Clevelandclinicmagazine Fall / 2005

clevelandclinicmagazine Fall / 2005

DEFUSING AORTIC ANEURYSMS

Beyond Earth: Exploring Space Medicine Life and Breath with Asthma Changing Transplantation Sophisticated.

The finest traditions of international service and elegance live at the Cleveland Clinic InterContinental Hotel & MBNA Conference Center.

Elegant guest rooms, high-tech amenities and easy access to medical facilities make this world-class hotel your choice for the perfect accommodations in Cleveland.

Classics, the hotel’s AAA Five-Diamond restaurant, offers the most sophisticated dining experience between New York and Chicago.

For reservations, call 1.877.707.8999 clevelandclinicmagazine FALL / 2005 contentscontentscontentscontentscontentscontentscontents Volume2Issue2

ADVISORY BOARD: CONTRIBUTORS: Glenn M. Bieler Susan Brachna Director, Communications Kathleen Colan Institutional Relations and Sandra B. Erlanger Development John Ettorre COVER STORY Kristin Hampshire James M. Blazar Wendy Hoke Chief Marketing Officer Keith Jameson Chairman, Division of Marketing Chrissy Kadleck Bruce A. Loessin Martha Laschomb Senior Vice President and Elizabeth Lear Chairman & Executive Director Cora Liderbach Institutional Relations and Lynn Novelli Development Kristin Ohlson Pamela Smith O’Hara Carol L. Moss Peter Strozniak Vice Chairman & Steve Szilagyi Executive Director Jesse Bryant Wilder Institutional Relations and Development COVER PHOTOGRAPHY: Steve Travarca William Ruschhaupt, M. D. Staff Physician, PHOTOGRAPHY: Cardiovascular Medicine Lilias Hahn Physician Director, Institutional Russell Lee Relations and Development Tom Merce Marilyn G. Wilker Joseph L. Pollack Director, Communications Steve Travarca Division of Marketing ILLUSTRATION: MANAGING EDITOR: Mark Sabo Suzanne C. Anthony Dave Schumick Institutional Relations DESIGN: Silent Bomb: Defusing the Aortic Aneurysm 28 and Development Epstein Design Partners, Inc. It affects two million people nationally and can kill in a minute. Ninety percent of people affected don’t even know they have one. Thanks to new research, much of it done at The Cleveland Clinic, patients with aortic aneurysms can now be treated with less risk, less invasive surgery and with better long-term results. Questions, comments or requests for more information: E-mail: ON THE COVER: CardioMEMS Wireless Pressure Implant. Image used with permission. [email protected] Mail: Managing Editor Features Cleveland Clinic Magazine The Cleveland Clinic/W14 Life and Breath with Asthma 10 Changing Transplantation 16 9500 Euclid Avenue Cleveland, OH 44194 Asthma is one of the most common, “The imbalance between patients waiting Phone: chronic diseases in the United States. Yet, for an organ and the available organs isn’t 216/445-4908 for all the advances made, the total as bad as it could be, but it’s still insuffi - Web: number of deaths and illnesses related to Please visit our Web site at cient to meet the demands of the waiting www.clevelandclinic.org/clevelandclinicmagazine asthma each year is increasing. While list,” says John Fung, M.D., Ph.D., many aspects of asthma remain a mystery, Cleveland Clinic Magazine is a biannual publication of Director of the Transplant Center and The Cleveland Clinic. Copyright © 2005 The Cleveland research into the infl ammatory process is Chairman of the Department of General Clinic. All rights reserved. Reproduction or use without yielding new tests and potential therapies written permission of written or pictorial content in Surgery. Meeting this challenge is spurring any manner is prohibited. Printed in the United States. that will bring much-needed relief to innovation on many fronts. Periodicals postage paid at Cleveland, Ohio. The maga- asthmatics. zine accepts no unsolicited manuscripts, photography or artwork. Publishing office: 216/445-4908. Send change Beyond Earth: Center for Space of address to: Managing Editor, Cleveland Clinic Magazine, The Cleveland Clinic/W14, 9500 Euclid Medicine Explores Solutions for Avenue, Cleveland, OH 44195 Long-Term Space Travel 22 The Cleveland Clinic realizes that individuals would like to learn more about its particular programs, services or Strange things happen to astronauts after developments. At the same time we fully respect the long periods in space: Their blood pressure privacy of our readers. If you no longer wish to receive any materials containing this information, please write drops and the lack of gravity leaches away to us at the Office of Development, The Cleveland Clinic, strength and muscle tone. The Cleveland 9500 Euclid Avenue, Cleveland, OH 44195. Clinic’s newly created Center for Space This publication is for informational purposes only and should not be Medicine is helping NASA break down relied upon as medical advice. It has not been designed to replace a physician’s medical assessment and medical judgment. Always consult first with medical barriers for long-term space fl ight. your physician about anything related to your personal health. contentscontentscontentscontentscontentscontentscontentscontentscontentscontentscontents

In This Issue

The First Word 3 Readers’ Survey 9 On the Horizon Metrics Make Sense We want to hear from you. Lights, Camera ... Readers’ Poll 9 Prevent Knee Injuries 41 The Medicine Chest The Gift of Life: Organ Donation The Chemotherapy Clock Of Masks and Men 4 42 Artiﬁ cial Disc Ask the Experts 32 Turning Off IBD Triggers 42 Provides Real Relief 4 Statin Intolerance Snifﬁ ng Out Cancer 43 Metal-Free Heart Patch 5 Millions of patients take statins to treat their high cholesterol. While most patients have no Tissue Damage Early New View for in Multiple Sclerosis 43 Detecting Heart Blockages 6 problems taking these drugs, a small number Better Foot Health experience intolerable side-effects. Heart My Story 44 and Diabetes 7 specialist Steven Nissen, M.D., discusses the This Soldier’s Battle On the Web alternatives these statin-intolerant patients By Corey Carter have to lower cholesterol and the risk of heart Diagnosis Challenge 8 as told to Cleveland Clinic Magazine attack and stroke. “I knew something was going down. There The Patient With the Can’t-Stop Cough Philanthropia were too many people standing around. Just Physicians see hundreds of patients a year, standing and looking. We had stopped with every day bringing new challenges. In Albert Maroone: 34 Good Business in Cars and Medicine traffic to let the convoy pass. Suddenly, a taxi this section, we offer our readers the chance pulled up. Two men got out and started to follow a physician through the diagnosis Karen Wilson: 35 walking away...” process. What diagnosis would you make? Building Hope Through Cancer Research Living Healthy 9Dana Hamel: 36 The Unhealthy Tan Helping Others When Fortune Smiles To read more stories from this issue go Last year, more than 50,000 Americans were to our Web site: www.clevelandclinic.org/ diagnosed with melanoma, most of them over Robert Tomsich: 37 clevelandclinicmagazine the age of 40. But what’s catching the eyes Sharing the Passion to Give of the experts is that now more teenagers Florida Focus 38 and young adults are learning they have the A Good Night’s Sleep disease, too. For many people, getting enough sleep is easier said than done. The Sleep Disorders Program at Cleveland Clinic Florida Weston diagnoses and treats patients for sleep apnea and other sleep disturbances.

2 cleveland clinic magazine wordthefirstwordthefirstwordthefirstwordthefirstwordthefirstwordthefirstwordthefirstwordthe

METRICS MAKE SENSE

The Cleveland Clinic is determined to meet and exceed didn’t. The more we learned, the better we became. Mor- the expectations of its patients. To do this, we are coming tality and complication rates went down. We were able to to rely more and more on metrics. What are metrics? They lower costs. Cardiac care at The Cleveland Clinic came to are objective measures of quality. Metrics are the numbers be ranked number one in America for 11 years in a row that enable us to remove variation, promote consistency, (and counting) in U.S. News & World Report. It’s a textbook lower costs and assure our patients that they are getting the example of metrics in action. best and most effective care for their health condition. Over the past year, The Cleveland Clinic has begun an Metrics are basic to scientifi c inquiry. That’s why their initiative to duplicate this experience in every department. application to health care is often called “scientifi c medi- I have challenged our specialists to discover precisely what cine.” Businesses like General Electric use metrics to in- measures defi ne quality in their areas of expertise. We will crease output, reduce errors and ensure that complex proj- use this information to improve quality, safety and patient ects are done right the fi rst time. Some of the most satisfaction. We also are sharing this information with re- successful companies in the world have made metrics an ferring physicians and the public in a series of specialty- integral part of their corporate culture. specifi c outcomes booklets. So far, medicine has lagged behind other industries in Establishing relevant metrics is a complex process, but the application of metrics to quality improvement. But we are determined to be successful. I have no doubt that things are changing. Increasingly, payers, regulators and li- these pioneering metrics will be closely observed by censors are demanding an accounting of health care prac- other health care providers. My hope is that they pro- tices based on sound objective data. Employer health plans vide a foundation for quality improvement throughout are offering more choice. Many plans now give members the world of medicine. the option of spending a fi xed amount for the services they When it comes to managing data, The Cleveland Clinic want at whatever provider they want. These patients need already enjoys a distinct advantage. We have made nearly a some objective basis for choosing the doctor and hospital complete transition from the paper to the electronic medi- for their care. cal record. Our databases hold an enormous But who is to lay down the law on which range of health information that can be re- metrics best measure quality in medicine? I be- trieved at the touch of a fi nger, and sliced and lieve it should be the responsibility of those who diced in a thousand different ways – without know medicine best: The people who provide it. compromising patient privacy or security. Decades ago, the Department of Thoracic You might be asking: Does scientifi c medi- and Cardiovascular Surgery began measuring cine reduce the importance of physician insight, volumes, outcomes, mortality and other data intuition and compassion? Let me assure you relevant to heart surgery. This Cardiovascular that it does not. Rather, it provides a solid Information Registry allowed us to analyze foundation where these skills can be practiced data from every possible angle. We looked for with greater effectiveness, fewer errors, and at relationships between practices and outcomes, lower cost. In this way, scientifi c medicine is fi nding evidence for what worked and what the very essence of the concept, “patients fi rst.”

Delos M. Cosgrove, M.D. CEO and President

www.clevelandclinic.org 3 themedicinechestthemedicinechestthemedicinechestthemedicinechestthemedicinechest

When Cleveland Cavaliers star for- says. “Depending on the patient’s needs, ward LeBron James was elbowed in an orthosis can be designed to restrict the face during the heat of a game, motion, protect ligaments or bones, or the force of the blow fractured a bone provide support for weakened muscles.” in his face. Fit is crucial, so the process starts with Devising a defensive strategy to let careful measurements. For James, Piel James play safely while the bone healed took the precise dimensions of his up- was the mission of orthopedic surgeon per face and skull and then used Richard D. Parker, M.D., Education and plaster to cast a facial impression, a Fellowship Director of Cleveland Clinic “negative” of his face. “We have to Sports Health and Cavaliers’ head team balance comfort with protection,” Piel physician. “If LeBron was going to explains. “The mask had to ﬁ t snugly to continue to play, he would be at high protect the facial bones, but not create risk for re-injury,” Dr. Parker explains. any pressure points.” OF “We have to balance Masks comfort with protection.” AND MEN Chris Piel, C.O., Chief of Orthotics and Prosthetics

“We wanted to fabricate a protective From the impression, Piel crafted a orthosis that would immobilize and “positive” model of James’ face to use protect the area and allow him to in fabricating the custom orthosis. play without compromising his pe- Made from high-performance plastic, ripheral vision.” “the weight of the ﬁ nished orthosis is Dr. Parker referred James to Chris another critical point,” Piel adds. “It has Piel, C.O., Chief of Orthotics and Pros- to be durable, but light enough to be thetics at the Clinic. worn daily.” “We create custom protective devices James wore his mask for six weeks, for a wide range of problems - children playing in more than 20 games, until with spina biﬁ da or cerebral palsy, peo- his facial bone healed. ple with arthritis, injured high school athletes and weekend warriors,” Piel

Image courtesy of David Liam Kyle/NBAE - Getty Images

About 65 million Americans suffer from lower back pain every year. Of these, more than 12 million are reported to have degenerative disc dis- Artificial Disc ease. As time goes by, many of these people become so disabled that Provides they need to stay motionless in bed for long hours. A new surgical procedure approved by the Food and Drug Administration (FDA) Real Relief in October 2004 may bring relief to some of those who are suffering. This new procedure, called total disc arthroplasty, involves the use of the ﬁ rst FDA-approved artiﬁ cial spinal disc implant made completely of metal and plastic. Says R. Douglas Orr, M.D., staff surgeon with the Cleveland Clinic Spine Institute, “The difference between this procedure and other options is that we are able to relieve back pain

4 cleveland clinic magazine themedicinechestthemedicinechestthemedicinechestthemedicinechestthemedicinechest

METAL-FREE HEART PATCH For several decades doctors have been trying to find ways to close holes in the heart without the need for open-heart surgery.

Now, pediatric heart specialists at The Children’s Hospital at The over the patch, making it stick to the edges of the hole. The tis- Cleveland Clinic have a completely metal-free patch that uses the sue continues to grow over several months, eventually covering body’s own healing power to seal up the hole. This option was the patch. especially appealing to the parents of seven-year-old Kelly Horn. This treatment option also appealed to the Horn family be- Kelly was diagnosed with a special kind of hole in her heart, cause Kelly has a nickel allergy, discovered when she developed called an atrial-septal defect or ASD, which is located between a reaction to nickel earrings. Although the presence of nickel in the heart’s left and right fi lling chambers. Without repair, oxygen- the metal-based devices has not been shown to cause signifi cant rich blood can back up into the lungs, causing breathing diffi - problems, Kelly’s parents felt more comfortable not having nickel culty, heart rhythm problems, heart failure or even stroke. or any other kind of metal in her heart. After the procedure, Kel- Although surgery was once standard for the four percent of ly’s mother kept her active daughter in bed for two days in the children like Kelly born with ASD, Kelly and her family were of- hospital, while the patch fused with the lining of Kelly’s heart, fered three non-surgical treatment possibilities. The option they permanently sealing the hole. chose, the “transcatheter patch,” is made of stretchy polyure- “We feel that this patch closure is a great improvement. It’s thane foam that bonds to the hole’s edges without sutures or wire. almost like having the body’s own tissue covering the defect,” PlacedLeBron against James the heart defect, the patch is held in place for 48 says Lourdes Prieto, M.D., the interventional pediatric cardiolo- hours by a small balloon. Gradually the patient’s own tissue grows gist with the team who performed Kelly’s procedure.

while preserving motion. This new scoliosis. Although not for everyone, the surgery may beneﬁ t surgical procedure is designed to patients who have a single-level degenerative disc in the lower address pain and movement issues as back and who are not experiencing nerve compression. well as reduce healing time.” The procedure generally takes two and a half to three hours Dr. Orr, who performed this pro- and patients remain in the hospital one or two days. Dr. Orr cedure for several years in Canada notes that most people ﬁ nd that their original back pain is gone before joining the Clinic, says that within a day or so; other pain resulting from the surgery usually the ideal patient is between the ages subsides within four to six weeks. Although the procedure is of 35 and 55, has not already had sur- relatively new in the United States, about 12,000 have been gery in the lumbar (lower) spine and performed worldwide. has no signs of osteoporosis and no

www.clevelandclinic.org 5 themedicinechestthemedicinechestthemedicinechestthemedicinechestthemedicinechest

New View for Detecting HEART BLOCKAGES

The coronary computed tomogra- “We can determine if soft, unsta- phy angiogram (CTA) is revolu- ble or calcified deposits are present tionizing cardiology by revealing in the arteries,” says Dr. Garcia, coronary artery blockages within adding that those results determine minutes and for about one-tenth of how a cardiologist can treat the the cost of invasive catheterization. patient - with close monitoring and Studies have shown that early lifestyle changes, use of statin drugs, detection of calcium deposits in the angioplasty, surgery or some combi- arteries can help predict whether a nation of those treatments. patient is likely to have a heart The coronary CTA is not with- attack. Usually a patient arriving out its downside, namely that it in the emergency room with chest requires training and expertise to pains is admitted for 24-hour maximize its effectiveness. “It’s more observation and diagnostic testing, common for physicians untrained in including X-rays and scans. Images this technology to see things that produced by the coronary CTA aren’t there,” explains Dr. Garcia. illustrate whether there are calcium “Training is crucial.” deposits in the arteries. Cardiologists also are concerned This three-dimensional CTA image shows “The speed, processing and qual- that the coronary CTA could be severe narrowing of the ﬁ rst diagonal coro- ity of images compared to other overused and lead to incorrect diag- nary artery. cardiac imaging, such as ultrasound, noses and unnecessary surgical treat- cardiac catheterization or MRI, is ments. Patients need to be aware superior,” explains Mario Garcia, that, as with most computed tomog- During the cardiac catheterization proce- M.D., Co-director of the Center for raphy scans, it involves higher doses dure of the same patient, this standard two-dimensional angiogram image con- Integrated Noninvasive Cardiovas- of radiation exposure. In addition, ﬁ rmed the narrowed artery. cular Imaging. The CTA scan some patients may be allergic to the produces 64 images in about five to contrast dye used. The technology’s 10 seconds. limitations also make it unsuitable Just before the scan, technicians for extremely obese patients and administer a beta-blocker to slow those with irregular heart rhythms. down the patient’s heartbeat. Using an electrocardiogram, the scan is timed to photograph the heart at the same point in the pumping cycle for six or seven beats. Once the image is received on the computer screen, technicians use tools similar to those found in graphics editing software to isolate the coronary arteries.

