Surgery Sooner Rather Than Later May Be Best for Drug-Resistant Epilepsy (Johns Hopkins Medical School)

George Jallo and Fred Lenz: 

 

When medications aren’t controlling seizures, there are alternatives.

Many epilepsy patients spend years searching for a drug that can control their seizures, a quest that can lead them to try a dozen or more different medications. Until recently, many of those patients and their doctors considered surgery a last resort: Patients receiving surgery for epilepsy have had the condition, on average, for 22 years.

Now some epilepsy specialists are shifting their view; they say that patients with certain forms of the disorder, whose seizures cannot be controlled with medication should not wait that long before considering surgery. “Seizure surgery is really not a last option,” says neurologist Greg Bergey, director of the Johns Hopkins Epilepsy Center. “There’s more of an appreciation that surgery can render people seizure free and should be considered after several years if medications do not provide seizure control.”

Not having seizures managed isn’t a reasonable option, says neurosurgeon Fred Lenz. The health consequences include memory loss, an increased risk of accidents and reduced life expectancy.

What’s brought the change in philosophy about surgery, Lenz explains, arises from a growing body of research on the 20 percent to 40 percent of epilepsy patients who fall into the “intractable” category—most with the form called temporal lobe epilepsy.

In one set of studies, results suggest that patients whose seizures persist even after they’ve tried as few as two or three different epilepsy drugs are unlikely to find effective medication. “The odds of improving your chances on the third or fourth or fifth drug are vanishingly small,” says Lenz.

Still other research examines how patients fare after surgery for temporal lobe epilepsy. In the typical procedure, surgeons remove the small, focal portion of brain tissue that generates a patient’s seizures. Some 60 percent to 90 percent of patients who undergo an operation no longer have disabling seizures, even though some may still need to take anti-epilepsy medication.

Technical advances have influenced most neurosurgeons’ views on epilepsy surgery. The ability to image seizures in the brain through MRI and PET has improved dramatically in recent years. In addition, epilepsy specialists now have improved methods to analyze the electrical activity of a patient’s seizures using advanced digital recording technology. “And the quality of the technology has improved a lot,” says Lenz. “We can now localize seizures’ focal points in the brain with a definition we never had before.”

Hopkins neurosurgeons perform about 45 epilepsy operations per year, about one quarter of them pediatric cases. The latter reflects a pediatric shift to the sooner-is-better-than-later approach for children with intractable seizures, says pediatric neurosurgeon George Jallo, who’s operated on children as young as 1 year. (In contrast to adults’ temporal lobe seizures, most children’s seizures arise in the frontal lobe or other non-temporal areas.) “Children tend to do great,” Jallo says. “They generally recover better than adults.”

That said, surgery isn’t appropriate for every epilepsy patient. It generally works best on those whose seizures originate in a relatively small focal area of the brain, says Lenz. Patients with more diffuse seizures or with seizures that come from multiple regions or both sides of the brain are often not good surgical candidates.

As in any form of brain surgery, there are risks, including stroke, hemorrhage and infection. “Patients need to assess these and the likely benefits carefully with a neurologist before considering surgery,” advises neurologist Gregory Krauss. Still, for many patients, he adds, the consequences of continued uncontrolled seizures far outweigh any risks.

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Cartilage Replacement Using The Body's Own Cells: Fast, Affordable And A Perfect Fit

Injuries to joints and cartilage can have serious consequences, including osteoarthritis. Cartilage degeneration in joints is a widespread disease in Germany and worldwide. Prof. Dr. Prasad Shastri is an expert in tissue engineering (TE), tissue construction and tissue cultivation using the body's own cells. He is Professor of Biofunctional Macromolecular Chemistry at the Centre for Biological Signalling Studies (BIOSS), a Cluster of Excellence at the University of Freiburg, where he has been researching for the last year. Together with peers from Maastricht and Nashville, he has developed a fast and cost-efficient method for producing sufficient amounts of bone and cartilage tissue using the body's own cells.

