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an online version of the magazine Fall 2007
Medical Rounds
Mohamad Allaf
Photo by Keith Weller
Surgeon Mohamad Allaf’s new “access technique” unfolded without a hitch in late January.
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An Easier Kidney Donation

New extraction route offers hope to those on the waiting list.

 

AS AN EXPERT in both minimally invasive urological surgery and biomedical engineering, Mohamad Allaf already knew a thing or two about how to extract a human kidney through a patient’s vaginal canal. He and a few others have done it multiple times with kidneys that were cancerous or otherwise diseased.

But his case on January 29 presented an entirely new challenge. This time, it was a healthy donor kidney intended for immediate transplant. Allaf, who directs minimally invasive and robotic surgery here, had practiced the novel technique for months using animal models. Now his goal was to remove a human organ through the vaginal canal in such a way that it would emerge in perfect condition, untouched by any of the normal bacteria that dwell in a structure with external exposure. If all went according to plan, it would be the first successful transplant of a kidney removed through the vagina.

The donor, 48-year-old sales manager Kimberly Johnson, had previously undergone a hysterectomy, which meant fewer natural obstacles for Allaf. For Johnson, the advantage of the new approach was obvious. She’d be spared the five-centimeter abdominal scar offered by the usual laparoscopic technique, along with weeks of pain and compromised activity. She’d also be able to help out her sick 23-year-old niece.

“This is just an access technique,” Allaf says, explaining that the goal is to reduce the donor’s trauma while ensuring no compromise of any kind in outcomes for the recipient.

To do the procedure, Allaf used a “hybrid technique” in which a lighted endoscope and surgical wands were introduced through a small incision through Johnson’s navel. At the same time, another member of the surgical team inserted a sponge-tipped stick up through the vagina and pressed it against the organ’s back wall as a visual cue for Allaf to make a small incision for access into the vaginal canal.

Next, Allaf identified the healthy kidney and snipped away its connective vessels, then slipped it into an impermeable, sealable plastic pouch within the operational cavity. Once the pouch was sealed up with the clean donor kidney safely enclosed, an assistant with a string attached to the bag retrieved it through the small opening in mere seconds.

The elapsed time between snipping the kidney’s blood vessels and flushing it with a preservative solution is important for the organ to maintain its maximum viability. Allaf says the usual time for traditional laproscopic nephrectomy is about four minutes. With the transvaginal approach, this detail unfolded in less than three minutes. “That’s an added bonus,” he smiles.

Allaf was then able to suture the vaginal wall’s small incision from the inside. The transplant was a success, and Johnson was able to go home the next day, comparing her level of surgical discomfort to that of a tooth extraction.

The introduction of laparoscopic techniques for removing kidneys has tripled donations in the United States to 6,000 as of last year—important since some 60,000 Americans remain on the waiting list for a kidney.  From the early indications of interest, Allaf expects this breakthrough to bring forward donors in even greater numbers. He says the transplant team has taken calls from places like California and Texas.

Hoping to broaden the applications of the transvaginal extraction, Allaf is exploring ways to perform the procedure without introducing surgical instruments through the navel. “The goal,” he says, “is to do the entire thing transvaginally.”  Ramsey Flynn

 


Got Fruit?

For healthier bones, don’t overlook acid-buffering bananas and yams.

 

Floating Bananna

Yogurt’s fine. So is cottage cheese. However you can also do your bones a favor by drinking an 8-ounce glass of carrot juice and eating a banana, says Deborah

Sellmeyer ’91, the first director of the new metabolic bone center at Johns Hopkins Bayview Medical Center.
Sellmeyer studies the effect of nutrition on bone health. Her research suggests that certain potassium-rich fruits and vegetables may help prevent calcium from leaving bones, making them stronger in the long run.

“The number of people with serious health consequences because of osteoporosis is growing rapidly, especially with the aging population,” she says. “A quarter of the people who fracture their hips die within a year. Another half must use a cane or a walker. We need to do a lot more to help people from losing bone density.”

