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an online version of the magazine Fall 2008
Medical Rounds
The author, post-op, with Tufano
The author, post-op, with Tufano
Photo by Rich Riggins


Spare the Voice, to Avoid Spoiling the Singer

Tufano’s new tools alleviate vocal damage in oft-tricky thyroid surgery.


It’s a tradition to sing Handel’s “I Know That My Redeemer Liveth”—the soprano aria with the killer high G—the Sunday after Easter at my church. When I stood up with music in hand last spring, I thought it might be the last solo I’d ever sing. I just let that G rip from the back of the church. People in the pews jumped. I didn’t care.

A benign mass—a goiter—and a smaller indeterminate “nodule” had swelled my thyroid gland to the size of a small plum. Not only was it visually noticeable but it had begun to affect my breathing and swallowing. And singing. My lower range had dropped, and I had to raise the palate higher to keep the same vocal quality.

I needed a thyroidectomy, doctors told me. Even though the surgery is generally safe and effective, the risk of vocal damage can run as high as 8 percent, depending on the surgeon and institution—a figure particularly troubling to solo singers like me, and professional speakers.

So I turned to Ralph Tufano, who directs Otolaryngology’s division of Thyroid and Parathyroid Surgery at Hopkins. In his seven years at Hopkins, Tufano has developed a wary respect for the anatomy and it drives his surgical approach. New technology has let him indulge that respect, so that now his surgical team works under a risk of vocal injury close to negligible.  Last year Tufano relieved 125 patients of their thyroid glands—many of them voice professionals—operating for goiters, thyroid cancers, or, less often, overactive tissue that resists medication, as, occasionally, in Graves disease

The challenge comes in preserving nerves to the larynx. While the operation is no Whipple, neither is it a snap. Neck anatomy is compact. The thyroid area is crossed by blood vessels, notably the common carotid and external jugular and their tributaries, giving it a greater perfusion of blood, ounce for ounce, than the kidneys. “But what’s really remarkable,” he says, “is that the anatomy is so variable. You can assume nothing.” One surgeon catalogued 29 variations in the lay of a single nerve around the thyroid and its blood vessels. Goiters and large tumors “excavate” nerves and push them into odd places.  “When I present this operation to my residents,” Tufano adds, “I channel Forrest Gump. Thyroidectomy is like a box of chocolates.”

Two nerves are of concern: the so-called recurrent nerve and a smaller spur of the superior laryngeal—a wisp, really, some 0.2 millimeters wide. The recurrent controls the larynx’s main muscles for speech or everyday singing; hoarseness is the usual price of damage. But the spur is what singers should cherish and what Tufano calls the “forgotten nerve” because it’s easily overlooked. By allowing vocal cord lengthening and tension, it controls pitch and power. Lost high notes, then, are a quick sign of injury since they demand sustained tension.

In the OR, an electrode-based monitoring system helps Tufano confirm his sighting of the recurrent nerve and assure it’s fine. Not everyone does this. But saving the superior laryngeal, as it parallels the thyroid artery, depends on skill. Tufano uses a new device, the harmonic focus dissector, that lets ultrasonic energy cut and seal off vessels with a gentleness that doesn’t threaten nearby nerves. “It ends up being a dry, meticulous operation,” he says.
Last year, Tufano introduced MIVAT to Hopkins—minimally invasive video assisted thyroidectomy. Begun in Italy, the endoscopic surgery halves the usual 4-to-6-centimeter neck incision, leaving a tiny scar without sacrificing benefits of the traditional method. “We’re able to remove all thyroid tissue,” Tufano says—a feat for this technique. Nearly 20 percent of his patients qualify for it.

I opted for the larger incision, which wasn’t all that large. Now several months post-op, I’m back in the choir with full soprano range. My voice isn’t quite the same—how could it be, with tissue missing? But there’s a new clarity and, with the extra space, a powerful resonance I never had. 


Marjorie Centofanti

On the Deficit Trail

Painstaking sleuthing has turned up the makings of a new schizophrenia gene.


Andersen, with his ultrasonic wonder

Of those who go through life pressed under the thumb of schizophrenia, a smaller group is nearly flattened by it. They’re patients who suffer with deficit schizophrenia. It’s an add-on, essentially, to the disease’s usual disordered thinking and reality, explains psychiatrist Nicola Cascella. People with “deficit” lack drive. Their emotional range is narrow and any budding sense of purpose from their early teens has withered—all with a hallmark low verbal ability. For them, steady work, marriage, and families are rarely checked off life’s list. “Ask a patient what gives him the greatest joy in life,” Cascella explains, “and he’s hard-pressed for an answer. ‘I went for a walk this morning,’ is what I’ll hear.”

