(2) A drug that acts through receptors on the surface of the cell or within the cell and provokes a biological response. As the body contains natural agonists that combine with cell receptors, any ‘occupation’ of these cell receptors by drug molecules will have a pharmacological e?ect on the individual. The intensity of that pharmacological e?ect is believed to be directly proportional to the number of receptors on the cell that combine with the drug molecule. For example, the natural agonist noradrenaline contracts the smooth muscle of blood vessels; the drug agonist phenylnephrine has a similar e?ect.
Antagonists are drugs which will combine with the receptor site to prevent another agent from producing its greatest e?ect. If the drug has no e?cacy of its own, but simply prevents the agonist from acting at the receptor site, it is called a full antagonist. A partial antagonist is a drug that provokes some activity at the receptor site. An example of an antagonist is prazosin, which acts against the natural agonist noradrenaline at the receptor site of the cells of blood-vessel muscle and prevents the vascular muscle from contracting.... Medical Dictionary
Alkylating agents are important because they interfere with the growth and reproduction of cells, disrupting their replication. This CYTOTOXIC property is used to retard the division and growth of cancer cells, and alkylating drugs are widely used in the chemotherapy of malignant tumours – often in conjunction with surgery and sometimes with radiotherapy. Unfortunately, troublesome side-e?ects occur, such as: damage to veins when the drug is given intravenously, with resultant leakage into adjacent tissues; impaired kidney function due to the formation of URIC ACID crystals; nausea and vomiting; ALOPECIA (hair loss); suppression of BONE MARROW activity (production of blood cells); and adverse e?ects on reproductive function, including TERATOGENESIS. Indeed, cytotoxic drugs must not be given in pregnancy, especially during the ?rst three months. Prolonged use of alkylating drugs, especially when accompanying radiotherapy, is also associated with a sign?cant rise in the incidence of acute non-lymphocytic LEUKAEMIA. Among the dozen or so alkylating drugs in use are CYCLOPHOSPHAMIDE, CHLORAMBUCIL, MELPHALAN, BUSULFAN and THIOTEPA. (See also CHEMOTHERAPY.)... Medical Dictionary
|Zinc||0.06 mg||0.5– 0.8*|
|Thiamin||0.02 mg||1.6 –1.8*|
|R iboflavin||0.09 mg||7– 8*|
|Vitamin B6||0.17 mg||13|
Scientists have engineered appropriate genes from other organisms into BACTERIA, or sometimes plants, to accelerate this natural evolutionary process. For e?ective ‘digestion of waste’, a micro-organism must quickly and completely digest organic waste without producing unpleasant smells or noxious gases, be non-pathogenic and be able to reproduce in hostile conditions. For example, American researchers have discovered an anaerobic bacterium that neutralises dangerous chlorinated chemical compounds such as trichlorethane, which can pollute soil, into a harmless molecule called ethens. But the bacteria do not thrive in soil. So the dechlorinating genes in this bacterium are transferred to bacteria that are acclimatised to living in toxic areas and can more e?ciently carry out the required detoxi?cation. Other research has been aimed at detoxifying the byproducts of DDT, a troublesome and resistant pollutant. Bioremediation should prove to be an environmentally friendly and cost-e?ective alternative to waste incineration or chemically based processes for washing contaminated soils.... Medical Dictionary
Each year around 50 people in the United Kingdom are reported as dying from carbon monoxide poisoning, and experts have suggested that as many as 25,000 people a year are exposed to its e?ects within the home, but most cases are unrecognised, unreported and untreated, even though victims may su?er from long-term e?ects. This is regrettable, given that Napoleon’s surgeon, Larrey, recognised in the 18th century that soldiers were being poisoned by carbon monoxide when billeted in huts heated by woodburning stoves. In the USA it is estimated that 40,000 people a year attend emergency departments su?ering from carbon monoxide poisoning. So prevention is clearly an important element in dealing with what is sometimes termed the ‘silent killer’. Safer designs of houses and heating systems, as well as wider public education on the dangers of carbon monoxide and its sources, are important.
Clinical e?ects of acute exposure resemble those of atmospheric HYPOXIA. Tissues and organs with high oxygen consumption are a?ected to a great extent. Common e?ects include headaches, weakness, fatigue, ?ushing, nausea, vomiting, irritability, dizziness, drowsiness, disorientation, incoordination, visual disturbances, TACHYCARDIA and HYPERVENTILATION. In severe cases drowsiness may progress rapidly to COMA. There may also be metabolic ACIDOSIS, HYPOKALAEMIA, CONVULSIONS, HYPOTENSION, respiratory depression, ECG changes and cardiovascular collapse. Cerebral OEDEMA is common and will lead to severe brain damage and focal neurological signs. Signi?cant abnormalities on physical examination include impaired short-term memory, abnormal Rhomberg’s test (standing unsupported with eyes closed) and unsteadiness of gait including heel-toe walking. Any one of these signs would classify the episode as severe. Victims’ skin may be coloured pink, though this is very rarely seen even in severe incidents. The venous blood may look ‘arterial’. Patients recovering from acute CO poisoning may su?er neurological sequelae including TREMOR, personality changes, memory impairment, visual loss, inability to concentrate and PARKINSONISM. Chronic low-level exposures may result in nausea, fatigue, headache, confusion, VOMITING, DIARRHOEA, abdominal pain and general malaise. They are often misdiagnosed as in?uenza or food poisoning.
