transplantation, medical, surgical procedure by which a tissue or organ is removed and replaced by a corresponding part, either from another part of the body or from another individual. A life-saving medical technique, transplantation also is an important tool in experimental biology; it is used to investigate endocrine gland functions, to study the interactions of cells in developing embryos, and to culture malignant tissue in cancer research.

Types of Transplanted Tissues and Organs

Transplantation to replace such diseased or defective tissue as corneas and hearts necessarily requires a dead donor; paired organs such as kidneys, or large or regenerating organs or tissues such as skin, bowel, lung, liver, or blood, can be donated by live donors (see blood transfusion). Skin autografts, employing skin from the patient's own body, are used to replace lost skin; autograft transplants are also done with bowel, bone, cartilage and other connective tissue, and ovarian tissue. Replacement skin for autografts is now also grown in laboratories, and autograft bladders have been laboratory grown and implanted. Bone marrow transplants can come either from a donor or from stored host bone marrow. Controversial fetal tissue implants have been used for some neurodegenerative diseases and experimentally for fetus-to-fetus transplants in certain genetic disorders. In addition to transplanted human tissues and organs, artificial parts ranging from heart valves to hip sockets are routinely implanted. See also heart, artificial.

Immunological Rejection of Transplanted Tissue

In transplanting complex organs (but not small tissue grafts), the larger blood vessels of the organ are surgically connected to those of the recipient. Connective tissue cells gradually link together the graft and host tissue. The main obstacle to successful transplantation is the rejection of foreign tissue by the host (see immunity). Transplanted tissue from another individual (i.e., homograft, or allograft, tissue) contains antigens that stimulate an immune response from the host's lymphocytes. Homograft tissue is normally destroyed within a few weeks; the rejection mechanism is similar to that by which the body resists infection. The greater the number of foreign antigens on the donor organ, the more rapid and severe the rejection reactions.

Organs donated from one identical twin to another are usually viable because such organs are antigenically identical, but even organs transplanted between individuals who are fairly closely matched antigenically, such as siblings, have a good chance of being rejected. An antigenic typing system based on human lymphocyte antigens (HLA typing), pioneered by Jean Dausset in Paris and Rose Payne at Stanford Univ., has made it possible to identify histocompatibility and minimize rejection.

Today, most recipients of transplants are maintained on immunosuppressive drugs. The side-effects of such antirejection drugs, which can themselves be life threatening, include increased risk of infection, cancer, diabetes, and other conditions. In time, however, many patients develop a tolerance to the implanted organs, and some can eventually be weaned off the drugs.

Researchers continue to study various ways to fool the immune system into accepting foreign tissues or to take advantage of the immune response. A new technique for nerve transplant begins with the patient taking immunosuppressive drugs, but after the patient's damaged nerves begin to grow and connect along the transplant, the drugs are discontinued and the immune system is allowed to destroy the transplanted nerve.

Noncellular tissues or tissues where the donor cells are not important to the graft (e.g., bone and cartilage) can usually be successfully transplanted without rejection. In these transplants the grafts provide nonliving structural support within which the recipient's living cells gradually become established. Corneal transplants have a high success rate largely because there are so few blood vessels in the cornea that corneal antigens may never enter the host's system to stimulate an immune reaction. Bone-marrow transplants effectively bring their own immune system with them, often rejecting the new host, instead of the other way around, in a reaction known as graft-versus-host disease.

Implantation of artificial organs, such as artificial bone, is successful because such organs (prostheses) do not produce antigenic substances. Artificial joints made of stainless steel have been developed; newer implants have used nonrusting titanium joints with the midsection of bone substitute composed of lightweight polyethylene.

