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an online version of the magazine Spring/Summer 2005
Medical Rounds
Surgeon to the Seniors.
SURGEON TO THE SENIORS:
Steve Yang: "Lung cancer isn't a death sentence anymore."
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Surgeon to the Seniors

When it comes to major chest procedures, Stephen Yang is moving into new territory. By Yang's own count, 120 of his thoracic surgery patients in the last decade have been older than 80. And whereas nationally the mortality-rate average among patients in this age range falls between 5 percent and 20 percent, for Yang's cases it comes in at 3 percent.

One of the thoracic surgeon's more memorable encounters involved an 85-year-old woman from Pennsylvania suffering from lung cancer. Area doctors had told her she wasn't a good candidate for surgery, but her son, a physician, learned of Yang' s track record. When Yang called her operation a “go,” everyone felt relieved. Today, three years out, she's cancer-free.

“Lung cancer isn't a death sentence anymore,” Yang says. When it's caught early and surgically removed, at least 70 percent of patients can be cured. That promise, he believes, can now be extended to octogenarians. “There's a big push toward geriatric surgery in general,” he says, fueled in part by major advances in care and a larger aging population. “It's a field that should grow quickly over the next few years as aging boomers swell the ranks of senior citizens.”

Yang has a predilection for working with older patients who might otherwise be rejected as poor candidates. He typically invites hopeful patients to his office for consultation, where he performs what he calls his “eyeball test,” appraising the person's stamina and condition. Key issues that make many surgeons shy away from geriatric procedures, he notes, are their age and low lung capacity. “But I tend to look for a gut feeling that they're going to do well. I keep an open mind.”

Ramsey Flynn


Viagra Marches On

Viagra Marches On

The human body works in marvelous ways. Who'd have guessed, for instance, that Viagra, famed for curing, well, you know what, could restore a damaged heart? But that's exactly what a research team here, headed by cardiologist David Kass, has now determined.

When the Kass group, whose basic research on heart failure has already brought new insights to cardiac treatment, gave daily doses of sildanefil (the generic name for Viagra) to mice with enlarged hearts resulting from high blood pressure, the mice not only stopped developing the condition (called hypertrophy) but began getting better. And with more than a quarter of the 65 million Americans who have high blood pressure now suffering from that same potentially fatal heart condition, the study could obviously have big implications.

Understand that it wasn't purely serendipity that researchers began experimenting with sildanefil in the first place as a remedy for hypertrophy. The drug, which has the ability to relax smooth muscle and allow blood to flow easily into an organ, first gained attention among scientists as a possible treatment for heart problems. But early studies didn't pan out. What did come to light though, was Viagra's famous side effect in the male member.

This time, Kass and his fellow researchers carried out their hypertrophy study by clamping the aortas of their test mice and forcing their hearts to work harder and enlarge—exactly what happens in high blood pressure. They then gave some of the mice daily doses of sildanefil and the rest of them no medication. Weeks later, when they compared the hearts of the two groups, the mice that hadn't received the drug exhibited the usual symptoms of hypertrophy, while the Viagra group showed minimal or no heart damage.

The next step for the Hopkins researchers will of course be to test sildanefil on patients. “But if the drug works in people the way it works in mice, there's no question it will save lives,” Kass told the Baltimore Sun. Once it's clear it has that capability, Viagra would no doubt move to market more quickly than usual as a new and safe treatment for hypertrophy. After all, it is already a known entity, albeit for a rather different organ.

ERN

 


Consultation with Constantine Lyketsos

Constantine Lyketsos

The neuropsychiatrist who heads the Johns Hopkins Memory Center, talks about preparing for the coming surge in Alzeheimer's.

 

Is the sky really falling with respect to Alzheimer's disease and baby boomers?

 

It's not falling yet but it's going to. The dementia rate should start to rise in five years as the first boomers reach their 60s. In 10 years, it'll near 13.5 million. Hopkins plans to double its capacity for patient care in the next three years. We'll “grow” training programs for caregivers while developing very sensitive computerized memory tests to let us catch patients earlier in their illness and help us monitor them once it progresses. Of course, we want a cure.

 

It all sounds terribly grim.

 

It is and it isn't. Go study people living independently and you get a surprise. The majority of 90- to 100-year-olds are in their own homes! They're doing okay. You just hear more about those with problems.

 

Not to be an institutional pawn, but what's so special about what we offer patients?

 

We've worked years to develop a systematic approach to dementia that doesn't let people slip through the cracks. We offer therapy, of course, including the recently approved Memantine, which works on a new principle of damping down the excitotoxicity that follows atypically stimulated neurons in the brain. But since nothing yet stops the progression, we also treat symptoms like depression and delusions.

