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November 25, 2009

Research Notes

Pitt becomes AsthmaNet research site

Researchers from the University of Pittsburgh Asthma Institute at UPMC and the School of Medicine have received a seven-year, $529,000 grant from the National Heart, Lung and Blood Institute (NHLBI), an arm of the National Institutes of Health, to bring cutting-edge clinical trials to asthma patients in Pittsburgh.

Pitt’s asthma institute is one of nine sites across the country chosen to participate in AsthmaNet, the group of adult and pediatric centers chosen by the NHLBI to receive money to study the latest asthma medications.

The grant also supports research investigating innovative approaches to improving the care of patients at high risk of hospitalization and death from asthma, including African Americans and children.

Nearly 10 percent of the U.S. population suffers from asthma, making it one of the most common chronic diseases in both adults and children. Asthma attacks are responsible for over 1 million visits to the emergency room, 500,000 hospitalizations each year and billions of dollars in health care costs. While many patients are able to control their symptoms through medication, as many as 20 percent of asthma patients don’t experience relief from symptoms with current medications.

Sally Wenzel, director of the asthma institute and a faculty member in medicine, said, “This grant will help us bring the most innovative and promising clinical trials to Pittsburgh, giving our patients and the Pittsburgh asthma community access to the best treatment available while at the same time helping us advance our understanding of asthma.”

ICU care improvements studied

Pitt researchers will lead one of five U.S. teams that were awarded grants to study how nurses contribute to and improve the quality of patient care.

Co-principal investigators Mary Beth Happ of the School of Nursing and Amber Barnato of the School of Medicine and Graduate School of Public Health will lead the two-year, nearly $300,000 project, “Study of Patient-Nurse Effectiveness With Assisted Communication Strategies” (SPEACS-2). The project, funded by the Robert Wood Johnson Foundation’s Interdisciplinary Nursing Quality Research Initiative, will focus on improving patient care outcomes in the intensive care unit.

Happ stated, “Each year, more than 2.7 million ICU patients are temporarily unable to speak due to breathing tubes and artificial respiration. These patients face additional communication challenges such as hearing loss, impaired vision and confusion during hospitalization in the ICU. Researchers on the SPEACS-2 team will strive to improve the patient’s ICU experience by learning to more accurately interpret the patients’ messages about their symptoms, as well as their care needs.”

Happ and Barnato’s team of nurses, physicians, speech-language pathologists and biostatisticians will examine the impact of a web-based nurse communication training program on patient care outcomes.

Barnato stated, “We know these tools improve communication. The obvious next question is whether improved communication measurably improves patient outcomes and reduces costs. It would be very exciting if a low-tech tool in the ICU can improve critical care nursing care, patient outcomes and efficiency.”

Collaborative care helps bypass blues

Coronary artery bypass graft (CABG) patients who were screened for depression after surgery and then cared for by a nurse-led team of health care specialists via telephone reported improved quality of life and physical function compared to those who received their doctors’ usual care, according to a School of Medicine study recently presented at the American Heart Association annual meeting and published in the Nov. 18 edition of the Journal of the American Medical Association.

With more than 450,000 procedures performed annually, CABG surgery is one of the most frequently performed and costly medical procedures in the United States. Although the procedure clearly benefits many individuals, 20-25 percent experience depressive symptoms following the surgery and have worse clinical outcomes, including poorer quality of life, continued chest pains and a higher risk of re-hospitalization and death.

“Bypassing the Blues” is the first trial to examine the impact of a collaborative care strategy for treating depression following an acute cardiac event.

The intervention included weekly telephone follow-up by a nurse using an evidence-based treatment protocol for depression. The nurse collaborated with the patients’ primary care physicians and the study’s clinical management team, composed of a psychiatrist, psychologist and internist. This approach has proven effective for treating major depression in primary care settings but had never  been applied to a population with cardiac disease.

