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March 16, 2006


Experience based cognition study funded

The U.S. Navy has granted Walter Schneider of Pitt’s Learning Research and Development Center $1.1 million for a study to map the brain architecture that supports experience-based cognition (EBC) in order to develop a computerized way to match humans’ EBC capabilities.

The human brain is by far the best computational device on the planet at performing real-time perception, encoding and problem solving. A critical aspect of human computation is its ability to learn, index and relate current experience to the past lifetime of experience.

EBC is a computational ability fundamental to human cognition in which lifetime experiences are indexed to allow content-based retrieval of experience for review and manipulation in response to queries or problem solving.

The project will use the modern brain imaging methods including functional magnetic resonance imaging (fMRI) and diffusion tensor imaging to map the structural and temporal aspects of human EBC with sufficient detail to provide a foundation for guiding the development of computer EBC.

The project will entail identifying the brain mechanisms associated with representing experience as well as brain mechanisms for executive and social/emotional processing. The process will provide a detailed understanding of the time course, specialization of representation, operations and distribution of function underlying human experience-based cognition.


Chest pain is cut with a squeeze

Patients with angina (chest pain) and left ventricular dysfunction respond very well to treatment using enhanced external counterpulsation (EECP), with few or no future heart failure events, according to researchers from the UPMC Cardiovascular Institute. The researchers suggest that EECP is an effective therapy for the 2.4 million Americans with coronary artery disease who are not candidates for invasive revascularization procedures such as balloon angioplasty, heart bypass or stent implantation. Their findings were reported in the January issue of the American Journal of Cardiology.

EECP is a non-invasive circulatory procedure whereby long inflatable cuffs are wrapped around a patient’s calves, thighs and buttocks. While the patient lies on a table, the cuffs are inflated sequentially while the heart is at rest (diastole), and then simultaneously deflated just before the heart begins to pump (systole). The heart rhythms are picked up through a computerized EKG machine. The benefits of EECP include increased blood flow to the heart and coronary arteries, thereby enabling the heart to perform at an optimal level.

Using data from the International EECP Patient Registry, the study included 363 patients age 67 and older with chest pain accompanied by severe left ventricular dysfunction. Patients underwent 32 one-hour EECP sessions five days a week for seven weeks. Prior to the study, most of the patients reported that their quality of life was poor. Among the patients in the study 85 percent previously had a heart attack, 72 percent had coronary bypass and 70 percent had some other type of invasive heart procedure.

All were assessed at six months, one year and two years. By the end of the study, the patients reported significantly less chest pain and an improvement in quality of life. The overall two-year survival rate was 83 percent and event-free survival rate was 70 percent. Forty-three percent of patients reported no hospitalizations and 81 percent had no congestive heart failure episodes. Additionally, more than half of the patients discontinued their nitroglycerin use.

“EECP is an effective, non-invasive treatment for congestive heart failure because it significantly reduces chest pain, increases exercise tolerance and reduces nitrate use,” according to Ozlem Soran, associate professor of medicine research at the UPMC Cardiovascular Institute and director of the UPMC EECP Research Laboratory.

The U.S. Food and Drug Administration approved EECP as a treatment for angina in 1995. At that time, EECP treatment was considered contraindicated in heart failure patients. Due to feasibility studies initiated at Pitt, the FDA approved EECP for the treatment of heart failure in 2002. Since then, the procedure has been used widely for the treatment of chest pain and as adjuvant therapy for revascularization.

Collaborating with Soran on this study were Elizabeth D. Kennard and Sheryl F. Kelsey of the Department of Epidemiology at the Graduate School of Public Health, and Abdallah Georges Kfoury of the University of Utah.


Researchers present at conference

At this month’s scientific conference of the American Psychosomatic Society, Pitt researchers presented results of a study that shows a link between serotonin and hardening of the arteries and a study that shows omega-3 polyunsaturated fatty acids may influence mood, personality and behavior.


Serotonin-atherosclerosis link could affect treatment of heart disease, strokes

A less-active brain serotonin system is associated with early hardening of the arteries, according to a study presented by the Pitt researchers. These findings, the first to establish a link between serotonin messages in the brain and atherosclerosis, could lead to an entirely new strategy for preventing heart disease and stroke.

