Late in 1998, Sara Sami Mufti was living happily in her home city of Jeddah, Saudi Arabia, and a few months into her first pregnancy when she began feeling dizzy and weak and suffering agonizing pain in her head, arms and upper back. Her weight plummeted. Local doctors found the 22-year-old had a decreased hemoglobin level and suspected anemia, but could find no reason for the low hemoglobin.
Over the next year and a half, Muftiís condition went steadily downhill. When she no longer could walk, her physician uncle insisted she come with him to Johns Hopkins. And here, within minutes of entering the office of internist William Schlott, Mufti knew that her mysterious illness would soon have a name. "Dr. Schlott touched my hand, and I knew he knew what was wrong with me," she says.
Indeed, Schlott intuited Muftiís disease almost immediately. His first clue came when he felt no pulse in her hand and no blood pressure in her armóthus her blue hands and cold arms. Schlott then picked up another telltale sign of the condition he suspected. Mufti had abnormal blood vessels in the back of her eyes. He confirmed his diagnosis when X-rays revealed that his patientís arteries were dramatically constricted.
Mufti had a classic, but potentially lethal, case of Takayasuís arteritis, an inflammation of the walls of the arteries that makes the blood vessels constrict, obstructing blood flow to the limbs and vital organs. Indeed, the carotid artery in the young womanís neck was almost blocked, causing her anguishing headaches and dizziness. A bulging aneurysm in the aorta explained Muftiís excruciating back pain, and her dramatic weight loss proved the result of a partially blocked artery that had reduced circulation to the mesentery vessel leading to the stomach and other organs that aid digestion. Finally, a totally obstructed blood supply to the neck and arms through the subclavian arteries was causing the intense arm pain.
"We had to turn this off before she had a major complication," Schlott explains, noting that untreated the disease can lead to blindness, a heart attack or stroke.
†His patientís condition was dangerous, but Schlott knew he could treat it. Anti-inflammatories would unblock the arteries and restore normal circulation. And although in some cases of Takayasuís the intense scarring of the arteries left by the inflammation requires opening through surgery or catheter angioplasty, Mufti responded well to anti-inflammatories alone. The morning after she started taking the medication she began feeling a change in her condition. Today, Mufti is back in Saudi Arabia, stretching her arms and walking. "I feel," she says, "freshlike a new person."
As for Schlott, the case offered him one more example of whatís thrilled him about medicine for decadesdetecting a rare disorder and providing lifesaving treatment. In this situation, what he found particularly satisfying was making it possible for a young mother to hold her 7-month-old baby for the first time.
As recently as a decade ago, the standard method for treating advanced cancer of the larynx was a laryngectomy to get rid of the cancer. To provide patients who no longer had their voice box with the power to speak, physicians offered two methods: learning to talk through their esophagus in the strange, gruntlike sounds that characterize esophageal speech or speaking through a small electronic speaker implanted in the neck in a tinny, microphonelike voice. Both methods were far from satisfactory, and patients often ended up depressed and hesitant to communicate once their own voice was gone.††
Then, in the early í90s, the ability to shrink and kill tumors of the larynx took a giant step forward. A landmark study demonstrated that the survival rate for larynx cancer patients treated with chemotherapy or radiation was as good as for those who had their larynx removed. Suddenly, about two-thirds of patients didnít have to face life without their voice box. A full one-third, however, still required the laryngectomy.
Now, Arlene Forastiere has reduced that number by 50 percent. In an eight-year trial of more than 500 patients, Forastiere has shown that by giving chemo drugs and radiation therapy at the same time, the larynx can be saved in 88 percent of patients for up to two years, and in 85 percent for up to five years. The simultaneous treatment works because the chemotherapy makes the cancer cells more sensitive to radiation.
Radiation oncologist D.J. Lee explains it this way. "If you expose 100 cells in a test tube to radiation, 50 cells will die. But if you inject chemotherapy into the test tube at the same time, 60 or more cells will die."
Some cells, Forastiere acknowledges, are resistant to both radiation and chemotherapy. "But by giving the treatments together, we can overcome the resistance." The new approach isnít for everyone, she makes clear. It depends on the tumor size and location.