First-aid treatment is to remove the victim from the source of exposure, ensure an e?ective airway and give 100-per-cent oxygen by tight-?tting mask. In hospital, management is largely suppportive, with oxygen administration. A blood sample for COHb level determination should be taken as soon as practicable and, if possible, before oxygen is given. Ideally, oxygen therapy should continue until the COHb level falls below 5 per cent. Patients with any history of unconsciousness, a COHb level greater than 20 per cent on arrival, any neurological signs, any cardiac arrhythmias or anyone who is pregnant should be referred for an expert opinion about possible treatment with hyperbaric oxygen, though this remains a controversial therapy. Hyperbaric oxygen therapy shortens the half-life of COHb, increases plasma oxygen transport and reverses the clinical e?ects resulting from acute exposures. Carbon monoxide is also an environmental poison and a component of cigarette smoke. Normal body COHb levels due to ENDOGENOUS CO production are 0.4 to
0.7 per cent. Non-smokers in urban areas may have level of 1–2 per cent as a result of environmental exposure. Smokers may have a COHb level of 5 to 6 per cent.... Medical Dictionary
|Calcium Content of Cheese|
|Pasteurized processed American||oz.||174|
|Saturated fat (g)||Monounsaturated fat (g)||Polyunsaturated fat (g)||Cholesterol (mg)|
Many modi?cations have been devised of the basic steroid molecule in an attempt to keep useful therapeutic e?ects and minimise unwanted side-e?ects. The main corticosteroid hormones currently available are CORTISONE, HYDROCORTISONE, PREDNISONE, PREDNISOLONE, methyl prednisolone, triamcinolone, dexamethasone, betamethasone, paramethasone and de?azacort.
They are used clinically in three quite distinct circumstances. First they constitute replacement therapy where a patient is unable to produce their own steroids – for example, in adrenocortical insu?ciency or hypopituitarism. In this situation the dose is physiological – namely, the equivalent of the normal adrenal output under similar circumstances – and is not associated with any side-e?ects. Secondly, steroids are used to depress activity of the adrenal cortex in conditions where this is abnormally high or where the adrenal cortex is producing abnormal hormones, as occurs in some hirsute women.
The third application for corticosteroids is in suppressing the manifestations of disease in a wide variety of in?ammatory and allergic conditions, and in reducing antibody production in a number of AUTOIMMUNE DISORDERS. The in?ammatory reaction is normally part of the body’s defence mechanism and is to be encouraged rather than inhibited. However, in the case of those diseases in which the body’s reaction is disproportionate to the o?ending agent, such that it causes unpleasant symptoms or frank illness, the steroid hormones can inhibit this undesirable response. Although the underlying condition is not cured as a result, it may resolve spontaneously. When corticosteroids are used for their anti-in?ammatory properties, the dose is pharmacological; that is, higher – often much higher – than the normal physiological requirement. Indeed, the necessary dose may exceed the normal maximum output of the healthy adrenal gland, which is about 250–300 mg cortisol per day. When doses of this order are used there are inevitable risks and side-e?ects: a drug-induced CUSHING’S SYNDROME will result.
Corticosteroid treatment of short duration, as in angioneurotic OEDEMA of the larynx or other allergic crises, may at the same time be life-saving and without signi?cant risk (see URTICARIA). Prolonged therapy of such connective-tissue disorders, such as POLYARTERITIS NODOSA with its attendant hazards, is generally accepted because there are no other agents of therapeutic value. Similarly the absence of alternative medical treatment for such conditions as autoimmune haemolytic ANAEMIA establishes steroid therapy as the treatment of choice which few would dispute. The use of steroids in such chronic conditions as RHEUMATOID ARTHRITIS, ASTHMA and DERMATITIS needs careful assessment and monitoring.
Although there is a risk of ill-e?ects, these should be set against the misery and danger of unrelieved chronic asthma or the incapacity, frustration and psychological trauma of rheumatoid arthritis. Patients should carry cards giving details of their dosage and possible complications.
The incidence and severity of side-e?ects are related to the dose and duration of treatment. Prolonged daily treatment with 15 mg of prednisolone, or more, will cause hypercortisonism; less than 10 mg prednisolone a day may be tolerated by most patients inde?nitely. Inhaled steroids rarely produce any ill-e?ect apart from a propensity to oral thrush (CANDIDA infection) unless given in excessive doses.
General side-e?ects may include weight gain, fat distribution of the cushingoid type, ACNE and HIRSUTISM, AMENORRHOEA, striae and increased bruising tendency. The more serious complications which can occur during long-term treatment include HYPERTENSION, oedema, DIABETES MELLITUS, psychosis, infection, DYSPEPSIA and peptic ulceration, gastrointestinal haemorrhage, adrenal suppression, osteoporosis (see BONE, DISORDERS OF), myopathy (see MUSCLES, DISORDERS OF), sodium retention and potassium depletion.... Herbal Medical
To allow it to ful?l its vitally important function as the carrier of genetic information in living cells, DNA has the following properties. It is stable, so that successive generations of species maintain their individual characteristics, but not so stable that evolutionary changes cannot take place. It must be able to store a vast amount of information: for example, an animal cell contains genetic information for the synthesis of over a million proteins. It must be duplicated exactly before each cell division to ensure that both daughter cells contain an accurate copy of the genetic information of the parent cells (see GENETIC CODE).... Medical Dictionary
The diagnosis of certain disorders can be helped by measuring the concentrations of various enzymes in the blood. After a heart attack (myocardial infarction – see HEART, DISEASES OF), raised levels of heart enzymes occur as a result of damage to the cells of the heart muscle. Some inherited diseases such as GALACTOSAEMIA and PHENYLKETONURIA are the result of de?ciencies of certain enzymes.
