Oriented to Thoracic Transplant Recipients -- October 1997

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Lifesaving Cyclosporine Takes Toll on Kidneys

Cyclosporine has long been hailed as transplantation's "magic bullet." Although it remains an effective, lifesaving drug for fighting rejection, it has unintentionally claimed another casualty, though: the kidney.

As transplant recipients are living longer and thus receiving the drug for prolonged periods, cyclosporine-induced kidney damage has become a growing challenge to the transplant community as researchers explore ways to fight this potentially life-threatening condition.

The long-term effects of cyclosporine may cause some transplant patients without any prior kidney disease, particularly those receiving heart, liver and lung transplants, to require dialysis or kidney transplantation. This growing category of potential kidney transplant candidates could create additional demands on the already severe shortage of donor organs, further compounding the organ shortage crisis, researchers say.

"Treatment with cyclosporine for more than 12 to 24 months can cause progressive injury to the kidney that is rarely reversible and has the potential to lead to end-stage renal failure," said Bryan D. Myers, M.D., a professor of medicine and chief of the division of nephrology at Stanford University Medical Center in Stanford, Calif. "Alternative agents that are efficacious and not nephrotoxic are needed to enhance the immunosuppressive regime of transplant recipients while averting serious injury."

Retrospective study

Myers' conclusions are based on a paper he published in 1991 in which he retrospectively studied the kidneys of 200 heart transplant recipients treated with either low or high dose cyclosporine' and compared the results to a group of 100 heart recipients who were never exposed to cyclosporine.

After I2 months, renal damage (as measured by the occlusion of renal microvessels) was as much as three times higher in the cyclosporine-treated group.

Statistical analysis showed that after 10 years, approximately 10 percent of the cyclosporine-treated patients had progressed to end-stage renal failure, Myers said.

Since that study, there have been relatively few new findings regarding the longterm relationship between cyclosporine and kidney damage. Other studies have found that FK506 has very similar effects.

Myers' findings are being confirmed by other researchers who are also finding kidney damage in heart transplant patients who have had no previous kidney disease. In particular, researchers have now identi fled a particular type of lesion, afferent arteriolapathy, which is found in many heart transplant patients with chronic kidney damage.

Similar observations of kidney damage have been seen among other transplant patients, particularly liver recipients. Myers believes liver transplant patients may be more susceptible to cyclosporine-induced kidney damage than heart transplant patients, possibly due to hepatorenal syndrome-a condition in which the kidney's blood supply becomes severely compromised as a consequence of liver failure. The resulting underperfusion may make the kidney more susceptible to damage by cyclosporine, he noted.

Whether or not cyclosporine causes kidney damage in patients who have received kidney-only transplants is unclear. Chronic kidney rejection and cyclosporine nephrotoxicity both injure the blood vessels of the kidney similarly, so the exact cause of the damage is difficult to distinguish after several years, Myers acknowledged.

Risk factors

Many actors play a role in the development of cyclosporine-induced kidney damage. Although higher doses of cyclosporine appear to cause more damage, duration of treatment appears to be the most important factor: the longer one remains on cyclosporine, the greater the damage.

As a rule, heart, lung and liver recipients, who generally receive high doses of cyclosporine for long periods and have no other treatment recourse, are among the most vulnerable.

In particular, there appears to be a subgroup of liver recipients who are more susceptible than others. Liver recipients with hepatorenal syndrome, which affects about one-third of recipients, appear to develop more severe and long-term kidney damage than patients who do not have the syndrome. according to Myers.

Cyclosporine-induced kidney damage may take as many as one to two years to detect. It is generally characterized by a drop in kidney function, as measured by serum creatinine levels. High blood pressure is another identifying hallmark. Biopsies. which may reveal histological damage to the afferent arterioles, are used to make a more accurate diagnosis.

"To my knowledge, there is no known way of preventing cyclosporine damage." Myers said, adding that once structural damage is revealed on biopsy, it cannot be reversed.


