20071011

Organ Transplants

In the not-too-distant past, people stricken with failing hearts, damaged eyes, or diseased kidneys had little hope of recovery. Today, after years of medical research, these people have renewed hope, thanks in part to the ever-growing success of organ transplants—the process by which organs are taken from one person and implanted into another.

From One to Another

The earliest successful transplant operations were autografts, grafts from one part of a person's body to another. This process is valuable in grafting skin, blood vessels, and nerves. However, if a person has a diseased organ, a replacement must come from a primate or some other higher mammal.

If an organ donor is another person, the transplant is called a homograft. The first successful homograft was performed in 1954, when Richard Herrick had a kidney from his twin brother grafted into his body. Earlier kidney grafts were surgically successful, but Richard was the first to enjoy a long period (nine years) of normal life after the transplant.

A heterograft is a transplant between different species. The first heart transplant in humans was actually a graft of a chimpanzee heart into a man. Unfortunately, the patient died soon after the operation. Despite this failure, surgeons learned that a primate heart could support human blood pressure. A few baboon and chimpanzee kidneys have also been transplanted into humans, with limited success.

Rejection

Surgeons have mastered the techniques for transplanting most major organs, but the body often rejects a donor organ, causing the recipient to die soon after the operation. Such rejection occurs due to the action of complex molecules called antigens. A person may have any number and combination of antigens, and rarely will they be identical in two people. The most familiar antigens in the human body are the A, B, and Rh red-blood-cell antigens, which help define an individual's blood type.

The body has a vital line of defense—protein substances called antibodies—to fight against the foreign antigens that provoke infections. Antibodies are produced by lymph cells and are a vital link in the body's immune system against disease. And while antibodies are a valuable defense against disease, they also fight foreign antigens like those in a donor organ—and thus cause the organ to be rejected.

Cloning technology may allow us to harvest tissue from "transgenic" animals engineered to overcome the problem of rejection. Transplant patients may one day "grow" their own donor organs, therefore bypassing rejection. For now, we must rely on tissue typing, drugs, and radiation therapy to combat rejection.

Tissue typing.

The antigens that sensitize a recipient to a grafted organ are found in white blood cells called lymphocytes. Tissue typing identifies the combination of these antigens present in an individual. A potential recipient who has been tissue-typed will receive the best-matched donor organ available, dramatically reducing the chances of rejection. Rules for matching donor tissues and recipients must be rigorously observed. Otherwise, mismatches—like the one that led to the death of a 17-year-old girl at the Duke University Medical Center in 2003—may recur.

Immunosuppressive drugs.

Immunosuppressive drugs limit antibody production. The drug cyclosporine—combined with steroids—has dramatically improved survival rates. New research has suggested that the drug sirolimus (sold as Rapamune), an antirejection drug for kidney patients, is less toxic than the mainstay medicine most transplant recipients take. Patients given Rapamune were weaned off cyclosporine without increasing the risk of kidney rejection.

Immunosuppressive drugs must be used with care; they tend to weaken antibodies and expose the body to opportunistic infections such as pneumonia, which has killed many transplant recipients.

Radiation.

X-ray radiation can reduce the threat of organ rejection when applied to the site of the graft and to the tissues where antibodies are produced, such as the lymph nodes and the spleen. Radiation therapy is usually restricted to short-term use, because high doses of radiation can severely damage cells in the patient's body.

Finding Donors

When a person dies, many organs remain viable for several hours. Some of these cadaver organs are suitable for transplantation. Doctors cannot use organs of people who have died from cancer, diseases, old age, or other causes in which the organs have deteriorated.

The odds for a successful transplant are best when the donor organ is taken from a young person who has met an untimely death. After a suitable cadaver is found, and the necessary legal permission is obtained, transplant surgeons remove the donor organ. The removed organ must be kept viable until a recipient is located and prepared for surgery.

Survival Rates

Kidneys.

The kidney is well suited for transplantation. It has a simple blood supply and only one connecting outlet, the ureter, a duct that carries urine from the kidney to the bladder. Neither the lymphatic system nor the nervous system is crucial to the kidney's survival. It is more accessible than most organs and can be inserted in several sites in the abdomen.

Approximately 16,000 people in the United States receive new kidneys each year. The one-year survival rate for kidney recipients is 95 percent; it is higher for patients who receive kidneys from related, living donors rather than from cadavers.

Heart.