6 cleveland clinic magazine themedicinechestthemedicinechestthemedicinechestthemedicinechestthemedicinechest

(Image, below) This proﬁ le of the pressure distribution under a patient’s foot during walking - with the heel to the left and toes to the Better right - shows a peak of high pressure under the ball of the foot, FOOT indicating an area at high risk for ulceration. Health and Diabetes

In the United States, some 60,000 to 80,000 people with ping gives us the ability to know exactly where on the foot diabetes lose part of their leg each year to amputation - there may be problems in the future,” Dr. Cavanagh explains. usually resulting from a foot ulcer. “We know how to heal ulcers,” says Dr. Cavanagh. “We People who have lived with diabetes for 10 to 15 years can can do it within about six weeks, using a special fi berglass develop long-term complications such as peripheral neurop- cast proven to be one of the most effective ways of healing athy, which is a loss of nerve function and deadening of sensa- a foot ulcer.” tion in the legs and feet, and peripheral vascular disease, which Patients also benefi t from advanced wound-healing meth- is impaired circulation in the legs and feet. ods such as “off-loading devices,” which are inserted in the “What happens is that people will injure themselves and not shoe to redistribute weight off the affected foot, and sophisti- know it,” says Peter Cavanagh, Ph.D., D.Sc., Academic Direc- cated antibiotic therapy. “Bioengineered skin substitutes, tor of the Clinic’s Diabetic Foot Care Program. “A common which are cells grown in culture to form an artifi cial, living example is walking too far in a shoe that doesn’t fi t right or skin, also can be grafted to heal a stubborn ulcer,” adds doesn’t have any cushioning.” Patients end up with fi rst a blis- Georgeanne Botek, D.P.M., Medical Director of the Diabetic ter or abrasion which, if unnoticed and untreated, can become Foot Care Program. an ulcer - a wound that penetrates through the deeper layers The design of therapeutic footwear is a cornerstone area of of skin to the underlying tissue. Then, once they have such a research for the program.“Footwear becomes absolutely key to wound, their compromised vascular status may cause them to solving problems in the diabetic foot. We have computer mod- heal more slowly. els that help us better understand how we can manage these The Diabetic Foot Care Program sees about 50 to 60 peo- feet to prevent them from ulcerating,” Dr. Cavanagh says. ple each week. “When people fi rst come to our clinic, we “Many people with diabetes feel that amputation is inevitable map the pressure underneath their foot when they’re walk- but, in fact, it isn’t. If we can prevent the foot ulcer, there is a ing, since it’s mostly the pressure that causes ulcers. That map- strong possibility that we can prevent the amputation.”

www.clevelandclinic.org 7 onthewebonthewebonthewebonthewebonthewebonthewebonthewebonthewebontheweb

Physicians are often called upon to diagnose a wide range of symptoms and Diagnosis Challenge conditions. In this section, we offer our readers the chance to follow a physician through the diagnosis process. What diagnosis would you make?

The Patient with the Can’t-Stop Cough

Gary* was exhausted. He could barely keep his eyes on the Gastroesophageal Reflux – Characterized by a backwash of road. Not even the strongest cup of coffee could perk him stomach contents and acid into the airway, symptoms of this up. Several times during the drive to work he caught himself condition include coughing, gagging and vomiting. Also, it is veering off the road, jerking the wheel in the other direction to common for these symptoms to occur at night. get his car back on the highway. Pertussis (Whooping Cough) – Pertussis is a highly contagious For weeks he had been suffering severe and repetitive bacterial disease that affects the respiratory system. It produces coughing fits. His sleep was constantly being interrupted by spasms of coughing that may end in a high-pitched, deep inha- spasms of coughing. Midnight. 2 a.m. 4 a.m. He had hacking lation in children, although the “whoop” is rare in adults. bouts during the day, too, often ducking out of meetings to Asthma – With asthma, inflammation of the airways causes avoid the annoyed stares of his boss and co-workers. airflow into and out of the lungs to be restricted, producing Gary assumed it was nothing more than a cold, writing off the characteristic wheezing sound. Mucus production also is his symptoms as a typical winter-weather bug. But after three increased. weeks of excusing himself from the table at restaurants, sup- pressing coughing fits in public, and waking up with choking As a next step, Dr. Sabella ordered a test for whooping episodes so violent he sometimes gagged, he decided a visit cough bacteria from the back of Gary’s nose to culture in the to the doctor was in order. laboratory. In addition, he ordered a chest X-ray. Dr. Sabella then continued with his assessment. After a The Office Visit careful history and physical examination, Dr. Sabella deter- Cleveland Clinic physician Camille Sabella, mined that Gary did not have bronchitis. Although bronchitis M.D., listened to Gary explain his symptoms: symptoms can last for a couple of weeks, Gary’s symptoms several weeks of violent coughing, sometimes were too severe and prolonged for bronchitis. to the point of vomiting, and feelings of dehy- A cold was the least likely conclusion. Gary didn’t display dration. Gary didn’t experience sinus-related related complications, such as a stuffy or runny nose, sore throat problems - no stuffy head or trouble breath- or fever. Also, colds generally run their course in two weeks. Camille Sabella, M.D. ing - other than when he couldn’t catch his Because Gary is careful not to eat late or consume exces- breath during a coughing fit. sive amounts of alcohol, the likelihood of gastroesophageal Gary has no history of asthma or respiratory infections, reflux was minimal. Reflux is common following meals, and and he has no fever or abnormal temperature. Dr. Sabella Gary experiences coughing symptoms most of the time. inquired about Gary’s lifestyle and discovered that he is In addition, asthma seemed unlikely since Gary has no not a smoker and maintains a fairly healthy diet, avoiding past history of asthma, no history of wheezing or shortness of late-night dinners or excessive alcohol consumption. Gary is breath, and his physical examination was normal. married, without children, and his wife has not developed a Gary’s chest X-ray was normal and the nasal culture came cough or similar symptoms. A thorough physical examination back negative for the whooping cough bacteria, meaning Dr. of Gary was completely normal. Sabella did not find anything in the culture that alerted him Based on the described symptoms, Dr. Sabella formed a to pertussis. few theories about what Gary’s condition might be: So, what could be the cause of Gary’s condition?

Bronchitis – Gary’s cough alerted Dr. Sabella to the possibility For Dr. Sabella’s diagnosis, go to our Web site at of this common breathing condition in which the bronchial www.clevelandclinic.org/clevelandclinicmagazine tree inside the lungs becomes infected by a virus. Symptoms You can also send us an email at of bronchitis come on quickly and can persist for weeks. [email protected] and we will email Common Cold – Winter weather and an office atmosphere you the diagnosis. harbor a slew of common cold viruses. Gary might have picked up a virus from a co-worker. Fatigue and stress can *The patient and history presented in “Diagnosis Challenge” are fictional. cause colds to linger.

8 cleveland clinic magazine onthewebonthewebonthewebonthewebonthewebonthewebonthewebonthewebontheweb

Living Healthy

Microscopic image of skin cancer. The Unhealthy Tan In the United States, the percentage of people who develop violet (UV) rays. Tanning beds can provide hours of sunlight melanoma, a form of skin cancer caused by sun exposure, in minutes, and that is highly dangerous for a person’s skin, has more than doubled in the past 30 years. Each year, more especially when the practice begins at younger ages. than 50,000 new cases are diagnosed. Some people use tanning beds to get a “base tan” so they While those numbers are disturbing, another alarm is don’t burn on sun-filled vacations. However, a person doesn’t sounding: young people, without years of sunlight exposure need to have excessive sunlight to develop melanoma, Dr. like the majority of skin cancer sufferers, are increasingly Kim warns. “I have diagnosed patients with melanoma who being diagnosed with melanoma. have had very brief exposure to sunlight and may have only “Although it is still fairly rare in children, I’ve seen studies visited a tanning bed once or twice.” where cases of melanoma are found in children as young as Unfortunately, many young people still sunbathe and visit four years old,” says Julian Kim, M.D., a staff physician who tanning beds regularly. Dr. Kim believes this is because “the specializes in surgical oncology. “The concern now is that concept of cancer hasn’t sunk in to young people yet. I have we are seeing people in their late teens and early 20s being to tell college students they have a deadly disease, and they diagnosed more and more with melanoma.” look at me like it’s impossible.” In this day and age, the mental connection between tanned With all the pressure to have that sun-loving look, what do skin and good health still prevails. This concept has driven doctors tell their young patients to encourage them to avoid people to seek a sun-kissed look, whether it’s through sweating overexposure to the sun? on the beach, using artificial tanners, or “fake baking”- spend- “I tell them that the damage the sun can do to their skin is ing 10 or 20 minutes in a tanning bed. irreparable, even if it doesn’t show up until years later,” says “Although the cause of this trend of more young people Dr. Kim. “You only have one set of skin, and it has to last you with melanoma is not yet known, tanning booths are prob- your whole life.” ably a contributing factor,” says Dr. Kim. The major concern For more information about melanoma risks and safeguards, go to with tanning beds is the extremely intense, damaging ultra- our Web site at www.clevelandclinic.org/clevelandclinicmagazine

Readers’ Survey Readers’ Poll

Information From You The Gift of Life: Makes the Information Organ Donation On our Web site, readers are invited to share their in Here Better opinions about subjects from the magazine. In the “Changing Transplantation” story (this issue, page We want to hear what you think about 16), we talk about innovations on several medical fronts that Cleveland Clinic Magazine. Please take a few are changing the way we approach organ donations and minutes to go online and fi ll out our survey. transplantation. Tell us what you think in our next Readers’ Poll “The Gift of Life: Organ Donation” at As a special thanks, we’ll send you our exclusive www.clevelandclinic.org/clevelandclinicmagazine Cleveland Clinic Magazine 7-day pillbox. You can also visit our Web site to fi nd out what readers Go to www.clevelandclinic.org/clevelandclinicmagazine had to say in our last poll, “A New Kind of Offi ce Visit: Shared Medical Appointments.”

www.clevelandclinic.org 9 At fi rst, my chest is only lightly compressed; an unseen hand pushes inward against my breastbone. Refl exively, I draw a deeper breath and my ribs expand with air. Then the infl ow stops prematurely. To go on feels like my lungs are being seared, as if, ahhhh, I have stepped too close to a fi re and breathed in hot fl ame. My throat begins to tighten. I exhale and try again, the panic building. Where is my inhaler? Oh, God, where is my inhaler? Anonymous, asthma sufferer

Life and Breatha wthmaih

Asthma is one of the most common, chronic diseases in the United States, affecting approximately one in 20 people. It claims the lives of 12 people every day in the United States and the Twenty-year-old Nikki Nguyen has total number of deaths and illnesses known the perils of asthma since she related to asthma each year is increas- was three years old. “It’s been with ing. Although asthma can develop at me my whole life. I live with it every any age, it is growing fastest among chil- day,” she says. Her asthma triggers are dren - incidence among the very young many and include grass and weeds, has almost doubled since 1980 and there pollen, animal hair and viruses. She are now nine million children living with also can suffer an attack if she gets the disease. This means that not only are upset about something and starts cry- more people living with asthma, but they ing. “It’s not one thing or another also will be living longer with the disease. that brings on an asthma attack. I have to be extremely careful about where I am and what’s going on around me,” says the College of Wooster junior and chemistry major.

10 cleveland clinic magazine Despite all her precautions and The discovery that asthma is an and infections, the incidence of asth- compliance with her doctor’s orders, inflammatory disease changed the way ma has risen. Nguyen still has an asthma attack about the disease is treated. Instead of lim- “The hygiene theory is based on every other month. She can usually iting treatment to opening the air- early studies that showed that chil- end these attacks herself, within a half ways, doctors now treat the underlying dren who were around many other hour, using an assortment of medica- inflammation as well. children or animals early in life, and tions. Every now and then, though, so were exposed to more germs, had she’ll have an attack so severe that it Many aspects of asthma remain a less incidence of asthma than children sends her to the emergency room. mystery. Just as no one is sure why some not exposed,” explains Dr. Erzurum. Once, she got off a roller coaster at immune systems overreact to certain “These findings led to the hypoth- an amusement park and felt a headache generally harmless triggers, no one is esis that we may have not one, but coming on. A friend handed her a sure why the incidence of asthma keeps two types of immune defense systems painkiller that contained aspirin and, increasing in the United States and against microbes. The thought, then, soon after she swallowed it, all her other westernized countries. is that if one system lacks practice friends were looking at her with alarm. One area under investigation is fighting bacteria and viruses early in “They noticed that my eyes were swell- heredity. About one-third of all per- life - perhaps due to a very clean life- ing,” she recalls. “Then my chest tight- sons with asthma share this condi- style - the other defense system com- ened and my throat closed up. I was in tion with another member of their pensates, becoming overly powerful the middle of a full-blown attack.” immediate family. It is believed that and leading to unusual reactions to inherited asthma is more likely to come harmless substances like pollen and cat It was Hippocrates, the Greek physi- from the mother than from the father. dander. Those overreactions become cian, who first described asthma using Both allergies and asthma are strongly allergic reactions and asthma.” the Greek word for “panting.” Several associated with hereditary factors and A study done in 2000 adds another hundred years later, a Greco-Roman they share certain genetic markers, but element to the hygiene theory - the doctor named Galen determined they are not always inherited together. overuse of antibiotics in very young that asthma was caused by bronchi- Research, then, on the genetics of these children. This study found that seven- al obstruction. Galen’s treatment of conditions is confusing and difficult. and eight-year-old children who were choice was owl’s blood in wine. While studies suggest that asthma genetically predisposed to allergic dis- By the 1800s, asthma treatments runs in families, researchers don’t orders were more likely to have asthma were a little more effective, though believe there is only one gene that and allergies if they were given antibi- no less unusual. The most popular accounts for it. “There are many otics in the first year of life. cures of the time frequently contained gene regions involved, depending on Today, the hygiene theory remains alcohol, cocaine or morphine. In the the population studied,” says Serpil just that - a theory. “We need to con- late 19th century, atropine - derived Erzurum, M.D., Chairman of the sider the flip side,” says Dr. Erzurum. from the deadly nightshade plant - Department of Pathobiology. “Many “Asthma is at its worst in poor neigh- was added to cigarettes to help treat different genes are capable of leading borhoods, where there is likely to asthma. Smoking a medicinal cigarette to the same observable characteristics be more exposure to infections early made from jimson weed and chopped of the asthma phenotype.” in life, as well as greater exposure camphor, drinking strong coffee or Another hypothesis addressing the to environmental pollutants. This alcohol, taking a daily potion made of rise of asthma in westernized nations evidence runs counter to what the garlic, mustard seed and “vinegar of is called the “hygiene” theory. This hygiene theory proposes. We still are squills” - a dried plant also used for theory notes that in countries that have not sure what’s causing the increasing rat poison - were all methods used to won the battle against dirt, microbes incidence in asthma.” ward off “the asthma.” Fortunately, advances in asthma treatment were made in the early- and mid- 20th century. The big breakthrough The Annual Price of Asthma came in the 1960s when asthma was discovered to be an inflammatory dis- • Treating asthma ...... $9.4 billion ease - an overreaction of the immune • Missed days of work ...... 14.6 million system to benign substances like pollen, • Missed days of school ...... 10 million pet dander and mold spores. This overreaction causes immune cells through- • Restricted days of activity ...... 100 million out the body to increase their numbers • ER visits ...... 1.9 million in the lungs, setting off a chain of events that produces swelling in the • Deaths (approximate) ...... 5,000 airways, heavy mucus, and spasms and constriction in the smooth muscles Source: Asthma and Allergy Foundation of America surrounding the airways (see illustration, page 15). When this inflammation becomes severe, the asthma sufferer has an attack. www.clevelandclinic.org 11 “In some studies, overuse of bron- chodilator inhalers has been linked to mortality,” notes Dr. Erzurum. “Clinically, we understand how this happens: sometimes patients are overly reliant on their rescue inhalers for daily control. They may use them as much as ten or twelve times a day. What that really means is that their asthma is out of control.” If these patients have an asthma attack, the outcome can be severe - requiring emergency room care and Serpil Erzurum, M.D. hospitalization. With the exception of a few extremely invasive tests, there hasn’t been a good way to monitor ongoing inflammation in the lungs. “New tests for asthma “It’s one of the most What is known is that asthma is inflammation would help us prevent a chronic condition with continu- over-treatment, as well as avoid under- frightening things a per- al relapsing. Even between outright treatment,” says Dr. Wiedemann. attacks, constant inflammation can “With such a tool,” adds Dr. son can go through. It’s cause progressive long-term damage Erzurum, “patients could make use in the lungs, including the permanent of their medications before they get almost as if someone, to narrowing of the airways. This, in turn, symptoms and ward off an attack or, if leads to further breathing problems. there was no ongoing inflammation, “Asthma requires chronic therapy,” prevent patients from unnecessarily me, is putting me in a says Herbert Wiedemann, M.D., Chair medicating.” of Pulmonary, Allergy and Critical Two new tests that can sound an early bottle and then they put Care Medicine. “Our goal when we alert are currently under develop- treat asthma is the right medication ment. Both are tools that detect traces on the top of that bottle at the right time. If we only rely on of inflammation byproducts using less a patient’s symptoms to guide their invasive methods - one through a to cut off the circulation… treatment, then we’re lagging behind. person’s breath and the other through Their asthma-induced inflammation blood or urine. can get worse before their breathing The first tool is a breathalyzer that no air whatsoever.” capability changes and other symp- - instead of sniffing out alcohol in a toms show up. person’s exhaled breath - detects min- “However,” Dr. Wiedemann con- ute levels of nitric oxide, a byproduct tinues, “we don’t want patients taking of inflammation in the lung. medication if they don’t need it.” Nitric oxide is mostly known as an Bronchodilators, which can be environmental pollutant, produced in JACKIE JOYNER-KERSEE administered as pills, liquids or inhal- the high-temperature combustion of OLYMPIC GOLD MEDALIST ers, are still used as “rescue” medica- fuel, especially in cars. In the late tions for quickly opening up the air- 1980s, researchers determined that way. Over-reliance on bronchodila- nitric oxide also is produced by enzymes tors, however, can be dangerous. within the cells of the human body.