“Many of the known risk factors for heart disease and stroke — high blood pressure and cholesterol, obesity, diabetes, smoking and lack of exercise — can, to some extent, be controlled by our lifestyle choices,” said Matthew F. Muldoon, associate professor at the School of Medicine. “Until now, no one had studied the possibility that brain abnormalities could explain why some people make these poor lifestyle choices and have multiple risk factors for heart disease.”

The study included 244 adult volunteers between the ages of 30 and 55 years. Researchers measured serotonergic activity using a pharmacological approach and carotid artery thickness using ultrasonography. At the time of testing, participants were free of clinically evident vascular disease. Yet, those with low levels of serotonergic function were more likely to have thickening of the carotid artery than those with higher levels.

“If, through further studies, we can establish that risk factors for heart disease and stroke are, in part, controlled by the serotonin systems in the brain, it could open a whole new avenue for preventing heart disease and stroke,” said Muldoon.

Serotonin is a type of neurotransmitter, a chemical that sends messages between neurons in the brain. It is thought to play an important role in the regulation of mood, appetite and blood pressure. Previous studies by Muldoon and his colleagues have found that people who get little exercise, are overweight and have high blood pressure, blood sugar and cholesterol have low levels of serotonergic function.

This study was funded by a grant from the National Heart, Lung and Blood Institute of the National Institutes of Health.

Other contributors to the study were Rachel H. Mackey and Kim Sutton-Tyrell of Pitt’s Graduate School of Public Health Department of Epidemiology, Stephen B. Manuck of Pitt’s Department of Psychology, Janine D. Flory of Mt. Sinai School of Medicine and Bruce G. Pollock, University of Toronto.


Omega-3 may affect mood, personality, behavior

A Pitt study has established a link between omega-3 polyunsaturated fatty acids and mood, personality and behavior. In a study of 106 healthy volunteers, researchers found that participants who had lower blood levels of omega-3 polyunsaturated fatty acids were more likely to report mild or moderate symptoms of depression, have a more negative outlook and be more impulsive. Conversely, those with higher blood levels of omega-3s were found to be more agreeable.

“A number of previous studies have linked low levels of omega-3 to clinically significant conditions such as major depressive disorder, bipolar disorder, schizophrenia, substance abuse and attention deficit disorder,” said Sarah Conklin, a postdoctoral scholar with the cardiovascular behavioral medicine program in the School of Medicine psychiatry department. “However, few studies have shown that these relationships also occur in healthy adults. This study opens the door for future research looking at what effect increasing omega-3 intake, whether by eating omega-3 rich foods like salmon, or taking fish-oil supplements, has on people’s mood.”

The American Heart Association recommends that all Americans consume fish, which is high in omega-3 fatty acids, twice per week. This recommendation is based upon evidence that a diet high in fish is associated with improved heart health and reduced risk for heart-related problems. While the cardiovascular benefit of increasing omega-3 intake is well recognized, relatively little is known of the potential mental health effects among the general public.

Comparisons were made by analyzing levels of omega-3 fatty acids in participants’ blood and comparing that data to the participants’ scores on three accepted tests for depression, impulsiveness and personality. The amount of omega-3 circulating in blood reflects dietary intake of the fatty acid. The study did not require participants to make changes in their normal diet habits.

Pitt co-authors of the study, which was funded by the National Institutes of Health included: Matthew F. Muldoon, associate professor in the School of Medicine Department of Medicine, and Stephen B. Manuck, a University Professor of Health Psychology and Behavioral Medicine in the Department of Psychology.

Other co-authors were Jennifer I. Harris, Brown University, and Joseph R. Hibbeln, National Institute on Alcohol Abuse and Alcoholism Lab of Membrane Biophysics and Biochemistry.


Better medicine through fossils

Collaboration between the School of Medicine and the Carnegie Museum of Natural History will have paleontologists teaching medical students in hopes of producing fresh thought on prevention and treatment of human diseases.

This partnership is unique among medical schools,” said John S. Lazo, Allegheny Foundation Professor of Pharmacology at the medical school and Carnegie Museum of Natural History board member.

“Our goal is to give medical students insight into the interrelationships between medicine and natural science, which we believe will enhance their understanding of the scientific discovery process while getting them to think about medicine in new ways. Together, the two institutions are able to create a uniquely enriching environment with an approach to medical education that focuses on how research themes of interest to museum scientists can reveal so much about contemporary medicine.”

Four museum curators will have faculty appointments at the School of Medicine, teaching workshops, seminars and courses as well as mentoring medical students choosing to conduct scholarly research projects at the museum.

