For AS, at Last, a
Charles Gaskell was never a great golfer—he just
loved playing the game. Then at 28 he was hit by the
crippling spine disease ankylosing spondylitis (AS).
As is typical, the condition struck Gaskell in early
adulthood, inflaming the spine and peripheral joints
so severely that eventually he couldn’t perform
standard activities, let alone golf. Over time, it causes
the spine to grow rigid, severely limiting the range
of motion in the back and neck. Walking turns into strenuous
exercise; hip replacements are routine.
Today Gaskell is 45. In 17 years, AS had made his
job in the construction industry too taxing and sitting
for more than 10 minutes impossible. No medication provided
ongoing relief. Then last summer, he met Johns Hopkins
internist John Flynn, who put him on a new treatment:
infusions of a tumor necrosis factor (TNF) inhibitor.
And suddenly the crippling inflammation that had spread
to Gaskell’s back and neck began to disappear.
He could walk longer distances, even take up sports
To create that kind of response, TNF inhibitors block
cytokines that play a critical role in inflammation.
Several years ago, the drugs were found useful in treating
rheumatoid arthritis, but it wasn’t until 2003
that the FDA gave the go-ahead for their use in AS patients.
“What we’ve found,” Flynn says, “is
that for the first time, we can help these people live
normal lives. Their stiffness lessens remarkably, their
Today, Charles Gaskell takes an occasional pain pill
for residual discomfort and sees Flynn every eight weeks
for a TNF treatment. Other than that, he is virtually
pain-free. He’s also hitting his drives 40 yards
farther on the golf course.
An Operation No One Else Would Tackle
There are some cases that can make even a surgeon take a deep breath. Eighteen-month-old
Maison Jackson was like that. When Anthony Tufaro, who
specializes in head and neck surgery, first took a look
at Maison last summer, the tumor on the toddler’s
face had ballooned to the size of a softball and inched
dangerously close to his left eye. Tufaro couldn’t
tell if the growth was cancerous or if Maison’s
eye and socket would need to be removed to excise the
growth. “What I did know, the moment I saw this
little boy,” he says, “was that he needed
Maison after surgery with his mom.
Maison had what’s called an ossifying fibroma—a
rare tumor that’s usually benign but very aggressive.
It had grown so large that it had displaced his upper
teeth and jaw. He couldn’t eat, he couldn’t
breathe, he was snoring. “He was so dysfunctional
from the tumor,” Tufaro remembers, “we had
to do something.”
According to Maison’s mother, Tammie, the tumor
had appeared around the time of his first birthday and
then enlarged week by week, distorting his mouth, inflating
his left cheek and closing his left nostril. At first,
physicians had said it was simply part of the port wine
stain Maison had been born with. The reddish facial
birthmark, with its overabundance of capillaries just
beneath the skin’s surface, typically signals
the presence of Sturge-Weber syndrome, a congenital
neurological disorder than can include excessive blood
vessel growth on the surface of the brain. What Tufaro
discovered, however, was that the tumor was sitting
amid a bed of dilated blood vessels caused by the Sturge-Weber
syndrome. Not only would he have to remove the boy’s
upper jaw to excise the massive growth, he would have
to perform that surgery with extreme adeptness to avoid
the risk that the child could bleed to death.
For help, Tufaro turned to interventional radiologist
Sally Mitchell. She used magnetic resonance imaging
to make the tangle of blood vessels visible during surgery
and then limited the blood flow throughout the four-hour
procedure by remaining with Tufaro and floating coils
in the vessels. Even so, says Tufaro, “I had to
go slowly. One of the blood vessels feeding that tumor
was the size of my finger.”
In the end, Tufaro removed virtually all of the toddler’s
5-centimeter mass. And to everyone’s relief, it
proved noncancerous. “Maison will probably need
further reconstructive surgery down the line,”
Tufaro says, “but he bounced back one two three.
He’s growing. He’s thriving.”
Mary Ann Ayd
Consultation with John Burton
One of the founding fathers of modern geriatrics and
the former chief of Hopkins’ now #1-ranked Division
of Geriatric Medicine talks about the challenges and
joys of treating older people.
