University Times

Researcher gets CDC grant to study youth violence

Anthony Fabio, assistant professor of neurosurgery at the Pitt’s School of Medicine and investigator with the university’s Center for Injury Research and Control (CIRCL), has received a nearly half-million dollar, three-year research and training grant from the U.S. Centers for Disease Control and Prevention to study trends in youth violence.

The CDC’s mentored research scientist awards are designed to help develop promising young investigators into experts in a particular field. Fabio’s research project titled, “Why Some Generations Are More Violent Than Others – A Contextual Model for Understanding Crime Trends,” seeks to determine the role of social influence on violence in adolescents over time and will draw primary data from the Pittsburgh Youth Study.

“I am honored to receive this award. My hope is that through this research, we will be able to better identify both analytical and theoretical techniques in order to provide effective problem solving strategies with regard to youth violence,” Fabio said.

Using data from the Pittsburgh Youth Study — a study of 1,517 inner-city boys from Pittsburgh, between the ages of 7 and 25 to better understand how and why boys get involved in delinquent behaviors — Fabio will look at two age groups from the study; those 7 years old at the beginning of the study in 1987, and those aged 13 years at the beginning of the study.

The older group reported higher rates of violence than the younger group throughout the study. The primary question that Fabio and his colleagues plan to answer is whether this difference is due to some inherent distinction between the groups, or to some special or cultural factor such as poor economy, increased gang participation or drug dealing that played a greater risk during the time that the older group was growing up. Understanding these differences may help to predict future increase in violence.

The principal investigator of the Pittsburgh Youth Study is Rolph Loeber, distinguished university professor of psychiatry, departments of psychiatry and epidemiology, at the University’s Western Psychiatric Institute and Clinic and Graduate School of Public Health.

Loeber’s findings on dynamics of youth violence have yielded nearly 100 peer-reviewed publications. He will be collaborating with Fabio, along with David Farrington, professor of psychological criminology at the University of Cambridge, England. Fabio also will spend one semester at Cambridge next fall as part of his training grant.

According to the Office of Juvenile Justice and Delinquency Prevention, juvenile violent crime arrests increased substantially through the late 1980s through 1994, and then decreased for eight consecutive years. In 2002, the juvenile arrest rate for violent crimes was 47 percent below its peak in 1994.

Other collaborators on this study include Frederick Rivara, director of the Harborview Injury Prevention and Research Center in Seattle; Steve Wisniewski, associate professor of epidemiology at Pitt’s Graduate School of Public Health; and David R. Jacobs, a statistician from Johns Hopkins University in Baltimore.

Asymptomatic cardiac changes are powerful predictor of heart disease

An index of early cardiovascular changes measurable even before symptoms appear is a more powerful predictor of future stroke, heart attack or other coronary heart disease than traditional risk factors such as smoking, obesity and a sedentary lifestyle. More aggressive intervention at the time these changes are first detected could have a positive impact on cardiovascular disease-related illness and death, according to a study presented recently at the American Heart Association’s Scientific Sessions 2004 in New Orleans.

Lewis Kuller, professor and past chair of the department of epidemiology at the University’s Graduate School of Public Health, reported on the short-term outcome of patients in the Cardiovascular Heart Study, a population-based longitudinal study of coronary heart disease and stroke in adults over age 65 sponsored by the National Heart, Lung and Blood Institute of the National Institutes of Health.

“Now we can identify older men and women who don’t have any clinical disease or other risk factors, and yet who are at very high risk,” Kuller said. “Especially among women, these measures are really quite powerful.” Measures of early cardiovascular changes before symptoms appear, such as narrowing of the carotid arteries, electrocardiographic abnormalities and ankle-arm blood pressure index and carotid intima-media thickness (markers of early atherosclerosis), all were found to be strong, independent risk factors for future cardiovascular events including heart attack and stroke, he said.

Black women with subclinical disease had more than a two-and-a-half-fold higher risk of a subsequent cardiac event than those who did not have early evidence of cardiovascular changes – the highest risk noted. Black and white men were found to be nearly two times as likely to have clinical disease after 10 years if evidence of disease was present earlier. White women with subclinical disease had a 60 percent higher risk of a subsequent cardiac event, the study found.

“In contrast to traditional measures that prove a snapshot picture of risk factor levels at one point in time, the index of measures reflects cumulative vascular burden that can more accurately point to later risk for coronary artery disease,” Kuller continued. “Earlier interventions, perhaps with drugs to treat cholesterol and hypertension, as well as controlling diabetes and making modifications in exercise and diet could perhaps help to reverse the process.”