"Cyclosporine-induced kidney damage is very concerning," concurred Pedro VergneMarini, M.D., medical director of transplantation at Methodist Medical Center in Dallas. "It's significant and progressive, and the problem is not going to get any smaller."

Like Myers' landmark study, Vergne has tracked kidney damage among 88 heart transplant recipients at his clinic for the past 10 years. Based on preliminary studies of glomerular filtration rates, an index of kidney function, he estimates that 40 percent oœ these patients have lost more than 50 percent of their renal function.

He is particularly concerned that some of these heart recipients may one day need kidney transplants: three patients are currently on dialysis, while two others who were formerly on dialysis have since received kidney transplants.

"I estimate that 20 to 30 percent of patients with cyclosporine-induced kidney damage may ultimately need kidney transplants," Vergne said.

He agrees with Myers that the solution to the problem is complex. Reducing the dose of cyclosporine in these patients is not practical because if the dose is reduced too much, the patient will suffer rejection and die. Vergne points out an additional concern. Because these patients are immunosuppressed, they run a higher risk of developing infection while on dialysis than non-transplanted dialysis patients. As a result, they are at higher risk of dying while on dialysis than non-transplanted patients.

The problem is further compounded when these patients are added to the kidney waiting list, as they are likely to receive a lower priority than patients who have built up higher waiting time accrual for kidney alone transplants.

"I think these patients should have some sort of priority in the UNOS organ distribution system," Vergne said. Pending more comprehensive studies, however, UNOS currently has no plans to give patients with cyclosporine-induced kidney damage special preference on the waiting list.


According to Jerry McCauley, M.D., director of transplant nephrology at the University of Pittsburgh Medical Center, Vergne' s high estimates of the percentage of vital organ transplant patients who could ultimately acquire end-stage renal disease is possible in theory, but he believes the actual percentage is much lower. Based on observations of some 200 transplant patients over a 14-year period, only about 10 percent developed end-stage renal disease, he said, matching the figure suggested by Myers.

McCauley agrees that all patients are at risk of developing some level of chronic renal insufficiency from cyclosporine, particularly due to the high doses used in patients with vital organ transplants. However, he believes that in the vast majority of patients, stable renal function is maintained.

Pathology uncertain

The pathology of cyclosporine-induced kidney damage is still poorly understood, McCauley said. One reason is that transplant patients who develop kidney damage often do not receive kidney biopsies, which might reveal characteristics that could ultimately help predict the progress of kidney disease. More biopsies are needed so that the pathology oœ the disease can be better understood, he said

"Most of the time patients with renal insufficiency do not have any clear indications to do kidney biopsies and it's not done routinely," McCauley stated. He estimates that only 5 to 1 0 percent of patients with severe kidney damage who are referred to him have been biopsied. "The times that I have done biopsies, the findings have been largely consistent with cyclosporine nephrotoxicity." Since most transplant patients with cyclosporine induced kidney damage are stable and the etiology of this disease is poorly understood, McCauley does not agree with Vergne's assertion that these patients should get special priority for kidney allocation.

"The problem with giving preference to one group of patients who are at risk is that you make everyone else wait longer," he said. "I'm not sure if transplanting these patients earlier changes their mortality so much that they should get preference over other people who are waiting. That needs to be demonstrated."

Safety measures

McCauley advocates a number of measures to help identify or delay the progress of kidney damage. Among the most important, he says, is earlier referral to a transplant nephrologist.

Other suggested safety measures include a low protein diet, good blood pressure control and the use of ACE inhibitors, when appropriate. In patients with high cholesterol, use of a cholesterol-lowering agent such as pravastatin, simvastatin or fluvastatin may also be helpful, as high cholesterol can cause the kidney to fail more quickly. An NIH trial of pravastatin is being planned to evaluate the drug's effect on renal transplant rejection and cardiac mortality.

