Soft Shoulders

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 our results.”

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 nerves adapt.

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. 

Ramsey Flynn

Hidden Powers

A seemingly simple protein could be a major player in bodily functions.

>Steve 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 moonlighting. 

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 Gebel

Erika Gebel is a School of Medicine graduate student in biophysics.

Erica Gebel

Erica Gebel is a School of Medicine graduate student in biophysics.

Random Hearts

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 disease.

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.

Ramsey Flynn

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 hair.

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.

Ramsey Flynn

Child-Proofed

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 use.

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 a family?
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