Organ transplants from animals to humans are subject to hyperacute rejection, and transplantation of tissues from animals has been attempted for almost a century without much success. Some progress has been made, however, in circumventing the immune reaction. In one experimental approach, the tissues and organs of transgenic pigs, genetically engineered animals that have had human genes inserted, are combined with newly developed immunosuppressive drugs. In a potential step toward a different approach to developing swine that could be used as a source of organs, researchers have cloned pigs in which a gene that causes rejection by the human immune system has been genetically disrupted. The endangered species status of chimpanzees, genetically closest animals to humans, has eliminated their use as donors. Although transplants from animals to humans, called xenotransplants, might benefit the thousands of patients waiting for human organs, the possibility that they could spread some unknown animal virus into the human population has caused concern and delayed research experimentation.

History

Human tissue grafting was first performed in 1870 by a Swiss surgeon, Jacques Reverdin. In 1912 the French surgeon Alexis Carrel developed methods of joining blood vessels that made the transplantation of organs feasible. He advanced this technique further and stimulated the use of transplantation in experimental biology. He also developed fluids and the means of circulating them so that transplanted tissues could be kept alive outside a living body in artificial media. Theoretical work by Jean Dausset, George Davis Snell and Baruj Benacerraf on the genetic basis of histocompatibility paved the way for practical applications. In the 1940s, Sir Peter Brian Medawar and Sir Macfarlane Burnet described foreign tissue rejection and acquired immunological tolerance, opening the way for transplant operations. The first successful identical twin transplant of a human kidney was made by Joseph E. Murray in 1954. The first human heart transplant was performed by the South African surgeon Christiaan Barnard in 1967; in 1968, Edward D. Thomas performed the first successful bone-marrow transplant between people who were not twins. In the following decades liver, kidney, heart, pancreas, bone-marrow, small intestines, and multiple organ transplants became more and more routine.

As transplantation has become more common and more successful, the demand for organs has risen dramatically. The development of heart transplantation has produced an ongoing reexamination of the traditional biological and legal definitions of death, because obtaining a healthy organ for transplantation depends in large part on the earliest possible establishment of the donor's death. More than 2,000 heart transplants per year were being performed in the United States by the late 1990s, with thousands of patients waiting for available hearts. In all, more than 64,000 people were waiting to receive new organs, including hearts, kidneys, livers, lungs, and pancreases. Many people carry organ donor cards, which indicate their wish to donate if they are killed in an accident, and many states require hospitals to request donation from the families of eligible donors. A side effect of the demand for donated organs has been the increasing use of lung and liver tissue, as well as kidneys, from live donors.

In the late 1990s surprising successes were achieved in transplanting body parts other than organs. Surgeons in France and the United States were able to transplant hands that became partly functional without rejection crises. In 2005 a French surgical team achieved a partial face transplant, replacing damage areas (nose, lips, and chin) of a woman's face with skin and underlying tissues from a dead donor. Although receiving less attention, successful transplants of knees, the trachea (windpipe), and the larynx (voice box) have also been achieved. Such operations, called nonvital transplants, have become possible owing to improved surgical techniques, monitoring of rejection, and drug therapy. Still largely experimental, they must be approved by ethics committees before being undertaken, especially as the risk of taking immunosuppressive drugs may outweigh the benefits of the operation.

medical jurisprudence or forensic medicine, the application of medical science to legal problems. It is typically involved in cases concerning blood relationship, mental illness, injury, or death resulting from violence. Autopsy (see post-mortem examination) is often used to determine the cause of death, particularly in cases where foul play is suspected. Post-mortem examination can determine not only the immediate agent of death (e.g. gunshot wound, poison), but may also yield important contextual information, such as how long the person has been dead, which can help trace the killing. Forensic medicine has also become increasingly important in cases involving rape. Modern techniques use such specimens as semen, blood, and hair samples of the criminal found in the victim's bodies, which can be compared to the defendant's genetic makeup through a technique known as DNA fingerprinting; this technique may also be used to identify the body of a victim. The establishment of serious mental illness by a licensed psychologist can be used in demonstrating incompetency to stand trial, a technique which may be used in the insanity defense (see insanity), albeit infrequently.

Woman's Medical College of Pennsylvania: see Medical College of Pennsylvania.

