Susceptibility Health Dictionary

Susceptibility: From 3 Different Sources


A total or partial vulnerability to an infection or disorder.
Health Source: BMA Medical Dictionary
Author: The British Medical Association
A reduced ability to combat an illness, usually an infection. The patient may be in poor general health, or immunisation or disease may have affected his or her defence mechanisms. For example, a person with AIDS is particularly susceptible to infection.
Health Source: Medical Dictionary
Author: Health Dictionary
n. vulnerability to disease. It is partly a reflection of general health and health-related behaviour but is also influenced by vaccination or other methods of increasing resistance to specific diseases.
Health Source: Oxford | Concise Colour Medical Dictionary
Author: Jonathan Law, Elizabeth Martin

Allergy

A term generally used to describe an adverse reaction by the body to any substance ingested by the affected individual. Strictly, allergy refers to any reactions incited by an abnormal immunological response to an ALLERGEN, and susceptibility has a strong genetic component. Most allergic disorders are linked to ATOPY, the predisposition to generate the allergic antibody immunoglobulin E (IgE) to common environmental agents (see ANTIBODIES; IMMUNOGLOBULINS). Because IgE is able to sensitise MAST CELLS (which play a part in in?ammatory and allergic reactions) anywhere in the body, atopic individuals often have disease in more than one organ. Since the allergic disorder HAY FEVER was ?rst described in 1819, allergy has moved from being a rare condition to one a?icting almost one in two people in the developed world, with substances such as grass and tree pollen, house-dust mite, bee and wasp venom, egg and milk proteins, peanuts, antibiotics, and other airborne environmental pollutants among the triggering factors. Increasing prevalence of allergic reactions has been noticeable during the past two decades, especially in young people with western lifestyles.

A severe or life-threatening reaction is often termed ANAPHYLAXIS. Many immune mechanisms also contribute to allergic disorders; however, adverse reactions to drugs, diagnostic materials and other substances often do not involve recognised immunological mechanisms and the term ‘hypersensitivity’ is preferable. (See also IMMUNITY.)

Adverse reactions may manifest themselves as URTICARIA, wheezing or di?culty in breathing owing to spasm of the BRONCHIOLES, swollen joints, nausea, vomiting and headaches. Severe allergic reactions may cause a person to go into SHOCK. Although symptoms of an allergic reaction can usually be controlled, treatment of the underlying conditon is more problematic: hence, the best current approach is for susceptible individuals to ?nd out what it is they are allergic to and avoid those agents. For some people, such as those sensitive to insect venom, IMMUNOTHERAPY or desensitisation is often e?ective. If avoidance measures are unsuccessful and desensitisation ine?ective, the in?ammatory reactions can be controlled with CORTICOSTEROIDS, while the troublesome symptoms can be treated with ANTIHISTAMINE DRUGS and SYMPATHOMIMETICS. All three types of drugs may be needed to treat severe allergic reactions.

One interesting hypothesis is that reduced exposure to infective agents, such as bacteria, in infancy may provoke the development of allergy in later life.

Predicted developments in tackling allergic disorders, according to Professor Stephen Holgate writing in the British Medical Journal (22 January 2000) include:

Identi?cation of the principal environmental factors underlying the increase in incidence, to enable preventive measures to be planned.

Safe and e?ective immunotherapy to prevent and reverse allergic disease.

Treatments that target the protein reactions activated by antigens.

Identi?cation of how IgE is produced in the body, and thus of possible ways to inhibit this process.

Identi?cation of genes affecting people’s susceptibility to allergic disease.... allergy

Bioassay

Assessment of the efficacy and persistence of an insecticidal treatment by exposing mosquitoes of known susceptibility to a treated surface or area for a standard period of time.... bioassay

Bone, Disorders Of

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

Burnout

A mental state of physical and emotional exhaustion; an anxiety disorder that is a stress reaction to a person’s reduced capability to cope with the demands of his or her occupations. Symptoms of burnout include tiredness, poor sleeping pattern, irritability and reduced performance at work; increased susceptibility to physical illness and abuse of alcohol and addictive drugs can also occur. Treatment can be dif?cult and may require a change to a less stressful lifestyle, counselling and, in severe cases, psychotherapy and carefully supervised use of ANXIOLYTICS or ANTIDEPRESSANT DRUGS.... burnout

Dermatitis

Synonymous with eczema in all respects. Although the lay term ‘eczema’ usually refers to atopic (see ATOPY) or endogenous eczema, there are many other causes. Susceptibility to dermatitis is genetically determined in some cases; in others, environmental irritants and allergens are implicated. Symptoms typically include itching, dryness or cracking and, occasionally, soreness of the skin. Physical signs include redness (erythema), scaling, and vesiculation (tiny blisters just beneath the surface of the skin). (See also SKIN, DISEASES OF.)... dermatitis

Natural History Of Di Sease

The progressive development of a disease that runs its course without treatment. 1. Stage of susceptibility2. Stage of presymptomatic 3. Stage of clinical disease 4. Stage of disability/resolution Necator americanus See hookworm.... natural history of di sease

Side-effects

This refers to an e?ect of a drug which is not that which doctor and patient require. Some side-effects are almost inevitable: for example, drowsiness with older ANTIHISTAMINE DRUGS; others are very rare, such as REYE’S SYNDROME with ASPIRIN. Some can be predicted to occur if the dose is raised, while others may occur at the lowest of doses due to the individual patient’s susceptibility. In deciding whether to prescribe or take a drug, a balance must always be struck between its bene?ts and risks. (See also MEDICINES – Safe use of medicines.)... side-effects

Azathioprine

An immunosuppressant drug used to treat severe rheumatoid arthritis and other autoimmune disorders. It is also used to prevent organ rejection after transplant surgery. Increased susceptibility to infection is a side effect.... azathioprine

Ciclosporin

An immunosuppressant drug used following transplant surgery. The drug reduces the risk of tissue rejection and the need for large doses of corticosteroid drugs. Ciclosporin may need to be taken indefinitely after a transplant. It is also used to treat rheumatoid arthritis and other autoimmune disorders. Because ciclosporin suppresses the immune system, it increases the susceptibility to infection. Swelling of the gums and increased hair growth are fairly common. Ciclosporin may also cause kidney damage, and regular monitoring of kidney function is required.... ciclosporin

Heredity

The transmission of traits and disorders through genetic mechanisms. Each individual inherits a combination of genes via the sperm and egg cells from which he or she is derived. The interaction of the genes determines inherited characteristics, including, in some cases, disorders or susceptibility to disorders.

(See also genetic disorders; inheritance.)... heredity

Dosage

Many factors in?uence the activity with which drugs operate. Among the factors which affect the necessary quantity are age, weight, sex, idiosyncrasy, genetic disorders, habitual use, disease, fasting, combination with other drugs, the form in which the drug is given, and the route by which it is given.

Normally, a young child requires a smaller dose than an adult. There are, however, other factors than age to be taken into consideration. Thus, children are more susceptible than adults to some drugs such as MORPHINE, whilst they are less sensitive to others such as ATROPINE. The only correct way to calculate a child’s dose is by reference to texts supplying a recommended dose in milligrams per kilogram. However, many reference texts simply quote doses for certain age-ranges.

Old people, too, often show an increased susceptibility to drugs. This is probably due to a variety of factors, such as decreased weight; diminished activity of the tissues and therefore diminished rate at which a drug is utilised; and diminished activity of the KIDNEYS resulting in decreased rate of excretion of the drug.

