The meaning of the symbols of accelerated, resolutionrapy seen in a dream.

A machine in which positively charged atomic particles are so accelerated that they acquire energies equivalent to those produced by millions of volts. From the medical point of view, its interest is that it is a source of neutrons. (See RADIOTHERAPY.)... cyclotron

Bone is not an inert sca?olding for the human body. It is a living, dynamic organ, being continuously remodelled in response to external mechanical and chemical in?uences and acting as a large reservoir for calcium and phosphate. It is as susceptible to disease as any other organ, but responds in a way rather di?erent from the rest of the body.

Bone fractures These occur when there is a break in the continuity of the bone. This happens either as a result of violence or because the bone is unhealthy and unable to withstand normal stresses.

SIMPLE FRACTURES Fractures where the skin remains intact or merely grazed. COMPOUND FRACTURES have at least one wound which is in communication with the fracture, meaning that bacteria can enter the fracture site and cause infection. A compound fracture is also more serious than a simple fracture because there is greater potential for blood loss. Compound fractures usually need hospital admission, antibiotics and careful reduction of the fracture. Debridement (cleaning and excising dead tissue) in a sterile theatre may also be necessary.

The type of fracture depends on the force which has caused it. Direct violence occurs when an object hits the bone, often causing a transverse break – which means the break runs horizontally across the bone. Indirect violence occurs when a twisting injury to the ankle, for example, breaks the calf-bone (the tibia) higher up. The break may be more oblique. A fall on the outstretched hand may cause a break at the wrist, in the humerus or at the collar-bone depending on the force of impact and age of the person. FATIGUE FRACTURES These occur after the bone has been under recurrent stress. A typical example is the march fracture of the second toe, from which army recruits suffer after long marches. PATHOLOGICAL FRACTURES These occur in bone which is already diseased – for example, by osteoporosis (see below) in post-menopausal women. Such fractures are typically crush fractures of the vertebrae, fractures of the neck of the femur, and COLLES’ FRACTURE (of the wrist). Pathological fractures also occur in bone which has secondary-tumour deposits. GREENSTICK FRACTURES These occur in young children whose bones are soft and bend, rather than break, in response to stress. The bone tends to buckle on the side opposite to the force. Greenstick fractures heal quickly but still need any deformity corrected and plaster of Paris to maintain the correction. COMPLICATED FRACTURES These involve damage to important soft tissue such as nerves, blood vessels or internal organs. In these cases the soft-tissue damage needs as much attention as the fracture site. COMMINUTED FRACTURES A fracture with more than two fragments. It usually means that the injury was more violent and that there is more risk of damage to vessels and nerves. These fractures are unstable and take longer to unite. Rehabilitation tends to be protracted. DEPRESSED FRACTURES Most commonly found in skull fractures. A fragment of bone is forced inwards so that it lies lower than the level of the bone surrounding it. It may damage the brain beneath it.

HAIR-LINE FRACTURES These occur when the bone is broken but the force has not been severe enough to cause visible displacement. These fractures may be easily missed. Symptoms and signs The fracture site is usually painful, swollen and deformed. There is asymmetry of contour between limbs. The limb is held uselessly. If the fracture is in the upper

limb, the arm is usually supported by the patient; if it is in the lower limb then the patient is not able to bear weight on it. The limb may appear short because of muscle spasm.

Examination may reveal crepitus – a bony grating – at the fracture site. The diagnosis is con?rmed by radiography.

Treatment Healing of fractures (union) begins with the bruise around the fracture being resorbed and new bone-producing cells and blood vessels migrating into the area. Within a couple of days they form a bridge of primitive bone across the fracture. This is called callus.

The callus is replaced by woven bone which gradually matures as the new bone remodels itself. Treatment of fractures is designed to ensure that this process occurs with minimal residual deformity to the bone involved.

Treatment is initially to relieve pain and may involve temporary splinting of the fracture site. Reducing the fracture means restoring the bones to their normal position; this is particularly important at the site of joints where any small displacement may limit movement considerably.

with plaster of Paris. If closed traction does not work, then open reduction of the fracture may

be needed. This may involve ?xing the fracture with internal-?xation methods, using metal plates, wires or screws to hold the fracture site in a rigid position with the two ends closely opposed. This allows early mobilisation after fractures and speeds return to normal use.

External ?xators are usually metal devices applied to the outside of the limb to support the fracture site. They are useful in compound fractures where internal ?xators are at risk of becoming infected.

Consolidation of a fracture means that repair is complete. The time taken for this depends on the age of the patient, the bone and the type of fracture. A wrist fracture may take six weeks, a femoral fracture three to six months in an adult.