$1 million grant given to UPCI

Many cancers are diagnosed only after symptoms have appeared and the cancer has already spread, making it difficult to treat effectively. A major $1 million gift, from Mark E. Pasquerilla, president, CEO and chairman of Crown American Enterprises in Johnstown, Pa., may enhance the ability to detect cancer at the earliest stage possible through research efforts at the University’s Cancer Institute (UPCI).

The research support will be focused solely on the study of genomics and proteomics – emerging fields of research that hold great promise to help detect cancer early and potentially improve cancer prognoses.

“The key to cures, or at least long term survival from cancer, lies in our ability to detect cancer early, before symptoms have appeared and before the cancer has had a chance to grow,” said Ronald B. Herberman, director of UPCI and the UPMC Cancer Centers. The donation will support the development of innovative genomic and proteomic technologies.

“Through these technologies, researchers look forward to a future when we can analyze a single drop of blood to identify a pattern, or fingerprint, that can distinguish cancer from non-cancer,” he said.

Genomics, the study of the expression of genes in tumors and normal tissues, and proteomics, the study of the shape, function and expression of proteins, may allow researchers to diagnose cancer early by identifying specific proteins in blood, other fluids and tissues that indicate the presence of disease at its earliest stage, leading to better prevention, screening and treatment options. Clinical application of these technologies also may make it possible to tailor treatment to individual patients by matching specific genomic and proteomic patterns to a particular disease stage. This, in turn, may help determine which patients can benefit most from a given therapy.

In addition to the potential to diagnose cancer early, genomic and proteomic techniques are can monitor patients’ responses to molecularly targeted drugs. Monitoring the changing levels of proteins in the blood inside cells during treatment may help physicians to determine whether a particular drug is working for a specific type of cancer. “The downstream therapeutic benefit of this center is to not only develop protein nanoengineering and new therapeutic approaches to diagnosing cancer as early as possible, but also to make significant advances in the efficacy of therapy for individual patients,” Herberman said.

Ventricular assist devices can be used as bridge to recovery without heart transplant

A heart ventricular assist device (VAD) is used as a bridge to organ transplantation, maintaining a patient’s cardiac function until a donor organ becomes available. In some cases, the device rests the heart and allows it to heal without the need for heart transplantation. The frequency of this occurrence and the patients most likely to benefit from VAD as a bridge to heart recovery remains poorly defined.

In a study presented today at the American Heart Association’s Scientific Sessions 2004 in New Orleans, Marc A. Simon, fellow in transplantation cardiology at Pitt’s School of Medicine, reported on the long-term outcome of patients successfully weaned from VADs at the University’s Medical Center (UPMC).

“We found that seven percent of patients implanted with heart assist devices were successfully weaned from the devices without the need for a heart transplant,” Simon said. “Our study found that when utilized in acute inflammatory cardiomyopathy or post-partum cardiomyopathy (PPCM), VAD support appears to allow long-term restoration of cardiac function. VAD support as a bridge to recovery (BTR) should be an important component of the care of acute inflammatory myocarditis.”

“With the availability of VADs, no patient should die from acute myocarditis or severe peripartum cardiomyopathy. This study demonstrates that ventricular support can facilitate dramatic recovery even in patients who are gravely ill,” said Dennis McNamara, associate professor of medicine at the University’s School of Medicine and senior author of the study.

“Successful therapeutic strategies for end-stage congestive heart failure now include not only cardiac replacement with assist devices or transplantation, but the true opportunity for repair and recovery of myocardial function through the synergy between advanced medical therapy and ventricular assist devices,” said Robert L. Kormos, director of Heart Transplantation, and director of the Artificial Heart Program at UPMC.

NSF grant targets better teaching of computer programming

Two Pitt professors have been awarded a grant to improve visualization tools for teaching computer programming. Their results, they say, will create better programmers and, in turn, better programs, with fewer loopholes for viruses and worms.

“We wouldn’t let a substandard plumber work on our heating system, but people buy software all the time that is written by substandard programmers,” said the project’s coprincipal investigator Michael Spring, associate professor of information science at Pitt.

“The weaknesses in programs that allow users’ machines to be violated can almost always be traced back to programming errors that were made by less than competent programmers,” he said. “This research is designed at improving our ability to teach programming in a way that will insure that we turn out programmers who have A-level, rather than C-level, skills.”

Spring and the principal investigator of the project-Peter Brusilovsky, assistant professor of information science at Pitt-were awarded a three-year, $220,000 grant from the National Science Foundation. The focus of the grant is to extend the power of the educational tool visualization, which allows the student to see inside an otherwise invisible process.

