Health Sciences Report Winter 2003

Research in Brief
Summaries of Selected Research Projects at the University of Utah Health Sciences Center

School of Medicine:

  • Alan R. Light, Ph.D., professor in the Department of Anesthesiology, is studying Persistent Pain: Peripheral and CNS Mechanisms. Following injury or disease, pain often is increased or "enhanced," which can be debilitating and may serve no useful purpose. Light has determined that the brain and spinal cord's own unique immune system is partly responsible for long-term enhancement. He is investigating the mechanisms by which the spinal cord and brain immune systems receive information about injury and disease in peripheral tissues, and how the unique brain immune system causes the enhancement of pain. His goal is to determine how to block the pathway as a means to control pain.
  • Lisa Cannon-Albright, Ph.D., professor of genetic epidemiology in the Department of Medical Informatics, is principal investigator on a study to Identify Melanoma Predisposition Loci. Funded by the National Cancer Institute, the project will use the University's Utah Population Database and the Familial Melanoma Research Clinic to identify and sample high-risk melanoma pedigrees; perform a genomic search on the pedigrees; and map predisposition regions to identify melanoma predisposition genes. The results will increase physicians' ability to appropriately screen high-risk patients and researchers' ability to identify molecular pathways that may serve as targets for the diagnosis and treatment of melanoma. Cannon-Albright is collaborating with John J. Zone, M.D., professor and chair of the U Department of Dermatology; Sancy A. Leachman, M.D., Ph.D., assistant professor of dermatology and director of the Tom C. Mathews Jr. Familial Melanoma Research Clinic at the University's Huntsman Cancer Institute; and Nicola J. Camp, Ph.D., assistant professor of medical informatics (see pg. 6).
  • R. Lor Randall, M.D., director of the University's Huntsman Cancer Institute's Sarcoma Service and assistant professor in the U Department of Orthopedics, is investigating the Use of Antigene or Antisense DNA Sequence to block the expression of genes that help keep synovial sarcoma cancer cells alive. Synovial sarcoma is a deadly form of cancer that afflicts patients of all ages. The study, funded by Primary Children's Medical Center Research Foundation, is designed to support a national clinical study designed by Karen Albritton, M.D., chief of clinical affairs for the Sarcoma Service and assistant professor in the medical school's Division of Oncology (see pg. 21).
  • John Kestle, M.D., associate professor of neurosurgery, completed a five-year international multi-center randomized trial that evaluated Endoscopic Placement of Ventriculoperitoneal Shunts in Children. The 383 subjects, including patients at Primary Children's Medical Center (PCMC) and 16 other centers in the United States, Canada, and Europe, were 18 years old and under, with newly diagnosed hydrocephalus. Results showed that endoscopic shunt placement did not improve shunt survival. The findings were published in the February 2003 issue of the Journal of Neurosurgery. The trial was funded by the Spina Bifida Association of America; Medical Research Council of Canada, Ottawa, Ontario; Hospital for Sick Children Foundation, Toronto, Ontario, Canada; and the PCMC Foundation.
  • Kenneth Spitzer, Ph.D., director of the Nora Eccles Harrison Cardiovascular Research and Training Institute, and professor of physiology, is researching pH Regulation in Heart Cells with funding from the National Institutes of Health. The acid base status of the heart has profound effects on its ability to generate electricity and contract. This sensitivity is thought to play a major role in the cardiac dysfunction induced by myocardial ischemia. This project combines patch-clamp techniques and confocal imaging of intracellular pH and calcium to study the cellular basis of pH-induced changes in electrical and contractile activity in cardiac cells, and to determine the ion transports that control their intracellular pH.
  • Sabine Fuhrmann, Ph.D., research assistant professor in the Department of Ophthalmology and Visual Sciences, is investigating the Regulation of Early Eye Development in Vertebrates. Many congenital eye disorders stem from disruptions in early eye development. Fuhrmann's goal is to understand the cellular and molecular mechanisms that regulate the patterning and differentiation of ocular tissues, especially of the neural retina and retinal pigmented epithelium. Recently she found that the TGFb family of growth factors is required for proper development of the retinal pigmented epithelium. She is investigating the role of these and other extracellular factors in early eye development. An important aspect of her research is to investigate the potential of signaling factors as therapeutic agents for retinal degeneration.
  • Jeffrey Rosenbluth, M.D., assistant professor in the Division of Physical Medicine and Rehabilitation, and director of Spinal Cord Injury Medicine, is the U's lead investigator for a multi-center study of Fampridine-SR and Spinal Cord Injury. The double blind, placebo-controlled study began in fall 2002 to evaluate the safety and efficacy of oral Fampridine-SR in subjects with spasticity resulting from incomplete spinal cord injury. In previous studies, the medication has been associated with a range of functional benefits. This study, involving nearly 180 subjects nationwide, is tracking the drug's effects on bladder, bowel, and sexual function, in addition to spasticity.
  • David Gaffney, M.D., Ph.D., associate professor and medical director in the Department of Radiation Oncology, and resident Chris M. Lee, M.D., conducted the Expression of HER2neu (c-erbB2) and Epidermal Growth Factor Receptor (EGFR) in Cervical Cancer: Prognostic Correlation with Clinical Characteristics and Comparison of Manual and Automated Imaging Analysis. Lee evaluated the expression of two oncogenic proteins from the Epidermal Growth Factor Receptors family of cell surface receptors "EGFR and HER2neu" on 55 cervical cancers. Increased expression of HER2neu and decreased EGFR identified patients with improved survival; however, only decreased EGFR membranous staining was significant on multivariate analysis. Cervix adenocarcinomas had increased expression of HER2neu, while cervix squamous cell carcinomas had increased expression of EGFR. These findings may lead to better treatment options for cervical cancer patients.