Complications of fractures are fairly common. In non-union, the fracture does not unite

– usually because there has been too much mobility around the fracture site. Treatment may involve internal ?xation (see above). Malunion means that the bone has healed with a persistent deformity and the adjacent joint may then develop early osteoarthritis.

Myositis ossi?cans may occur at the elbow after a fracture. A big mass of calci?ed material develops around the fracture site which restricts elbow movements. Late surgical removal (after 6–12 months) is recommended.

Fractured neck of FEMUR typically affects elderly women after a trivial injury. The bone is usually osteoporotic. The leg appears short and is rotated outwards. Usually the patient is unable to put any weight on the affected leg and is in extreme pain. The fractures are classi?ed according to where they occur:

subcapital where the neck joins the head of the femur.

intertrochanteric through the trochanter.

subtrochanteric transversely through the upper end of the femur (rare). Most of these fractures of the neck of femur

need ?xing by metal plates or hip replacements, as immobility in this age group has a mortality of nearly 100 per cent. Fractures of the femur shaft are usually the result of severe trauma such as a road accident. Treatment may be conservative or operative.

In fractures of the SPINAL COLUMN, mere damage to the bone – as in the case of the so-called compression fracture, in which there is no damage to the spinal cord – is not necessarily serious. If, however, the spinal cord is damaged, as in the so-called fracture dislocation, the accident may be a very serious one, the usual result being paralysis of the parts of the body below the level of the injury. Therefore the higher up the spine is fractured, the more serious the consequences. The injured person should not be moved until skilled assistance is at hand; or, if he or she must be removed, this should be done on a rigid shutter or door, not on a canvas stretcher or rug, and there should be no lifting which necessitates bending of the back. In such an injury an operation designed to remove a displaced piece of bone and free the spinal cord from pressure is often necessary and successful in relieving the paralysis. DISLOCATIONS or SUBLUXATION of the spine are not uncommon in certain sports, particularly rugby. Anyone who has had such an injury in the cervical spine (i.e. in the neck) should be strongly advised not to return to any form of body-contact or vehicular sport.

Simple ?ssured fractures and depressed fractures of the skull often follow blows or falls on the head, and may not be serious, though there is always a risk of damage which is potentially serious to the brain at the same time.

Compound fractures may result in infection within the skull, and if the skull is extensively broken and depressed, surgery is usually required to check any intercranial bleeding or to relieve pressure on the brain.

The lower jaw is often fractured by a blow on the face. There is generally bleeding from the mouth, the gum being torn. Also there are pain and grating sensations on chewing, and unevenness in the line of the teeth. The treatment is simple, the line of teeth in the upper jaw forming a splint against which the lower jaw is bound, with the mouth closed.

Congenital diseases These are rare but may produce certain types of dwar?sm or a susceptibility to fractures (osteogenesis imperfecta).

Infection of bone (osteomyelitis) may occur after an open fracture, or in newborn babies with SEPTICAEMIA. Once established it is very di?cult to eradicate. The bacteria appear capable of lying dormant in the bone and are not easily destroyed with antibiotics so that prolonged treatment is required, as might be surgical drainage, exploration or removal of dead bone. The infection may become chronic or recur.

Osteomalacia (rickets) is the loss of mineralisation of the bone rather than simple loss of bone mass. It is caused by vitamin D de?ciency and is probably the most important bone disease in the developing world. In sunlight the skin can synthesise vitamin D (see APPENDIX 5: VITAMINS), but normally rickets is caused by a poor diet, or by a failure to absorb food normally (malabsorbtion). In rare cases vitamin D cannot be converted to its active state due to the congenital lack of the speci?c enzymes and the rickets will fail to respond to treatment with vitamin D. Malfunction of the parathyroid gland or of the kidneys can disturb the dynamic equilibrium of calcium and phosphate in the body and severely deplete the bone of its stores of both calcium and phosphate.

Osteoporosis A metabolic bone disease resulting from low bone mass (osteopenia) due to excessive bone resorption. Su?erers are prone to bone fractures from relatively minor trauma. With bone densitometry it is now possible to determine individuals’ risk of osteoporosis and monitor their response to treatment.

By the age of 90 one in two women and one in six men are likely to sustain an osteoporosis-related fracture. The incidence of fractures is increasing more than would be expected from the ageing of the population, which may re?ect changing patterns of exercise or diet.