"I think if patients are seen early. and these measures are instituted early, then we have a better chance of stabilizing their renal function," McCauley said. "once they are referred with a creatinine level of 3 or 4. it' s very difficult in my experience to turn those patients around."

Another safety measure involves using other drugs to lower the dosage of cyclosporine and other immunosuppressants. such as tacrolimus and Neoral. One promising agent is Cellcept, which is being used in a number of multi-center trials across the country to examine its ability to lower the required doses of immunosuppressants among liver and heart transplant patients. Such studies will determine whether or not this drug improves renal function over time. McCauley said.

Connie Davis, M.D., a transplant nephrologist and associate professor of medicine at the University of Washington Medical Center, believes that the actual percentage of liver, heart and lung transplant patients who develop end-stage renal disease lies somewhere between the 10 percent estimate suggested by Myers and McCauley and the 30 percent suggested by Vergne. Based on her hospital's patient population, she estimates this figure to be between 10 and 15 percent.

Additional factors

Davis believes that the real source of the kidney damage in transplant patients taking cyclosporine is unclear. She questions how much is due to cyclosporine and how much is due to other factors such as pre-existing ischemic damage, hepatorenal low output states in cardiac failure, primary kidney disease, hepatitis-related renal disease (HCV, HBV), recurrent hypotensive episodes (GI bleeding), infection and other drug toxicity (antimicrobials). All of these factors can lead to kidney damage, she says. "It's difficult to prove unless you find specific matrix characteristics in the kidneys for cyclosporine damage," Davis said.

She agrees that cyclosporine is a strong candidate for the majority of cases of long term kidney damage seen in patients with vital organ transplants. "I do think thai cyclosporine increases the production of collagen, so there is good reason to think that it is the cause," Davis said, referring to studies that have shown correlations between collagen increases and kidney damage.

According to Vergne, one of the most important measurements for detecting cyclosporine-induced kidney damage is not measurements of serum creatine levels, as some physicians believe, but glomerular filtration rates.

"You can lose 40 percent of your kidney function and serum creatine won't change," Vergne said. "Physicians must do accurate clearance studies to detect early toxicity."

More studies needed

Despite the risk associated with cyclosporine-induced nephrotoxicity, the risk is significantly lower than in the early '70s and' 80s, when higher doses of the drug were used, says David E. R. Sutherland, M.D., Ph.D., director of the transplant program at the University of Minnesota Hospital in Minneapolis and chairman of the UNOS Kidney/Pancreas Transplantation Committee. Although estimates vary regarding the extent of risk, there have been too few studies and publications to accurately assess the risk, he says.

Sutherland believes that rapamycin is a promising drug that may one day replace cyclosporine or be used in conjunction with lower doses of the drug. Like McCauley, he recommends reducing hypertension and perhaps prescribing a low protein diet to minimize the effects of kidney damage.

For now, cyclosporine continues to represent a proverbial "friendly fire": designed to fight the enemy of rejection, the drug inadvertently damages the healthy kidney. The situation has become more urgent as transplant patients are living longer and taking these drugs over prolonged periods. Unless a solution is found, cyclosporine induced kidney damage will remain a growing challenge to the transplant community.

Mark T. Sampson

UNOS Update, Summer 1997, pp. 18-20. With permission of Editor Esther L. Benenson.

UpBeat Ed Note: This article pulls no punches, something rarely done in the public forum when discussing the "wonder drug from the wonderful people at Novartis ". The average Tx shouldn't panic, but perhaps use the article to open a friendly discussion of the problem and how it is being monitored in your case with your Tx Doc next clinic visit. We salute Ms. Benenson for her forthrightness in bringing this information to print.


Ethical issues arise when it's an inmate seeking a transplant.
By Judy Putnam, Gazette Lansing Bureau

PLYMOUTH, MI (8/17/97) - At age 38, Mindy Brass needs a new heart.

