic surgical instruments. Hand tremor is filtered by the computer and translated via the robotic arms into precise micro movements at the operative site.

"The use of robotics for cardiac surgery is an extremely exciting development for the field. It is anticipated that the future will soon see all cardiac procedures employing such technology, and surgery will become less and less invasive for the patient," said Bartley P. Griffith, Henry T. Bahnson professor of surgery and chief, Division of Cardiothoracic Surgery at Pitt's School of Medicine. Griffith is a co-investigator of the study and assisted Zenati during the operation.

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Researchers win grants funded by state income tax refunds

The Pennsylvania Department of Health's Cancer Control Program has awarded four researchers associated with the University of Pittsburgh Cancer Institute (UPCI) grants to study breast cancer through an initiative funded by taxpayers who donated their state income tax refunds to the Breast and Cervical Cancer Research Fund.

The UPCI researchers received four of the eight grants awarded this year, each totaling $35,000.

Grants to UPCI investigators all focus on the role of estrogen in breast cancer, including biochemical, genetic and tissue studies that should improve the understanding of breast cancer risk and the development of highly specific hormone-based therapies against this disease.

UPCI's grant recipients are: Jean J. Latimer, assistant professor of obstetrics/gynecology and reproductive sciences; Kenneth McCarty Jr., professor of medicine and pathology; Francesmary Modugno, assistant professor of epidemiology, and Mark Nichols, assistant professor of pharmacology.

Researchers from the University of Pennsylvania, Temple University and Penn State University received the state's four other awards.

"UPCI investigators have received 12 of the 25 grants awarded in the three years this program has been in existence," said Ronald B. Herberman, director of UPCI and Pitt associate vice chancellor for research, Health Sciences.

"The grants are very important in that they enable these researchers to conduct preliminary studies and obtain additional findings that become the basis for obtaining major grant support from sources such as the National Institutes of Health.

"In effect," Herberman added, "each dollar donated through the tax check-off initiative is leveraged to far more research dedicated to the understanding of and cure for breast or cervical cancer."

Taxpayers can indicate their desire to donate all or a portion of their refunds to one of five causes, including breast and cervical cancer research, by "checking off" the line on their state income tax form.

During the 1999 tax season, $194,788 was raised; more than $700,000 has been raised since the check-off program was initiated in 1997.

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Contraceptives offer women no protection from pelvic inflammatory disease

Contraception does not reduce a woman's risk of pelvic inflammatory disease (PID), according to a study led by Pitt's Graduate School of Public Health. The results are published in the May issue of Epidemiology.

"This study addresses the controversy surrounding the protective effect of hormonal and barrier methods of contraception against PID in women," said principal investigator Roberta Ness, associate professor of epidemiology, medicine and obstetrics/gynecology. "The risk of upper genital tract infection was not reduced by any contraceptive method among women in this study. In fact, inconsistent condom use actually increased the risk of infection in this group of women."

PID is a common condition in which microorganisms spread from the lower genital tract to infect and inflame the upper genital tract, including the endometrium, fallopian tubes, ovaries and peritoneum. Women with PID have elevated rates of infertility, ectopic pregnancy and chronic pelvic pain.

Previous studies testing the ability of various contraceptive methods to protect against PID showed inconsistent results, perhaps due to the inclusion of women both with and without symptoms, and the use of older, higher-dose oral contraceptives in the studies.

The Pitt-led study looked at contraceptive use among 563 women who had signs and symptoms of PID and who were enrolled in the PID Evaluation and Clinical Health Study, a randomized clinical treatment trial.