University Times

First successful fetal lung gene transfer done using retrovirus University of Pittsburgh Medical Center (UPMC) scientists have performed the first successful fetal lung gene transfer using a retrovirus.

"This research is a significant step in developing clinical trials to treat inherited lung disorders in utero," said Bruce Pitt, a professor of pharmacology. "Using this method, clinicians could treat the genetic abnormality before it gives rise postnatally to a disorder that permanently damages the lungs." The two most common lethal inherited genetic disorders in Caucasians are cystic fibrosis and alpha-1 anti-trypsin deficiency. Both cause progressive, debilitating lung injury and afflict more than 50,000 people.

The UPMC study involved transferring a gene into the lungs of fetal sheep while they were developing inside the womb. The vector used to transport the gene was a retrovirus that had been altered so it could not replicate once inside cells but could integrate normally into a host cell's genetic material.

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Researchers find anti-clot agents in Vitamin E

Pitt researchers have discovered anti-clotting agents in Vitamin E that could help heart disease and stroke patients.

Chemistry professor Paul Dowd and graduate student Zhizhen Barbara Zheng reported in the Proceedings of the National Academy of Sciences that Vitamin E produces a metabolite, called Vitamin E quinone, as it scavenges the body for highly reactive and damaging "free radical" oxygen. This Vitamin E quinone is a potent inhibitor of the Vitamin K-dependent carboxylase — an enzyme that controls blood clotting.

Dowd and Zheng suggest exploring the use of Vitamin E as an alternative or supplement to Coumadin and Warfarin, currently given to heart attack and stroke victims.

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UPMC uses new heart bypass technique

University of Pittsburgh Medical Center (UPMC) heart surgeons recently began using a "minimally invasive" heart bypass technique, called keyhole surgery, to treat patients with blocked heart arteries.

Unlike standard heart bypass surgery in which a large incision is made in the chest and the breast bone is divided, the new technique uses only four "Band-Aid"-size incisions. UPMC is the only medical center in the region using this procedure, which is expected to reduce hospital stays and the stresses of the more invasive operation.

The new technique involves making three one-inch incisions on the left side of the chest. A tiny video camera and a miniature knife are inserted through the incisions. Watching the operation on a television monitor, surgeons free the mammary artery, which is inside the chest wall, from the back of the breast bone. The patient is positioned on his or her back, and a two-inch incision is made directly below the left breast. The surgeon can then connect the mammary artery to the heart's anterior descending artery.

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Pitt studying drug for hepatitis B in liver transplant patients

UPMC is studying a new drug for the treatment of hepatitis B in liver transplant patients as part of a multi-site trial involving centers in the United States and Canada. Glaxo Inc., of Research Triangle Park, N.C., has awarded UPMC's newly established Center for Liver Diseases more than $275,000 to conduct two pilot studies to evaluate the drug lamivudine.

"This drug holds a lot of promise for those with hepatitis B and end-stage liver disease," said Jorge Rakela, professor of medicine, chief of the Division of Transplantation Medicine and interim chief, Division of Gastroenterology and Hepatology. Rakela also is director of the Center for Liver Diseases.

Hepatitis B is the most serious form of viral hepatitis, affecting about 1 million people in the United States. For 5 to 10 percent of patients, hepatitis B can become chronic and lead to cirrhosis. Liver transplantation is the only treatment for patients with cirrhosis and liver failure. However, patients in whom the virus is actively replicating are not currently considered eligible for transplants because of the greater likelihood the infection would recur in the new liver. Even in patients with non-active hepatitis B who are transplanted, the virus recurs in up to 40 percent of the cases.

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PSC receives $6 million research grant

The Pittsburgh Supercomputing Center has received a five-year, $6 million grant from the National Institutes of Health (NIH) to support work by PSC scientists applying supercom-puting to research in molecular biology. The grant also funds PSC programs to develop software and provide computational resources, consulting and training to biomedical researchers around the country.