Heart disease has long been the leading cause of death in developed nations. A transplant can offer new hope to someone who is dying from a severely damaged heart. The first successful human-to-human transplant was performed in 1967 by Dr. Christiaan Barnard. The recipient lived for 18 days.

Today, more than 2,000 heart-transplant operations are performed each year in the United States. One-year patient-survival rates have risen to 87 percent, thanks in part to improved transplant techniques. Usually a heart-lung machine is used to take over the recipient's circulatory and respiratory functions while the damaged heart is removed. The donor heart is removed from a cadaver and reattached to the appropriate blood vessels in the recipient.

Heart transplants are currently justifiable only for a clearly terminal patient, and then only when all other modes of therapy have been exhausted.

Liver.

People cannot live more than 36 hours without a properly functioning liver. It makes bile, metabolizes and stores foods, produces antibodies, and manages hundreds of other functions. It is the largest single organ in the body, with intricate connections to the body's digestive and circulatory systems. These complexities make the liver-transplant operation riskier than the heart-transplant procedure.

The first liver-transplant operation was performed in 1963 by Dr. Thomas Starzl. Approximately 6,000 liver transplants are performed yearly in the United States, and the first-year patient-survival rate has risen to between 85 and 88 percent. Surgeons generally perform liver transplants on patients suffering from liver cancer, cirrhosis, or hepatitis.

Lungs.

The surgical technique to replace a lung is straightforward. The new organ is simply connected to the pulmonary artery, the two pulmonary veins, and the bronchus (the main airway to the lungs). However, the function of the new organ is limited because the transplant is not connected to the brain's respiratory center through the nervous system. Also, fluids tend to accumulate in the new lung, and the breathing process exposes the transplant to outside air and germs. Many lung recipients, their resistance already weakened from both the trauma of major surgery and from the high level of immunosuppressive drugs in their systems, ultimately die of opportunistic infections.

In 1963, Dr. James Hardy at the University of Mississippi Medical Center performed the first lung transplant. The patient, a 58-year-old man, lived for 18 days before dying of preexisting kidney disease. About 1,000 Americans receive lung transplants each year; the one-year patient-survival rate is about 80 percent.

Eye.

Some eye diseases render the cornea opaque, leaving patients unable to see well. Grafting an entire healthy cornea onto an eye can restore sight to these people. Tissue rejection is not an issue, because the cornea does not connect to blood vessels in the eye. Corneal transplants are the most frequently performed transplant operation. More than 40,000 such operations are performed annually in the United States.

Surgeons are refining methods of grafting a living lens to the eye of a person whose lens has been removed because of disease. Artificial lenses have restored vision for far distances, but vision at near distances must still be aided by glasses.
Other Organs, Tissues, and Cells.

Transplantation is advancing on many other fronts. For example, several hundred pancreas transplants, first performed in 1966, are now done annually in the United States, usually together with a kidney transplant in patients suffering from severe diabetes. The first successful transplants of the small intestine were achieved in 1991.

Each year, hundreds of thousands of tissue transplants are performed. In addition to corneas, commonly transplanted tissues include bone, ligaments, tendons, cartilage, and skin tissue. Bone-marrow cells are transplanted to treat patients with blood-cell diseases such as leukemia and aplastic anemia. The first transplant of a hand occurred in France in 1998.

Researchers are working to perfect the transplantation of cells that produce hormones and other chemicals. The healthy cells could replace lost or malfunctioning cells in patients with diabetes, Parkinson's, and many other diseases. In Parkinson's patients, for example, implantation of adrenal tissue into the brain appears to cause the brain to produce dopamine, the neurotransmitter whose deficiency may be responsible for the symptoms of Parkinson's.

Recipients

On any given day, some 95,000 Americans are awaiting organ transplants. A scarcity of donor organs means thousands of people die while waiting for their "gifts of life." The United Network for Organ Sharing (UNOS), a nonprofit organization, operates a national transplant waiting list under contract with the U.S. Department of Health and Human Services (HHS). Organs are allocated first to recipients within the same local area as the donor, and then over regional and national areas if no local recipients are found. In the late 1990s, efforts by the federal government to change the distribution system were debated. A new Advisory Committee on Organ Transplantation to advise the HHS secretary on all aspects of organ procurement, allocation, and transportation was later established.

The information provided should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies.

Copyright Information: Public domain information with acknowledgement given to the U.S. National Library of Medicine.

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