One New Shinbone Later
For three years at Glenelg High School in Maryland,
Eric Elmer, the 6-foot-1-inch, 190-pound tight end on
the football team, played every game in pain. The gnawing
discomfort, which kept Elmer up at night and on Tylenol
all day, stemmed not from a gridiron injury but from
a pea-size growth on his shinbone. By last fall, when
the 19-year-old met Frank Frassica and Kieran Murphy
at Hopkins, he despaired of ever being pain-free.
The two specialists quickly gave the culprit a name:
a bone lesion called an osteoid osteoma that strikes
mostly in children and young adults. Though benign,
these tiny tumors can be painful and difficult to get
rid of. They typically require complex surgery to remove.
But Elmer was in luck. Frassica, chair of orthopedic
surgery, and Murphy, director of neurointerventional
radiology, belong to a small cadre of surgeons nationwide
who can now do the job with a one-hour outpatient procedure.
The key to the advance in treatment is CT fluoroscopy,
a high-tech imaging technique that makes it possible
to scan simultaneously in three places at 13 frames
per second. That capability allowed Murphy to pinpoint
the growth exactly and then insert electrode-tipped
probes through the skin into the core of the osteoma.
He then used radiofrequency energy to produce heat strong
enough to destroy the growth.
Today, Elmer, who’s just finished his freshman
year at West Virginia University, is pain-free for the
first time in years. “It’s like having a
new leg,” he says.
Behold the Zebra Fish
As schools of zebra fish dart across their tanks, Steve
Leach’s research team is learning to understand
one of mankind’s deadliest killers—pancreatic
cancer. Thanks to technologies like immunofluorescent
staining—which makes each fish’s pancreas
look like a tiny neon squiggle—the group is unraveling
the mysteries of early pancreatic development by taking
a close look at the growth and movement of the cells
in this large gland in their earliest stages.
Steve Leach and his striped swimmers.
This year 30,000 people will die from pancreatic cancer.
It’s the fifth leading cause of cancer death in
the United States and has only a 5 percent five-year
survival rate. Leach, who’s the Paul K. Neumann
Professor in pancreatic cancer and chief of surgical
oncology, is on a mission to improve those numbers by
identifying the genes that regulate the development
of the exocrine pancreas, the part that makes the digestive
enzymes that organ secretes. “We already know
exocrine cells are involved in pancreatic cancer,”
he says. “And we’ve shown that genes regulating
the development of these cells in the embryo also regulate
the development of cancer in the adult.”
So, why study zebrafish? They offer two undeniable
virtues: Because the tiny, striped swimmers lay hundreds
of eggs, researchers gain immediate access to hordes
of embryos at the one-cell stage. And, since their eggs
are transparent, it’s possible to evaluate developmental
events as they take place. Every day, Leach’s
group injects the fish with candidate genes and watches
how their cells develop. Even at one and a half hours
old, the fish embryos show their worth. Already, the
scientists have found that a major developmental gene
(the Notch pathway gene) is a critical regulator of
exocrine pancreatic development and is also abnormally
activated in human pancreatic cancer. Early findings
suggest that when the gene behaves normally it acts
to delay the “flowering” of the exocrine
pancreas. And that’s something that would be impossible
to see in a mouse, Leach says.
But mouse studies are an important next step, Leach
says. As they move forward, his team is using a mouse
model to investigate how inhibiting the Notch gene might
alter the course of pancreatic cancer. “It’s
amazing how similar embryonic development is between
species,” he says.
Consultation with Jeff Geschwind
The director of cardiovascular and interventional radi-ology
talks about how his booming field is changing the way
physicians treat cancer and a range of other conditions.
It’s dramatic how rapidly your specialty
is offering new treatments for so many conditions. What
It’s true, there’s been an explosive growth
and interest in minimally invasive image-guided therapeutic
techniques. In fact, some of these techniques have totally
replaced more traumatic surgical procedures. We interventional
radiologists use high-tech imaging to tell us the story
about what’s going on in the patient’s body,
and then we move right in with a treatment. We’ve
learned to shrink tumors and to treat aneurysms. We’ve
given patients easier procedures for draining fluid
and for shrinking fibroids.
For which kinds of conditions would you say
your capabilities have made the most difference?
The areas that stand out are gynecology, specifically
fibroid disease, and some cancer treatments. We’ve
made a world of difference in the length of recovery
and severity of what patients have to go through. Many
of our new procedures can be done on an outpatient basis.
What procedures would you say you’re
We’re treating more patients for advanced liver
cancer using chemoembolization and radiofrequency ablation.