Typically, geriatric patients have been cared
for by adult medicine specialists, but you’ve
made the point that physicians who treat older people
need special training. Why?
Older patients have complicated, multiple illnesses
and often minimal physiological reserves. Caring for
them puts a premium on diagnostic and therapeutic judgment.
You just can’t look in a textbook to find the
answers. In geriatrics, you need above all to be an
effective communicator, to possess deep compassion and
exercise outstanding judgment. All these skills take
particular training and focus. Serving as a primary
care physician for older patients was both the most
challenging and the most rewarding experience I’ve
The program you shaped here has been called
a model. What’s different about it?
You can’t have a hospital, a doctor’s
office and a nursing home as the only options when it
comes to caring for frail older people. Older people
need clinics that specialize in problems like osteoporosis
and incontinence. We’ve got them. We also have
geriatric fellows, residents and attending geriatricians
making house calls all over the community around Johns
Hopkins Bayview to visit older people, who would have
a hard time coming into the hospital. We offer adult
day care that has specialized activities and nursing
for this population. All of these programs dovetail
as a continuous, almost seamless system. Very few medical
centers have anything like this.
Have you found any hurdles that seem particularly
inherent to this specialty?
For one thing, practicing geriatric medicine is challenging
from a financial point of view. Since it’s predominantly
primary care, the specialty can be very labor-intensive.
Yet, Medicare limits your reimbursement. Also, geriatricians
are more dependent on developing partnerships with the
medical school and hospital leaders to create and manage
innovative care programs.
Where does the field go from here?
We are about to publish our study of the National
Home Hospital initiative, in which we’ve examined
the merits of taking care of acutely ill geriatric patients
in a home setting rather than in the hospital. I believe
that will be one of the models for the future. Patients
Alternative to Angiography?
Joao Lima gets the clearest views yet
of the heart with the 32-slice CT machine.
Each year, almost 6 million people come into an ER
with chest pain. To determine if the patient has a heart-related
ailment, physicians order an array of tests including
angiograms, in which dyes are injected in the arteries.
But, at the end of the day, “we often still don’t
know whether the patient has coronary artery disease,”
says cardiologist Joao Lima.
Now, Lima and other cardiologists here are using a
new 32-slice CT scanner to get high-resolution, three-dimensional
images of coronary arteries. The scanner gives them
transparent views through different layers of the vessels,
allowing them not only to detect obstructions, but also
to evaluate the actual pathology of the arterial wall.
They’ll be able to judge the density of the plaque
and infer whether it’s a plaque that may rupture.
And that’s something that even angiography can’t
“To our knowledge, it’s the only 32-slice
machine in the United States,” says Mike Weisfeldt,
the cardiologist who chairs Hopkins’ Department
of Medicine. “More slices mean better quality.
The pictures are just great.”
So, does that mean the multislice CT can replace angiography,
the gold standard for diagnosing coronary artery disease?
To begin to answer that question, over the coming months,
internal studies using the scanner will focus on evaluating
patients admitted with chest pain. Those studies then
will be compared with angiograms done on the same patients.
“Eventually, the explosion of technology in
CT will replace angiography,” Hopkins cardiologist
Edward Shapiro says. “The only question is, Will
this generation be the one that does it?”
Surgery can be the Solution to Too Much Pain
Betty Berlin's trigeminal neuralgia
"came out of nowhere."
On Mother’s Day last year, Betty Berlin received
a horrendous present—excruciating facial pain.
Home alone, Berlin, 81, says she “danced and screamed
for about 15 minutes,” until the anguish subsided.
But the attack turned out to be no passing symptom.
Berlin was diagnosed with a condition called trigeminal
Classic TN like Berlin’s is characterized by
overwhelming, unpredictable pain to areas served by
the trigeminal nerve—the upper, middle and lower
face. Patients liken what they feel to being struck
with a 220-volt electrical wire for seconds to minutes
at a time, making their previous heart attacks or kidney
stones a walk in the park.
