University Times

Comprehensive care aids diabetics

Educating people with diabetes in a primary care setting with sustained, comprehensive intervention resulted in significant improvement in disease management and overall health, according to a study published in the current issue of Diabetes Care, a journal of the American Diabetes Association. In the study, University of Pittsburgh Diabetes Institute (UPDI) researchers report the first evidence from a randomized, controlled clinical trial to show a clear association between a more comprehensive approach to diabetes management and improved health.

“Patients who received the chronic care model (CCM) intervention experienced substantial improvements both physically and psychologically,” said Gretchen Piatt, a doctoral candidate in epidemiology at the Graduate School of Public Health and the study’s first author.

“As a result of this study, the University of Pittsburgh Medical Center has redesigned the way in which diabetes care is delivered.”

CCM is designed to guide systematic efforts to improve health care for people with chronic illness by motivating patients, caregivers and health care professionals to work as a team.

“Not everyone will be able to see a diabetes specialist,” noted Janice Zgibor, assistant professor of epidemiology, director of evaluation at UPDI and senior author of the study. “Most people with diabetes, especially those in smaller communities, are managing their illness in the primary care setting. The CCM intervention gives them and their providers better tools with which to do this.”

The study involved diabetic patients who visited 11 primary care physician practices in one of Pittsburgh’s eastern suburbs between 1999 and 2003. Physician practices were randomized among the CCM intervention, provider education about diabetes or standard diabetes care. Ultimately, 119 patients took part in the study. Thirty received CCM intervention, 38 were in the group whose providers received a single diabetes education session and the remainder got standard care.

In the CCM group, patients and their providers received diabetes-control education. They showed significant improvements in clinical, behavioral and psychological indicators compared to the other patient groups. Average blood glucose measures, levels of HDL (good) cholesterol and non-HDL (bad) cholesterol and knowledge about diabetes control, improved significantly for patients receiving the CCM intervention but were little changed in the other two groups.

The Lions Clubs and UPMC’s Division of Community Health Services were among the funders of the study.

Additional Pitt authors were Trevor Orchard, Thomas Songer and Maria Brooks of epidemiology, and Sharlene Emerson, Mary Korytkowski and Linda Siminerio of UPDI.

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Fish oil can ease arthritis pain

A UPMC study has found fish oil supplements with omega-3 essential fatty acids (EFA) to be a safe and effective alternative to non-steroidal anti-inflammatory drugs (NSAIDs) for the majority of patients with neck and low-back inflammation and pain from disc and arthritic causes. Results were published in the April issue of Surgical Neurology.

Joseph C. Maroon, vice chairman of neurological surgery at the School of Medicine, was lead author.

Co-author Jeffrey W. Bost, physician assistant in neurological surgery, said that although NSAIDs are widely used to treat neck and back pain caused by inflammation, complications can include gastric ulcers, bleeding, heart complications and even death.

“A fish oil supplement containing omega-3 EFAs is a natural alternative treatment that reduces the inflammatory process and thereby reduces pain, with fewer side effects. People should be careful to choose a pharmaceutical grade fish oil supplement that is free of potentially harmful heavy metals.”

In the study, Maroon prescribed fish oil supplements to 250 patients who were taking NSAIDs. Of those patients, 125 returned questionnaires showing that 60 percent experienced improved overall pain and 59 percent discontinued use of NSAIDs including Vioxx, Motrin, Celebrex and Bextra.

The study also found that most patients had no significant side effects and that 88 percent planned to continue the use of omega-3 EFAs.

“Our study adds to the numerous previously published studies showing the health benefits of omega-3 EFAs, which include blood clot prevention, pain reduction, immune system boosting and healthy blood vessel dilation.” Maroon said the FDA now recognizes that omega-3 EFAs can help to prevent coronary artery disease.

“Additional clinical trials have shown that arthritis patients who take fish oils could eliminate or sharply reduce their use of NSAIDs,” he added.

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Cancer research findings presented

Pitt studies presented at the annual meeting of the American Association for Cancer Research offer insights into the prevention, treatment and mechanism of certain cancers.