Osteoporosis may be classi?ed as primary or secondary. Primary consists of type 1 osteoporosis, due to accelerated trabecular bone loss, probably as a result of OESTROGENS de?ciency. This typically leads to crush fractures of vertebral bodies and fractures of the distal forearm in women in their 60s and 70s. Type 2 osteoporosis, by contrast, results from the slower age-related cortical and travecular bone loss that occurs in both sexes. It typically leads to fractures of the proximal femur in elderly people.

Secondary osteoporosis accounts for about 20 per cent of cases in women and 40 per cent of cases in men. Subgroups include endocrine (thyrotoxicosis – see under THYROID GLAND, DISEASES OF, primary HYPERPARATHYROIDISM, CUSHING’S SYNDROME and HYPOGONADISM); gastrointestinal (malabsorption syndrome, e.g. COELIAC DISEASE, or liver disease, e.g. primary biliary CIRRHOSIS); rheumatological (RHEUMATOID ARTHRITIS or ANKYLOSING SPONDYLITIS); malignancy (multiple MYELOMA or metastatic CARCINOMA); and drugs (CORTICOSTEROIDS, HEPARIN). Additional risk factors for osteoporosis include smoking, high alcohol intake, physical inactivity, thin body-type and heredity.

Individuals at risk of osteopenia, or with an osteoporosis-related fracture, need investigation with spinal radiography and bone densitometry. A small fall in bone density results in a large increase in the risk of fracture, which has important implications for preventing and treating osteoporosis.

Treatment Antiresorptive drugs: hormone replacement therapy – also valuable in treating menopausal symptoms; treatment for at least ?ve years is necessary, and prolonged use may increase risk of breast cancer. Cyclical oral administration of disodium etidronate – one of the bisphosphonate group of drugs – with calcium carbonate is also used (poor absorption means the etidronate must be taken on an empty stomach). Calcitonin – currently available as a subcutaneous injection; a nasal preparation with better tolerance is being developed. Calcium (1,000 mg daily) seems useful in older patients, although probably ine?ective in perimenopausal women, and it is a safe preparation. Vitamin D and calcium – recent evidence suggests value for elderly patients. Anabolic steroids, though androgenic side-effects (masculinisation) make these unacceptable for most women.

With established osteoporosis, the aim of treatment is to relieve pain (with analgesics and physical measures, e.g. lumbar support) and reduce the risk of further fractures: improvement of bone mass, the prevention of falls, and general physiotherapy, encouraging a healthier lifestyle with more daily exercise.

Further information is available from the National Osteoporosis Society.

Paget’s disease (see also separate entry) is a common disease of bone in the elderly, caused by overactivity of the osteoclasts (cells concerned with removal of old bone, before new bone is laid down by osteoblasts). The bone affected thickens and bows and may become painful. Treatment with calcitonin and bisphosphonates may slow down the osteoclasts, and so hinder the course of the disease, but there is no cure.

If bone loses its blood supply (avascular necrosis) it eventually fractures or collapses. If the blood supply does not return, bone’s normal capacity for healing is severely impaired.

For the following diseases see separate articles: RICKETS; ACROMEGALY; OSTEOMALACIA; OSTEOGENESIS IMPERFECTA.

Tumours of bone These can be benign (non-cancerous) or malignant (cancerous). Primary bone tumours are rare, but secondaries from carcinoma of the breast, prostate and kidneys are relatively common. They may form cavities in a bone, weakening it until it breaks under normal load (a pathological fracture). The bone eroded away by the tumour may also cause problems by causing high levels of calcium in the plasma.

EWING’S TUMOUR is a malignant growth affecting long bones, particularly the tibia (calfbone). The presenting symptoms are a throbbing pain in the limb and a high temperature. Treatment is combined surgery, radiotherapy and chemotherapy.

MYELOMA is a generalised malignant disease of blood cells which produces tumours in bones which have red bone marrow, such as the skull and trunk bones. These tumours can cause pathological fractures.

OSTEOID OSTEOMA is a harmless small growth which can occur in any bone. Its pain is typically removed by aspirin.

OSTEOSARCOMA is a malignant tumour of bone with a peak incidence between the ages of ten and 20. It typically involves the knees, causing a warm tender swelling. Removal of the growth with bone conservation techniques can often replace amputation as the de?nitive treatment. Chemotherapy can improve long-term survival.... bone, disorders of

(Roxb.) G. Don.

Synonym: C. fragrans (Moon) Alston.

Family: Apocynaceae.

Habitat: Dense moist forests throughout India up to 1,500 m altitude.

English: Wood Vine.

Ayurvedic: Used in the Southern states as Muurvaa.

Action: Powdered root and stems— laxative, antibilious.