 

And research is ongoing as well?

 

Yes. We believe that depression and dementia are somehow related, and we are studying that. We're looking at cardiovascular disease as a possible link between the two. There's also research based on the idea that Alzheimer's is really several diseases, that different people slip into it by different paths. So we're doing large epidemiological studies of people at risk. Using blood tests, imaging and cognitive testing, we'll follow them for some time and hope some sort of marker appears that lets us make predictions.

 

Anything else?

 

One of my postdocs believes she's found a molecule in blood serum that reflects brain degeneration. And even more basic, two colleagues are exploring how an overactive immune system might influence buildup of the amyloid that's AD's hallmark.

 

 Interviewed by Marjorie Centofanti

 


The Scoliosis Doctor

Paul Sponseller with Jaclyn Bower after her complex surgery.
> Paul Sponseller with Jaclyn Bower after her complex surgery.

By the time Jaclyn Bower entered her teenage years, she was missing school weeks at a time. Scoliosis had induced such a severe curvature in her spine that standing erect for more than a few minutes had become unbearable. Then, two years ago, the teenager caught a break. A physician in Frederick , Md. , told her he'd heard that Paul Sponseller, an orthopedic surgeon at Johns Hopkins, was doing some innovative things with teenage scoliosis.

“From the day I met Dr. Sponseller, my life began changing,” Jaclyn says now. “The curvature in my spine was more than 75 degrees at that point, and he told me he might be able to correct it.”

In cases as severe as Jaclyn's, Sponseller takes a different approach. Rather than using the traditional hook-and-wire procedure—which requires two incisions, one in the chest, one in the back—to straighten and graft the bones in the deformed spinal column, Sponseller uses metal screws to attach the pedicles, or neural arches of the vertebrae, to the back surface of the spine—the lamina. The highly delicate operation requires a single incision in the back. “But pedicle screws provide a sturdier anchor,” the surgeon says. “It enables us to stabilize the entire vertebrae in a single operation.”

Still, the pedicle screw approach is complex and not without risk. In teenagers, the vertebrae are so misshapen that many of the pedicles are small. The screws must be inserted accurately and carefully. Otherwise, they might hit a nerve root, which could result in weakness or numbness in one or both legs. “It's technically more demanding,” Sponseller says, “but you get improved results,”—a higher rate of spinal fusion, fewer complications and quicker recovery. And while the traditional operation leaves a hump where the ribs have rotated with the spine, this technique removes it.”

Jaclyn's recovery after the four-hour surgery took time, “in part because her entire posture became radically different,” Sponseller says. But today, the high school junior is 100 percent recovered. “I can't do extreme moves like somersaults,” she reports, “but I can do almost anything else. And with 15 inches of hardware in my back, that's not bad.”

Michael Levin-Epstein



Fibroid Removal Without Surgery

 

These days, patients who question a physician's treatment plan regularly head for the Internet. Diana Gould-Riley is a case in point. When the Annapolis travel agency owner in her early 40s learned from her gynecologist that she'd need a hysterectomy to get rid of her fibroid tumors, she balked at the idea of having her uterus removed at her age. If she could possibly avoid surgery, she wanted to know. Online Gould-Riley found what she was looking for just a half-hour away: Hyun Kim, an interventional radiologist at Hopkins was using a host of noninvasive treatments to destroy fibroids.

Griffith and Kim in the fibroid center.
> Griffith and Kim in the fibroid center.

In Gould-Riley's case, Kim determined he'd apply ultrasound heat to get rid of her fibroids. On the day of the procedure, he used an MRI to show him the precise location of each tumor and guide him in focusing the ultrasound heat energy. The procedure took more than three hours. “And it wasn't easy being confined to one spot for such a long time,” Gould-Riley admits. “But there was no pain, no incision and no hospitalization.”

To put such new techniques into practice, Kim works side by side with gynecologist John Griffith, director of the Fibroid Center . Another two-hour approach, called uterine artery embolization, shrinks fibroids by injection of tiny pellets through the groin to the arteries that feed the tumor. The pellets then block the blood flow to the fibroids, starving them of nutrients and causing them to shrink. The procedure can be painful and requires an overnight hospital stay, according to Griffith . “Nevertheless, the patient avoids days or even weeks of recovery.” Gould-Riley was back at work two days later, “and didn't even need that beach vacation I always recommend to my recovering clients.”

 

 

Michael Levin-Epstein



Getting The Baby Out Whole

Edith Gurewitsch shows where an infant's shoulder can be injured during delivery.
> Edith Gurewitsch shows where an infant's shoulder can be injured during delivery.

