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April 27, 2006


Researchers present diet findings

Diet research from Pitt’s School of Nursing was presented recently at the annual meeting of the Society of Behavioral Medicine.

* Benefits of a vegetarian diet

Preliminary results of a Pitt study on the impact of adding a vegetarian diet to standard behavioral treatment for weight loss found that those assigned to a fat- and calorie-restricted ovo-lacto-vegetarian diet had no significant difference in weight loss than did those who ate a standard fat- and calorie-restricted diet that included meat.

Those in the vegetarian group showed greater reductions in carbohydrate and protein consumption, polyunsaturated to saturated fat ratio and low-density lipoprotein (LDL) cholesterol.

And those in the vegetarian group who adhered to the diet and did not eat meat, showed greater reductions in weight, fat and carbohydrate consumption, LDL and total cholesterol and glucose than those who were not adherent.

Researchers were Lora E. Burke, Mindi A. Styn, Ann R. Steenkiste, Edvin Music, Melanie Warziski and Jina Choo, all of the School of Nursing.

*Weight loss & quality of life

The same team investigated how weight loss affects health-related quality of life to determine whether those who achieved a 10 percent or greater weight loss had a better quality of life than those who lost less weight.

Adjusting for body mass and education, the team found that those who lost 10 percent or more of their weight after six months showed greater improvements in physical functioning, vitality and general health than those with lower weight loss levels, but in comparing participants’ baseline and six-month scores, overall physical health significantly increased only in those with a 10 percent or more weight loss.

Researchers concluded that weight loss produces beneficial effects on several quality-of-life factors, but that substantial weight loss may be necessary to improve physical functioning in overweight or obese adults.

*Electronic diet monitoring

In addition, researchers Music, Choo, Styn, Warziski and Burke also found the use of personal digital assistants (PDAs) and PDA-based dietary software for self-monitoring to be a feasible alternative to paper diaries. Participants in their feasibility study all had used paper diaries to monitor their diet, but none had used PDAs. After training on the use of PDAs and DietMate Pro software, they recorded their daily food intake using the devices.

After six months, the researchers found overall response to the PDA and software was favorable and that participants had a positive attitude toward using technology.


Are charismatic CEOs worth their pay?

Research has shown that charisma contributes significantly to the compensation of CEOs. But what’s personality worth? Although a corporate leader’s magnetism often is considered a valuable company asset, scholarly studies of the relationship between CEO charisma and firm performance have yielded mixed results.

A new Pitt-Yale study published in the Academy of Management Journal finds that CEO charisma bears little or no relationship to how a company will do in the future.

“The present study is not able to provide stock analysts, investors and boards of directors with evidence that CEO charisma is necessarily beneficial in terms of predicting future financial performance, even under conditions of uncertainty, and suggests that they need to be cautious when considering the potential benefits of charismatic leaders,” conclude the study’s authors, Bradley R. Agle, Pitt associate professor of business administration and director of Pitt’s David Berg Center for Ethics and Leadership, Nandu J. Nagarajan, Pitt professor of business administration, Dhinu Srinivasan, Pitt associate professor of business administration, and Jeffrey A. Sonnenfeld, Yale.

Charisma and firm performance are not entirely unrelated, however: The impression that a CEO is charismatic, the study found, does stem to some degree from prior firm performance under his or her leadership.

“The better a company has been doing under a CEO, the more likely its top managers are to view the chief as charismatic,” said Agle. “We call it the ‘halo’ effect. But, in the end, by far the best predictor of a company’s future is its recent performance. If a company is doing well, the likelihood is that it will continue to do well, whether the CEO is charismatic or not.”

The study found that when executives view their chief as charismatic, they also tend to overestimate their firm’s financial performance. Thus, CEO charisma ratings had much more to do with top managers’ subjective impressions of company performance than with actual financial results.

“Our evidence suggests that CEOs who are perceived to be more charismatic appear to be perceived as more effective. In this subjective sense CEOs matter. However, the lack of corroborating evidence from objectively assessed CEO performance suggests that the search for charismatic CEOs may be based more on implicit theory or halo effects than on solid evidence that charisma really does make CEOs more effective,” the study found.

The findings are based on a survey of 770 top managers at 128 companies averaging $6.5 billion in assets and 16,000 employees. Participants were asked to rate their CEOs on five elements of charisma: dynamic leadership, exemplary leadership, concern and respect for others, high expectations and willingness to take personal risks.

The researchers then analyzed the ratings with respect to the company’s previous performance under the CEO and its performance during the seven years following the survey or until the CEO’s departure, whichever came first.

The CEOs in the sample had an average tenure of 6.6 years at the time the questionnaire was administered and stayed for an average of 4.5 years after the survey.

Performance was measured by stock returns, returns on assets, returns on sales, returns on equity and sales growth. The researchers also asked managers for their subjective assessments of the firm’s performance on sales, earnings, market share and return on investment since the CEO’s ascension.

The researchers found that, when they controlled for pre-survey firm performance, CEO charisma had no subsequent effect on any of the five performance measures, even in firms that confronted uncertain or turbulent business conditions. This was something of a surprise, since, as the study’s authors wrote, “under conditions of uncertainty and crisis, followers feel the need for greater direction and guidance and their inclination to accept influence may be greater.”


