Oriented to Thoracic Transplant Recipients -- July 1999

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FIXING BRAINS

By Daniel Q. Haney - AP Medical Editor

BOSTON (AP 5/2/99) Scientists want to fix the things that go wrong inside your head. Their plan: Grow replacement parts for broken brains.

They make it sound easy. Just brew a batch of gray matter. Drill a hole in the skull. Put in the new stuff. Wire it up like the original.

Voila! New brains.

Despite its whiff of mad scientist run amok, this scenario is surprisingly close to reality. Researchers can already do amazing things with mouse brains. And as they so fondly and frequently point out, mice really are an awful lot like us.

Some human experiments already hint at what's possible. Since the 1980s, doctors have cautiously tested transferring brain cells from aborted fetuses to victims of Parkinson's disease. For some, it seems to work remarkably well, restoring lost control of movement.

But to those on the cusp of this new technology, Parkinson's is almost too easy. It involves the death of just one small bit of material, the brain cells that make the message-carrying neurotransmitter dopamine.

Now they have their sights on much more complicated targets. In the years to come, they see the possibility of rewiring broken spines, patching up strokes, correcting multiple sclerosis, undoing inherited metabolic disorders, maybe even rebuilding the wrecked brains of Alzheimer's disease victims.

"I mean not just putting in cells to produce a neurotransmitter or make a little local connection," explains Dr. Jeffrey Macklis of Children's Hospital and Harvard Medical School in Boston. "I mean really rewiring complex circuitry in the brain. Ten years ago, this would have been considered totally crazy. Five years ago, it would have been a little bonkers."

Macklis goes on to talk about his mice, the critters of choice for those who study such things. When immature cells are transplanted under precisely the right conditions, they migrate across the animals' tiny damaged brains. They take root in just the spots where they are needed. They morph into the exact brands of cells that are missing. They connect up with other parts of the brain. In short, they seem to work.

"Mice brains are fundamentally not that different from humans'," says Macklis. "The idea of using immature cells and guiding their differentiation to rebuild complex circuitry is no longer crazy."

Until recently, human fetuses were the only source of brain material for such jobs, but they were never ideal. Doctors' qualms go beyond the ethical thickets of recycling aborted material.

Fetuses will always be in short supply; it takes several to treat just one patient. And quality is hard to control, especially considering that many were aborted for a reason, such as genetic abnormalities. But now scientists seem certain that transplanting brain material - what they call cell therapy - is about to become practical. The reason is the discovery of entirely new reservoirs of brain material. At dozens of universities and biotech firms, they are developing three main varieties - animal brains, cancerous growths and the tissue wellspring called stem cells.

One of these sources can be found at a gleaming biomedical lab off a country road about 60 miles west of Boston. The first thing that makes the place seem a little odd is the technicians' getups: green surgical scrubs with knee-high black rubber boots. Then there's the smell.

Despite fans that turn over the air 19 times an hour and filter it cleaner than an operating room's, the lab carries a certain barnyard redolence, an unmistakable eau de pig. This lab is also a barn, home to 65 or so grunting, rooting animals. But the end product is brain parts, not pork chops. "This is literally the cleanest pig facility on the face of the earth," says David Boucher, the veterinary technician who makes sure the walls sparkle, the germs stay far away and the animals themselves enjoy unpiglike spotlessness.

It may be the world's most expensive pig facility, too. The 275-pound Yorkshire sows - "the girls," Boucher affectionately calls them - cost between $20,000 and $30,000 apiece to raise this way. However, the price will fall dramatically if pig cells are approved for routine human medical use, and production scales up.

When it's time for a still-experimental transplant, the technicians kill three artificially inseminated pigs that have been pregnant exactly 27 days. Then they surgically remove their fetuses. (Killing the sows, they say, is the only way to get the unborn pigs out antiseptically.) It takes the brains of 26 pig fetuses to gather 48-million dopamine producing cells, enough for one person with Parkinson's. The cells are shipped to a hospital, and less than 72 hours later, they are inside someone's brain.

So far, these pig cells have been tested on 20 people with Parkinson's, six with epilepsy and six with Huntington's disease. Of the first 11 Parkinson's patients treated, three improved significantly.

"I have no doubt this can work and produce tremendous benefit," says Dr. Greg Stewart of Genzyme, which is developing the treatment with Diacrin, another biotech firm.

While the supply of fetal pig cells is not a problem, there are other drawbacks. Patients may need to take immune-suppressing drugs to keep their bodies from rejecting the tissue, and there is a remote chance that dangerous animal viruses might be passed along.