Weight and sex have both to be taken into consideration. Women require slightly smaller doses than men, probably because they tend to be lighter in weight. The e?ect of weight on dosage is partly dependent on the fact that much of the extra weight of a heavy individual is made up of fatty tissue which is not as active as other tissues of the body. In practice, the question of weight seldom makes much di?erence unless the individual is grossly over- or underweight.

Idiosyncrasy occasionally causes drugs administered in the ordinary dose to produce unexpected effects. Thus, some people are but little affected by some drugs, whilst in others, certain drugs – for example, psychoactive preparations such as sedatives – produce excessive symptoms in normal or even small doses. In some cases this may be due to hypersensitivity, or an allergic reaction, to the drug, which is a possibility that must always be borne in mind

(e.g. with PENICILLIN). An individual who is known to be allergic to a certain medication is strongly advised to carry a card to this e?ect, and always to inform medical and dental practitioners and/or a pharmacist before accepting a new prescription or buying an over-the-counter preparation.

Habitual use of a drug is perhaps the in?uence that causes the greatest increase in the dose necessary to produce the requisite e?ect. The classical example of this is with OPIUM and its derivatives.

Disease may modify the dose of medicines. This can occur in several ways. Thus, in serious illnesses the patient may be more susceptible to drugs, such as narcotics, that depress tissue activity, and therefore smaller doses must be given. Again, absorption of the drug from the gut may be slowed up by disease of the gut, or its e?ect may be enhanced if there is disease of the kidneys, interfering with the excretion of the drug.

Fasting aids the rapidity of absorption of drugs, and also makes the body more susceptible to their action. Partly for this reason, as well as to avoid irritation of the stomach, it is usual to prescribe drugs to be taken after meals, and diluted with water.

Combination of drugs is to be avoided if possible as it is often di?cult to assess what their combined e?ect may be. In some cases they may have a mutually antagonistic e?ect, which means that the patient will not obtain full bene?t. Sometimes a combination may have a deleterious e?ect.

Form, route and frequency of administration Drugs are now produced in many forms, though tablets are the most common and, usually, convenient. In Britain, medicines are given by mouth whenever possible, unless there is some degree of urgency, or because the drug is either destroyed in, or is not absorbed from, the gut. In these circumstances, it is given intravenously, intra-muscularly or subcutaneously. In some cases, as in cases of ASTHMA or BRONCHITIS, the drug may be given in the form of an inhalant (see INHALANTS), in order to get the maximum concentration at the point where it is wanted: that is, in the lungs. If a local e?ect is wanted, as in cases of diseases of the skin, the drug is applied topically to the skin. In some countries there is a tendency to give medicines in the form of a suppository which is inserted in the rectum.

Recent years have seen developments whereby the assimilation of drugs into the body can be more carefully controlled. These include, for example, what are known as transdermals, in which drugs are built into a plaster that is stuck on the skin, and the drug is then absorbed into the body at a controlled rate. This method is now being used for the administration of GLYCERYL TRINITRATE in the treatment of ANGINA PECTORIS, and of hyoscine hydrobromide in the treatment of MOTION (TRAVEL) SICKNESS. Another is a new class of implantable devices. These are tiny polymers infused with a drug and implanted just under the skin by injection. They can be tailored so as to deliver drugs at virtually any rate – from minutes to years. A modi?cation of these polymers now being investigated is the incorporation of magnetic particles which allow an extra burst of the incorporated drug to be released in response to an oscillating magnetic ?eld which is induced by a magnetic ‘watch’ worn by the patient. In this way the patient can switch on an extra dose of drug when this is needed: insulin, for instance, in the case of diabetics. In yet another new development, a core of drug is enclosed in a semi-permeable membrane and is released in the stomach at a given rate. (See also LIPOSOMES.)... dosage

Hyperthermia, Malignant

A rapid rise in body temperature to a dangerously high level, brought on by general anaesthesia. The condition is rare. In most cases, susceptibility is inherited; people suffering from certain muscle disorders may also be at risk. The patient’s body temperature rises soon after the anaesthetic is given. Emergency treatment and intensive care are needed.... hyperthermia, malignant

Lipoprotein

Particles comprising a fatty core and protein outer layer (apoliprotein) that allow the transport of fats in the bloodstream.

Genetic variations in the structure of apoliproteins and lipoproteins play an important part in determining susceptibility to cardiovascular disorders and Alzheimer’s disease.... lipoprotein

Melphalan

An anticancer drug used to treat multiple myeloma as well as certain

types of breast cancer and ovarian cancer (see ovary, cancer of).

Possible adverse effects include nausea, vomiting, sore throat, loss of appetite, aplastic anaemia, abnormal bleeding, and increased susceptibility to infection.... melphalan

Methotrexate

An anticancer drug used to treat lymphoma (cancer of the lymph nodes) and some forms of leukaemia. Methotrexate is also used to treat cancers of the uterus, breast, ovary, lung, bladder, and testis, and severe psoriasis when other treatments are ineffective. Methotrexate may cause nausea, vomiting, diarrhoea, mouth ulcers, anaemia, increased susceptibility to infection, and abnormal bleeding.... methotrexate

Drugs In Pregnancy

Unnecessary drugs during pregnancy should be avoided because of the adverse e?ect of some drugs on the fetus which have no harmful e?ect on the mother. Drugs may pass through the PLACENTA and damage the fetus because their pharmacological effects are enhanced as the enzyme systems responsible for their degradation are undeveloped in the fetus. Thus, if the drug can pass through the placenta, the pharmacological e?ect on the fetus may be great whilst that on the mother is minimal. WARFARIN may thus induce fetal and placental haemorrhage and the administration of THIAZIDES may produce THROMBOCYTOPENIA in the newborn. Many progestogens have androgenic side-effects and their administration to a mother for the purpose of preventing recurrent abortion may produce VIRILISATION of the female fetus. Tetracycline administered during the last trimester commonly stains the deciduous teeth of the child yellow.

The other dangers of administering drugs in pregnancy are the teratogenic effects (see TERATOGENESIS). It is understandable that a drug may interfere with a mechanism essential for growth and result in arrested or distorted development of the fetus and yet cause no disturbance in the adult, in whom these di?erentiation and organisation processes have ceased to be relevant. Thus the e?ect of a drug upon a fetus may di?er qualitatively as well as quantitatively from its e?ect on the mother. The susceptibility of the embryo will depend on the stage of development it has reached when the drug is given. The stage of early di?erentiation – that is, from the beginning of the third week to the end of the tenth week of pregnancy – is the time of greatest susceptibility. After this time the risk of congenital malformation from drug treatment is less, although the death of the fetus can occur at any time.... drugs in pregnancy

Environment And Health

Environment and Health concerns those aspects of human health, including quality of life, that are determined by physical, biological, social and psychosocial factors in the environment. The promotion of good health requires not only public policies which support health, but also the creation of supportive environments in which living and working conditions are safe, stimulating and enjoyable.

Health has driven much of environmental policy since the work of Edwin Chadwick in the early 1840s. The ?rst British public-health act was introduced in 1848 to improve housing and sanitation with subsequent provision of puri?ed water, clean milk, food hygiene regulations, vaccinations and antibiotics. In the 21st century there are now many additional environmental factors that must be monitored, researched and controlled if risks to human health are to be well managed and the impact on human morbidity and mortality reduced.

Environmental impacts on health include:

noise

air pollution

water pollution

dust •odours

contaminated ground

loss of amenities

vermin

vibration

animal diseases

Environmental risk factors Many of the major determinants of health, disease and death are environmental risk factors. Some are natural hazards; others are generated by human activities. They may be directly harmful, as in the examples of exposure to toxic chemicals at work, pesticides, or air pollution from road transport, or to radon gas penetrating domestic properties. Environmental factors may also alter people’s susceptibility to disease: for example, the availability of su?cient food. In addition, they may operate by making unhealthy choices more likely, such as the availability and a?ord-ability of junk foods, alcohol, illegal drugs or tobacco.