Damage to larger joints such as knees, feet, hips and shoulders is often the beginning of a painful process during which mobility continues to decrease. Because cartilage cannot regenerate after the body has stopped growing, defects caused by injuries and "wear and tear" cannot be absorbed by producing new cartilage. Genetic engineering and molecular biology have now made it possible to remove healthy cartilage cells and grow these outside the body in special solutions. This cartilage tissue is then applied to the defective cartilage where it attaches and grows. Repairing cartilage and bone damage using the body's own cells is still a difficult process. Cultivating the body's own tissue is still time-consuming and expensive, and much time is needed until the implant has reached its desired functionality. In their article published in the renown American journal PNAS, Dr. Prasad Shastri and his co-authors present a strategy for the "de novo engineering" of cartilage and bone tissue which requires only three weeks.

The scientists even successfully generated large pieces of bone tissue using Agarose gel, a common biomaterial in biochemistry. The gel is injected into the double membrane surface on bones, using this space as a biological reactor. According to the main argument in the article, the resulting lack of oxygen (hypoxia) in that confinement induces and stimulates the development of bone tissue and cartilage. Studies have shown that the cultivated cartilage tissue adapts well to its new environment and shows no signs of calcification even after nine months.

Source: Albert-Ludwigs-Universitat Freiburg

Why Do People Become Lactose-Intolerant? Scientists Turn to DNA in an Attempt to Answer Why Adults Develop Trouble Digesting Milk But Can Eat Ice Cream (from the Wall Street Journal)

By Shirley S. Wang

Most of us drank milk every day when we were young without a problem. Then, sometime in our teens or early 20s, we start to feel bloated or have discomfort after consuming a lot of milk, typically two or more glasses at a time.
Scientists have discovered that most people develop some degree of lactose intolerance as they get older. Why we lose this ability to break down lactose, the key sugar found in milk, is a puzzle that researchers have been trying to figure out. The National Institute of Child Health and Human Development, part of the National Institutes of Health, will hold its first conference on the topic next week.
It is unusual for people to lose the ability to digest a nutrient as they age. But most people stop making large quantities of "lactase"—the enzyme that breaks down lactose—after childhood, says Eric Sibley, an associate professor of pediatrics at the Stanford University School of Medicine, who has been studying why people develop lactose intolerance as they get older.

So Young Lee/Journal of Biological Chemistry 2002

 

Most people stop making large amounts of lactase—the enzyme that breaks down lactose, pictured above—as they age.

Most people continue to produce some lactase, but at much-diminished levels. After they reach their individual threshold and can no longer break down lactose, it passes intact through the intestine until it reaches the colon, where it is finally fermented by the bacteria that reside there. As the bacteria do their job, they produce gas as a byproduct, which causes discomfort and pain as well as symptoms such as cramping and diarrhea.

Training the Bacteria

Some people, after diagnosing themselves, cut out regular consumption of dairy—which can potentially make symptoms worse when they do consume it. The bacteria in the gut can become less efficient at processing lactose if they aren't continually asked to do it. Conversely, people can train the bacteria to tolerate more dairy if they consume it regularly.
By understanding which genes and proteins are responsible for turning off lactase production, scientists are hoping they can then flip a genetic switch to turn the system back on—but only in the intestine. The hope is one day to be able to "program the intestine to take on the ability to maximally use nutrients," says Dr. Sibley.
This type of complex localized gene therapy isn't likely to be used in run-of-the-mill lactose-intolerant individuals, who can just watch the amount of dairy that they consume or take enzyme supplements. Instead, says Dr. Sibley, it could be used to treat children with serious digestive diseases, such as short bowel syndrome, get the nutrients they need.
Dairy products that have gone through some processing, such as cheese and ice cream, tend to have less lactose because the fermentation process breaks some of it down. But those with an intolerance should keep an eye out for lactose that has been added to products like cookies by reading the food label, says Gilman Grave, acting director of the National Institute of Child Health and Human Development's Center for Research for Mothers and Children.
A separate group of individuals have an allergic reaction to milk that isn't related to lactose. Instead, they are allergic to a protein in cow's milk and tend to have more blood in their stool and abdominal pain, instead of bloating. The allergy typically fades after childhood.
For years, doctors thought that lactose intolerance primarily affected individuals from certain parts of the world, such as Asia and Africa. But newer evidence suggests the opposite is true. Most adults develop lactose intolerance. Only a minority—those descended from herding cultures in northern Europe and parts of Africa—have a mutation that allows them continue to break down lactose into adulthood. The misperception likely developed in part because so many Americans are of northern European descent and have the mutation.
"A lot of people are self-diagnosing themselves with being lactose-intolerant just because they're a member of a certain ethnicity, and they may not be," Dr. Grave says.
Dr. Sibley, who holds a doctorate in biochemistry and also is a pediatric gastroenterologist at Lucile Packard Children's Hospital at Stanford, has spent more than 15 years in the lab investigating genes and proteins that tell the lactase system to shut down production.
To track whether the lactase gene is turned on or off, Dr. Sibley borrowed the firefly's "luciferase" gene, which is responsible for lighting up the firefly's tail. Light is emitted when the gene is turned on.
In the lab, Dr. Sibley and his colleagues take fragments of DNA from regions they think are important to lactase production and graft them into the luciferase gene. They then implant the combination gene into human intestine cells in a dish and allow them to grow. If the DNA fragment indeed starts the lactose production process, it turns the gene on. Thanks to the graft, the turned-on gene emits light, which can be measured.
Using these methods, Dr. Sibley figured out what section of DNA appeared to be responsible for turning the lactase system on and off. In cells from people descended from northern Europeans, a single genetic mutation was associated with the continued ability to tolerate lactose.
They then took cells with those mutations, and in a dish, showed that they increased luceriferase production, which suggests the mutation does change the cell's behavior. These findings were published in 2003 in the journal Human Molecular Genetics.
With the small segment of the African population that is lactose-tolerant, the mutations appear to be slightly different but are located in the same region of the DNA.