"This program fills a crucial need in biomedical research," said Caroline Holloway, acting director of the Biomedical Research Technology Program of NIH's National Center for Research Resources, which approved the grant. "It bridges the gap between complex biomedical problems and the unique capabilities of supercomputers. PSC provides the national biomedical research community with the world's most advanced high-performance computing resources. It provides excellent user support, and it expands the range of biomedically relevant software, databases and visualization capability that are available to biomedical researchers." PSC, a joint project of Pitt and Carnegie Mellon University together with Westinghouse Electric Corp., develops and makes available state-of-the-art high-performance computing for scientific researchers nationwide. The center was established in 1986 by a grant from the National Science Foundation, with support from the state.

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Engineering researchers study knee replacement

A study in the Department of Mechanical Engineering may have a major influence on the ability of knee replacement patients to avoid some of the post-operative problems associated with reconstructive surgery.

Doctoral candidate A. Xingguang Zhang and assistant professor Mark Miller have begun a new phase of study in knee joint replacement in conjunction with Harry Ruback and Savio Woo of the Musculoskeletal Research Center.

The researchers will explore the effects of component replacement on knee dislocation, component wear, knee fracture and lingering pain that occur after some patellar joint replacement procedures.

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Bypass more effective than angioplasty for some diabetics, Pitt study shows

Patients taking drugs for diabetes who had blockages in two or more heart arteries and were treated with coronary bypass surgery had, after five years, a markedly lower death rate than similar patients treated with the artery-widening procedure called angioplasty, according to an international study coordinated by researchers at the Graduate School of Public Health.

The finding was announced last month by the study's funding agency, the National Heart, Lung and Blood Institute.

Results of the study by the Pitt-based Bypass Angioplasty Revascularization Investigation (BARI), were released in a clinical alert to physicians nationwide.

The clinical alert was prompted by an analysis of five-year mortality data from the study. The analysis showed that in a subgroup of 353 drug-treated diabetics, those who were randomly assigned to have coronary angioplasty had a 35 percent death rate after five years compared with a 19 percent death rate among those assigned to have bypass surgery.

"This information will significantly affect the care of patients with diabetes and coronary artery disease," said Kim Sutton-Tyrrell, a BARI principal investigator and a faculty member in Pitt's public health school. Some 1.5 million people in the United States have both diabetes and coronary heart disease. An estimated 14 million Americans have diabetes (diagnosed and undiagnosed), which increases the risk of heart disease, the No. 1 killer in this country. Sixty-five percent of diabetics die of some form of heart or blood vessel disease.

Angioplasty and coronary bypass surgery share a common goal of improving blood flow to the heart. In angioplasty, a catheter with a tiny balloon at one end is used to flatten the buildup of plaque against the artery wall. This opens up the artery and stretches it so that blood flow is improved. In a coronary bypass operation, a blood vessel, usually taken from the leg or freed from the chest, is grafted onto a blocked artery, bypassing the obstruction.

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UPMC, Nimbus receive grant to develop artificial heart assist device

The University of Pittsburgh Medical Center and Nimbus, Inc., a medical device research and development firm in Rancho Cordova, Calif., have been awarded a $4.8 million, five-year contract from the National Institutes of Health to develop an advanced artificial heart assist device.

The contract is for the development of an innovative system using an implanted rotary blood pump, similar to a turbine, intended for long-term use in patients with end-stage heart disease. It will be capable of serving the needs of 40,000 to 50,000 patients each year who are unable to join the approximately 2,000 people who do receive heart transplants. According to Bartley P. Griffith, chief of cardiothoracic surgery at UPMC and co-principal investigator of the NIH award, "This device, which represents the state of the art in circulatory support, is smaller and less costly than currently available devices and will be applicable to a broader range of patients." A goal of the program is to demonstrate the feasibility of a completely implanted heart assist system that is capable of operating for five years or longer. "We feel confident that the long-term goals can be achieved," said Robert Kormos, associate professor of surgery, director of the artificial heart program and co-principal investigator.