Populations at risk Children are among the populations most sensitive to environmental health hazards. Their routine exposure to toxic chemicals in homes and communities can put their health at risk. Central to the ability to protect communities and families is the right of people to know about toxic substances. For many, the only source of environmental information is media reporting, which often leaves the public confused and frustrated. To bene?t from public access to information, increasingly via the Internet, people need basic environmental and health information, resources for interpreting, understanding and evaluating health risks, and familiarity with strategies for prevention or reduction of risk.

Risk assessment Environmental health experts rely on the principles of environmental toxicology and risk assessment to evaluate the environment and the potential effects on individual and community health. Key actions include:

identifying sources and routes of environmental exposure and recommending methods of reducing environmental health risks, such as exposure to heavy metals, solvents, pesticides, dioxins, etc.

assessing the risks of exposure-related health hazards.

alerting health professionals, the public, and the media to the levels of risk for particular potential hazards and the reasons for interventions.

ensuring that doctors and scientists explain the results of environmental monitoring studies – for example, the results of water ?uoridation in the UK to improve dental health.

National policies In the United Kingdom in 1996, an important step in linking environment and health was taken by a government-initiated joint consultation by the Departments of Health and Environment about adding ‘environment’ as a key area within the Health of the Nation strategy. The ?rst UK Minister of State for Public Health was appointed in 1997 with responsibilities for health promotion and public-health issues, both generally and within the NHS. These responsibilities include the implementation of the Health of the Nation strategy and its successor, Our Healthy Nation. The aim is to raise the priority given to human health throughout government departments, and to make health and environmental impact assessment a routine part of the making, implementing and assessing the impact of policies.

Global environmental risks The scope of many environmental threats to human health are international and cannot be regulated e?ectively on a local, regional or even national basis. One example is the Chernobyl nuclear reactor accident, which led to a major release of radiation, the effects of which were felt in many countries. Some international action has already been taken to tackle global environmental problems, but governments should routinely measure the overall impacts of development on people and their environments and link with industry to reduce damage to the environment. For instance, the effects of global warming and pollution on health should be assessed within an ecological framework if communities are to respond e?ectively to potential new global threats to the environment.... environment and health

Osteopetrosis

A very rare inherited disorder in which bones harden and become denser. Deficiency of one of the 2 types of bone cell responsible for healthy bone growth results in a disruption of normal bone structure. In its mildest form, there may be no symptoms; more severe forms of osteopetrosis result in abnormally high susceptibility to fractures; stunted growth; deformity; and anaemia. Pressure on nerves may cause blindness, deafness, and facial paralysis.

Most treatments for osteopetrosis aim to reduce the severity of symptoms. Bone marrow transplants of cells from which healthy bone cells might develop are undertaken in some cases.... osteopetrosis

Hla System

The major histocompatibility complex, or human leucocyte antigen (HLA) region, consists of genetically determined antigens, situated on chromosome 6. Found in most tissues, though to a di?ering extent, the four gene loci are known as A, B, C, D, while the individual alleles at each locus are numbered 1, 2, 3, etc. The number of possible combinations is thus enormous, and the chance of two unrelated people being identical for HLA is very low.

HLA incompatibility causes the immune response, or rejection reaction, that occurs with unmatched tissue grafts. Strong associations between HLA and susceptibility to certain diseases – notably the AUTOIMMUNE DISORDERS such as rheumatoid arthritis, insulin-dependent diabetes, and thyrotoxicosis – have been described. Certain HLA antigens occur together more frequently than would be expected by chance (linkage disequilibrium), and may have a protective e?ect, conferring resistance to a disease. (See IMMUNITY.)... hla system

Leprosy

Also known as Hansen’s disease, this is a chronic bacterial infection caused by Mycobacterium leprae affecting the skin, mucous membranes, and nerves. Infection is now almost con?ned to tropical and subtropical countries – mostly in Africa and India. There are two distinct (polarised) clinical forms: tuberculoid and lepromatous. The former usually takes a benign course and frequently burns out, whereas the latter is relentlessly progressive; between these two polar forms lies an intermediate/dimorphous group. Susceptibility may be increased by malnutrition. Nasal secretions (especially in lepromatous disease) are teeming with M. leprae and constitute the main source of infection; however, living in close proximity to an infected individual seems necessary for someone to contract the disease. M. leprae can also be transmitted in breast milk from an infected mother.

Only a small minority of those exposed to M. leprae develop the disease. The incubation period is 3–5 years or longer. The major clinical manifestations involve skin and nerves: the former range from depigmented, often anaesthetic areas, to massive nodules; nerve involvement ranges from localised nerve swelling(s) to extensive areas of anaesthesia. Advanced nerve destruction gives rise to severe deformities: foot-drop, wrist-drop, claw-foot, extensive ulceration of the extremities with loss of ?ngers and toes, and bone changes. Eye involvement can produce blindness. Laryngeal lesions produce hoarseness and more serious sequelae. The diagnosis is essentially a clinical one; however, skin-smears, histological features and the lepromin skin-test help to con?rm the diagnosis and enable the form of disease to be graded.

Although the World Health Organisation had originally hoped to eliminate leprosy worldwide by 2000, that has proved an unrealistic target. The reason is an absence of basic information. Doctors are unable to diagnose the disorder before a patient starts to show symptoms; meanwhile he or she may have already passed on the infection. Doctors do not know exactly how transmission occurs or how it infects humans – nor do they know at what point a carrier of the bacterium may infect others. The incidence of new infections is still more than 650,000 cases a year or about 4.5 cases per 10,000 people in those countries worst affected by the disease.

Treatment Introduction of the sulphone compound, dapsone, revolutionised management of the disease. More recently, rifampicin and clofazimine have been added as ?rst-line drugs for treatment. Second-line drugs include minocycline, o?oxacin and clarithromycin; a number of regimens incorporating several of these compounds (multi-drug regimens – introduced in 1982) are now widely used. A three-drug regime is recommended for multi-bacillary leprosy and a two-drug one for parcibacillary leprosy. Dapsone resistance is a major problem worldwide, but occurs less commonly when multi-drug regimens are used. Older compounds – ethionamide and prothionamide

– are no longer used because they are severely toxic to the liver. Corticosteroids are sometimes required in patients with ‘reversal reaction’. Supportive therapy includes physiotherapy; both plastic and orthopaedic surgery may be necessary in advanced stages of the disease. Improvement in socio-economic conditions, and widespread use of BCG vaccination are of value as preventive strategies. Early diagnosis and prompt institution of chemotherapy should prevent long-term complications.... leprosy

Phenothiazines

A group of major antipsychotic drugs, colloquially called ‘TRANQUILLISERS’, widely used to treat psychoses (see PSYCHOSIS). They can be divided into three main groups. Chlorpromazine, methotrimeprazine and promazine are examples of group 1, usually characterised by their sedative effects and moderate antimuscarinic and extrapyramidal side-effects. Group 2 includes pericyazine, pipothiazine and thioridazine, which have moderate sedative effects but signi?cant antimuscarinic action and modest extrapyramidal side-effects. Fluphenazine, perphenazine, prochlorperazine and tri?uoperazine comprise group 3. Their sedative effects are less than for the other groups and they have little antimuscarinic action; they have marked extrapyramidal side-effects.