"I don't think it's an elegant way to solve the problem," says Dr. Michael Levesque of Cedars-Sinai Medical Center in Los Angeles.

A bit more elegant, perhaps, is a method being tested at the University of Pittsburgh. Doctors there are experimentally transplanting human cells into the brains of stroke victims.

The cells are similar to stem cells, the factories that manufacture various kinds of tissue inside the body. But there's a catch: These cells began as cancer, grown in test tubes from a 22 year-old's testicular tumor.

The transplants are being tested on 12 stroke victims. All suffer paralysis or other serious disability, even though the strokes destroyed only a small bit of their brain tissue.

Three seem to have improved. One walks better; another is less stiff, while a third has better control of arm and leg movements. Are the extra cells responsible? Or is this the natural course of recovery?

Dr. Douglas Kondziolka, the surgeon in charge, does not know. Still, he says, "We were hoping for a glimmer of efficacy so we could continue on. We've seen even a little more than a glimmer."

Fixing a stroke, however, is far more challenging than relieving Parkinson's. A stroke leaves a dead zone inside the brain. Missing are many kinds of cells that were hooked up in complex patterns.

In their attempt at repair, surgeons add their cancer-derived cells to the ring of damaged tissue that surrounds the dead area. Just why this might do some good isn't completely clear. But the doctors speculate that the new cells help the hurt ones by restoring connections, releasing neurotransmitters and pumping in amino acids.

As best they can tell, the transplanted cells have been transformed from cancerous gonadal cells to stable nerve cells through a series of manipulations. But the idea of using cancer cells makes some doctors uneasy. Others worry that the challenges of repairing strokes are just too vast to even attempt yet.

"I do believe that we will be able to treat strokes and the more complicated disorders. I just don't think we're ready to do that yet," cautions Dr. John Kessler of Albert Einstein College of Medicine in New York City.

Many agree that the most elegant solution of all to the supply problem is stem cells. These are the body's mother cells. They divide over and over to form new tissue, such as blood cells and skin.

For generations, scientific dogma held that the adult brain cannot repair itself, because it lacks stem cells. Wrong. Recently, scientists found that adult brains do indeed harbor stem cells, although their exact function is still a mystery. But when coaxed properly in a test tube, they will divide over and over again, making brand-new neurons.

Suddenly, it seems, cancer cells and animal cells may be unnecessary. The real thing, human brain cells, will be available. But what kind of stem cell is the proper seed?

Since stem cells divide endlessly, a single sample started from a human fetus could provide all that's needed. But the recipient's immune system might attack these as foreign. Perhaps the patient's own body is a better source of stem cells.

At Cedars-Sinai, scientists isolate stem cells from tissue saved during brain operations on Parkinson's patients. In the lab, these stem cells produce new brain cells. These in turn mature into dopamine makers, the specific kind of brain cells that people with Parkinson's lack. Finally, they are put back into the patients' brains.

Even if this works, however, the approach has an obvious shortcoming. The only source of these brain stem cells is the patient's own brain, not a particularly accessible reservoir.

However, brain stem cells may not be a necessary ingredient for custom-making new brain tissue. Scientists believe it may be possible to reprogram more readily available kinds of stem cells, such as the ones that produce skin, so that they will churn out brain cells, instead.

But are transplants necessary at all? Maybe not. Repairs might actually be engineered by remote control without ever putting anything into the head.

Some scientists talk of stimulating the stem cells still inside the brain so they divide and send off new nerve cells. Farfetched as this sounds, they say it may be possible to direct the cells to travel to distant parts of the brain and then take on the specialized duties of cells that are missing or damaged.

Still, to cure a stroke or head injury, a reliable supply of brain cells is just the start. Somehow they must be wired up so each communicates with its neighbor in a sensible way.

"The biggest hurdle is not getting cells into the nervous system," says Kessler. "It's not getting them to differentiate and to live. The biggest hurdle is getting them to reconnect in the proper way. That is an extraordinarily daunting process, when you think of the billions of connections that have to be formed."

Yet scientists such as Macklis and Dr. Evan Snyder, a Children's Hospital colleague, think this is entirely possible. For one thing, their experiments suggest that damaged parts of the brain send out help signals that can recruit transplanted cells and show them what to do.

In mice, at least, immature neurons injected into the head will travel across the brain to where cells are dying. There they assume the form of the missing cells, stitching themselves seamlessly into the brain's circuitry.