Veggies vs. cancer

Chemicals in cruciferous vegetables such as broccoli, watercress, cabbage and cauliflower appear to stop human prostate cancer cells from growing in mice by affecting the expression of proteins, according to a University of Pittsburgh Cancer Institute (UPCI) study.

Shivendra Singh, lead investigator and professor of pharmacology and urology at the School of Medicine, said, “From epidemiologic data, we know that increased consumption of vegetables reduces the risk for certain types of cancer, but now we are beginning to understand the mechanisms by which certain edible vegetables like broccoli help our bodies fight cancer and other diseases.”

Singh’s study is based on phytochemicals found in several cruciferous vegetables called isothiocyanates (ITCs), which are generated when vegetables are either cut or chewed. His laboratory has found that phenethyl-ITC, or PEITC, is highly effective in suppressing the growth of human prostate cancer cells at concentrations achievable through dietary intake of cruciferous vegetables.

The study was supported by the National Cancer Institute. UPCI co-investigators wee Stanley W. Marynowski, Dong Xiao, Karen L. Lew, Yan Zeng, Rajiv Dhir and Hui Xiao.

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Mole proteins predict melanoma risk

For the first time, researchers studying patients with abnormal moles have identified proteins that could help predict whether such moles will progress into melanoma, the deadliest form of skin cancer.

The study also looked at the effect of a common treatment for melanoma, interferon, on the levels of these biomarker proteins.

While investigating the mechanisms of action of interferon treatment on patients who had multiple abnormal moles and were at high risk for melanoma recurrence, investigators found that two intracellular signaling proteins called signal transducers and activators of transcription, STAT1 and STAT3, were correlated with the degree of mole abnormality when examined under a microscope.

The researchers also found that interferon regulated the proteins in a manner that was dependent on its dose.

“While abnormal moles are a major risk factor for new primary melanoma development, it is difficult to know who among these patients will eventually develop the disease,” said principal investigator John Kirkwood, professor of medicine and director of the melanoma center at UPCI.

“Our hope with further study is to potentially test for these proteins and select those patients most likely to benefit from specific doses of interferon therapy.”

Researchers treated 40 patients at various levels of risk for recurrence of melanoma with either high or low doses of interferon.

They then examined changes in the appearance of the patients’ moles under a microscope and used molecular markers to determine the expression levels of STAT1, a protein associated with anti-tumor effects, and STAT3, a protein linked to melanoma progression.

“Our study found that interferon regulates expression of STAT1 and STAT3 in a dose-dependent manner and provides a useful biomarker of interferon impact on these well-established precursor lesions, which have the potential to become cancerous,” said Kirkwood.

Lead author of the study was Wenjun Wang; co-authors were Howard Edington, Uma N. Rao, Drazen Jukic, Hong Wong, Ruth Mascari and Cindy Sander, all of the UPCI melanoma center.

The study was funded by the Grant Channell Memorial, Roche Pharmaceuticals and Schering Plough Research Institute.

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Red hot cancer fighter

Pitt researchers have found that an ingredient in red chili pepper has cancer-fighting properties that prevent or slow the growth of pancreatic cancer tumors implanted in mice.

The study found that capsaicin, the “hot” ingredient in red chili pepper, caused pancreatic cancer cells to die through a process called apoptosis. Apoptosis, the body’s normal method of disposing of damaged, unwanted or unneeded cells, is often defective in cancer cells, causing them to thrive.

“We discovered that capsaicin fed orally to mice with human pancreatic tumors was an extremely effective inhibitor of the cancer process, inducing apoptosis in cancer cells,” said Sanjay K. Srivastava, lead investigator and assistant professor in pharmacology at the School of Medicine.

“Capsaicin triggered the cancerous cells to die off and significantly reduced the size of the tumors.”

Srivastava and colleagues fed mice grafted with human pancreatic tumors different amounts of capsaicin for five days per week or three days per week according to their weight, then compared tumor size and levels of apoptotic proteins in the tumors to a control group of mice that received normal saline only. They found that the mice that received capsaicin had increased levels of proteins associated with apoptosis and significantly smaller tumors than the control group. Tumors treated with capsaicin were half the size of tumors in non-treated mice.