Uses Phenothiazines should be prescribed and used with care. The drugs di?er in predominant actions and side-effects; selection depends on the extent of sedation required and the susceptibility of the patient to extrapyramidal side-effects. The di?erences between the drugs, however, are less important than the variabilities in patients’ responses. Patients should not be prescribed more than one antipsychotic drug at a time. In the short term these therapeutically powerful drugs can be used to calm disturbed patients, whatever the underlying condition (which might have a physical or psychiatric basis). They also alleviate acute anxiety and some have antidepressant properties, while others worsen DEPRESSION (see also MENTAL ILLNESS).... phenothiazines

Paclitaxel

An anticancer drug that is used to treat certain types of cancer, such as ovarian cancer (see ovary, cancer of) and breast cancer. The possible side effects of paclitaxel can include nausea, vomiting, anaemia, and increased susceptibility to infection.... paclitaxel

Predisposing Factors

Factors that lead to increased susceptibility to a disease.... predisposing factors

Braxton Hicks Contractions

irregular painless contractions of the uterus that occur during pregnancy and may become stronger towards term. [J. Braxton Hicks (1825–97), British obstetrician]

BRCA1 and BRCA2 genes associated with susceptibility to breast and ovarian cancer. Women with mutations in either of these genes have a 56–85% risk of developing breast cancer, and this form of the cancer tends to develop at a relatively young age. The risk of ovarian cancer is 36–66% in women with BRCA1 mutations and 10–20% with BRCA2. Targeted therapy specific to these mutations using a *PARP inhibitor is undergoing investigation.... braxton hicks contractions

Nature Of The Disease Tuberculosis Has

been recognised from earliest times. Evidence of the condition has been found in Egyptian mummies; in the fourth century BC Hippocrates, the Greek physician, called it phthisis because of the lung involvement; and in 1882 Koch announced the discovery of the causative organism, the tubercle bacillus or Mycobacterium tuberculosis.

The symptoms depend upon the site of the infection. General symptoms such as fever, weight loss and night sweats are common. In the most common form of pulmonary tuberculosis, cough and blood-stained sputum (haemoptysis) are common symptoms.

The route of infection is most often by inhalation, although it can be by ingestion of products such as infected milk. The results of contact depend upon the extent of the exposure and the susceptibility of the individual. Around 30 per cent of those closely exposed to the organism will be infected, but most will contain the infection with no signi?cant clinical illness and only a minority will go on to develop clinical disease. Around 5 per cent of those infected will develop post-primary disease over the next two or three years. The rest are at risk of reactivation of the disease later, particularly if their resistance is reduced by associated disease, poor nutrition or immunosuppression. In developed countries around 5 per cent of those infected will reactivate their healed tuberculosis into a clinical problem.

Immunosuppressed patients such as those infected with HIV are at much greater risk of developing clinical tuberculosis on primary contact or from reactivation. This is a particular problem in many developing countries, where there is a high incidence of both HIV and tuberculosis.

Diagnosis This depends upon identi?cation of mycobacteria on direct staining of sputum or other secretions or tissue, and upon culture of the organism. Culture takes 4–6 weeks but is necessary for di?erentiation from other non-tuberculous mycobacteria and for drug-sensitivity testing. Newer techniques involving DNA ampli?cation by polymerase chain reaction (PCR) can detect small numbers of organisms and help with earlier diagnosis.

Treatment This can be preventative or curative. Important elements of prevention are adequate nutrition and social conditions, BCG vaccination (see IMMUNISATION), an adequate public-health programme for contact tracing, and chemoprophylaxis. Radiological screening with mass miniature radiography is no longer used.

Vaccination with an attenuated organism (BCG – Bacillus Calmette Guerin) is used in the United Kingdom and some other countries at 12–13 years, or earlier in high-risk groups. Some studies show 80 per cent protection against tuberculosis for ten years after vaccination.

Cases of open tuberculosis need to be identi?ed; their close contacts should be reviewed for evidence of disease. Adequate antibiotic chemotherapy removes the infective risk after around two weeks of treatment. Chemoprophylaxis – the use of antituberculous therapy in those without clinical disease – may be used in contacts who develop a strong reaction on tuberculin skin testing or those at high risk because of associated disease.

The major principles of antibiotic chemotherapy for tuberculosis are that a combination of drugs needs to be used, and that treatment needs to be continued for a prolonged period – usually six months. Use of single agents or interrupted courses leads to the development of drug resistance. Serious outbreaks of multiply resistant Mycobacterium tuberculosis have been seen mainly in AIDS units, where patients have greater susceptibility to the disease, but also in developing countries where maintenance of appropriate antibacterial therapy for six months or more can be di?cult.

Streptomycin was the ?rst useful agent identi?ed in 1944. The four drugs used most often now are RIFAMPICIN, ISONIAZID, PYRAZINAMIDE and ETHAMBUTOL. Three to four agents are used for the ?rst two months; then, when sensitivities are known and clinical response observed, two drugs, most often rifampicin and isoniazid, are continued for the rest of the course. Treatment is taken daily, although thrice-weekly, directly observed therapy is used when there is doubt about the patient’s compliance. All the antituberculous agents have a range of adverse effects that need to be monitored during treatment. Provided that the treatment is prescribed and taken appropriately, response to treatment is very good with cure of disease and very low relapse rates.... nature of the disease tuberculosis has

Quarantine

1. Complete quarantine: The limitation of freedom of movement of such well persons or domestic animals as have been exposed to a communicable disease, for a period of time not longer than the longest usual incubation period of the disease, in such manner as to prevent effective contact with those not so exposed. 2. Modified quarantine: A selective, partial limitation of freedom of movement of persons or domestic animals, commonly on the basis of known or presumed differences in susceptibility but sometimes because of danger of disease transmission. It may be designed to meet particular situations. Examples are exclusion of children from school; or exemption of immune persons from provisions required of susceptible person, such as contact acting as food handlers; or restriction of military populations to the post or to quarters. 3. Personal surveillance: The practice of close medical or other supervision of contacts in order to promote prompt recognition of infection or illness but without restricting their movements. 4. Segregation: The separation for special consideration, control or observation of some part of a group of persons or domestic animals from the others to facilitate control of a communicable disease. Removal of susceptible children to homes of immune persons, or establishment of a sanitary boundary to protect dis infected from infected portions of a population, are examples.... quarantine

Carcinogen

n. any substance that, when exposed to living tissue, may cause the production of cancer. Known carcinogens include ionizing radiation and many chemicals, e.g. those found in cigarette smoke and those produced in certain industries. They cause damage to the DNA of cells that may persist if the cell divides before the damage is repaired. Damaged cells may subsequently develop into a *cancer (see also carcinogenesis). An inherent susceptibility to cancer may be necessary for a carcinogen to promote the development of cancer. See also oncogenic. —carcinogenic adj.... carcinogen

Dick Test

an obsolete immunological test for susceptibility to *scarlet fever. [G. F. Dick (1881–1967) and G. R. H. Dick (1881–1963), US physicians]... dick test

Factor V Leiden

an inherited mutation in the gene coding for coagulation Factor V, which results in an increased susceptibility to develop venous *thrombosis.... factor v leiden

Preventive Medicine

The term ‘preventive medicine’ may be used both in a general ‘lay’ sense and to cover a speci?c range of activities carried out by health professionals. The de?nition and scope vary from country to country. Some people use the term widely and almost synonymously with ‘public health’; others limit its use to speci?c measures directed at individuals, such as an immunisation against an infectious disease, preferring other terms such as ‘health promotion’ for educational activities and ‘health protection’ to cover consumer-protection regulations such as food inspection. The preventive approach is an essential component of a broader public-health strategy, and, for example, in relation to diet and physical activity a normal part of the lifestyle of many in the population.