Time is running out for Brass A massive coronary in 1994 left her with a damaged and failing heartú

Although Brass hopes to become one of the lucky few chosen for a transplant, she faces a huge barrier: She is serving a life sentence with no parole for a drug charge.

"I get tired. I get chest pains. There's no question in anybody's mind, my only option is a heart transplant, but I'm an inmateú" Brass said in an interview at Scott Correctional Facility in Plymouth.

The California woman was a single mom and owner of a small marketing firm when she was nabbed in 1991 under Michigan's controversial drug lifer law. It carries mandatory life for dealing more than 60 grams - I 1/4 pounds of cocaine or heroin.

Brass' efforts to practice her Jewish faith inside prison have' attracted a long list of prominent supporters, including doctors, rabbis and executives from the Detroit area. They've organized a "Justice for Mindy" campaign to fight the lifer law.

Although transplant authorities say a person's "social worth" isn't considered when selecting organ recipients, Brass' supporters still fear she won't get a heart because she is a prisoner.

'Taxpayer-supported transplant] surgery outrages critics such as Rep. David Jaye, RWashington Township, a member of the House Corrections Committee who frequently questions prisoner expenses.

"No way should taxpayer dollars be spent to provide a heart transplant to prisoners. Not when we have law-abiding citizens who are waiting and cannot get them," .Faye said.

Prison officials around the country say it's an emerging issue. Should precious organs be given to those who commit crimes? And who should pay?

There's been little study on the issue because prisons are only now getting inmates who are aging or very sick. said Dr. Howard Stone. director of a research program on legal and ethical issues on correctional health at the University of Texas medical branch.

A first for Michigan

In Michigan, Brass is the state's first inmate to be evaluated for major organ transplant surgery said Gayle Lafferty, head of health care for the Department of Corrections.

But in May, Brass was rejected by doctors at Henry Ford Hospital in Detroit, one of Michigan's three heart transplant teams. Henry Ford rejected Brass because cause of her history of drug use prior to prison, said Dr. Robert Decosta Higgins, head of the heart transplant team.

"She appears to be a bright, otherwise healthy young woman who presents a compelling case. Nonetheless, her drug abuse history is one of the things we look for," he said.

"We did not make any judgments about her value or whether it was right or wrong to transplant her because of her incarceration status.

Now Brass is turning her hopes to the University of Michigan transplant program. She was seen by a U-M doctor in July, and is expected to go for another appointment before the end of the summer, Lafferty said.

David Wilkins, a spokesman for the U-M Medical Center, said transplant doctors will look at medical criteria only.

"Someone's status as an inmate would not be held against them," Wilkins said.

Waiting list is long

Even if she is listed by a transplant team. getting a heart is another matter.

Only 47 Michigan patients received hearts last year, while 18 died waiting for a transplant. according to the Ann Arbor based Transplantation Society of Michigan. There are 74 Michigan heart patients on a national list.

It's also expensive. It costs an average of $150,000, for the transplant surgery itself. but total cost or care rises to $316,000 for the first five years following surgery.

Lafferty said the state will review organ transplants on a case-by-case basis. But if a transplant team Oks Brass, "we'd give serious consideration to paying if it were medically necessary." Much of the cost would be borne by a California company under a new managed care contract. she said.

Competing pressures

Prison health officials say they are caught between court rulings that say they must care for in- mates, ,and public opinion, which resents tax dollars spent on criminals.

In Tennessee, James Earl Ray, the convicted assassin of the Rev. Martin Luther King Jr.. needs a new liver, but the state will not pay for it.

"Our policy is that we do not provide. at taxpayer's expense, an organ transplant." said

Pam Gehman, spokes man for Tennessee prisons. The Federal Bureau of prisons, too. refuses

to pay for organ, transplants, but will consider an early release.