The study was supported by a grant from the National Cancer Institute. Co-investigators were Ruifen Zhang, Ian Humphreys and Jeffrey Richards, all of pharmacology in the School of Medicine and UPCI.

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Multiple protein analysis may aid ovarian cancer diagnosis

Researchers have been stymied in their search for a single protein that could help diagnose ovarian cancer in its early stages. But Pitt researchers have identified a combination of several biomarkers that could help detect the disease much earlier than it currently is being diagnosed.

Anna E. Lokshin, lead investigator and assistant professor of medicine and pathology at the School of Medicine, said, “By the time women are diagnosed, their cancers have already spread and are extremely difficult to treat successfully.”

Researchers used a new technology called LapMAP to analyze a large number of proteins, or potential biomarkers, from a very small sample of serum from women with ovarian cancer.

They tested 450 serum samples for 46 biomarkers that previously had been correlated with ovarian cancer and were able to identify a multi-marker panel that correctly recognized more than 98 percent of serum samples from women with ovarian cancer, offering higher diagnostic power than any other published assay for ovarian cancer.

“Our goal is to develop this screening assay into a diagnostic test to improve the early detection of ovarian cancer and to monitor therapeutic response and recurrence in women with the disease,” said Lokshin.

Co-authors were Zoya Yurkovetky, Alex Lisovich, Brian Nolen, Adele M. Marrangoni, Lydmila Velikokhatnaya, Steven Skates and Elieser Gorelik, all of UPCI.

The study was funded by the National Institutes of Health.

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Omega-3s slow liver cancer cells

Two studies by a Pitt research team suggest that omega-3 fatty acids — substances that are found in high concentrations in fish oils and certain seeds and nuts — significantly inhibit the growth of liver cancer cells. The results suggest that omega-3 fatty acids may be an effective therapy for both the treatment and prevention of human liver cancers.

The first study looked at the effect and mechanism of omega-3 and omega-6 polyunsaturated fatty acids in human hepatocellular carcinoma cells. Hepatocellular carcinoma accounts for 80- 90 percent of all liver cancers and usually is fatal within three to six months of diagnosis.

The investigators treated the hepatocellular carcinoma cells with either the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or the omega-6 fatty acid arachidonic acid (AA) for 12-48 hours. DHA and EPA treatment resulted in a dose-dependent inhibition of cell growth, whereas AA treatment exhibited no significant effect.

In the second study, the investigators treated cholangiocarcinoma tumor cells with omega-3 and omega-6 fatty acids for 12 to 48 hours. Cholangiocarcinoma is a particularly aggressive form of liver cancer that arises in the ducts that carry bile from the liver and has an extremely high mortality rate. Again, the omega-3 fatty acids DHA and EPA treatments resulted in a dose-dependent inhibition of cancer cell growth, while the omega-6 fatty acid AA treatment had no significant effect.

According to Tong Wu, a member of the Division of Transplantation Pathology at the School of Medicine, in whose laboratory the research was conducted, these findings suggest that omega-3 fatty acids not only may be an effective therapy for the treatment of human liver cancers but may also be a means of protecting the liver from steatohepatitis, a chronic liver disease characterized by the buildup of fat in the liver and believed to be a precursor of hepatocellular carcinoma.

This work was supported by the National Cancer Institute. Kyu Lim in Wu’s laboratory performed the major experiments. Other Pitt investigators were research associate Chang Han and postdoctoral fellow Lihong Xu of pathology.

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Study finds 2 kinds of AIDS-related cognitive impairment

Cognitive impairment in people with AIDS exists in two forms — one mild, another severe — each affecting different areas of the brain, according to a School of Medicine study presented at the American Academy of Neurology annual meeting.

The researchers say their findings indicate there probably are two separate mechanisms that can cause cognitive impairment in people with AIDS.

“The advent of combination antiretroviral therapies to treat AIDS has significantly changed the course of the disease,” said James T. Becker, professor of psychiatry, neurology and psychology. “Not only are people living longer with AIDS, but we are finding that a number of the other co-existing conditions that people with AIDS often experience are becoming less severe. Such is the case with cognitive impairment — we are finding less people have severe cases while more have milder forms.”