In Britain, for instance, preventive medicine is usually taken to encompass a range of activities whose purpose is:

to reduce the chance of a person contracting a disease or becoming disabled.

to identify either an increased susceptibility to develop a disease, or an early manifestation of a disease at a stage which will still allow treatment to be e?ective. The American College of Preventive Medi

cine (1983) de?ned it as ‘a specialised ?eld of medical practice composed of distinct disciplines which utilise skills focusing on the health of de?ned populations in order to promote and maintain health and well-being and to prevent disease, disability and premature death’.

However de?ned, the spectrum of activities encompassed by preventive medicine is wide and includes actions, such as counselling about lifestyle, where there may not be a clear cut-o? between a preventive and a curative act. For example, advice about smoking and exercise to a recent victim of a myocardial infarction (see under HEART, DISEASES OF) is both essential to treatment and preventive against a future attack. Action aimed at a whole population – such as the addition of ?uoride to drinking-water to protect against dental caries (see under TEETH, DISORDERS OF) – is part of a population-based public-health strategy but would also be widely regarded as preventive medicine.

A common and widely accepted classi?cation of preventive medicine is as follows:

Primary prevention which aims at the complete avoidance of a disease (for example, by immunising a child against an infectious disease – see IMMUNISATION).

Secondary prevention which aims at detecting and curing a disease at an early stage before it has caused any symptoms. This requires ‘screening’ procedures to detect either the early pre-symptomatic condition, or a risk factor which may lead to it. (An example of the former is cervical cytology, where a sample of cells is scraped from the cervix of the UTERUS and examined microscopically for abnormality.

An example of the latter is CHOLESTEROL measurement as part of assessing an individual’s risk of developing ischaemic heart disease (see under HEART, DISEASES OF). If it is signi?cantly raised, dietary or drug treatment can be advised.)

Tertiary prevention aims at minimising the consequences for a patient who already has the disease (e.g. advising people to take more exercise and stop smoking after a heart attack).

Many prefer to limit the term ‘preventive medicine’ to primary and secondary prevention, emphasising the focus on risk-reducing interventions targeted at ‘well’ individuals. Others prefer the wider emphasis because of the importance of a preventive approach in reducing further disability by recognising and treating symptoms early. This can be particularly important in older people, where, for example, vigorous treatment of an orthopaedic problem can enable the patient to maintain physical mobility with all the bene?ts to health that brings. Whether primary, secondary or tertiary prevention, some form of screening question or test is normally necessary to identify a problem.

The range and extent of opportunities for prevention are expanding as research identi?es the causes of diseases and more e?ective treatment becomes feasible. Inevitably there is economic and political debate about the cost-e?ectiveness of prevention versus cure, as well as about the ETHICS. The situation varies in relation to the natural history of the speci?c disease. Some conditions can easily be prevented but once contracted cannot be cured

(e.g. RABIES); others are easily cured but are not yet preventable.

Screening Screening involves carrying out tests either to identify a treatable disease at a very early stage, before it has caused symptoms or damage; or to identify a risk factor which can lead to a disease. The tests might be by simple questioning (e.g. ‘Do you smoke cigarettes?’ – this predicts a considerable increase in the risk of chronic bronchitis, heart disease, bronchial cancer and many other diseases, and enables targeted advice and help to stop smoking to be given). Other screening tests involve carrying out complex special investigations such as blood tests or the microscopic investigations of cells – for example, for precancerous changes.

Many conditions can be identi?ed at an early stage before they cause symptoms or signs of disease and in time for e?ective treatment to be carried out. Inevitably, some of the screening tests proposed can be expensive (particularly if used in large populations), painful or inaccurate and may not improve the results of treatment. Screening can also provoke considerable anxiety in those waiting for tests or results. Therefore, over the years considerable research has been carried out into the appropriateness and ethics of screening, and the World Health Organisation in 1968 identi?ed a set of rules for evaluating screening tests:

The condition sought should be an important health problem, for which there should be an accepted treatment for patients with recognised disease.

Facilities for diagnosis and treatment should be available if a case is found.

The screening test or examination must be suitable and valid. A false positive test will cause massive anxiety and also considerable expense in proving that there is no disease. Similarly, false negatives can lead people to be reassured and to ignore serious symptoms until too late. If large numbers of positive tests or false positives occur during a screening programme, health services can be swamped.

The test, and any treatment as a possible result, should be acceptable. For example, there is little point in screening for a fetal abnormality which, if found, would lead to a recommendation for termination if the mother will refuse it on religious or moral grounds.

Screening tests also need to be considered from an economic perspective and the cost of case-?nding (including diagnosis and treatment of patients diagnosed) balanced in relation to possible expenditure on medical care as a whole.

Finally the programme should re?ect the natural history of the disease, and case-?nding should normally be a continuing process and not a ‘once for all’ project. If these rules are followed, considerable

bene?ts can result from well-planned and well-managed screening programmes, and they form an important part of any health-care system. The extent to which manipulation of genetic material will be added to more traditional approaches such as counselling, immunisation and drug treatment cannot yet be predicted but, as time goes by, it is often likely to be ethical and social controls which limit developments rather than technical and scienti?c limits.... preventive medicine

Teratogenesis

The production of physical defects in the FETUS. A drug may interfere with a mechanism that is essential for growth, and result in arrested or distorted development of the fetus – and yet cause no disturbance in adults, in whom these growth processes have ceased. Whether and how the EMBRYO is affected depends on what stage of development it has reached when the drug is given. The age of early di?erentiation – that is, from the beginning of the third week to the end of the tenth week of pregnancy – is the time of greatest susceptibility. After this time the likelihood of CONGENITAL malformation resulting from drug treatment is less, although the death of the fetus can occur at any time as a result of drugs crossing the PLACENTA or as a result of their e?ect on the placental circulation.

Although the risks are nil or very small with most drugs, no medication should be given to a pregnant woman, particularly during the ?rst few months of pregnancy, unless it is absolutely essential for her health or that of her unborn child. Alcohol is regarded as ‘medication’ in this context.... teratogenesis

Aids

Acquired immune deficiency syndrome, a deficiency of the immune system due to infection with HIV (human immunodeficiency virus). In most countries, illness and death from is a growing health problem, and there is, as yet, no cure or vaccine.

does not develop in all people infected with. The interval between infection and the development of is highly variable. Without treatment, around half of those people infected will develop within 8–9 years.

is transmitted in body fluids, including semen, blood, vaginal secretions, and breast milk. The major methods of transmission are sexual contact (vaginal, anal, or oral), blood to blood (via transfusions or needle-sharing in drug users), and mother to fetus. has also been transmitted through blood products given to treat haemophilia, artificial insemination by donated semen, and kidney transplants; but improved screening has greatly reduced these risks. is not spread by everyday contact, such as hugging or sharing crockery. The virus enters the bloodstream and infects cells that have a particular receptor, known as the CD4 receptor, on their surface. These cells include a type of white blood cell (a CD4 lymphocyte) responsible for fighting infection and cells in other tissues such as the brain. The virus reproduces within the infected cells, which then die, releasing more virus particles into the blood. If the infection is left untreated, the number of CD4 lymphocytes falls, resulting in greater susceptibility to certain infections and some types of cancer.

Some people experience a short-lived illness similar to infectious mononucleosis when they are first infected with. Many individuals have no obvious symptoms; some have only vague complaints, such as weight loss, fevers, sweats, or unexplained diarrhoea, described as -related complex.

Minor features of infection include skin disorders such as seborrhoeic dermatitis. More severe features include persistent herpes simplex infections, oral candidiasis (thrush), shingles, tuberculosis, and shigellosis. may also affect the brain, causing a variety of neurological disorders, including dementia.