The combination therapy is also more toxic and includes side effects like low blood counts and swallowing problems. Patients must first be evaluated by a head and neck surgeon and oncologists. If the tumor is small, radiation alone or surgery to remove only a portion of the larynxpreserving the vocal cordsmay be recommended. If the cancer is pervasive, a laryngectomy may be the best option.
"Still, weíve gone from everyoneís needing their larynx out to only 15 percent," Forastiere says.
A combination of chemotherapy and radiation given at the same time, says Arlene Forastiere, gives patients a greater chance of keeping their voice box.
Otolaryngologist Paul Flint recalls a patient in his 70s who arrived in the clinic complaining of persistent hoarseness. Conventional diagnostic tools like mirrors, lights and scopes couldnít determine a problem in the manís larynx. But Flint used a stroboscope, a machine with a strobe light and video camera, thatís fed through the nasal passage to capture slow-motion pictures of the voice box in action. With this instrument, Flint detected stiffness in one of the vocal foldsa sign of cancer not visible to the naked eye. A biopsy showed a very early malignant lesion in the larynx that could be treated with radiation alone.
"The best way to avoid losing your larynx because of cancer is to pick it up early," says Flint. "The stroboscope offers the most useful way to do that."
Speech pathologist Robin Samlan explains that the tiny lesion was detected "because cancer doesnít vibrate very well" in the vocal folds, which quiver at up to 220 times per secondspeeds far too fast for the human eye to keep up with. By using the pulsed strobe light to illuminate segments of the foldsí motion, clinicians can differentiate subtle changes like stiffness not visible to the unaided eye. These indicate early stages of laryngeal cancer or other voice box disorders.
The stroboscope comes with a hefty price tag for hospitalsabout $50,000so itís not available at all facilities.
If the triple pelvic osteotomy sounds like a back flip by a trapeze artist, it does have similarities. The procedure, designed for the 20-to-40-year-old patient with a severely degenerated and misshapen hip, called developmental hip dysplasia, is complex and risky. Indeed, only a handful of orthopedic surgeons around the world attempt it.
"Youíre operating fairly deep in the body around structures like the femoral artery and the sciatic nerve that can be injured with drastic results," says orthopedic surgeon Marc Hungerford. "Most surgeons donít feel comfortable with this procedure."
But Hungerford, who learned the procedure in Dortmund, Germany, prefers it to the traditional treatment, total hip replacement, in almost all of his dysplasia patients. A new artificial hip relieves the pain caused by friction in an abnormal hip, he says, but it may cause infections, fall out of place or wear out over time, requiring a second operation. "For younger, more active patients, wearing out and dislocation are even more likely," says Hungerford, noting that the average age for hip replacement in the United States is 65.
With the triple pelvic osteotomy, natural bone is realigned and restored, reducing the risk of displacement, infection, and wear and tear. But pulling the procedure off is no easy trick. Hungerford first makes three small incisions over the buttock, hip and pubic areas, then cuts the pelvis in each place to free the hip socket, or acetabulum, from the pelvis. Using X-ray guidance, he rotates and repositions the socket fragment, fixing it with screws and wires. Correct rotation of the acetabulum is critical, as the newly positioned socket has to be able to hold the ball-like head of the thigh bone.
"You can rotate both laterally and forward to get the bone to cover the top of the ball part of the socket joint," Hungerford explains. "The cartilage has to be in a weight-bearing position and not off to the side." Dysplasia patientsí sockets donít adequately cover the ball of the femur, which results in the early degeneration.
All this must be done while deftly feeling for hidden underlying arteries and nerves. "You have to be careful to cut the bone and not anything else," stresses Hungerford. Cut the femoral artery and you could permanently weaken quadriceps muscles in the leg or, worse, trigger uncontrolled bleeding. Just nick the sciatic nerve and the patient may experience lifelong weakness in the lower legs. Damage the pudendal nerve and numbness in the groin could result.
Once the hip fragment is rotated into place, it will healand eventually functionnaturally. "Itís a durable, natural hip that has a normal distribution of forces across the joint," Hungerford says.
