Oriented to Thoracic Transplant Recipients -- June 1996

The UPBEAT! Archive

A Complete Overview of all the Potential Systems for Organ Donation


Ethical Issues in Organ Transplantation
by James F. Childress, Ph.D.

Exactly 25 years ago, I was seduced by the emerging field of biomedical ethics, or bioethics, which explores ethical issues in the life sciences, medicine, and health care. This enticement occurred during my second year of teaching at the University of Virginia, when law and medicine faculty set up an interdisciplinary seminar on Artificial and Transplanted Organs and needed a faculty member from the humanities to round out their roster.

Two questions dominated our discussion of ethics and public policy in organ transplantation: How can we increase the supply of transplantable organs? How can we distribute available organs in an effective, efficient, and just way? These two questions continue to dominate ethical and policy debates. Here I will address only the first question, while noting that the two are interconnected, since increasing the supply of organs could reduce some of the dilemmas in distribution, and the public's perception of the fairness of the allocation scheme appears to influence its willingness to donate organs.

Acceptability and preferability

I ask you to grant me two assumptions even though they are not controversial: (1) We need to increase the supply of organs in order to save lives and/or enhance the quality of those lives, and (2) our societal efforts to increase the supply of organs should remain within certain ethical boundaries.

The first assumption may be problematic for some of you, depending on your view of the overall success/failure and costs of organ transplantation. No doubt there are problems, as well as excessive media hype, but there is no single entity labeled "organ transplantation." However, let us grant, at least, that kidney transplantation should be expanded to extend lives at a reasonable quality and to save End-Stage Renal Disease Program considerable money over time. I also believe that several other transplants pass a reasonable benefit-cost analysis, but all we need for this discussion is to assume that some cadaveric organ transplants should be performed and we don't have enough cadaveric organs to perform all of them.

The second assumption is that our efforts to increase the supply of organs should respect certain ethical boundaries or limits. The goal of increasing the supply of cadaveric organs will not justify every conceivably effective means of doing so-the ends do not always justify the means. Even if you concede that point, we will still have, I am sure, vigorous debates about where ethical boundaries or limits should be set. Assessments of actual and proposed laws and policies often appeal to general moral principles or values, such as respect for personal autonomy, non-infliction of harm, voluntarism, altruism, and communal solidarity, all of which are widely recognized in our pluralistic society. In what follows, I will appeal to such general moral norms to support judgments of ethical acceptability and ethical preferability. Both types of judgment are important. For instance, even though two or more laws or policies may be ethically acceptable, because they pass our minimal ethical screening tests, one of them may be ethically preferable because it promotes communal altruism.

We still have to ask which of these policies is politically feasible. By this I don't mean only which policies can survive in the legislatures and the courts, but also which can elicit cooperation from institutions, professionals, and individuals and their families. Eliciting cooperation is very complicated because the human body is associated with various emotions, sentiments, symbols, and beliefs, and tied to various rituals and communal practices. Policies that appear to be feasible from a strictly rationalistic standpoint may turn out to be ineffective and even counterproductive because they do not adequately attend to the psychosocial significance of the human cadaver - hence, the limited success or outright failure of some of the policies implemented over the last decade. In addition to being too rationalistic, our policies are often too individualistic, formalistic, and legalistic.

A case study of our system

You will certainly be familiar with the following case because one of the recipients of the donated organs was famous. However, I want to present it from the standpoint of the organ source/donor, whose story is not so well known. Indeed, I have read it in only one brief account in the sports section of the Washington Post (August 4, 1995).

In early June 1995, a popular, athletic Texan in his twenties, who was still trying to decide what he wanted to do and to be died unexpectedly; an aneurysm took his life. "In death," as one newspaper sports page noted, "He gave half a dozen people their futures, among them a truck driver, a farm manager, a backwoods-resort operator and an American legend named Mickey Mantle."

Newspaper reporters managed to identify who had provided the organs, but, at the family's request, did not name him in the report or to the recipients. The mother explained the family's decision to donate: "Once his soul and spirit is gone, nothing is left. His body is of use to somebody else only in this way. It never even crossed my mind not to donate. To me, it's the decent thing to do. It's the thing we should do."