Enzymes can be a useful part of treatment for some disorders. STREPTOKINASE, for example, is used to treat THROMBOSIS; wound-dressings containing papain from the pawpaw fruit – this contains protein-digesting enzymes – assist in the healing process; and pancreatic enzymes can be of value to patients with malabsorption caused by disorders of the PANCREAS.... Dictionary of Tropical Medicine
Genes carry, in coded form, the detailed speci?cations for the thousands of kinds of protein molecules required by the cell for its existence, for its enzymes, for its repair work and for its reproduction. These proteins are synthesised from the 20 natural AMINO ACIDS, which are uniform throughout nature and which exist in the cell cytoplasm as part of the metabolic pool. The protein molecule consists of amino acids joined end to end to form long polypeptide chains. An average chain contains 100–300 amino acids. The sequence of bases in the nucleic acid chain of the gene corresponds in some fundamental way to the sequence of amino acids in the protein molecule, and hence it determines the structure of the particular protein. This is the genetic code. Deoxyribonucleic acid (see DNA) is the bearer of this genetic information.
DNA has a long backbone made up of repeating groups of phosphate and sugar deoxyribose. To this backbone, four bases are attached as side groups at regular intervals. These four bases are the four letters used to spell out the genetic message: they are adenine, thymine, guanine and cystosine. The molecule of the DNA is made up of two chains coiled round a common axis to form what is called a double helix. The two chains are held together by hydrogen bonds between pairs of bases. Since adenine only pairs with thymine, and guanine only with cystosine, the sequences of bases in one chain ?xes the sequence in the other. Several hundred bases would be contained in the length of DNA of a typical gene. If the message of the DNA-based sequences is a continuous succession of thymine, the RIBOSOME will link together a series of the amino acid, phenylalanine. If the base sequence is a succession of cytosine, the ribosome will link up a series of prolines. Thus, each amino acid has its own particular code of bases. In fact, each amino acid is coded by a word consisting of three adjacent bases. In addition to carrying genetic information, DNA is able to synthesise or replicate itself and so pass its information on to daughter cells.
All DNA is part of the chromosome and so remains con?ned to the nucleus of the cell (except in the mitochondrial DNA). Proteins are synthesised by the ribosomes which are in the cytoplasm. DNA achieves control over pro-tein production in the cytoplasm by directing the synthesis of ribonucleic acid (see RNA). Most of the DNA in a cell is inactive, otherwise the cell would synthesise simultaneously every protein that the individual was capable of forming. When part of the DNA structure becomes ‘active’, it acts as a template for the ribonucleic acid, which itself acts as a template for protein synthesis when it becomes attached to the ribosome.
Ribonucleic acid exists in three forms. First ‘messenger RNA’ carries the necessary ‘message’ for the synthesis of a speci?c protein, from the nucleus to the ribosome. Second, ‘transfer RNA’ collects the individual amino acids which exist in the cytoplasm as part of the metabolic pool and carries them to the ribosome. Third, there is RNA in the ribosome itself. RNA has a similar structure to DNA but the sugar is ribose instead of deoxyribose and uracil replaces the base thymine. Before the ribosome can produce the proteins, the amino acids must be lined up in the correct order on the messenger RNA template. This alignment is carried out by transfer RNA, of which there is a speci?c form for each individual amino acid. Transfer RNA can not only recognise its speci?c amino acid, but also identify the position it is required to occupy on the messenger RNA template. This is because each transfer RNA has its own sequence of bases and recognises its site on the messenger RNA by pairing bases with it. The ribosome then travels along the chain of messenger RNA and links the amino acids, which have thus been arranged in the requisite order, by peptide bonds and protein is released.
Proteins are important for two main reasons. First, all the enzymes of living cells are made of protein. One gene is responsible for one enzyme. Genes thus control all the biochemical processes of the body and are responsible for the inborn di?erence between human beings. Second, proteins also ful?l a structural role in the cell, so that genes controlling the synthesis of structural proteins are responsible for morphological di?erences between human beings.... Medical Dictionary
Haemoglobin exists in two forms: simple haemoglobin, found in venous blood; and oxy-haemoglobin, which is a loose compound with oxygen, found in arterial blood after the blood has come into contact with the air in the lungs. This oxyhaemoglobin is again broken down as the blood passes through the tissues, which take up the oxygen for their own use. This is the main function of haemoglobin: to act as a carrier of oxygen from the lungs to all the tissues of the body. When the haemoglobin leaves the lungs, it is 97 per cent saturated with oxygen; when it comes back to the lungs in the venous blood, it is 70 per cent saturated. The oxygen content of 100 millilitres of blood leaving the lungs is 19·5 millilitres, and that of venous blood returning to the lungs, 14·5 millilitres. Thus, each 100 millilitres of blood delivers 5 millilitres of oxygen to the tissues of the body. Human male blood contains 13–18 grams of haemoglobin per 100 millilitres; in women, there are 12–16 grams per 100 millilitres. A man weighing 70 kilograms (154 pounds) has around 770 grams of haemoglobin circulating in his red blood corpuscles.... Medical Dictionary
Acquired immunity depends upon the immune system recognising a substance as foreign the ?rst time it is encountered, storing this information so that it can mount a reaction the next time the substance enters the body. This is the usual outcome of natural infection or prophylactic IMMUNISATION. What happens is that memory of the initiating ANTIGEN persists in selected lymphocytes (see LYMPHOCYTE). Further challenge with the same antigen stimulates an accelerated, more vigorous secondary response by both T- and B-lymphocytes (see below). Priming the immune system in this manner forms the physiological basis for immunisation programmes.