Her current clinical study, funded by the NIH, was conducted at the University of California San Franciso where she previously worked. It looks at how the source of protein in the diet determines how calcium is metabolized. Because calcium is an early marker of what leaves the bone, she says, learning how to preserve it can help arrest bone breakdown.

In the study, a group of 176 post-menopausal women was randomized to one of four diets based on a different protein source: animal, dairy, soy, or vegetarian. All diets were equal in calories as well as in total amounts of protein, calcium, and salt. Dietitians bought the food, weighed and measured it, and prepared it. Study participants picked up their meals every day for eight weeks.

“We used actual food that real people could buy in the store to see what kind of impact we could have,” Sellmeyer says.

Although she is still analyzing the data, her initial findings show that diets based on meat and other animal and dairy-based proteins cause more calcium loss because they increase the amount of acid in the body. On the other hand, low-acid vegetable and soy-based diets reduce the excretion of calcium.

“The take-home message at this point is that we need to get more fruits and vegetables into our diets for healthy bones,” she says. “There’s nothing wrong with animal foods or dairy foods, we just need to make sure we ingest high potassium fruits and vegetables—like bananas, yams, tomatoes, and oranges—that can buffer the acid.”

She hopes her data will merit a future study of such diets’ effects on bone density. Meanwhile, she’s also raising awareness of the risks of osteoporosis and other bone disorders with help from the center’s multidisciplinary team of endocrinologists, geriatricians, orthopedists, dietitians, and other specialists.

National statistics show that only 16 percent of hip fracture patients are treated for osteoporosis. She intends to make sure that all such patients at Hopkins—roughly 300 a year at Bayview—receive follow-up help and guidance at the bone center. Linell Smith

 



Birth of a Ration

How stressed plump rats could hold clues to reducing obesity in inner cities.

 

CHarles Hong
Photo by Keith Weller
> Tamashiro with one of her chubby rats.

IN 1944, AFTER the Nazis blocked supply lines, Holland suffered a famine that, naturally, affected that country’s pregnant women. As the war ended, newly-born but underweight babies were able, at last, to have normal nutrition. But ultimately, all was not well. A follow-up years later found a high proportion of the “famine babies” had become obese adults suffering from diabetes, hypertension, and cardiovascular disease.

Psychiatry’s Kellie Tamashiro, in Hopkins’ Behavioral Neuroscience Lab, says that example has partly informed her research to understand what’s behind the tripling of obesity worldwide in the last 30 years. “Like the Dutch situation, some specific interplay of environment and behavior is at work. It has to be more than genes,” she says.

Everybody knows people now eat more and exercise less. But that’s not as precise as translating a specific environmental factor or eating behavior into metabolic pathways gone wrong. And that, she explains, is where her studies are leading.

Tamashiro focuses on the effects of having sub-optimal environments either in utero or just after birth. A solid body of animal research and human studies suggests those problems create adults who avoid mirrors and populate hospitals. It’s called the Barker hypothesis: A bad early environment somehow sets metabolism to favor later obesity and diabetes.

Most research has centered on giving pregnant rats too-high or too-low nutrition. But Tamashiro also adds the effects of stress. She aims to reflect the human condition in inner cities where obesity is epidemic.

“In 1944,” Tamashiro explains, “the Dutch babies’ bodies were programmed to be more efficient than normal at saving energy.” Animal models shore this up: Short-changing maternal diet leads to obesity as pups mature. But the other extreme is true as well. In Tamashiro’s latest study, mother rats on fatty animal chow produced lardy pups at risk of abnormal adult metabolism. 

That study helped clarify underlying physiology. Starting with pregnant rats fed high-fat chow, Tamashiro noted that, as little as a month after birth, their fat pups had the elevated levels of the leptin hormone that parallels onset of metabolic disease. And glucose intolerance that foreshadows diabetes had also begun.