In Michigan, services provided by Medicaid, the health program for the poor. are the benchmarks for prison health care. Michigan' is one 34 states where Medicaid pays for heart transplants. It paid for 13 transplants in 1993 and 15 in 1994.

After serving; five years in prison. Brass said she is still hopeful her sentence will be overturned. Her attorney recently filed a motion for a new trial based on withheld evidence.

Brass said she was a recreational cocaine user. She admits to trying to arrange a purchase of a kilo in California, where penalties are lighter, not Michigan, when she was arrested.

Brass talks weekly with her daughter, Erika, 13. who is in group home care in California. Brass' friends are trying to arrange Erika's placement with a Michigan foster family.

Brass said she knows She faces an uphill fight to survive. "I'm a realist. l want that heart, believe me, but l also am practical. 1 can understand to a certain degree that it's a difficult decision to be made," she said.

Kalamazoo Gazette 8/17/97 Contributed by Dr. Don Marshall, Kalamazoo


Weekend Edition - Sunday (NPR), 03-13-,1994. t .....

LIANE HANSEN. Host: Last September. we broadcast a story about Paul Jewel. who was waiting at the Pittsburgh Medical Center for a heart transplant. He talked about the uncertainty of getting a heart. knowing that there were others on the waiting list. What he may not have known is that some of those people might have jumped ahead of him on the list. even though they were Waiting for a second transplant while he was waiting for his first.

We were recently in touch with Mr. Jewel. He told us he received a new heart shortly after our broadcast. He returned to his job as a banker at the beginning of this year. and he said he considers himself extremely fortunate.

There is a growing debate about how the medical community determines who gets a heart. and many questions have been raised about re-transplantation. Joining us to discuss the issue are Weekend Edition's medical commentators. Drs. Miriam Shuchman and Michael Wilkes. Good morning, both of you.

HANSEN: Miriam. fill us in on the arguments concerning this issue.

Dr. SHUCHMAN: Well, Liane, who gets on to a transplant waiting list is determined by the local transplant center after they consider a whole host of factors. For example, they'll consider age because there's data to suggest that older people don't do as well with transplants.

And they also will consider whether or not this person has ever had a transplant be%re. And if the person is getting are-transplant, that doesn't put them lower on the list, in fact, it may put them higher on the list. And there's a feeling that this is not fair and that this sort of policy needs much more public input.

Dr. WILKES: On the other hand, these transplant decisions are really quite complex. and involve a committee which examines not only social aspects like age and income and family support. but also very complicated medical aspects. These decisions need to be made by nurses and social workers together with physicians who work on a regular basis: with transplant patients.

Now. the medical community becomes very attached to these patients. When their heart gets into trouble and eventually fails. the medical community begins to share their desperation. They know the patient. they know the' patient's family, they fought to keep the patient alive for several years:and it's only natural that they want to hold on to offer the person another chance, even if that means giving them a second heart

Dr. SHUCHMAN: Any doctor would be committed to their patients. but the question here is. who's more deserving. There aren't enough hearts and livers to go around. and here you have one person who's already gotten one heart transplant and now their heart is failing and they need another one to survive But you have another person who's never been transplanted Their heart's also failing. Maybe they should get a chance before that first person gets a second turn.

It also turns out that when they've done studies comparing re-transplant patients with first-time transplant patients, the first-timers have a better prognosis. They're more likely to be alive two years and five years after transplant than the re-transplant patients.

HANSEN: Miriam, tell us some of the reasons why someone would need a second transplant.

Dr. SHUCHMAN: Well, it's mostly that the body rejects the new heart in some way. For example. studies have shown that about five years after heart transplant, over half of patients develop coronary artery disease that will eventually lead to their death. This is a type of chronic rejection.

In this way, transplants are similar to coronary bypass surgery. Most people who have bypass surgery are going to need another heart operation a decade or so later. And likewise, most people who have a heart transplant operation are going to need another new heart within five to ten years. So as more and more heart transplants are performed, there will arise this question of whether people with new hearts should get a second new heart or if that should only be done if there are extra organs available.