Let's consider the act of donation in this case to answer some questions about our system of organ procurement. First, who is an "organ donor?" As obvious as this question sounds, the answer is far from obvious. By the term "donor," do we refer to the decision maker (i.e., the one who decides to donate organs), or to the cadaveric source of the organs themselves? Obviously, these two may be the same, but the decision maker may not be the source, and the source of the organs may never have been competent to make a decision about donation or may never have made a decision to donate. For instance, a dead child is the source of organs, but is not himself/herself the donor. Likewise, someone who sells an organ is not a donor, but rather a seller or vendor. I have long protested the promiscuous use of the terms "donor," "donation," and "gift" in imprecise and often misleading ways, but my protest may well be fruitless. My protest is important, however, because these terms refer to a certain kind of social-moral practice, which has an extremely high value as well as its own internal logic. We have to be careful not to transfer its moral aura indiscriminately and inappropriately to other social-moral practices. Other examples of problematic terms in organ transplantation include "harvesting," "salvaging," "procurement," and "retrieval" of organs, each of which has ambiguous and even controversial implications.

Second, who was the donor in this case? From the brief report I read, it appears that the mother was the donor. The mother said, "It never even crossed my mind not to donate." Now she apparently made her decision to donate on the basis of a felt obligation ("the decent thing to do") because the organs were no longer valuable to son or to her they were now valuable only in their use for others. Thus, the donation appears to have been her decision. At least from the case report, it appears that she was the donor, and her son only the source or provider of the organs. We have no indication that he had signed a donor card or had otherwise indicated that he wanted to donate his organs.

Let' s suppose, however, that the mother could have rightly claimed that donation is what her son wanted. If he had expressly told her that he wanted to donate his organs, even though he didn't sign a donor card, then he was the donor as well as the source, and his mother merely conveyed or expressed his wishes. She was simply the recorder of his prior donation. In the absence of any prior oral or written indication of his preferences, his mother could still have argued, not implausibly in this case, that he would have wanted his organs donated. After all, just a week before his death he was at a nearby lake when a man who was trying to swim to an island started to sink, and, as a former lifeguard, he swam out a long distance and pulled the man safely to shore. His mother could have constructed his willingness to donate on the basis of the way he lived, for example, by taking his heroic act a week before as indicative of his moral character and of his desire to save others, even at some risk to himself.

Third, how does this case fit with contemporary law and practice? In view of the laws and practices that have evolved in the U.S., we should not be surprised that the mother was the actual donor of her dead son's organs. The law establishes who has dispositional authority over the cadaver (and its parts) and within what limits. In theory it could recognize various rights holders and assign them various rights (and responsibilities). The rights holder could be, for example, the individual while alive, the family after the individual's death, or the community at large. The rights held could include rights to use, to destroy, to transfer by any means, to transfer by gift but not by sale, to sell, and so on. Such rights could thus be limited or full, parallel to rights in property.

Regarding rights and the cadaver

What exactly is our legal structure of rights regarding the cadaver? As organ transplantation emerged in the 1960s as a legitimate medical option, mainly for patients with end-stage renal disease, our laws were marked by inconsistencies regarding rights holders, whether the individual while alive or the family after the individual's death.

Transplantation really could not proceed or succeed without consistency and even uniformity in laws governing the transfer of organs. As a result, the Uniform Anatomical Gift Act (UAGA) was formulated and then rapidly adopted by all 50 states and the District of Columbia. That law established a "gift" or "donation" framework for the transfer of organs. Within that framework, competent individuals have the right to determine what will be done with their organs after their deaths. In the absence of a valid expression of the decedent's prior wishes, the family legally can decide whether to donate his or her organs. The family's right to decide is a default mechanism.

As a matter of social practice, in contrast to the law, the default mechanism has itself become primary - individuals rarely sign donor cards, organ procurement teams rarely find them. Some organ procurement organizations (OPOS) report never having obtained an organ on the basis of a signed donor card. OPOS and others virtually always consult the family if available, and, in cases of conflict, which occasionally arise, between the decedent's expressed wish to donate and the family's opposition, OPOS yield to the family for misguided legal reasons and understandable ethical reasons.

The common fear of legal liability is misguided because the UAGA provides blanket immunity from civil and criminal liability for good faith actions on the basis of signed donor cards. The ethical reasons include concerns not to increase the family' s personal trauma by neglecting or overriding its wishes in tragic circumstances, and not jeopardize organ procurement through creating an image of professional "vultures" taking organs over the protests of a grieving family.

In the U.S., then, the transfer of solid organs occurs by express donation by an individual and/or family. (Express donation laws also operate in such countries as Australia, Canada, Denmark, Holland, Japan, Sweden, Turkey, the United Kingdom, and most of Central and South America.) While the law in the U.S. is primarily individualistic, practice is primarily social, with the individual viewed as part of a small community, the family. One ethical and practical problem is bringing the two together for educational and other purposes.