But stress, she found, did the same thing—unsurprising, she says, because the neural pathways that regulate mammals’ stress responses also guide metabolic balance. So pregnant rats upset by stressors such as bright lights or small quarters also have high-risk fat pups. It’s these early changes, she says, that may prime animals—or humans, perhaps—for later disease.

“Of course, it’s dangerous to generalize to people,” Tamashiro adds. “But it still lets us hope that intervening early in life could sidetrack disease.” Marjorie Centofanti


Synergy At Last

New center pools Alzheimer’s expertise, raising ability to find cures.

 

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cardin & bush
> Neurophysicist Susumu Mori's atlas of the brain's white matter helps reveal early dementia's telltale losses.

Hopkins’ Memory and Alzheimer’s Treatment Center is new, just opened last fall, and it’s something of a phoenix—having risen, not out of ashes but from a welter of clinics, patient units, and research projects across three departments and as many campuses. “We kept bumping into each other while Alzheimer’s explodes as a public health problem,” says Constantine Lyketsos, director of the center. Yet with ample clinic space now available on Hopkins’ Bayview campus and funding freed up, the value of sharing what’s best became amazingly obvious.

While the center still spans the Hopkins Hospital, Bayview Medical Center, and The Copper Ridge Institute in Sykesville, it now pools expertise. Diagnosis, therapy, dementia care—as outpatient, intermediate, or long-term—and experience in educating caregivers continue but without duplication.

Benefits to research are clear. “If you see enough patients under clinical care—our objective for next year is 1,000—a substantial number enter studies, raising our ability to find cures,” Lyketsos explains. But the new center isn’t research-driven, he points out. “We offer a continuum of care from diagnosis to death, whether or not patients are in a research protocol. We’re likely unique in the extent of that. Our studies are grounded, however, in that top-shelf clinical care.”

What Lyketsos calls “little pieces of added value” are typical:

 

  • When an Alzheimer’s diagnosis is especially difficult, center clinicians apply advanced imaging techniques originally developed for research. Working with radiologists, they’ve developed a dementia-specific protocol for the 3 Tesla MRI scanner. The scanner’s high magnetic field strong-arms needed resolution into images—enough, for example, to detect microbleeds that underlie some dementia. Combining this with more traditional PET scans brings a new capability to expose brain damage. Combined MRI and PET make diagnosis more trustworthy.
  • With Alzheimer’s being a most demanding disease, ongoing care is hard to do well. Years of research and patient contact has let center staff develop the Johns Hopkins Dementia Care Needs Assessment, an 86-item checklist and explanatory manual: Is it time to stop driving? Are you on too many medications? Are guns in the house? The approach keeps patients and caregivers from falling through the cracks. MC

Getting to the Heart of Amyloid

Drugs could hold promise in treating inherited version of a deadly heart ailment.

 

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Dan Judge
Photo by Keith Weller
> Judge hopes drugs can avert surgery.

Ten years ago, a diagnosis of cardiac amyloid was a near-certain death sentence, its perpetrator often the rogue misfolding of certain proteins that cause organ failure. Since then, says cardiologist Dan Judge, most efforts have been focused on identifying the type of amyloid in order to make better treatment decisions.

“That’s helped,” says Judge. “But the condition is still under-recognized by many physicians.” And, that’s to the detriment of thousands of patients who might be helped by promising drugs currently in trials, particularly for the inherited type.

Part of the diagnostic challenge of cardiac amyloid is its presentation. Symptoms usually occur later in life and include shortness of breath, fatigue, leg swelling, weight loss, arm and leg numbness, and even carpal tunnel—which resemble a host of other medical problems. But, cardiologists may suspect the presence of amyloid in the heart if there is discordance between an echocardiogram and electrocardiogram.

“The echocardiogram shows enlargement of the heart but the electrocardiogram shows the opposite,” Judge explains.

Then, there are several different amyloid types, and that’s where specialists like Judge have been able to make some headway in the last decade.

“Today, we now make great efforts to sort out the type of amyloid and look into additional treatment depending on the cause,” he says. Some types of amyloid—including the light chain type that begins in the bone marrow, and another type caused by inflammatory disease—are treated very differently.