A lignan derivative has been isolated from the stem. It accelerated uptake of low density lipoprotein by Hep G2 cell by 67.0%.

The root bark contains 3.03% of total alkaloids consisting mainly of chonemorphine. Chonemorphine di- hydrochloride is an anti-amoebic principle. It showed in vitro activity against Entamoeba histolytica and trichomo- nas vaginalis. It proved efficacious against hepatic amoebiasis in golden hamsters and intestinal amoebiasis in Wister rats.... chonemorpha macrophylla

Linn.

Family: Iridaceae.

Habitat: Cultivated in Kashmir up to 2,000 m and in Chaubattia in Uttar Pradesh.

English: Saffron, Crocus.

Ayurvedic: Kumkuma, Rudhira, Vadrika, Kaashmira, Kaashmiraka, Vaalhika, Agnishikhaa, Ghrusrrn, Rakta, Kshataja. Keshara (usually Keshara indicates Naagakeshara, Mesuaferrea Linn.)

Unani: Zaafraan.

Siddha/Tamil: Kumgumappoo (dried stigma).

Action: Stigma and style—nervine tonic, sedative, antispasmodic expectorant (in dry cough, whooping cough, bronchitis), stomachic, diaphoretic, emmenagogue.

The Ayurvedic Pharmacopoeia of India indicated the use of the stigma and style in migraine, chronic sinusitis, and in urinary obstruction, inflammation of the urinary tract.

The saffron is used in Chinese medicine for melancholia, depression, shock and menstrual disorders.

Saffron contains a volatile oil composed of terpenes, terpene alcohols and esters. The herb also contains crocin, picrocrocin, crocetin, carotenoids and riboflavin and thiamine.

Preliminary evidence suggests that crocetin may improved atherosclerosis by increasing plasma oxygen diffusion and decreasing cholesterol and triglyceride levels. In addition, cro- cetin binds to albumin, potentially increasing oxygen diffusion and improving atherosclerosis. (Natural Medicines Comprehensive Database, 2007.)

The stigma showed remarkable inhibitory effect on blood coagulation due to the presence of platelet aggregation inhibitor containing adenosine. It accelerated in vitro fibrinolytic activity of urokinase and plasmin.

Small amounts of Saffron stimulate gastric secretion; larger amounts stimulate uterine smooth muscle and exhibit emmenagogue and abortifacient effects.

Saffron extract showed cytotoxic and antimutagenic activity and antitu- mour activity against ascites tumours in mice. Chemical analysis indicated that the naturally occurring crocin may be the active principle responsible for the observed anticancer activity.

A xanthone, carotenoid glycosidic conjugate, mangi-crocin, isolated from saffron, showed significant adapto- genic activity. A natural antioxidant, isolated from saffron stem callus, showed better antioxidant activity than vitamin E. Saffron bulbs are toxic, stigmas in overdoses narcotic.

The dose of stigma and styles at 1.55.0 g is toxic. (Recommended dose : 0.5-1.5 g per day).

Dosage: Dried style and stigma—20-50 mg (API Vol. IV.)... crocus sativus

The process of systematically identifying, appraising and using the best available research ?ndings, integrated with clinical expertise, as the basis for clinical decisions about individual patients. The aim is to encourage clinicians, health-service managers and consumers of health care to make decisions, taking account of the best available evidence, on the likely consequences of alternative decisions and actions. Evidence-based medicine has been developing internationally for the past 25 years, but since around 1990 its development has accelerated. The International COCHRANE COLLABORATION ?nds and reviews relevant research. Several other centres have been set up to look at the clinical application of research results, including the Centre for Evidence-Based Medicine in Oxford.... evidence-based medicine

Accelerated inspiration, followed by slow expiration is usually not serious. May accompany fevers and certain nervous disorders for which no specific treatment is necessary. Where condition is chronic the causal factor should be investigated. Any underlying condition should be treated. For transient irregularity:–

Teas: Balm, Motherwort, Mistletoe, Lime flowers. Tablets/capsules. Lobelia, Hawthorn, Motherwort, Valerian. ... breathing irregularities

n. (in dentistry) non-carious tooth-surface loss caused by tooth-to-tooth contact. A small amount of attrition occurs with age but accelerated wear may occur in *bruxism and with certain diets.... attrition

n. continuous hyperfractionated accelerated radiotherapy: a radiotherapy technique aimed at the rapid destruction of tumour cells when they are actively proliferating – and therefore most sensitive to radiation – by treating them several times a day over a greatly shortened total treatment time. The technique has been shown to be of benefit in the treatment of lung cancer.... chart

accelerated thinking that occurs in psychosis, mania, hypomania, and attention-deficit/hyperactivity disorder. Speech is rapid, moving from one topic to another and reflecting casual associations between ideas. In contrast to *loosening of associations, the link between themes is preserved, albeit often difficult to follow.... flight of ideas

Mill.