Cells injected into the brain's fluid-filled ventricles eventually migrate all through the head. The researchers say such an approach might eventually conquer diseases that involve many parts of the brain.

The whole idea of bringing in replacement cells from someplace else grew out the belief that the brain cannot repair itself. But with the discovery of brain stem cells, that dogma is crumbling.

"Cell therapy might be even more interesting, not less," says Snyder. "Not only might it mean we put back cells that the brain does not grow on its own, but maybe we will do it by augmenting a natural response."

In short, these scientists envision a day when repairing a broken brain will involve no transplants, no operations. Instead, it will mean triggering the brain to awaken its supply of stem cells, to grow its own spare parts, to literally fix itself.

PVCS

Part of living with a solid organ transplant is to just get used to the fact that potentially at more times than you could ever grow to like, you will return to the hospital for treatment of one ailment or another At such times you are usually cared for in the area that specializes in your problem. The results can be interesting. Sometimes there is over-protection when it is learned you are a transplant recipient. This scenario works, but can really get to be a pain. Other times you have to be on your own guard to make sure your special problems (like getting as far from contagious people as possible) are considered.

Then there are days when Murphy takes over the entire show with his attendant Laws. The following is the story of a recent brief stay the Editor had in a hospital for some surgery to his ailing throat. The hospital shall remain nameless, because there is absolutely no rancor or criticism involved; it was just one of those days when some sections were singing from the Messiah, while others were doing Old Macdonald Had a Farm in original costume.

JUST ANOTHER DAY FOR A TRANSPLANT RECIPIENT AT THE HOSPITAL

By Don S. Marshall Oh my goodness what a day! We rolled out of bed at 3:45 AM and were on the road at 4:30 AM. I drove with the help of a medically banned small cup of coffee that I required for medicinal purposes - just to stay awake and therefore drive the car. We were supposed to arrive at 6 AM and made it by 6:05. My checking in as George Smith (usual wise guy stupidity) may have set up the day wrong as we got what I deserved and waited a good 45 minutes before any action whatsoever took place. Actually, I was scheduled for 7:30 AM in the OR, but I don't think the Doc was even there until about 7:45 AM.
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As I played corpus on the gurney in the pre-op room, a room run with two MD anesthesiologists and perhaps seven techies who do the needle shoving, one of the MDs came stretcherside and started thumbing through my record. He asked why I had put down being allergic to atropine. I nonchalantly replied, "Because it stops my heart." He said, "Wow that's a definite allergy isn't it." I allowed as how no heart transplant recipient should ever be given atropine for that stated reason. He had no further comment on that subject.

Then after sort of thumbing the last page and slamming the file shut, he turned to me and asked, "Do you know how they put you to sleep the last time you had this procedure?" I thought quickly against being totally righteous with a "How the hell would I know, I was ASLEEP!" Instead I simply said to the effect: "I don't know, but my overall file in this hospital is slightly longer than War and Peace and perhaps you should take a quick look there." He did.

While we were having this discussion the techie was trying to insert an IV in the underside of my left wrist. In between questions from the Doc I told her that would be a poor place because only once had anyone been successful in getting an IV into my left arm anywhere, and besides the underside of either wrist hurts like hell when you stick it with an IV. She allowed as how that wouldn't be a problem because she would numb it. I'm still conversing and answering questions from the Doc when she takes a tiny needle and proceeds to run it to the hilt into the inside of my left wrist. I screamed, and just as I finished I heard her peep, "Now just a little prick." Oh my, there was truth to that! Then the Doc asked how tall I was and what did I weigh? He was commenting to the effect that I was a tall "bugger" when techie struck with the full IV pipeline. I winced, arched, and growled! The Doc leaned over the table, looked at the site and knowledgeably said, "That shouldn't hurt." I took issue with the statement and she literally plowed on. After she had inserted the full 16th" tube to its 3" length, I told both her and he that it hurt now, it would hurt later, and it was a lousy "stick." She volunteered that while I was in the OR under sedation they would find a new and better site. Even the ENT Doc told my wife, Sue, they were finding a better site for the IV when he came out of surgery. When I came to, the IV was right where it had started on the white part of the underside of the left wrist, my using hand. In addition there was a well bandaged new battle scar on the top of the left hand and another hole on the bottom of my hand, obviously well failed attempts, abandoned!