Foreign substances which can provoke an immune response are termed ‘antigens’. They are usually proteins but smaller molecules such as drugs and chemicals can also induce an immune response. Proteins are taken up and processed by specialised cells called ‘antigenpresenting cells’, strategically sited where microbial infection may enter the body. The complex protein molecules are broken down into short amino-acid chains (peptides – see PEPTIDE) and transported to the cell surface where they are presented by structures called HLA antigens (see HLA SYSTEM).
Foreign peptides presented by human leucocyte antigen (HLA) molecules are recognised by cells called T-lymphocytes. These originate in the bone marrow and migrate to the THYMUS GLAND where they are educated to distinguish between foreign peptides, which elicit a primary immune response, and self-antigens (that is, constituents of the person themselves) which do not. Non-responsiveness to self-antigens is termed ‘tolerance’ (see AUTOIMMUNITY). Each population or clone of T-cells is uniquely responsive to a single peptide sequence because it expresses a surface molecule (‘receptor’) which ?ts only that peptide. The responsive T-cell clone induces a speci?c response in other T-and B-lymphocyte populations. For example, CYTOTOXIC T-cells penetrate infected tissues and kill cells which express peptides derived from invading micro-organisms, thereby helping to eliminate the infection.
B-lymphocytes secrete ANTIBODIES which are collectively termed IMMUNOGLOBULINS (Ig)
– see also GAMMA-GLOBULIN. Each B-cell population (clone) secretes antibody uniquely speci?c for antigens encountered in the blood, extracellular space, and the LUMEN of organs such as the respiratory passages and gastrointestinal tract.
Antibodies belong to di?erent Ig classes; IgM antibodies are synthesised initially, followed by smaller and therefore more penetrative IgG molecules. IgA antibodies are adapted to cross the surfaces of mucosal tissues so that they can adhere to organisms in the gut, upper and lower respiratory passages, thereby preventing their attachment to the mucosal surface. IgE antibodies also contribute to mucosal defence but are implicated in many allergic reactions (see ALLERGY).
Antibodies are composed of constant portions, which distinguish antibodies of di?erent class; and variable portions, which confer unique antigen-binding properties on the product of each B-cell clone. In order to match the vast range of antigens that the immune system has to combat, the variable portions are synthesised under the instructions of a large number of encoding GENES whose products are assembled to make the ?nal antibody. The antibody produced by a single B-cell clone is called a monoclonal antibody; these are now synthesised and used for diagnostic tests and in treating certain diseases.
Populations of lymphocytes with di?erent functions, and other cells engaged in immune responses, carry distinctive protein markers. By convention these are classi?ed and enumerated by their ‘CD’ markers, using monoclonal antibodies speci?c for each marker.
Immune responses are in?uenced by cytokines which function as HORMONES acting over a short range to accelerate the activation and proliferation of other cell populations contributing to the immune response. Speci?c immune responses collaborate with nonspeci?c defence mechanisms. These include the COMPLEMENT SYSTEM, a protein-cascade reaction designed to eliminate antigens neutralised by antibodies and to recruit cell populations which kill micro-organisms.... Herbal Medical
Foreignness: molecules recognised as ‘self’ are generally not immunogenic; the body tolerates these self-molecules. To be immunogenic, molecules must be recognised as non-self or foreign.
Molecular size: proteins with high molecular weights (over 100,000) are the most e?ective immunogens; those below 10,000 are weakly immunogenic; and small ones, for example, AMINO ACIDS, are non-immunogenic.
Chemical complexity: the greater the chemical complexity, the more immunogenic the substance.
Dosage, route and timing of antigen administration: all these are important factors.... Medical Dictionary
The disease is rare under the age of 30, frequency increasing with age to peak between 60 and 70 years. There may be a long preclinical phase, sometimes as long as 25 years. When symptoms do occur, they tend to re?ect bone involvement, reduced immune function, renal failure, anaemia or hyperviscosity of the blood. Vertebral collapse is common, with nerve root pressure and reduced stature. The disease is eventually fatal, infection being a common cause of death. Local skeletal problems should be treated with RADIOTHERAPY, and the general disease with CHEMOTHERAPY
– chie?y the ALKYLATING AGENTS melphalan or cyclophosphamide. Red-blood-cell TRANSFUSION is usually required, together with plasmapheresis (see PLASMA EXCHANGE), and orthopaedic surgery may be necessary following fractures.... Medical Dictionary
The oestrogenic hormones of the ovary are OESTRADIOL and oestrone. The rapid degradation of natural oestrogens limits their use as therapeutic agents. Chemical substitution of the steroid molecule, as in ethinyl oestradiol, or the use of a non-steroidal synthetic oestrogen such as STILBOESTROL, greatly reduces the rate of degradation and enhances the therapeutic action. A further development has been the use of compounds which are not actually oestrogenic themselves, but which are slowly metabolised to oestrogenic substances, or substances such as chlorotrianisene, which are taken up in the body fat and then slowly released into the circulation. There is in fact little to choose between the various synthetic oestrogens. Ethinyl oestradiol is the most potent oral oestrogen, being 20 times more active than stilboestrol.
