A brachial plexus injury can be repaired—but see an expert and act fast.
Denise McCreery came to in the front seat of her car,
which was pressed against a guard rail on I-95 in Maryland.
She was covered in fine bits of blue glass, with the
chill March wind blowing easily through the jagged
space where her windshield used to be. The engine was
still humming, the radio still on. Noticing that she
couldn’t move her left side, she dialed 911 with
her right hand.
That was two years ago. The 31-year-old educator had
been struck in the left shoulder by a 13-pound brake
drum that had broken off a truck ahead of her. The
hurtling shard had bounced off the asphalt, penetrated
deeply into her left shoulder and sliced through the
intricate brachial plexus area of her upper torso.
It broke McCreery’s collarbone, two ribs and
six vertebrae, paralyzing her left shoulder and arm
down to the wrist. After weeks of physical therapy,
a specialist near her home in Virginia imparted the
bad news: Injuries to the brachial plexus complex are
notoriously unresponsive to even the most skillful
medical interventions: “I’m afraid there’s
no way you’re going to get your arm back.”
Such predictions are all too common, according to
neurosurgeon Allan Belzberg. What happens then is that
patients fail to seek out proper help within an adequate
time frame. “Don’t wait,” Belzberg
says. “The earlier we get the patients, the better
Denise McCreery is a case in point. Just weeks after
her accident, McCreery sought a second opinion that
brought her to Belzburg. “Her arm was hanging,” he
recalls, “and the hand is almost useless if the
arm can’t bend.” But what McCreery recalls
most about that meeting is Belzberg’s description
of the wonders of nerve transfer. “We’ll
see what we can do,” he told her.
The operation was scheduled for three months post-accident. “A
good window,” Belzberg says. When the surgical
team opened McCreery’s brachial plexus structure,
they had to navigate around formidable stretches of
inflexible scar tissue that had rendered some portions
of nerve material unusable. But they also identified
working nerve portions they could use for grafts.
For a time, Belzberg explains, the transplanted nerves “remember” their
old functions, so McCreery would have to think “make
a fist.” But thanks to their plasticity, transplanted
Those predictions proved right. Seven
months post-op, McCreery could lift her left arm over
her head. Today, she can hold her 23-pound niece aloft “We
got in there nicely,” Belzberg says.
A seemingly simple protein could be a major player in bodily functions.
Desiderio, the protein prober.
A name can be a powerful thing—a label, as it
were. Happily, in the case of one protein called TFII-I,
Steve Desiderio looked beyond the label and discovered
the true nature of a multitalented protein. In a paper
published in Science, Desiderio showed that TFII-I—originally
identified as a simple regulator for a few genes—actually
controlled entire cells’ ability to grow up.
First, a word about TFII-I. Originally noticed by
scientists in 1991, the protein seemed to dwell mainly
in a cell’s nucleus, sitting right on the DNA.
From that vantage point, scientists found, it dictated
whether a gene would be turned on when it transmitted
its message through a process called transcription.
Naming the new protein then became straightforward.
TF stands for “transcription factor.”
How Desiderio came upon TFII-I, though, was completely
accidental. Searching for proteins that nurture immune
cells, he and his lab team started working with one
called Bruton’s tyrosine kinase (BTK). Without
BTK around, they knew, immune cells remain immature.
So, years ago, to unearth BTK’s workings, Desiderio
began looking for other proteins that would stick to
it. Enter TFII-I, a protein with an established reputation
for regulating transcription. But why would this transcription
factor—which should be shacked up in the nucleus
close to DNA—be sticking to BTK?
Perhaps, Desiderio speculated, the answer lay
in BTK’s business—managing the fluctuating
calcium concentration in immune cells. Through its
interactions with BTK, TFII-I might somehow be masterminding
the whole calcium affair. Things didn’t get rolling,
though, until Gabriela Caraveo, a graduate student
in the lab, learned how to test that hypothesis with
some clever experiments to expose TFII-I’s prospective
First, to see what would happen without TFII-I, the
researchers blocked it in an experimental cell line.