Multiple Proteins

Dr. Sibley and his colleagues have also identified several key proteins that must be bound to specific regions of the lactase gene and in the right combinations in order to turn on the gene. One protein they are currently studying, called PDX-1, appears to suppress lactase production in cells in the dish. But when the group generated mice that don't make PDX-1, lactase production was only slightly increased. This suggests that there are multiple proteins working together to suppress lactase and that PDX-1 alone isn't enough to turn the system off completely, says Dr. Sibley.
They also are working to figure out which segment of the DNA sequence tells the lactase gene to produce lactase in certain cells of the intestine but not others, and when the system should be turned off. The ultimate goal of this line of research would be to be able to turn on genes in cells in the intestine that don't naturally produce it, says Dr. Sibley.
Individuals who are worried they are lactose-intolerant can do a self-test by cutting out dairy for two weeks and seeing if their symptoms subside, says Dr. Sibley. There is also a breathalyzer test that measures the amount of hydrogen in the breath, which is a byproduct that bacteria produce if they are breaking down lactose. Most individuals don't need it to be diagnosed with lactose intolerance, according to Dr. Sibley.
For most individuals, lactose intolerance doesn't mean they should permanently cut out all dairy. Studies have shown that people who are lactose intolerant can drink one to two glasses of milk a day without symptoms, says Dr. Grave, who encourages all people without allergies to drink this amount. Many people say their symptoms actually improve when they regularly drink milk, perhaps because the bacteria in the colon break down lactose more efficiently or the number of bacteria build up, he says.
Another reason to drink milk: calcium. If children in particular don't get the amount of calcium they need, their growth and skeletal health may be compromised, says Dr. Grave. A New Zealand study showed that kids on a dairy-free diet get only one-third of their needed daily calcium and had a higher fracture rate, compared with kids who consumed dairy.
It is certainly possible to get calcium from other foods, but people would have to eat vast amounts of it in order to get the same amount found in dairy, says Dr. Grave. For instance, you would have to eat many servings of spinach in order to absorb the same amount of calcium you would get in one cup of milk.
Write to Shirley S. Wang at shirley.wang@wsj.com

Molecular Pathways Linked to Sex, Age Affect Outcomes in Lung Cancer

By Duke Medicine News and Communications
The biology of lung cancer differs from one patient to the next, depending on age and sex, according to scientists at Duke University Medical Center.

The findings, appearing in the Journal of the American Medical Association, may help explain why certain groups of patients do better than others, even though they appear to have the same disease.

“Our study supports two key findings: First, the biology of lung cancer in women is dramatically different from what we see in men. Women, in general, have a less complex disease, at least in terms of the numbers of molecular pathways involved. We also discovered that there is a subset of elderly patients would probably benefit from treatments that we’ve normally reserved for younger patients,” says Anil Potti, MD, an oncologist in the Duke Institute for Genome Sciences & Policy (IGSP), and the senior author of the study.