In computer science, what is typically seen on the screen is just what the program “prints.” To see how programs actually work, it’s necessary to create a visualization. “Good visualizing techniques allow you to see what’s going on inside your computer,” said Brusilovsky.

Brusilovsky and Spring are investigating how to make visualization more explanatory and more sensitive to students’ differing levels of knowledge.

“Normal visualization is passive-you just look, and you’re not really learning by looking, even if it’s a nice visual,” said Brusilovsky. “Students can see what’s happening, but they can’t relate it to their basic knowledge. Without narration, they don’t understand what’s going on. That’s why we want to get explanatory visualization.”

The researchers also want to make their tools more adaptive. Different students have different levels of knowledge and skill: Some need concepts to be explained in less detail, some more. The technology will compile information on a student’s knowledge level from quizzes and build a profile of the student’s skills. Then, whatever knowledge is new to that particular student will be explained in more detail.

In the last phase of the project, faculty members of local colleges and universities will teach courses at Pitt using the technology and then take the tools back with them. Brusilovsky and Spring also will hold workshops to demonstrate the usefulness of the tools.

Researchers identify biomarkers for lupus

Pitt researchers have identified biomarkers that could result in earlier and more accurate diagnosis of systemic lupus erythematosus (SLE), a devastating disease that affects as many as 1.5 million Americans, and occurs 10 to 15 times more frequently in women. The results were published in the November 2004 issue of Arthritis & Rheumatism.

Lupus is a widespread and chronic autoimmune disease that, for unknown reasons, causes the immune system to attack the body’s own tissue and organs, including the joints, kidneys, heart, lungs, brain, blood and skin.

“This is the first report of abnormal levels of the protein erythrocyte-C4d in human disease,” said lead author Susan Manzi, associate professor of medicine, epidemiology and dermatology at Pitt’s School of Medicine and the University’s Graduate School of Public Health. “Abnormally high levels of erythrocyte-C4d and low levels of erythrocyte-CR1 are characteristic of SLE and combined measurement of the two proteins has high diagnostic sensitivity and specificity for lupus,” she said.

The significance of the finding is substantial, according to Joseph Ahearn, associate professor of medicine at the School of Medicine and senior author of the study.

“Today we are one step closer to providing patients with an immediate and accurate diagnosis, one step closer to providing physicians with the ability to offer better treatment options and one step closer to providing incentive to lower the cost of health care for patients suffering from lupus,” Ahearn said.

“Lupus is the prototypical autoimmune disease and arguably the greatest diagnostic challenge among rheumatologic diseases,” he said. “The spectrum of disease among patients with SLE is broad and ranges from subtle or vague symptoms to life-threatening multiorgan failure, and the manifestations of lupus often mimic those of other diseases makes it difficult to diagnose.”

It is not unusual for a patient with lupus to seek advice from a variety of specialists and subspecialists over a period of years before being accurately diagnosed, which results in delays in receiving proper therapy and an ultimately greater cost for treating the disease and its complications. Although there is no cure for lupus, there are many ways to treat symptoms, including chemotherapy.

Currently, most physicians rely on blood abnormalities to aid in the diagnosis of SLE, but according to Manzi, these tests are inadequate because they are not sensitive or specific enough.

The study was supported by grants from the National Institutes of Health, the Lupus Foundation of Pennsylvania, the Alliance for Lupus Research, the Lupus Foundation America, Southeastern Pennsylvania Chapter and the National Arthritis Foundation.

Bacteria resistant to antibiotics more likely to result with use of clindamycin

In the first study to directly compare the emergence of antibiotic resistance following topical treatment between two antibiotics routinely prescribed for a common vaginal infection, researchers from the Magee-Womens Research Institute have found antibiotic-resistant bacteria more likely to develop with the drug clindamycin than metronidazole. The study was published in the October issue of the American Journal of Obstetrics and Gynecology.

Researchers followed 99 women between the ages of 18 and 45 who were being treated for bacterial vaginosis (BV), a common gynecological complaint that infects up to 50 percent of women in some populations. BV is characterized by an increase in vaginal alkalinity and substitution of certain beneficial bacteria, particularly those that produce hydrogen peroxide, with more toxic bacteria. Among the infection’s more prominent symptoms is a milky, foul-smelling discharge.

“Symptoms of discharge are one of the most common reasons women visit a gynecologist,” said Sharon Hillier, professor in the departments of obstetrics, gynecology and reproductive sciences and molecular genetics and biochemistry at University’s School of Medicine and senior author of the study. “For years, clinicians have thought of BV infection as a minor problem, but studies have shown that women who have BV are more likely to get herpes and other sexually transmitted diseases, including HIV.”