Psychiatry sees deficit—which affects perhaps 20 percent of schizophrenia patients—mostly as a difference of degree within the disorder’s spectrum of symptoms. But Cascella, who is with Hopkins’ schizophrenia program and has made deficit something of a specialty, thinks something more might be at work. For one thing, a decade of his and others’ study has consistently turned up telltale differences from the more common illness. And now, work out this fall by a mostly Hopkins team, including Cascella, gives clout to the idea that deficit has its own biology.

Besides the distinct symptoms, the epidemiology stands out, he says: People with common schizophrenia are typically born in the spring, mostly in March. But deficit patients’ birthdays fall in June or July. Also, they resist medications, Cascella says. “These patients are notorious for being hard to treat.”

The reason why may be linked to genetics. Recently, he and Psychiatry colleagues had their attention caught by a gene, called PCM1, with interesting possibilities. Cascella had come across the gene one Christmas vacation four years ago when he’d retreated to his computer. He happened on a Hopkins study about an obscure genetic disorder, Bardet-Biedel syndrome, that linked the ailment—it brings obesity and kidney damage—with PCM1. But Bardet-Biedel patients also risk schizophrenia, psychiatrist Cascella knew—it’s twice as common as in healthy people. “And what struck me, for some reason, was that BBS patients have problems with body symmetry.” Men with schizophrenia have symmetry issues as well—in the brain.

Mostly out of curiosity, Cascella called up PCM1’s particulars on an online database. The gene’s address was on chromosome 8, at spot 22 on its short arm. More clicks brought up a 1998 mammoth Hopkins study that had linked a mystery gene at 8p22 to schizophrenia. Excited, Cascella confided in psychiatrist Akira Sawa, a colleague who directs molecular psychiatry.

It took two years, but the two assembled a team that included Hopkins geneticist Nicholas Katsanis, an expert in the molecular aspects of Bardet-Biedel syndrome. They showed, in lab mice, that disrupting PCM1 sparks significant flaws in brain development before birth—likely by upsetting natural cell scaffolding. Most important, the flaws mimic those brought about by another known schizophrenia gene Sawa has long researched. This implies a common mechanism for some forms of the disease.

PCM1, then, has the makings of a new schizophrenia gene. But where’s the proof in people? And what’s the tie to deficit schizophrenia?

Fortunately, Hopkins psychogeneticist Ann Pulver kept blood samples from people in her decade-earlier 8p22 search for schizophrenia genes. “Ann saw the promise of our ideas,” says Cascella, and soon they were analyzing DNA from 32 of her volunteer subjects with an especially strong family history of the disease. When that DNA was sequenced, one family surfaced with a PCM1 mutation. And, amazingly, only family members with schizophrenia had it. “That find was fantastic,” Cascella grins.

But there’s one more clue. Last year, a British group tied abnormal PCM1 to a loss of brain volume, specifically in the orbitofrontal cortex. “We’re well aware of that area,” says Cascella. “People with lesions there get an apathy syndrome that looks a lot like deficit schizophrenia. We know it’s speculation, but it’s tantalizing to think that, given such evidence, flawed PCM1 might be a deficit schizophrenia gene.”

Of course, he says, both repeat and expanded studies are in order. But the beauty of the work is that it sketches a reasonable outline for one sort of schizophrenia, from gene to cell to brain to person. It’s the start of just the sort of daisy chain that psychiatrists pray for, the sort that inspires therapy. 





Synergy S Hits the Spot

Targeting tumors is now more accurate than ever.


Tracking the brain’s blood flow
> DeWeese with Synergy S
Photo by Keith Weller

Delivering radiation to a tumor site is tricky business. Patients can shift imperceptibly during treatment—even breathing moves organs—and tumors can change shape, increasing the risk for healthy tissue to be inadvertently zapped.

Enter Synergy S, the newest addition to Radiation Oncology’s arsenal here, which uses vacuum technology to immobilize patients and a built-in 3D imaging system that assures ultra precision and the safest angles.

“We can see a new 3D image of the tumor right before treatment and re-verify the position using another 3D image during treatment, each time making adjustments as necessary,” says Ted DeWeese, director of the Department of Radiation Oncology.

With Synergy S, Hopkins has expanded stereotactic radiosurgery to parts of the body besides the brain. In addition to the spine, the machine is used to give ultra-high doses of radiation to cancers in the liver and lung, applications for radiosurgery previously considered off-limits chiefly because of difficulty tracking the motion of tumors in locations that move when you breathe.

Key to the team that developed Synergy S is John Wong, chief of medical physics at Hopkins, who invented the on-board CT technology and an automated breathing controller. The patient-controlled device allows the radiation beam to turn on only when the patient holds his breath and signals the machine to fire.

The new machine can be used to treat any type of brain tumor (especially those inappropriate for gamma knife surgery) and even for brainstem tumors. “It’s been done with limited success, but with Synergy, we hope to be able to start treating those patients on a protocol,” says DeWeese. 


Anne Bennett Swingle

Sun for Your Life

Lack of vitamin D shortens lifespan, but one researcher sees a natural solution.