12 cleveland clinic magazine “Nitric oxide is the chemical media- While the exact role of nitric oxide tor for signaling in the brain - this is in asthma remains a clinical question, how our brain does much of its neu- the Food and Drug Administration rotransmission,” says Dr. Erzurum, has approved a machine - called a “‘Why, bless my life who is the principal investigator of a NIOX system - for clinical mea- five-year National Institutes of Health surements of nitric oxide in the and soul!’ said Mr. study to determine the factors lead- lungs. Patients take a deep breath, ing to asthma. “Nitric oxide also is blow into the NIOX machine, and Omer, ‘how do you produced by the cells lining the blood the level of nitric oxide is regis- vessels of our body, and it is the pri- tered instantly on a screen. When fi nd yourself? Take mary vasodilator of our system. By the patients undergo anti-inflam- a seat. Smoke not causing the muscle walls of the blood matory therapy, the machine shows vessels to dilate, it prevents hyperten- that their nitric oxide levels drop. disagreeable, I hope?’ sion. Overall, nitric oxide is essential While the machine has been used for our body to function normally.” mostly in laboratories thus far, its By the mid-1990s, new, highly sen- manufacturer is developing a small ‘By no means,’ said I. sitive tools were developed to detect hand-held model that can be used nitric oxide in the much more pre- by asthma patients at home. With ‘I like it - in somebody cise parts-per-billion range. Using this device, patients can monitor the these tools, researchers found that level of inflammation in their lungs else’s pipe.’ nitric oxide was present in the exhaled once a day or even more frequently, breath of all humans and elevated in just as diabetics monitor their blood the lungs of patients with asthma. sugar at home, and modify their ‘What, not in your own, According to Raed Dweik, M.D., therapy accordingly. The Cleveland staff physician with the Department of Clinic and three other research cen- eh?’ Mr. Omer returned, Pulmonary, Allergy and Critical Care ters began clinical trials to test the laughing. ‘All the better, Medicine, there are several theories hand-held device earlier this year. about the role of this excessive amount An even newer tool for identifying sir. Bad habit for a of nitric oxide. One theory is that asthma infl ammation involves a test for the nitric oxide found in the lungs of detecting a by-product of infl ammation young man. Take a asthmatics is produced by a different in the airways, called bromotyrosine, kind of cellular enzyme than the ones in an asthmatic’s blood or urine. seat. I smoke, myself, that produce the “good” nitric oxide, Bromotyrosine is formed within the and that this nitric oxide acts as a free lungs and airways when a group of white for the asthma.’” radical, causing damage to the cells in blood cells known as eosinophils are the airways. A second theory holds that activated and release an enzyme called the high level of nitric oxide in the eosinophil peroxidase (EPO). lungs of those with asthma is merely a “Eosinophils are the professional hit harmless by-product of the inflamma- men in the body,” says Stanley Hazen, DAVID COPPERFIELD tory process and plays no significant M.D., Ph.D., Section Head, Preventive BY CHARLES DICKENS role, either good or bad. “The third Cardiology and Director of the Center theory, suggested by some research for Cardiovascular Diagnostics and here and elsewhere, is that this nitric Prevention. “Their job is to kill invad- oxide is protective,” Dr. Dweik says. ing parasites and bacteria.” “There is some evidence that it binds with more toxic oxidants in the lungs and neutralizes them.”

www.clevelandclinic.org 13 Researchers have long known that molecules like poisons or drugs in mation causes a rearrangement of the eosinophils play a role in allergic con- bodily fluids. lung’s matrix components that, in ditions, presumably causing tissue Subsequent studies confirmed that turn, leads to the remodeling and damage and contributing to asthmat- levels of bromotyrosine relate to the narrowing of the airways, as well as to ic inflammation. However, the exact severity of asthma and may be useful as decreased elasticity. This remodel- nature of eosinophil-triggered tissue a check on the effectiveness of asthma ing has been found even in children damage had been unclear. therapy. A more portable means for with asthma, and some researchers In the late 1990s, Dr. Hazen and physicians to detect bromotyrosine, believe these changes to the extracel- several researchers at the Clinic, using blood or urine, is under devel- lular matrix may be a factor in the including Dr. Dweik, Dr. Erzurum opment at PrognostiX, Inc., a com- persistence of asthma into adulthood. and Mani Kavuru, M.D., ran a pany launched by the Clinic in 2004 Dr. Aronica hopes to determine how series of studies in which asthmatics to commercialize diagnostic tests and these particular molecules contribute were subjected to an allergic trig- treatments for inflammatory diseases. to inflammation and the development ger. During the initial study, the Dr. Hazen is the primary inventor of of severe, unremitting asthma. researchers discovered EPO-damaged these diagnostic tests and presently he Also at the Clinic, Fred Hsieh, proteins in asthmatic lungs, forming serves as a member of PrognostiX’s M.D., associate staff in Pulmonary, a specific product, bromotyrosine. Board of Directors, Scientific Advisory Allergy and Critical Care Medicine, is In additional studies, Dr. Hazen and Board and management team. studying the role of the mast cell - yet his team confi rmed that the presence The mass spectrometry-based test- another immune cell - in asthma. of bromotyrosine indicated that ing for bromotyrosine is currently In an allergic individual, mast cells eosinophil-related infl ammation was available through the specialty ref- move into the airways, proliferate on happening in asthmatic lungs. They also erence lab at PrognostiX. Scientists the inner, mucous-laden surface and were able to prove that the amount of there are also intent on creating ver- help set off asthma attacks in the bromotyrosine directly corresponded sions of the test that can be more presence of allergens like pollen or to the amount of infl ammation. widely used by general clinical labo- mold spores. “Our goal is to identify In 2000, Clinic researchers pub- ratories. The hope is that this new, specific proteins or receptors on the lished an article in the Journal of Clinical portable method will help physicians mast cells that direct their function in Investigation on their discovery, noting gauge asthma severity and responses asthma,” says Dr. Hsieh. “Then, the that this by-product of tissue damage to therapy, which in turn will help to next step is to develop a therapeutic caused by eosinophils was detectable more accurately tailor therapies for tool to specifically block this mast cell by a sophisticated form of analysis, individual asthmatics. activation in the airways.” He smiles in called mass spectrometry, in the blood anticipation, “That would be a novel and urine of asthmatics. Mass spec- While inhaled corticosteroids are treatment for asthma.” trometry is a device used by scientists the staple of current asthma therapy, Until some of this research leads to define the precise chemical struc- new drugs are under development as to new treatments, asthma sufferer ture and composition of a material, researchers painstakingly identify the Nikki Nguyen will stick to the regi- and to quantify trace levels of specific cascade of events behind the inflam- men that’s working for her: tracking matory process in the lungs and deter- the outdoor pollen counts, changing mine which chemicals can block some her routine when they’re high, keep- of these events. ing her inhalers handy, and going “For many years, asthma therapy was to regularly scheduled appointments “The lungs suffer and pretty stagnant,” says Mark A. Aronica, with her asthma and allergy special- M.D., a staff physician in Pulmonary, ist with questions and prescriptions Allergy and Critical Care Medicine that need refilling. “When I was little the parts which assist who spends 80 percent of his time and had an asthma attack it was really on asthma research. “Not any more. frightening. I would gasp and gasp and respiration sympathize Potentially, over the next five to ten never get enough air - like something years, there will be a large number of was blocking my throat.” She frowns with them.” immune-modulating therapies.” thoughtfully, then smiles. “It still can Dr. Aronica himself is studying the be scary, but I work hard to stay healthy role of the extracellular matrix - the and keep my symptoms under control. mixture of proteins and molecules With my inhalers and my meds, I’m in ARETAEUS THE CAPPADOCIAN between the cells that keeps our bodies charge, not my asthma.” 2ND CENTURY AD glued together - in the lungs during chronic inflammation. Some studies To read more about asthma, go to www.cleve- have shown that long-term inflam- landclinic.org/clevelandclinicmagazine

14 cleveland clinic magazine ALLERGIC ASTHMA ATTACK

Allergic triggers are encountered.

Inside the bronchioles of the lungs, immune cells are activated to ﬁ ght the trigger, releasing chemicals that amplify inﬂ ammation.

mast cells nitric oxide molecules Nitric oxide also triggers secretion and helps to activate mast cells that signal the smooth muscle bands around the airways to constrict, narrowing the airway itself.

infl ammation Infl ammation increases the nitric oxide production, leading to toxic reactions that further infl ame the airway.

As the attack escalates, mucus wheezing and coughing occur.

www.clevelandclinic.org 15 ChangingTransplantation

Photo by Lilias Hahn A teenage girl shouldn’t have yellow eyes. But Christine Tabar was born with biliary atresia - a liver disease where the bile ducts designed to drain bile into the small intestine aren’t functioning properly. When she was eight weeks old, Tabar had surgery, called a Kasai procedure, to reconstruct her liver and create a new bile duct. This was a stopgap measure, a “bridge” that would allow her to strengthen and grow until she was old enough to tolerate a liver transplant.

Throughout Tabar’s life, health problems suffered through two comas, from which her persisted. From as young as fi ve months doctors didn’t expect she would recover. old, she had attacks of bacterial infec- “My whole lifestyle changed,” she says. tions, called cholangitis, caused by her “I had to take early retirement, which was scarred bile ducts. When she was in sixth diffi cult. I worked there 35 years - it was grade, her malfunctioning liver caused my second home.” severe breathing problems as the blood In the fall of 2001, she went on the vessels in her esophagus dilated. Despite waiting list for a new liver. “It was the these and other setbacks, Tabar’s child- sickest time of my life,” she says. “It was hood was a happy and adventurous time. right after the September 11 terrorist at- She excelled at sports and never feared tacks and I turned on the TV and saw all trying new things. those people die, and I’m thinking I’m “I never let it stop me from doing the going to die, too.” Instead, this single things I wanted,” says Tabar. At age 14, woman was surrounded by a warm and however, her liver problems were once supportive network that helped her get again threatening her life. Blood was through her personal turmoil. backing up outside her lungs. She couldn’t dents, and more deaths due to age-related Today, Schtscherbak lives on about one- breathe. The time had come: Tabar need- diseases, such as stroke. Lastly, consent rates third of her normal liver function. “You ed a liver transplant. She was placed on have remained stagnant, with only 57 per- have to be really sick to get a transplant,” the waiting list for an available organ. cent of families of suitable donors giving she says. Every three months she goes in consent for donation. for blood work and every six months she The Long Wait for Organs A look at the offi cial solid organ trans- submits to a larger battery of tests. These Despite continuing advances in medicine plant waiting list for the United States tells yield a seriousness scale from six to 40. and technology, the demand for organs a sobering story. More than 88,000 pa- “I’ve gotten as high as 13. When you get drastically outstrips the number of organ tients are currently awaiting a transplant. up in the 20s, they tell you to be ready for donors. According to the United Network More than 61,000 need a kidney, and a transplant.” for Organ Sharing (UNOS), a private more than 17,000 need a new liver. The “The imbalance between patients wait- nonprofi t charitable organization, the average wait nationally for a new kidney is ing for an organ and the available organs chronic shortage of organ donors is the now approaching three years. isn’t as bad as it could be, but it’s still insuf- most critical issue facing the fi eld of organ Fifty-nine-year-old Helen Schtscherbak fi cient to meet the demands of the waiting transplantation today. It’s easy to see why: is one of those 17,000 hopefuls eagerly list,” says John Fung, M.D., Ph.D., Director The number of deceased organ donors has awaiting a new liver. Five years ago, she of the Transplant Center and Chairman of increased by 26 percent over the past 10 accidentally walked into a table in her the Department of General Surgery. The years (from 5,099 in 1994 to 6,455 in Parma, Ohio apartment. She thought little lingering problem has prompted the Clin- 2004), while the number of patients on of it, until awakening the following morn- ic to expand its on-site Transplant Hospi- the waiting list has increased by 160 per- ing to the sight of one leg that was black tality Unit, a 38-room guesthouse where cent over the same period of time (from and blue from ankle to hip. “It looked like transplant patients and their families who 35,751 to 82,882 candidates). a truck had hit me,” she recalls. come from out of town can live near the In addition, donor characteristics have Still, she ignored it, putting in a full day of hospital campus. “It’s a way to provide changed dramatically, with fewer deaths work at an American Greetings factory. But low-cost housing for patients who some- from trauma, such as motor vehicle acci- she soon went to the emergency room of times stay months while waiting for an her local hospital, where she learned she had organ,” says Dr. Fung. liver problems, and was quickly put on med- Image, left: Kidney surgery Image, above: Christine Tabar ication. It didn’t help. Instead, she says, she

www.clevelandclinic.org 17 Dr. Fung, who joined the Clinic in 2004, is a heavy hitter in the world of transplant surgery.

Dr. Fung, who joined the Clinic in 2004, is a heavy hitter in the world of transplant surgery. A member of the team that performed the world’s fi rst successful baboon- to-human liver transplant, he arrived at the Clinic from the University of Pittsburgh where he served as chief executive offi cer of the medical center’s renowned Transplanta- tion Institute. His impressive resume includes almost 20 years of practice with one of the most prominent transplantation specialists in the world, Thomas Starzl, M.D., who pio- neered organ transplantation techniques in the 1950s and performed the world’s fi rst successful liver transplant in 1967. The Starzl- Fung team’s breakthrough work is standard reading in many a medical textbook.