Certain conditions, known as AIDSdefining illnesses, are characteristic of full-blown. These include cancers (Kaposi’s sarcoma and lymphoma of the brain), and various infections (pneumocystis pneumonia, cytomegalovirus infection, toxoplasmosis, diarrhoea due to CRYPTOSPORIDIUM or ISOSPORA, candidiasis, disseminated strongyloidiasis, and cryptococcosis), many of which are described as opportunistic infections.

Confirmation of infection involves testing a blood sample for the presence of antibodies to. Diagnosis of fullblown is based on a positive test along with the presence of an AIDSdefining illness.

The risk of infection with can be reduced by practising safer sex. Intravenous drug users should not share needles. There is a small risk to health workers handling infected blood products or needles, but this risk can be minimized by safe practices.

Treatment of infection with a combination of antiviral drugs can slow the disease’s progress, and may prevent the development of full-blown. The 2 main types of antiviral drug used are protease inhibitors, such as indinavir, and reverse transcriptase inhibitors such as zidovudine. Treatment is also available for -defining illnesses.... aids

Anaemia, Aplastic

A rare but serious type of anaemia in which the red cells, white cells, and platelets in the blood are all reduced in number. Aplastic anaemia is caused by a failure of the bone marrow to produce stem cells, the initial form of all blood cells.

Treatment of cancer with radiotherapy or anticancer drugs can temporarily interfere with the cell-producing ability of bone marrow, as can certain viral infections and other drugs. Long-term exposure to insecticides or benzene fumes may cause more persistent aplastic anaemia, and a moderate to high dose of nuclear radiation is another recognized cause. An autoimmune disorder is responsible in about half of all cases. Aplastic anaemia sometimes develops for no known reason.

A low level of red blood cells may cause symptoms common to all types of anaemia, such as fatigue and breathlessness. White-cell deficiency increases susceptibility to infections; platelet deficiency may lead to a tendency to bruise easily, bleeding gums, and nosebleeds.

The disorder is usually suspected from blood-test results, particularly a blood count, and is confirmed by a bone marrow biopsy.

Blood and platelet transfusions can control symptoms.

Immunosuppression is used to treat anaemia due to an autoimmune process.

Severe persistent aplastic anaemia may be fatal unless a bone marrow transplant is carried out.... anaemia, aplastic

Hypogammaglobulinaemia

n. a deficiency of the protein *gammaglobulin in the blood. It may occur in a variety of inherited disorders or as an acquired defect, as in chronic lymphocytic *leukaemia (CLL). Since gammaglobulin consists mainly of antibodies (*immunoglobulins), hypogammaglobulinaemia results in an increased susceptibility to infections.... hypogammaglobulinaemia

Hypoproteinaemia

n. a decrease in the quantity of protein in the blood. It may result from malnutrition, impaired protein production (as in liver disease), or increased loss of protein from the body (as in the *nephrotic syndrome). It results in swelling (*oedema), because of the accumulation of fluid in the tissues, and increased susceptibility to infections. See also hypogammaglobulinaemia.... hypoproteinaemia

Idiosyncrasy

n. an unusual and unexpected sensitivity exhibited by an individual to a particular drug or food. Drug idiosyncrasy commonly takes the form of undue susceptibility or hypersensitivity, so that the standard dose causes an excessive effect; the normal effect is produced by a small fraction of the standard dose. —idiosyncratic adj.... idiosyncrasy

Anticancer Drugs

Drugs that are used to treat many forms of cancer. They are particularly useful in the treatment of lymphomas, leukaemias, breast cancer, cancer of the testis (see testis, cancer of), and prostate cancer and are often used together with surgery or radiotherapy.

Most anticancer drugs are cytotoxic (kill or damage rapidly dividing cells), but some act by slowing the growth of hormone-sensitive tumours. Anticancer drugs are often prescribed in combination to maximize their effects.

Treatment with cytotoxic drugs is often given by injection in short courses repeated at intervals. Some drugs cause nausea and vomiting and may result in hair loss and increased susceptibility to infection. Others, such as tamoxifen, which is used for breast cancer, are given continuously by mouth for months or years and cause few side effects.... anticancer drugs

Asthma

A lung disease in which there is intermittent narrowing of the bronchi (airways), causing shortness of breath, wheezing, and cough. The illness often starts in childhood but can develop at any age. At least 1 child in 7 suffers from asthma, and the number affected has increased dramatically in recent years. Childhood asthma may be outgrown in about half of all cases.

During an asthma attack, the muscle in the walls of the airways contracts, causing narrowing. The linings of the airways also become swollen and inflamed, producing excess mucus that can block the smaller airways.

In some people, an allergic response triggers the airway changes. This allergic type of asthma tends to occur in

childhood and may develop in association with eczema or certain other allergic conditions such as hay fever (see rhinitis, allergic). Susceptibility to these conditions frequently runs in families and may be inherited.

Some substances, called allergens, are known to trigger attacks of allergic asthma. They include pollen, house-dust mites, mould, and dander and saliva from furry animals such as cats and dogs. Rarely, certain foods, such as milk, eggs, nuts, and wheat, provoke an allergic asthmatic reaction. Some people with asthma are sensitive to aspirin, and taking it may trigger an attack.

When asthma starts in adulthood, there are usually no identifiable allergic triggers. The 1st attack is sometimes brought on by a respiratory infection.

Factors that can provoke attacks in a person with asthma include cold air, exercise, smoke, and occasionally emotional factors such as stress and anxiety. Although industrial pollution and exhaust emission from motor vehicles do not normally cause asthma, they do appear to worsen symptoms in people who already have the disorder. Pollution in the atmosphere may also trigger asthma in susceptible people.

In some cases, a substance that is inhaled regularly in the work environment can cause a previously healthy person to develop asthma. This type is called occupation asthma and is one of the few occupational lung diseases that is still increasing in incidence.

There are currently about 200 substances used in the workplace that are known to trigger symptoms of asthma, including glues, resins, latex, and some chemicals, especially isocyanate chemicals used in spray painting. However, occupational asthma can be difficult to diagnose because a person may be regularly exposed to a particular trigger substance for weeks, months, or even years before the symptoms of asthma begin to appear.

Asthmatic attacks can vary in severity from mild breathlessness to respiratory failure. The main symptoms are wheezing, breathlessness, dry cough, and tightness in the chest. In a severe attack, breathing becomes increasingly difficult, resulting in a low level of oxygen in the blood. This causes cyanosis (bluish discoloration) of the face, particularly the lips. Untreated, such attacks may be fatal.

There is no cure for asthma, but attacks can be prevented to a large extent if a particular allergen can be identified.

Treatment involves inhaled bronchodilator drugs (sometimes known as relievers) to relieve symptoms. When symptoms occur frequently, or are severe, inhaled corticosteroids are also prescribed. These drugs are used continuously to prevent attacks by reducing inflammation in the airways and are also known as preventers.

Other drug treatments include sodium cromoglicate and nedocromil sodium, which are useful in preventing exerciseinduced asthma.

A new group of drugs called leukotriene receptor antagonists may reduce the dose of corticosteroid needed to control the condition.

Theophylline or the inhaled anticholinergic drug ipratropium may also be used as bronchodilators.