New dyes reveal cardiac voltage changes

A team from Pitt’s School of Medicine and Carnegie Mellon University describe in the Journal of Membrane Biology seven new chemical dyes that have made it possible to see the action potentials, or voltage changes, of cardiac cells — including those deep inside the heart, which trigger and determine the pace of heartbeats.

“What exactly causes arrhythmias and sudden cardiac death remains an important question we hope to answer through our studies that make use of a combination of novel imaging approaches,” said lead author Guy Salama, professor of cell biology and physiology at the School of Medicine. “Toward this end, these dyes have proved to be particularly important for recording membrane potential changes and capturing in detail, and in real time, the synchronicity or asynchronicity of the heart. Obtaining such images had long been a challenge due to confounding motions of the heart.”

Salama, along with Alan Waggoner and Lauren Ernst of Carnegie Mellon’s Molecular Biosensor and Imaging Center developed the voltage-sensitive dyes. The long wavelength dyes emit fluorescent light according to changes in voltage across cell membranes that are produced by activity of sodium and potassium channels, which open and close as the cardiac cell’s voltage changes. The dyes make it possible to see changes in the electrical potential of a single cell, multiple cells or even the entire heart. Importantly, the researchers found that the dyes also could be used simultaneously with other probes, such as for calcium, to provide a more complete picture of the processes influencing normal and abnormal rhythms. They can now map, in real time, voltage changes of cardiac cells below the surface of the heart while following calcium transients (a measure of the local force generated by each cell) during each action potential.

The new voltage-sensitive dyes, together with novel optical techniques, have greatly enhanced the understanding of how the heart works. Research will continue toward the development of a high-speed, depth-resolved 3-D imaging system that makes use of a camera with the ability to capture 10,000 images per second.

Other authors of the paper are Bum-Rak Choi, Ghassan Azour and Mitra Lavasani, all of the School of Medicine; Brian M. Salzberg of the University of Pennsylvania, and Michael J. Patrick of Carnegie Mellon University.

The research was supported by the National Heart Lung and Blood Institute, the National Institute of Neurological Disorders and Stroke and the National Cancer Institute.


Psychiatry research grant awarded

Wesley K. Thompson of statistics and psychiatry has been awarded a National Institute of Mental Health career development grant of $172,651 for his project, “Modeling Dynamic Co-variation of Brain Function, Health and Symptoms in Depression.”

The research into psychiatric statistics will focus on the relationships between depression and physical health. Thompson plans to study the scientific and computational models of functional MRI (fMRI) studies of depression and cardiovascular reactivity, and consultations on causal inference in psychiatric research.

He plans to adapt statistical methodologies from the field of functional data analysis for the examination of potentially causal dynamic co-variation in multiple functional processes. Thompson also seeks to validate the techniques on fMRI studies of depression and cardiovascular reactivity.

His specific research goals include: 1) exploring potential moderators of patterns of brain activation in depressed and non-depressed subjects; 2) modeling functional integration among specialized brain regions related to depression and cardiovascular reactivity; 3) examining the moderating effect of psychopathological variables on patterns of brain activation in response to emotional stimuli and to stressors, and 4) relating patterns of activation in specialized brain regions to cardiovascular responses to stressors.


Cardiologist receives career development award

Prem Soman, assistant professor in the School of Medicine and assistant director of nuclear cardiology at the UPMC Cardiovascular Institute, has been awarded the 2006 American College of Cardiology Foundation/GE Healthcare Career Development Award in Cardiovascular Imaging.

Soman, who also is director of nuclear cardiology research at the UPMC Cardiovascular Institute, was honored for his research project “Feasibility of Integrated Cardiac Imaging Using Separate Gantry SPECT and CT Systems.” His work focuses on noninvasive imaging of the heart with radionuclide techniques and echocardiography.

In nuclear cardiology imaging, the patient is injected intravenously with a drug containing small amounts of a radioactive tracer to help cardiologists better evaluate blood flow to the heart, both during stress testing and at rest. The nuclear camera then picks up the radioactive tracer and produces detailed images of the functioning heart to detect where blood flow has slowed in the coronary arteries.

CT imaging is another noninvasive procedure that can diagnose heart disease. It provides frozen, cross section images of the anatomy of the heart and coronary arteries.

Soman’s research will use a combination of both SPECT and CT imaging in order to diagnose heart disease at earlier stages more accurately. “While there already are combined SPECT/CT machines out there, they are enormously expensive. Here at the UPMC Cardiovascular Institute’s advanced imaging center, we already have access to both machines. My goal is to get patients tested on both devices on the same day and combine the information obtained. By merging the use of these technologies, we can better identify which patients can be treated through medication, and which patients need to be referred to more invasive testing such as cardiac catheterization,” said Soman.


Leptin-CRP interaction a clue to obesity?