This is a catheter-driven treatment that kills liver
tumors by delivering chemotherapy drugs directly to
the site. Then, we’re using embolization to get
rid of uterine fibroids. And we’re using embolotherapy
to break up the dangerous blood clots known as arterio-venous
malformations. And, of course, we’re handling
more everyday problems like varicose veins with endovenous
laser therapy. That interests a lot of people.
What do you see as the field’s biggest
Well—training remains insufficient. Residents
need to have more exposure to the latest interventional
techniques. But that should start happening. The increase
in physicians going into the field is astounding.
Any other obstacles?
I’d have to say the toughest thing is being accepted
by clinicians in other specialties. They’re not
used to thinking of radiologists as clinicians. That’s
less a problem in academic centers like ours, where
relations with colleagues are excellent, but in private
practice things may not be as collegial. That’s
going to have to change. We all need to keep in mind
our common goal: treating patients with the most effective
Gastric Bypass Bonus
When surgeon Michael Schweitzer began performing the
laparoscopic gastric bypass three years ago, he was
certain the procedure would offer morbidly obese patients
an easier operation for dropping weight. The old-style
bypass had required major surgery and a lengthy recovery
period; this one used tiny incisions 1/4 to 1/2 inches
long, meaning less pain and recovery time. What the
director of minimally invasive bariatric surgery at
Johns Hopkins Bayview Medical Center never guessed was
the profound effect the new bypass would have on patients
Riley Wymer after dropping 80 pounds.
Today, Schweitzer has done more than 500 of the minimally
invasive gastric procedures, and the numbers are in.
More than 85 percent who undergo the operation lose
an average of 70 percent of excess body weight after
a year and a half. The change improves their overall
health in ways they never imagined: blood pressure drops
and conditions like sleep apnea disappear. But the most
stark difference has occurred among patients with type
II diabetes: Some 80 percent no longer experience any
symptoms of the disease. “Most go off their meds
completely,” Schweitzer reports. “and the
other 20 percent usually go from heavy doses of insulin
injections down to just one low-dose pill a day.”
For truck driver Riley Wymer, those results literally
meant his livelihood. Before the surgery, he weighed
315 pounds and took four different kinds of medication
to avoid insulin injections, which would prohibit him
from truck driving professionally. Five months after
his bypass, Wymer weighed 235 pounds, was off all medication
and hauling an 18-wheeler between Maryland and Michigan.
“If it weren’t for Dr. Schweitzer and the
bypass, I probably wouldn’t have my job right
now,” he says.
When Kathy Gabrielson started riding horses as an eighth-grader,
it didn’t take long for her to know she wanted
to become a veterinarian, and specialize in large animals.
These days, her focus has grown far bigger. And much
Kathy Gabrielson checks one of her furry
As one of four veterinary pathologists in the Department
of Comparative Medicine, Gabrielson, who earned her
Ph.D. in toxicology at the School of Public Health,
helps maintain the health of the thousands of laboratory
animals, from mice to pigs to monkeys, that are housed
on campus. Over the course of her career, the assistant
professor has indeed worked with her share of jumbo
species, including an elephant at the San Diego Zoo
and a beluga whale from the National Aquarium that was
brought here for a necropsy to determine why it had
But today, Gabrielson also makes time for one more
group of animals—the rats and mice in her own
lab. Working with the little furry creatures, she’s
created the only known animal model geared to explain,
and perhaps one day circumvent, the severe and sometimes
fatal heart problems that can occur when two potent
anticancer drugs are used together.
“I was interested in brain neurodegeneration,”
says Gabrielson, “and one toxin I studied also
causes cardiac degeneration. So I began looking at other
things that injure the heart. One is chemotherapy. The
cancer gets treated but the patient dies of heart failure.”
Doxorubicin, a drug widely used for breast cancer,
has long been known to carry this risk. Then in 1998,
a new promising agent called Herceptin was approved
for a highly aggressive form of breast cancer. Problem
is, 30 percent of patients given both drugs in clinical
trials got heart disease. Since Herceptin isn’t
cardiotoxic in animals, probably because it binds only
to a human protein, the challenge Gabrielson successfully
took on was to produce the same heart effects in rats
that Herceptin plus doxorubicin cause in patients. Furthermore,
needing to monitor her animals’ cardiac status
over time, her lab developed a way to do echocardiography
in awake, unsedated rats.
Gabrielson’s aim is to find out why the two drugs
together don’t result in dire consequences all
the time. Answers to that question could kill the cancer
but save the heart.
For Heart Failure Patients,
A Change in the Picture
Congestive heart failure leaves its victims with a dim
future. About 1,000 usually older Americans die daily
because their damaged, enlarged hearts pump so ineffectively.
Those who keep going experience such shortness of breath
and exhaustion that even simple activities wear them out.