Cognitive impairment in people with AIDS is caused when the HIV virus attacks the brain. It can be a complicated syndrome resulting in deficits in mood, behavior, motor coordination and thought processes.

The study evaluated 54 participants with AIDS and 23 HIV-negative control subjects. Participants completed a detailed neurobehavioral evaluation, which included neuropsychological testing to assess what level of cognitive impairment they had, and underwent an anatomical MRI scan. Using the data from the neurological tests, each participant was classified as either normal, mildly impaired or severely impaired. The MRI data were analyzed separately using voxel-based morphometry, a technique that allows researchers to analyze the entire brain and identify areas where tissue has atrophied.

Of the 54 participants with AIDS, 17 demonstrated some level of mental impairment. The mild impairment group only showed problems in the area of psychomotor speed, which is a measure of the time it takes a person to receive a signal, process it and respond. Based on the MRI scans, this group demonstrated atrophy in the frontal and anterior cingulate cortices, areas of the brain that control many vital functions, including memory, emotion and stimulus response.

Those in the severe impairment group showed impairments in psychomotor speed as well as in memory and visual-spatial processing. This group had more significant atrophy that was located in the caudate and putamen, different areas than the mild group.

The caudate and putamen also have some of the highest levels of HIV found in the brain. The caudate and putamen are part of a circuit between the cortex and other areas of the brain, and are especially vulnerable to HIV infection.

“Once we gain a better understanding of what causes the mental impairment and how it is caused, we can begin to look into new ways to treat or even prevent the symptoms,” said Becker.

The study was sponsored by the National Institutes of Health’s National Institute on Aging and National Institute of Mental Health.

In addition to Becker, other authors from the School of Medicine were Oscar L. Lopez of neurology and Howard J. Aizenstein, Shannon Juengst and Donna Marteneck, all of psychiatry.

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Do religious services aid good health?

In a study comparing the associations between faith and health, a UPMC physician has shown the improvements in life expectancy of those who attend religious services on a weekly basis to be comparable to those who participate in regular physical exercise and to those who take statin-type medications. The findings were published in the March-April issue of the Journal of the American Board of Family Medicine.

The study uses life expectancy tables to compare the impact of regular exercise, statin therapy and religious attendance, and shows that each accounts for an additional two-five years of life, suggesting that the real-world, practical significance of weekly religious attendance is of similar magnitude to other widely recommended therapy or health behaviors.

“This is not to say that religious attendance should replace primary prevention such as exercise, or a proven drug therapy, such as statin therapy, but it does suggest that regular religious attendance is associated with a substantially longer life expectancy, and this warrants further research,” said author Daniel Hall, who is a resident in general surgery at UPMC and an Episcopal priest.

Hall’s analysis shows regular physical exercise to be the most effective, accounting for 3-5.1 years of additional life. Although not as effective as regular exercise, both statins and religious attendance also accounted for longer life expectancy, with statins accounting for 2.1-3.7 additional years of life and regular religious attendance accounting for 1.8-3.1 additional years of life.

A secondary cost analysis suggests that religious attendance may be more cost effective than statins. The lifetime monetary cost of each therapy or behavior was calculated using insurance data for the average yearly cost of statins, census data for the average annual household contribution to religious institutions, and the cost of a modest gym membership for exercise. This lifetime cost was then divided by the additional years of life attributable to each behavior. Each year of life gained from statin therapy cost about $10,000 while religious attendance cost $7,000 per year of life gained. Physical exercise was the most cost effective at approximately $4,000 per year of life gained.

“While this study was not intended for use in clinical decision making, these findings tell us that there is something to examine further,” said Hall.

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Ad analysis may prevent teen smoking

Teens would be less likely to smoke if they learned to view ads and other types of media more analytically, the results of a study in Archives of Pediatric and Adolescent Medicine suggest. The study of 1,200 suburban Pittsburgh teenagers provides some of the first quantitative evidence that training teens about the messages and motivations behind various types of media has the potential to reduce teen smoking.

Researchers from the School of Medicine developed a scale to measure smoking media literacy (SML), or the ability to analyze and evaluate the messages, motivations and tactics behind advertisements and other mass media portrayals of tobacco. They found that the results correlated with teens’ current smoking patterns, intentions to smoke and attitudes about smoking.