Why don't individuals donate by signing donor cards? According to several very or somewhat likely to donate their organs after their deaths (Gallup Organization, 1983, 1985, 1987), and even fewer actually sign donor cards or other documents of gift. Perhaps this figure shouldn't be too surprising since only about 20 percent of the decedents leave a will. The specific reasons for failure to sign donor cards include lack of thought about donation and reluctance to face the prospect of death. Other significant reasons reflect distrust, or limited trust, in the system: Many people worry that if they sign a donor card, physicians might act prematurely to obtain their organs before they are really dead or might even hasten their deaths to gain the organs. In contrast to current figures, in 1968, around the time of the first heart transplant, 70 percent indicated a willingness to donate.

Why the shift? The 1970s brought increasingly adversarial relations between the public and medical and health care professionals, as witnessed by the dramatic increase in malpractice suits. Suspicion has replaced trust. In addition, the stated willingness to become organ donors is even lower among minority groups, who perceive themselves to be on the margins of the system and to have even less reason to trust it.

Inquiry and choice

Supporters of organ transplantation have proposed ways to encourage voluntarism or altruism on the part of individuals while alive. One policy is "routine inquiry" directed at individuals in various settings. Concerns have arisen about whether it is appropriate (as well as effective) to inquire in certain settings. To many it appears both inappropriate and counterproductive to ask routinely of patients entering the hospital for an appendectomy, for example, whether they have signed a donor card, as recommended in the amended UAGA (1987) and enacted by some states. However, few people have major objections to routine inquiry in other contexts, such as obtaining a driver's license.

Another proposal is "mandated choice" by which individuals would have to indicate, perhaps when they obtain a driver's license or file income tax forms, if they want to donate and their choice would be entered into a national registry. But, according to the survey data about why people do not sign donor cards, many individuals, if forced to choose, would check "no," because they are afraid of being on record as donors of organs, not because they oppose their family' s donation of their organs after their deaths. However, their "no" would then preclude familial donation. Hence, it is likely that a policy of mandated choice would thus reduce rather than increase the number of acts of donation. I have long made this claim but now there is some empirical evidence to support it. In Texas, mandated choice has resulted in a refusal rate of 80 percent. And those refusals block possible familial decisions to donate. It is likely that similar blocks occur in Virginia, where applicants for new or renewed drivers' licenses are asked whether they are organ donors, and they are given the options of "yes," "no," and "undecided." The choice is then imprinted on the license itself. Perhaps the category of "undecided" will be selected often enough to keep open family options.

Both routine inquiry and mandated choice arguably concentrate too much on the donor card. They confuse the requirement of respect for individual autonomy, a legitimate requirement of both morality and law regarding the transfer of organs, with the promotion of personal autonomy and even with a particular exercise of autonomous choice. Proponents of mandated choice fail to appreciate that individuals may choose to let others decide after their deaths what will happen to their organs. This waiver of the right to choose for themselves may itself be autonomous choice.

Extending this point, another possible policy is to allow individuals to designate surrogate decision makers who can express their values after death. Individuals may be more willing to designate a decision maker whom they trust than to sign a document of gift that might put them at risk at the hands of strangers in large, impersonal, bureaucratic institutions that appear eager to gain organs. This proposal has a parallel in advance directives regarding life-sustaining treatment in case of incompetence.

Why don' t families donate the organs of dead relatives? In the U.S. as in most other countries, the family is the primary donor of cadaveric organs. Opinion surveys indicate that individuals are more willing to donate the organs of family members, particularly if they know the decedent's wishes, than they are to donate their own organs by signing donor cards (Gallup Organization, 1983, 1985, 1987, 1993).

The main bottleneck in obtaining cadaveric organs thus appeared to be the failure of health care professionals to ask families about donation when a relative died. The problem was construed as a shortage of askers rather than a shortage of familial givers. In this context, Arthur Caplan proposed "required request" directed at the decedent's next of kin. This policy has now been enacted in the U.S. by most state legislatures, mandated in federal legislation for all institutions receiving Medicare or Medicaid funds, and required by the Joint Commission on Accreditation of Healthcare Organizations.

Despite required request, which once appeared to be so promising, the number of acts of donation of solid organs each year remained relatively constant for several years, at 4,300 to 4,850, with most increases occurring as a result of changes in the criteria of organ eligibility (e.g., accepting donations from older persons whose organs would not have been used earlier). However, the overall donor pool has shrunk for various reasons, including the decline in automobile-related deaths and the spread of the human immunodeficiency virus (HIV). In this context, "slow increases in the number of donors, or having the numbers of donors hold steady... suggest that the present level of donation may be higher than it would be without the laws." Required request policies may also have had positive, indirect effects in making requests for donation more routine in hospitals. Nevertheless, many have wondered whether the reluctance of physicians and other health care professionals to make such requests accounts for the modest direct effects.