An asthma attack that has not responded to treatment with a bronchodilator needs immediate assessment and treatment in hospital.... asthma

Immunosuppressant

n. a drug, such as *azathioprine or *cyclophosphamide, that reduces the body’s resistance to infection and other foreign bodies by suppressing the immune system. Immunosuppressants are used to maintain the survival of organ and tissue transplants and to treat various *autoimmune diseases, including rheumatoid arthritis (see disease-modifying antirheumatic drug). *Ciclosporin is the immunosuppressant usually used in organ transplant recipients. Because immunity is lowered during treatment with immunosuppressants, there is an increased susceptibility to infection and certain types of cancer.... immunosuppressant

Long Qt Syndrome

prolongation of the *Q–T interval on the electrocardiogram. It indicates susceptibility to ventricular tachycardia (especially *torsades de pointes), ventricular fibrillation, and sudden death. It may be familial or caused by certain drugs (e.g. sotalol, amiodarone, certain antipsychotic drugs).... long qt syndrome

Neutropenia

n. an abnormal decrease in the number of *neutrophils in peripheral blood. Neutropenia may occur in a wide variety of diseases, including certain hereditary defects, aplastic *anaemias, tumours of the bone marrow, *agranulocytosis, and acute leukaemias. In cancer patients it is often due to the deleterious effects of *cytotoxic drugs on bone marrow cells. Neutropenia results in an increased susceptibility to infections; if patients become unwell, due to infection, this can lead to neutropenic sepsis, which can be life-threatening. —neutropenic adj.... neutropenia

Psychoneuroimmunology

n. the study of the effects of the mind on the functioning of the immune system, especially in relation to the influence of the mind on susceptibility to disease and the progression of a disease.... psychoneuroimmunology

Cancer

A group of diseases characterized by the abnormal and unrestrained growth of cells in body organs or tissues. Tumour-forming cells develop when the oncogenes (genes controlling cell growth and multiplication) in a cell or cells undergo a series of changes. A small group of abnormal cells develop that divide more rapidly than normal, lack differentiation (they no longer perform their specialized task), and may escape the normal control of hormones and nerves. Cancers differ from benign neoplasms (abnormal growths, such as warts) in that they spread and infiltrate surrounding tissue and may cause blockages, destroy nerves, and erode bone. Cancer cells may also spread via the blood vessels and lymphatic system to form secondary tumours (see metastasis).

Causes of cancer include environmental factors such as sunlight, smoking, pollutants, alcohol consumption, and dietary factors. These factors may provoke critical changes in body cells in susceptible people. Susceptibility to certain cancers may be inherited.

Many cancers are now curable, usually by combinations of surgery, radiotherapy, and anticancer drugs. For information on particular cancers, refer to the organ in question (for example lung cancer; stomach cancer).... cancer

Cushing’s Syndrome

A hormonal disorder caused by an abnormally high level of corticosteroid hormones in the blood. Cushing’s syndrome is characterized by a red moon-shaped face, wasting of the limbs, thickening of the trunk, and a humped upper back. Other symptoms

include acne, stretch marks, bruising, weakening of the bones by osteoporosis, susceptibility to infection and peptic ulcers, and, in women, increased hairiness. Mental changes frequently occur, causing depression, insomnia, paranoia, or, euphoria. Hypertension, oedema, and diabetes mellitus may develop. In children, growth may be suppressed.

The excess hormones are most commonly due to prolonged treatment with corticosteroid drugs. Such cases of Cushing’s syndrome are usually mild. In other cases, high hormone levels are due to overactivity of the adrenal glands as a result of an adrenal tumour, or of a pituitary tumour affecting production of ACTH (adrenocortocotrophic hormone), which stimulates the adrenal glands.

Cushing’s syndrome caused by corticosteroid drugs usually disappears if the dose is gradually reduced.

A tumour of an adrenal gland is removed surgically.

A pituitary tumour may be removed surgically or shrunk by irradiation and drug treatment.

In both cases, surgery is followed by hormone replacement therapy.... cushing’s syndrome

Immunodeficiency Disorders

Disorders in which there is a failure of the immune system’s defences to fight infection and tumours. They may be due to an inherited or a congenital defect or may be the result of acquired disease. The result is persistent or recurrent infection, including those with organisms that would not ordinarily cause disease, and an undue susceptibility to certain forms of cancer. The infections in people with immunodeficiency disorders are sometimes called opportunistic infections; examples include pneumocystic pneumonia, fungal infections, and widespread herpes simplex infections.

Congenital or inherited deficiencies can occur in either of the 2 prongs of the adaptive immune system: humoral or cellular. Deficiencies of the humoral system include hypogammaglobulinaemia and agammaglobulinaemia. The former may cause few or no symptoms, depending on the severity of the deficiency, but agammaglobulinaemia can be fatal if not treated with immunoglobulin. Congenital deficiencies of T-lymphocytes may lead to problems such as persistent and widespread candidiasis (thrush). A combined deficiency of both humoral and cellular components of the immune system, called severe combined immunodeficiency (SCID), is usually fatal in the 1st year of life unless treatment can be given by bone marrow transplant.

Acquired immunodeficiency may be due either to disease processes (such as infection with HIV, which leads to AIDS) or damage to the immune system as a result of its suppression by drugs. Severe malnutrition and many cancers can also cause immunodeficiency. Mild immunodeficiency arises through a natural decline in immune defences with age.... immunodeficiency disorders

Oestrogen Drugs

A group of synthetically produced drugs that are used in oral contraceptives and to supplement or replace the body’s own oestrogen hormones.

Oestrogen drugs are often used together with progestogen drugs.

Oestrogens suppress the production of gonadotrophin hormones, which stimulate cell activity in the ovaries. High doses are used in postcoital contraception to prevent conception (see contraception, emergency). They are also used to treat, or sometimes prevent, menopausal symptoms and disorders. Oestrogens may be used to treat certain forms of infertility, female hypogonadism, abnormal menstrual bleeding, prostatic cancer (see prostate, cancer of), and certain types of breast cancer.

Oestrogens may cause breast tenderness and enlargement, bloating, weight gain, nausea, reduced sex drive, depression, migraine, and bleeding between periods. Side effects often subside after 2 or 3 months. The drugs can increase the risk of abnormal blood clotting and susceptibility to high blood pressure (see hypertension). Oestrogen drugs should not be taken in pregnancy as they may adversely affect the fetus.... oestrogen drugs

Silicosis

n. a lung disease – a form of *pneumoconiosis – produced by inhaling silica dust particles. It affects workers in hard-rock mining and tunnelling, quarrying, stone dressing, sand blasting, and boiler scaling. Silica stimulates *fibrosis of lung tissue, which produces progressive breathlessness and considerably increased susceptibility to tuberculosis.... silicosis

Vitamin B Complex

A group of watersoluble vitamins comprising thiamine (vitamin B1), riboflavin (vitamin B2), niacin, pantothenic acid, pyridoxine (vitamin B6), biotin (vitamin H), and folic acid. Vitamin B12 is discussed above.

Thiamine plays a role in the activities of various enzymes involved in the utilization of carbohydrates and thus in the functioning of nerves, muscles, and the heart. Sources include whole-grain cereals, wholemeal breads, brown rice, pasta, liver, kidney, pork, fish, beans, nuts, and eggs.

Those susceptible to deficiency include elderly people on a poor diet, and people who have hyperthyroidism, malabsorption, or severe alcohol dependence. Deficiency may also occur as a result of severe illness, surgery, or injury.

Mild deficiency may cause tiredness, irritability, and loss of appetite. Severe deficiency may cause abdominal pain, constipation, depression, memory impairment, and beriberi; in alcoholics, it may cause Wernicke–Korsakoff syndrome. Excessive intake is not known to cause harmful effects.

Riboflavin is necessary for the activities of various enzymes involved in the breakdown and utilization of carbohydrates, fats, and proteins; the production of energy in cells; the utilization of other B vitamins; and hormone production by the adrenal glands. Liver, whole grains, milk, eggs, and brewer’s yeast are good sources. People who are susceptible to riboflavin deficiency include those taking phenothiazine antipsychotic drugs, tricyclic antidepressant drugs, or oestrogen-containing oral contraceptives, and those with malabsorption or severe alcohol dependence. Riboflavin deficiency may also occur as a result of serious illness, surgery, or injury.