Other commonly used oestrogen drugs are dienoestrol and oestrol. The use of oestrogens in hormone replacement therapy (HRT) is dealt with in the entry on the MENOPAUSE.... Medical Dictionary
Acute pain is caused by internal or external injury or disease. It warns the individual that harm or damage is occurring and stimulates them to take avoiding or protective action. With e?ective treatment of disease or injury and/or the natural healing process, the pain resolves – although some acute pain syndromes may develop into chronic pain (see below). Stimuli which are su?ciently intense potentially to damage tissue will cause the stimulation of speci?c receptors known as NOCICEPTORS. Damage to tissues releases substances which stimulate the nociceptors. On the surface of the body there is a high density of nociceptors, and each area of the body is supplied by nerves from a particular spinal segment or level: this allows the brain to localise the source of the pain accurately. Pain from internal structures and organs is more di?cult to localise and is often felt in some more super?cial structure. For example, irritation of the DIAPHRAGM is often felt as pain in the shoulder, as the nerves from both structures enter the SPINAL CORD at the same level (often the structures have developed from the same parts of the embryo). This is known as referred pain.
The impulses from nociceptors travel along nerves to the spinal cord. Within this there is modulation of the pain ‘messages’ by other incoming sensory modalities, as well as descending input from the brain (Melzack and Walls’ gate-control theory). This involves morphine-like molecules (the ENDORPHINS and ENKEPHALINS) amongst many other pain-transmitting and pain-modulating substances. The modi?ed input then passes up the spinal cord through the thalamus to the cerebral cortex. Thus the amount of pain ‘felt’ may be altered by the emotional state of the individual and by other incoming sensations. Once pain is perceived, then ‘action’ is taken; this involves withdrawal of the area being damaged, vocalisation, AUTONOMIC NERVOUS SYSTEM response and examination of the painful area. Analysis of the event using memory will occur and appropriate action be taken to reduce pain and treat the damage.
Chronic pain may be de?ned in several ways: for example, pain resistant to one month’s treatment, or pain persisting one month beyond the usual course of an acute illness or injury. Some doctors may also arbitrarily choose the ?gure of six months. Chronic pain di?ers from acute pain: the physiological response is di?erent and pain may either be caused by stimuli which do not usually cause the perception of pain, or may arise within nerves or the central nervous system with no apparent external stimulation. It seldom has a physiological protective function in the way acute pain has. Also, chronic pain may be self-perpetuating: if individuals gain a psychological advantage from having pain, they may continue to do so (e.g. gaining attention from family or health professionals, etc.). The nervous system itself alters when pain is long-standing in such a way that it becomes more sensitive to painful inputs and tends to perpetuate the pain.
Treatment The treatment of pain depends upon its nature and cause. Acute pain is generally treated by curing the underlying complaint and prescribing ANALGESICS or using local anaesthetic techniques (see ANAESTHESIA – Local anaesthetics). Many hospitals now have acute pain teams for the management of postoperative and other types of acute pain; chronic pain is often treated in pain clinics. Those involved may include doctors (in Britain, usually anaesthetists), nurses, psychologists and psychiatrists, physiotherapists and complementary therapists. Patients are usually referred from other hospital specialists (although some may be referred by GPs). They will usually have been given a diagnosis and exhausted the medical and surgical treatment of their underlying condition.
All the usual analgesics may be employed, and opioids are often used in the terminal treatment of cancer pain.
ANTICONVULSANTS and ANTIDEPRESSANT DRUGS are also used because they alter the transmission of pain within the central nervous system and may actually treat the chronic pain syndrome.
Many local anaesthetic techniques are used. Myofascial pain – pain a?ecting muscles and connective tissues – is treated by the injection of local anaesthetic into tender spots, and nerves may be blocked either as a diagnostic procedure or by way of treatment. Epidural anaesthetic injections are also used in the same way, and all these treatments may be repeated at intervals over many months in an attempt to cure or at least reduce the pain. For intractable pain, nerves are sometimes destroyed using injections of alcohol or PHENOL or by applying CRYOTHERAPY or radiofrequency waves. Intractable or terminal pain may be treated by destroying nerves surgically, and, rarely, the pain pathways within the spinal cord are severed by cordotomy (though this is generally only used in terminal care).
ACUPUNCTURE and TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION (TENS) are used for a variety of pain syndromes, particularly myofascial or musculoskeletal pain. It is thought that they work by increasing the release of endorphins and enkephalins (see above). It is possible to implant electrodes within the epidural space to stimulate directly the nerves as they traverse this space before passing into the spinal cord.
Physiotherapy is often used, particularly in the treatment of chronic backache, where pain may be reduced by improving posture and strengthening muscles with careful exercises. Relaxation techniques and psychotherapy are also used both to treat chronic pain and to help patients cope better with their disability.
Some types of chronic pain are caused by injury to sympathetic nerves or may be relieved by interrupting conduction in sympathetic nerves. This may be done in several ways. The nerves may be blocked using local anaesthetic or permanently destroyed using alcohol, phenol or by surgery.