Dr. WILKES: But I'd be very hesitant to enact any kind of strict rules that forbid re-transplantation. I think that each of these decisions need to be based on an individual basis. As I've been looking into this. I spoke with one man who had a second heart transplant. He described how scared he was when his first transplant began to fail.

Heart Transplant. Recipient: I spent the last several weeks in intensive care, unable to get out of bed and hooked up to a variety of machines anti tubes and things that prevented me from. almost from moving, ' till the very last. And I was extremely relieved when my physician came in and said they found a heart.

Dr. WILKES: This man had waited in line with the others on the list for a chance for another transplant if a heart had not come available at the right time, he would have died, He needed our help just as much as everyone else on that list.

Now,the difference, if there is one. for thins man, is that he had a proven record of being an ideal patient. Experts didn't need to guess. They knew that he'd take his medicine as they directed. They knew that he would show up for appointments. They knew that he would recognize the early warning signs that needed immediate attention.

Dr. SHUCHMAN: Of course this man felt relieved-he was getting a second chance. But ,n these sorts of situations, doctors can't be objective. They have a special relationship with this man. They've already operated on him once.

Dr. WILKES: Right, but we've also made a substantial investment in the re-transplant patient. Re-transplanting him is just protecting that investment. We've made a commitment to the patient. Now that the transplant goes bad. through absolutely fault of his own, what, are we just going to abandon him?

Dr. SHUCHMAN: No, we don't abandon him. We give him good care, we give him attention. The question is whether or not we give him a second new heart when there are other people who still haven't gotten their first new heart. And I'm not sure that should happen.

HANSEN: You know, it sounds like, listening to you, that there should he some kind of very clearly defined system of organ rationing.

Dr. SHUCHMAN: Well, unfortunately. we already have a system of rationing. Because there aren't enough hearts and livers to go around. some people get them and others don't. And in this country, almost no one who's uninsured or very poor will receive a new heart.

And in fact, this is in direct conflict with guidelines issued by the World Health Organization. which states that financial considerations shouldn't be a factor in decisions about who gets transplanted. But as it happens now. people who are insured may get two new hearts while the uninsured person gets no new heart. I think that the medical community can't be allowed to make all these decisions on its own. And that there should be a societal and public involvement.

Dr. WILKES: Well, maybe society should be involved, but I'm not sure realistically how that's going to be done. Are we going to have some sort era system where there's a selection process like there is for juries?

Where people from the community serve on some sort of a panel? And what about the issues of confidentiality for the patient? I think that realistically the decision needs to be made by the medical community. Now that doesn't mean just doctors. Medical ethicists, clergy, social workers, nurses, all need to be involved.

The criteria could be made more explicit. Decisions could be open to review by government experts. And patients could be told ahead of time about the criteria of who's going to get another heart and who's not.

HANSEN: Now, what do people with serious heart disease say about whether or not they should be allowed to receive a second new heart?

Dr. WILKES: Well, I'm sure it depends on who you talk to. The patient I spoke with had some real ambivalence.

Heart Transplant Recipient: It's a very difficult ethical question, as well as one that's naturally difficult to look at. Put simply, it costs hundreds of thousands of dollars to do this. My second transplant cost well in excess of $200,000. That same amount of money, spread in prevention programs, could have prevented disease and death for any number of people. I know in a personal sense that I'm very glad the money was spent. But I'm not sure that as a society we should be doing that.

HANSEN: Well, perhaps it's time that society did begin to examine these issues. Our medical commentators, Drs. Michael Wilkes and Miriam Shuchman. Thanks, both of you.