Calcium gushed into the cells. In more experiments,
the team showed that TFII-I manages to put the kibosh
on calcium entry without behaving like a transcription
factor at all. Eventually, it turned out that BTK actually
enlists TFII-I to keep calcium channels from popping
up on the cells’ surface.
Fortunately for Desiderio, all this calcium hoopla
suggests that TFII-I is a major player in immune cell
maturation. “Calcium is a universal currency
in almost every signaling mechanism,” he says. What’s
more, calcium levels, as adjusted by TFII-I, can indicate
whether an immune cell is ready for promotion to the
next stage of development.
“We started looking at immune cells, but it’s
actually a much bigger phenomenon,” says Desiderio,
who has now found calcium regulation by TFII-I in a
variety of cell types. Calcium signaling influences
everything—from muscle contractions to the potency
of prescription drugs. So maybe TFII-I needs a flashier
name—something like “the calcium police.” Erika
Erika Gebel is a School of Medicine graduate student
Erica Gebel is a School of Medicine
graduate student in biophysics.
Is it time to tailor treatment for heart failure?
David Kass says all failing hearts aren’t created
equal and physicians may want to adjust their remedies.
Half of America’s 5 million cases stem from “systolic” heart
failure, which leaves patients feeling perpetually
fatigued. Cardiologists typically prescribe beta blockers,
which reduce the toxic effects of the neurohormones
that tax the heart muscle. Patients with the lesser-known “nonsystolic” heart
failure also typically get beta blockers, but for a
different reason. Cardiologists hope that by slowing
their hearts, the organ’s chambers will have
time to fill with more blood before pumping it out
to the rest of the body.
But Kass, an expert on heart failure, says therapies
for nonsystolic cases should be revisited. This problem
is harder to detect, because the heart’s pumping
strength can look normal when the patients are at rest,
the scenario in a doctor’s office. Yet when these
same patients become active, their hearts fail to deliver.
Tasks as simple as getting dressed in the morning leave
them gasping for breath.
When these patients are properly diagnosed, Kass says,
treating them with beta blocker therapy might have
an undesirable effect. Why would a cardiologist want
to slow down a patient’s heart when it needs
to speed up? Kass suspects these patients would be
better served by pacemakers, which can detect physical
activity and then adjust the heart rate accordingly.
This approach could be critical. More than half a
million heart failure cases develop yearly, and nonsystolic
cases are growing. “It’s mostly women over
50,” Kass says, “whose heart pumping appears
to be normal.” Further examination reveals their
To come up with his premise, Kass compared 19 such
patients to 17 with similar cardiac issues but no symptoms
of heart failure. When both groups pedaled stationary
bicycles at increasing speeds, those with nonsystolic
heart failure quickly fell behind. On average, their
hearts beat 44 percent slower than the other patients’.
Similarly, the affected group’s blood vessels
failed to dilate adequately in response to activity.
But Kass wants to go deeper. He’ll study 80 nonsystolic
heart failure patients with pacemakers. Half will receive
beta blockers; half won’t. Which ones will feel
Testing, 1... 2...
Increasingly sophisticated hearing implants expand the soundscape.
Have you ever wondered what Beethoven’s Ninth
sounds like to a grasshopper? Now you can find out
through a cochlear implant device currently gaining
traction in the United States. The Baha system, depicted
at right, can enhance hearing for people who haven’t
been helped with a traditional hearing aid. The system
works through the same principles that allow grasshoppers
to hear. In the insect, the exoskeleton of the head
connects directly to its cochlea; in the implant, a
tiny transducer picks up sound vibrations and transmits
them directly into the bones of the skull.
According to John Niparko, director of otology here,
the implant technology can restore hearing to a level
that allows a person to converse naturally. It works
especially well, he says, for people with single-sided
deafness. A national leader in cochlear implants, Niparko
successfully treated the only deaf Miss America.