College of Pharmacy:

  • Arthur G. Lipman, Pharm.D., professor in the Department of Pharmacy Practice, and Keri L. Fakata, Pharm.D., postdoctoral fellow in pain and palliative care clinical research, are conducting a clinical trial on the Efficacy of Mathylnaltrexone (MNTX) in the Management of Opioid-induced Constipation. This is a major problem in terminally ill patients, which erodes their quality of life. Constipation can cause pain, in addition to preventing adequate pain control by not allowing use of a sufficient opioid dose due to patients' intolerance of constipation. Only about 50 percent of constipation can be alleviated by a good bowel protocol. Patients who don't respond to laxatives are at high risk of developing complications, such as small bowel obstruction or perforation, which can be life-threatening. If effective, MNTX will be the first drug approved by the U.S. Food and Drug Administration for this indication in this population. The trial is sponsored by Progenics Pharmaceuticals; Gregory J. Miller, M.D., of CareSource Hospice, is the sub-investigator.
  • Garold S. Yost, Ph.D., professor in the Department of Pharmacology and Toxicology, is investigating Cytochrome P450 Gene Regulation in the Lung. Cytochrome P450 enzymes are responsible for the oxidation of carcinogens found in cigarette smoke into DNA-reactive intermediates that cause lung cancer. Several P450 genes are selectively expressed in specific lung cells in humans, but the mechanisms responsible for this organ-selective transcription are not known. Yost and his research team reported in the May 2 issue of the Journal of Biological Chemistry that a previously unknown protein in certain human lung cells binds specifically to a portion of a P450 gene to help direct the selective transcription of this gene. Identification and characterization of this new protein should provide clues about why some people are more susceptible than others to lung cancer from smoking. The research is funded by the National Heart Lung and Blood Institute, National Institutes of Health.

College of Nursing:

  • Ginette Pepper, Ph.D., R.N., professor and holder of the Helen Lowe Bamberger Colby Presidential Endowed Chair in Gerontological Nursing, is studying the Pharmacological Mechanisms of Falls and Sway in Elderly Adults. Medication use is one of the most readily modifiable risk factors in preventing falls in the elderly, but preventive intervention is limited by conflicting information on the pharmacological mechanisms by which specific medications contribute to falls. In this pilot study funded by the National Institutes of Health, Pepper will determine the relative contributions of anticholinergic activity, postural hypotension, and/or sedation to imbalance, falling, near-falls, and fear of falling. She will test and collect data on 110 individuals who live in Salt Lake and Davis counties in non-institutional settings and are more than 70 years old. They will be followed longitudinally for one year.

College of Health:

  • Blomgren, Ph.D., assistant professor in the Department of Communication Sciences and Disorders, is studying the Functional Neuroimaging of Speech Production in People Who Stutter. The aim of the project is to combine behavioral and functional brain-imaging studies (fMRI and MEG) to compare patterns of speech behavior and correlated brain activation patterns in stuttering and fluent speakers. He is examining the neural bases for speech planning, production, and feedback. He also is planning to study behavioral and neurobiological changes that occur as a result of intensive stuttering therapy.
  • J. David Symons, Ph.D., assistant professor in the Department of Exercise and Sport Science, is investigating Is Exercise Training Cardioprotective? When blood flow can't meet the heart's requirements for oxygen, myocardial ischemia ensues. If this supply/demand "mismatch" evokes ischemia of sufficient intensity and/or duration, coronary arteries become dysfunctional. Since aerobic exercise training improves coronary artery function, Symons tested the hypothesis that prior exercise training lessens ischemia-induced dysfunction of small coronary arteries. His laboratory findings suggest that the mechanism responsible for greater improvement after high-intensity treadmill running involves the relationship between elevated myocardial blood flow, vascular shear stress, and endothelial cell nitric oxide synthase. Taken together, stimulus intensity may be important in determining whether training-induced improvements are maintained in coronary arteries exposed to ischemia and reperfusion.
  • Jim Sibthorp, Ph.D., assistant professor, and Eddie Hill, doctoral candidate, both in the Department of Parks, Recreation, and Tourism, are researching the Effects of Intentional Recreation Programming on Internalization of Type 1 Diabetes Management among Adolescents. Teens struggle to take responsibility for managing their diabetes. This project, in conjunction with the Foundation for Children and Youth with Diabetes (FCYD) and the Utah Association of Diabetes Educators, is assessing the effectiveness of using self-determination theory to increase autonomous self-regulation of diet, exercise, glucose monitoring, and injections. The project, which began in 2002, will continue through FCYD's 2003 winter diabetes camp. Results so far indicate that a diabetes camp built around an autonomy-supportive environment can foster increased perceptions of relatedness and competence for diabetes management. This should lead to internalized diabetes management among adolescent participants.

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