UpBeat apologizes to any and all who have been having problems either sending or receiving e-mail from our listed address. Somehow about the last week in September the string over the tidewater swamps broke on our "Net" access provider's system and flat put us back in the dark ages of snail mail and telephone. We' re not out of it yet, but hopefully will be by the time you read this. So try donmarsh@inna.net first. If that "bounces" on you we've gotten fed up waiting and moved our address.

Tx Cliff Steer, The Heart Man of San Jose, recently wrote, "Your computer will probably go into overload with another cyclo/mosquito repellent story, but ........ while waist deep in glacier water learning to fly fish in Whistler, Canada; my guide/tutor was being eaten alive (even Deet didn't help). I was catching Dolly Vardens, bug free. Twelve and a half years and about a million dollars worth of cyclosporine later - what a deal!!"

Tx Ralph Thornton reveals what may be the coming protocol in "annuals". "My transplant team (UT Southwestern Health Sciences Center/St. Paul Medical Center, Dallas) really surprised me at my annual. I am 8 1/2 years post-transplant. They said that out of all the left-right caths that had been done on those more than a year out, the procedure only ever quit and don't ever look back.

Times they do change in the transplant business. I can remember 8 or 9 years ago nearly begging my transplant center to give me a flu shot. It was given grudgingly the first time, but with decreasing reluctance as the years went by. Today I received a post card signed by the clinic Tx physician and sent to all heart recipients from this same center reminding me how important it is for both myself and my family to get flu shots.



by Jan Davis, BUMED Public Affairs

WASHINGTON (NWSA) -- Navy medical researchers believe they have found a way to prevent"mismatched" transplanted organs from being rejected, thanks to new therapy that reeducates the immune system.

CAPT David M. Harlan and LCDR Allan D. Kirk, both doctors at the Navy Medical Research Institute, and other Navy researchers have developed a new medical therapy that re-educates the immune system so that it recognizes transplanted organs -- even transplanted organs that are completely mismatched -- as being the individual's own. This "acceptance" of the organ prevents it from being rejected.

The researchers reached a significant milestone in their research when they transplanted very mismatched kidneys into two monkeys and treated them with the therapy. No other therapy. including the use of anti-rejection drugs. was administered. Six months later, the monkeys are robust and suffering virtually no side effects. The expected lifespan for monkeys with mismatched kidneys is about 21 days. A summary of Harlan and Kirk's research is published in the Aug. 5 issue of the Proceedings of the National Academy of Science. Harlan and Kirk's research stemmed from earlier Navy work that suggested that some immune responses could be turned "off" or "on" at will. Controlling this off or on response are T lymphocytes, or T cells, which play a key role in the immune system by fending off infectious agents. However, the T cells can also attack "invading" transplanted organs, which ultimately leads to organ rejection.

T cells are, in turn, controlled by chemicals known as co-stimulators and receptors. Harlan, Kirk and their fellow Navy researchers discovered a way to control the T cell co-stimulators and receptors to keep the immune response turned off against invaders so the T-cells won't attack transplanted organs, no matter how mismatched.

"Our mission is to replace tissue that is damaged and provide a reliable way that a Sailor. as a result of combat, can have an organ replaced." said LCDR Kirk. According to the United Network for Organ Sharing, which tracks organ transplant data, almost 4,000 Americans died in 1996 as they waited for a compatible organ donor. Tens of thousands of other have decrease quality of life while they wait for an organ match or suffer from the side effects of anti-rejection drugs.

Harlan and Kirk believe that in addition to preventing organ transplant rejection, their research may provide help for immune system illnesscs ranging from the relatively innocuous, such as hay fever, to severe and life-threatening, such as multiple sclerosis and lupus.

"We believe this product... will save the lives of U.S. service men and women," said CAPT Harlan.


by Roger Taylor

(F.T. 7/14/97) Ms Gail Naughton, president of Advanced Tissue Sciences, the US biotech company, believes she will soon be able o grow a human heart in a box in her laboratory at La Jolla, California.