A Short History The concept of transplanting a healthy organ to replace a failing one is quite an- cient. Reports going back as far as 800 B.C. mention skin grafting for new noses and the replacement of tissue damaged from burns, injury and disease. Yet it wasn’t until the early 20th century that the transplant of vital, solid organs became scien- tiﬁ cally documented. In 1954, Joseph E. Murray, M.D., performed the ﬁ rst successful human-to-human kidney transplant. Earlier in his career as a surgeon at an army hospital, Dr. Mur- ray had noticed that the skin grafts from unrelated patients died quickly, while the grafts between identical twins survived long enough for the patient’s own skin to heal. Dr. Murray and other surgeons dis- cussed this observation, hypothesizing that John Fung, M.D., Ph.D. the closer the patients were genetically, the

18 cleveland clinic magazine slower the graft dissolution would be. cipient to a particular donor organ before After proving his hypothesis in animals, a transplant occurs. This way, you could Dr. Murray performed the world’s fi rst “The idea of predetermine the strength of the immune successful kidney transplant between the response, then tailor the [post-transplant] identical Herrick twins, Richard and therapy to that response. By being able to Ronald, at the Peter Bent Brigham Hos- transplant measure the immune response, we have pital in Boston. something to hang our hat on - before, Despite new transplant successes, rejec- tolerance is to during and after the transplant.” tion continued to be a source of frustra- tion and exploration for Dr. Murray and trick your body Building Bridges other transplant physicians, including Organ shortage and immune suppression Christiaan Barnard, M.D., who is credited into thinking are the core motivators for innovation in with the world’s fi rst successful human- transplantation. One of the areas showing to-human heart transplant. In 1967, Dr. promise is in the development of various Barnard transplanted the heart of a young the new organ assist apparatus. These are biomedically- female automobile accident victim into a engineered devices that can serve as a 59-year-old man, Louis Washkansky. isn’t from “bridge” strategy, helping patients survive Washkansky, however, did not survive longer while waiting for an eventual very long. The drugs used to suppress his another body.” organ transplant. immune system had so weakened him that This strategy has worked, perhaps best of pneumonia set in and he died 18 days after all, in cardiac transplants. Nicholas Smedira, the operation. Dr. Barnard continued ad- Peter Heeger, M.D. M.D., Director of the Clinic’s Heart Trans- vancing the science of cardiac transplanta- plant Program, says that with all the atten- tion, though the lack of effective immune tion being paid to innovative forms of suppression hampered his progress. other therapies, the number of heart transplants has stabilized in recent years. “We Tricking the Body used to do about 70 heart transplants a year, Even today, one of the most vexing but Peter Heeger, M.D., and colleagues, who and in recent years it’s been closer to 60 a critical issues in organ transplantation in- are part of an emerging transplant research year. My sense is that the number of heart volves beating the body’s natural tendency unit at the Clinic, are working on this prob- transplants is down all across the country.” to reject the new organ or tissue. The lem. The Cleveland Clinic is one of fi ve What’s on the rise, however, is the im- body’s immune response is one of the key academic medical institutions in North plantation of innovative cardiac assist de- ways it fends off invaders. Unfortunately, it America collaborating on a major fi ve-year vices. Dr. Smedira has been a key innova- cannot distinguish between a harmful in- transplant study funded by the National In- tor in one such device, the left ventricular fection and the “benefi cial” invasion of a stitutes of Health (NIH). This study intends assist device, or LVAD. This battery-oper- transplanted organ. to follow the immune responses of heart ated synthetic pump is surgically implant- It was this hurdle, in fact, that stymied and kidney transplant patients, and then ed and regulates the heart’s left ventricle, transplantation advances for years after the suggest ways to better calibrate and tailor the source of most heart attacks and other fi rst rush of excitement in the fi eld with therapies so that future transplant patients chronic cardiac problems. the successes of doctors Murray, Barnard will have positive responses. Heart pump devices have been used since and Starzl. Transplant specialists noticed at “Your body has a low-grade infl amma- the 1950s, but a new generation of these as- the time that, while they could success- tory response to a new organ, thus creat- sist devices, some of which purr along at an fully perform the transplant surgery, pa- ing the need for immunosuppressive drugs. astounding 10,000 revolutions per minute, tient survival rates were dismal. We try to understand why an organ is re- offer a real alternative to the need for trans- That picture changed for the better in jected, what the cellular and other com- planting a completely artifi cial heart. “Ob- the wake of a new and more powerful plications are,” explains Dr. Heeger. “The viously, if you could put a device that’s the generation of immunosuppressive drugs - idea of transplant tolerance is to trick your size of a wallet onto the left ventricle, you’d therapies that prevent the body’s immune body into thinking the new organ isn’t rather do that than transplant a totally artifi - system from rejecting foreign tissue. In from another body.” cial heart,” says Dr. Smedira. 1983, the Food and Drug Administration The goal driving much of the clinical While ventricular assist device (VAD) approved cyclosporine, which had an in- research on transplantation, he adds, is to technology for adults has constantly im- stant effect on the fi eld. “It was the drug understand how to improve the long-term proved, currently available devices are that most people would say revolutionized survival rates of patients who undergo much too large for children - in fact, some solid organ transplantation,” says Dr. Fung. these procedures. As recently as 1985, the adult VADs are larger than the entire body “Everything took off from there.” one-year survival rate for a transplanted of the smallest newborn. Cyclosporine works by reducing the kidney was between 50-75 percent. Today, Last year a team of Clinic pediatric spe- body’s natural immunity, thereby prevent- the national average is well over 90 per- cialists and biomedical engineers were ing white blood cells from rejecting the cent. “We’ve made great strides in short- awarded a $4.2 million, fi ve-year govern- newly implanted organ. term survival for transplant patients,” Dr. ment contract from the National Heart, Even with the success of cyclosporine, Heeger notes. “But not for long-term.” Lung and Blood Institute, a part of the chronic organ rejection remains a prob- The ultimate goal is to go beyond the NIH, to continue the development of the lem. The majority of transplant patients use of anti-rejection drugs. “What we need PediPump pediatric VAD designed espe- require long-term treatment of large doses are ways to minimize the drug treatments cially for infants and small children. of immunosuppressants, depressing their and still have good results,” says Dr. Heeger. immune system and increasing the chance “It would be helpful to be able to predict for infection and malignancies. the immune response of a particular re-

www.clevelandclinic.org 19 “Heart disease is very different in children compared to adults – extreme abnormalities of heart structure are common,” says Brian Duncan, M.D., lead investigator for the PediPump project and staff surgeon with the Department of Pediatric and Congenital Heart Surgery. “For example, some of our children are born with a single pumping chamber of the heart, while in others the heart may actually be completely backward.” The PediPump, which is still in the development phase, is about the size of a golf tee. It is designed to support the wide range of patient sizes encountered in pedi- atrics, and to provide circulatory support even in the case of extreme physical ab- normality that frequently occurs in infants and small children with heart disease. The next four years will see the early development and testing of the pump, fol- lowed by clinical studies. Although eligi- bility for FDA approval is still a long way off, the PediPump research team hopes to eventually have a fully implantable system that could support newborns with hearts no larger than a walnut.

Living Donors While the shortage of available organs from deceased donors shows little sign of abating, one of the more benefi cial movements in the fi eld is the number of transplants coming from living donors. Living donors increased from 3,102 in 1994 to 6,820 in 2004. Keith Libby and his brother Craig are just one example of this trend. Keith was born with a rare malady that mostly affects boys, called prune belly syndrome. His abdominal muscles failed to develop while he was still in the womb, leading to a number of childhood kidney infections, among other problems. Many who suffer from this syndrome die in their fi rst two years of life, or suffer chronic renal failure or clubfoot. “I spent a lot of time in the hospital as a kid,” he says today. In June 2004, after a long wait Keith received a kidney transplant at the Clinic. The donor was older brother Craig, a former Marine offi cer who served in the fi rst Gulf War. When questioned how Craig felt about offering up a kidney to save his brother’s life, Keith says with a shrug, “Craig’s attitude is, ‘see the hill, take the hill.’ You just do it. Even if it’s a really big hill. He’s tough.” But even this tough Ma- rine came to respect the grueling regimen that his civilian brother endured to prepare for an organ transplant. As a living organ donor, he went through several medical The PediPump, an artifi cial heart pump designed specifi cally to treat end-stage heart failure in screenings, blood work and countless other children, would be placed inside the blood vessels to assist in pumping blood. Brian Duncan, M.D., holds a PediPump prototype.

20 cleveland clinic magazine kinds of preparation, prompting him to ask kidney donors and recipients by looking the new organ. Today, Tabar is back at home his younger brother: “Is this what you’ve at the usual transplant list variables, such as playing the sports she enjoys most. been going through your whole life?” age and blood type, but with one distinct “Dr. Miller contributed signifi cantly to Since the fi rst living donor transplant by difference. With the new program, run by the split-liver technique used with living Dr. Murray on the Herrick twins in 1954, the Ohio Solid Organ Transplant Consor- donors and he continues to improve upon thousands of these transplants have been tium (OSOTC), someone in need of a this same technique,” says Dr. Fung. “When performed. In 2001, history was made kidney cannot get onto this registry alone. split-liver transplants were fi rst performed when more transplanted organs came from He or she must have another person sign in the early 1990s, the results were not op- living than from deceased donors, with the up as a living organ donor. This paired ex- timal. With more experience and the de- most common donation being a kidney. change program allows for better matches termination of the surgical profession, these “In the last fi ve years, there’s been a shift as many times a person willing to donate procedures now produce results that are in where kidneys are coming from,” says an organ to a loved one or a friend can’t comparable to whole liver transplants.” David Goldfarb, M.D., a transplant surgeon because they are not a match. This pro- with the Glickman Urological Institute. gram allows them to donate to someone Expanding the Donor Pool “More are coming from living donors and who is a match, as long as that person has As transplant specialists develop a better the outcomes are better. All of these things someone who can donate back to the understanding of what constitutes a are pushing us toward living donors.” original person in need. healthy donor organ, many are shedding Today, 50 percent of all kidney trans- Dr. Goldfarb, who performed the second the more rigid parameters that might have plants are performed using living donors. such paired kidney exchange transplant ruled out accepting organs from donors “The long-term safety of living with one made possible through the OSOTC pro- over a certain age. “We now use livers kidney has been established by the data,” gram, says the program is a “win-win to all from people who are up to 86 years old,” says Dr. Goldfarb. “And the emergence of parties involved.” He hopes the program at- says Dr. Miller. “That change is a result of minimally invasive surgery for donors has tracts many more people to join and that our better understanding of what makes a helped, because there’s less pain and dis- other states develop similar programs of good liver good. We now have better in- ruption involved in being a donor now.” their own. formation regarding the risks over time of The ability to perform transplant sur- any one part of the donor pool.” geries using minimally invasive techniques Splitting Livers Some of that increasing sophistication also has helped increase the use of living In November 2004, the Clinic’s liver in assessing the potential donor organ pool donors for other organs, including the transplant team learned there was a donor comes as a result of better data from re- liver, lung and pancreas. “With the liver, organ available in Michigan that was a searchers, and some comes from simply we remove only a section from the living match for Christine Tabar, the 14-year-old having more medical expertise in-house. donor to use as a transplant,” explains Dr. born with biliary atresia whose liver was “The liver transplant team here, com- Fung. “And because the liver has the abil- rapidly failing. The organ, however, was posed of six surgeons, has a collective ex- ity to regenerate, it eventually becomes designated for a local child. Not wanting perience of more than 100 years. With whole again.” to forfeit this rare opportunity, Liver Trans- more experience and better data, we can Though the lung cannot regenerate it- plant Program Director Charles Miller, make better judgments,” says Dr. Miller. self, a single lobe can be donated and the M.D., and his Clinic colleagues proposed Benefits of the improvements in remaining lung tissue expands to fi ll the performing a split-liver transplant. “This transplantation are being felt by donors donated area. way,” says Dr. Miller, “both lives could be everywhere. With living organ donations accounting saved using this one organ.” A year after his surgery, Keith Libby for only 10 percent of all liver transplants In a split-liver transplant, the liver is di- calls himself “a blessed man. They say the and less than 2 percent of lung transplants, vided along the lines of its sections or lobes, average transplanted kidney lasts just fi ve various efforts are being made to increase so that instead of one person receiving a to ten years. But, personally, I think I’m organ donations, particularly from living donated liver, two people can benefi t. going to go 30 years, based on how well donors. Recently, the American Medical Most split-liver transplants involve cut- it’s going so far.” Association (AMA) adopted a new ethics ting the liver into a three-quarter section Helen Schtscherbak, meanwhile, hopes policy to guide physicians involved in and a separate one-quarter piece, with the to join Libby some day soon. She remains transplanting organs from living donors. larger piece going to an adult and the as upbeat as she can, as she patiently According to the AMA, these are the fi rst smaller to a child. Dr. Miller, however, has awaits her new liver. “You have to trust national guidelines to be developed. The perfected a method of bisecting the organ your doctor and the whole team that’s guidelines include assigning living donors into two equal halves. “The advantage of looking out for you, because you’re in an advocacy team that is primarily con- this method is that two people still can their hands now.” cerned with the well-being of the donor, benefi t, but one doesn’t have to be a very and physician support for the develop- small child.” ment and maintenance of a national data- It was this innovative technique that base of living donor outcomes. helped to save Christine Tabar’s life. With Other groups also continue to innovate precise timing, Dr. Miller fl ew to Michigan in an effort to increase living organ dona- and removed the necessary tissue and blood tions. In Ohio, a new computer organ- vessels, while Dr. Fung began the surgery in matching program - the only one of its Cleveland to remove Tabar’s malfunction- kind in the nation - matches would-be ing liver. When Dr. Miller returned with the split liver, Dr. Fung completed the nearly day-long operation that transplanted

www.clevelandclinic.org 21 Center for Space Medicine Explores Solutions for Long- Term Space Travel

Strange things happen to astronauts after long periods in space: THEIR FACES APPEAR SWOLLEN, THEIR LEGS GET THINNER, THEIR BLOOD PRESSURE DROPS.

22 cleveland clinic magazine The lack of gravity leaches away strength and muscle tone, while radiation from solar winds, ﬂ ares and galactic cosmic rays increases the possibility of cancer.

Risks aside, humans have long gram Manager for NASA Glenn. “It’s a high-energy particles pass through dreamed of getting off the “rock” and wonderful opportunity for NASA. The human tissue with ease, causing exploring the worlds around the Earth Center for Space Medicine provides us damage to DNA and greatly increas- - not to mention traveling throughout with a direct link to the premier re- ing cancer risk. the rest of the Milky Way. As the space search at The Cleveland Clinic as we When they pass through the visual race of the 1960s propelled us for- identify biomedical issues that must cortex of the brain, the perception is ward to the current day space shuttle be resolved in support of NASA’s ‘Vi- one of bright fl ashes of light. Dr. Cava- program and the International Space sion for Exploration’ plan, which was nagh says these particles are probably Station, scientists and researchers outlined by President Bush last year.” the cause of the bright fl ashes the have attacked the problems that are Apollo astronauts commented on when part and parcel of living and working The biomedical issues involved they were on the moon. in space. Building and testing solu- in long-term space flight present To protect current and future space tions on the ground and in orbit, they major challenges. travelers, two very different approaches work toward our most ambitious goal “Two show-stoppers for interplane- to the radiation issue are being stud- yet: the odyssey to Mars. tary fl ight are radiation and bone loss,” ied. One team at the Clinic is working At The Cleveland Clinic, the newly says Dr. Cavanagh. “Until those two on a way to shield, screen and defl ect created Center for Space Medicine is problems are solved, there is very little the particles in the same way the Van lending the National Aeronautics and hope we can really spend long periods Allen belt does. This method requires Space Administration (NASA) a hand of time in space.” high fi eld magnets that have not yet in solving some of the many medical Radiation exposure becomes a criti- been fl own in space. When used aboard problems experienced by humans dur- cal concern for travel outside of low the spacecraft, these magnets would ing long-term space fl ight. Headed by Earth orbit. Intense solar fl ares release provide a safe haven for astronauts Peter Cavanagh, Ph.D., D.Sc., Chair- very-high-energy particles that can be where at least a portion of the vehicle man of the Cleveland Clinic’s Depart- as hazardous to human health as the would be sheltered from radiation. ment of Biomedical Engineering; and low-energy radiation from nuclear Another team is working on inter- James Thomas, M.D., Section Head of blasts. The Van Allen radiation belt, a vention at the cellular level to protect Cardiovascular Imaging, the center is broad band of magnetism that sur- sensitive tissues from radiation. Says working closely with engineers and sci- rounds the Earth and defl ects particles, Andrei Gudkov, Ph.D., Chairman of entists at NASA Glenn Research Cen- protects the planet from the harmful Molecular Genetics, “Specifi cally, ter in Cleveland. effects of solar fl are radiation. we’re developing drugs that repress “NASA brings the rich heritage of our “Once you travel outside the belt, the natural mechanism in each cell understanding of microgravity [zero you’re subject to very-high-energy that normally triggers cell death. gravity] to this collaboration. Working particles from the Sun and deep cos- We’ve already identifi ed several com- with the Clinic allows us access to a mic spaces, and these particles cause pounds that, acting through this large, expert staff of biomedical re- damage to the body,” says Dr. Cava- mechanism, are effective ‘radiopro- searchers and clinicians,” says Marsha nagh. “They literally destroy cells and tectants,’ allowing the cells, and our Nall, Bioscience and Engineering Pro- make a tunnel through the brain, models, to survive otherwise lethal leaving a track behind them.” These doses of radiation.”