Principal investigator Bruce Rollman, faculty member in medicine and psychiatry in the medical school’s Center for Research on Health Care, said, “Dozens of studies have described a link between depression and heart disease, and the most recent science advisory from the American Heart Association recommends screening patients with heart disease for depression. However, few depression treatment trials have involved cardiac patients and none used the collaborative care model or examined the impact of treating post-CABG depression on quality of life, re-hospitalizations or health care costs, as we did.”

Investigators recruited 453 post-CABG patients from seven Pittsburgh-area hospitals from 2004 through 2007. They included 302 depressed patients who were assigned randomly either to an eight-month course of telephone-delivered collaborative care or to their doctors’ usual care for depression. Investigators also randomly sampled an additional 151 non-depressed, post-CABG patients to facilitate comparisons to depressed patients. They tracked patients to monitor quality of life, physical functioning, mood symptoms, re-hospitalizations, health care costs and deaths.

The researchers found that intervention patients reported greater improvements in mental health-related quality of life, physical functioning and mood symptoms. Overall, 50 percent of intervention patients reported a 50 percent or greater reduction in mood symptoms from baseline to eight-month follow-up versus 29.6 percent of patients in usual care.

“Men with depression were particularly likely to benefit from the intervention. However, the mean health-related quality of life and physical functioning of intervention patients did not reach that of the non-depressed comparison group,” said Rollman.

Pitt co-authors of the study included Bea Herbeck Belnap and Peter Counihan of medicine; Wishwa N. Kapoor, director of the Center for Research on Health Care; Charles F. Reynolds III of psychiatry; biostatistics faculty member Sati Mazumdar and statistical services administrator Patricia Houck of the Graduate School of Public Health, and Herbert C. Schulberg, a Pitt professor emeritus of psychiatry now on the faculty at the Weill Cornell Medical School.

More information is available at

Dental researchers to study facial birth defects

Researchers at Pitt and the University of Iowa will lead a $9 million, five-year initiative to study the cause of facial birth defects. The FaceBase Consortium will create an encyclopedic database of how the faces of children develop and what goes wrong to cause malformations.

FaceBase will build a list of the genes and proteins that drive embryonic cell differentiation around the forming mouth. These cells become bone, cartilage, ligament, nerve and soft tissue, which are visible as the developing face in the first sonogram of a fetus. However, questions remain about how this development occurs.

“FaceBase will bring together data that’s never before been in the same location,” said Mary Marazita, co-principal investigator of the FaceBase Management and Coordination Hub and director of the Center for Craniofacial and Dental Genetics in Pitt’s School of Dental Medicine. “The hope is that this database will help us to piece together the information needed to intervene when facial development starts to go wrong —  or prevent it from going wrong in the first place.”

Marazita and dental medicine professor Seth Weinberg also have received one of 10 independent FaceBase research and technology grants. This $1.5 million, five-year research grant will focus on acquiring three-dimensional facial images and a large number of genetic markers from participants in Pittsburgh, Seattle and Houston. The resulting data will be available through FaceBase and will allow discovery of genes related to facial features.

Co-investigator Michael Becich, chair of the Pitt Department of Biomedical Informatics, will collaborate in the development of the FaceBase portal and database. A prototype is expected to be ready within the next year. The FaceBase portal and database will be free and publicly accessible to the scientific community.

FaceBase is funded by the National Institute of Dental and Craniofacial Research, part of the National Institutes of Health.

Genetics of heart defects studied

Developmental biologists at the University have been chosen to participate in a $100 million federal “bench to bassinet” network that is dedicated to learning about the formation of the cardiovascular system and applying that knowledge to create new diagnostic and intervention strategies for congenital heart disease.

The Pitt team, led by developmental biology chair Cecilia Lo, will identify and describe the core set of genes that play an essential role in producing structural heart defects, including holes in the heart walls, transposition of major blood vessels that connect to the heart and other problems of cardiac development that can affect up to 1 percent of live births.

Lo’s $8.6 million project will expose fetal mice to a chemical that increases the likelihood of gene mutations and use non-invasive fetal echocardiography to spot any heart defects that result. The DNA of the affected mice will be examined to identify the gene changes that caused the abnormality. A zebrafish model will be used as a quick bioassay to validate the findings.

