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School of Medicine



Simulating stent placement
Post-stent:keeping arteries open in diabetes
Highest honors
Metabolic syndrome and stress
Mapping an anti-cancer molecule
How estrogen prevents bone loss
Radiation robots

Fear factor
A new day and a new chair of pediatrics
Creating an anti-reflux barrier
Controlling seizures deep within the brain
New leader of radiology

Simulating stent placement

The Food and Drug Administration (FDA) recently approved a new technique for treating potentially life-threatening blockages in the arteries of the neck that lead to the brain. The carotid stenting procedure offers a minimally invasive alternative to carotid endarterectomy in patients with carotid artery disease who are at risk for stroke.
     The procedure has fewer bad outcomes compared with carotid endarterectomy, according to Emory Heart Center cardiologist Christopher Cates.
     FDA approval of the Guidant carotid stent and embolic protection system (the latter, a tiny filter to catch clots stirred up by the procedure before they float to the brain) will allow treatment of patients with blocked carotid arteries who have been unable to undergo surgery due to lung disease, heart disease, or other illnesses. However, the FDA recommends that physicians who use the carotid stenting device undergo special training.
     Working with the Society of Cardiovascular Angiography and Interventions, the Emory Heart Center is one of 30 training sites for carotid stenting across the nation and one of the first to develop a training program using virtual reality simulators. With the simulators, which look like human mannequins, physicians practice threading a catheter through an artificial circulatory system as they view angiograms of the “patient’s” heart.
     “For the first time, physicians are able to practice on simulators,” says Cates. “Just as airline pilots learn to fly on simulators, physicians can practice on simulators before performing carotid artery stenting on patients.”


Post-stent: keeping arteries open in diabetes

Following angioplasty, stents are frequently used to keep newly widened arteries open. However, renarrowing, or restenosis, is a frequent problem, especially in diabetic patients. A multi-center study, led by Emory cardiologist John Douglas has found that restenosis in diabetics undergoing coronary stenting can be reduced significantly with the drug cilostazol. The CREST (Cilostazol for RESTenosis) trial found a statistically significant decrease in restenosis in diabetic patients receiving cilostazol over placebo. This benefit persisted even in a group of diabetic patients with smaller vessel sizes, the most challenging population to achieve durable results with stenting.


Highest honors

The Institute of Medicine (IOM) has elected four Emory faculty to its new class of leading national health scientists: Mahlon DeLong (neurology), Stephen Warren (human genetics), Ricardo Martinez (emergency medicine), and Ruth Berkelman (Rollins School of Public Health). In addition, the IOM elected two adjunct Emory faculty members: CDC Director Julie Gerberding and James Marks, also of CDC. Whereas a decade ago, Emory had only one member in the IOM, today it boasts 20 in the institute. Membership represents one of the highest honors in medicine.


Metabolic syndrome and stress

Could autonomic dysfunction, signaled by changes in heart rate variability, play a role in the development of metabolic syndrome? Could this explain an increased coronary artery disease mortality risk in persons with metabolic syndrome? Emory research suggests that’s the case.
     The American Heart Association estimates that approximately 47 million U.S. adults now have metabolic syndrome, a nearly five-fold increase in the past 40 years. People with the syndrome display a combination of symptoms that include increased abdominal fat, obesity, high blood sugar, raised levels of triglycerides, and low levels of HDL. A key underlying abnormality in metabolic syndrome is insulin resistance.
     An Emory research team, headed by Viola Vaccarino, examined whether autonomic dysfunction (as measured by heart rate variability) is associated with insulin resistance. Among the participants (160 middle-aged male twins free of symptomatic coronary artery disease), those with greater insulin resistance had lower heart-rate variability scores. The association was unchanged with adjustments for age, education, and smoking behavior.
     While the actual causes of metabolic syndrome remain uncertain, data are accumulating to suggest that autonomic and neuroendocrine abnormalities typical of the stress response may play a role. “Our findings fit into this picture,” says Vaccarino. “If the role of stress in everyday life and its impact on metabolism is clarified, this may have a huge impact on our understanding of what causes metabolic syndrome as well as help us to better prevent diabetes and heart disease.”


Mapping an anticancer molecule

Emory scientists, collaborating with researchers at three national laboratories, have solved the structural puzzle of how an emerging class of cancer drugs work to halt cell division. The findings may lead to the creation of more effective cancer treatments.
“Uncovering and mapping the structure of this model system will assist scientists around the world in creating new compounds that could lead to new cancer drugs, says Jim Snyder, an Emory chemist and director of biostructural research.
     Published in Science, the report includes the first 3D, atomic-scale images of the binding site where one of the drugs, epothilone A, interacts with a key protein controlling cell division. The researchers have examined two drug families—the epothilones and taxanes. The drugs work to halt the division of cancer cells by binding to the same site on a protein called tubulin that is involved in cell division.
Jim Nettles, an Emory doctoral candidate in molecular and systems pharmacology and first author on the paper, hopes that the model system will be useful as a clinical tool for matching the best drug to a given patient.