On May 19th, 2005, NASA’s Mars Exploration Rover Spirit captured this view as the sun sank below the rim of Gusev crater on Mars.

www.clevelandclinic.org 23 Equally problematic for long-term Providing astronauts with calcium- duce the amount of exercise you need space travel is bone loss. As soon as rich foods to replace lost calcium isn’t by tenfold.” astronauts are launched into space, the solution. “That would actually com- One possible solution to developing a they start developing a negative calci- pound the problem,” says Dr. Davis. more effi cient exercise system for as- um balance by excreting more calcium “The blood then would be absorbing tronauts is a machine Dr. Davis invent- than they can absorb. “This negative calcium from both the stomach and ed called the Dynamic Exercise Coun- balance, which begins immediately as the bones. The kidneys then would ter Measure Device (see lower image, far as we know, continues unabated for have to fi lter out even more calcium, page 25). “I call it the ‘Jolly Jumper,’” as long as a human is in space,” says placing the astronaut at increased risk laughs Dr. Davis. “It’s not unlike the Dr. Cavanagh, who leads the Bone Loss for kidney stones.” infant jumper parents attach to a door- Team for the National Space Biomedi- For now, the best solution is to rein- frame to allow their infants to hop up cal Research Institute. troduce physical forces to the legs and down in. While it’s fun for the in- Astronauts can lose as much bone in while in space. “You can do that by fant, it’s also strengthening the infant’s a single month as a post-menopausal performing resistance exercise, run- legs.” The Jolly Jumper would allow as- woman can lose in a year. “Think of the ning on a treadmill or jumping up and tronauts to exercise through jumping, astronaut’s bones as a sponge whose in- down,” Dr. Davis says. “We’re looking knee bends and calf-raises. ner walls are getting thinner by the sec- at both running and jumping.” In ei- “Not only will it cut down on the ond,” explains Dr. Cavanagh. “If only a ther case, astronauts would have to be amount of time needed to exercise,” little of the bone minerals are lost, say strapped down to do the exercise. “You adds Dr. Davis, “but because it is a 1.5 percent each month, it doesn’t want their legs to experience high forc- very simple device, it needs no elec- seem like a lot. But after a 24-month es, but you don’t want the surrounding tricity and it’s easy to fi x when things time period, that sponge won’t be able spacecraft to shudder as they do it,” go wrong. That’s also key when you’re to hold up much of anything since about notes Dr. Davis. millions of miles away from the nearest a third of its support is lost.” Currently, there is a treadmill on the hardware store.” Dr. Cavanagh and his team are cur- International Space Station, but it is a rently conducting an experiment on the complex machine that requires con- As part of their space life research, International Space Station that exam- stant maintenance. The astronauts Dr. Cavanagh and his team also are ines the interconnection between exer- also have a bicycle and a resistance conducting a bed-rest study that simu- cise and bone loss in space. On board exercise device that, while effective, lates conditions in space. Previously, the station, astronauts wear a specially haven’t been successful in completely researchers noticed that patients who designed suit (see top left image, page warding off bone loss. were bed-ridden for prolonged periods 25) that measures muscle activity, “NASA doesn’t send people into of time experienced bone loss and joint movement, and forces on the feet. space to spend hours and hours exer- changes in heart function similar to By comparing the data from the same cising,” comments Dr. Davis. Existing those experienced by astronauts. “This astronaut during a day on Earth and a guidelines provide about two hours study will help us to better understand day in space, researchers hope to gain per day for each astronaut to exer- why these changes occur and what we more insight into the role of exercise in cise, including set-up and tear-down might be able to do to correct them,” preventing bone loss. time. “For four astronauts, that’s says Dr. Cavanagh. Brian Davis, Ph.D., a member of the eight hours of time when they could The study involves placing twenty- Center for Space Medicine, says that be doing experiments,” says Dr. Davis. four people in bed for three months the amount of bone loss astronauts ex- “We’re trying to learn how to keep with their bodies tilted in a slightly perience is vastly underestimated by their skeletons healthy, but reduce the head-down position. “The lack of grav- the general public. “On Earth, bone time required to do it.” ity in space causes fl uid to fl ow around loss occurs because people tend to be- To accomplish this goal, Dr. Davis and pool in the head, so we use the come less active as they grow older. employs a concept called “daily load head-down position to simulate the When astronauts are fl oating around on stimulus,” which measures the amount space condition,” says Dr. Cavanagh. long-duration space missions, their of work required by the body to keep a During the study, half of the test sub- legs are subjected to no forces whatso- healthy skeleton. “It depends on the jects are placed each day in a Zero ever.” The legs fi gure out that they number of times you put your legs Gravity Locomotion Simulator (see im- don’t need heavy minerals weighing down - as well as the magnitude of the age, page 26). Using this device, cre- them down. The calcium that comes forces. If you double the magnitude, ated a decade ago by Dr. Cavanagh, out of the bones goes into the blood- you may need only 1/10th the amount Dr. Davis and a team at The Pennsyl- stream and is fi ltered into the kidneys. of exercise. For example, if you move vania State University, subjects are This increases the risk that astronauts from walking to jumping, you may suspended horizontally off the fl oor, will develop kidney stones. double your forces, and therefore re- simulating weightlessness. With a

(continued on page 26) 24 cleveland clinic magazine ASTRONAUT MIKE FOALE WEARS SPECIAL PANTS THAT RECORD HIS PHYSICAL DATA WHILE ASTRONAUT KENNETH BOWERSOX ON THE INTERNATIONAL HE IS PERFORMING AN EXPERIMENT WITH THE SURROUNDING EQUIPMENT. SPACE STATION TREADMILL.

DYNAMIC EXERCISE COUNTER MEASURE DEVICE

www.clevelandclinic.org 25 three years away.” In March 2001, the space shuttle Discovery brought along an echocardiograph machine - which takes pictures of the heart using sound waves - to be placed on the International Space Station. This is part of the plan to fi nd new ways to diagnose and treat heart problems from long distance. “NASA knew they needed medical imaging. But most of the usual choices on earth, such as x-ray and CT [computed tomography] scan machines, are not options in space because of weight, power and safety reasons,” says Dr. Thomas. “The echocardiograph was the ZERO GRAVITY LOCOMOTION SIMULATOR obvious choice.” The long-term goal is for physicians to be able to make a space “house combination of elastic cords and causing it to swell slightly, while less call.” Prior to their space fl ight, astro- springs attached by cuffs to their blood travels to the legs, causing nauts would be given a three-dimen- arms, legs, torso, chest, and head, the them to shrink, a condition dubbed sional CT or total body scan. Once in subjects will run on a treadmill mount- “Puffy-Head, Bird-Legs” syndrome space, imaging tools such as the echo- ed vertically to the wall, pushing off a by the astronauts. cardiograph sent up in 2001 will send little with each step. “By the time astronauts get back to images of the astronauts’ hearts back In space, this push would be Earth, some of them can barely sit up down to Earth. “We’ll be able to down- enough to send the subject shooting without fainting. We need to fi nd out load their heart data from space and across the room. But the springs and just what happens to the heart in space compare the before, during and after,” pulleys of the device bring the sub- and how to keep it working properly says Dr. Thomas. jects back to the “fl oor,” simulating once back on Earth,” says Dr. Thomas. Working with NASA, the Center for gravity. “This way we’re replacing “It’s still a mystery exactly why these Space Medicine team also has been gravity. We’ll fi nd out if, by replacing things happen.” able to develop the largest echocardio- the load, we can prevent the bone Because it is so diffi cult to work in gram laboratory in the world. The ref- loss,” explains Dr. Cavanagh. space, Dr. Thomas and his team look erence information from this repository for ground-based analogs - where the will allow physicians to take data about Dr. James Thomas also is looking to load on the heart is suddenly changed how an astronaut’s heart is functioning work with these bed-confi ned sub- - to see if they can learn to predict what in space, make comparisons with infor- jects, but with a slightly different fo- will happen in space. mation from the lab and prescribe a cus. “Maneuvers to help preserve For example, because the heart has course of action. bone mass may also work for cardiac less workload in space, blood pressure All this new imaging technology health. We’re hoping to get two solu- goes down. Dr. Thomas says this is sim- will help planet-bound physicians tions for the price of one.” ilar to what happens in the body with better study the function of the heart Astronauts who have been in space aortic valve replacement. “Take the case and detect unseen leakages through for long periods of time experience car- of someone on the ground who has aor- heart valves and subtle abnormalities diovascular de-conditioning. “They re- tic stenosis [blockage of the aortic ar- that can lead to congestive heart fail- turn to Earth weakened,” Dr. Thomas tery valve]. You remove that tiny valve ure. “There is great value in under- says. “They have low blood pressures, and put in a prosthetic one: the patient’s standing how the heart responds to less blood volume and loss of tone to blood pressure drops - similar to the way an increased load, as on Earth, or a the blood vessels that haul blood the astronaut’s blood pressure drops in decreased load, as in space. It may around the body.” space.” By studying the loss of muscle allow doctors to intervene in disease While researchers have not studied mass experienced by people with aortic both in space and on Earth much ear- the long-term effects of this decon- valve replacement, Dr. Thomas and his lier,” Dr. Thomas says. ditioning on the heart, they do know team can make predictions about the heart in space. that the absence of gravity makes To read more about the health challenges of “We’re also trying to fi nd out how to pumping blood much easier in space. long-term de-conditioning, go to www.cleveland- “The heart begins to think it’s on va- deliver plain old medical care in clinic.org/clevelandclinicmagazine cation, and the blood vessels get less space,” adds Dr. Thomas. “We don’t fi rm,” says Dr. Thomas. Without grav- have the option of a twelve-hour re- ity, more blood circulates to the head turn to Earth to get to a hospital. If they’re halfway to Mars, they’re about 26 cleveland clinic magazine “The Cleveland Clinic made traveling for my care so much easier.” LORI RUMBERG Tampa, Florida

THE CLEVELAND CLINIC MEDICAL CONCIERGE A special complimentary service for our out-of-state patients and their families

From coordinating multiple medical appointments to arranging airline reservations, ground transportation and hotel accommodations, our Medical Concierge service is here to assist you before, during and after your Cleveland visit.

FOR INFORMATION ABOUT OUR MEDICAL CONCIERGE SERVICE, please call 1.800.223.2273 EXT. 55580 or email us at [email protected] It affects two million people nationally and can kill in a minute. Ninety percent of people who have one don’t even know it. Silent Bomb

DEFUSING THE AORTIC ANEURYSM

“It’s a hidden time bomb,” says Lars Svensson, M.D., Director of the Center for Aortic Surgery and Marfan and Connective Tissue Disorder. “When a patient is told they have an aortic aneurysm, their ﬁ rst reaction is usually one of shock.” An aortic aneurysm is a bubble or bulge much higher than the risk of rupture in in the aorta, the body’s main artery, people who don’t smoke.” Aortic Aneurysms in the which extends from the heart through Dr. Greenberg cautions that an ultra- United States the chest and stomach and splits into sound only detects aneurysms below the iliac arteries that feed the pelvis and the renal or kidney arteries, which • Approximately one legs. The aorta is roughly the thickness constitute about 50 percent of the cases. of a garden hose and resembles a large It takes a computed tomography (CT) in 1,500 people has horseradish or ginger root. Aneurysms scan, magnetic resonance image (MRI) an aortic aneurysm. form where the three-layer artery wall or echocardiogram to detect chest or has weakened from a breakdown in thoracic aneurysms. • 5 to 7 percent of elastin or collagen (see images, lower right). The number of aortic aneurysm people over age 60 This weakening may be caused by smok- cases in the United States has tripled ing, arteriosclerosis, hypertension (high over the past 20 years. Part of the have abdominal aortic blood pressure) or various genetic dis- increase is due to improved early detec- aneurysms. eases such as Marfan’s Syndrome. tion. “We see many more patients with If detected, aneurysms typically are chest aneurysms now because they get • Aortic aneurysm treated when they expand to twice CT scans, MRIs or echocardiograms for disease is the 13th the thickness of the aorta, about 2 other reasons, and so these aneurysms inches. Smaller aneurysms are simply are being picked up incidentally,” notes deadliest disease, monitored. Over a period of years, blood Dr. Svensson. killing 25,000 per pressure gradually inflates the aneurysm - According to Dr. Svensson, if a patient year – more than like blowing air slowly into a balloon - has an operation before an aneurysm AIDS or brain tumors. until it bursts or dissects, separating the bursts, the risk of death with surgery layers of the aorta, and usually causing is only 1 to 3 percent. “However, if a fatal internal bleeding. patient develops aneurysm dissection, “In patients who rupture the abdomi- which is different from rupture, 40 nal aorta, between 50 and 75 percent percent of those patients will die imme- die immediately,” says Dr. Svensson. “If diately, and between 1 to 2 percent will patients rupture the aorta in the chest, 95 die every hour that surgery is delayed.” percent die immediately. That’s why it’s Long-term survival also is much better very important that these aneurysms are for patients who have surgery before an picked up and treated electively before it aneurysm ruptures, rather than after. becomes an emergency situation.” Thanks to recent research, much of it done at The Cleveland Clinic, many Because aneurysms rarely exhibit aneurysm patients now can be treated symptoms before erupting, most people with less risk, less invasive surgery, and feel they can’t protect themselves against better long-term results. One of the the disease. But experts believe that advances, a sensor that measures blood many lives can be saved with a simple pressure in the vicinity of an aneurysm, ultrasound screening. is currently in trials at the Clinic. In February 2005, the U.S. Preventive Services Task Force advised all males over Like a modern-day wizard, Dr. Ouriel CT IMAGE OF A NORMAL AORTA, THE KIDNEYS AND SPLEEN. age 65 who have ever smoked to have waves a tennis-racket shaped wand over an ultrasound. Kenneth Ouriel, M.D., the abdomen of Gene Zeppernick of CT IMAGE OF AN ABDOMINAL Chair of the Division of Surgery, says he Salem, Ohio, the first person in the AORTIC ANEURYSM. would expand the recommendation. “I United States to have a wireless sen- wouldn’t say just males over 65 who’ve sor implanted inside his aneurysm. smoked. I would include other people Dr. Ouriel treated the 70-year-old - women, younger people.” Zeppernick’s aortic abdominal aneu- Roy Greenberg, M.D., Director of rysm with a stent - also known as an Endovascular Research, also believes the endograft - in July 2004. The coiled, indication should be expanded. “I think tube-like Dacron stent was threaded anyone over age 60 with a history of through Zeppernick’s groin and insert- smoking, a history of peripheral vascular ed into his aorta where it expanded disease or a family history of aneurysms into a section of tightly woven cloth should be screened.” He adds that, “the pipe only slightly smaller than the aorta, risk of rupture in people who smoke is channeling blood past the aneurysm.

www.clevelandclinic.org 29 WIRELESS PRESSURE SENSOR INSIDE ANEURYSM SAC WIRELESS SENSOR PROBE SENSOR IMPLANT