According to an important recent study, even if health care professionals remain reluctant to ask, they generally do ask. In close to 90 percent of the cases in which the decedent could possibly provide transplantable organs, some member of the health care team asked for permission to use the decedent's organs. However, only 46.5 percent of the families asked agreed to donate organs (and only 34.5% agreed to donate tissue). This study did not address the question of whether professional reluctance, perhaps even on moral grounds that they do not want to burden the grieving family, may persist in when and how professionals ask the family.

One proposal to overcome professional reluctance is "routine referral," or "required referral," which would require that institutions and health care professionals routinely notify a trained procurement team in circumstances in which cadaveric organs and tissues might be available. Presumably such a trained team could be more effective while at the same time assisting the family in its grieving.

Other methods of obtaining organs

Possible methods of transferring cadaveric organs and tissues include: (1) express donation by the individual while alive or by the next of kin after his death; (2) presumed donation, with consent to donation presumed of the individual while alive and/or of the next of kin; (3) routine removal or salvaging (with the possibility of opting out); (4) expropriation or conscription (perhaps with the possibility of conscientious refusal); (5) abandonment or failure to claim bodies and parts; and (6) sales. Having now considered the first method, I will try to show that, for solid organs, all of these other possible modes of transfer suffer from one or more of the following defects: They are ethically inferior, ethically unacceptable, or politically infeasible. Sometimes proposed policies are ineffective or counterproductive and are thus problematic on both ethical and feasibility grounds.

All of these methods of transfer play some role in access to living or cadaveric organs, tissues, and fluids. For example, in the U.S., express donation is virtually the only method of transferring solid organs, while presumed donation or routine removal is used for corneas in several states. Sales remain prevalent in the transfer of tissues for purposes of research. While expropriation or conscription is rare and more controversial, it appears in legally required autopsies and tests for the use of illicit drugs.

Presumed donation or routine removal. Laws authorizing presumed donation or routine removal (frequently called routine salvaging) have been adopted for corneas in several states in the U.S. and for organs and tissues in several countries including Austria, Belgium, Finland, France, Norway, Portugal, and Singapore. These laws authorize the removal of organs or tissues, usually without familial notification, in the absence of the decedent's prior and/or the family's current explicit dissent. They thus involve "opting out" rather than "opting in" - that is, individuals and, in principle, their relatives must take affirmative action to stop the process of donation or removal rather than to initiate it.

How should we interpret and evaluate such laws? Presumed donation and routine removal are often considered interchangeable, but in fact their moral bases are quite different. A policy of presumed donation assumes that the individual (and/or the family) owns and thus has dispositional authority over cadaveric organs and that the decedent's prior failure (or the family's current failure) to dissent constitutes consent. By contrast, routine removal presupposes that the society has a right of access to cadaveric organs and tissues because it owns them or because individuals and families have an enforceable social duty to provide them. Such a communitarian approach to organ removal may allow opting out for various reasons, such as conscientious objection.

In order to identify the operative moral basis of laws that authorize removal without express consent, it is necessary to look beyond society's rhetoric to determine what occurs in practice. If the policy is really presumed donation, then society should undertake vigorous efforts to ensure public understanding and voluntariness. If, however, the policy is routine removal, public understanding and voluntariness are superfluous, even though they may be sought for practical reasons.

The main objections to routine removal rest on what William May calls the "principle of extraterritoriality," which holds that even the deceased individual is not reducible to the needs of the social order. Many people concede that presumed donation, based on understanding and voluntariness, may actually be less cost-effective than enhanced and redirected educational efforts for express donation. Furthermore, many view express donation as ethically preferable to presumed donation because it manifests and supports active altruism.

Objections to the presuppositions of routine removal may in part explain why the rhetoric of presumed donation is so widespread. And uneasiness about society's dispositional authority over cadavers, or about the meaning of and individual's (or family's) failure to dissent, may account for the fact that actual practices of organ procurement are similar in most countries, despite their different legal frameworks.

For example, in most countries with so-called presumed consent, professionals regularly ask the family or follow the families known wishes, just as they do in countries with express donation. Among European countries with presumed donation or routine removal, only Austria, with its long tradition of authorizing autopsies on all persons without requesting permission, does not in practice notify the next of kin.

Neither presumed donation nor routine removal appears to be politically feasible in many social contexts, including our own. In light of widespread public opposition in the U.S. to the removal of organs on the basis of presumed consent, such a policy would probably reduce rather than increase the number of donated organs (as has happened under mandated choice).

The attitudes of distrust that now obstruct express donation would probably lead individuals to remove themselves from the list of presumed donors and thereby preclude familial decisions to donate. However, supporters of presumed donation note that several states already have laws that authorize the removal of corneas, without consent, by medical examiners or coroners who examine bodies following accidents or homicides. These laws have survived constitutional challenges in some states, even when they do not require notification of or consent from the next of kin. Furthermore, they have been effective.