In some cases, the association between SML and smoking behaviors was stronger than other known predictors such as socioeconomic status, parental smoking and stress.

“Many of the other factors that influence smoking behaviors are things that we cannot control,” said Brian Primack, assistant professor in general internal medicine and lead author of the study. “Media literacy is one of the few areas in which we can actively affect change.”

After controlling for 17 variables such as peer smoking, self-esteem and rebelliousness, SML still had a statistically significant association with current smoking (defined as smoking within the last 30 days), intention to smoke and general attitudes about smoking.

These findings could be particularly valuable for traditional school-based intervention programs, which tend to rely heavily on negative messages and reprimands and frequently fail in their objective to prevent teen smoking.

Despite the study’s promising findings, several areas warrant further examination. For example, norms — students’ expressed perception of how acceptable or unacceptable smoking is among their family and friends — was the one area that showed no significant independent association with SML after controlling for all variables. Researchers plan to explore whether there truly is no link or the norm measurement tool that they used was not representative of the true nature of smoking norms.

Other Pitt study authors were Michael Fine, Melanie A. Gold and Galen E. Switzer of the School of Medicine and Stephanie R. Land of the Graduate School of Public Health.

The study was funded by the Maurice Falk Medical Fund and Tobacco Free Allegheny.

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Neutrinos do have mass

Particles called neutrinos are produced by nuclear reactions in the sun and other stars. These particles are so small that scientists, until recently, thought they weighed nothing.

But an international collaboration including Pitt researchers recently announced the results of the most complete experiment of its kind — the Main Injector Neutrino Oscillation Search (MINOS) experiment at the U.S. Department of Energy’s (DOE) Fermi National Accelerator Laboratory — that determined that neutrinos oscillate, or change back and forth from one type to another.

This provides further proof that neutrinos have mass, because only particles with mass oscillate.

“I wasn’t 100 percent convinced that the oscillations were real until we saw these results,” said Donna Naples, a Pitt associate professor of physics and astronomy and one of the experiment’s principal investigators. Vittorio Paolone, physics and astronomy, also was involved in the study.

In the experiment, a beam of one kind of neutrinos was sent from the lab’s site in Illinois to a detector in Minnesota. Researchers observed that some of the neutrinos didn’t arrive in the same form as when they left, which meant they changed along the way.

These findings corroborate a recent Japanese study, and they verify that the signal recorded by the detector really is the result of neutrino oscillation. This experiment also offers a better measure of the mass of neutrinos.

The results of the experiment have important implications for cosmology. Because the neutrino doesn’t decay like other particles, neutrinos produced in the early universe are still around.

“When cosmologists model how the universe evolved into galaxies, they need to know how matter ‘clumps’ over time, and that depends on the mass of the neutrino,” said Naples.

The MINOS experiment included researchers from 32 institutions in six countries. The DOE provided the major share of the funding, with additional funding from the U.S. National Science Foundation and from the United Kingdom’s Particle Physics and Astronomy Research Council.

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More students are seeking counseling

More than 90 percent of the directors of college counseling centers in the United States and Canada report an increase in the number of students seeking psychiatric or psychological help for severe problems on campus.

The 25th annual survey of counseling center directors, conducted by Robert Gallagher, former vice chancellor for Student Affairs and former director of the counseling center, includes data from 366 campus counseling centers.

The survey found that 9 percent of college students sought counseling in 2005 and showed that increasing numbers of counseling center directors are reporting concerns about student self-inflicted injuries, eating disorders and sexual assault. Some 2,462 students were hospitalized in 2005 for psychological reasons, up from 2,210 in 2004.

More directors (90.3 percent, compared to 85 percent in 2005) are reporting an increase in the number of students coming to counseling centers with severe psychological problems, and 95 percent say they believe that the number of students coming to campus who are already taking psychiatric medication has increased.

“Colleges and universities are facing a growing problem that, if unchecked, could impact college life significantly,” said Gallagher, who is an adjunct professor in administrative and policy studies in the School of Education.

“Mental health problems can adversely affect academic achievement, classroom management and student retention, in addition to an individual student’s well-being.”