Then the ENT surgeon arrived and I told him the knockout guy needed to talk with him. All I heard was, "Looks like you used .%3+\xicero the last time." The ENT surgeon responded to the effect: "I'm not familiar with that, use what ever you want to use, but remember he's a transplant recipient which might make some difference."

PART 2

Ok, so it's the grand wake up in the operating observatory or whatever, trouble is, they tell me to open my eyes and I'm nearly BLIND. All I can see is blur! Thinking things might just improve with my glasses, I requested them. They had been wrapped in a washcloth prior to OR, which had given me pause as to their relocation later in the dirty linen hamper. I was nearly right, but eventually they were retrieved.

No help with vision there. The glasses didn't do a thing, so I felt my eyes to make sure they were still in with the pointy holes in front. My hand came away feeling like it had been stuck in a can of Crisco! It turns out that some for the first time in a number of surgeries I have undergone, I must have opened my eyes under anesthesia, which automatically prompts a nurse to cover them with goo to protect the cornea from drying out and resultant instant injury. (I only learned this fact far later after presenting a more insulting version of what I thought happened to my retired ophthalmologist father.) It took a nurse 10 minutes to just get them to a situation where I could begin to tell the sex of the people around the table without waiting for them to speak.

It was now about 8:50 AM. I was told I'd be moved to a room as soon as it was ready. The Doc came in already in street garb and said, "Every thing went fine." I was still a bit groggy and had already primed Sue with a list of questions for him, but I did manage to mumble, "And there was no cancer?" As he turned to leave he replied, "I didn't see any." Not one's totally affirmative statement to take to the bank, but better than, "Well it looked kinda funny in there."

About then someone looked at the heart monitor on the wall and "discovered" I was running a high blood pressure 160/90, not at all unusual for me under certain drug conditions, but there was little I could say, at least coherently. Next thing I knew I was being given a sub-lingual shot of Procardia squirted out of a pinhole in the capsule directly under the tongue. As I saw the nurse's hand go up I realized immediately what she was going to do, but it was too late to protest. I believe "they" have recently found that this method of direct blood pressure lowering can cause more harm than good!

At 9:05 the doctor came to see Sue in the surgery waiting area. He agreed to move up his time of review as to whether I would have to stay the night from 3 PM until 1 PM based on the fact that we had such a long way to go home. Think about that if you have nothing else to do.

At 10 AM I was still in recovery. At 9:30 Sue had been told I would be in room #320 and had gone there. Finding it with 2 empty beds, but the TV and lights on, she assumed I might have gone for a walk or something. She sat down to wait. At about 10 AM she walked into the hall and happened on a nurse, the only one in the area, and she offered to help Sue. Sue described her situation of a lost husband having to get into some detail about the nature of the surgery and the fact that I was a heart recipient as well. The nurse allowed as how the room to which Sue told her she had been told I was assigned to would never do. "We'll have to get him moved to somewhere near the nursing station so you can get him immediate help if he has a breathing problem. (Note here that Sue is being given a chance to act directly on the terms of the Living Will with a mere snap judgement not to cross the hall to the nursing desk.) Also it must be a single occupant because he is immunosuppressed and we have a lot of pneumonia on this floor right now!"

She goes to the nursing station and gets me assigned to room #340. Sue goes to get a sandwich and the camps out in room 340 for my quickly expected arrival.

Finally after an interminable wait in recovery, at 11 AM I am at last motoring toward my room on my trusty gurney, even though I told them a wheel chair or my feet would do just fine. Nope, we're down the road and up the elevator to an all prepared 2 bed, 1 bed already occupied, room with the number 300! As we arrived on the floor I heard some words exchange to the effect, "Ah, we've got a slight problem." Well heck so did I, and besides I couldn't hear anymore. As we got to the room, the pusher nurses discovered they couldn't get the gurney even through the door, so I was asked if I could get off and walk into the room and get into bed as they in duo held up my IV bag so I wouldn't suck too much air. Of course I complied, wondering a bit about what makes medical expenses so high, when we send two RNs and a gurney up 3 floors to a room, only to have the patient then get off and walk.

Hester, my assigned nurse (who would later wish she had taken the day off) entered. Her first words were, "Do you have family with you?" Again I should have said, "Why yes, my wife is over there in the chair, since menopause she's had this ongoing problem with invisibility." But I didn't, I allowed as how I was sure, or almost sure I had a wife in the hospital somewhere, in fact it might help if they summoned her from the waiting room. "Sure we'll call down there right away."