Family: Umbelliferae; Apiaceae.

Habitat: Native to the Mediterranean region; now cultivated mainly in Punjab, Assam, Maharashtra and Vadodara (Gujarat).

English: Fennel. (Poison hemlock has been misidentified as fennel.)

Ayurvedic: Mishreyaa, Mishi, Mad- hurikaa, Madhuraa, Shatapushpaa, Shataahvaa. (Shatpushpaa is equated with Saunf and Shataahvaa with Soyaa. Some authors treat these as vice-versa.)

Unani: Baadiyaan, Saunf.

Siddha/Tamil: Sombu.

Action: Carminative, stomachic, antispasmodic, emmenagogue, galactagogue, anti-inflammatory, diuretic. Relieves bloating, nausea, settles stomach and stimulates appetite. Also used in amenorrhoea and enuresis.

Key application: In dyspepsias such as mild, spastic, gastrointestinal afflictions, fullness, flatulence. Fennel syrup or honey can be used for the catarrh of the upper respiratory tract in children. Fennel oil preparations not recommended during pregnancy. (German Commission E, ESCOP, WHO.)

German Commission E reported that fennel seed promotes gastrointestinal motility and in higher concentrations acts as antispasmodic. In experiments anethole and fenchone have been shown to have a secre- tolytic action in respiratory tract. The British Herbal Pharmacopoeia and Indian Herbal Pharmacopoeia report its carminative and spasmolytic property.

Fennel seed contain about 8% volatile oil (about 50-60% anethole, among others 10-15% fenchone and methyl- chavicol), flavonoids, coumarins (including bergapten) and sterols.

The extract of seeds inhibits the growth of micro-organism, especially Streptococcus mutans, that are responsible for dental caries and periodontal diseases.

The essential oil from the seed is reported to be antibacterial, antifungal, antioxidant, emmenagogue, oxytocic and abortifacient.

The fatty acid, petroselenic acid, obtained from the oil, exhibited antimicrobial activity.

Anethole, a major constituent of fennel seed/oil has been found to be an active estrogenic agent with minimal hepatotoxicity and no teratogenic effect.

The oil also exhibits anticarcino- genic activity and can be used as a che- moprotective agent.

It possesses antioxidant activity close to BHT.

Anethole and limonene are used in pharmaceutical compositions for decreasing the side effects of chemotherapy and increasing the immune function.

Limonene showed the capacity to inhibit mammary tumours in rats.

The boiling water extract of leaves shows hypotensive effect in rats.

The methanolic extract of seed showed antispasmodic activity, while aqueous extract accelerated the spontaneous movement of rabbit stomach.

Dosage: Dried fruit—3-6 g powder. (API Vol. I.)... foeniculum vulgare

This is de?ned as comprehensive care of patients and families facing terminal illness. The care focuses primarily on comfort and support. Such care includes:

careful control of symptoms, especially PAIN.

psychosocial and spiritual care.

a personalised management plan centred on the patient’s needs and wishes.

care that takes into account the family’s needs and that is carried into the bereavement period.

provision of coordinated services in the home, hospital, day-care centre and other facilities used by the patient. Palliative care should include: managing

chronic cancer pain with planned use of common ANALGESICS including opioids (see SYRINGE DRIVERS); planning ahead to preserve as far as possible the patient’s autonomy and choice as death approaches and the ability to make decisions may decline; and an understanding and use of arti?cial feeding and hydration. Palliative care seeks to improve the satisfaction of both patient and family, to identify their needs and, if possible, to reduce the overall cost because the patient can often be looked after at home or in a HOSPICE instead of in hospital.

A well-publicised question that may arise in the context of palliative care is physician-assisted suicide. This subject is referred to in the entry on ETHICS. A request by a patient for accelerated death may suggest that he or she is depressed – a treatable condition – or that the palliative care is inadequate and needs reviewing and, if possible, improving.... palliative care

adj. affecting or peculiar to the ventricles of the heart. The term is most often used to describe the very slow beat of the heart’s ventricles under the influence of their own natural subsidiary pacemaker (idioventricular rhythm). An accelerated idioventricular rhythm of 80–120 beats per minute is often seen in patients a few hours after being admitted with a heart attack (see myocardial infarction). Its presence is a good sign since it usually indicates restoration of blood flow down the occluded coronary artery.... idioventricular

The body’s defence against foreign substances such as bacteria, viruses and parasites. Immunity also protects against drugs, toxins and cancer cells. It is partly non-speci?c – that is, it does not depend on previous exposure to the foreign substance. For example, micro-organisms are engulfed and inactivated by polymorphonuclear LEUCOCYTES as a ?rst line of defence before speci?c immunity has developed.