Potti says that in the past, physicians have had to rely on very rough measures to categorize patients’ lung cancers, factors such as the size of the tumor, the tissue type and the degree to which the cancer had spread.

“But this new information tells us that we can analyze patients’ disease much more discretely,” says Potti. He says the information could also be used to enrich the selection process in clinical trials designed to evaluate new drugs aimed at specific molecular targets.

Physicians have long observed that over time, women with lung cancer tend to do a little better than men, and that younger patients do better than older ones. Potti found that women tend to have only a few cancer-promoting pathways activated in their tumors, where men may have twice as many.

Potti and a team of researchers in the IGSP studied clinical data and accompanying genomic information obtained from tumors of 787 patients with predominantly early stage non-small cell lung cancer (NSCLC), the most common form of the disease. They gathered tumor samples and corresponding microarray data showing which genes were activated in the tumors, then selected twelve of the most common molecular pathways that become dysregulated in NSCLC.

The goal was to identify any patterns linking the pathways to age, sex and time to recurrence. They sorted the patients by age and sex and then again into low- and high-risk groups, based on five-year, recurrence-free survival.

They found that certain molecular pathways were more frequently activated in some groups than others and that certain pathway patterns were associated with better long-term survival in patients with lung cancer. Specifically, they found that:
High-risk patients -- those with the shortest time to recurrence -- were significantly more likely to have increased activation of the pathways responsible for tumor metastasis and necrosis, when compared with low-risk patients.
High-risk patients 70 or older were found to have higher activation of pathways regulating blood supply and invasiveness.
In comparing high-risk women to high-risk men, they found that men were more likely to have a much more complex pattern of multiple pathways being activated than women with the same type of lung cancer.

The study also identified a subset of patients over age 70 who had a low-risk profile, meaning the molecular pathways activated in their tumors would likely give them a better chance at long-term survival. Potti says that’s important because people over age 70 are generally not included in many clinical trials and physicians often hesitate to offer them the option of conventional chemotherapy.

“The thinking has been that they may not withstand the treatment or benefit from it much. But now we know that it probably makes sense to consider treating this population, by risk-stratifying the disease,” says Potti.

Potti says it is likely that there are additional cancer-promoting pathways that are involved in the development and progression of NSCLC and adds that these findings must be validated in other studies. But he said the set of 12 known oncogenic pathways they chose to study are significant “because we already have drugs that can regulate many of them.”

“People still don’t realize how bad a disease this is,” says Jeffrey Crawford, MD, a study co-author and the chief of medical oncology at Duke. “Lung cancer kills more than 150,000 patients each year in the U.S. -- more than breast, prostate, colon and ovarian cancer combined. Unfortunately, there is a patient dying from lung cancer every three minutes in this country. So being able to better understand the disease and stratify patients by their individual molecular profiles means we can do a much better job pairing the right drug with the right patient.”

The study was funded by grants from the Emilene Brown Cancer Research Fund, the Harold and Linda Chapman Lung Cancer Fund, the Jimmy V Foundation, the American Cancer Society and the National Cancer Institute.

Duke colleagues who contributed to the study include lead authors William Mostertz, Marvaretta Stevenson, Chaitanya Acharya, Isaac Chan, Kelli Walters, Wisut Lamlertthon, William Barry, Jeffrey Crawford and Joseph Nevins.

How To Recognize A Heart Attack, Or Avoid One All Together

Not everyone who suffers aheart attack clutches their chest and falls to the floor. "I woke up and felt like a pill was stuck in my throat," says Betsy, a 68-year-old patient from Upper Providence. "I was taking antibiotics at the time and really didn't think much of it," she adds. "So I tried drinking water and when the "stuck" feeling didn't go away after 45 minutes, I thought something might be wrong."

"My son took me to the Emergency Room and yes, now I realize I should have called 9-1-1 immediately." After the ER staff ran an EKG (a test that measures the electrical activity of the heart), they told Betsy she was having a heart attack. "Next thing I knew, they took me right to the cardiac cath lab and inserted a stent to open up my artery. After two days in the hospital, I came home and started cardiac rehab three times a week for about the last 5 weeks."

Betsy's recovery also involved making important changes to her lifestyle like quitting smoking, "which I really didn't want to do, but I had to," watching her cholesterol, and making time for daily exercis whether it's walking or using free weights.

"What's amazes me most is that I didn't even realize I was having heart attack. Had I waited much longer, things may have turned out very differently."