Well, it's now about 11:45 AM. Sue is patiently waiting in Rm. #340, I'm impatiently waiting in Rm. #300 and my roommate is telling me not to worry. Seems when he was carted away by ambulance to the hospital about 3 hours ago, his wife couldn't join him because she was right in the middle of her 3 times weekly duplicate bridge game.

About that time the heart transplant Doc shows up at my previous request with the hope I can get him to certify that I'm OK for immediate release. He does and his nurse says she will call the surgeon's office. (Yes, I did have the nurse call the TX office because I knew if nothing else they would try and "spring me" because they know I make a lousy, whining patient, and in addition at the very least they might clarify that outside of immunosuppression I could be treated more like the "normal" grumpy old man.)

At 12 N I arranged for the nurse to have Sue paged over the "big" public address system, something that is not supposed to be permitted. I heard the message go out twice in Rm.#300, but somehow Sue didn't catch it in Rm#340. At 12:15 I'm sitting on the bed trying to figure out how I can get a long distance call through to our house without a credit card, which is in my wallet, which Sue has along with everything else my not so sharp heart desired for use in the hospital. At 12:20 PM Sue again approached the nursing desk, which I should have noted served one nursing station above where I was. They finally went back to the source, the recovery room, to see if I was still there. "No he went out of here about 2+ hours ago." "Where did you take him?" "Rm. #300" Then the phone lines started to get hot and Sue took her leave to find room #300, which she entered as I was still working on the phone gimmick. She gave me "the look" she learned from watching Home Improvement re-runs. I then knew I had to hear her side of the story before I exploded into a demeaned patient's rage. As I really wasn't allowed to talk, the latter just fizzled into some attempted negative sounding grunts followed by a quick question if she had any information as to what time I was going to get out.

Sue relates how she has agreed that the doctor will call at 1 PM. He doesn't. At 1:30 the nurse calls his office and relates a story close to "If you don't let this guy out of here, I'm out of here!" He gets her to swear that she can't hear any "stridors", a whistling noise caused by cancer or some other swelling of the larynx, usually on breathing in. She crosses her fingers and promises him she doesn't. Of course by this time I'm standing over her with IV stand and all looking as threatening as a 63 year old man can who's general appearance is that of having just been run over.

About this time a nurse from Respiratory Therapy shows up and prepares to hook up a mega-oxygen system "to assist my breathing." I indicate that the patient intends to exercise his right to refuse treatment reason: he is being discharged as we speak, and as soon as she leaves he will be dressing to go home. She leaves to contact "headquarters." I get dressed. She returns and prepares to hook up oxygen. I tell her the project is a dead duck. Hester returns and apologizes for not calling Respiratory and canceling. Nurse says OK, but I'm willing to wager the Oxygen System charge will still show up on the bill.

As in the normal final hospital departure tradition, Hester reaches up under my shirt to remove the hook-up patches for the heart monitor I had been wearing. Apparently she was totally shocked by the medical anomalies she found there, because later at home as I undressed both Sue and I noted the patches were still there. The end of a not-so perfect day!

The best part of the entire day was that evening when the surgeon called to see if I was doing well. That's the kind of thing one hopes never leaves the true practice of medicine.

ORGAN DONORS ARE SHOWING A LITTLE HEART

By Eboni Davis - Daily Press

The number of organ donors has skyrocketed in Virginia, all because DMV clerks are asking a simple question: "Do you want to be an organ donor?"

Once a customer says "yes" the status of his or her driver's license record changes in minutes, said Marcia Gallan, a customer service representative at the Department of Motor Vehicles office in Newport News. "If I die, I don't really need them. I figured I'd help somebody out," said Cefenno Gil as he sat with his wife and daughter waiting to receive his license.

Since customer service representatives began asking customers about organ donation in February, the number of donors has soared to more than 240,000 from more than 70,000 in 1998. The procedure is different from previous years, when customers weren't questioned about the blank spaces on their application for drivers' licenses, state Ids and voter registration cards.

When organ donor status is changed at the time of renewal, the cost is free. But the cost is $5 if a customer chooses to have the organ donor symbol - a small red heart - placed on his or her license or identification card prior to renewal time. On a recent Saturday morning at the busy and crowded DMV office in Newport News, customers were scattered - some in seats, others at service windows - as they waited to be photographed for licenses or ID cards.

Cindy Elliot waited for her 15-year-old daughter to be photographed for her temporary license. Elliot said she hasn't always wanted to be an organ donor, but her 19-year-old niece began advocating organ donation as a beauty pageant contestant and changed her mind.