It’s the inherited or familial amyloid type that may primarily affect the heart that has been the trickiest and has had the fewest treatment options, says Judge. Because it’s genetic and caused by a protein defect—in this case mutation-induced misfolding of a protein called transthyretin—the first line of defense is transplantation of the liver, which is where the mutant transthyretin is produced.

“The idea behind a liver transplant is to stop production of the bad transthyretin in order to prevent it from depositing into other organs like the heart,” says Judge. That’s not ideal and it’s difficult to do, but it’s been among the very few treatment options for this type of amyloid.

But researchers have been looking into drug therapies that can stabilize the mutant transthyretin protein. Judge is the principal investigator for Johns Hopkins in one of those drug trials, and he’s encouraged.

“This is extremely promising for patients with familial cardiac amyloid,” he says. “I’m very hopeful.”  Daphne Swancutt


Creating an EXIT

A partial delivery approach proves life-saving, allowing twin to breathe easy.

 

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cardin & bush
Photo by Carol Gentry
> The Hopkins team's surgical task was daunting: only the third such case on record.

Johns Hopkins is not known as a fetal surgery center, but don’t tell that to a large multidisciplinary team who last October faced delivering a baby with congenital high airway obstruction syndrome, or CHAOS, a condition so rare that fewer than 50 cases have been published. Not too long ago, surgeons had to make an incision in the neck and insert a tracheotomy tube to provide an airway for these newborns as soon as they emerged from the birth canal. Racing against the clock to prevent brain damage or death from lack of oxygen, surgeons most often found their efforts were futile. But in the mid-1990s, a procedure called EXIT (ex-utero intrapartum treatment) was developed, in which these babies were only partially delivered in a C-section, allowing them to remain connected to the placenta and the mother’s oxygen supply while surgeons created an airway.

“Without this procedure, this baby would die,” says Richard Elliott, a pediatric anesthesiologist who was part of the Hopkins team.

But this EXIT last fall was even more daunting because this CHAOS baby was a twin—only the third such case on record. That meant not only was the life of the sick baby—Tessa—at risk, but the life of her healthy twin sister—Juliana—and their mother, Lisa Davila, too. All aspects of care, especially anesthesia, became more complex. The same medicines given to the mother to relax her uterus and prevent contractions to reduce the risk of separation of the placenta during the procedure, for instance, would also put her at risk of potentially fatal bleeding upon delivery.

There were also the numerous unknowns of this complex case, what imaging couldn’t allow the team members to entirely see. The first one came after obstetrician Jude Crino made an incision in Davila’s abdomen and checked the position of the twin placentas within the uterus. He knew from earlier imaging that the sick baby was in a breech, or butt first, position, which ultrasound in the OR now confirmed. This position would make an EXIT impossible, and there was only one way around it. Crino reached through the abdominal incision and, with his hands pressing the outside of the uterus, manually began to turn the sick baby into the correct position.

Confident that Tessa was in position for partial delivery, Crino made an incision in the uterus, then delivered and handed Juliana off to neonatologists. Moments later, the head, chest, and one arm of Tessa emerged like a swimmer coming to the surface. But this swimmer was still connected to her mother and receiving nutrients (including oxygen) through the placenta. Otolaryngologists Stacey Ishman and Emily Rudnick quickly stepped in to see the full extent of blockage in the trachea. A cyst or a lesion might mean a natural opening they could enlarge, avoiding a tracheostomy. But looking down Tessa’s throat past the vocal cords, Ishman found only tissue where there should have been air. The only option was a tracheotomy, but looking at this trachea filled with tissue, she didn’t know precisely where to make the incision.

“Normally we assume we have a full windpipe and we can go anywhere that’s reasonable,” says Ishman. “This wasn’t the case.”