Walter Reed Army Medical Center, major hospital complex in Washington, D. C., and Forest Glen, Md.; est. 1923 and named for U.S. army surgeon Walter Reed. It is composed of seven units including a general hospital and a research institute. There are several thousand beds.

Meharry Medical College, at Nashville, Tenn.; coeducational; organized 1876 as the medical department of Central Tennessee College, granted an independent charter 1915. There are schools of medicine, dentistry, allied health professsions, and graduate studies. Although it was founded to train black doctors, it has never been segregated.

Medical College of Pennsylvania, formerly in Philadelphia; chartered and opened 1850 as the Female Medical College of Pennsylvania; became Woman's Medical College of Pennsylvania 1867, Medical College of Pennsylvania 1970. It was the first women's medical college in the world. In 1970 it began accepting male students. The school merged (1993) with Hahnemann Univ., becoming the MCP Hahnemann School of Medicine of Allegheny Univ. of the Health Sciences, and was acquired in 1998 by Tenet Healthcare Corp., becoming MCP Hahnemann Univ. In 2002, Drexel Univ. assumed operation of the school, which became the Drexel College of Medicine.

Hughes Medical Institute: see Howard Hughes Medical Institute.

Howard Hughes Medical Institute, (HHMI), nonprofit medical research organization founded in 1953 by Howard Hughes and largly funded from proceeds of the 1984-85 sale of Hughes Aircraft. Headquartered in Chevy Chase, Md., it is one of the world's largest and wealthiest philanthropies. HHMI supports the research of several hundred "investigators," largely geneticists and biologists, at universities, hospitals, and laboratories throughout the United States; it also has an international program. HHMI also provides funds for labs and equipment, and in all grants about $1 million per researcher. In 2006 HHMI opened a new scientific research campus, Janelia Farm, at Ashburn, Va. There groups of researchers—biologists, geneticists, computer scientists, engineers, physicists, and others—undertake basic biomedical research that requires input from a variety of areas as well as long-term effort or that is outside the scope of other funders.

American Medical Association (AMA), professional physicians' organization (founded 1847). Its goals are to protect the interests of American physicians, advance public health, and support the growth of medical science. The AMA investigates alleged cases of medical quackery, engages in medical research on drugs, foods, cosmetics, and other substances, and sponsors health education programs. The organization also approves in-hospital doctor training programs; it was largely responsible for the upgrading of American medical education in the early 20th cent. Other functions include monitoring professional ethics and supervising continuing medical education for physicians. In recent years, problems associated with the high cost of medical care and health insurance, as well as the ramifications of the AIDS crisis, have been extensively examined by the influential Journal of the American Medical Association. Another pressing issue has been complaints by many physicians about problems they have encountered in working for managed care organizations. AMA members have consistently voted to oppose a comprehensive system of national health insurance. Subdivisions of the AMA deal with such medical topics as maternal and child care, medical education, medicolegal problems, and mental health. There is also a section for each of the medical specialties. In 1999, the AMA had approximately 300,000 members.

or medical imaging

Use of electromagnetic radiation to produce images of internal body structures for diagnosis. X-rays have been used since 1895. Denser tissues, such as bones, absorb more X-rays and show as lighter areas on X-ray film. A contrast medium can be used to highlight soft tissues in still X-ray pictures or can be followed on X-ray motion-picture films as it moves through the body or part of the body to record body processes. In computerized axial tomography, X-rays are focused on specific tissue planes, and a series of such parallel “slices” of the body are processed by computer to produce a 3-D image. The risks of X-ray exposure are reduced by more precise techniques using lower doses and by use of other imaging techniques. Seealso angiocardiography; angiography; magnetic resonance imaging; nuclear medicine; positron emission tomography; ultrasound.

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Organization of U.S. physicians. It was founded in 1847 “to promote the science and art of medicine and the betterment of public health.” It has about 250,000 members, about half of all practicing U.S. physicians. It disseminates information to its members and the public, operates as a lobbying group, and helps set medical education standards. Its publications include Journal of the American Medical Association, American Medical News, and journals on medical specialties.

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