For Berlin and most others who develop the condition,
the antiseizure drugs typically prescribed are effective
at first, but eventually not enough. “The peaks
of pain get higher, and the valleys aren’t as
low and don’t last as long,” says Carol
James, longtime physician assistant with neurosurgeon
And so, to give patients a chance for lasting pain
relief and also address the source of the pain—an
overstimulated, hyper-reactive trigeminal nerve—three
Hopkins neurosurgeons, Richard Clatterbuck, Benjamin
Carson and Richard North, now offer treatments. And
though surgery may sound like an extreme choice for
facial pain, the suffering caused by the condition is
“far more deleterious than the risks of the procedure,”
James says. The oldest patient we did, at 100, “fared
In one noninvasive approach, the neurosurgeons use
the Leskell gamma knife to send a forced blast of radiation
to the trigeminal nerve, which lies just outside the
brain stem, and damage it just enough to reduce its
sensitivity. In other cases, they actually perform a
craniotomy and shift the abrasive blood vessels away
from the nerve. Another treatment involves gently inserting
a needle through the cheek and delivering nerve-toxic
glycerol to the nerve. And finally, a small, carefully
directed radiofrequency-emitting probe sometimes can
be inserted that generates damaging heat to the nerve.
The surgeons help patients choose the procedure that’s
best for their case.
With Clatterbuck’s guidance, Berlin opted for
the gamma knife approach. Answering a question this
summer about how his patient was faring, the neurosurgeon
responded, “Last I saw her she was pain-free and
I believe off all medicines.” And in a final piece
of advice, Clatterbuck added, “Patients with this
problem should be referred to us early, before their
pain becomes agonizing.”
A Tough Female Procedure Gets Easier
Any woman who’s had the condition known as pelvic
organ prolapse can testify that it causes an array of
upsetting symptoms: urinary leakage, constipation and
difficulties with intercourse among them. For years,
though, women who wanted to correct the disturbing bulge
of the pelvis that occurs when the support system for
the vagina gives way had one choice: undergo a major
abdominal operation with its lengthy recovery and risk
of complications. Now, happily, laparoscopic surgery
has also come to this urological condition.
In the last two years, at Johns Hopkins Bayview, James
Wright, director of female urology, and Li-Ming Su,
director of pelvic laparoscopy, have performed almost
two dozen “laparoscopic colpopexies.” It
takes between three and five hours to reconstruct the
pelvic floor using the minimally invasive procedure.
Recovery takes weeks rather than months.
“We make only four small, keyhole incisions
across the abdomen, there’s reduced blood loss,
and patients return to work and resume normal activities
much sooner,” Wright says.
What makes it possible to do the complex procedure
without opening the abdomen is the high-powered telescopic
lens attached to a camera that surgeons use to gain
excellent magnification of the pelvic organs. With this
kind of clear view, they are able to resupport the vagina
and pelvic organs internally through a combination of
sutures and a mesh sling. If the prolapse involves the
uterus, a hysterectomy may be necessary to repair all
the damage, but that procedure can be done at the same
time. So can a bladder suspension and rectocele repair.
“In every case we’ve done, we’ve had
no significant complications and very successful outcomes,”
Long-Acting Ragweed Vaccine Nothing to Sneeze At
Peter Creticos, searching for the solution to allergies.
In trying to find a better solution for allergy sufferers,
Peter Creticos, medical director of the Johns Hopkins
Asthma & Allergy Center, appears to have demonstrated
that a long-acting ragweed vaccine in which patients
receive just six weekly shots works as well as, if not
better than, the current allergy injection regimen in
which shots go on for four or five years. The vaccine
induces counter-regulatory T-cells to produce specific
“suppressor chemicals” that block the action
of the harmful Th2 cells—the “bad guys”
responsible for the inflammatory reaction in ragweed-allergic
In an NIH clinical trial, Creticos and his team of
researchers administered the vaccine only once a week
for six weeks. Those receiving the long-term anti-allergen
showed far more rapid improvement than patients receiving
the conventional treatment. “With just six injections,
patients showed the kind of improvement it usually takes
at least three years for us to see,” the researcher
says. “Since the long-lasting injections aren’t
nearly as much of a nuisance, patients will be more
likely to take them.”