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.... immunity

Tuberculosis results form infection with Mycobacterium tuberculosis. The lungs are the site most often affected, but most organs in the body can be involved in tuberculosis. The other common sites are LYMPH NODES, bones, gastrointestinal tract, kidneys, skin and MENINGES.

The weight loss and wasting associated with tuberculosis before treatment was available led to the disease’s popular name of consumption. Enlargement of the glands in the neck, formerly called scrofula, was known also as the ‘king’s evil’ from the supersition that a touch of the royal hand could cure the condition. Lupus vulgaris (see under LUPUS) is another of the skin manifestations of the disease.

The typical pathological change in tuberculosis involves the formation of clusters of cells called granulomas (see GRANULOMA) with death of the cells in the centre producing CASEATION.

It is estimated that there are 7–8 million new cases of tuberculosis worldwide each year, with 2–3 million deaths. The incidence of tuberculosis in developed countries has shown a steady decline throughout the 20th century, mainly as a result of improved nutrition and social conditions and accelerated by the development of antituberculous chemotherapy in the 1940s. Since the mid-1980s the decline has stopped, and incidence has even started to rise again in inner-city areas. In 2002, 7,239 cases of tuberculosis were noti?ed in the UK compared with 6,442 a decade earlier; more than 390 deaths in 2003 were attributed to the disease. Factors involved in this rise are immigration from higher-prevalence areas, poorer social conditions and homelessness in some urban centres and the association with HIV infection and drug abuse. The incidence of tuberculosis is also rising in many developing countries because of the emergence of resistant strains of the tubercle bacillus (see below). In the UK recently there have been serious outbreaks in a handful of urban-based schools.... tuberculosis

Diseases developing during a person’s lifetime may be the result of his or her lifestyle, environment, genetic factors and natural AGEING factors.

Lifestyle While this may change as people grow older – for instance, physical activity is commonly reduced – some lifestyle factors are unchanged: for example, cigarette smoking, commonly started in adolescence, may be continued as an adult, resulting in smoker’s cough and eventually chronic BRONCHITIS and EMPHYSEMA; widespread ATHEROSCLEROSIS causing heart attacks and STROKE; osteoporosis (see BONE, DISORDERS OF) producing bony fractures; and cancer affecting the lungs and bladder.

Genetic factors can cause sickle cell disease (see ANAEMIA), HUNTINGTON’S CHOREA and polycystic disease of the kidney.

Ageing process This is associated with the MENOPAUSE in women and, in both sexes, with a reduction in the body’s tissue elasticity and often a deterioration in mental and physical capabilities. When compared with illnesses described in much younger people, similar illnesses in old age present in an atypical manner

– for example, confusion and changed behaviour due to otherwise asymptomatic heart failure, causing a reduced supply of oxygen to the brain. Social adversity in old age may result from the combined effects of reduced body reserve, atypical presentation of illness, multiple disorders and POLYPHARMACY.

Age-related change in the presentation of illnesses This was ?rst recognised by the specialty of geriatric medicine (also called the medicine of ageing) which is concerned with the medical and social management of advanced age. The aim is to assess, treat and rehabilitate such patients. The number of institutional beds has been steadily cut, while availability of day-treatment centres and respite facilities has been boosted – although still inadequate to cope with the growing number of people over 65.

These developments, along with day social centres, provide relatives and carers with a break from the often demanding task of looking after the frail or ill elderly. As the proportion of elderly people in the population rises, along with the cost of hospital inpatient care, close cooperation between hospitals, COMMUNITY CARE services and primary care trusts (see under GENERAL PRACTITIONER (GP)) becomes increasingly important if senior citizens are not to suffer from the consequences of the tight operating budgets of the various medical and social agencies with responsibilities for the care of the elderly. Private or voluntary nursing and residential homes have expanded in the past 15 years and now care for many elderly people who previously would have been occupying NHS facilities. This trend has been accelerated by a tightening of the bene?t rules for funding such care. Local authorities are now responsible for assessing the needs of elderly people in the community and deciding whether they are eligible for ?nancial support (in full or in part) for nursing-home care.