1 1 1
cardin & bush

A cardiologist who recommends more time in the sun? Erin Michos knows she’s going out on a limb, but she’s talking about very modest levels of sunlight—and she’s got a weighty new study to back her up.

Michos, an assistant professor here, co-authored a study in the Archives of Internal Medicine showing that people with deficient levels of vitamin D suffered a 26 percent increased risk of death even after other factors were taken into account. Those low on D can boost their intake of oily fish or add supplements to their diet, says Michos, but “one of the quickest and easiest ways is to take in natural sunshine.”

She knows about the risks of skin cancer, Michos says. “I’ve seen people die from melanoma.” But fewer than 8,000 of the 580,000 cancer deaths per year come from melanoma, typically from too much sun.

More experts now believe D-deficient people suffer conditions related to the deficiency—peripheral artery disease, heart disease, diabetes, and a number of non-skin cancers. The rewards of a thrice-weekly 15-minute exposure to the sun, the new experts say, appear to outweigh the risks (with sunscreen for prolonged exposures).

Michos has already heard some of D-therapy’s early doubters, many of whom cite the recent rise and fall of vitamin E. Yes, admits Michos, but she believes D won’t suffer the same fate. For one thing, she says, D is more like a natural hormone. “Your body can make vitamin D after sun exposure,” she says. But she also allows one hedge: “We still need a clinical trial to show that boosting D for those with the deficiency can prevent a heart attack.”

The D deficiency appears to be artificially induced, says Michos. Modern societies have migrated into more northerly latitudes with less sunlight. They wear more clothing. They work indoors under fluorescent lighting that lacks the D-producing ultraviolet rays—and they get less physical activity. The obesity epidemic factors, too. Fat cells trap the D nutrients, preventing their flow through the bloodstream.

Michos is hoping more physicians will soon be checking D levels in their patients. “Some savvy doctors have been ordering it,” she says, “but it’s not done automatically.” 



Families Round Out the Rounds

At the Children’s Center, the time-honored tradition gets an update.


      Illustration by Sherrill Cooper

It’s Monday morning in the Johns Hopkins Children’s Center. Medical student Sonya Babar stands, clipboard in hand, running down details of the condition of Leah, an adorable 17-month-old with tiny ponytails springing all over her head. A semi-circle of residents, medical students, nursing staff, and an attending physician listens closely.

Business as usual on morning rounds, except for one crucial difference: Sitting on the bed in the middle of the Stonehenge of white coats, holding Leah in her lap, is Leah’s mom. Barbara Thompson is there both to listen and to provide input about her daughter’s health history.

Babar runs through the events that brought Leah to the hospital: Fever and vomiting for four to five days. Did not respond to antibiotics prescribed for an ear infection at another hospital. Face began to swell two days ago. Legs began swelling yesterday. When Babar mentions that Leah has a slight heart murmur, the mother interrupts: “Excuse me, I didn’t know she had a heart murmur.” Babar explains that the murmur is very soft and could be temporary. Mom nods.

That sort of exchange is exactly what Children’s Center leaders had in mind when they implemented the new family-centered patient rounds this past March. The move is part of the broader family-centered initiative the Children’s Center is taking to recognize the critical role that families play in ensuring the health of children.

“We used a model from the Cincinnati Children’s Center,” explains Jason Custer, who was chief resident of pediatrics when the family-centered rounds began. “Instead of rounding in a conference room, we are now going to the bedside and including families, nursing staff, social workers, discharge coordinators, and a pharmacist to be sure everyone is on the same page.”

At first, he notes, some medical staff were leery of discussing things in front of parents that could worry them. “But I think we can underestimate how much parents know and how much they’ve picked up, in terms of medical lingo—especially parents who’ve been in the hospital a lot,” he says. “Also, a lot of parents imagine the worst-case scenario, so this can save them a lot of anxiety.”

And although it can take extra time to answer parent questions during the rounds, he says, staff end up saving time in the long run since they don’t need to double back later to answer questions and bring the family up to speed.

For her part, medical student Babar has found she likes having parents on hand, especially to correct the medical record, if need be. “When you’re telling the story of why [a child] came to the hospital, it’s good to have the parent there to confirm it,” she says.

Back in Room 646, as the rounding doctors prepare to move on, it’s still not clear what’s wrong with Leah, but the little girl is feeling better. And just listening to what they’ve begun to eliminate—kidney disease, Kawasaki disease—has brought some measure of comfort to the toddler’s mother.

“It just makes me more comfortable, like I’m part of the healing process,” says Leah’s mom. “They don’t act like they’re the doctors and that’s it. This is a great idea.”



 Get a Life!?
 Washing Out My Distressed Genes
 Guardians of the Heart
 Sleep Interrupted
 Circling the Dome
 Medical Rounds
 Annals of Hopkins
Class Notes
 After the Prize
 Learning Curve
Johns Hopkins Medicine

© The Johns Hopkins University 2008