To refine the technology, Niparko partnered up with
its Swedish inventor 10 years ago. The model shown
here is their latest. When viewed with the naked eye,
it’s slightly larger than a sugar cube. At 11
grams, it weighs about the same as a robin’s
egg. Small is good, in this case, because the Baha
unit must be anchored intobone just behind the patient’s
ear, where it can easily be covered by the person’s
Niparko’s younger patients are often proud of
their implants and not at all interested in hiding
them. Some even decorate them with brilliant purple
and pink stickers.
As for results, studies have shown, this hearing expert
says, that the device corrects deafness in most patients
to a level that is “close to how someone with only
a mild loss would hear.” Less than 10 were implanted
in the United States during the ’90s, but Niparko
now implants that same number here monthly—the
highest volume nationally. About 30,000 units are currently
in use worldwide. The outpatient procedure takes about
one hour. Cost to the patient: $4,500.
It’s one of the first questions that parents
ask when physicians propose to send a mapping probe
into their child’s brain after a frightening
neurological incident. Is this procedure safe?
Yes it is, says pediatric neurologist Lori Jordan,
who recently announced the results of cerebral angiograms
performed on 205 children here between 1999 and 2006.
The number of complications from the procedures? Zero.
That’s good news, says Jordan, because these
tests provide the most accurate view of brain vessels
in diagnosing strokes, brain tumors and other brain
diseases. The procedure involves threading a catheter
into the groin and eventually into the arteries of
the neck. Because children’s vessels can be so
small, some doctors had shunned the probes for fear
of vessel damage. The study gives neurologists hard
data in proposing the diagnostic tool’s safe
Opening Up About a Discouraging Condition
How does a patient with bowel disease handle intimacy?
The symptoms can be embarrassing
and devastating: Chronic diarrhea and bleeding from
the anus, abnormal tissue growths between organs
and other body structures, painful abscesses that
can burst and drain. As if to make matters worse,
inflammatory bowel disease, or IBD, typically strikes
before the age of 30—prime
child-bearing years. The ensuing inflammation of the
lower intestines combines with the growth of ulcers
to spawn a host of challenges to the quality of any
couple’s intimacy. Expert Mary Harris uses candor
and data to help sufferers work through the issues.
Can living with IBD discourage the idea of having
Absolutely. You need self-esteem to have an intimate
relationship. Patients may be afraid they’ll
be incontinent during intercourse. They can have body-image
problems due to the abnormal growths, perineal disease,
difficult surgery, excess body hair and medication
side effects. Women, especially if they have the abnormal
tissue growths, may find intercourse painful. A small
percentage of men experience erectile dysfunction after
surgery. Part of what I do is bring up these issues
to help patients deal with them.
Do genetic factors make patients skittish about conceiving?
One of the most common worries is that they’ll
pass on their IBD, and some factors do increase that
possibility—being Ashkenazi Jewish or having
one particular condition within the IBD group: Crohn’s
disease. If both parents have IBD, there’s a
35 percent risk their child will too.
What about fertility?
When a woman’s disease is in remission, conception
shouldn’t be a problem. Active Crohn’s,
however, could affect her ability to conceive, and
an anal pouch could cause an 80 percent drop in fertility.
Certain IBD drugs can also interfere with the formation
of sperm or impair the motility of sperm cells.
Should women worry that their medication could affect
a pregnancy and breast-feeding?
That shouldn’t be a deal breaker. The key is
education and planning. I’ve prepared a packet
for my patients and their obstetricians on all the
IBD medications that are safe in pregnancy and breast-feeding.
Patients should be in remission at least three months
before conception. I see mine during each trimester
and six to eight weeks postpartum.
So, for you, reassuring your patients is everything?
Of course. This is about quality of life. Patients
are reinvigorated and rejuvenated knowing they can
lead a normal or near-normal reproductive life.
Mary Ann Ayd