During the same surgery, a separate me was like a breeze going by.” His first all in one case,” explains Dr. Greenberg. catheter placed the wireless pressure post-operative check-up revealed that “Before, we always had this question: sensor inside the aneurysm sac, next to the stent had not leaked and that the Who is a candidate for an endograft? the endograft (see image, above center). A aneurysm had actually deflated. Now everyone is a candidate. It’s not month later, Zeppernick returned to The sensor implant has been in who can we put a stent in, it’s who should the Clinic to have his sensor read. trials for about one year. “The FDA we put a stent in. Ultimately, the ability “When he passes the wand over my will hopefully approve this within the to place conventional stent-grafts, fenes- stomach it looks like he’s detecting for year,” says Dr. Ouriel, who believes trated stent-grafts, as well as perform metal, for lost treasure,” says Zeppernick. the sensor will save lives by detecting open surgery, allows us to choose the Actually, Dr. Ouriel is looking for leaks leaks that CT scans miss. best procedure for each patient.” in Zeppernick’s stent. Even with this revolutionary endo- “Some of these aneurysms, even Until recently, some aneurysms have graft, some aneurysms in the second- though you think they’re fixed, really been untreatable. “There’s a very signifi- ary arteries remain beyond the reach aren’t. The stent can leak,” says Dr. cant number of people with heart con- Ouriel. “Sometimes you can’t even see ditions who can’t survive standard open the leak on a CT scan.” The new sen- surgery for aneurysms. It’s too invasive sor detects leaks by measuring increas- for them, too risky,” says Dr. Greenberg. Waves emanating from es in blood pressure in the aneurysm These same patients also may not be the wand, which also is sack. A high-pressure reading indicates candidates for endovascular surgery. If the stent has a leak and blood is seep- the patient’s aortic aneurysm is too close a power source, activate ing into the aneurysm. If this blood to any of the major arteries branching flow isn’t arrested, the aneurysm could from the aorta, such as the renal or iliac the sensor like a solar eventually rupture. arteries, a stent-graft inserted in that cell charged by sunrays. The sensor implant, designed in section of the aorta could obstruct those conjunction with Clinic cardiologist secondary arteries - like running a piece “It’s really slick,” says Jay Yadav, M.D., and manufactured by of hose through a branched duct and CardioMEMS, a private company, works blocking off the secondary ducts. Dr. Ouriel. like a pressure gauge in a tire. Within the past year, Dr. Greenberg “It’s a wireless sensor you place has developed a new breed of stent that outside the endograft but inside the looks like a tree trunk with cropped of the short arms of the fenestrated aneurysm,” explains Dr. Ouriel. Waves limbs forking off of it (see image right, stent. In these cases, another new type emanating from the wand, which also is page 31). A physician threads this “Zenith of endograft is used - a “helical” stent. a power source, activate the sensor like a Fenestrated Stent-Graft” - which is com- This stent, which is shaped like a cylin- solar cell charged by sunrays. “It’s really pressed to the size of a pencil - using a drical spring (see image left, page 31), slick,” says Dr. Ouriel. “The powered-up catheter through the groin.Then, using was designed by Dr. Greenberg and his sensor measures blood pressure in the X-rays to guide it, the physician inserts colleagues in collaboration with fluid neighborhood of the aneurysm, then the stent’s trunk into the aorta and plugs dynamics engineers at the NASA Glenn sends back signals to the probe, which the branches into the appropriate arter- Research Center in Cleveland. also functions as an antenna, picking up ies. Finally, the stent’s snug covering is “Our intention with the helical and reading the waves, which are then peeled off, allowing the endograft to device is to mimic what the blood relayed to a computer.” expand and fill the artery cavities. flow patterns would be normally, but The procedure takes five to ten min- “We’ll go into the two branches in the substituting the implanted graft for the utes and is painless. “I didn’t feel a thing,” intestines, the two branches to the kid- actual arteries,” says Dr. Greenberg. “We says Zeppernick. “The wand passing over neys, and the two branches to the pelvis

30 cleveland clinic magazine HELICAL STENT WITH CT OF THE ZENITH FENESTRATED TWISTING BRANCH TO STENT-GRAFT, WITH THE HOLES IN ALLOW MORE NATURAL THE GRAFT ALIGNING WITH THE BLOOD FLOW THROUGH KIDNEY ARTERIES. THE ANEURYSM THE GRAFT ONCE IT IS SAC IS STILL VISIBLE, HOWEVER, Endograft branches IN PLACE. THE BLOOD IS NOW CHANNELED to both kidneys THROUGH THE GRAFT.

developed the helical design with the stents a week and maybe two open sur- goal of preserving blood flow through geries a week,” Dr. Greenberg says. the twists and turns of the artery in the Dr. Greenberg notes that the Clinic TREATING THE best way possible, mimicking human treats more than 1,000 aneurysms a year, SMALL ONES physiology.” three times more than any other institu- To determine which variety of stent tion. “The advantage of coming to the The Clinic is participating in a - straight, fenestrated or helical - best Clinic is that you’ve got two or three study to test the benefits of treat- meets a patient’s needs, Dr. Greenberg, top experts in their fields here and we ing small aneurysms - those that who also is a radiologist, analyzes x-ray work as a team. The result is that the are less than five centimeters in images of patients’ aortas. patient gets the best operation based on diameter. Sitting at his desk, he taps the key- physical shape and the type or stage of “We don’t treat all aneurysms,” board of his computer until a color- aneurysm he or she has.” Dr. Ouriel points out. “We treat them ized X-ray of a human chest flashes when they reach a certain size. Only on the monitor. Leaning forward, Dr. Sixty-six-year-old Donald Servatka large aneurysms rupture; you don’t Greenberg points to the screen, “You was one of the first patients to have a want to do open surgery on a small subtract away everything that’s not nec- helical stent. His aneurysm was discov- aneurysm that you know isn’t going essary, like bones and other organs,” he ered by accident, although he has a fam- to rupture, so we use a cut-off of says. With a mouse click, the rib cage, ily history of the disease. “My father died about 5.5 centimeters – a little over heart and kidneys fade into the gray fog of the same thing in 1998,” he says. two inches. Aneurysms bigger than background of the X-ray, leaving the After attending a wedding in June that we recommend fixing; smaller root-like, red-brown aorta isolated and 2004, Servatka felt sick and thought ones we simply watch with ultra- much easier to study. he had contracted Legionnaires’ disease. sound and CT scans.” Dr. Greenberg examines the aneu- “A couple of days later I went to the The goal of the new study, rysm by reviewing cross-section images hospital. By that time I believed I had launched in collaboration with sliced through the width of the aorta. a bad case of bronchitis. The doctor ran medical device maker Medtronic “To evaluate the patient properly, I me through an MRI, then I was sent to and seventy other institutions, is to need to view the cross sections like the Clinic. That’s when they found aneu- determine if proactive treatment of this, sideways to the twists and turns of rysms.” Dr. Greenberg inserted Servatka’s patients with smaller aneurysms - 4 the aorta. Because it’s very contorted, helical stent in November 2004. to 4.5 centimeters - is in the best I have various complicated techniques “I was awake during the entire sur- interest of the patient. The aneu- to straighten the aorta out so that it’s gery,” says Servatka. “They’d say, ‘breathe rysm patients participating in the perpendicular to the aneurysm. If we’re in deep, and hold your breath.’ I was study are randomly distributed into going to put a stent in, this allows me in there for three and a half hours, but two groups. One group is treated to figure out the best positioning of the it seemed like twenty minutes. I was with stents; the other group is sim- stent; it has to fit just so, or else it may home three days later by two o’clock in ply monitored with ultrasound. Says block something else.” the afternoon. I couldn’t believe it. It’s Dr. Ouriel, “Three years from now Studying computer-processed imag- utterly remarkable what they did.” we’re going to look and see how the es of the aorta helps Dr. Greenberg Servatka was so impressed with his patients in the two groups did to decide how best to treat the patient treatment that he saved the box in determine if we should be treating and to develop a plan for the operating which the stent was shipped. “It came aneurysms at a smaller size with room, whether it’s a stent or an open from Australia,” he says. “The box is five endovascular grafts.” surgery. “I personally will do maybe six feet long. It looks like a model airplane came in it.”

www.clevelandclinic.org 31 expertsasktheexpertsasktheexpertsasktheexpertsasktheexpertsasktheexpertsaskthe

Steven E. Nissen, M.D. Medical Director, Cardiovascular Coordinating Center, Cleveland Clinic Heart Center President, American College of Cardiology

ANSWERS QUESTIONS ABOUT Statin Intolerance

Millions of people take statins. These drugs are the only first-line treatment for high cholesterol. Statins significantly lower levels of bad cholesterol (LDL) in the blood and reduce the risk of heart attack and stroke. They also can lower inflammation, which is increasingly recognized as a risk factor for coronary heart disease. Most patients have no problems taking statins. But for a small number of patients, intolerable side effects may occur. For these statin-intolerant patients, what are their alternatives to lower cholesterol and the risk of heart attack and stroke?

32 clevelandQ clinic magazine expertsasktheexpertsasktheexpertsasktheexpertsasktheexpertsasktheexpertsaskthe

By way of background, what are statins? How are side effects diagnosed and treated? Are there other drug alternatives? Statins are a class of drugs that reduce the They can be very hard to pin down. One A drug called ezetimibe was introduced production of LDL cholesterol by the liver. helpful test measures the level of CPK recently. A small dose of this drug effec- enzymes in patients’ blood. CPK is an tively blocks the system that transports enzyme that is released by the muscles dietary cholesterol from the bowel into the How is the liver involved? The body takes in saturated fat from sourc- when muscle cells are injured. If the CPK bloodstream. Imagine someone eating a es such as meat fat, tropical oils (coconut, enzymes are elevated, we reduce the bunch of eggs, meat or milk and having palm), butter and other sources, and the statin dosage. If it is very high, we stop the cholesterol just pass through your liver makes cholesterol out of them. About the statin. Thoughtful physicians don’t body. This is how it works. However, the 85 percent of the cholesterol in the body is give up at this point, however. They will drug can only lower LDL about 16 to 18 made, not eaten. Statins cause the liver to try a different statin. For reasons we don’t percent, because most cholesterol comes make less LDL cholesterol. understand, different statins affect certain from the liver, not the diet. Ezetimibe has individuals differently than others. not been shown to reduce the risk of heart attack or stroke. How effective are statins? Very. Since they were introduced in 1987, When do you classify a patient as “statin There’s also a treatment called niacin, we’ve accumulated extraordinary data intolerant?” which is a vitamin that is known to raise on various populations that show statins Sometimes when we’ve tried every brand HDL, the good cholesterol, and lower LDL. reduce morbidity and mortality from coro- of these drugs at even the lowest dosages, If you push the dose high enough, it can nary heart disease and stroke. the patient still experiences muscle pain, reduce cholesterol by 20 to 25 percent. weakness and/or high muscle enzymes. But niacin has its own tolerance problems. That’s when we classify them as statin It can produce muscle injury, intense Are all statins alike? intolerant. Up until that point, we work flushing of the skin and sometimes itching. There are a variety of statins available, very hard with patients to find a drug and There is some evidence for reduced mor- but each lowers cholesterol to a different dosage that might work. bidity and mortality with niacin. extent. Some are, milligram for milligram, more potent than others. Some cause more side effects in some patients than How many people are statin intolerant? Do any other over-the-counter products in others. Statins also differ in their ability Approximately 1 to 2 percent of the people lower cholesterol? to turn off inflammation. Earlier this year, who try statins cannot tolerate them. That Not really. There are advertising claims I published an article in the New England may not sound like many, but when you for everything from garlic products to food Journal of Medicine suggesting that the consider that tens of millions of people take supplements like red yeast rice. Most of ability of a statin to lower CRP [C-reactive statins, this becomes a significant number. what’s sold out there is not useful, possibly protein, a marker for inflammation] was fraudulent, and will likely not do anything an important predictor of its ability to slow What alternatives do statin-intolerant to lower levels of bad cholesterol. the progression of coronary artery disease. patients have? One of the drugs I tested gave patients a There is a class of drugs called bile acid How can a patient find the right alternative much greater reduction in CRP and also sequestrants – also known as a cholesterol- to statins? seemed to play a major role in slowing binding resin. These are resins that actually Work with a specialist. We have a preven- atherosclerosis. bind up the cholesterol and pass it out of tion clinic here that’s very sophisticated. the system. They are taken several times a They will hang in there with patients and day as a powder mixed in fluid or pills. What are the side effects of statins? work with them to find the right therapy. The most common side effect is muscle When you are a statin-intolerant patient, pain or weakness. As many as 3 to 5 How effective are bile acid sequestrants? you’ve got to seek out an expert. You’re percent of patients who take statins experi- These sequestrants can remove 12 to 15 getting into an area where you want some- ence some muscle symptoms. The most percent of the cholesterol from the body. body with a lot of experience and who’s concerning side effect is rhabdomyolysis, Statins, by comparison, can lower choles- going to keep trying alternatives and find which is the breakdown of muscle tissue terol levels by 50 percent or more. So the something that works for you rather than into the bloodstream. Fortunately, this is sequestrants are much less effective. They giving up. extremely rare. also can cause bloating and other unpleas- ant gastrointestinal effects.

A www.clevelandclinic.org 33 philanthropiaphilanthropiaphilanthropiaphilanthropiaphilanthropiaphilanthropiaphilanthropia

GOOD BUSINESS IN CARS AND MEDICINE

Dealership leader Maroone gives to continue legacy of care and research.

Al and Kit Maroone

ard work and good and get back home around 10:00 at In 2003, Mr. Maroone needed spine service are two of the night,” says Mr. Maroone. “I’m lucky to surgery and he became a patient of outstanding charac- be married to Kit. She’s amazing. She’d Robert Biscup, D.O., Chairman and teristics Al and Kit have potential customers lined up in the Director of the Cleveland Clinic Florida Maroone embody. living room waiting for me when I got Spine Institute. Although the Maroones’ These qualities have been key to their home. I’d sell cars at the dealership dur- admiration for the Clinic had begun in success in the last 50 years, helping them ing the day and then sell more at home earlier years, after his surgery Mr. create a dealership network that contin- until maybe midnight.” Maroone became a fan of Dr. Biscup ues today. The Maroones also perceived The hard work paid off and the and the Clinic’s exceptional work in the these same traits in Cleveland Clinic Maroones were able to purchase a sec- spine and neuromuscular areas. In sup- Florida, inspiring them to pledge $2 mil- ond dealership, this time in a Buffalo port of these endeavors, the Maroones lion in support of continuing world-class suburb. Innovative advertising through have dedicated $2 million to expanding care for generations to come. full-page newspaper ads, personally star- the Cleveland Clinic Florida Spine To say that in his early life Mr. ring in his own television commercials Institute in Weston. Maroone was driven to succeed would and back-of-the-bus ads, and sponsor- “They just don’t come any better be an understatement. In the early 1950s, ship of numerous athletic teams brought than Dr. Biscup,” Mr. Maroone says at age 26, he achieved success as one of people into the dealership. But the good enthusiastically. “Thanks to him, I’m in the youngest general foremen at the Ford service, such as a car wash and follow-up pretty good shape now. I play golf, exer- Motor Company in Buffalo, N.Y. phone calls, kept customers coming cise every day, walk, ride a bike, lift However, he and his wife, Kit, agreed he back for all of their car needs. weights - I’m able to do just about any- should learn the other end of the business Mr. Maroone explains his core phi- thing I want, even after two surgeries.” - selling cars. losophy, “Once you get a customer, you Just as word-of-mouth advertising “So I quit my job where I was making make sure you give them the right deal, worked for their dealership business, the good money and went into selling cars the right service and take care of them Maroones are hard at work for the for about a third of that,” Mr. Maroone even after the service. You want that Clinic. Mr. Maroone, who recently laughs. Eventually, with a little direction customer for life.” retired from being Chairman of the from Ford, he purchased a dealership in In 1977, the Maroones, along with Cleveland Clinic Florida Leadership tiny Middleport, N.Y., using his mother- son Michael, took their strategy to Board, explains, “We spread the word in-law’s house as collateral. After that, Miami, purchasing a bankrupt dealer- about the Clinic wherever we can. After the work really began. ship and, again applying hard work and you get people to go to the Clinic and “The key to my success? It was all good service, made a profit in their first they experience the great patient care about hard work. I was a 24/7 type of year. The business continued to grow there, they’re a customer for life.” guy - I’d leave early in the a.m., drive 32 and in the late ‘90s became a part of the miles away to run the dealership all day, Auto Nation group.

