University Times

Geriatric nursing grant awarded

Grace Campbell, a pre-doctoral student in the School of Nursing, is among 15 candidates in the United States to receive a Hartford Grant for studies in academic geriatric nursing.

She was selected for her doctoral research project, “Predicting Fall Risk in Older Adults in Post-Stroke Rehabilitation.” Campbell will receive $45,000 per year for two years in support of her geriatric research.

The Hartford Grant is part of the American Academy of Nursing’s program aimed at building capacity in academic geriatric nursing to care for an aging population.

“Elderly stroke patients are at high risk for falls, many of which are catastrophic. The Hartford Grant is validation that the medical community sees this as a very important issue,” said Campbell, who also is certified as both a rehabilitative nurse and brain injury specialist.

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Biomarkers point to better transplant survival

Higher levels of the immune protein interleukin-6 (IL-6), a biomarker for inflammation, are associated with decreased survival in patients receiving organs for transplant from brain-dead donors, School of Medicine researchers report in the June issue of Critical Care Medicine.

The Pitt study is “the first time that a marker of inflammation in an organ donor has been shown to predict outcome in the transplant recipient,” the authors wrote.

The results suggest that biomarkers such as IL-6 might be used to help identify organs that are more suitable for transplant, improving survival and health outcomes for recipients.

Significant numbers of organs for transplant come from patients left brain-dead following traumatic injury or illness. While it is known that brain death induces a massive inflammatory response, the influence of this immune response on organ procurement, transplantation and long-term survival for recipients has been less clear.

Led by investigators in Pitt’s Clinical Research, Investigation and Systems Modeling of Acute Illness (CRISMA) Laboratory, researchers evaluated data from 30 brain-dead organ donors at UPMC and the University of Texas Health Science Center in Houston who provided 91 organs for transplant to 78 recipients between April and November 2004.

Bloodstream levels of immune system proteins IL-6, IL-10 and tumor necrosis factor were measured in organ donors hourly for four hours following declaration of brain death, and again immediately prior to organ procurement.

“We found that lower concentrations of IL-6 in the bloodstream of donors prior to organ procurement were significantly associated with improved survival,” said John A. Kellum, senior author of the study and a professor of critical care medicine. “Patients who received organs from donors with lower IL-6 levels were substantially less likely to have complications following transplant requiring hospitalization and were more likely to have longer survival after hospital discharge.”

All organ donors experienced increases in bloodstream concentrations of the three cytokines measured following brain death, but increases in IL-6 were linked most closely with decreased survival.

“These data strongly suggest that the ‘cytokine storm’ seen immediately following brain death negatively affects organ function,” said Raghavan Murugan, study first author and assistant professor in the Department of Critical Care Medicine.

The Pitt team suggests that it is premature to recommend routine screening of IL-6 levels in potential organ donors, but that the study findings open a distinct avenue of future scientific inquiry related to minimizing the inflammatory response in organ donors. “This is one relatively small study, but if the findings are confirmed, I think there is promise to possibly use this technique to ultimately improve organ selection and patient outcomes,” said Kellum.

Other Pitt study authors were Ramesh Venkataraman, Michele Elder, Melinda Carter and Nicholas J. Madden, all of the CRISMA Laboratory, and Abdus S. Wahed of biostatistics.

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ADHD/autism treatment study funded

Researchers at Pitt and Western Psychiatric Institute and Clinic have received $3 million from the National Institute of Mental Health to conduct a national study of the treatment of attention deficit hyperactivity disorder (ADHD) in children with autism spectrum disorders.

“ADHD symptoms are common in children with autism, but children with autism often do not respond well to stimulant medications, the conventional treatment for ADHD,” said Benjamin Handen, principal investigator of the study and associate professor of psychiatry and pediatrics at the School of Medicine.

In the 10-week clinical trial, which will start enrolling patients in September, Pitt researchers and colleagues from the University of Rochester and Ohio State University will recruit 144 children ages 5-13 who have autism with ADHD symptoms.

The researchers will assess the safety and effectiveness of two treatments: atomoxetine (also known as Strattera), a non-stimulant medication for treating ADHD, and parent management training in which parents learn how to use behavioral interventions as another form of conventional ADHD treatment.

At the close of the trial, the researchers will continue to follow for six months all participants who respond favorably to treatment to examine the safety, effectiveness and tolerability of long-term treatment.

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Math-medicine modeling project begun

The National Science Foundation awarded mathematics faculty members G. Bard Ermentrout, Beatrice Riviere, Jonathan Rubin, David Swigon and Ivan Yotov a nearly $1.8 million Research Training Group (RTG) grant for a $2.5 million project that will create models of how the brain and immune system function and change over time in response to certain illnesses, infections and treatment. The models are intended to help doctors better understand and predict the possible short- and long-term responses of a patient’s body to treatment.

The RTG includes resources for creating training programs in which math students would work with physicians and biologists to help resolve complicated medical problems through mathematics. Pitt’s School of Arts and Sciences provided additional funds.

The team will create a variety of computer models based on differential equations, which predict how systems evolve over time, with the medical guidance of scientists and doctors in Pitt’s biological sciences and neuroscience departments, the School of Medicine and UPMC, said Rubin.

The immune system models will plot the various chemical and physical changes that occur as the body battles influenza, inflammation, sepsis and necrosis, and wounds.

Ultimately, Rubin said, the researchers want to pinpoint the origin of such conditions as multiple organ dysfunction syndrome (multiple organ failure), a potentially deadly, uncontrollable inflammation that usually strikes ailing patients with compromised immune systems.

“Infection and inflammation kill people in the intensive care unit,” Rubin said. “We hope that by building this model and calculating how to control the system, we can help doctors design a clinical strategy for intervention based on a condition’s progression.”

The neurological models will outline the typical course of activity in various brain regions, communication among brain cells and time-dependent changes in the synapses. The team will look for how electrical signals and brain waves transmit between brain cells and, in turn, the manner in which those impulses alter the cells.

The complicated models simulate the extensive, constant interaction of various cells and organs operating on multiple time scales. The complexity of these models will require the development of new simulation and mathematical techniques, but the work could apply to several other biological systems.

“We’re exploring mathematical and computational territory that has not been understood yet,” Rubin said. “For instance, the brain contains millions of neurons that in turn contain very small molecules [neurotransmitters]. This network functions on a time scale measured in submilliseconds, a scale so small that no one can really grasp how short it is. At the same time, the brain manages and abides by the circadian rhythm, the body’s 24-hour cycle.

“If we make a breakthrough on how to map these time scales, it would apply to multiple systems,” Rubin added.

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WISER training aids residents

In a study published in the Open Anesthesiology journal, three Department of Anesthesiology professors have shown the value of simulator training in increasing the confidence and knowledge of new medical residents prior to clinical training.

Todd M. Oravitz, David G. Metro and William R. McIvor conducted the study in which first-year anesthesia residents took a three-day simulator course through Pitt’s Peter M. Winter Institute for Simulation Education and Research focusing on operating room preparation, airway management, induction and maintenance of general anesthesia and post-operative transfer of care. The residents completed a knowledge test and questionnaires about performing basic anesthesia skills both before and after the course.

The residents’ confidence in performing the anesthesia skills increased numerically after completion of the course. The mean percentage correct on the knowledge test rose from 53 percent to 69 percent after training.

“We concluded that a brief three-day simulator course can improve new first-year anesthesiology resident confidence and competence to begin clinical training,” the authors wrote.

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