For example, after Georgia adopted presumed donation, cornea transplants increased from 25 in 1978 to over 1,000 in 1984. Such laws may survive without major vocal opposition because of different views about different body parts (corneas versus solid organs) or because the public is largely unaware of these laws. If the last reason holds, then presumed donation is, I believe, ethically invalid because of a lack of understanding on the part of the putative "donors," whose silence is construed as passive consent to donation. Under such circumstances, the policy touted as presumed donation is actually closer to routine salvaging or perhaps even to expropriation with a right to refuse, perhaps on conscientious grounds. (To be completed in July issue of UpBeat)

Dr. Childress is Kyle Professor of Religious Studies, professor of medical education, and co-director, Virginia Health Policy Center, University of Virginia, Charlottesville, VA

Bulletin of the American College of Surgeons, March 1996
Contributed by Don Marshall, M.D.


I suppose I could wax poetic, or whatever, about the nature of the mind of the human beast, however, ye shall be spared. It's just that the human mental make-up can get quite ridiculous, to wit: Nine years ago I was in the height of frustrated and even tearful depression about the recently discovered fact that it was almost assured that I would never live to the relatively young age of sixty, and without a transplant the next month was questionable. Now today, having just passed that now seemingly ugly 60 year milestone, I'm totally depressed about having reached it!

It's obvious some of us "just don't get it." Claire Silvia, of "I definitely have taken on characteristics of my heart/lung donor" fame has now signed a movie contract for her yet to be completed book A Change of Heart. The lead will be played by Sally Field. It is noted that the option price was "well into six figures." Is it not time to put a stop to this kind of hokum, before it gives the public a very nonscientific impression of a very technical life saving medical field? It is also noted that no mention has been made of any large donations being made in Ms. Silvia's name to any area of transplantation patient welfare

And just to prove that exceptions are the rule, former Pennsylvania Gov. Robert Casey, now President of T.R.I.O. among other ventures, is releasing his memoirs in a book called Fighting for Life.

The only squib we've seen says the book, "details Casey's Catholic upbringing and his rise to the governorship, documenting how Christian principles shaped his life and helped him stand firm against abortion." It's a 272 page book retailing for $21.99.


By Ed Susman

DALLAS, (UPI 5/28/96) -- Researchers admitted Tuesday that they have been prescribing their organ transplant patients too much of too many drugs for years.

In a series of reports at the annual meeting of the American Society of Transplant Physicians in Dallas, doctors said they are now learning to use lower doses of old immunosuppressive drugs as well as newer medications to provide the same survival benefits to patients often with fewer side effects.

In one study, Dr. Jean Tchervenkov of the department of surgery at McGill University in Montreal explained how liver transplant patients were carefully weaned off use of steroid and other anti-rejection drugs and were successfully maintained by use of just cyclosporine, the drug most often used in the treatment of transplant patients to prevent organ rejection.

Almost all of Tchervenkov's patients were able to continue on just cyclosporine. Standard treatment of liver transplant patients as well as other organ recipients has involved multiple drugs to prevent organ rejection -- often a fatal occurrence -- and other drug side effects.

"We have probably been over-immunosuppressing patients for 20 years," agreed Dr. Sue McDiarmid, assistant professor of pediatrics at the University of California at Los Angeles Medical Center.

McDiarmid told United Press International that in addition to knowing how to use medications such as cyclosporine better, doctors now have more anti-rejection medications available as well.

A new formulation of cyclosporine, a microemulsion called Neoral. Manufactured by Sandoz, the same company that produces oral cyclosporine, Neoral was cited in several studies as having the same effectiveness as cyclosporine, but with far greater bioavailability.

So strong was the ability of Neoral to be absorbed, said Dr. Leslie Miller, head of the heart transplant program at St. Louis University, that 58 percent of patients required dose reductions.

Dr. Barry Kahan, professor of surgery at University of Texas Health Science Center at Houston, said that variability in absorption of cyclosporine is a major risk factor for organ rejection, estimating that 29 percent of patients who suffer organ rejection due so as a result of inconsistent levels of anti-rejection drugs.

Neoral's more consistent absorption rate is "likely to reduce rejection risk."

Another drug, tacrolimus, manufactured as Prograf for Fujisawa USA, Inc., reduced episodes of acute organ rejection by nearly 50 percent in patients, Miller said, noting that major studies in the use of the drug are still lacking. But dosages of Prograf most likely will have to be reduced due to toxicities, he said.

Other studies indicated an increased risk of development of worrisome lymph node disorders with tacrolimus, disorders which could be precursors of cancers.