"Hearing her and the research she's done made me realize how important it really was," said Elliot. Shaking her head, she added: I think about a kid who needs a kidney and they don't get it while I have one here."

So she will change her status, Elliot said. Outside Bernadine Richardson explained that she has been an organ donor for seven years. "It's the gift of life," said Richardson. "It's something I have that can be carried on to someone else."
She glanced down at her 8-year-old daughter. "Who knows?" Richardson said. "She may need something one day."

NEW TRANSPLANT POLICY FAVORS SICKLY

By Laura Meckler - Associated Press Writer

WASHINGTON (AP 6/25/99) - People across the country whose livers suddenly fail and are given less than a week to live will have a much better shot at getting a liver transplant under a new policy.

The policy, which should take effect within months, brings the United Network for Organ Sharing closer to the position of the Clinton administration, which has been pressing the network to send scarce organs to the sickest patients first, rather than favoring patients in the area where the organs were donated.

But network officials emphasized that they would have made the change even without the pressure. Their insistence offers fresh evidence that the dispute between the network and the Department of Health and Human Services is about who makes the decisions as much as what those decisions are.

"This change has been coming along for a long time," said Dr. William Payne, a surgeon at the University of Minnesota, who is the network's new president.

The network's board, meeting in Atlanta, also agreed today to back off its long-standing refusal to release information about individual transplant centers and their performance. In the past, it has been unwilling to release transplant waiting times at each center and has only released outdated data on patient survival rates.

The change in liver policy will direct more livers to the sickest patients who are considered the most medically urgent, or "status 1," and are given a week or less to live. That includes people whose-livers suddenly fail, for instance, due to an infection, drug reaction or rejection of a previous transplant.

But patients classified as "status 2a," who are also expected to die within a week, are not affected by the change. These patients are sick from chronic, rather than acute, liver failure.

"We think the community needs to go a little further," said Dr. Claude Earl Fox, who directs the HHS agency in charge of transplant policy.

The heart of the problem is supply and demand: The waiting list for organs has grown much faster than the number of donations, and more than 4,000 people die each year waiting. That has created intense competition for the organs that are available.

For the past year and a half HHS and the network have been fighting over who should direct transplant policy.

HHS issued rules ordering that more data be released and directing the network to create a new allocation system that would get organs more often to the sickest patients. The network responded with an intense lobbying effort and persuaded Congress to delay the regulations until this fall.

But on Thursday the network moved closer to what HHS wants on liver transplants, which have engendered the most debate. The change will take effect as soon as it can be implemented, network officials said.

The network has opposed giving organs more often to the sickest people, arguing they are less likely to survive a transplant. But officials calculated that the effect of this policy change will be minimal: 78 percent of patients would survive one year, down from 79 percent.

The current system offers livers first to status 1 patients in the designated local area, which can vary from part of a city to several states. If there are no medical matches, the livers are offered to other local patients, in order of medical urgency. If there are still no local matches, livers are offered to patients in the surrounding region, sickest first.

The new policy, approved on a 30-3 vote, would kick in if no local patients are in the greatest medical need. In this case, livers would be offered to status 1 patients throughout the region.

Six of the nation's 11 regions have already adopted similar agreements on their own.

As it stands, 14.5 percent of donated livers go to status 1 patients. The network expects that to rise to 22.3 percent under the new policy and the percentages going to less urgent patients to drop slightly. Livers are the most controversial organ because they can survive outside the body for 24 hours, making it possible to transport them anywhere in the nation. Also, medically, there is no way to keep someone in liver failure alive while awaiting a transplant.

The network board also adopted a new policy Thursday on allocating livers that have been divided, with part to go to an adult and part to a child. Hospitals that agree to split all medically suitable livers will be part of the group that gets the first chance at other donated split livers.

BONE MARROW RECIPIENTS' FIRST 2 YEARS RISKIEST

By Linda A. Johnson - Associated Press Writer

AP (7/1/99) Cancer patients who get bone marrow transplants can live pretty close to a normal life if they can make it past the first two years, according to a study published in today's New England Journal of Medicine.

The risk of dying from a recurrence of the cancer, infection, rejection of the transplanted marrow or other causes is highest during this period.

The study looked at patients with any of four diseases that are sometimes treated with transplants of bone marrow. It found that those who are disease-free after two years have only a 1 -in-9 chance of dying over the next five years.