Betsy is one of an estimated 650,000 Pennsylvanians, ages 35 and over, who have been told by a doctor that they've had a heart attack. In the January 2010 Patient Poll conducted by the Institute for Good Medicine at the Pennsylvania Medical Society, 34 percent of those surveyed said they'd know they were having a heart attack because their chest and arms would hurt.

Not necessarily so, says C. Richard Schott, MD, a Philadelphia-area cardiologist and Pennsylvania Medical Society member. "Pain isn't always an indictor. Any new pressure or discomfort in the upper body can signal a heart attack."

Warning Signs

Dr. Schott urges patients to pay close attention to these heart attack warning signs:

-- Pressure or discomfort in the chest/upper body

-- Discomfort radiating to the left arm, jaw, back, neck or stomach

-- Shortness of breath

-- Sweating, nausea, dizziness

If you experience one or more of these symptoms, it's best to call 9-1-1 right away. "Err on the side of caution and assume it may be a heart attack. The longer you wait, the more damage is done to your heart." Dr Schott also notes, "And the only ride you should take to the ER is in an ambulance they can alert the cardiac team in advance of your arrival and, if your heart stops, emergency personnel can begin treatment immediately."

Who's at risk?

Betsy's smoking, age, and sedentary job put her at risk for a heart attack. Here's what else matters:

1. Family History If your father had heart problems before age 55 or your mother had problems before age 65, or if your brothers or sisters have had heart attacks, talk with your doctor and be especially careful to minimize other risks.

2. Smoking Heart health is only one of many reasons to quit.

3. Cholesterol Cholesterol abnormalities, meaning both high LDL (bad cholesterol) and low HDL (good cholesterol), in some cases, can be controlled through diet and exercise. Often, however, medication may be needed.

4. High Blood Pressure Hypertension (chronic high blood pressure), is a condition with few or no self-evident symptoms. It may be controllable through diet and exercise and, as with cholesterol levels, with medication.

5. Diabetes If you have diabetes, you have a much higher risk of heart attacks which may occur with atypical symptoms. It is extremely important to work with your doctor to manage your diabetes.

6. Physical inactivity -- Regular, moderate-to-vigorous physical activity can help control blood cholesterol, diabetes, and obesity, as well as help lower blood pressure and reduce your risk of heart attack.

Prevention

Beyond recognizing and responding to heart attack symptoms, Dr. Schott says that he and his member colleagues encourage patients to take steps now to prevent heart attacks or repeat heart attacks.

"The same advice applies, whether you've had a heart attack or would like to keep your heart healthy:

-- Don't smoke.

-- Manage your blood pressure and cholesterol.

-- Eat healthy and exercise daily.

Betsy fortunately got the message about a healthier lifestyle and we've worked together to help her make those important changes. But she did the hard work." James Goodyear, MD, president of the Pennsylvania Medical Society sums up, "Our job as physicians is not just to treat sick patients. We're here to work with our patients to provide the information and support they need to prevent illness and improve their health in the long run."

January 2010 Patient Poll background

Conducted: January 2010

Margin of Error: 5.67 percent

Eligibility: Pennsylvania adults age 21 or older

Survey Consultants: Taylor Brand Group, Lancaster, Pa., and Greenfield Online, Connecticut.

Question: Please answer true or false to the following statements:

Heart disease can start while you are still a teenager. True = 95.5%; False = 4.5%

A little alcohol is good for the heart. True = 71.9%; False = 28.1%

Two eggs contain more than the daily recommended allowance for cholesterol intake. True = 49.7%; False = 50.3%

If you ever have a heart attack, you'll know because your chest and arms will hurt. True = 33.7%; False = 66.3%

The patient-doctor relationship has been the priority of the Pennsylvania Medical Society since its founding in 1848. While there are many issues being debated about health system reform, the physician members will continue to focus on better health for all Pennsylvanians.

Source: Pennsylvania Medical Society 

Targeted Therapy Prolongs Life in Patients with HER2-Positive Breast Cancer

By Duke Medicine News and Communications
Lapatinib plus trastuzumab are significantly better than lapatinib alone in extending the lives of breast cancer patients whose tumors are HER2-positive, according to Kimberly Blackwell, MD, associate professor of medicine at Duke University Medical Center.