For the antibiotic-resistance study, investigators traced the frequency and median concentrations of vaginal microbes from women with BV before and after treatment with vaginal preparations of clindamycin or metronidazole, according to Richard Beigi, a former fellow in the department of obstetrics, gynecology and reproductive sciences at the University’s School of Medicine, who now is with MetroHealth Medical Center in Cleveland, and the study’s first author. Beigi was part of the Magee program when the antibiotic-resistance study was completed. Vaginal specimens were collected before treatment began and were compared with those collected during three consecutive follow-up visits. Antibiotic resistance testing also was performed.

While some bacterial concentrations decreased for both groups, women treated with clindamycin experienced more frequent increases in bacterial concentrations of E. coli than those who were treated with metronidazole. In addition, women treated with metronidazole showed more significant decreases in concentrations of other bacteria such as P. bivia, pigmented Prevotella spp and U. urealyticum compared to clindamycin treatment, Beigi said.

“Fewer than 1 percent of bacterial samples we tested demonstrated resistance to metronidazole,” said Beigi. “In contrast, 12 percent demonstrated baseline clindamycin resistance, and 53 percent demonstrated resistance to clindamycin after therapy.”

In addition, women treated with clindamycin (but not metronidazole) showed evidence of clindamycin-resistant bacteria that persisted for 90 days after treatment at rates as high as 80 percent, he said. Metronidazole therapy resulted in increased colonization by protective Lactobacillus species in the week following therapy compared to the women treated with clindamycin.

Testing of pigmented Prevotella spp and P. bivia also revealed significant resistance – 75 percent and 57 percent, respectively – to clindamycin following therapy. Metronidazole resistance was far more rare at 0.5 percent and did not increase after treatment.

“Study results suggest that metronidazole and clindamycin differ in their effects on microbes in women with BV,” said Beigi. “Increased bacterial resistance following clindamycin treatment may account for persistence of some pathogens after therapy.”

Hillier said she believes these study results have the possibility to significantly impact standard BV treatment. “I think any time you find out that use of an antibiotic results in a huge antibiotic resistance, it’s important,” she said. Treatment decisions, however, remain the province of individual physicians and patients, Hillier added.

In addition to Beigi and Hillier, other study authors include Michele Austin, Leslie Meyn and Marijane Krohn, all of the University. The study was funded by an unrestricted grant from 3M Pharmaceuticals, manufacturer of MetroGel-Vaginal, a metronidazole-containing treatment for bacterial vaginosis, and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Concussion research results in international position paper 

Two Pitt sports medicine concussion researchers recently delivered three presentations at the Second International Symposium on Concussion in Sport, considered one of the most prestigious and important gatherings of experts in the world concerning sports concussion management.

The symposium, held Nov. 3 – 6 in Prague, Czech Republic, will result in the publication of a position paper co-authored by Mark Lovell, a neuropsychologist and director of UPMC’s Sports Medicine Concussion Program.

The position paper summarizes the international group’s consensus and recommendations for the advancement of the best possible management of sports-related concussions in athletes of all levels, based on the presented scientific research findings.

The First International Symposium on Concussion in Sport, held in 2001 in Vienna, has proven to be one of the most important and most referenced meetings in the young specialty field of sports concussion management. The position paper issued from that meeting, also co-authored by Lovell, is still widely referenced today. “Sports-related concussion is arguably the most challenging condition to face the sports medicine practitioner on a day-to-day basis,” said Lovell, whose first presentation outlined the common neuropsychological effects of injury, based on research data of more than 500 professional and amateur athletes. “There is tremendous variability from athlete to athleteregarding post-injury signs and symptoms, and the brain mechanisms involved in injury and recovery historically have been poorly understood,” he said.

Studies during the past decade have led to the development of more advanced injury assessment technology and have enabled researchers to document that impairments involving attentional, multi-tasking and working memory systems within the brain are common following injury, according to Lovell. He also discussed how research has shown that post-injury symptoms are dependent on factors such as the biomechanics of the injury, the athlete’s history of prior concussions and genetic make-up.

Lovell’s second presentation discussed the development and refinement of neuropsychological testing methods over the past 20 years, including the evolution of the tests from a paper-and-pencil version — a time-consuming and laborious method — to those being done more quickly and efficiently on laptop computers. Lovell serves as the director of such testing for the National Football League and National Hockey League. Also, he developed ImPACT (Immediate Post-concussion Assessment and Cognitive Testing), the first and most widely used computerized concussion evaluation system in the world today.