According to Christopher Beard, curator and head of the museum’s section of vertebrate paleontology, there is much that paleontologists can teach medical students.

“Many orthopaedic problems occur because human ancestors walked on all fours,” Beard said. “When our ancestors began walking on only their hind legs, it allowed modern humans to do things with our hands. But at the same time, it made it harder for women to give birth, led to chronic lower back pain, hernias and other orthopaedic conditions.

“Using what we know about the fossil record and anatomical changes through time, we, as museum scientists, are beginning to piece together information about how genetics has influenced evolution, and vice versa. Interestingly, some physicians, including those at Pitt, are becoming increasingly aware of how medicine itself is evolutionary.”

Beard, a former John D. and Catherine T. MacArthur Foundation “genius award” recipient, and Lazo, who directs Pitt’s Drug Discovery Institute after 17 years as chair of the School of Medicine’s Department of Pharmacology, originally conceived the idea for the initiative.

John Mahoney, assistant dean for medical education at the School of Medicine, has been working with the museum on developing the initiative’s specific programs and planning for their incorporation into the medical student curriculum.

The initiative’s first offering will be a mini-elective course, “The Natural History of Medicine” for first-year medical students. It will cover the evolutionary origins of human disease, including the history of disease-causing pathogens, a topic that should help students better understand contemporary public health concerns such as avian flu, and think about treatment and prevention approaches that modern society may have overlooked.

Mahoney stated, “This course, which is one-of-a-kind, represents just one way we hope to expand students’ horizons about how medicine is a single discipline within the broad domain of natural sciences, and how understanding the natural sciences will enhance learning about medicine. Our students and our faculty, me included, have so much to learn from the museum’s eminent researchers.”

In addition to Beard, students will work with Zhe-Xi Luo, curator of vertebrate paleontology and associate director for research and collections, who is considered one of the world’s leading authorities on the evolution of the earliest mammals; Sandra L. Olsen, curator of anthropology, whose work focuses on cultures in north-central Kazakhstan from the Neolithic to Bronze Age, and John Wible, curator and head, section of mammals, whose work includes the evolutionary history of mammals and the evolution of the mammalian skull.


New stent opens brain arteries

Physicians at UPMC are the first in western Pennsylvania to successfully implant a stent that is designed specifically to open narrowed arteries in the brain. Left untreated, these arteries are associated with a high risk of subsequent stroke.

The trademarked Wingspan stent system is the only device available in the nation to treat atherosclerotic lesions or accumulated plaque in arteries of patients who are at high risk for repeat stroke.

Although it has been possible to open narrowed brain vessels prior to Wingspan by using stents made of stainless steel, this new device is specifically for use in the brain.

“This highly flexible stent is designed to navigate through the brain’s small and fragile vessels. It gives physicians an important tool to treat patients with intracranial atherosclerotic disease (ICAD) who have not responded to medical therapy and have no other medical options available to them,” said Tudor Jovin, assistant professor of neurology and neurosurgery at the School of Medicine and co-director of the Center for Endovascular Therapy at UPMC.

ICAD accounts for 8-10 percent of all ischemic strokes in the United States. Approximately 60,000 Americans suffer an ICAD-related stroke each year. Until recently, the only treatment for these patients was medical management, using either warfarin, an anti-coagulant, or simple aspirin. Even then, patients still remained at high risk for another stroke.

Ischemic stroke is caused by a blocked blood vessel that obstructs blood flow and deprives the brain of oxygen, which can lead to death or disability.

ICAD, the specific condition that Wingspan is designed to treat, results from plaque build-up in the vessels of the brain. Studies suggest that 11-22 percent of ischemic stroke patients will experience another stroke within a year despite medical therapy.

During the stent procedure, the Wingspan system is guided through the femoral artery in the leg to the blockage in the brain. A balloon catheter is expanded to crack the plaque and then is withdrawn. The stent, which is a wire-mesh tube, is inserted and maneuvered to the plaque. A protective sheath is removed and the self-expanding stent automatically opens against the inside of the vessel wall.

When inserted into the brain’s vasculature, the stent applies minimal pressure to the vessel wall and is designed to adapt to the vessel opening. The stent’s flexibility allows it to conform to curved and tapered vessels, and provides the ability to treat long and/or difficult to access lesions.


