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Use of the electroencephalogram is also recommended as being of value in confirmation of irreversible coma or death. If there is a flat electroencephalographic reading at the time of apparent death and a second flat reading 24 hours later, then the patient may be declared dead.
There are two exceptions to the above criteria. These are in regard to patients exhibiting marked hypothermia (body temperature below 32.2°C), and those suffering from severe central nervous system depression as a result of drug overdose.
It is recognized that the above criteria are limited in that the notion of irreversibility is not readily agreed upon and may take on new meaning as medical technology advances. The criteria are especially helpful as complements to the traditional criteria of absence of heart beat and lack of spontaneous respiration as indications of death.
In 1981, a Presidential Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research strongly recommended that all of the United States recognize the cessation of brain function as a definition of death, even in cases in which life-support systems could maintain respiratory and circulatory functions by artificial means.
ap·o·pto·sis(ap'op-tō'sis, ap'ō-tō'sis), In the diphthong pt, the p is properly silent only at the begining of a word. Many speakers in the U.S. nonetheless silence it in this word.
Whereas some cells (for example, cardiac and skeletal muscle fibers, CNS neurons) last a lifetime, others (for example, epithelial and glandular cells, erythrocytes) have limited life-spans, at the end of which they are genetically programmed for self-destruction by apoptosis, usually to be replaced by others formed by mitosis from surviving cells. Apoptosis also plays an essential role in morphogenesis and tissue homeostasis by eliminating transitory organs and tissues (for example, pronephros and mesonephros) and cells formed in excess of bodily needs during embryogenesis, as well as cells that have been damaged or virally infected. Cells in tissue cultures spontaneously undergo apoptosis after about 50 cell divisions. In contrast to cell death caused by injury, infection, or circulatory impairment, apoptosis elicits no inflammatory response in adjacent cells and tissues. Features of apoptosis detectable by histologic and histochemical methods include cell shrinkage, due chiefly to dehydration; increased membrane permeability, with a rise in intracellular calcium and a fall in pH; nuclear and cytoplasmic condensation; endolytic cleavage of nuclear DNA into oligonucleosomal fragments; and ultimately formation of apoptotic bodies, which are absorbed and removed by macrophages. Besides being due to genetic programming, apoptosis can be induced by injury to cellular DNA, as by irradiation and some cytotoxic agents used to treat cancer. It can be suppressed by naturally occurring factors (for example, cytokines) and by some drugs (for example, protease inhibitors). Apoptosis typically does not occur in malignant cells. Such cells therefore escape the destiny of their nonmalignant precursor cells and are said to be immortal. Immortalization can occur in various ways. The BCL2 gene, present in many cancers, directs the production of an enzyme that blocks apoptosis and immortalizes affected cells. Injury to DNA normally triggers apoptosis by activating the p53 tumor suppressor gene, which is missing or mutated in about one half of all human cancers. Cells that lack this gene can survive chemotherapy and irradiation intended to destroy cancer cells. Failure of apoptosis to occur is also involved in some degenerative diseases, including lupus erythematosus, and may be responsible for cellular damage caused by certain viruses, including HIV. Apoptosis has thus far been observed only in animal cells.
apoptosisAn intrinsic, highly complex programme of auto-orchestrated cell death, which is as complex and important as proliferation. Apoptosis is morphologically characterised by chromatin condensation and DNA degradation, and is a mechanism used by the immune system for antigen-induced clonal deletion of cortical thymocytes (i.e., immune tolerance). It is the most common form of eukaryotic cell death in embryogenesis, metamorphosis, tissue atrophy and tumour regression; it is induced by cytotoxic T cells, NK and killer cells, lymphotoxins, Ca2+, glucocorticoids, withdrawal of interleukins, heat shock, viral infection, oxidants, free radicals, by some monoclonal antibodies (e.g., APO-1), chemotherapeutic agents (e.g., bleomycin, cisplatin, cytosine arabinoside, methotrexate, vincristine and others), gamma radiation and UV light. Cells that die by apoptosis do not usually elicit the inflammatory responses seen in necrosis.
Apoptosis is inhibited by physiologic factors (growth factors), extracellular matrix, CD40 ligand, neutral amino acids, zinc, sex hormones, viral genes (e.g., adenovirus E1B, baculovirus p35, EBV LMP-1 and others) and pharmacologic agents (e.g., inhibitors of calpain and cysteine protease and tumour promoters, such as PMA and phenobarbital).
Apoptosis and disease
Defects in apoptosis have been pathogenically linked to AIDS, Alzheimer’s disease and other neurodegenerative phenomena, autoimmune disease, cancer, ischaemic injury, liver toxicity (.g., by alcohol), myelodysplastic syndrome, viral infections and other conditions.
Synonym(s): programmed cell death.
apoptosisCell ‘suicide’. A form of programmed cell death, by endonuclease digestion of DNA. Apoptosis is necessary to make way for new cells and occurs constantly in the growing fetus and elsewhere. The p53 gene can induce an organismally-protective apoptosis in cells whose DNA has been dangerously damaged to the point where cancerous change is liable to occur.
apoptosisprogrammed cell death, whereby the body disposes of damaged, unwanted and unneeded cells at precisely controlled times. This is a natural process occurring during development and ageing. For example, in embryogenesis development of the fingers from the limb buds involves precisely timed death of cells between the finger bones. During MENSTRUATION the sloughing of cells from the wall of the UTERUS is another case of normal cell death. The activation of a family of PROTEASES, sometimes involving extracellular signals, mediates apoptosis.
Cell death is characterized by distinctive morphological changes in the NUCLEUS and CYTOPLASM. The chromosomes, and ultimately the cell itself, fragment. The degradation products are released so that they can be taken up and re-used by neighbouring cells. Dysfunction of the programme is implicated in various pathological conditions, such as autoimmune diseases (see AUTOIMMUNITY and CANCER.
The proper dose of anti-CANCER drugs or irradiation can kill cancer cells by triggering apoptotic death.
The other mechanism of cell death is NECROSIS.
Synonym(s): programmed cell death.