Many of these techniques may be used in the management of cancer pain. Opioid drugs are often used by a variety of routes and methods, and management of these patients concentrates on the control of symptoms and on providing a good quality of life.... Medical Dictionary
Development of such mechanical and biomechanical devices points the way to a much wider use of e?ective prostheses, enabling people who would previously have died or been severely handicapped to lead normal or near normal lives. The technical hazards that have already been overcome provide a sound foundation for future successes. Progress so far in producing prostheses should also ensure that organ replacement is free from the serious ethical problems that surround the use of genetic manipulation to cure or prevent serious diseases (see ETHICS).
Limbs These are best made to meet the individual’s requirements but can be obtained ‘o? the shelf’. Arti?cial joints normally comprise complex mechanisms to stimulate ?exion and rotation movements. Leg prostheses are generally more useful than those for arms, because leg movements are easier to duplicate than those of the arm. Modern electronic circuitry that enables nerve impulses to be picked up and converted into appropriate movements is greatly improving the e?ectiveness of limb prostheses.
Eyes Arti?cial eyes are worn both for appearance and for psychological reasons. They are made of glass or plastic, and are thin shells of a boat-shape, representing the front half of the eye which has been removed. The stump which is left has still the eye-muscles in it, and so the arti?cial eye still has the power of moving with the other. A glass eye has to be replaced by a new one every year. Plastic eyes have the advantage of being more comfortable to wear, being more durable, and being unbreakable. Research is taking place aimed at creating a silicon chip that stimulates the visual cortex and thus helps to restore sight to the blind.
Dental prostheses is any arti?cial replacement of a tooth. There are three main types: a crown, a bridge and a denture. A crown is the replacement of the part of a tooth which sticks through the gum. It is ?xed to the remaining part of the tooth and may be made of metal, porcelain, plastic or a combination of these. A bridge is the replacement of two or three missing teeth and is usually ?xed in place. The replacement teeth are held in position by being joined to one or more crowns on the adjacent teeth. A denture is a removable prosthesis used to replace some or all the teeth. The teeth are made of plastic or porcelain and the base may be of plastic or metal. Removable teeth may be held more ?rmly by means of implants.
Heart The surgical replacement of stenosed or malfunctioning heart-valves with metal or plastic, human or pig valves has been routinely carried out for many years. So too has been the insertion into patients with abnormal heart rhythms of battery-driven arti?cial pacemakers (see CARDIAC PACEMAKER) to restore normal function. The replacement of a faulty heart with an arti?cial one is altogether more challenging. The ?rst working attempt to create an arti?cial heart took place in the early 1980s. Called the Jarvik-7, it had serious drawbacks: patients had to be permanently connected to apparatus the size of an anaesthetic trolley; and it caused deaths from infection and clotting of the blood. As a result, arti?cial hearts have been used primarily as bridging devices to keep patients alive until a suitable donor heart for transplantation can be found. Recent work in North America, however, is developing arti?cial hearts made of titanium and dacron. One type is planted into the chest cavity next to the patient’s own heart to assist it in its vital function of pumping blood around the body. Another replaces the heart completely. Eventually, it is probable that arti?cial hearts will replace heart transplants as the treatment of choice in patients with serious heart disorders.
Liver Arti?cial livers work in a similar way to kidney dialysis machines (see DIALYSIS). Blood is removed from the body and passed through a machine where it is cleaned and treated and then returned to the patient. The core of the device comprises several thousand ?exible membrane tubules on which live liver cells (from pigs or people) have been cultured. There is an exchange of biological molecules and water with the ‘circulating’ blood, and the membrane also screens the ‘foreign’ cells from the patient’s immune system, thus preventing any antagonistic immune reaction in the recipient.
Nose The making of a new nose is the oldest known operation in plastic surgery, Hindu records of such operations dating back to 1,000 BC. Loss of a nose may be due to eroding disease, war wounds, gun-shot wounds or dog bites. In essence the operation is the same as that practised a thousand years before Christ: namely the use of a skin graft, brought down from the forehead. Alternative sources of the skin graft today are skin from the arm, chest or abdomen. As a means of support, the new nose is built round a graft of bone or of cartilage from the ear.... Medical Dictionary
Ionising radiation comprises X-RAYS, GAMMA RAYS and particle radiation. X-rays are part of the continuous electromagnetic-wave spectrum: this also includes gamma rays, infra-red radiation, ultraviolet light and visible light. They have a very short wavelength and very high frequency, and their ability to penetrate matter depends upon the electrical energy generating them. X-rays that are generated by 100,000 volts can pass through body tissue and are used to produce images – popularly known as X-rays. X-rays, generated at several million volts can destroy tissue and are used in RADIOTHERAPY for killing cancer cells. Gamma rays are similar to X-rays but are produced by the decay of radioactive materials. Particle radiation, which can be produced electrically or by radioactive decay, comprises parts of atoms which have mass as well as (usually) an electrical charge.