With a substantial proportion of hospital inpatients in the United Kingdom being over 60, it is sometimes argued that all health professionals should be skilled in the care of the elderly; thus the need for doctors and nurses trained in the specialty of geriatrics is diminishing. Even so, as more people are reaching their 80s, there seems to be a reasonable case for training sta? in the type of care these individuals need and to facilitate research into illness at this stage of life.... medicine of ageing

The physical and mental changes that occur with the passing of time. Aging is associated with degenerative changes in various organs and tissues, such as loss of elasticity in the skin and a progressive decline in organ function. Mechanical wear and tear causes cumulative damage to the joints, and the muscles lose bulk and strength. Wound healing and resistance to infection also decline. Gradual loss of nerve cells can lead to reduced sensory acuity and difficulties with learning and memory. However, dementia occurs in only a minority of elderly people.

Heredity is an important determinant of life expectancy, but physical degeneration may be accelerated by factors such as smoking, excessive alcohol intake, poor diet, and insufficient exercise.... aging

A type of leukaemia, also called chronic granulocytic leukaemia, which is caused by the overproduction of granulocytes, neutrophils, or polymorphonuclear leukocytes (see blood cells). The cause is unknown. This type of leukaemia usually has 2 phases: a chronic phase, which may last for several years, and a more cancerous phase, which is known as the blastic, accelerated, or acute phase.

During the chronic phase, symptoms may include fever, night sweats, and weight loss. Visual disturbances, abdominal pain, and priapism may also occur. The symptoms of the more cancerous phase are like those of the acute forms of leukaemia (see leukaemia, acute). The diagnosis is made from blood tests and a bone marrow biopsy. Treatment of the chronic phase includes anticancer drugs. When the disease transforms into the acute phase, treatment is similar to that given for acute leukaemia.... leukaemia, chronic myeloid

Stroke, or cerebrovascular accident (CVA), is sudden damage to BRAIN tissue caused either by a lack of blood supply or rupture of a blood vessel (see ISCHAEMIC STROKE). The affected brain cells die and the parts of the body they control or receive sensory messages from cease to function.

Causes Blood supply to the brain may be interrupted by arteries furring up with ATHEROSCLEROSIS (which is accelerated by HYPERTENSION and DIABETES MELLITUS, both of which are associated with a higher incidence of strokes) or being occluded by blood clots arising from distant organs such as infected heart valves or larger clots in the heart (see BLOOD CLOT; THROMBOSIS). Hearts with an irregular rhythm are especially prone to develop clots. Patients with thick or viscous blood, clotting disorders or those with in?amed arteries – for example, in SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) – are particularly in danger of having strokes. Bleeding into the brain arises from areas of weakened blood vessels, many of which may be congenital.

Symptoms Minor episodes due to temporary lack of blood supply and oxygen (called TRANSIENT ISCHAEMIC ATTACKS OR EPISODES (TIA, TIE)) are manifested by short-lived weakness or numbness in an arm or leg and may precede a major stroke. Strokes cause sudden weakness or complete paralysis of the muscles controlled by the part of the brain affected, as well as sensory changes (e.g. numbness or tingling). In the worst cases these symptoms and signs may be accompanied by loss of consciousness. If the stroke affects the area of the brain controlling the larynx and throat, the patient may suffer slurring or loss of speech with di?culty in initiating swallowing. When the face is involved, the mouth may droop and the patient dribble. Strokes caused by haemorrhage may be preceded by headaches. Rarely, CVAs are complicated by epileptic ?ts (see EPILEPSY). If, on the other hand, numerous small clots develop in the brain rather than one major event, this may manifest itself as a gradual deterioration in the patient’s mental function, leading to DEMENTIA.

Investigations Tests on the heart or COMPUTED TOMOGRAPHY or ultrasonic scans (see ULTRASOUND) on arteries in the neck may indicate the original sites of distantly arising clots. Blood tests may show increased thickness or tendency to clotting, and the diagnosis of general medical conditions can explain the presence of in?amed arteries which are prone to block. Special brain X-rays show the position and size of the damaged brain tissue and can usually distinguish between a clot or infarct and a rupture of and haemorrhage from a blood vessel in the brain.

Management It is better to prevent a stroke than try to cure it. The control of a person’s diabetes or high blood pressure will reduce the risk of a stroke. Treatment with ANTICOAGULANTS prevents the formation of clots; regular small doses of aspirin stop platelets clumping together to form plugs in blood vessels. Both treatments reduce the likelihood of minor transient ischaemic episodes proceeding to a major stroke.