After the surgery, patients participate in sports and walk as far as theyíd like to. And unlike some hip replacement patients, they donít worry about dislocation. "It may be the only hip procedure theyíll ever need," the surgeon says.
Sarah Ben was driving in College Park, Md., one day last August when she was hit broadside at an intersection by another car. The results were devastating. The 21-year-old college studentís head injuries were so serious they caused seizures, and both her hip and pelvis were shattered. It seemed unlikely she would ever again walk normally or without pain.
When Clif Turen, a Hopkins orthopedic surgeon who specializes in treating severe trauma to the pelvis, took a look at Benís X-rays he was astounded. She had a serious two-column fracture of her hip socketthe most complex of complex fractures. In most such fractures, some part of the joint is still attached to the pelvis, which surgeons use to begin rebuilding. But in two-column fractures, the socket becomes disconnected, free-floating fragments of bone. Benís fracture was one of the worst Turen had seen.
Turen knew he had to operate fast as the pelvis tends to heal quickly, making it difficult to move fragments from connective tissue and muscleand reducing the chances for a successful surgery. He also had to expose as much of the pelvis as possible to see what imaging didnít reveal. In these fractures, he explains, "he hard part isnít knowing how to get to the pelvis, but figuring out whatís broken."
In Benís case, Turen got a good view of the wreckage, and it was extensive. He began what would be five hours of painstaking work in which he pieced and screwed the fragments together as he visualized how the reset pieces would work in a moving hip. The surgeon, Turen explains, must constantly think about the relationship of the hip ball and socket as it sits within the pelvis, which is more complex than the mechanism of joints like the knee or ankle: "And we also have to anticipate how work on one side of the pelvis will affect function on its other side. Youíre working very much on indirect maneuvers in strange territory, and you donít have that same control as you do with other joints."
†The goal is to reduce any friction between the bones. If the surgeon leaves any boney bends or ridges, the patientís risk of painful, post-traumatic arthritisand another operationincreases. Ben came through it all wonderfully. "Iím walking fine, and I donít have any pain at all,Ē she reports. "I get a little more tired, but thatís about it."
"As physicians, weíve always thought that we knew how to identify a frail person, yet thereís been no standard definition," notes Linda P. Fried, the internist who directs Johns Hopkinsí Center on Aging and Health.
Now, in a gigantic study supported by the National Heart, Lung and Blood Institute of more than 5,000 people ages 65 to 101, Fried and colleagues around the country have given us a definition. The hallmarks of frailty, the researchers write, are unexplained weight loss, low energy and exhaustion, a weak grip and the ability to walk only slowly. Those most likely to become frail are older women, ages 75 to 84, especially African Americans, the less educated and the poor. The condition is more common in those with such chronic diseases as cardiovascular and pulmonary diseases and diabetes. Some people, however, become frail simply as a result of aging.
To establish their definition, the clinicians performed physical exams and evaluated each subjectís lifestyle and ease of performing daily tasks. They concluded that a diagnosis of frailty requires at least three of the following symptoms:
With the over-65 age group growing faster than any other, Fried says, this new information should be of concern to every physician who treats older adults, since up to 20 percent may suffer from the condition. The frail, she points out, are the most vulnerable, the most at risk for disability or death, the highest users of medical care and the most likely to be admitted to nursing homes.
The heart disease known as ARVD, or arrhythmogenic right ventricular dysplasia, behaves like a snake. It silently sneaks up on victims, strikes violently and often kills. Those with the condition typically athletic 20-to-40-year-oldsmay feel palpitations in their chest or fainting sensations and see their doctor, but for many, an out-of-control, wildly racing heart is their first symptom and their last. According to cardiologist Hugh Calkins, the heart takes off, and a significant portion of them die before theyíve ever been diagnosed.
In a normal heart, the healthy smooth muscles lining the right ventricle enhance conduction of the electrical current that produces a heart beat. In ARVD patients the tissue on the wall of the right ventricle is fatty and scarred, causing the current to short-circuit and triggering the life-threatening arrhythmias.
Whatís especially troubling about this condition, Calkins says, is that itís treatable. An implanted defibrillator that shocks the heart back to a regular rhythm can correct the deadly arrhythmia when it occurs and give a patient with ARVD a full life.