Non-ionising radiation includes ultraviolet light, radio waves, magnetic ?elds and ULTRASOUND. Magnetic ?elds are used in magnetic resonance imaging (MRI) and ultrasound, which is inaudible high-frequency sound waves, and is used for both diagnoses and treatment in medicine.... Medical Dictionary
(2) A small, discrete area on the cell membrane or within the cell with which molecules or molecular complexes (e.g. hormones, drugs, and other chemical messengers) interact. When this interaction takes place it initiates a change in the working of the cell.... Medical Dictionary
In the ?rst, the information is transcribed from DNA on to a molecule of mRNA. In the second, the messenger RNA-intermediary transports the information to the protein-manufacturing centres of the cell where the information is translated from the linear sequence of codons in the RNA into a linear sequence of amino acids which are concurrently converted into protein. (See also GENES.)... Medical Dictionary
Transfusion of blood is a technique that has been used since the 17th century – although, until the 20th century, with a subsequent high mortality rate. It was only when incompatibility of BLOOD GROUPS was considered as a potential cause of this high mortality that routine blood-testing became standard practice. Since the National Blood Transfusion Service was started in the United Kingdom (in 1946), blood for transfusion has been collected from voluntary, unpaid donors: this is screened for infections such as SYPHILIS, HIV, HEPATITIS and nvCJD (see CREUTZFELDT-JAKOB DISEASE (CJD)), sorted by group, and stored in blood-banks throughout the country.
In the UK in 2004, the National Blood Authority – today’s transfusion service – announced that it would no longer accept donations from anyone who had received a blood transfusion since 1980 – because of the remote possibility that they might have been infected with the PRION which causes nvCJD.
A standard transfusion bottle has been developed, and whole blood may be stored at 2–6 °C for three weeks before use. Transfusions may then be given of whole blood, plasma, blood cells, or PLATELETS, as appropriate. Stored in the dried form at 4–21 °C, away from direct sunlight, human plasma is stable for ?ve years and is easily reconstituted by adding sterile distilled water.
The National Blood Authority prepares several components from each donated unit of blood: whole blood is rarely used in adults. This permits each product, whether plasma or various red-cell concentrates, to be stored under ideal conditions and used in appropriate clinical circumstances – say, to restore blood loss or to treat haemostatic disorders.
Transfusion of blood products can cause complications. Around 5 per cent of transfused patients su?er from a reaction; most are mild, but they can be severe and occasionally fatal. It can be di?cult to distinguish a transfusion reaction from symptoms of the condition being treated, but the safe course is to stop the transfusion and start appropriate investigation.
In the developed world, clinicians can expect to have access to high-quality blood products, with the responsibility of providing blood resting with a specially organised transfusion service. The cause of most fatal haemolytic transfusion reactions is a clerical error due to faulty labelling and/or failure to identify the recipient correctly. Hospitals should have a strict protocol to prevent such errors.
Arti?cial blood Transfusion with blood from donors is facing increasing problems. Demand is rising; suitable blood donors are becoming harder to attract; the processes of taking, storing and cross-matching donor blood are time-consuming and expensive; the shelf-life is six weeks; and the risk of adverse reactions or infection from transfused blood, although small, is always present. Arti?cial blood would largely overcome these drawbacks. Several companies in North America are now preparing this: one product uses puri?ed HAEMOGLOBIN from humans and another from cows. These provide oxygen-carrying capacity, are unlikely to be infectious and do not provoke immunological rejections. Yet another product, called Oxygene®, does not contain any animal or human blood products; it comprises salt water and a substance called per?ubron, the molecules of which store oxygen and absorb carbon dioxide more e?ectively than does haemoglobin. Within 24 hours of being transfused into a person’s bloodstream, per?ubron evaporates and is harmlessly breathed out by the recipient. Arti?cial blood is especially valuable in that it contains no unwanted proteins that can provoke adverse immunological reactions. Furthermore, it is disease-free, lasts for up to three years and is no more expensive than donor blood. It could well take the place of donor blood within a few years.
Autologous transfusion is the use of an individual’s own blood, provided in advance, for transfusion during or after a surgical operation. This is a valuable procedure for operations that may require large transfusions or where a person has a rare blood group. Its use has increased for several reasons:
fear of infection such as HIV and hepatitis.
shortages of donor blood and the rising cost of units of blood.
substantial reduction of risk of incompatible transfusions. In practice, blood transfusion in the UK is
remarkably safe, but there is always room for improvement. So, in the 1990s, a UK inquiry on the Serious Hazards of Transfusion (SHOT) was launched. It established (1998) that of 169 recently reported serious hazards following blood transfusion, 81 had involved a blood component being given to the wrong patient, while only eight were the result of viral or bacterial infections.
There are three ways to use a patient’s own blood in transfusion:
(1) predeposit autologous donation (PAD) – taking blood from a patient before operation and transfusing this blood back into the patient as required during and after operation.
(2) acute normovalaemic haemodilution (ANH) – diluting previously withdrawn blood and thus increasing the volume before transfusion.
(3) perioperative cell salvage (PCS) – the use of centrifugal cell separation on blood saved during an operation, particularly spinal surgery where blood loss may be considerable.
The government has urged NHS trusts to consider the introduction of PCS as a possible adjunct or alternative to banked-blood transfusion. In one centre (Nottingham), PCS has been used in the form of continuous autologous transfusion for several years with success.