John Conte: One of a handful of cardiac
surgeons who does ventricular remodeling.
Treatments present problems of their own. Medication
may not work; a heart transplant puts patients on immunosuppressive
drugs for the rest of their lives; and the new mechanical
pumping devices, while promising, won’t be ready
for widespread use until the question of mechanical
failure can be resolved.
Now, John Conte, director of heart and lung transplant
programs here, has another approach. Called ventricular
restoration, the procedure is part of a four- to six-hour
operation that typically also includes a coronary artery
bypass and/or mitral valve repair. Conte actually reshapes
the patient’s enlarged heart to its normal and
more elliptical form to restore its ability to contract.
The key is a plastic shaper, which he inserts into the
left ventricle, the main pumping chamber, and then inflates
to the patient’s ideal ventricular size, based
on body measurements. Conte remodels the heart around
the shaper and removes the device. Many of the nearly
800 patients who have had the procedure, say it gives
them back their vigor.
“It’s a far safer and more economical treatment
than a heart transplant or putting in a mechanical device,”
Conte says, of the new device, which the FDA approved
just two years ago, But he makes clear that only a careful
evaluation can determine if a patient is actually a
candidate for the procedure.
Although the ventricular restoration was initially
designed for patients with damage only in one “territory”
of the heart involving the anterior wall, Conte says,
“I’m looking for people with one-, two-
or three-territory damage to their hearts who may not
have many alternatives at this point. I’m pushing
the envelope, so to speak.”
Hopkins is now the only training ground in the nation
for the innovative technique.
Understandings in Aneurysm Surgery
Rafael, you don’t put in as many shunts as everybody
else!” This offhand remark to neurosurgeon Rafael
Tamargo began a flurry of record examining that has
lessened a hazard of surgery for ruptured brain aneurysms.
“When an aneurysm ruptures and patients come
in with a subarachnoid hemorrhage,” says Tamargo,
“wayward blood gums up drainage of cerebrospinal
fluid. They can develop hydrocephalus.” Sometimes
“water on the brain” resolves, but 15 percent
of patients need implantation of a fluid-draining shunt.
That’s unfortunate because shunts typically require
replacement surgery down the road.
Tamargo was perplexed, though. His 2 percent shunting
rate was five times lower than colleagues’. Was
he under-shunting? Scanning a decade of neurosurgical
records showed him he was fine in recommending shunting.
But why did his patients need it less? A chance reading
of a small study and discussions with fellow surgeons
gave the answer. Following a mentor’s advice,
Tamargo routinely punctured the membrane that borders
one of the brain’s spinal fluid reservoirs. “It
helps deflate a turgid brain,” he says. No one
else at Hopkins was taking this “quick and simple”
step as a matter of course. Now, he says, it’s
become standard and the Hospital’s rate matches
The practice is one of several Tamargo initiated that
has dramatically changed outcomes for danger-fraught
aneurysm surgery. His research team has also devised
a way to tackle giant aneurysms that previously defied
care. “We’ve chipped away at the problem,”
he says. “And our progress is real.”
One Smart Surgeon Saves Two Lives
Omayma Ahmad checked into the Hopkins emergency department
last September in a panic. Not only was she experiencing
another bout of the gasping and piercing angina that
had sent her into the OR two years earlier for an aortic
valve repair and put her on medication for the rest
of her life, this time she was pregnant. Surgery would
endanger the child.
Omayma Ahmad, now mother of one infant
and twin toddlers.
Testing confirmed Ahmad’s worst fears: She needed
emergency surgery to correct an aortic valve stuck wide
open because of a blood clot. During the operation,
the cardiopulmonary bypass (CPB) pump circuit would
take over the job of circulating her blood, and that
would threaten the fetus she was carrying. Every physician
Ahmad talked to advised ending the pregnancy first.
She and her husband decided to take their chances.
They were in luck. The cardiac surgeon assigned to
Ahmad’s case knew a lot about this particular
problem. David Yuh had arrived at Hopkins recently,
fresh from a year of learning the intricacies of performing
open heart surgery on pregnant patients.
Moments after Yuh began this emergency valve replacement,
his team initiated full CPB, cross-clamped the ascending
aorta and stopped Ahmad’s heart. Worried that
scarring from the earlier surgery might present complications,
Yuh immediately dissected the heart and aorta away from
the adherent scar tissue, then removed the clotted valve
and inserted an identical mechanical one. Meanwhile,
the anesthesiologists monitored the two sets of vital
signs like hawks.