How estrogen prevents bone loss

a new link in the chain of immune system events through which estrogen prevents bone loss. Through research in mice, scientists found that an immune-signaling molecule called type b transforming growth factor (TGFb) is responsible for a cascade of events that leads estrogen to prevent bone loss. When TGFb signaling in T cells is blocked, the bone-sparing effects of estrogen are lost.
     Garland Herndon Professor of Medicine and Director of the Division of Endocrinology Roberto Pacifici and research associate Yuhao Gao led the study, published in Proceedings of the National Academy of Sciences.
     Pacifici and colleagues removed ovaries from mice and then studied the effects of estrogen on immune cells and on bone marrow in culture. They found that the level of TGFb in the bone marrow macrophages of mice lacking ovaries was about half that of mice with ovaries. When they treated the mice with estrogen, levels of TGFb in the bone marrow increased about three-fold in mice with ovaries and about eight-fold in mice without ovaries.
     To test the effects of TGFb on bone-marrow density, the scientists used a transgenic mouse model in which TGFb signaling in T cells is blocked. Although these mice had the same level of bone density as control mice at birth, they gradually lost bone density over time, suggesting that when T cells are insensitive to TGFb signaling, they stimulate the loss of bone. These findings could lead to new therapeutic approaches for preventing bone loss.


Radiation robots

Emory is the first health care facility in the United States to deliver new, ultra-precise radiotherapy treatments using a fully robotic, on-board imaging system for tracking tumor locations and positioning patients. The image-guided radiation therapy uses a newly developed On-Board Imager and Clinac linear accelerator from Varian Medical Systems. The technology is expected to improve the precision and effectiveness of cancer treatments by giving doctors the ability to accurately track and adjust for tumor movements at the moment of treatment.
     With the precision of techniques like image-guided radiation therapy, doctors can deliver higher doses to the tumor while reducing the dose to nearby critical structures, says Lawrence Davis, chair of Radiation Oncology, “which can only translate into better tumor control and fewer complications.”
     The On-Board Imager is a digital imaging system mounted on the treatment machine via robotically controlled arms that operate along three axes of motion so that they can be positioned optimally for the best possible view of the tumor and surrounding anatomy. The device produces high-resolution images of the tumor, and it also can track tumor motion to provide doctors a clear indication of exactly how a tumor will move during treatment due to normal breathing and other physiologic processes.




Afraid of heights? Emory scientists have found a potential cure. In a study of 28 people suffering from acrophobia, study participants received either a tuberculosis drug (D-cycloserine, or DCS) or a placebo, followed by two virtual reality sessions that simulated standing in a rising glass elevator. Compared with subjects who took only placebo, those treated with DCS experienced a significant reduction in their fear of heights that was maintained for at least three months after concluding therapy.
The mechanisms governing the fear response, located in the amygdala region of the brain, function abnormally in an acrophobic’s brain. DCS binds to neurotransmitter receptors in the amygdala, and when combined with virtual reality exposure therapy, DCS facilitates fear extinction in the acrophobic’s brain.
The study, led by Michael Davis, Kerry Ressler, and Barbara Rothbaum in Emory’s Department of Psychiatry and Behavioral Sciences, appeared in the November issue
of Archives of General Psychiatry.



A new day and a new chair for pediatrics

Barbara Stoll, an internationally recognized pediatrician who specializes in issues of neonatal infectious disease and child survival, has been named chair of the Department of Pediatrics and medical director of Children’s Healthcare of Atlanta at Egleston.
     Stoll’s appointment to the newly combined posts will further cement a strong leadership connection between Emory and Children’s, which have enjoyed a long historical association at their adjacent Clifton Road campuses. Many of the doctors at Children’s at Egleston are Emory pediatrics department faculty members.
     Shortly after Stoll’s appointment, Emory Children’s Center physicians moved from modular buildings located behind Children’s at Egleston into a nearby, newly constructed $42 million Emory Pediatrics Building. Children’s at Egleston is launching a hospital expansion project on the 2.4 acres of land vacated by Emory upon the opening of the new pediatrics center.
     Stoll has been a faculty member at Emory since 1986, serving as interim chair of the pediatrics department for the past year, following the departure of former chairman Devn Cornish. She also has been named to serve as president and CEO of the Emory Children’s Center, the largest pediatric multispecialty group practice in Georgia, and as president of the Emory Egleston Children’s Research Center.
“This is a new day for pediatrics at Emory,” says Stoll. “Our new building is a wonderful metaphor for a fresh and invigorated department. There are challenges ahead, but for the first time in the history of the Department of Pediatrics, we have beautiful new space—consisting of both a wonderful pediatric clinic and state-of-the-art, 21st century laboratories for scientific research.”
Along with her appointment as chair, Stoll is the first holder of the new George W. Brumley Jr. Chair in Pediatrics, supported by a $2 million gift and pledge from the Zeist Foundation of Atlanta. Brumley, who served as chair of pediatrics from 1981 to 1995, died along with 11 family members in a tragic plane crash during a family trip to Kenya in 2003.
“George Brumley was the man who hired me and one of my mentors. There is a certain poignancy every time I think about holding a chair that bears his name,” says Stoll. “He left big shoes to fill, and I am humbled and honored to serve as the George Brumley Chair.”


