Healing the heart may help headaches
Closing a common opening in the heart called patent foramen ovale (PFO) not only lowers the risk of stroke, it seems to reduce migraines. Researchers now plan to test this phenomenon with a multicenter clinical trial of PFO closure for migraines called ESCAPE: Effect of Septal Closure of Atrial PFO on Events of Migraine with Premere.

About 25 percent of the population has this hole in the heart, and most experience no symptoms. However, studies show the chance of having a PFO is as high as 50 percent for people who suffer from migraines.

The opening, in the upper chambers of the heart between the left atrium and the right atrium, is present during regular fetal development and normally closes soon after birth.

In people with PFO, the flap of tissue between the left atrium and right atrium doesn't seal properly. Exercise, coughing, or stress can push open the flap, allowing unfiltered venous blood to shunt into the left atrium and travel to the brain. Researchers suspect that chemicals or tiny blood clots in the venous blood may trigger migraines.

Doctors treating stroke through PFO closure first noted its effect on migraines -- their patients reported fewer migraines after the procedure. PFO raises the risk of ischemic stroke in people under 55; closing the PFO in stroke victims reduces the likelihood of a second stroke, according to several studies.

Several clinical trials are now under way to determine if PFO closure can successfully treat migraines. The results of the first small clinical trial were presented in March during the 55th Annual Scientific Sessions of the American College of Cardiology in Atlanta.

The study of 147 British patients found a 37 percent reduction in the length and frequency of migraines, compared with a 17 percent reduction in the placebo group. The study participants reported at least a 50 percent decline in the number of days they had headaches. However, the procedure did not prevent migraines altogether.

"These data are interesting, but further studies to answer the question definitively are crucial since many patients showed improvement," says Duke cardiologist John Rhodes, MD, an expert in pediatric and adult congenital cardiac catheterization.

Duke is one of 10 implant sites in the U.S. for the randomized, double-blinded ESCAPE study. The trial will enroll 500 patients with PFO who have failed to find relief through preventive migraine medications.

The closure device is implanted during a routine cardiac catheterization procedure. All participants will proceed to the catheterization laboratory and be placed under anesthesia. Some will have the PFO closed with the Premere device; the placebo group will have a sham procedure with only a catheter incision in the groin.

Rhodes likens the procedure to sealing a trap door with two anchors attached by a string. "We place the first anchor in the left atrium, pull the trap door closed, and then release the second anchor in the right atrium -- after which the PFO is closed," he says.

Rhodes carried out the national multicenter trial's first PFO closure on April 7 on a female patient from northern Virginia. This was the first patient with migraines to undergo PFO closure in a U.S. trial.

The trial sponsor is St. Jude Medical, which manufactures the Premere septal closure device for sealing PFOs. There is a potentially lucrative market for the closure devices -- perhaps 1.5 million migraineurs could qualify for the procedure. Approximately 28 million Americans suffer from migraines.

For more information, visit the ESCAPE trial Web site at escapemigraine.com.

The cutting edge of hip replacement
A profesional back-up singer takes a gig less than three weeks after her surgery. A retired university chancellor goes hunting 22 days after his operation.

These stories of rapid postoperative recovery are not particularly notable in these days of minimally invasive surgery. But after a total hip replacement? It’s nothing short of remarkable, says Duke orthopedic surgeon Scott Kelley, MD, about the results he's seen after employing a new muscle-sparing total hip replacement (THR) technique.

Discussions at a surgical meeting last year piqued Kelley’s interest in the new anterolateral approach developed by German orthopedic surgeon Heinz Röttinger, MD (currently most surgeons use a posterior approach).

Röttinger adapted a procedure from the 1930s and devised a modified split surgical table that accommodates the correct leg position during the operation. Kelley met with Röttinger at the meeting, took two field trips to observe the procedure, then practiced in a cadaver surgical lab before offering it to patients. The results from 50-plus procedures -- and the kudos from his patients -- have convinced Kelley that this is the way to go.

During muscle-sparing THR, the surgeon obtains access to the hip joint by passing between the abductors and the tensor fascia lata, instead of cutting through muscle as with traditional approaches. Less muscle damage means less pain, less blood loss, and faster recovery.