Once the latter has occurred, there is no e?ective treatment to reduce the damage to brain tissue. Function will return to the affected part of the body only if and when the brain recovers and messages are again sent down the appropriate nerves. Simple movements are more likely to recover than delicate ones, and sophisticated functions have the worst outlook. Thus, movement of the thigh may improve more easily than ?ne movements of ?ngers, and any speech impairment is more likely to be permanent. A rehabilitation team can help to compensate for any disabilities the subject may have. Physiotherapists maintain muscle tone and joint ?exibility, whilst waiting for power to return; occupational therapists advise about functional problems and supply equipment to help patients overcome their disabilities; and speech therapists help with diffculties in swallowing, improve the clarity of remaining speech or o?er alternative methods of communication. District nurses or home helps can provide support to those caring for victims of stroke at home. Advice about strokes may be obtained from the Stroke Association.... stroke

a disorder of carbohydrate metabolism leading to an abnormally high blood sugar (glucose) level (hyperglycaemia). As the blood sugar rises the typical symptoms of urinary frequency and increased thirst emerge. Tiredness, blurring of vision, and weight loss are also common. The long-term complications of diabetes are damage to the eye (diabetic *retinopathy), the kidney (*diabetic nephropathy), and the nerve supply to the feet (*diabetic neuropathy), as well as accelerated vascular disease leading to coronary heart disease or stroke. These can be delayed or avoided by good control of blood glucose levels, combined with blood pressure control and a healthy lifestyle. Type 1 diabetes is an autoimmune disease in which the *insulin-producing beta cells of the pancreas are damaged or destroyed, thought to be triggered by a viral environmental factor. It typically starts in childhood or adolescence (more than 80% of type 1 diabetes is diagnosed in people under the age of 20 years). Treatment with insulin injections needs to be started within a few weeks of the onset of symptoms and is almost invariably lifelong. Type 2 diabetes is a genetically determined resistance to insulin action on target tissues, primarily the liver, skeletal muscle, and adipose tissue, and has become increasingly common in the UK and the developed world with the associated rise in obesity. People with type 2 diabetes outnumber those with type 1 diabetes by at least ten to one. The mainstay of treatment is a healthy diet, regular physical activity, weight control, and avoidance of tobacco in conjunction with *oral hypoglycaemic drugs. Insulin treatment is often required after 5–10 years from diagnosis, although less likely in people who have followed successful lifestyle management and have lost weight over time. A relatively new class of injectable treatment – the *GLP-1 receptor agonists – can help with both blood glucose and weight control. The rarer forms of diabetes mellitus include *maturity-onset diabetes of the young (MODY) and diabetes secondary to destruction of the pancreas (e.g. by pancreatitis, pancreatic cancer, and surgery). *Gestational diabetes mellitus is any form of diabetes first diagnosed in pregnancy.... diabetes mellitus

Also known as Röntgen rays, these were discovered in 1895 by Wilhelm Conrad Röntgen. Their use for diagnostic imaging (radiology) and for cancer therapy (see RADIOTHERAPY) is now an integral part of medicine. Many other forms of diagnostic imaging have been developed in recent years, sometimes also loosely called ‘radiology’. Similarly the use of chemotherapeutic agents in cancer has led to the term oncology which may be applied to the treatment of cancer by both drugs and X-rays.

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-effects. 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.... x-rays

an electronic device that provides a TV image from an X-ray source. The X-rays strike a fluorescent screen after passing through the patient, giving off electrons, which are accelerated using an electron lens before striking a second fluorescent screen, which is usually attached to a video camera. The acceleration of the electrons amplifies the signal from the original image, giving a brighter picture, so that the radiation dose can be reduced. Images can be taken from the camera to be observed in real time on a video monitor or, using a brief higher-dose exposure, to provide a more detailed static image (see digital spot imaging).... image intensifier

(thyroid storm) a life-threatening condition due to an acute and severe exacerbation of previously undiagnosed or inadequately treated *thyrotoxicosis. It often follows infections, childbirth, nonthyroid surgery, or trauma but can occur without an obvious cause. The presenting features are a fever, severe agitation, nausea and vomiting, diarrhoea, and abdominal pains. An accelerated heart rate and irregularity of the heart rhythm can cause heart failure, and psychotic episodes or coma can result. Blood tests will reveal hyperthyroidism and may also show altered liver function, high blood sugar, high calcium levels, a high white blood cell count, and often anaemia. Treatment is with intravenous fluids, oxygen, antithyroid drugs (such as *carbimazole or *propylthiouracil), high-dose iodide solution (see Lugol’s solution), high-dose steroids, and beta blockers. The patient must be cooled and given antipyretics, such as paracetamol. Any underlying cause must also be treated.... thyroid crisis