34 cleveland clinic magazine philanthropiaphilanthropiaphilanthropiaphilanthropiaphilanthropiaphilanthropiaphilanthropia

BUILDING HOPE THROUGH CANCER RESEARCH

Wilson endows Brain Tumor Institute chair.

fter losing both her father and Dr. Barnett. Her mother’s husband, mother to brain tumors, Karen Melvin H. Burkhardt, also continues Wilson is taking an active role active support of the Brain Tumor in advancing research and treat- Institute, including the establishment of ments at the Cleveland Clinic an additional endowed chair. Brain Tumor Institute. She “My mother’s gift, given 11 years recently committed $2 mil- ago, helped to create the Brain Tumor lion to establish an endowed chair in Institute. These gifts build on each pediatric brain tumor research and fund other. Through them, patient care and other laboratory research at the Brain treatment improve and provide for the Tumor Institute. research that will ultimately lead to a “This gift is dedicated cure. They make a difference,” says to my parents, to support Ms. Wilson. research, develop new The grandmother and former teacher treatments and find a felt especially compelled to help chil- cure,” says Ms. Wilson. dren with her endowment. In addition “Back when my dad to the pediatric chair, a portion of her had his tumor, we didn’t gift will support the investigative work have the diagnostics, so we of Robert J. Weil, M.D., the newly didn’t even know what recruited Associate Director of Basic kind of tumor he had. Research at the Brain Tumor Institute. We’ve come such a long “It is my hope that this gift will help way in diagnosing and to make a positive difference in the treating cancer,” she notes. treatment and survival rate of future Ms. Wilson’s father died of cancer patients,” Ms. Wilson says. a malignant brain tumor Beyond her own philanthropy to when he was 49 years old. expand what her mother helped start, Ms. Wilson’s family Ms. Wilson serves on the Brain Tumor has played an instrumental Institute Leadership Board. As chair- Karen Wilson (back) with her grandchildren (front, role in the evolution of the Brain Tumor man of the board and chief executive left to right): Morgan Lyons, Rachel Partain, Hannah Institute. Before her passing, her mother, officer of her family-run business, Lyons, Stacey Partain and Samantha Partain. Rose Ella Burkhardt – who was a patient Central Distributors of Beer, Inc., of Gene Barnett, M.D., Chairman, Brain Romulus, Mich., she organizes an Tumor Institute – made a gift to help annual golf outing, which has raised establish the institute and create the Rose $70,000 in four years to benefit the Ella Burkhardt Chair, currently held by Brain Tumor Institute.

www.clevelandclinic.org 35 philanthropiaphilanthropiaphilanthropiaphilanthropiaphilanthropiaphilanthropiaphilanthropia

HELPING OTHERS WHEN FORTUNE SMILES

Entrepreneur Dana Hamel pledges gift to create endowed Cosgrove Chair.

t his summer “I have tremendous respect for Dr. end of November that I said to Dr. Cos- home on beautiful Lake Winnipesaukee Cosgrove and I believe in supporting grove, ‘How about after Christmas?’ He in New Hampshire, Dana Hamel enjoys medical research and education at The countered, ‘How about this week?’” Mr. his retirement activities: the manage- Cleveland Clinic. I knew the money Hamel laughs. “So our kids came to ment of investments, along with a little would be spent wisely by the Clinic.” Florida for Thanksgiving. When it was fi shing, a little tennis, and lots of visiting Mr. Hamel worked with Clinic devel- over, they hopped on a plane to go home with his children and grandchildren. opment offi cers to set up the endowment and I was off to Cleveland.” But Mr. Hamel has yet another, avid fo- in the area of cardiothoracic surgery. The Mr. Hamel was one of the fi rst of Dr. cus for his retirement - he spends a gen- funds have been used to bring in visiting Cosgrove’s patients to have minimally in- erous amount of time and effort on phi- physicians to share their research and ex- vasive double bypass surgery, which only lanthropy. “It’s important to remember pertise with Clinic physicians. “The peo- required two small incisions, rather than a that you didn’t get where you are by ple in development were friendly and got single large one through the chest. “I had yourself,” he remarks. “You should help to know me and my family very well. surgery on Friday and less than a week others if you’re fortunate enough to be That’s important when you’re fi guring later I was back in Florida riding my bike able to.” An entrepreneur throughout out how to set up your philanthropic sup- three miles,” recalls Mr. Hamel. his life, Mr. Hamel achieved success as port,” Mr. Hamel says. “The service they After his heart surgery, Mr. Hamel the co-founder of a Princeton, N.J., provided was superb and we worked out and his late wife, Kathryn, became company that specialized in consumer all the details together.” friends with Dr. Cosgrove. “He [Dr. products. Mr. Hamel’s relationship with the Cosgrove] has been extremely helpful to “I try to put my money where it will Clinic began in 1997 when he was diag- me over the years, and is always willing have the biggest bang for the buck,” says nosed at another institution with heart to make time when I need him,” Mr. Mr. Hamel. One of his more recent disease. “When I tried to evaluate where Hamel says. “I enjoy visiting with him, charitable ventures was the creation of a to go for treatment, every place I talked but don’t like to bother him,” he adds. $1.5 million endowed chair at The to compared themselves to The Cleve- “He’s got a great hospital to run.” Cleveland Clinic, in the name of Delos land Clinic,” he recalls. “A close friend Cosgrove, M.D., now the Chief Execu- in Florida recommended the Clinic and tive Offi cer and President of the Clinic. Toby [Delos] Cosgrove.” At the time, Dr. Cosgrove was Chairman of Thoracic and Cardiovascular Surgery. “I knew how bad the blockages were in my arteries,” Mr. Hamel says, “and I was trying to fi gure out how long I could wait before having surgery. It was at the

36 cleveland clinic magazine philanthropiaphilanthropiaphilanthropiaphilanthropiaphilanthropiaphilanthropiaphilanthropia

SHARING THE PASSION TO GIVE

Tomsichs’ enthusiasm and dedication expand national, global support for the Clinic.

obert Tomsich regularly Mr. Tomsich also Mr. Tomsich and fields calls from friends has taken a hands-on his wife Suzanne’s and acquaintances across approach at the Clinic as enthusiasm for the the nation who are seek- the lead volunteer fund- Clinic inspired their ing a physician referral at raiser. His involvement personal pledge The Cleveland Clinic. began with spearheading at the Medallion This may seem like a the effort to raise $15 Society level to the strange role for the million for the Cleveland campaign for a new chairman of Nesco, Inc., an international Clinic Digestive Disease Center. In just 10 Heart Center. However, they feel that industrial and service business, but as Mr. months the campaign reached its philan- this is only the beginning of their work Tomsich explains, it’s a natural fit when thropic goal. Soon after, Mr. Tomsich was for the Clinic and have offered their hos- you consider community loyalty. asked to serve as volunteer chair of the pitality to many prospective supporters, Mr. Tomsich views himself and others $300 million campaign for a new Heart spreading the excitement for the Clinic’s not by their contributions in business, but Center. In this capacity, he initiated the work across the country. through personal efforts to better their Medallion Society, a special recognition In the past few years, Mr. Tomsich communities. He not only generously for those who contribute $1 million or also has been instrumental in establish- supports the arts, education and health more to the Heart Center campaign. To ing organized groups of Clinic support- care in the Cleveland region, but also gives Mr. Tomsich’s surprise and delight, many ers, referred to as “chapters,” across the his time and business sense to many not- people have joined at this level. United States and worldwide from South for-profit organizations’ governing boards, “I have found that people are so willing Africa to the United Kingdom, generat- including the Clinic’s Board of Trustees. to donate time and money - they get the ing excitement and international support As one of the Clinic’s most passion- same passion,” he marvels. “People who for the Clinic. The Heart Center cam- ate and devoted volunteers - holding have never been asked to support before paign has achieved three record-breaking a position on the Board of Trustees are giving their millions to this new years of donations and is nearing its goal Executive Committee and chairing the Heart Center.” of $300 million. Heart Center Campaign - Mr. Tomsich Mr. Tomsich’s personal allegiance to In addition to the Clinic, Mr. Tomsich is pleased to serve as a medical messen- the Clinic stems back to his youth, when has supported many worthy endeavors in ger, connecting people in need with the Charles Brown, M.D., saved his mother’s the community. Volunteering his time and Clinic, whether they require medical care life. “The physician dedication today is resources to support medicine, though, or philanthropic information. the same as back in my mother’s time,” has proven especially fulfilling. “It’s the he explains. “The Cleveland Clinic is a institution itself that inspires you to help. powerful, moving institution of fine doc- When supporting health care, I feel there’s tors and nurses. They have such intensity an almost immediate, concrete benefit to for their work.” everyone. Once you’re involved as a trustee or donor, you become very passionate about advancing the work of the Clinic.”

www.clevelandclinic.org 37 floridafocusfloridafocusfloridafocusfloridafocusfloridafocusfloridafocusfloridafocus A good night’s slee

SLEEP CENTER SETS SLEEPLESS ON PATH TO SWEET SLUMBER In May 2004, Floridian Robert Bartolotta packed up his motorcycle and cruised to the nation’s capital where he met his father, a veteran, and other relatives for the dedication of the National World War II Memorial. He could have ﬂ own to this historic event with the rest of his family, but instead jumped at the chance to tour the scenic Blue Ridge Parkway.

f the dedication had been ﬁ ve months “I was shocked. I knew I had apnea, but body’s blood pressure does not temporarily earlier,I Bartolotta would have passed on this I didn’t realize I was on the ‘top ten’ list,” drop as it would during deeper sleep. When once-in-a-lifetime experience. His then undi- he says. breathing stops during an apnea, additional agnosed sleep apnea, which involves inter- Surprise and denial are common reac- stress is placed on the heart. All this effort ruptions in breathing throughout the night, tions to an obstructive sleep apnea diagno- prevents both the mind and body from reju- deprived him of deep sleep and turned him sis, says Laurence Smolley, M.D., Sleep venating and can lead to cardiovascular into a “walking zombie” by early afternoon Center Medical Director and Chairman of problems such as a round-the-clock in- every day. He simply would not have felt safe the Department of Pulmonology at Weston. crease in blood pressure. on the nearly 3,000-mile roundtrip motorcy- These episodes of halted breathing, referred “It’s like exercising all night,” explains cle excursion. He didn’t even feel entirely to individually as an “apnea,” cause a drop Sleep Center chief polysomnographic tech- safe on his daily drive to work. in blood oxygen levels and trigger the brain nologist Patrick McMahon. “That’s why ex- “At least two times on my 24-mile com- to try to wake the body, which is when an cessive night sweating is a common side mute I can remember doing a quick nod be- apnea sufferer gasps for air and rouses from effect of sleep apnea.” hind the wheel,” says Bartolotta. In February, sleep. But because the individual awakens The most drastic treatments for obstruc- this ongoing fatigue brought him to the Sleep for such a short period, he or she does not tive sleep apnea include surgery to remove Disorders Program at Cleveland Clinic Florida remember the apnea. the tonsils, uvula (the little piece of ﬂ esh Weston, where he was diagnosed with severe The effects, however, can be serious. that hangs down in the back of the throat) obstructive sleep apnea. Through overnight Each apnea occurrence dis- or other tissue, while mild to moderate cas- observation, it was determined that Bartolotta rupts the body’s natural pro- es can be addressed with dental applianc- actually stopped breathing several hundred gression to deep sleep. In a es. Losing excess weight and avoiding alco- times a night, anywhere from a few seconds perpetually lighter sleep, the hol and smoking can eliminate or improve to a minute at a time. heart does not enter its nor- the severity of obstructive sleep apnea as mal resting state well. For his severe case, Bartolotta didn’t and the want to undergo surgery, which is not

Robert Bartolotta

38 cleveland clinic magazine floridafocusfloridafocusfloridafocusfloridafocusfloridafocusfloridafocusfloridafocus

Image, left: Electrode placement for a sleep study.

Image, right: A sleep technologist monitors a patient during a study.

guaranteed to fi x the problem, and instead Though all this wiring and equipment In cases of suspected sleep apnea, the opted for a treatment called Continuous might seem a bit intimidating, the room in sleep study is recommended to confi rm di- Positive Airway Pressure (CPAP). which Bartolotta sleeps is anything but. agnosis, which is based mainly on medical Sleep Center technologists fi tted Barto- With soft lighting, rich wood paneling and history. A follow-up study, usually performed lotta with a mask and machine to keep his jewel-toned bed linens framed by an ornate on a second night but sometimes during the airway open at night. This CPAP device is a headboard, the accommodations are more second half of a single-night study, allows shoebox-sized air pump connected to a reminiscent of a hotel than a medical labo- technologists to customize the pressure set- facemask by a long tube. It pressurizes the ratory. “Except, of course, for the white ting on a CPAP machine. air he breathes just enough to prevent his board with the ‘Nursing Assistant’ note on airway from collapsing as his throat muscles it,” laughs Bartolotta. yes light up behind metal-rimmed relax during sleep, but not so much that he The unusually inviting hospital setting is Eglasses when Dr. Smolley, an exuberant pul- can’t easily exhale. Bartolotta compares it to one of the quality assurance requirements monologist, describes his team’s work. The wearing a scuba regulator, from the feel of that recently earned the four-bed Sleep Cen- center’s contributions have been added to a the mask to the oddly comforting sound of ter accreditation by the American Academy recent wave of change in the fi eld of sleep air streaming in and out. of Sleep Medicine (AASM). To gain this sta- medicine, a development driven by the seri- From the first night Bartolotta wore the tus, the center passed a full inspection by an ous health risks posed to at least 40 million CPAP device, the number of apneas he accrediting physician who scrutinized every- Americans who suffer from chronic sleep experienced was significantly reduced. thing from lab techniques to bathroom facili- disorders, according to the National Insti- He felt more energetic during the day ties. The academy standards are designed to tutes of Health. and his daytime blood pressure went ensure the highest quality levels in patient While physicians have been aware of down as well. His commute was no lon- care and comfort. cardiovascular implications of sleep apnea ger a cause for worry. After nearly a year Staff credentials also are an important since the 1970s, it was only in the late of using the device, he returned to the factor in AASM accreditation. After a patient 1990s that physicians and researchers Sleep Center to undergo evaluation for a such as Bartolotta visits the lab, one of three started assembling solid clinical and labora- more compact, travel-friendly version. registered polysomnographic technologists tory data, says Dr. Smolley, who built the pours over the sleep study, called a poly- Sleep Disorders Program from the ground t the Sleep Center, a technologist somnogram, viewing six hours’ worth of up when he came to Cleveland Clinic carefullyA measures Bartolotta’s head and captured data in 30-second increments. Florida in 1995. attaches small metal electrodes to his scalp (see graph, page 40). As lines plotting the “There’s strong evidence today that CPAP and face with a toothpaste-like adhesive. patient’s life functions zigzag across the treatment for obstructive sleep apnea is in- These will measure brain waves and facial computer screen, the technologist notes valuable. It not only helps a patient get a muscle movements as he sleeps. The sleep transitions into various sleep states and good night’s sleep and feel better the next technologist also adheres electrodes trailed sleep disturbances, such as apneas. He as- day, but it can abort the cardiovascular con- by a rainbow of wires to Bartolotta’s legs signs a score based on the number of dis- sequences of sleep apnea - the high blood and chest to track muscle motion and turbances. As the American Board of Sleep pressure, the heart failure and cardiac ar- heart rate. A blood oxygen monitor clips Medicine-certifi ed director, Dr. Smolley re- rhythmia,” says Dr. Smolley. “And there’s a onto a fi nger, and a tube to measure airfl ow views any conclusions made. very strong association between atrial fi brilla- is inserted in his nostrils. Belts around the Almost all of the more than 1,000 patients tion and sleep apnea.” chest and waist will measure the physical referred to the Sleep Center each year are Beyond cardiovascular consequences, in motion of breathing, and a video camera suspected sleep apnea sufferers. The Sleep April 2005 the Archives of Internal Medi- stands by to capture tossing and turning. Center also evaluates individuals with other cine reported study results associating Two technologists will be on hand all night sleep disorders, such as restless leg syn- sleeping for less than six hours or for more to ensure the electrodes stay attached and drome and narcolepsy, which entails ex- than nine hours a night with increased risk indicate activity in patient data logs. treme sleepiness and a tendency to fall asleep at inappropriate times. www.clevelandclinic.org 39 floridafocusfloridafocusfloridafocusfloridafocusfloridafocusfloridafocusfloridafocus

Tracking Apnea In the sleep study graph below, each line represents the signal from a different electrode on the body. By tracking brain waves, breathing, heart rate and muscle movements, technicians can identify sleep patterns and disturbances, such as the apnea evidenced here by the halt in airﬂ ow through the nose and mouth (green box).