Patients who underwent the new technique after conventional THR on the opposite leg were amazed when their recovery time went from months to weeks, Kelley notes. Patients are often on their feet the day of their surgery, go home after two days, and walk without assistance after two weeks.

"Also, there are no precautions, allowing patients to immediately cross their legs and sleep in any position that’s comfortable," Kelley adds. "People can sit however they want and reach down to tie their shoes."

To aid in preoperative planning, the surgical team employs digital templating -- a technology which superimposes an image of the prosthetic over a digital x-ray of the pelvis. To guide patients through the experience, the team developed an educational DVD that explains all aspects of their care and offers tips on preparing the home to accommodate the patient.

Other Duke orthopedic surgeons are performing other cutting-edge hip replacement techniques, Kelley adds. "We have a very strong hip program."

And, patients would concur, some very strong hips.

Tiny trial therapy
Duke pulmonary specialists are testing an experimental implantable valve designed to improve lung function in emphysema patients. The so-called intrabronchial valve (IBV) limits airflow to selected parts of the lung while allowing the normal clearance mechanisms of secretions to occur.

Using an endoscope, "We place the IBV in the bronchial tubes of the most damaged parts of the lungs," says Momen Wahidi, MD, director of the Interventional Pulmonology Program at Duke, who is leading the study along with co-investigator Thomas D’Amico, MD.

"This allows the more effective parts of the lung to have more space -- replicating what lung volume reduction surgery would do but in a less invasive way."

If the IBV proves effective in clinical trials, it could alleviate the shortness of breath and improve the quality of life for many of the 16 to 30 million U.S. citizens with emphysema, says Wahidi.

Since the IBV is implanted endoscopically, patients can be discharged within 24 to 48 hours, Wahidi says. Another advantage is that the device can be removed if no benefits are obtained or complications arise, he adds.

Duke is one of 10 sites around the country enrolling patients in this study and the only site in North Carolina. To be eligible, patients must have moderate to severe emphysema and must have abstained from smoking for at least six months.

For more information, contact Linda Brown, study coordinator, at 919-668-3380.

Killing two birds -- psoriasis and depression
A drug approved for treating rheumatoid arthritis not only effectively reduces the physical symptoms of psoriasis but also the depression and fatigue patients often experience, according to Duke researchers involved in a multi-site study of etanercept (Enbrel).

The drug is an antibody that blocks the pro-inflammatory cytokine tumor necrosis factoralpha, high concentrations of which have been associated with depression. Until now, however, no research team has examined this relationship in humans.

The primary objective of the clinical trial was to find out if etanercept would improve the clinical symptoms of psoriasis. In severe cases, people with psoriasis can experience joint pain similar to that of rheumatoid arthritis as well as depression and fatigue.

The researchers found that nearly half (47 percent) of subjects taking etanercept achieved 75 percent or greater improvement in their clinical symptoms of
psoriasis at week 12, compared to 5 percent of those on placebo.

In addition, researchers found significant improvements in the etanercept group as measured by two commonly used rating scales for depression. The etanercept group also showed lower levels of fatigue, which strongly correlated with improvements in joint and skin pain.

The results appeared in the December 14, 2005 online Lancet.

Repairing leaky valves
Duke cardiologists and cardiac surgeons are enrolling patients with leaky mitral valves in a clinical study evaluating a new catheter-based approach for mitral regurgitation (MR), a condition in which blood flows back toward the lungs with each heartbeat.

The researchers said should the new system be proven safe and effective in clinical studies, it could give cardiologists a new, less invasive option for mitral valve repair.

Duke is one of more than two dozen other North American medical centers participating in the Phase II clinical study comparing the safety and effectiveness of the new approach to standard open heart surgery. An earlier Phase I feasibility study found that the procedure had a very low rate of adverse events or complications. The MitraClip device reduced MR at hospital discharge to ≤1+ in the majority of patients (MR severity is rated on a scale from Grade 1, mild, to Grade 4, severe).

To enroll a patient or for more information, contact Dana Glisson at 919-681-3810 or dana.glisson@duke.edu.

Move over, mammograms
Duke scientists have created a new breast scanner that will dramatically improve their ability to visualize small tumors while also reducing radiation exposure to one-tenth that of normal mammograms. Moreover, the new device does not compress the breast, as do traditional mammograms.