The directors report that 42.8 percent of their clients have severe psychological problems. While about 34 percent can be treated and remain in school, 8.5 percent have impairments so serious that they cannot remain in school.

Some reasons cited for the increasing need for on-campus mental health care include increased family dysfunction and early exposure to drugs, alcohol and sex.

But counseling directors also suggest that better psychiatric medications are enabling more students who perhaps would not have been able to attend college because of their psychological problems now can do so.

The survey also revealed that colleges are allocating more resources to address mental health issues and more schools (58 percent) are offering psychiatric services on campus, up 4.5 percent from 2004.

The annual survey is funded by Pitt, the Association of University and College Counseling Center Directors and the American College Counseling Association.

The report is available on line at www.iacsinc.org.

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Global studies gives grants

Three Global Academic Partnership (GAP) grants have been awarded by Pitt’s global studies program to fund projects on globalization in Latin America, sustainable community development and the role of children in armed conflict. The grants, intended to strengthen interdisciplinary research and curriculum development regarding global themes and to enhance international scholarly ties, are a joint initiative of the University Center for International Studies (UCIS) and the Graduate School of Public and International Affairs (GSPIA).

The GAP grants support international research conferences and workshops that result in publications and curricular enhancement.

Two awards of $20,000 each, sponsored by the Office of the Provost and UCIS, were awarded to:

• Elizabeth Monasterios, associate professor of Latin American literatures in the School of Arts and Sciences (A&S), Aníbal Perez-Liñan, assistant professor of political science, and partners from the Universidad Mayor de San Andrés for the project, “Globalization and Diversity/Inequality in Latin America: Challenges, Opportunities, Dangers.” The funding will support an international conference to be held in March 2007 on the issues currently facing the neocolonial and neoliberal structural modes of society-building.

• Kathleen DeWalt, professor of anthropology and professor in the Graduate School of Public Health; Larry Shuman, professor and associate dean for academic affairs in the School of Engineering; Eric Beckman, Bayer Professor of Chemical and Petroleum Engineering and co-director of the Mascaro Sustainability Initiative, and partners from the University of Brazil and the University of Puerto Rico. The project, “Research in Sustainable Community Development,” will support an international workshop to generate a research agenda in the areas of green construction and water that is attentive to cross-cultural and ethical issues. The project also will provide training for Pitt’s Integrative Graduate Education and Research Traineeship Sustainable Engineering Fellows to conduct research in Brazil.

A $25,000 Carnegie Corp.-sponsored grant was awarded jointly to Simon Reich, professor of public and international affairs and director of the Ford Institute for Human Security; Barry Ames, professor of political science; Maureen McClure, associate professor of administration and policy studies in the School of Education; Charli Carpenter, assistant professor of international affairs in GSPIA, and partners from the Peace Research Institution of Oslo and the Norwegian Institute of International Affairs. The project, “Building Knowledge About Children in Armed Conflict,” will support one in a series of international workshops to be held in September.

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Pitt-UPMC partner in brain imaging center

UPMC and the Pitt School of Medicine have formed the Center for Advanced Brain Magnetic Source Imaging (CABMSI) to use a new real-time brain imaging technology, called magnetoencephalography or MEG, for basic and applied research applications.

At UPMC, a scanning device that measures the brain’s magnetic field in real-time is allowing clinicians to pinpoint more accurately those areas of the brain causing epileptic seizures. The scanner also can aid in the diagnosis and study of disorders such as Parkinson’s disease, multiple sclerosis, dementia and schizophrenia.

“This device is a powerful tool for studying the function of the brain. We now can map nerve cell activity non-invasively in the brain in real-time. With MEG, the brain is seen ‘in action’ rather than viewed as a still image,” said L. Dade Lunsford, Lars Leksell Professor of neurological surgery and radiation oncology and chairman of neurological surgery at the School of Medicine.

“Initially we are using MEG to determine the location of seizures in patients with epilepsy and to determine the functional centers in the brain that are responsible for language, vision, motor and sensory information that are critical in the pre-surgical planning for epilepsy surgery,” said Lunsford, who also is director of the Center for Image-Guided Neurosurgery at UPMC.