As a result of this preliminary success, Creticos,
in conjunction with the developing company, Dynavax
Technologies Inc., has initiated a multi-center U.S.
clinical trial to study the safety and benefits of the
new vaccine in a larger group of ragweed-allergic patients.
If those trials prove successful, the vaccine would
move on to pivotal Phase III trials, the precursor to
FDA approval. And if all goes well, there’s no
reason, in theory, why a similar vaccine wouldn’t
work for allergies to cats, dust mites or cockroaches,
according to Creticos.
It’s Going to Be a Bumpy Ride
Mark Tso and his lycium barbarum
The idea seems utterly simple: If there’s any
truth to the therapeutic value claimed for dietary supplements
and other alternative treatments that Americans spend
billions on every year, the best way to find out is
to put these potions under the same microscope—double-blind,
placebo-controlled trials—that U.S. researchers
have been using for years to establish a therapy’s
worth. And despite initial skepticism in some quarters
here (why diddle with snake oil when there are real
therapies to be tested?), Hopkins four years ago launched
its Center for Complementary and Alternative Medicine
to examine such seemingly far-out cancer remedies as
red wine and bamboo grass leaves. With a $7.8 million,
five-year grant from the National Institutes of Health,
the center now has more than a dozen faculty affiliated
with it. Among its first outcomes were two studies published
this year by pain research director Srinivasa Raja showing
that inflammation-induced pain in rats does respond—fasten
your seatbelt—to both soy and tart cherries.
Any behind-the-back snickers about such research,
however, have proven to be the least of some CAM investigators’
headaches. Center Director Adrian Dobs was all set to
test the Chinese herb combination PC-SPES on the immune
systems of prostate cancer patients when the FDA put
her trial on hold. The world’s only manufacturer
had just recalled batches laced with prescription drugs,
then promptly folded. (Dobs now is evaluating fish oils
as a remedy for extreme weight loss in pancreatic cancer
Pharmacology expert Charles Flexner had better luck
but faced a mountain of work after the FDA insisted
the ginseng he planned to study as a possible treatment
for cancer drug side effects had to come from a manufacturer
making reliable stock and also willing to share production
details. To win the government’s imprimatur, which
came in June, Flexner had to enlist the help of the
American Ginseng Board to sort through the hundreds
of producers of the pungent root.
Still, if anyone understands the tribulations of CAM
research, it’s Mark Tso. As a young boy in China,
the Wilmer professor ate bowl after bowl of orange-red
berries that his grandmother cooked. The berries—lycium
barbarum—contain a pigment believed to preserve
vision. Tso has grown them in his Maryland backyard
and adds a spoonful to his cereal every morning. But
when he approached the FDA about formally testing the
berries, the regulators were adamant that he needed
a placebo. Try raisins, they suggested, or dates. There
is no look-alike, Tso replied. Negotiations dragged
on for months, and by the time both parties settled
on dried dates as the placebo, the study had lost its
The good news is, the lycium barbarum pigment is now
available in a capsule. And Tso, who’s revised
his protocol, is gearing up for round two.
My Cousin Michael, Five Years After His Trip to Hell
In the autumn of 1999, a cancer patient named Michael
Billig appeared on the cover of this magazine. Billig,
a 43-year-old associate professor of anthropology at
Franklin & Marshall College in Lancaster, Pa., had
chronic lymphocytic leukemia (CLL) and had just come
through a two-and-a-half-month stem cell transplant
to try to halt the life-threatening disease. In an article
called “To Hell and Back with My Cousin Michael,”
Bill Glovin, senior editor at Rutgers Magazine, documented
Billig’s experience in Hopkins’ special
inpatient/outpatient (IPOP) unit during the hard days
after his transplant.
Michael Billig after his stem cell transplant.