The new scanner uses computed tomography (CT) with a unique variation: it provides a three-dimensional image of the breast. The new scanner rotates around the breast to obtain a complete image, from the nipple to the chest wall.

Traditional mammograms provide only a two-dimensional image and they compress the breast, thereby distorting the image and causing discomfort for many women.

The Duke scientists have successfully demonstrated that their new CT scanner can detect lesions as small as five millimeters in artificial breast models and in cadavers.

Mammograms are considered able to detect soft tissue lesions around one centimeter in diameter -- about the size of a marble -- although they can detect far smaller micro-calcifications, which could be indicators of disease.

The Duke team plans to begin testing in women within two years and is in the process of developing a start-up company to commercialize the device.

ER drug dosing often inaccurate
When patients come to emergency rooms with symptoms of heart attack, they may be getting more than they bargained for.

A new analysis by Duke Clinical Research Institute (DCRI) cardiologists has found that because of inaccuracies in prescribing, 42 percent of patients rushed to emergency rooms with symptoms of a heart attack received inaccurate doses of powerful drugs intended to stop clotting in coronary arteries.

While numerous clinical trials have proven that these drugs can save lives, correct dosing is crucial, the researchers say, since the therapeutic window is narrow. Too much of the drug can lead to bleeding episodes, while too little may be ineffective at stopping the clotting process.

"These drugs are clearly beneficial, and when dosed correctly are also safe," says Duke cardiologist Karen Alexander, MD, lead investigator of the study published in the December 28, 2005, Journal of the American Medical Association.

The Duke researchers believe that when evaluating these patients in emergency rooms, physicians should spend a little more time clarifying information necessary for accurate dosing, such as weight and kidney function.

The researchers also hope that the results of their analysis provide concrete steps to improve safety, thereby increasing physician confidence in using these drugs on high-risk patients, who have the most to gain.

Say, what's your PSA?
The diagnostic criterion currently used to indicate prostate cancer in all men needs to be age-adjusted to more effectively detect the cancer in younger men, Duke researchers have found.

The researchers found that the criterion -- how fast the level of the telltale protein prostate specific antigen (PSA) is rising -- needs to be set at a lower threshold for men under age 70.

The current threshold for the rate of increase, known as PSA velocity (PSAV), is 0.75 ng/ml/yr, meaning if a man's PSA level rises more than 0.75 in one year, he should consider a biopsy for prostate cancer.

In their study of the medical records of nearly 12,000 men, the researchers, led by Judd Moul, MD, found that using that PSAV criterion for younger men prevented physicians from detecting possible prostate cancers in those men.

To have an accurate picture of their PSA levels over time, men should have a baseline test done at age 40, especially if they are at greater risk for developing the disease, Moul says. Those at greater risk include African American men and those with a family history of prostate cancer.

Those at average risk -- Caucasian men and those with no family history -- should have a baseline test at 45. If the baseline PSA value is 1.5 ng/ml or less, a man need only be screened every five years. A value greater than 1.5 ng/ml warrants an annual screening.

Time to weigh the options
In another recent study at the Duke Prostate Center, researchers found that waiting up to 180 days to treat low-risk prostate cancer poses little or no threat of disease progression.

The multi-university study, published in the March 2006 Journal of Urology, should reassure men that they can take time to choose the best treatment option for them, researchers say.

Macular degeneration: Finding a smoking gun
An interaction between cigarette smoking and a susceptibility gene greatly increases the risk of developing all forms of age-related macular degeneration (AMD), researchers at Duke and Vanderbilt University Medical Center have found.

The combination of these factors accounts for as many as one-third of the cases of AMD. The study, published in the May 2006 American Journal of Human Genetics, represents one of the first examples of an interaction between genetic and environmental factors in the development of a common disease.

The new study of the gene, called LOC387715, represents discovery of the second major susceptibility gene for AMD. An earlier study by this group and others identified the first major genetic risk factor for the disease, a gene called complement factor H (CFH). CFH is believed to play a role in the regulation of the immune system.

A second research group at the Duke Eye Center has found that, in an animal model, cigarette smoke and its component tar trigger the formation of deposits and thickening in the retina that cause AMD. In addition, the combination of the three oxidant "hits" -- smoke, UV light, and a high-fat diet -- exacerbated the effects of smoking on AMD.