One of the bigger challenges faced by obstetricians during delivery occurs when the baby gets stuck in the birth canal after the head is already out. Gauging exactly how much force to use to dislodge the infant becomes crucial—too little and it could suffocate, too much and bones could break or nerves could be injured. Especially worrisome is the fact that the complication, called shoulder dystocia, occurs in up to 5 percent of all births, and leaves one in 10 of the infants who are injured with permanent damage to the brachial plexus nerve network of the shoulder and arms.

Now, a team of Johns Hopkins researchers has invented a device that pinpoints the best practices to use in difficult vaginal deliveries, while measuring the amount of force that's being applied. They're sharing these skills with community obstetricians in a CME course.

The new birth simulator tool features a maternal and fetal model that obstetricians practice on and a measuring device they can work with in the lab or take with them into the delivery room. The maternal model consists of a mock pelvis, uterus and birth canal, and a pump that simulates birth contractions and maternal pushing. Used in conjunction with a fetal mannequin that measures tension in the infant's neck and brachial plexus, it helps determine the degree of force the obstetrician applies during delivery. Measuring that force is a separate device that contains three electrodes attached to the forearm of the physician which send data to a nearby computer.

Robert Allen, the Hopkins biomedical engineer who co-invented the birth stimulator with Gyn/Ob specialist Edith Gurewitsch, says it finally makes it possible to study the relationship between clinical force and the baby's response. Initial results show that repositioning the baby's shoulders relative to the mother's pelvic bones (the Rubins maneuver) requires less force to deliver the baby than other positions, such as flexing the mother's legs back (the McRoberts positioning).

"We're still conducting clinical evaluations,” Gurewitsch says, “but there's no doubt we've already begun advancing the science.”

 

 

Michael Levin-Epstein



Cardiac Killer Exposed

For the leading cause of sudden cardiac death in Americans under 35, there is no longer a place to hide. Hypertrophic cardiomyopathy, characterized by abnormal thickening of the heart walls, affects one in 500 people and often runs in families.

Now, according to Daniel Judge, the cardiologist who oversees the Johns Hopkins Familial Cardiomyopathy Initiative, clinical genetic testing makes it possible to identify individuals in certain families who have a predisposition to the condition. And while there is no cure for hypertrophic cardiomyopathy, Judge emphasizes that early detection combined with new treatments can slow the progression of the disease or even prevent sudden cardiac death.

But the cardiologist also cautions that, despite genetic testing's benefits, it can have profound psychological and social implications for patients, including complications with their insurance. “So it's important to provide appropriate counseling,” says Judge. That service is offered here by Nicole Johnson, one of the few certified clinical genetic counselors working primarily with cardiovascular conditions. The initiative also maintains a Web site for patients and health care professionals (www.hopkinsmedicine.org/cardiology/heart/Familial_Cardiomyopathy_center.htm), a clinical research registry and a support group.

The Hopkins effort to pinpoint family members with a predisposition to cardiomyopathy extends to the two other forms of the disease, which also can run in families: dilated cardiomyopathy, characterized by an enlarged heart with thin walls, and restrictive cardiomyopathy, in which the size and walls of the heart remain normal but blood flow becomes impaired.

Michael Levin-Epstein

 


The Genetics of Healing

Antonio De Maio with a mouse that's helping him understand sepsis.
> Antonio De Maio with a mouse that's helping him understand sepsis.

Trauma, says Antonio De Maio, is the Cinderella of science. It's never in the limelight, even though it's the third leading cause of death in developed countries, and a major killer of children. The reason why, he maintains, is that people don't consider trauma a disease.

But ever since De Maio arrived in Baltimore as a postdoc in 1988, he's been trying to answer one question: “If you and I have the same injury, why do you respond very well, and I struggle for days and die?” One reason, he believes, is because we're genetically different.”

De Maio is an oddity—a basic scientist residing in the Department of Surgery. During his early years here, the native Venezuelan would go on rounds, and came up with his hypothesis by talking with frustrated physicians seeking an explanation for the tremendous variability in outcomes in patients with similar injuries. Now, he uses mice to test his hypothesis—that the interaction of age, sex, environment and genetics accounts for the complex response to sepsis, a condition in which the inflammatory response goes haywire and can't turn off. More than 750,000 cases of sepsis occur each year in the United States , initiated by traumatic injury or even elective surgery. Half are fatal.

In his experiments, De Maio induces an inflammatory response by injecting mice with endotoxin, and controls for every factor except genetics. Aided by physiologist Roger Reeves, his lab has identified the first candidate gene, called macrophage scavenger receptor 1 (MSR1). The next step will be to study the gene in humans, a complex task given confounding factors like smoking, alcohol abuse or underlying disease that differentiate humans. His ultimate goal is preventive medicine. “The idea is if you have a series of markers, you can predict the possibility of kidney or lung failure and monitor it before it actually happens.”