"Even though the mortality rate is higher than in the normal population, it's pretty low," said Dr. Mary Horowitz, scientific director of the International Bone Marrow Transplant Registry at the Medical College of Wisconsin in Milwaukee. "Every day you survive, your chance of making it another day gets better."

Horowitz and colleagues studied records of 6,691 patients at 221 transplant centers worldwide. The patients received marrow from a donor between 1980 and 1993 and, two years after the transplant, were still healthy.

The patients had one of three types of leukemia or an anemia in which the marrow, the blood-forming system inside the bones, wasn't working. They received high-dose cancer drugs, and often high-dose radiation, to kill their nonfunctioning marrow. Then they were injected with the donated marrow essentially getting a new blood and immune-cell factory.

Horowitz said the lingering risk, while slight, shows patients need frequent checkups for years after the transplant.

"What I'm hoping is the results will increase the likelihood that some of these patients will (be able to) get health and life insurance after their transplants," she said.

Dr. Andrew Pecora, chief of the Blood and Marrow Stem Cell Transplant Program at Hackensack University Medical Center in New Jersey, said the encouraging results confirm what specialists suspected.

He said the study may help doctors save patients by pushing them to eat better, take vitamins, exercise and quit smoking.

COMMON ANTI-VIRAL DRUG HELPS PREVENT ARTERIAL CLOGGING

STANFORD (BW Health Wire) (7/6/99) Heart transplant recipients who received a common anti-viral drug have a significantly lower incidence of life-threatening coronary artery disease than untreated patients, according to a new study by researchers at the Stanford School of Medicine.

The drug, ganciclovir, is routinely used to control an infection that is harmless in most people but can cause serious problems for transplant recipients, whose immune systems are compromised.

The Stanford researchers reanalyzed data from a study of the effectiveness of ganciclovir for treating cytomegalovirus (CMV) in transplant patients and found that patients who received the drug were nearly three times less likely to suffer some blockage of their coronary arteries. Coronary artery disease is the leading cause of death for heart transplant recipients who have survived at least one year after surgery. The authors of the study, published in the July 6 issue of Circulation, believe the results are significant enough to warrant a larger investigation of ganciclovir treatment in heart transplant patients.

"I'm hoping that this will result in a randomized, controlled clinical trial," said Hannah Valantine, MD, Stanford associate professor of medicine and lead author of the study. If the results mirror those in the recent analysis, transplant surgeons and patients will have gained a powerful new tool in their quest to make organ transplantation more successful. Additionally, this apparent prevention of coronary artery disease could have important implications for atherosclerosis in non-transplanted hearts, Valantine said.

For most people awaiting organ transplants, finding an appropriate donor is wonderful news. But often their troubles don't end after a successful transplant surgery. Heart transplant recipients must contend with the fact that their healthy new heart frequently develops dangerous plaque build-up in its arteries shortly after transplantation. Studies have shown that half of patients develop this condition, known as coronary atherosclerosis, within five years after the transplant.

CMV Infection Doubly Dangerous

Although the exact reason for the increased plaque formation is not known, previous studies have identified a correlation between infection with CMV and coronary artery disease in both transplanted and non-transplanted hearts. CMV is a member of the herpesvirus family and is commonly acquired in early childhood. It can remain latent in the body indefinitely, often with no ill effects. Recent studies have shown that the virus can hide out in the smooth muscle cells of the heart during these latent periods. For immunosuppressed transplant patients, however, CMV infection can pose a two-fold threat.

When the body's immune system is compromised, either by illness or by the use of immunosuppressive drugs after organ transplantation, CMV can come out of hiding. In severe cases, the resurgence of active CMV infection can be life threatening. The virus multiplies rapidly, affecting multiple organ systems and resulting in pneumonia, blindness or terminal secondary infection.

The anti-viral drug ganciclovir was first tested at Stanford in the early 1990's for its ability to prevent CMV illness in 149 heart transplant recipients. Ganciclovir inhibits viral replication by interfering with the protein that synthesizes viral DNA. Patients were given the drug or a placebo immediately after surgery, and the treatment was continued for 28 days. Ganciclovir treated patients who were infected with CMV were significantly less likely to develop CMV illness during the first year of follow-up. The results of the study were published in the New England Journal of Medicine in 1992.

In addition to causing CMV illness, the virus is believed to stimulate the proliferation of infected cells, which serve as a focal point for inflammation. When these cells are in the arterial wall, the inflammation and accumulation of immune cells, such as macrophages and monocytes, can result in plaque formation and blockage of the artery.