Last spring, five years later, Michael Billig paid
one more annual visit to his Hopkins oncologist, Ian
Flinn, and went through his final bone marrow biopsy
to check that he was still cancer-free. Glovin sent
us this update on what had changed in his cousin’s
life since last we heard from him:
“Deciding to do the transplant was one of the
hardest decisions I’ve ever faced,” says
the now 48-year-old full professor. “I was in
remission after months of chemotherapy. People said,
‘Why run the risk of dying from the transplant
when you may stay in remission for 10 years? If and
when you relapse, a magic pill for CLL may exist by
By September 1999, just two months after completing
his transplant, Michael felt elated to return to teaching.
“But I was naive in thinking that I’d rolled
the dice on the transplant, come out a winner and would
only have to worry about a once-a-year bone marrow biopsy
now. My red blood cell counts fluctuated wildly, and
I had less energy and a weak immune system. Early on,
after being absolutely convinced that I’d relapsed,
Dr. Flinn assured me I hadn’t. I’ve been
hospitalized for pneumonia the last two winters and
always seem to have some lingering illness. All I wish
for is two weeks of good health.”
Michael also went through a second divorce. Just four
months before he was diagnosed with leukemia, he’d
married Jane Rossetti, an economics professor at F&M.
The marriage didn’t make it, even though Rossetti
had put her squeamishness aside to meet IPOP’s
requirement that patients have full-time caregivers.
She was so moved, in fact, by what she saw in the special
bone-marrow-transplant unit that she enrolled in nursing
school and went on to become a cardiothoracic surgical
Billig today, on campus at Franklin
& Marshall College, where he's on
The magazine article proved useful to Michael. It helped
family and friends—and complete strangers who
might be considering a transplant—to understand
the emotional and medical aspects of the procedure.
Now, he recommends the story to people on a CLL Internet
listserv and to others he counsels for the Leukemia
and Lymphoma Society’s First Connection Program.
“I talk about the ups, the downs,” Michael
says. “I tell them that for me, there are some
lingering difficulties, but that the sum total of my
experience has been mostly positive. I’ve been
able to complete a book, buy a house and see my children
go off to college. I work hard and energetically, have
a sex life, and I’m back in good physical shape.
I rolled the dice—and for the most part, I’ve
Not Just a Bag of Chromosomes
Walk into the office of cell biologist Kathy Wilson
and her hand shoots up instantly for a toy perched on
the shelf above her computer. “It’s not
perfect,” she says, opening her Hoberman sphere
(known among the cognoscenti as a trapezoidal icosatetrahedron
), “but it’s the closest thing to the cell
nucleus I’ve been able to find.”
Cell nucleus expert Kathy Wilson sees
Wilson should know. Her lab is one of a handful worldwide
that’s investigating links between a collection
of proteins inside the nucleus and a group of diseases
that affect specific combinations of tissues, such as
heart, skeletal muscle and bone.
“The old view,” says the associate professor
in Hopkins’ Institute for Basic Biomedical Sciences,
“is that the cell nucleus is simply a chromosome
But that notion—still hanging around in virtually
every college textbook—couldn’t be further
from the reality that Wilson and others are just now
beginning to explain. “There’s a whole world
of structures and processes inside the nucleus,”
she says. “It’s really the cell’s
Two different membranes form the nuclear wall. The
inner membrane, facing the chromosomes, contains a unique
set of proteins that attach to chromosomes, other proteins
named lamins, or both. The two membranes periodically
join together to form pores that control what enters
and exits the nucleus. In the nucleus, lamins assemble
into filament networks on which many other proteins
depend. Wilson is seeking clues to lamin mutations that
give rise to at least 10 diseases now termed laminopathies.
Among them are Emery-Dreifuss muscular dystrophy and
a syndrome called Hutchinson-Gilford progeria that causes
kids to look like 90-year-olds by the time they’re
teenagers and die from heart disease or stroke. “Small
mutations in one type of lamin,” says Wilson,
“are enough to produce all these diseases.”
Wilson was just entering the University of Washington
to major in geophysics—her stepfather was a polar
ice expert— when she learned her mother had been
diagnosed with a terminal illness. The news changed
everything. Wilson went from being a straight A-er to
getting two “major, face-slapping C’s.”