What the team did know for certain is that even on placental support they were on the clock. No matter the amount of muscle relaxants, Mother Nature was not going to wait forever to finish bringing this baby into the world. Anesthesiologists and obstetricians poured warm solutions into the uterine cavity to keep it distended and to keep contractions at bay. At the same time, Ishman and Rudnick found a little dilation in the trachea just below the obstruction, where they made the incision to insert the trach tube. Just as quickly Crino moved in and completed delivery, finally cutting the cord. Tessa joined her twin sister in the world.

The mood lightened a bit in the OR, but Elliott knew this was a worrisome time for the mother: “You have to turn off all your anesthetics and hope that mom’s uterus starts to contract and get firm and not have her bleed to death. That’s the biggest risk.”

Also, the end of this operation for some now became the beginning for neonatologists like Janine Bullard, who had myriad concerns: CHAOS babies may have underdeveloped lungs that can result in respiratory and subsequent heart problems. Some come into the world blue from lack of oxygen. But Tessa came out pink and breathing fine through the trach tube. Smiles, Bullard says, could be seen beneath the surgical masks: “The baby clinically appeared to be much healthier than we were expecting, which was a huge relief.”

“Everything that we planned for and did fell into place,” concluded Elliott.

A few weeks after the delivery, Ishman evaluated Tessa for airway reconstruction surgery, which is now scheduled for the fall: “Without this surgery, she’d never be able to breathe without the tracheostomy tube. We’re confident she will.”

Lisa Davila says she’s anxious about the surgery but looking forward to hearing her daughter’s voice for the first time after the trach tube is removed: “Her vocal cords look good, so she’ll be able to speak,” she says. “This is a very happy little baby.” Gary Logan

 


New Support for the Pelvic Floor

“Tension-free” approach meshes well with anatomy.

 

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cardin & bush
Photo by Keith Weller
> E. James Wright: A new answer for women at the end of their rope.

When she first came under his care in October of 2005, the 63-year-old office manager told urologist  E. James Wright that she’d “had enough” with recurring pelvic floor problems. She’d recently been to two other gynecologists who told her they were out of permanent solutions. Now she felt like her “insides were falling out,” as her bladder “was more on the outside of me than the inside of me.” It didn’t take Wright very long to reach an assessment. He had some long-term answers.

About 100 times in the last five years, Wright has performed a type of minimally invasive prolapse surgery to address loss of support in women’s pelvic organs. He says one in four women will suffer from the disorders in some form during their lifetime, and that up to 20 percent will experience prolapse.

The compromised support issues are a consequence of a life well-lived. His patients have typically given birth to multiple children and have been physically active over many years. Many are smokers. Some are overweight. Most are past menopause and have had hysterectomies and other surgeries that can weaken support of pelvic structures.

The condition can cause urinary retention or leakage, stool trapping and difficulty with intimacy as the bladder drops and/or the uterus slips lower, sometimes working its way through the birth canal.

Traditional techniques have shown a high rate of prolapse recurrence—in up to 15 percent of cases. Laparoscopic and open surgical techniques can also be used, but require entrance into the abdomen, adding to recovery and greater risk.

Wright says his less invasive method leaves fewer external scars, lasts longer, reduces pain and allows patients to leave the hospital and resume normal activities much faster. He describes his approach as “tension-free,” in that he creates a hammock-like structure with the mesh that cradles the targeted pelvic structures. He says the procedure is mostly accomplished trans-vaginally with a minimum number of external incisions. It can be done on an outpatient basis or a single overnight stay. Patients resume normal activities in about one or two weeks.

Wright says the mesh he uses is self-anchoring with the patient’s native pelvic tissues. “It integrates with the body’s natural supporting points,” he says, “getting back to a situation close to the normal anatomy.”

The office manager patient, Georgina Page, says she enjoyed the quick turnaround time and zero complication rate. “Dr. Wright was excellent,” she says. “He repaired the floor, the ceiling, the back wall and also touched up the bowel.” Her only remaining issue, she reports, is a rare instance of urinary leakage when she sneezes. “Otherwise,” she says, “I just want more people to know that this procedure is out there. I wouldn’t have heard about it unless a friend had told me.”  RF

 


 
 
 
 
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