The company, which already sells artificially manufactured human skin, recently announced it had grown a human finger joint from a few cells. It has also managed to grow valves, heart muscles and blood vessels. Ms Naughton says it is only a matter of time before the company grows a complete heart.

ATS's technique, co-invented and patented by Ms Naughton. uses chemical "scaffolds" to shape growing human tissue. A few cells are planted on the scaffold and fed with nutrients.

The key to growing durable organs is to recreate conditions in the human body, Ms Naughton says. When ATS scientists grow a ligament, they stretch it so it grows strong. Cartilage is put under pressure to make it tough, while arteries, she says, pulsate in their boxes as they grow. Scientists, including Professor Robert Langor of the Massachusetts Institute of Technology say most of technology needed to create a bio-engineered hand or arm is already in place. The main difficulty is regenerating nerve tissue. Researchers are investigating using microchips as an alternative.

Contributed by
Tx Steve Olowiany - Los Angeles


CHICAGO (UPI 10/7/97) -- Organ transplant specialists have identified an early warning sign of future heart transplant failure.

In a study of 121 patients who received new hearts between 1988 and 1995, researchers found that recipients who developed certain blood vessel changes shortly after the operation faced four times the risk of rejection years later.

The hearts failed because of an accelerated hardening of the arteries, which strikes about half of transplant patients five years after surgery, says the research team, which was led by Dr. Carlos A. Labarrere of the Methodist Research Institute (MRI) in Indianapolis.

Dr. Douglas Pitts, a transplant cardiologist at MRI, says a transplanted heart from a 20-yearold "may look like that of a 70-year- old" in three years in a patient prone to the problem. Pitts says patients with these markers, an immune system reaction that affects blood vessel linings, should be monitored carefully and entered in clinical trials of new drugs.

Currently, there are no effective treatments for this condition, although lowering cholesterol appears to help, he says. Coronary artery disease is the leading cause of death in transplant patients after the first year, he says.

The study is published in the Journal of the American Medical Association (JAMA).

Transplanted hearts failed in more than 25 percent of the patients who developed the markers within eight months after the operation, while only 7 percent failed when the marker molecules did not appear.

In an editorial in JAMA, Drs. H. Thomas Aretz and Robert B. Colvin of Massachusetts General Hospital say this is a "potentially valuable measurement" to evaluate the risk of deadly artery disease in transplanted hearts.
(Written by Mara Boysun in New York)

ORGAN DONORS GET LIGHTER SENTENCE By Leslie Lloyd - Associated Press Writer

JOHNSON CITY, Tenn. (AP 10/1/97) -How much is a kidney or lung worth? Twelve days in Judge David Brand's court.

Brand wants more people to sign organ donor cards, and he's offering this deal: Those placed on probation for misdemeanors can get up to 12 days knocked off their community service if they sign an organ donor card.

"It's such a waste to bury those organs in the ground," Brand said Wednesday from his office in Rogersville. He plans to begin offering the deal to defendants in his General Sessions Court later this month. Hedy Weinberg of the American Civil Liberties Union of Tennessee does not like it. "I'm not sure it is the appropriate role of a judge to say, 'We will decrease community service if you donate your organs,'" she said. "It doesn't appear to fit into the appropriate role of punishment and rehabilitation."

Brand, who has a friend awaiting a kidney transplant, said he's not forcing anyone to give up organs, and noted the defendants can always revoke their donor cards later.

"It' s no skin off them," he said. "It's not like I'm saying I want their kidney now."

Under state guidelines, people convicted of misdemeanors must perform two days of community service for each month of probation.

Lee McCartt, executive director of Life Resources Regional Donor Center in Johnson City, is a bit uneasy about Brand's plan. but supportive.

"It's a little radical in terms of the way we go about things," he said. "It's not something we would go out and (encourage) the Bar Association of the judges" to do.

.With more than 53,000 people awaiting organ transplants nationwide, McCartt said anything that encourages donations is good.

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