And a word she remembered from grade school—catalyst—joined
forces with her newfound realization that there was
such a thing as medical research. “It’s
good to be motivated by real problems,” she says
of her mother’s death and her decision to shift
her focus to biology. “But you have to think creatively
and dive in playfully and let discoveries lead you in
their own directions.”
In 1985, Wilson earned the University of California
at San Francisco’s first Ph.D. in genetics (“that
was the era after Genentech was founded”) yet
quickly became restless. “I wanted something different,”
says the 48-year-old, “and the missing part of
the picture was cell biology. Science then was ignoring
the nucleus, which is really difficult to study—it’s
filled with chromosomes, you have to literally rip it
apart, and then you’ve destroyed most of what
you want to look at.”
The sheer difficulty alone makes this speaker of Chinese
and maker of Seminole quilts start to grin. Yet always
her eye is on the truly important prize.
Not long after her 1989 arrival at Hopkins as an assistant
professor, Wilson was asked to testify before a Congressional
committee on why the NIH, then in a budget crunch, should
fund basic science research. Whether her arguments influenced
the subsequent decision to double that agency’s
budget is anyone’s guess. Wilson does know how
her outlook affected one man.
“He has a Ph.D. in engineering, and his son
has Emery-Dreifuss muscular dystrophy,” she says.
“He contacted us and said, ‘I know you’re
studying the basic science, but what are you doing to
cure it.’ He ended up being a key donor to our
Mary Ann Ayd
Know Your Niche
To really understand stem cells, you have to understand
the niche they live in. Erika Matunis, a researcher
in the Department of Cell Biology, has one of the best
systems available for doing just that. Matunis uses
the highly structured environment in fruit fly testes
to examine how stem cells are regulated in vivo, where
they develop into sperm. What’s unique about her
system is that it’s easy to distinguish the stem
cells from the sperm cells they produce.
Matunis discovered that in the fly testis, stem cells
are clustered around a hub of cells that regulate them.
When the stem cell divides, one of the daughter cells
remains a stem cell while the other daughter cell is
pushed away from the hub, losing access to the signal,
and then differentiating into a sperm precursor.
What would happen if the signal were turned off and
on, Matunis began wondering. To find out, she used fruit
flies with a temperature-sensitive mutation in their
signaling gene that allowed her to turn off the insects’
signaling ability simply by moving them to a higher
temperature. As she’d expected, when she took
that step, the number of stem cells declined, but recovered
when the signal was restored. What happened next, though,
shocked even her. When she removed the signal long enough
for all of the stem cells to disappear and then turned
it back on, the whole population of stem cells still
“We thought getting rid of all the cells was
going to be our negative experiment,” Matunis
says, “so it was a real surprise to still see
all those stem cells coming back.” In follow-up
experiments, she and graduate student Christa Brawley
determined that this happened because even the sperm
precursors were reverting to stem cells when the signal
from the hub was restored.
“We always thought that when a cell starts to
differentiate, it doesn’t go backwards,”
Matunis says. “It just goes to show that the niche
is in charge.”
Mouse House Protector
Nowhere in Julie Watson’s CV will you find the
words asset manager. But for the researchers whose intellectual
capital is literally tied up in the four-footed patients
under her care, what this assistant professor of comparative
medicine does to protect their investments can mean
the difference between declaring a “profit”
or going belly up.
Julie Watson can't do enough for her
Watson is one of eight laboratory veterinarians on
call around the clock who maintain the health of tens
of thousands of animals (most of them genetically modified
mice) that help provide important breakthroughs in understanding
human disease. A single infection could wipe out years
of a researcher’s work, not to mention animals
that can cost as much as $25,000 each. To ensure that
all mice housed in the new Broadway Research Building
move in clean and stay that way, Watson has been combining
the latest high-tech—robotic delivery of fresh
bedding, cage-by-cage ventilation, computerized environment
control—with her own high vigilance. Among her
tactics are carefully placed sentinels, ordinary mice
that act as coal mine canaries, which she examines regularly
for signs of disease. And she’s virtually perfected
a method of disinfecting newborns and transferring them
to foster mothers to prevent the spread of infection
from mom to pup.
So, is Watson predicting a bull market? “Healthy
mice,” she says dryly, “increase research