Nanoparticles may help create self-healing composites

The demand to increase the sustainability of materials and reduce energy costs is driving researchers to rethink the design and fabrication of materials. Two key issues are rising to the forefront in the design of sustainable, energy-efficient systems. There is a need for materials that can respond automatically to environmental changes and perform a specific function without external intervention. This is particularly important with respect to mechanical damage, where responsive systems could prevent catastrophic failure. There also is a need for lightweight materials that show multifunctional behavior.

New research by Pitt chemical and petroleum engineering professor Anna Balazs, in conjunction with researchers from the University of Massachusetts, published Feb. 12 in Nature Materials on line shows that nanoparticles dispersed in a polymer matrix migrated to cracks at the interface between the polymer and a glassy layer.

The movement, based on the enthalpic and entropic reactions between the polymer and the nanoparticles, shows that nanoparticles may provide a way to make more durable, self-healing systems and may form the basis for materials that can respond to environmental changes.

The research may be helpful in developing stronger materials for components made up of multilayer composites used in optical communications, microelectronics and bioengineering applications.


Long-term drug therapy best for late life depression

Antidepressant treatment is the most effective way to prevent recurrence of depression in people over the age of 70, according to School of Medicine research published in the current issue of the New England Journal of Medicine.

Left untreated, 50-80 percent of people in this age group will experience another episode of depression. But researchers found that participants who took the serotonin reuptake inhibitor (SSRI) paroxetine for two years after an initial depressive episode were much less likely to experience a relapse than those who received a placebo.

“Prior to this study there was no standard of treatment for the elderly with first episodes of depression in old age; however, many considered six to 12 months of antidepressant therapy to be appropriate. We found that this course of therapy to be entirely too short. Patients who discontinued therapy after six to 12 months were much more likely to experience another episode of depression than those who continued to take antidepressants for two years,” said Charles F. Reynolds III, UPMC Professor of Geriatric Psychiatry at the School of Medicine and principal investigator of the study. “By continuing antidepressant therapy for two years, we were able to reduce by 60 percent the chance that another depressive episode would occur.”

This study represents the first long-term controlled trial of maintenance pharmacotherapy and psychotherapy in people over 70. It involved 116 participants age 70 and older who had experienced a first episode of major depression that responded to treatment consisting of both paroxetine and psychotherapy. To determine the best approach for preventing recurrence of depression, the researchers randomized the participants into four treatment groups in which they received either paroxetine or placebo combined with either monthly interpersonal psychotherapy (IPT) or clinical-management sessions. IPT is an effective form of therapy that focuses on relationships and events, such as bereavement or retirement, which may trigger depressive episodes. In clinical management sessions, participants only discuss their symptoms and no therapy is involved.

Major depression returned within two years in 35 percent of the participants treated with paroxetine and psychotherapy, 37 percent of those treated with paroxetine and clinical management therapy, 58 percent of those treated with placebo and clinical management therapy and 68 percent of those treated with placebo and psychotherapy.

Participants receiving placebo had a 2.4-times higher risk of recurrence than those receiving paroxetine. The results also indicated that interpersonal psychotherapy was not effective in preventing new episodes of depression in this age group.

Prior studies by Reynolds and colleagues have shown that psychotherapy is effective for treating people age 60 and older who had previously experienced depression. Of the current study, Reynolds and his co-authors believe that psychotherapy was not effective in the 70-and-older group in a larger part due to higher levels of cognitive decline that takes place in this age population.

“By preventing depression in the elderly, we can improve the quality of life significantly in this population,” said David J. Kupfer, professor and chair in the School of Medicine Department of Psychiatry, and co-author of the study. “This study provides evidence that SSRI treatment given for two years can improve the lives of the elderly with major depression and should be the gold standard of treatment for this population.”

The study was funded by the National Institute of Mental Health. GlaxoSmithKline provided study medication, but had no role in study design, data accrual or data analysis.

Also contributing to this study were Mary Amanda Dew, Bruce G. Pollock, Ellen Frank, Mark D. Miller, Patricia R. Houck, Meryl A. Butters, Jacqueline A. Stack, Mary Ann Schlernitzauer, Ellen M. Whyte, Ariel Gildengers, Jordan Karp, Eric Lenze, Katalin Szanto and Salem Bensasi, all from the School of Medicine and Western Psychiatric Institute and Clinic’s Advanced Center for Intervention and Services Research for Late-Life Mood Disorders; Sati Mazumdar of the Graduate School of Public Health’s Department of Biostatistics, and Benoit H. Mulsant, Pittsburgh Veterans Affairs Health Care System.

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