Michael Collins, a neuropsychologist and assistant director of the UPMC Sports Medicine Concussion Program discussed recent research data proving that loss of consciousness is not a reliable predictor of injury severity or of recovery time, as was previously thought for many years. “Studies have shown that either retrograde or post-traumatic amnesia – not loss of consciousness — is a much more potent predictor of injury outcome,” Collins said. Collins. “This research data is important because traditionally used injury severity grading scales have relied on loss of consciousness as a criterion for injury severity. We are concerned that no current grading scale explicitly includes amnesia as a severity marker,” he said.

“This analysis underscores the need for further refinement of currently used sports concussion symptom grading scales because almost all of them base injury severity and return-to-play recommendations on the presence of on-the-field loss of consciousness, not amnesia or other symptoms,” Collins added.

Grants awarded to researchers

The National Institute of Mental Health awarded Boris Birmaher of psychiatry $606,667 for a follow-up study of the children of bipolar parents. The five-year study, which examines 800 children and adolescents of 400 parents with bipolar disorder, is in its fourth year.

Chemistry’s Joseph Grabowski received $662,452 from the National Science Foundation to study proposed partnerships between teachers in grades 3 through 8 for energizing science in the Pittsburgh Public School District.

The Agency for Health Care Policy and Research awarded Stephen Raab of pathology $628,254 to study improving patient safety by examining pathology errors.

Barry Stripp of Environmental and Occupational Health received $306,163 from the National Institute of Environmental Health Sciences to study Clara cell secretion and ozidant lung pollutants.

The National Institute of Standards and Technology awarded Engineering’s Sachin Velankar $356,228 to research microfluidic technology to accelerate materials development.

Flu vaccine shortfall may produce more bacterial infections

Sinusitis and bronchitis take a significant toll on a person’s ability to participate in everyday life and have a sizable economic impact, accounting for more than 30 million missed workdays each year, according to survey results released by Berrylin J. Ferguson, associate professor of otolaryngology at the University’s School of Medicine. Both of these bacterial infections occur most frequently during the cold and flu season – November through January.

In a random survey of 606 self-identified recurrent chronic sinusitis or bronchitis sufferers, roughly one quarter (24.9 percent) reported missing three or more days of work and another 23 percent missed one to two days of work. Sinusitis and bronchitis sufferers were more likely to miss leisure activities (58 percent) than work as a result of their illness. Parents reported missing additional time from work to stay home with children who developed sinusitis or bronchitis. About 21 percent of parents missed one to two days of work to care for their children and an additional 20 percent missed three or more days.

“This cold and flu season, we should be particularly vigilant of our health as the flu vaccine is in short supply,” said Ferguson. “Increased prevalence of influenza may translate into an increase in bacterial infections, including sinusitis and bronchitis.”

Ferguson said a person should see a doctor if he or she experiences symptoms of bacterial sinusitis, such as nasal congestion or yellow nasal discharge, with facial pain or pressure that worsen after four days or persist beyond seven days. Symptoms experienced for fewer days are more likely due to a viral illness such as a cold. Bronchitis symptoms to be aware of include shortness of breath, chest pain and chronic cough accompanied by phlegm or mucus 24 to 48 hours following the cough. A persistent phlegm-producing cough that lasts more than three months may be chronic bronchitis.

While viruses and colds usually run their course, bacterial infections, such as sinusitis and bronchitis, may require treatment with an antibiotic in order to get better. Appropriate use of antibiotics may also help people get better faster.

According to the survey, 69 percent of sinusitis and bronchitis sufferers said they felt better more quickly when they took antibiotics versus over-the-counter medicines, with 53 percent experiencing improvement one to two days more quickly with an antibiotic.

Viruses or bacteria may cause sinusitis and bronchitis, with indistinguishable symptoms regardless of the cause. Bacteria usually cause more severe symptoms that persist for a longer period of time, and often follow a viral illness. Survey respondents associated the following symptoms most frequently with sinusitis: nasal congestion (61 percent), headache (53 percent), facial pressure and pain (37 percent), and sore throat (22 percent). Just 21 percent reported discolored or thickened mucus as a symptom they associate with sinusitis.

“While 85 percent of survey respondents said they had been afflicted with a sinus infection in the past 12 months, this survey suggests people may not be as familiar with the primary symptoms of sinusitis. While the other symptoms in combination may signal sinusitis, yellow or discolored drainage is the most specific sign of a sinus infection,” said Ferguson.

In bronchitis, bacteria attack the lining of the bronchial tubes, which carry air to the lungs, causing swelling and mucus. The symptoms respondents most frequently associated with bronchitis included coughing and coughing up phlegm with chest pain (60 percent) and shortness of breath (37 percent). Bronchitis may accompany or follow influenza.

The random survey, conducted in September and October 2004, was supported by an unrestricted educational grant from Abbott.