Mycophenolate mofetil, manufactured by Hoffman-La Roche as Cellcept reduced the incidence of acute rejection to 19 percent among pediatric patients, said Dr. Robert Ettenger of UCLA Children's Hospital.

Ettenger said additional studies of Cellcept are needed to determine exact doing schedules in children and to determine if there are serious side effects.

Several researchers noted that the tools for controlling organ rejection -- about half of organ transplants fail after five years -- are available; but scientists still are tinkering with dosages and are debating about how and when to use them.


Now with tacrolimus

By Ed Susman

DALLAS, (UPI 5/28/ 96)-- For transplant patients, a daily diet of grapefruit juice cuts the need for medication that can prevent rejection of transplanted organs, a Cleveland Clinic researcher said Tuesday.

The juice heightens the body' s ability to absorb the medication tacrolimus allowing patients to markedly reduce the amount of the drug they are taking -- without risking rejection of the organ, said Dr. James Mayes of the Cleveland Clinic Foundation.

"One 68-year-old woman who loves grapefruit juice has been able to reduce her medication to one milligram every other day," Mayes told United Press International. "Normally people take 2 to 4 milligrams of tacrolimus twice a day."

Tacrolimus is one of the new drugs that help prevent rejection of transplanted organs. It is often used in place of cyclosporine, the drug most commonly used among transplant patients.

In a presentation at the annual meeting of the Thorofare, N.J.-based American Society of Transplant Physicians in Dallas, Mayes said he became interested in the possibility of grapefruit juice having a reaction in tacrolimus because there is a similar reaction in patients taking cyclosporine. He said studies have shown that taking grapefruit juice around the time a person takes cyclosporine can increase absorption by as much as 52 percent.

In Mayes' study of eight liver transplant patients, concentrations of tacrolimus in the blood increase as much as 2.5 times over 24 hours among some patients.

Mayes said the study results show that grapefruit juice has an impact on medication absorption, something that doctors, patients and pharmacists should take into account.

On one hand, a reduction in dosage can result in a financial savings to the patients. But failure to recognize that there is heightened absorption can result in toxic reactions, Mayes said.

He said people on tacrolimus or other anti-rejection medication should talk to their doctor about the reaction the drug may have with co-administration of grapefruit juice.

Mayes says that grapefruit juice contains substances that stimulate a cascade of events which increase the ability of intestinal cells to absorb chemicals such as those in tacrolimus or cyclosporine.

For those who like orange juice, the news is bad: orange juice does not have the same substances as grapefruit juice. Mayes also noted that different consistencies of grapefruit juice could also affect absorption.


Doctor: In view of the fact that Dr. James Mayes has now reported to the Transplant Physicians Meeting that grapefruit juice increases the blood serum levels of tacrolimus in the same manner as the previously reported effect with the same juice on cyclosporine levels, what is the proper action for a transplant recipient?

  1. Stay away from grapefruit juice all together?

  2. If the recipient has a great fondness for grapefruit juice, once consumption is started, the blood level of cyclosporine or tacrolimus should be established and then the consumption must be held at the same level continuously?

  3. An occasional snort of grapefruit juice probably won't hurt anything, but keep to a. once a week b. twice a week c. 3 times a week?

  4. Processed grapefruit juice such as the Twister Light Pink probably has no effect?


Given the fact that grapefruit juice exerts its effect by inhibiting enzymes that would break down the drugs in the intestines, before they got into the bloodstream, I would say that one should refrain from taking grapefruit juice around the time that one takes the drug.

I don't know how quickly tacrolimus is absorbed, but Neoral peaks within 90 minutes. So if one takes Neoral at breakfast and dinner time (about 12 hours apart) I see no reason why one could not indulge in grapefruit juice at lunch time.

This is my considered opinion. I don't know anything about processed juices and their relation to regular juice, since I don't think anyone quantifies the amount of flavinoids in grapefruit juices, anyway.

M.D. Grebenau, MD Sandoz Pharmaceuticals

Question was submitted by: T.C. Marchion on 5/10/96

Question: What percent of transplants heart/heart-lung/and then of all transplants get some form of cancer and what percent survive cancer?

Answer: The overall incidence of cancer in organ transplant patients is said to be about 6%. Heart and heart/lung patients appear to be similar to other transplant patients. By far and away, the most common type of cancer that develops in transplant patients is skin cancer, which causes almost a third of the cancers. Transplant patients do have a higher than normal risk of skin cancer and !ymphoma, a cancer of the lymph system. Survival after skin cancer is nearly 100% since most of the skin cancers that occur in transplant patients are not deadly types. Survival after lymphoma is roughly 50%. Fortunately although lymphoma is more common in transplant patients than in the general population, lymphoma is still uncommon in transplant patients.