Prolonged deficiency may cause soreness of the tongue and the corners of the mouth, and eye disorders such as amblyopia and photophobia.

Excessive intake of riboflavin is not known to have any harmful effects.

Niacin plays an essential role in the activities of various enzymes involved in the metabolism of carbohydrates and fats, the functioning of the nervous and digestive systems, the manufacture of sex hormones, and the maintenance of healthy skin. The main dietary sources are liver, lean meat, fish, nuts, and dried beans. Niacin can be made in the body from tryptophan (an amino acid). Most cases of deficiency are due to malabsorption disorders or to severe alcohol dependence. Prolonged niacin deficiency causes pellagra. Excessive intake is not known to cause harmful effects.

Pantothenic acid is essential for the activities of various enzymes involved in the metabolism of carbohydrates and fats, the manufacture of corticosteroids and sex hormones, the utilization of other vitamins, the functioning of the nervous system and adrenal glands, and growth and development. It is present in almost all vegetables, cereals, and animal foods. Deficiency of pantothenic acid usually occurs as a result of malabsorption or alcoholism, but may also occur after severe illness, surgery, or injury. The effects include fatigue, headache, nausea, abdominal pain, numbness and tingling, muscle cramps, and susceptibility to respiratory infections. In severe cases, a peptic ulcer may develop. Excessive intake has no known harmful effects.Pyridoxine aids the activities of various enzymes and hormones involved in the utilization of carbohydrates, fats, and proteins, in the manufacture of red blood cells and antibodies, in the functioning of the digestive and nervous systems, and in the maintenance of healthy skin. Dietary sources are liver, chicken, pork, fish, whole grains, wheatgerm, bananas, potatoes, and dried beans. Pyridoxine is also manufactured by intestinal bacteria. People who are susceptible to pyridoxine deficiency include elderly people who have a poor diet, those with malabsorption or severe alcohol dependence, or those who are taking certain drugs (including penicillamine and isoniazid). Deficiency may cause weakness, irritability, depression, skin disorders, inflammation of the mouth and tongue, anaemia, and, in infants, seizures. In very large amounts, pyridoxine may cause neuritis.

Biotin is essential for the activities of various enzymes involved in the breakdown of fatty acids and carbohydrates and for the excretion of the waste products of protein breakdown. It is present in many foods, especially liver, peanuts, dried beans, egg yolk, mushrooms, bananas, grapefruit, and watermelon. Biotin is also manufactured by bacteria in the intestines. Deficiency may occur during prolonged treatment with antibiotics or sulphonamide drugs. Symptoms are weakness, tiredness, poor appetite, hair loss, depression, inflammation of the tongue, and eczema. Excessive intake has no known harmful effects.

Folic acid is vital for various enzymes involved in the manufacture of nucleic acids and consequently for growth and reproduction, the production of red blood cells, and the functioning of the nervous system. Sources include green vegetables, mushrooms, liver, nuts, dried beans, peas, egg yolk, and wholemeal bread. Mild deficiency is common, but can usually be corrected by increasing dietary intake. More severe deficiency may occur during pregnancy or breastfeeding, in premature or low-birthweight infants, in people undergoing dialysis, in people with certain blood disorders, psoriasis, malabsorption, or alcohol dependence, and in people taking certain drugs. The main effects include anaemia, sores around the mouth, and, in children, poor growth. Folic acid supplements taken just before conception, and for the first 12 weeks of pregnancy, have been shown to reduce the risk of a neural tube defect.... vitamin b complex

Creutzfeldt–jakob Disease

(CJD) a rapidly progressive rare neurological disease, a form of human *spongiform encephalopathy in which dementia progresses to death after a period of 3–12 months. There is no effective treatment. The causative agent is an abnormal *prion protein that accumulates in the brain and causes widespread destruction of tissue. CJD typically affects middle-aged to elderly people. Some 15% of cases are due to a form of the disease that is inherited as an autosomal *dominant trait but most cases are sporadic, susceptibility being genetically determined. A few cases of CJD are acquired: the agent is known to have been transmitted by tissue and organ transplantation and by human growth hormone injections, but the disease may take years to manifest itself. Variant Creutzfeldt–Jakob disease (vCJD) is the human form of bovine spongiform encephalopathy (BSE), which is most likely acquired by the ingestion of infected beef products. Patients are younger than those affected with sporadic CJD and present with psychiatric symptoms (e.g. depression, anxiety) and hypersensitivity to touch, which are followed after months by myoclonic jerks (see myoclonus) and dementia. [H. G. Creutzfeldt (1885–1964) and A. M. Jakob (1884–1931), German psychiatrists]... creutzfeldt–jakob disease

Leukaemia

n. any of a group of malignant diseases in which the bone marrow and other blood-forming organs produce increased numbers of certain types of white blood cells (*leucocytes). Overproduction of these white cells, which are immature or abnormal forms, suppresses the production of normal white cells, red cells, and platelets. This leads to increased susceptibility to infection (due to *neutropenia), *anaemia, and bleeding (due to *thrombocytopenia). Other symptoms include enlargement of the spleen, liver, and lymph nodes.

Leukaemias are classified into acute or chronic varieties depending on the rate of progression of the disease. They are also classified according to the type of white cell that is proliferating abnormally; for example acute lymphoblastic leukaemia (see lymphoblast), chronic lymphocytic leukaemia (see lymphocyte), acute myeloblastic leukaemia (see myeloblast), hairy-cell leukaemia (see hairy cell), and monocytic leukaemia (see monocyte). (See also myeloid leukaemia.) Leukaemias can be treated with *cytotoxic drugs or *monoclonal antibodies, which suppress the production of the abnormal cells, or occasionally with radiotherapy.... leukaemia

Ovarian Cancer

a malignant tumour of the ovary, usually a carcinoma. Because of its wide-ranging pathology and an imperfect understanding of its causes, ovarian cancer is not readily detected in the early stages of development, when the tumour is small and produces few suspicious symptoms. Increased susceptibility to the disease is associated with raised serum levels of *CA125 (see also risk of malignancy index; BRCA1 and BRCA2). Diagnosis is based on the finding of a solid or cystic mass arising from the pelvis; there may be associated *ascites. The incidence of ovarian cancer reaches a peak in postmenopausal women; treatment involves surgery and most cases also require combined chemotherapy and/or radiotherapy.... ovarian cancer

Preimplantation Genetic Diagnosis

(PGD) a diagnostic procedure carried out on embryos at the earliest stage of development, before implantation in the uterus. Access to these early embryos requires the *in vitro fertilization of egg cells: three days after fertilization one or two cells are aspirated from the six-cell embryo; alternatively, tissue is removed from an embryo at five or six days, when it has reached the *blastocyst stage. Isolated cells can then be genetically analysed, allowing the transfer of selected embryos to the mother. One of the major applications of PGD is for the detection (using the *FISH technique) of chromosomal abnormalities, especially *aneuploidies (e.g. Down’s syndrome); the procedure is used mainly in women who have had repeated miscarriages or have failed to achieve pregnancy after several IVF treatment cycles, which could be due to the presence of such abnormalities in the embryo. PGD can also be used to detect defective genes responsible for hereditary disorders (e.g. the commonest form of cystic fibrosis, Huntington’s disease) and genes associated with susceptibility to certain cancers. When a defect is detected, *genetic counselling is offered.... preimplantation genetic diagnosis



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