Anto Bagic, assistant professor of neurology and neurological surgery at the School of Medicine, and the director of CABMSI, said, “MEG allows researchers to study the brain in the fourth dimension. It not only provides revolutionary insights into the immense complexity of brain functions and mutual interactions between brain centers, but it also provides information about the mutual relationship between the vital centers and abnormalities.

“These graphic representations can be sent directly into a navigational system used by neurosurgeons in the operating room and help guide them to the area of the brain that should be taken out while at the same time marking the vital centers that have to be saved,” he said.

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Brain imaging may predict success of depression therapy

Whether or not cognitive behavior therapy (CBT) will help a person recover from depression may be predicted through brain imaging, according to research published by the School of Medicine in the April issue of the American Journal of Psychiatry.

More than 17 million adults in the United States will experience at least one episode of major depression this year. Of those who seek treatment, only 40-60 percent will respond to any given first-line treatment, whether it be therapy or medication. However, researchers have found that most eventually will respond once they find the right treatment. Being able to predict who will respond to CBT, and who will not, may prove to be a valuable tool for treating depression.

“For depression, there is no single medication or therapy that has been found to work as a primary treatment for most patients,” said Greg J. Siegle, assistant professor of psychiatry in the School of Medicine. “We found that people with depression who have increased activity in one area of the brain and decreased activity in another in response to emotional stimuli are more likely to respond to a specific treatment-cognitive therapy. If this finding holds true, we may be able to predict what therapies will be most effective for individual patients by using imaging technology, bypassing the lengthy trial and error process that is often necessary to find the right treatment.”

The study used functional magnetic resonance imaging (fMRI) to identify which areas of the brain were active or inactive when exposed to a negative stimulus. While undergoing fMRI, 14 unmedicated participants with depression and 21 control subjects who had never reported symptoms of depression were presented with emotional words and asked if those words applied to them. The participants with depression then completed 16 sessions of CBT over 12 weeks as part of a larger clinical trial.

Researchers found that compared to controls, nine participants with depression had decreased activity in a region of the brain called the subgenual cingulate cortex after they read negative words. Of those nine, seven recovered from their depressive symptoms after CBT. Only one of the five participants with depression who did not demonstrate decreased activity in the subgenual cingulate cortex recovered after CBT. Better recovery also was associated with increased activity after reading negative words in a brain region called the amygdala.

“The amygdala helps us to recognize things as being emotional. In some people with depression, the amygdala doesn’t turn off as fast as it should after it recognizes something as being negative. The subgenual cingulate cortex regulates emotions and plays a part in turning the amygdala on and off,” said Siegle.

“If the amygdala doesn’t get ‘turned off’ in a person with depression, when exposed to negative information, the person may ruminate, going over this information again and again. Cognitive behavioral therapy teaches people techniques to stop this rumination, so it makes sense that it would be a good treatment option for those people who can’t turn off their amygdala,” said Siegle.

The researchers recently received funding from the National Institute of Mental Health (NIMH) to replicate this study in a larger group of people.

This study was funded by NIMH, the National Alliance for Schizophrenia and Depression, and the Veteran’s Research Foundation.

Co-authors were Michael E. Thase, School of Medicine, and former Pitt professor Cameron S. Carter, now at the University of California-Davis.

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Grant awarded for pediatric brain tumor research

Marie E. Beckner, a research assistant professor of pathology in the School of Medicine, was awarded a $15,000 grant from the Nick Eric Wichman Foundation (NEWF) to study brain tumor invasion in children.

Beckner and Ian F. Pollack, co-director of the Brain Tumor Center of the University of Pittsburgh Cancer Institute and professor of neurological surgery at the School of Medicine, have been conducting research studies on pediatric brain tumor therapies since 2002, with funding from NEWF.

Beckner said, “Our previous studies have provided a rationale to begin testing promising combinations of drugs that should suppress biologic mechanisms of invasion and to identify markers of malignant invasion that are needed to evaluate the effectiveness of new therapies in future patients.”

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New wave of tsunami detection

The 2004 Indian Ocean tsunami was one of the deadliest disasters in human history, largely because it struck without warning. No detection or alert system existed in the region at that time.