Ganciclovir Can Also Inhibit Coronary Artery Disease

Because of the relationship between CMV infection and the development of coronary artery disease in transplanted hearts, Valantine and her team wondered if ganciclovir could also be protective against plaque formation. They analyzed the data from the previous study, this time categorizing the patients by the presence or absence of coronary artery disease during the four-to seven-year follow-up period.

Once again, ganciclovir treatment appeared protective, particularly among patients who were not receiving a second kind of drug, known as a calcium channel blocker. Although most of the patients were taking the channel blockers for a variety of reasons, the drug has since been shown to confer a protective effect against plaque formation.

When the researchers compared the relative risks of different variables in heart transplant recipients, the lack of ganciclovir treatment immediately after surgery was the most significant danger factor, increasing the risk of developing coronary artery disease by nearly three-fold. In contrast, neither the occurrence of CMV illness or infection by CMV was strongly correlated with plaque formation in this study group.

Ganciclovir May Have Multiple Mechanisms of Action

The ability of ganciclovir to inhibit the development of coronary artery disease and the somewhat surprising lack of correlation between the disease and CMV illness or infection hints that the drug may also be able to act independently of its ability to prevent viral replication.

In animal studies, ganciclovir has been shown to inhibit the division of muscle cells that are not infected with CMV, according to Valantine. Inhibiting the proliferation of even uninfected cells of the arterial wall may be another way that ganciclovir works to help prevent plaque formation in the donated heart. The authors of the current study plan to continue their research to fully understand the way that ganciclovir acts to prevent atherosclerosis in transplanted hearts.

LUNG TRANSPLANT WAITING TIMES COULD INCREASE

By Lidia Wasowicz - UPI Science Writer

Transplant guidelines could hurt those with cystic fibrosis: A study indicates there could be an increase in the number of patients with cystic fibrosis who die while awaiting lung transplants.

Dr. Robert Keenana, head of the lung transplant program at the University of Pittsburgh Medical Center, said he was concerned with new international wait-listing guidelines and the current geographic disparities in waiting times. He spoke at the International Society for Heart and Lung Transplantation's 19th annual meeting in San Francisco.

Keenan said the results of his study of 164 CF patients evaluated for transplantation indicate the medical criteria adopted last year by the transplant community are too restrictive.

In the United States, where organs are allocated in a local-first system, this would limit the window of opportunity that donor organs can be found, he said.

"At our center, and at other centers in the United States that tend to have longer waiting times, we expect there to be substantial mortality on the waiting list. If geographic disparities in waiting times were minimized, these guidelines might be more reasonable for medical practice," said Keenan, associate professor of surgery in the division of cardiothoracic surgery.

More than 25 percent of all patients needing lungs die waiting, according to the United Network for Organ Sharing. The rates vary from region to region. Patients with CF account for more than a third of those needing double lungs and about 15 percent of those needing hearts and lungs.

The guidelines have been incorporated into national policy by UNOS and are used by insurance companies to judge whether the costs of evaluation or transplantation will be covered.

BRITAIN PROBES ORGAN DONATION REPORT

LONDON (AP 7/6/99) Britain's health minister ordered an investigation Tuesday into a report that kidneys were donated to a hospital on the condition that they be given only to a white person.

Health Secretary Frank Dobson said he was "appalled" that there appeared to be a loophole in laws governing transplants that allowed such agreements. The family stipulated the condition, a British Broadcasting Corp. television program reported. A memo was attached to the donation, saying "this organ is not allowed to go to anyone who is not white."

The kidneys were subsequently transplanted to a white person at the Northern General Hospital in Sheffield in north England. But the BBC said it was impossible to say if a white person was chosen over others because no information was available about the transplant waiting list.

A spokeswoman for Britain's transplant authority said it did not condone the restrictions applied to the transplant, but under law are legally obligated to pass along any donor organs made available along with conditions.

A spokesman for the Northern General Hospital pledged to cooperate fully with the government investigation, but denied that the hospital would knowingly accept organs under such an agreement.


Disclaimer: The material in this document has been collected by Don Marshall and friends. New ideas and materials are welcome all the time. Nothing herein is ever to be construed as medical advice. As a policy, UpBeat is sent upon request to heart and heart/lung transplant recipients and other interested parties. Donations of $15 per year, or more, from Tx recipients, if not a burden, are vital. From all others the donation is specifically requested. The date shown after the name on the address label indicates the last time a donation was received. Please make checks payable to Don Marshall, as we cannot afford to become nonprofit. Send materials, letters, or checks to:

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