“The hardest part, Yuh says, “was hastening
the procedure to avoid circulatory damage to the mother
and the child. Things also were pretty tense because
usually we cool the patient on bypass to preserve organ
function. But in a case like this you have to maintain
higher pump rates at warmer temperatures while the heart
is stopped. Otherwise, all that cooling and the insufficient
flow rates might cause irreversible harm to the placenta
or kill the fetus.”
In the end, the operation took about three hours, and
Ahmad spent 99 minutes on CPB. But the fetal heart tones
remained strong throughout. “That baby’s
heartbeat was like beautiful music,” Yuh says.
In March, Ahmad gave birth to a healthy baby boy.
Hold the Gel, Pass the Salt
Every now and then, someone in a laboratory makes a mistake
and ends up benefiting science. Now, a misplaced decimal
point—a simple typo—in pancreatic cancer researcher
Scott Kern’s lab turns out to have made gene-hunting
simpler and less costly.
Brody and Kern with their new concoction.
It all began when Kern’s postdoctoral fellow
Jonathan Brody, searching for a cancer gene, found his
experiments going awry after following a simple recipe
to make an electrophoresis gel. Researchers use these
gel concoctions to separate strands of molecularly snipped
genetic material (they call it running a gel). The scientist
directs an electrical current across a slab of the dense
jelly, and the current pulls segments of DNA across
the gelatinous medium. The shortest, lightest pieces
drift the farthest, the longer pieces lag behind. When
Brody’s gels didn’t produce results, he
quickly realized it was botched by a mistyped decimal
in the recipe he’d inherited.
But instead of getting annoyed, Kern and Brody got
curious. They started reading up to find out about the
chemicals that make up a gel, especially the two essential
ingredients: Tris-acetate EDTA (or TAE) and tris-borate
EDTA (or TBE) act as “buffers” for balancing
the acidic genetic molecules and increasing the gel’s
conductivity. But nothing the two researchers found
justified those ingredients.
Electrophoresis, they found, dates back to the 1950s
when it was introduced for protein separation, but the
recipe for the gel has been conserved from mentor to
student since the 1970s when it was brought into use
for studying genes. Nobody thought to question it, Kern
says. Today, for companies that produce the pre-made
gels for laboratories worldwide, the age-old recipe
has added up to a multimillion dollar business.
Brody was so fascinated he took a two-month leave from
his cancer research to try making gels with other ingredients.
Within weeks, he’d discovered that TAE and TBE
not only were ineffective buffers but were actually
detrimental to the study of DNA. The chemicals created
so much heat during conductivity that both the gel and
the genetic material can melt.
Furthermore, buffering proved not to be necessary at
all in DNA separation. The optimal conductor proved
to be simple sodium boric acid—a salt that sends
a quick current without raising the temperature. The
salt produced crisper, easier-to-read, staggered lines
in the final snapshot and was such an efficient conductor
it cut the time for running the gel from more than an
hour to 15 minutes. It also cut production costs from
27 cents to 7 cents, a potential national savings of
more than $30 million. For Hopkins alone, using the
salt could shave as much as $40,000 from the budget.
Brody published his findings in the February issue
of BioTechniques and patented the sodium boric acid
with Kern, but their main interest is alerting the research
community that a speedier medium outperforms the old
He and Brody recently cooked up samples and offered
a public seminar to explain the new recipe. Several
high-power labs—including that of famed colon
cancer researcher Bert Vogelstein—aleady have
made the switch to the new recipe.
“The only complaint we’ve received,”
Brody reports, “is that the gels are so efficient,
we’ve ruined what used to be researchers’
Extracting Molly’s Brain Tumor
Do you think Molly has a limp?” Kody Taylor asked
her husband, Gary, as they watched their 3-year-old
walking to the car. “Nah, it’s just the
way she walks.” But when an orthopedist suggested
Molly have an MRI, the South Carolina couple learned
their daughter had a brainstem tumor, possibly a pontine
glioma, a usually inoperable cancer, located at the
seat of functions like breathing and heartbeat. The
Taylors’ search for the right neurologist led
them to Hopkins’ George Jallo.
“Brainstem tumors aren’t common in children,”
Jallo says, “and they’re not something you
want to see. They’re delicate, intricate growths.
Many consider them inoperable, even when benign, because
of the real estate they’re in.” But, in
Molly’s case, Jallo was fairly certain her tumor
wasn’t malignant and he could tackle her problem.
And, amazingly, he could do it endoscopically. He’d
arrived at Hopkins last year with more than 100 such
surgeries to his credit.
Jallo made a small opening in Molly’s skull,
gently feeding in the laser and necessary surgical tools.
The prune-size tumor he teased free turned out definitely
to be a low-grade astrocytoma, a benign growth. Now
Molly’s getting light physical therapy for temporary
arm weakness, but, says Jallo, “she should be
right as rain.”