Jeff Punch, Transplant Surgeon, University of Michigan from Transweb.


By Ed Susman

DALLAS, (UPI 5/29/96) -- Even as scientists struggle to understand and overcome basic mechanisms for creating animalto-human transplants, federal officials said Wednesday guidelines will be published in June that will govern the controversial field of xenotransplantation.

The proposed rules will require surveillance of transplant patients to trace diseases that might be passed from beast to man and then to the rest of humankind.

Louisa Chapman of the Centers for Disease Control and Prevention in Atlanta promised attendees at the annual meeting of the American Society of Transplant Physicians in Dallas that the guidelines would be published in the federal register in June. She admitted that the guidelines were already late.

"Zoonotic (animal-based) disease can be a threat to the community," said Chapman who said the evidence is mounting that pinpoints African monkeys as the source of acquired immunodeficiency syndrome (AIDS).

Chapman said the greatest risk for transmitting animal diseases in a human population would be to the health care workers who attend to the first human who receive the animal grafts, and then those at next greatest risk would be family members of the patients.

But Chapman said there should be community input into guidelines because there is a general risk to the community as well. She said groups likely to be involved in the guidelines are transplant physicians and surgeons, immunologists, infectious disease specialists, veterinarians, microbiologists and virologists.

The guidelines also will be subject to scrutiny by the CDC, the Food and Drug Administration and the National Institutes of Health.

Among the guidelines:

While attempts to transplant organs from animals to humans -- the Baby Fae case in the mid- 1980s, for example -- have failed, researchers at the Dallas meeting reported making strides in eliminating the obstacles between animal-to-human transplants.

Dr. Jeffrey Platt, a leading researcher in xenotransplantation at Duke University in Durham, N.C., said, "Hyperacute rejection can be prevented now." In hyperacute rejection, the body's own system for detecting foreign tissue viciously attacks xenografts. But genetic- engineering has allowed science to hurdle that problem.

Even so, Dr. Wayne Hancock of New England Deaconess Hospital in Boston said scientists can only keep the foreign organs and tissues from separate species such as a baboon and a pig alive for four to five days before blood vessels stop working.

Hancock said the developments around this hurdle are in development. "We think we can block the cell activation," he said, although the scientist acknowledged the feat had not yet been achieved.

Dr. David Sachs, a Massachusetts General Hospital researcher, said the obstacles to xenotransplantation still are formidable, but he expects they will be surmounted.

Researchers in Sach's laboratory reported on various methods of protecting xenografts from attacks by the host' s natural defenses. That work and scores of research papers presented at the meeting indicates that interest in xenotransplantation has not waned.

"Xenotransplantation is one of the hot subjects at this meeting," said Dr. John Curtis, professor of medicine at the University of Alabama at Birmingham Medical Center.


LONDON, (Reuter 5/20/96) - British surgeons have cut out bits from the living hearts of coronary disease patients in a new surgical technique pioneered in Brazil which is giving new hope to patients.

The team led by British Heart Foundation Professor Gianni Angelini removed about three ounces of the left ventricle -- the heart's muscle powerhouse -- and then sealed the wound with a "super-glue" strip of synthetic material.

The technique is being used on hearts dilated by disease. After the surgery, the heart works easier under reduced pressure. The operation is quicker and cheaper than a heart transplant and requires less after-care. "It is high-risk pioneering surgery and we are in largely uncharted waters. However it has enormous potential for greater numbers of patients than heart transplants," Angelini said after operating on five patients.

One of them, 50-year-old estate agent Garry Payne, said: "Down-sizing the heart is not a miracle cure but there is no doubt it does improve the quality of life."

"I am looking forward to the next 25 years, particularly seeing my grandchildren growing up," he added.

Angelini carried out the operation for the first time in Britain after studying the technique pioneered by Brazilian cardiac surgeon Randas Batista.

A worldwide study group is now being set up to assess the procedure and its long-term outcome. Surgeons are cooperating in Britain, France, Italy, Belgium, the U.S. and Japan.


COLUMBIA, Mo. (AP 5/30/96) -Researchers are looking to the day when farm animals could provide organs to be transplanted into humans.

Scientists at the University of Missouri-Columbia hope to learn how to reprogram a pig's genetic blueprint so that its organs would not be rejected by a human body. Such "transgenie" pigs can be bred in large numbers.

"Once you get the founder transgenic animal, it's all downhill from there," animal scientist Randall Prather told the St. Louis Post-Dispatch.

"But you have to get those animals with the gene in it functioning the way you want."

Prather leads the project with fellow researcher Billy Day.

The scientists began work on transgenie pigs after receiving a $500,000 grant from the National Institutes of Health. They are working with scientists at Biotransplant Inc., a Boston-area company that is developing methods for transplanting animal organs into humans.