Pitt researchers are forming an international team of experts to find an early and accurate way of detecting tsunamis and mobilizing a response to the threat. Funded by a $199,214 grant from the National Science Foundation (NSF), the study will be the first to propose a comprehensive, socio-technical framework that extends from detecting a tsunami to warning the population at risk.

Daniel Mossé and Taieb Znati of computer science and Louise Comfort of the Graduate School of Public and International Affairs have teamed up with an international group of experts from the computer science, seismology, information technology, public policy and disaster management communities.

“The innovative part of the detection system that we’re proposing is the linkage of information from a network of sensors at sea, to a network of organizational action on land,” said Comfort.

The Pitt team hosted a conference in Maui in February to examine the limitations of present tsunami warning systems and discuss areas for improvement. Among the issues is the frequency of false alarms that diminish the effectiveness of tsunami warnings because the public may begin to disregard them. In the current warning system in the Pacific, three out of four warnings are false alarms.

The team proposed that by having a large number of cost-effective sensors, the systems will be better equipped to determine when a tsunami is a real threat.

“The more economical the detection devices are, the more devices can be used. Not only would this ensure the safety of poorer populations, but the more devices we have, the less critical it is if some of the devices should fail,” Mossé said.

Future talks will discuss the technical challenges to building a complete socio-technical tsunami warning system.

Ultimately, the results of this research can create a framework for disaster detection and response that is general enough that it can be applied not just to tsunamis, but to other rapid-onset incidents such as earthquakes, landslides and mudslides.

The project was funded by the NSF small grants for exploratory research program.

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HHMI renews funding for teaching

Graham Hatfull is one of eight original Howard Hughes Medical Institute (HHMI) research award winners to receive renewed financial support to further his teaching talent. Hatfull is Eberly Family Professor and chair of biological sciences. HHMI awarded $20 million — $1 million apiece — to the first group of HHMI professors in 2002 to bring the excitement of scientific discovery to the undergraduate classroom in hopes of inspiring a new generation of scientists. The eight who were approved for additional support will receive smaller renewal grants to help them sustain the parts of their programs that worked best and to disseminate them to the broader community of teachers. Hatfull will receive $500,000.

Hatfull’s undergraduates mentored high school students as they unearthed and analyzed more than 30 new bacteriophages from yards and barnyards.

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CLAS receives Fulbright-Hays group grant

The Center for Latin American Studies, part of the University Center for International Studies (UCIS), has been awarded an $82,000 Fulbright-Hays Group Project Abroad grant for a teacher-training program in Brazil.

About a dozen 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 five-week seminar 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 world-language and social studies classrooms.

The lessons will enable U.S. educators to explore the many similarities and striking 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.

The new Brazilian lessons will serve as enrichment materials for use along with regular secondary level courses to give American students a better comprehension of U.S. and world history.

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Med school researcher wins national award

Merrill J. Egorin, professor of medicine and pharmacology at the School of Medicine, has been awarded the Joseph H. Burchenal Clinical Research Award by the American Association for Cancer Research (AACR) for his work in developing and refining the clinical use of a broad spectrum of cancer chemotherapy agents. The award was presented on April 5 at AACR’s annual meeting.

The award, established in 1996 and named after Burchenal, a pioneer of cancer chemotherapy and past president of the AACR, is bestowed annually to recognize outstanding achievements in clinical cancer research.

Egorin, co-director of the molecular therapeutics and drug discovery program at the University of Pittsburgh Cancer Institute (UPCI), carries on in the tradition of the award by striving to find new ways to develop and use drugs to treat and manage cancer.

Egorin’s findings have led to new paradigms for the use of chemotherapy agents based on their specific pharmacologic features and toxicity profiles. His ability to capture essential features of chemotherapy agents has resulted in the discovery of practical dosing recommendations for several drugs that otherwise would have been too difficult to use in the clinic.

He currently serves as principal investigator on a National Cancer Institute (NCI)-funded contract evaluating the pharmacokinetics, metabolism and pharmacodynamics of anti-tumor agents being considered for clinical trials. He also is the co-principal investigator of another NCI-funded cooperative agreement for conducting phase I studies at UPCI.