Exchange transfusion is the method of treatment in severe cases of HAEMOLYTIC DISEASE OF THE NEWBORN. It consists of replacing the whole of the baby’s blood with Rh-negative blood of the correct blood group for the baby.... Medical Dictionary
The rays are part of the electro-magnetic spectrum; their wavelengths are between 10?9 and 10? 13 metres; in behaviour and energy they are identical to the gamma rays emitted by radioactive isotopes. Diagnostic X-rays are generated in an evacuated tube containing an anode and cathode. Electrons striking the anode cause emission of X-rays of varying energy; the energy is largely dependent on the potential di?erence (kilovoltage) between anode and cathode. The altered tissue penetration at di?erent kilovoltages is used in radiographing di?erent regions, for example in breast radiography (25–40 kV) or chest radiography (120–150 kV). Most diagnostic examinations use kilovoltages between 60 and 120. The energy of X-rays enables them to pass through body tissues unless they make contact with the constituent atoms. Tissue attenuation varies with atomic structure, so that air-containing organs such as the lung o?er little attenuation, while material such as bone, with abundant calcium, will absorb the majority of incident X-rays. This results in an emerging X-ray pattern which corresponds to the structures in the region examined.
Radiography The recording of the resulting images is achieved in several ways, mostly depending on the use of materials which ?uoresce in response to X-rays. CONTRAST X-RAYS Many body organs are not shown by simple X-ray studies. This led to the development of contrast materials which make particular organs or structures wholly or partly opaque to X-rays. Thus, barium-sulphate preparations are largely used for examining the gastrointestinal tract: for example, barium swallow, barium meal, barium follow-through (or enteroclysis) and barium enema. Water-soluble iodine-containing contrast agents that ionise in solution have been developed for a range of other studies.
More recently a series of improved contrast molecules, chie?y non-ionising, has been developed, with fewer side-e?ects. They can, for example, safely be introduced into the spinal theca for myeloradiculography – contrast X-rays of the spinal cord. Using these agents, it is possible to show many organs and structures mostly by direct introduction, for example via a catheter (see CATHETERS). In urography, however, contrast medium injected intravenously is excreted by the kidneys which are outlined, together with ureters and bladder. A number of other more specialised contrast agents exist: for example, for cholecystography – radiological assessment of the gall-bladder. The use of contrast and the attendant techniques has greatly widened the range of radiology. IMAGE INTENSIFICATION The relative insensitivity of ?uorescent materials when used for observation of moving organs – for example, the oesophagus – has been overcome by the use of image intensi?cation. A faint ?uorographic image produced by X-rays leads to electron emission from a photo-cathode. By applying a high potential di?erence, the electrons are accelerated across an evacuated tube and are focused on to a small ?uorescent screen, giving a bright image. This is viewed by a TV camera and the image shown on a monitor and sometimes recorded on videotape or cine. TOMOGRAPHY X-ray images are two-dimensional representations of three-dimensional objects. Tomography (Greek tomos
– a slice) began with X-ray imaging produced by the linked movement of the X-ray tube and the cassette pivoting about a selected plane in the body: over- and underlying structures are blurred out, giving a more detailed image of a particular plane.
In 1975 Godfrey Houns?eld introduced COMPUTED TOMOGRAPHY (CT). This involves
(i) movement of an X-ray tube around the patient, with a narrow fan beam of X-rays; (ii) the corresponding use of sensitive detectors on the opposite side of the patient; (iii) computer analysis of the detector readings at each point on the rotation, with calculation of relative tissue attenuation at each point in the cross-sectional plant. This invention has enormously increased the ability to discriminate tissue composition, even without the use of contrast.
The tomographic e?ect – imaging of a particular plane – is achieved in many of the newer forms of imaging: ULTRASOUND, magnetic resonance imaging (see MRI) and some forms of nuclear medicine, in particular positron emission tomography (PET SCANNING). An alternative term for the production of images of a given plane is cross-sectional imaging.
While the production of X-ray and other images has been largely the responsibility of radiographers, the interpretation has been principally carried out by specialist doctors called radiologists. In addition they, and interested clinicians, have developed a number of procedures, such as arteriography (see ANGIOGRAPHY), which involve manipulative access for imaging – for example, selective coronary or renal arteriography.
The use of X-rays, ultrasound or computerised tomography to control the direction and position of needles has made possible guided biopsies (see BIOPSY) – for example, of pancreatic, pulmonary or bony lesions – and therapeutic procedures such as drainage of obstructed kidneys (percutaneous nephrostomy), or of abscesses. From these has grown a whole series of therapeutic procedures such as ANGIOPLASTY, STENT insertion and renal-stone track formation. This ?eld of interventional radiology has close a?nities with MINIMALLY INVASIVE SURGERY (MIS).
Radiotherapy, or treatment by X-rays The two chief sources of the ionising radiations used in radiotherapy are the gamma rays of RADIUM and the penetrating X-rays generated by apparatus working at various voltages. For super?cial lesions, energies of around 40 kilovolts are used; but for deep-seated conditions, such as cancer of the internal organs, much higher voltages are required. X-ray machines are now in use which work at two million volts. Even higher voltages are now available through the development of the linear accelerator, which makes use of the frequency magnetron which is the basis of radar. The linear accelerator receives its name from the fact that it accelerates a beam of electrons down a straight tube, 3 metres in length, and in this process a voltage of eight million is attained. The use of these very high voltages has led to the development of a highly specialised technique which has been devised for the treatment of cancer and like diseases.
Protective measures are routinely taken to ensure that the patient’s normal tissue is not damaged during radiotherapy. The operators too have to take special precautions, including limits on the time they can work with the equipment in any one period of time.
The greatest value of radiotherapy is in the treatment of malignant disease. In many patients it can be used for the treatment of malignant growths which are not accessible to surgery, whilst in others it is used in conjunction with surgery and chemotherapy.... Medical Dictionary