BRAIN ACTIVITY

FACIAL MOVEMENTS

HEARTBEAT LEG MOVEMENT

CPAP AIRFLOW NOSE AND MOUTH AIRFLOW CHEST AND ABDOMINAL MOVEMENT

BLOOD OXYGEN LEVEL HEART RATE

of diabetes and impaired blood sugar (glu- study drug therapies. He says that he typi- To further enhance the comfort and effec- cose) tolerance. cally fi nds success treating disorders, such tiveness of CPAP treatment, Dr. Smolley ex- With the dangerous effects of sleep disor- as insomnia, with behavioral therapies in- pects an explosion in engineering for new ders better defi ned, the latest industry re- cluding relaxation techniques and having CPAP masks and interfaces in coming years, search and development efforts have fo- patients get out of bed when not drowsy in- offering more consistent pressure and cus- cused on successful treatments. Recently a stead of “trying too hard” to fall asleep. tomized comfort. He also anticipates the new sleeping pill, eszopiclone, was deter- Dr. Smolley also applies his behavioral ex- fi ne-tuning of “smart” CPAP machine de- mined safe for use for up to 12 months. pertise to introducing the CPAP machine signs that automatically adjust air pressure “The conventional wisdom was that gradually. The Sleep Center team regularly on the fl y to improve the effectiveness for pa- sleeping pills shouldn’t be taken for more holds talks on sleep apnea and CPAP for at- tients such as Bartolotta. than two to three weeks,” says Dr. Smolley. risk groups, such as seniors and gastric by- “I would like to not have to use CPAP “The whole sleep community is in a bit of an pass surgery candidates. Education about someday,” says Bartolotta. “But until that upheaval regarding any possible change in sleep apnea and the benefi ts of CPAP treat- day comes, I’m really glad it’s there.” the AASM’s recommendations on how long ment and gradual acclimation to the device a sleeping pill can be taken.” are crucial to an individual sticking with the In addition to the Sleep Center in Weston, Fla., The Dr. Smolley believes the controversy is treatment, says Dr. Smolley. “A CPAP ma- Cleveland Clinic operates a Sleep Disorders Center going to be between behavioral and cogni- chine is like a pair of dress shoes: It takes with a sleep lab in Cleveland, Ohio. tive therapists and pharmacologists who some getting used to.”

RATE YOUR SLEEP ONLINE Do you wake up tired? Wonder if you should undergo a sleep study? The Epsworth Sleepiness Scale is a screening tool that helps determine whether individuals are candidates for a sleep study. Take the quiz online at www.clevelandclinic.org/clevelandclinicmagazine.

40 cleveland clinic magazine onthehorizononthehorizononthehorizononthehorizononthehorizononthehorizononthehorizon

Lights, Camera... Prevent Knee Injuries

And the Oscar goes to... osteoarthritis when they are only in their the same movements as the athlete,” a Cleveland Clinic research scientist? 30s or 40s (most people don’t get arthri- says Dr. van den Bogert. “Because the That’s right. Antonie J. van den Bogert, tis until their 70s). What’s more, women computer model moves the same way Ph.D., with the Lerner Research Institute’s athletes are five times more likely to injure that the athlete does, we can do hundreds Biomedical Engineering Department, won their knees, but no one knows why. Dr. of experiments on the computer model an Academy Award earlier this year for van den Bogert’s research aims to find the rather than on the person.” For example, his technical work in developing motion answer to that question and to determine by manipulating the computer model, capture software, which is being used by whether new athletic techniques can be researchers can find out what kind of top Hollywood producers to create three- developed to help athletes reduce or pre- knee stress is produced when the feet are dimensional animation based on human vent knee injuries. placed in different positions. movements. His software helped to build Dr. van den Bogert recently brought in “We think that these knee injuries occur some of the animated characters in block- 10 men and 10 women college basketball in athletes not because they run and jump buster movies such as “The Lord of the athletes to record their common move- along, but because their movement is Rings” trilogy and “I-Robot.” ments with special, high-speed cameras. poorly controlled,” he says. “We’re hoping So what does all of this have to do with The athletes wore tiny balls that acted as that our computer simulations will give us health care? Plenty. markers on their bodies, tracking their insights about improving the control of an Knee damage is the most common motions. The balls reflect light back to the athlete’s movements to see whether we injury for high school, college and profes- camera, creating a three-dimensional, high can reduce the propensity for injury.” sional athletes. While advances in orthope- contrast image. All of this information is Dr. van den Bogert’s software also is dic surgery can repair knee injuries, most then fed into the motion capture software. being used to study foot and ankle injuries athletes who have had such injuries suffer “We created a computer model of each incurred on uneven surfaces, and in gait person and that computer model performs and posture rehabilitation.

Data from the athlete’s motions are fed through motion capture software and a model (image, far left) is created that can be used again and again to simulate human movements and develop injury prevention strategies.

www.clevelandclinic.org 41 onthehorizononthehorizononthehorizononthehorizononthehorizononthehorizononthehorizon

Everyone has an internal clock, a genetic who reported on how the internal clock con- timepiece that controls a broad range of trols the response to one of the widely used metabolic, cellular, physiological and behav- chemotherapeutic drugs - cyclophospha- ioral activities. Understanding which genes mide. The results were published earlier this control the variations in these daily activities year in the Proceedings of the National could lead not only to new cancer therapies, Academy of Sciences. but also to the best time of day to apply “Within the last eight years, the genes the chemotherapy those therapies. that govern the circadian system have been The concept is simple: If you know when identified and explored and we’ve made clock a person is more sensitive to chemotherapy tremendous gains in the area,” says - that is, when less of a toxic chemical is Dr. Antoch. “This is the first link established needed to achieve the same cancer-fighting between the molecular mechanics of the effect with fewer physical side effects - drug internal body clock and the effect of thera- therapies can be directed accordingly. The peutic drugs.” result would be to more carefully administer Dr. Antoch and her colleagues also will therapies to the time of greater tolerance. be investigating biological and medical Marina Antoch, Ph.D., Cancer Biology, is possibilities for “re-setting” a person’s inter- among a group of researchers at the nal clock so that the body will think it’s Cleveland Clinic Lerner Research Institute receiving therapy during the most effective and the Howard Hughes Medical Institute part of its daily rhythm.

Turning Off IBD Triggers Inflammatory bowel disease (IBD) affects more compound called hyaluronan. This compound than one million Americans. During inflam- is essential for the body’s ability to repair itself matory flare-ups, a hallmark symptom of IBD, and is found in the joints, liver, skin, eyes erosion of the inner lining of the intestine and intestine. occurs, causing bleeding, diarrhea, fever and “When these long, complex cables of hyal- abdominal pain. uronan are produced, white blood cells will Cleveland Clinic researchers Scott Strong, come and sit on them,” says Dr. Strong. “The M.D., and Carol de la Motte, Ph.D., with the white blood cells then become activated, Department of Colorectal Surgery and the releasing their own chemicals, attacking and Department of Pathobiology, want to find a way eroding the interior lining of the intestine.” to stop the inflammation and erosion process Although much more research is needed to associated with IBD. To do this, they are focus- fully understand this cell mechanism, Clinic ing on how cell mechanisms within the bowel researchers are looking at several options that work and how they trigger IBD symptoms. would essentially prevent IBD flare-ups from Researchers believe that environmental occurring. These options include halting the triggers, including microbiological agents and excessive production of hyaluronan or promot- viruses, begin the process of inflammation and ing the breakdown of hyaluronan. Another keep it going in the intestine of patients who possible option is to interfere with the white are genetically susceptible to IBD. blood cells that attach to the hyaluronan, Dr. Strong’s team has found that when a preventing the release of chemicals that virus infects muscle cells in the intestine, perpetuate inflammation. the cells will make big, long cables of a

The long green hyaluronan cables attract white blood cells, shown here as the round blue balls, which then attach themselves to the cables.

42 cleveland clinic magazine onthehorizononthehorizononthehorizononthehorizononthehorizononthehorizononthehorizon

The electronic nose, a device long used for nose was programmed to detect certain safety and quality control in the food, wine characteristics in breath and used algo- Sniffing Out and perfume industries, may also be used rithms to create patterns viewable on a in the future to detect early evidence of computer screen. Researchers found the lung cancer. pattern characterizing the breath of lung CANCER Known as the Cyranose, the electronic cancer patients was distinctly different nose is a hand-sized device that uses from that of healthy patients and of people biosensor technology to produce a "smell with other lung diseases. Their findings print" of the volatile organic compounds were published in the American Journal of that comprise human breath and other Respiratory Medicine earlier this year. airborne compounds. “Our work indicates that the electronic Led by Serpil Erzurum, M.D., Chairman nose can be used as a non-invasive tool for of the Department of Pathobiology at the the early diagnosis of lung cancer and to Cleveland Clinic Lerner Research Institute, monitor the effectiveness of treatment on researchers speculated that the electronic lung cancer patients,” says Dr. Erzurum. nose could be used to detect and distin- The electronic nose could enable physi- guish between lung diseases, particularly cians to determine the appropriate course lung cancer. for a lung cancer patient’s treatment at an Testing their theory, they found the earlier stage, rather than after the cancer exhaled breath of lung cancer patients had has spread to other parts of the body and specific characteristics that, in fact, could is more difficult to treat. The small, be detected with the device. In their study, portable nature of the electronic nose Cleveland Clinic researchers examined the also will make it easy to use in physician exhaled breath of 14 lung cancer patients offices and outpatient settings. and 45 healthy patients. The electronic

Tissue Damage Early in Multiple Sclerosis

Multiple sclerosis (MS) is a debilitating disease that attacks “Although we’ve known that the progression of MS is associat- the brain and spinal cord, resulting in the loss of thinking ed with inflammation,” says Dr. Fisher, “what we didn’t know ability, muscle control, balance, vision and sensation. In a is how and when the inflammation contributes to brain tissue long-term research study that focuses on how the disease loss.” These inflammatory events attack the myelin, the tissue progresses and how it contributes to the that covers and protects the nerve fibers in loss of brain tissue over time, Elizabeth the brain and spinal cord. Oftentimes, Fisher, Ph.D., a biomedical engineer, the patients will recover from these and her colleagues have determined inflammatory events, especially in the that permanent damage in the brain early stages of the disease. can be detected at an earlier stage of “But because patients usually MS than previously thought by using recover from inflammatory events magnetic resonance imaging (MRI). during the early stages of the dis- Dr. Fisher says these findings could ease, it was difficult to determine help validate new treatments for whether or not there was residual MS patients, therapies that could be damage to the brain,” Dr. Fisher says. used to prevent inflammation at a much “However, when we look at the images, earlier stage of the disease and therefore prevent we’re seeing severe damage that results in permanent brain early brain tissue loss. tissue loss. We previously thought that the severe residual In 1997, Dr. Fisher developed landmark software that pro- damage was a late-stage complication of MS. Now it appears vides accurate measurements of minute changes in the brain the damage is actually happening early on in the disease.” even in the early stages of MS. In collaboration with Richard Rudick, M.D., and other neurologists at the Cleveland Clinic From the same patient, the image left is from 1990 and the image right Mellen Center, Dr. Fisher has been following about 60 MS is from 1998. With MS, the brain tissue atrophies over time and the fluid- patients over a period of five to 14 years with MRI exams. filled spaces, the black areas in these images, expand. This is an extreme case, with a lot of atrophy. A more typical amount of atrophy could not be detected by the eye, but is now detectable by the measuring software created by Dr. Fisher.

www.clevelandclinic.org 43 mystorymystorymystorymystorymystorymy storymystorymystorymystorymystorymystory

This Soldier’s battle

By Corey Carter as told to Cleveland Clinic Magazine

I knew something was going down. There were too many people standing around. Just standing and looking. We had stopped trafﬁ c to let the convoy pass. Suddenly, a taxi pulled up. Two men got out and started walking away...

Iraq is a hot place. Temperatures get up to not in the Red Zone. A stopped convoy is shrapnel had damaged a group of nerves 120 degrees in the shade during the day. a target for insurgents. So we have to keep under my collarbone. These particular Traveling the highways is even hotter - them moving. nerves, called the brachial plexus, control like an infernal hair dryer blasting non- We started the day at 5 a.m., escorting a my arm, my bicep. He thought that aggres- stop in your face. At night, you peel off small convoy down to Balad Air Base, 68 sive surgery and grafting might improve my your gritty, sweat-ringed uniform and kilometers north of Baghdad. At 7 a.m., we odds for a good recovery. Dr. Boulis was grab some sleep, sharing your bunk with came to an intersection. My truck was the skeptical, however, that I’d get back com- a bunch of sand fl eas. fi rst in to block off the intersection, stop- plete function. I was determined to prove But the worst part is that you wake up ping traffi c to let the convoy through. him wrong - I wanted full feeling and full every morning knowing you’ve got to I was in the back of the truck scanning motion in my arm, my hand and my fi n- leave the relative safety of your base and the area. I noticed a bunch of people stand- gers. I was determined. travel out into the “Red Zone” where the ing around on my right. I panned back to We did the surgery in December. Dur- farther you go, the more dangerous it gets. see what they were looking at, and that’s ing thirteen long hours, they took a nerve The adrenaline starts pumping. Everything when the explosion came. out of my left leg and sewed it into my is your business. You notice small details. It’s Shrapnel fl ew everywhere. I was knocked shoulder. A month later, I was able to not only your life at stake, but the lives off my feet. I tried to push myself up, but move my arm. you’re protecting. something was wrong: I couldn’t move my Dr. Boulis was amazed. I was way ahead It affects you. But you have to do it. I’ve arm. I couldn’t even feel it. I’d been hit. My of schedule. He didn’t expect that much been in the Air National Guard now for arm was paralyzed and bleeding. movement for another month. That was six 10 years, with the 121st Refueling Wing. Within an hour, I was back at the base, in months ago. Now, the feeling is coming In December 2003, I was living in Co- surgery. Shrapnel had shredded my shoul- back into my hand. My palm is almost back lumbus, Ohio, working as a mechanic at der, slashing through the nerve and artery. to normal. I can move my fi ngers and wrist. Ryder Truck Rental and taking care of I’d lost a lot of blood. But I wasn’t scared - I I can make a fi st. My tricep works. Now my family. In January 2004, I was called up knew they’d take the best care of me. Dr. Boulis and I are talking about a second for duty in Iraq. The docs at the base sealed me up and surgery for my bicep. I go to physical ther- My unit shipped out to Speicher Air sent me home. I ended up at Wright-Pat- apy twice a week. I’m working hard, and Base, in Tikrit, where I worked as a vehicle terson Air Force Base in Dayton. I was glad haven’t forgotten my goal of regaining full operator craftsman. In civilian terms, a to be back in Ohio, but I still couldn’t move feeling and motion. driver. My unit supplied traffi c security or feel my arm. I was getting concerned. Things are getting better. I’m not uptight for convoys. You see, a convoy can’t stop - The Wright-Patt docs couldn’t repair the about what happened. I served my country. nerve damage in my arm, so they sent me I did my job. I’d do it again – gladly. to see Dr. Nicholas Boulis at The Cleve- land Clinic. Dr. Boulis explained that the

44 cleveland clinic magazine We save lives 24/7. Now you can too.

Simple to use. Tax deductible. Always available. www.clevelandclinic.org/giving “29-year-old pediatric cardiology fellows aren’t supposed to need heart transplant surgery.”

Over 100 doctors select The Cleveland Clinic for their heart surgery every year.

Dr. Jennifer Shih of Cincinnati, Ohio was one of them. For more information on the heart center rated #1 in the nation by U.S.News & World Report, call us toll-free at 866/289-6911. Or visit www.clevelandclinic.org/heartcenter.

Non-Profit Org. U.S. Postage

Office of Development/UA20 PAID Cleveland, Ohio 9500 Euclid Avenue, Cleveland, OH 44195 Permit No. 4184 www.clevelandclinic.org/giving