Creating an anti-reflux barrier

Gastrointestinal surgeons at Emory are among the first in the world to treat patients suffering from gastroesophageal reflux disease (GERD) with a simple, outpatient endoscopic procedure that takes less than an hour. More than 15 million Americans suffer from daily heartburn, one of the most common symptoms of GERD.
     “Reflux can be a very debilitating condition, and this procedure gives patients a viable option to traditional surgery and costly medications,” says Edward Lin, assistant professor of surgery.
     The new procedure differs from traditional surgery, in which part of the upper stomach is wrapped around the esophagus to create a new anti-reflux valve from the exterior of the gastroesophageal junction. The new technique is a full suturing method that attempts to create a “ball-valve” anti-reflux barrier from inside the upper stomach relying completely on endoscopy.
     The technique uses a device consisting of a reusable instrument called a plicator, a single-use cartridge containing a suture-based implant, and a specially designed endoscopic tissue retractor. The device is passed orally into the stomach over a guide wire and sutures the inside of the stomach at the gastroesophageal junction to tighten the valve, stop reflux, and restore the natural anti-reflux barrier. Normally, a muscular valve at the end of the esophagus keeps stomach contents from refluxing into the esophagus. However, in GERD, this valve is weak or relaxes too frequently, allowing stomach contents to flow freely into the esophagus.
     “This is appropriate for patients with complex conditions—especially for those who cannot undergo more invasive surgery or who choose an intermediate procedure between medications and surgery,” says Lin. The procedure was approved by the FDA in April 2003.



Controlling seizures deep within the brain

ABOUT 20% OF PATIENTS WITH EPILEPSY lack control of their disorder because either anti-epileptic medications are ineffective or they fail to qualify for standard epilepsy surgery, according to Emory neurologist Thomas Henry. Emory is exploring two alternatives for these patients: deep-brain stimulation therapy and vagus nerve stimulation (VNS).
     Deep-brain stimulation has proved effective for other neurologic conditions such as Parkinson’s disease. In the SANTE trial (stimulation of the anterior nucleus of the thalamus for epilepsy), researchers at Emory and 11 other sites will study whether deep-brain stimulation of the thalamus (one of the areas of the brain most involved in seizure circuitry and development) will improve conditions for epileptics.
Under general anesthesia, participants will have a lead, or thin wire electrode, implanted in the anterior nucleus of the thalamus on both sides of the brain, which will be connected to a single pacemaker-like device implanted under the skin near the collarbone. The leads and pacemaker will then be connected by extension wires threaded under the skin of the neck. The stimulation from the device will deliver electrical pulses directly to the targeted areas in the brain through the extension wires and leads.
     The SANTE study is significant because it will enroll a larger number of participants than previous pilot studies, and it will include a longer study period, a total of 13 months.
     Already Emory researchers have found that VNS may activate areas of the brain for longer periods, up to months or longer, than previously thought. VNS is the only FDA-approved, implantable, electrical stimulation therapy for epilepsy. The scientists measured neuronal activity before and after long-term VNS and found a reduction in seizures when higher levels of VNS were used.
     Using positron emission tomography, the researchers found that cerebral blood flow changes showed increased synaptic activity in the so-called “sensory strip” of the brain’s cortex—an expected finding because the patient felt mild sensations during stimulation. VNS also activated the thalamus and other brain areas involved in memory, thinking, alertness, arousal, and emotional processing. With higher levels of stimulation, blood flow was increased more than at low stimulation in these areas.
     “These findings show that cerebral blood flow changes in various areas of the brain help in reducing seizures when activated by VNS,” says Henry. “Some types of seizures start in the thalamus, but this research suggests that we may be able to control widespread seizures that begin in other areas of the brain with VNS."


New leader of radiology

Sanjay Saini, widely recognized for applying his research expertise and business skills to developing top-tier working environments in academic medicine, has been appointed the William Patterson Timmie Professor and Chair of the Department of Radiology and professor of radiology. He also holds a joint appointment in the Goizueta Business School.
     A specialist in gastrointestinal radiology and liver imaging, Saini previously served on the faculty of Harvard Medical School for 23 years. He was director of Computed Tomography at Massachusetts General Hospital and vice chair of radiology for Health Systems Affairs. He also was director of Partners Radiology, a collaborative organization encompassing five acute care systems.
     Saini’s research interests included clinical research and management investigation. His early clinical research focused on developing novel contrast agents to improve imaging of liver tumors. More recently, he has been examining work flow of radiology departments, cost reduction, and improving quality of care.
     Saini succeeds William Casarella, who continues as executive associate dean for clinical affairs in the School of Medicine. Casarella, professor of radiology, is currently focusing on Emory’s clinical services at Grady and also providing clinical services in radiology.

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