“Ultimately, we want to build a diagnostic chip that can rapidly and accurately identify the genetic root causes of specific heart defects,” Lo explained. “That could enable us to examine how these genes influence disease progression, correlate them with long-term outcomes and better tailor treatment.”

Lo is particularly interested in mutations that affect the function of cilia, which are hair-like projections on cells that are best known for moving fluids along tissue surfaces. “We now know cilia are critical to heart development in the fetus,” she said. “For example, they help to correctly orient the heart, which is a left-right asymmetrical organ. This asymmetry is crucial for normal functioning and allows for efficient oxygenation of blood.”

The bench to bassinet program was devised by the National Heart, Lung and Blood Institute. Lo’s project is in the Cardiovascular Development Consortium, which includes research teams from the University of Utah, Harvard University and the University of California-San Francisco.

Another consortium comprising five research centers will focus its work on translational research in pediatric cardiac genomics. Both will work with an existing clinical pediatric heart disease network.

HIV protein coating structure described

Structural biologists at the School of Medicine have described the architecture of the complex of protein units that make up the coat surrounding the HIV genome and identified in it a “seam” of functional importance that previously went unrecognized. Their findings, reported recently in Cell, could point the way to new treatments for blocking HIV infection.

The researchers used a combination of nuclear magnetic resonance and cryoEM, which are standard structural biology tools, to see both the overall shape and the atomic details of capsid protein (CA) assembly. It takes about 1,500 copies of CA to make the coat, or capsid, that surrounds the genome of the AIDS virus.

“This strategy allowed us to see both the forest and the trees,” explained structural biology faculty member and study co-author Peijung Zhang. “Knowing what the CA protein looks like and how the capsid is built will allow scientists to rationally design therapeutic compounds that interfere with assembly of the protein and affect its function.”

Senior author Angela Gronenborn, chair of the Department of Structural Biology and director of the University of Pittsburgh Center for HIV Protein Interactions, said capsid proteins, and particularly the interfaces or seams where one connects to another, are very important for assembling and disassembling the HIV coat.

The study, conducted with researchers from the Vanderbilt University School of Medicine, indicates that these seams provide the flexibility to dismantle the coat efficiently after viral entry into the host and to put it back together when new viruses emerge from the cell.

“Our lab experiments show that if we replace a few of the pivotal stitches in the seam by mutation, the resulting viruses are less infectious or even non-infectious,” Gronenborn said. “The capsid, and therefore the virus, can no longer function properly.”

Pitt co-authors include In-Ja L. Byeon, Xin Meng, Jinwon Jung, Gongpu Zhao, Jinwoo Ahn and Jason Concel of the Department of Structural Biology.

Fat grafting for war injuries

Surgery professor J. Peter Rubin is leading a team that recently received a $1.6 million award from the Department of Defense to help wounded soldiers recover from devastating facial injuries using innovative surgical technologies based on the biology of fat tissue.

Working with core faculty at the McGowan Institute of Regenerative Medicine, researchers plan to treat 20 soldiers with facial injuries.

“As many as 26 percent of wounded soldiers suffer some kind of facial injury, which can have a huge impact on quality of life,” said Rubin, who also co-directs Pitt’s Adipose Stem Cell Center.

“While we can reconstruct bony structures very well, it is the surrounding soft tissues that give people a recognizable face. This project will investigate how soft tissue grafting can more precisely restore facial form and improve the lives of our wounded soldiers.”

The use of fat grafting for serious facial injuries, such as those resulting from roadside bombs, is facilitated in this project by using specially designed devices and instruments for harvesting fat tissue and implanting it into regions of scarred tissue.

“Fat grafting, or moving fat tissue from one part of the body to another, has been used as a cosmetic procedure for decades,” said Rubin. “We are now applying these same techniques for reconstructive surgery to accurately restore facial form after battlefield injuries.”

Other Pitt faculty involved in the project are Kacey Marra, director of Pitt’s plastic surgery laboratory, Gretchen Haas of psychiatry and Barton Branstetter of radiology and biomedical informatics.


The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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