Blackwell presented the findings today at the CTRC-AACR San Antonio Breast Cancer Symposium.

Blackwell says the combination-targeted therapy gave patients more than a four-month survival advantage over those who took lapatinib alone. She says the findings may be the first step toward a chemotherapy-free future.

"This is the first time that a pair of targeted therapies has been shown to be superior to any intervention that paired a targeted therapy with a hormonal or chemotherapy based approach," she said.

The results stem from a large, Phase III clinical trial where investigators randomized 296 patients with metastatic breast cancer to receive either lapatinib (also known as Tykerb) alone or lapatinib plus trastuzumab (Herceptin) once a day.

All participants had metastatic disease that had continued to spread even after treatments with several interventions that included trastuzumab plus chemotherapy.

Blackwell says trastuzumab binds to and blocks part of the HER2 growth factor that appears on the surface of some breast cancer cells while lapatinib binds to a second growth factor, EGFR, and part of HER2 that sits below the cell surface. "It's sort of a double whammy, disabling the HER2 protein in two places instead of one."

Women who enrolled in the single-agent arm of the study and whose cancer continued to spread after four weeks were allowed to cross over to the other arm of the study to continue on the combined approach.

Fifty-two percent of the women enrolled in the lapatinib-only arm of the study crossed over to the combination arm. The median overall survival following treatment with lapatinib plus trastuzumab was 60.7 weeks compared to 41.4 weeks for those who took only lapatinib.

Other researchers involved in the study include Hal Burstein, from the Dana Farber Cancer Institute; George Sledge, from Indiana University Cancer Center; Steven Stein, Catherine Ellis, and Michelle Casey, of GlaxoSmithKline; Jose Baselga, of Vall d’Hebron University Hospital, Barcelona, Spain; and Joyce O’Shaughnessy from Baylor Sammons Cancer Center, Texas Oncology, PA, US Oncology, Dallas.

Allegheny General Hospital Study Demonstrates Safety And Potential Efficacy Of Oral Allergy Treatment

An oral allergy treatment administered in drops under the tongue is a safe and effective alternative to injections for adults who are allergic to ragweed pollen, according to a study published in the Journal of Allergy and Clinical Immunology by allergic disease specialist at Allegheny General Hospital.

Widely used in Europe, but not yet approved by the U.S. Food and Drug Administration, sublingual allergen immunotherapy (SLIT) can be a more convenient and tolerable treatment approach that leads to greater patient compliance, said David Skoner, MD, director of AGH's Division of Allergy, Asthma and Immunology and a co-lead investigator in the study.

"The study's findings mark a step forward in gaining approval for sublingual administration of allergy medication," said Dr. Skoner, "We believe a large number of patients would greatly benefit from having access to this new oral treatment to ease their symptoms."

"The sublingual method so far has been safe, and the adherence rate should be better because no injections are involved and the medication is administered at home," said co-investigator Deborah Gentile, MD, Director of Research in AGH's Division of Allergy, Asthma and Immunology.

The AGH study, "Sublingual Immunotherapy in Patients with Allergic Rhinoconjunctivitis Caused by Ragweed Pollen," involved 115 patients in Pittsburgh, Madison, Wisc., Iowa City and Evansville, Ind. They were randomly assigned to a medium or high dose of standardized glycerinated short ragweed pollen extract or to a placebo. Participants kept diaries to monitor their symptoms over the course of 17 weeks during the ragweed pollen season.

The frequency of daily symptoms, as well as the need for additional medication to treat symptoms, both dropped significantly for those taking the high-dose medication, versus those taking a placebo. The frequency of adverse events was similar between the placebo and treatment groups.

The researchers concluded that SLIT was safe and can reduce symptoms in ragweed-sensitive patients, though more trials are needed to definitively establish the method's efficacy.

Shortcomings of previous trials with the sublingual method included small patient populations, high withdrawals and short treatment duration. Questions remaining on SLIT include treatment schedules, optimal doses and cost-effectiveness.

Other researchers involved in the study were Robert Bush, MD of the University of Wisconsin School of Medicine and Public Health; Mary Beth Fasano, MD, University of Iowa Hospitals and Clinics; Anne McLaughlin, MD, of Wellborn Clinical Research Center in Evansville, Ind., and Robert E. Esch, PhD, of Greer Laboratories Inc., Lenoir, NC.

Source: Allegheny General Hospital