The problem is that the condition has been almost impossible to diagnose until itís too late. Conventional imaging techniques simply havenít been able to detect the subtle strands of scarred and fatty tissue that signify the disease in the tiny, shaking wall of the right ventricle.
"Youíre talking about a very small space, about 1-to-2 millimeters wide, thatís moving every 15 milliseconds with breathing and the beat of the heart," explains radiologist David Bluemke. "This blurs out the fat signals in conventional MRI."
Now, Bluemke and Calkins are improving the outlook for ARVD patients by making new high-speed MRI scanners central to diagnosis. The scanners allow the physicians to freeze the motion of the heart and capture crisp, detailed images. "Itís made a night and day difference in detection," Bluemke says. To confirm the diagnosis, the images are correlated with other test results from the patient, like electrocardiography records of the activity of the heart.
Today, Calkins and Bluemke know for certain if a patient with suspicious palpitations has ARVD and warn the person immediately of the insidiousness of the condition. A defibrillator is then surgically implanted beneath the collarbone and must absolutely remain in place for the rest of the personís life.
TRAM-flap surgery was a huge breakthrough for women with breast cancer undergoing mastectomy in the 1980s and 1990s. Instead of using an artificial implant to build a new breast, surgeons took tissue from muscle in the abdomen to give a natural transplant that would thrive in the reconstructed breast, where many implants fail. But there was a downsidethe loss of abdominal muscle resulted in a loss of abdominal strength and, sometimes, a hernialike bulge. Also, in about 30 percent of cases, fat cells in the new breast tissue would die, due to poor blood supply that caused the breast to harden.
Now, using a new variation of the TRAM-flap called a perforator flap, plastic surgeon Maurice Nahabedian has been able to avoid such drawbacks. Instead of taking the abdominal muscle itself, he only dissects the skin, fascia, fat and blood vessels from the muscle to use in the breast. Because the abdominal muscle is left intact, the incidence of weakness or bulge is significantly less. And because the blood vessels are hooked up to veins in the armpit or along the sternum, ensuring healthy blood flow through the transplanted tissue, hardening of the breast is rare.
"From both an aesthetic and functional perspective, the muscle-sparing procedure with free tissue transfer is more beneficial," says Nahabedian. "Itís their own tissue, there is a natural shape, and it lasts forever."
In some patients, however, particularly women with large breasts, muscle still must be used. In such cases, Nahabedian takes only a plug of muscle, rather than the entire muscle, to rebuild the breast. And, again, he reattaches the blood vessels microsurgically to maintain the transplanted tissue.
And finally, in the few cases when abdominal tissue canít be used because the patient is too thin or had prior abdominal surgery, Nahabedian will perform a variation of the perforator flap called the S-GAP (superior gluteal artery perforator) flap, in which he takes tissue from the buttock.
Regardless of the perforator technique, patient satisfaction is high. "You see someone who is devastated by the diagnosis of cancer go through surgery and then get right back into society, strong, confident and happy," Nahabedian says.
Hopkins is one of only a few centers in the United States that performs the perforator flap procedure.
Sometimes the simplest things make a huge difference in medicine. A group of Johns Hopkins researchers led by neurologist Justin C. McArthur have found, for instance,† that using a portable device thatís a cross between a pager and your own mother can lead to a significant drop in the amount of virus HIV patients carry in their blood or spinal fluid within half a year.
†The device isnít a new therapy: Itís an electronic gadget that verbally reminds patients burdened with a complex schedule of anti-AIDS medications when to take pills and what side effects to watch out for.† Taking the right dose of the right pills at the right time is key in the treatment of AIDS, and adherence is a major problem.††††††††††††††
The pocket-size devicewhich the researchers call DMAS, for Disease Management Assistance System, and the inventor has named "Jerry the Pharmacist"proved especially helpful for a subgroup of patients with mild-to-moderate memory problems brought on by the disease. "Now we see that a little electronic help can substantially improve compliance," McArthur says.
Patients in the study who used the DMAS stuck with their therapy, on average, 11 percent more often than those who heard a monthly half-hour pep talk on how and why to use their medications.