This study, published in the February 2006 Investigative Ophthalmology & Visual Science, is the first to examine the mechanism by which smoking causes macular degeneration.

A completely new way to treat asthma
Pulmonary specialists from the United States, Canada, Brazil, Australia, and the United Kingdom are testing a new non-pharmacological strategy for treating difficult cases of asthma by delivering thermal energy to the airway walls to reduce the presence of airway smooth muscle, the tissue responsible for causing the disease's symptoms.

If the effectiveness of this minimally invasive approach is borne out by clinical trials, Duke pulmonologist Monica Kraft, MD, says it could mark a paradigm shift in how asthma patients are treated, in that physicians will now have a procedure-based therapy for the disease.

"While there are many underlying causes, or triggers, for asthma, the end result is inflammation of the airways and smooth muscle contraction leading to airway constriction," says Kraft, director of the Duke Asthma, Allergy, and Airway Center.

"This process leads to the hallmark symptoms of asthma -- shortness of breath, wheezing, and coughing."

In the new treatment, physicians insert a flexible bronchoscope either through the nose or the mouth. The scope is then threaded to the target airway, where thermal energy is deployed, heating the smooth muscle tissue at the specific site for 10 seconds. Physicians then move the scope farther down the airway and deliver therapy again, until the length of the airway has been treated.

For the multicenter trial, physicians will treat about one-third of the airways at each visit. Each treatment session takes about one hour, followed by a four-hour observation period. Patients in the control group will have the bronchoscope inserted, but the thermal energy will not be applied.

Researchers plan to enroll more than 300 patients between the age of 18 and 65 with severe asthma whose symptoms cannot be controlled by conventional therapies.

"We plan to follow patients for at least one year, and while the procedure will not cure asthma, we hope that it will improve patients' quality of life," Kraft says.

For more information about the Asthma Intervention Research 2 Trial (AIR2), please contact Denise Beaver at 919-660-6776 or beave006@mc.duke.edu.

Flying in the face of heart disease
The common fruit fly, that staple of high-school science experiments, could greatly accelerate the search for genetic causes of heart disease finding by serving as a powerful new model for testing human genes, Duke researchers have discovered.

"The difficulty in performing studies to find specific genes that cause disease in humans is that you need large families with members afflicted with the disease," says Duke cardiology fellow Matthew J. Wolf, MD, PhD, first author of a paper about the research published January 23, 2006, in the early online edition of the Proceedings of the National Academy of Sciences. "This can be a quite a complex and laborious undertaking.

"However, fruit flies, with their well-documented genome and rapid life cycle, have the potential to greatly speed the process of finding and verifying candidate human genes for heart disease. In our experiments, we were able to demonstrate for the first time that a mutated gene that causes a specific heart disease in a human causes the same disease in the fruit fly."

The team's bioengineers adapted an existing imaging technology to visualize in detail for the first time the beating of the heart of a fruit fly, an insect the size of a grain of rice.

After perfecting the new visualization technique, the researchers inserted into the fly genome a mutated gene that causes the heart muscle to enlarge and be unable to pump blood efficiently.

The moving images revealed that the fly heart looked and acted just like a human heart with the same condition.

In addition to enabling researchers to systematically screen genes to identify potential gene mutations or variants implicated in human heart disease, the achievement also raises the possibility of rapid screening in fruit flies of drugs to treat heart disease, researchers say.

In recognition of his research, the American Heart Association bestowed upon Wolf its prestigious Louis N. and Arnold M. Katz Basic Research Prize in November.

How to make a fly sit still
Matthew Wolf's field of research is genetics, but for his latest study, the first question was how to make a fruit fly stay still enough to get an image of its beating heart.

"I spent quite a bit of time peering at [the flies] under a microscope to figure out how to immobilize them without harming them," he says. "While I was studying them, my wife happened to take me into a craft store. I found some clear soft gel candlewax that you can melt and pour into molds, and I thought it might be worth a try.

"I took some home and melted it in an old frying pan I have from my bachelor days. When I poured it into petri dishes and let it cool, it created a sticky gel with a level surface."

Wolf brought his findings from the kitchen to the lab bench. He anesthetizes fruit flies with carbon dioxide. Then, watching through a microscope, he uses fine forceps to position the knocked-out flies into small slits in the gel.