 

Mary Ellen Miller



Stalking A Lethal Disease

Liz Jaffe and Daniel Laheru are progressing in their search for a vaccine.
> Liz Jaffe and Daniel Laheru are progressing in their search for a vaccine.

Daniel Laheru and Liz Jaffee might look like gluttons for punishment. As researchers, they've staked out pancreatic cancer, known for its ability to defeat just about every weapon in modern medicine's arsenal. Still, in their quest for a vaccine, Laheru and Jaffee have crossed another in a series of key thresholds. “I feel like we're on the brink of hope,” Laheru says.

A few years ago, Jaffee determined that an effective vaccine would rely on a manipulated version of the entire tumor cell. Those cells would be irradiated so they cannot grow, but still contain all of the proteins that the immune system can recognize as foreign invaders that must be killed. Next, Jaffee had to devise a way to draw the correct immune system cells to the rogue cancer cells. She did that by genetically engineering the vaccine cells to secrete a molecule, called GM-CSF, that would act as the lure. The modified cells then would be injected back into patients in staged doses.

Now, the duo has reported that three of 14 patients who took part in clinical trials of the vaccine are alive and cancer-free seven years out. Adding to their progress, pathologists linked to the research team have identified the first pancreatic cancer-specific proteins, which will allow Jaffee and Laheru to fine-tune their vaccine to hit its target.

All of the research team's data so far show that patients have no meaningfully adverse effects to the vaccine. But even more promising, Laheru says, is that “the patients who received the highest doses seemed to do better.” Armed with these findings, the research team has completed a study of 60 patients who received the highest vaccine doses yet.

What Laheru and Jaffee are counting on, of course, is that the vaccine will make possible a broader reversal of pancreatic cancer and improve long-term survival.

 

Ramsey Flynn



Last Resort For Vision

Merium Scott was at her wit's end by the time she met ophthalmologist Esen Akpek in late 2003. The 79-year-old great-grandmother's vision had deteriorated so badly she could no longer read the Bible, knit or solve crossword puzzles. She couldn't even see the gigantic “E” on the eye chart.

It didn't take Akpek long to diagnose the problem. The ulcers and “melting” on both of Scott's corneas characterized a dry-eye condition called Sjogrun's syndrome that causes this transparent surface of the eye to grow opaque. One eye was so infected it would have to be removed. But Akpek, director of the Ocular Surface and Dry Eye Clinic at the Wilmer Eye Institute, thought she might be able to save the other one with an artificial corneal implant.

This was no standard procedure. To restore Scott's vision, she would do a keratoprosthesis (K-Pro, for short), a version of the transplant that has been performed fewer than 200 times worldwide. “It's a measure of last resort,” she explains.

The operation requires three procedures simultaneously: implanting the artificial cornea, installing a tube shunt to help prevent glaucoma and cleaning out the eye socket to stave off infection. As usual, it requires a donor cornea, but in this case, it needn't be of transplantation quality—it will be sliced into the shape of a doughnut. The front and back plates of the implantation device then are screwed together with the donor cornea in the middle—a bit like a sandwich—and a titanium locking ring is placed on the back plate. Finally, the patient's opaque cornea is removed, and the transplant unit replaces it.

After her operation last March, Scott's eyesight was 20-40. A year later, her vision had grown a bit cloudy. Today, she uses eye drops every day and will wear a bandage contact lens indefinitely to protect the artificial cornea and keep it wet. But she has no regrets—she can see again.

Michael Levin-Epstein 


Cancer-Killing Cells

For Ivan Borello, a researcher at the Sidney Kimmel Cancer Center , who's been trying for awhile to teach the body to fight off cancer, the last few months have been heady. Working with two kinds of human T-cells—which come equipped with the power to identify cells foreign to the body and mark them for destruction—Borello and his team discovered that one group was “smarter.”

For the study, the researchers used only T-cells that had been primed to attack the bone cancer myeloma. They took some from the bone marrow, however, and the rest from the blood. When they tested the kill-rates of both T-cell groups, they found the bone marrow cells outperformed their blood counterparts by more than 90 percent.

“Now we have evidence that educating T-cells in the bone marrow may be the most effective way to get an anti-tumor response,” Borello says.

The next step will be to test the activated marrow T-cells in a few myeloma patients, both alone and in combination with a myeloma vaccine. What's especially exciting, though, is that the researchers believe that patients with other blood, bone marrow and solid tumors, such as breast cancer, may also benefit from this type of immunotherapy.

 

Vanessa Wasta

 

 
 
 
 
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