The big problem transplanting a pig heart, liver or other organ is the effectiveness of the aggressive human immune system. The system constantly seeks and destroys invading germs and foreign tissue, rejecting an animal organ within minutes of transplant.

Other researchers, including some at Washington University in St. Louis, have discovered ways around this line of defense.

Put simply, they found how human organs protect themselves from the immune system. They identified the parts of the human genetic blueprint that instruct the body to make this protection. Then they transferred these parts of the human genetic blueprint into pigs.

Experiments have shown promise, but organ farming is still several years away, scientists say. One problem is the difficulty of introducing human genes into the pig genetic blueprint in a useful way.


GLASGOW, Scotland (Reuter 5/16/ 96) - A green fungus that lives everywhere from the basement walls to the black pepper you shake over your spaghetti is threatening hospital patients and becoming impervious to drugs, doctors said Thursday.

Several experts speaking to a medical conference painted a frightening picture of bacteria and fungi that are rapidly mutating into drug-resistant forms, and they said pharmaceutical companies were not keeping up.

"There has not been a totally new class of drugs for a long, long time and this is what we need," Richard Wise of Birmingham University said.

Dr. David Denning of the University of Manchester said aspergillus, a common and usually harmless mold found in most households, was becoming a big killer of patients with AIDS, those having organ transplants and others who had weakened immune systems.

"We are starting to see the beginning of a hospital epidemic in coming years," he told reporters. "Six percent of all patients overall who die in big hospitals in Europe die of fungal infections."

Aspergillus, and to a lesser degree candida -- the source of "yeast infections" such as thrush -- were becoming resistant to all known drugs, Denning said. The first resistant cases were seen in 1990, but numbers were rising exponentially.

Aspergillus infection was responsible for 0.5 percent of hospital deaths in Frankfurt, Germany, from 1978 to 1982. In 1992 it was found in 2.5 percent of autopsies.

"These are bad diseases with a high mortality," Denning said.

Most people are completely immune to aspergillus, and tolerate candida well. The trouble comes when their immune systems are stressed, either by AIDS or with drugs used to keep transplant patients from rejecting donated organs.

Denning said 500,000 people got transplants around the world every year, and every single one was at risk.

To make matters worse, fungal infections are hard to diagnose. Patients have coughs or chest pain, which could be almost anything, and x-rays often showed little.

The most worrying was a form of staphylococcus that resists almost all antibiotics. It is extremely common but can cause infections ranging from a sore throat to deadly septicemia. As with the fungus, it was mostly affecting very ill patients in hospital, Casewell said. But unlike the fungi, bacteria can spread to healthy people.

Casewell said overuse of drugs by doctors and hospitals was also to blame, as was the use of antibiotics in animal feed, which meant people were exposed to low doses over long periods of time.


By Sam Greene

Bardstown, Ky. Three brothers who shared so much in health now share even more in sickness. All stricken with a rare and terminal heart disease, they wait together for scarce heart transplants.

How long they will live is uncertain, but their lives as they knew them are over.

Doug Greenwell, at 32, is both the youngest and the sickest of the three, all of whom have been diagnosed with dilated cardiomyopathy, which causes the walls of the heart to balloon so that the organ does not pump efficiently.

Keith, 35, and Ron, 36, have similarly enlarged and weakened hearts in different stages of the incurable disease, inherited in this case.

Shortly after Doug was diagnosed, the brothers dug up records showing that their father, who died at 45, also suffered from cardiomyopathy. Their mother died of unrelated illnesses last year, and their two other brothers have not been diagnosed with the disease. It is a rare disease, generally afflicting fewer than 35,000 people nationwide.

Because any physical or emotional stress could kill them, the brothers had to quit jobs they loved. The inactivity is hard to deal with, but necessary. The only long-term hope for the brothers is heart transplants.

It's a change from the lifestyle they've had since they were boys growing up on a farm in Kentucky's Marion County. They were always out in the fields, they said, either working the ground, mending fences or tending to the crops.

All three stay home now, seeing their kids off to school and their wives off to work in the morning.

"To get the transplant, though, and live through it, that's something to look forward to," Doug said, speaking for the three. Washington Post-Health 5/14/96 Submitted by Myrna Porter, VA

Disclaimer: The material in this document has been collected by Don Marshall and friends. If any of the views and opinions expressed here are taken the wrong way, we can be nothing more than sorry. New ideas and materials are welcome all the time. 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 non-profit. Send materials, letters, or checks to:

Don Marshall
P.O. Box 482
Mathews, VA 23109-0482
Compuserve 74016,1725
FAX 804-725-3686
Internet: donmarsh@inna.net

Site Stats: counter img