New research suggests obesity may be due in part to an attraction between leptin, the hormone that signals the brain when to stop eating, and a protein more recently associated with heart disease. Reporting in Nature Medicine, Pitt researchers provide evidence that C-reactive protein (CRP) binds to leptin, and when it does, its hold impairs leptin’s role in controlling appetite.

The results may help explain why obese people have so much trouble losing weight as well as point to a different target for the pharmaceutical treatment of obesity.

“There’s been a lot of interest in leptin as a means to curb appetite and reduce weight but clinical trials have had disappointing results,” said Allan Z. Zhao, assistant professor of cell biology and physiology at the Pitt School of Medicine and the study’s senior author. “Our studies suggest an approach that should be further studied is one that disrupts the interaction between leptin and CRP, thereby restoring leptin’s ability for signaling. We need to better understand how this interaction works and investigate the underlying mechanisms involved.”

Leptin is secreted by fat — the more fat, the more leptin — yet it is named for the Greek word leptos, which means “thin.” In a region of the brain called the hypothalamus, leptin binds to receptors residing on the surface of neurons, setting off signals that tell the brain to stop eating and the body to expend energy by burning calories. While obese people produce much higher levels of leptin than thin and normal-weight individuals, they are somehow resistant to its effects.

Researchers believe the binding of CRP to leptin may be the reason. Their argument seems all the more plausible since CRP also is elevated in obese people. CRP, which is produced by the liver and typically rises as part of the immune system’s inflammatory response, is gaining favor as a marker for hypertension and heart disease risk, known complications of obesity.

One of the many questions yet to be answered is whether too much fat increases CRP or if it’s the high levels of CRP that make one fat. Zhao and his team are continuing laboratory studies of animals, but also plan to follow the outcomes of obese patients who are being treated with statin drugs, such as Lipitor and Zocor, for high cholesterol. Recent studies have found that statin drugs lower levels of CRP as well.

Working with David E. Kelly, professor of medicine and director of Pitt’s Obesity and Nutrition Research Center and a co-author of the current paper, Zhao hopes to learn if such drugs also might help in reducing weight.

First authors of the paper are Ke Chen and Fanghong Li. Other Pitt authors are Ji Li, Hong Bo, Steven Strom and Alessandro Bisello.

Their work was supported in part by the National Institute for Digestive Disorders and Kidney Diseases of the National Institutes of Health and a career and development award from the American Diabetes Association.


Colitis study to evaluate antibody therapy

Researchers at the School of Medicine have begun a global clinical trial to evaluate an antibody therapy that potentially could delay the need for surgery for patients with severe ulcerative colitis (UC) that no longer responds to standard medical therapies.

Ulcerative colitis is a chronic disease of the colon, or large intestine, marked by inflammation and ulceration of its innermost lining, which can cause diarrhea, pain and bleeding. In some cases, severe diarrhea can lead to dehydration, fever, hospitalization and blood transfusions.

Study participants will receive visilizumab, a monoclonal antibody that is designed to target and block the action of T cells, the same cells believed to cause UC, with the aim of significantly reducing the symptoms of UC and potentially delaying the need for colectomy, or surgical removal of the colon.

“More than one million people worldwide suffer from ulcerative colitis, which primarily affects women and men in their 30s, but can occur at any age,” said Scott E. Plevy of the School of Medicine. “An estimated 25 to 40 percent of these patients eventually fail to respond to oral and intravenous steroids, and their only treatment option is invasive surgery to remove their colon.” Plevy also is a co-director of the Inflammatory Bowel Disease Center and a member of the Department of Immunology.

UPMC is one of 75 centers worldwide participating in the Phase 2/3 clinical study called Restore 1, which is evaluating the safety and effectiveness of visilizumab. During the clinical study, patients will receive two intravenous injections of either the study drug or placebo. Patients will be monitored for up to 36 months.

In an earlier clinical study, the most common adverse events observed in patients treated with visilizumab were transient fever, chills, headache, nausea, vomiting, fatigue and body aches on the days of drug administration.

Patients who respond to therapy but subsequently experience a worsening of UC symptoms may be eligible to enroll in the visilizumab retreatment study initiated at the School of Medicine.

“The definitive treatment for ulcerative colitis is colectomy, which has significant conse-quences including the devastating impact of the surgery on a patient’s quality of life, and post-surgical complications that frequently arise, such as small bowel obstructions, leakage, abscesses and inflammation,” said Plevy. “We are studying visilizumab to determine if it may delay or prevent colectomy for some patients with fulminant ulcerative colitis refractory to intravenous steroids.”


CLAS receives Fulbright-Hays group grant

The Center for Latin American Studies has been awarded an $82,000 Fulbright-Hays Group Project Abroad for a teacher-training program in Brazil.

Twelve to 14 educators from public and private secondary schools in Pennsylvania, Ohio and West Virginia will be selected to take part in “Northeastern Brazil: People, Culture and History” this summer. The project in the Brazilian states of Pernambuco and Bahia offers teachers the opportunity to research and collect materials to design interdisciplinary lessons and activities for U.S. middle and high school classrooms.

The lessons will enable U.S. educators to explore the many similarities and differences in historic events that were vital elements in the formation of two of the three largest countries in the Western hemisphere: Brazil and the United States.

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