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
Autoimmune disease ensues when the immune system attacks the target cells of the autoimmune reaction.... autoimmunity
Cancers are classi?ed according to the type of cell from which they are derived as well as the organ of origin. Hence cancers arising within the bronchi, often collectively referred to as ‘lung cancer’, include both adenocarcinomas, derived from epithelium (surface tissue), and carcinomas from glandular tissue. Sarcomas are cancers of connective tissue, including bone and cartilage. The behaviour of cancers and their response to therapy vary widely depending on this classi?cation as well as on numerous other factors such as how large the cancer is, how fast the cells grow and how well de?ned they are. It is entirely wrong to see cancer as a single disease entity with a universally poor prognosis. For example, fewer than one-half of women in whom breast cancer (see BREASTS, DISEASES OF) is discovered will die from the disease, and 75 per cent of children with lymphoblastic LEUKAEMIA can be cured.
Incidence In most western countries, cancer is the second most important cause of death after heart disease and accounts for 20–25 per cent of all deaths. In the United Kingdom in 2003, more than 154,000 people died of malignant disease. There is wide international variation in the most frequently encountered types of cancer, re?ecting the importance of environmental factors in the development of cancer. In the UK as well as the US, carcinoma of the BRONCHUS is the most common. Since it is usually inoperable at the time of diagnosis, it is even more strikingly the leading cause of cancer deaths. In women, breast cancer was for a long time the most common malignant disease, accounting for a quarter of all cancers, but ?gures for the late 1990s show that lung cancer now heads the incidence list – presumably the consequence of a rising incidence of smoking among young women. Other common sites are as follows: males – colon and rectum, prostate and bladder; females – colon and rectum, uterus, ovary and pancreas.
In 2003, of the more than 154,000 people in the UK who died of cancer, over 33,000 had the disease in their respiratory system, nearly 13,000 in the breast, over 5,800 in the stomach and more than 2,000 in the uterus or cervix, while over 4,000 people had leukaemia. The incidence of cancer varies with age; the older a person is, the more likely it is that he or she will develop the disease. The over-85s have an incidence about nine times greater than those in the 25–44 age group. There are also di?erences in incidence between sexes: for example, more men than women develop lung cancer, though the incidence in women is rising as the effects of smoking work through. The death rate from cancer is falling in people under 75 in the UK, a trend largely determined by the cancers which cause the most deaths: lung, breast, colorectal, stomach and prostate.
Causes In most cases the causes of cancer remain unknown, though a family history of cancer may be relevant. Rapid advances have, however, been made in the past two decades in understanding the di?erences between cancer cells and normal cells at the genetic level. It is now widely accepted that cancer results from acquired changes in the genetic make-up of a particular cell or group of cells which ultimately lead to a failure of the normal mechanisms regulating their growth. It appears that in most cases a cascade of changes is required for cells to behave in a truly malignant fashion; the critical changes affect speci?c key GENES, known as oncogenes, which are involved in growth regulation. (See APOPTOSIS.)
Since small genetic errors occur within cells at all times – most but not all of which are repaired – it follows that some cancers may develop as a result of an accumulation of random changes which cannot be attributed to environmental or other causes. The environmental factors known to cause cancer, such as radiation and chemicals (including tar from tobacco, asbestos, etc.), do so by increasing the overall rate of acquired genetic damage. Certain viral infections can induce speci?c cancers (e.g. HEPATITIS B VIRUS and HEPATOMA, EPSTEIN BARR VIRUS and LYMPHOMA) probably by inducing alterations in speci?c genes. HORMONES may also be a factor in the development of certain cancers such as those of the prostate and breast. Where there is a particular family tendency to certain types of cancer, it now appears that one or more of the critical genetic abnormalities required for development of that cancer may have been inherited. Where environmental factors such as tobacco smoking or asbestos are known to cause cancer, then health education and preventive measures can reduce the incidence of the relevant cancer. Cancer can also affect the white cells in the blood and is called LEUKAEMIA.
Treatment Many cancers can be cured by surgical removal if they are detected early, before there has been spread of signi?cant numbers of tumour cells to distant sites. Important within this group are breast, colon and skin cancer (melanoma). The probability of early detection of certain cancers can be increased by screening programmes in which (ideally) all people at particular risk of development of such cancers are examined at regular intervals. Routine screening for CERVICAL CANCER and breast cancer (see BREASTS, DISEASES OF) is currently practised in the UK. The e?ectiveness of screening people for cancer is, however, controversial. Apart from questions surrounding the reliability of screening tests, they undoubtedly create anxieties among the subjects being screened.
If complete surgical removal of the tumour is not possible because of its location or because spread from the primary site has occurred, an operation may nevertheless be helpful to relieve symptoms (e.g. pain) and to reduce the bulk of the tumour remaining to be dealt with by alternative means such as RADIOTHERAPY or CHEMOTHERAPY. In some cases radiotherapy is preferable to surgery and may be curative, for example, in the management of tumours of the larynx or of the uterine cervix. Certain tumours are highly sensitive to chemotherapy and may be cured by the use of chemotherapeutic drugs alone. These include testicular tumours, LEUKAEMIA, LYMPHOMA and a variety of tumours occurring in childhood. These tend to be rapidly growing tumours composed of primitive cells which are much more vulnerable to the toxic effects of the chemotherapeutic agents than the normal cells within the body.
Unfortunately neither radiotherapy nor currently available chemotherapy provides a curative option for the majority of common cancers if surgical excision is not feasible. New e?ective treatments in these conditions are urgently needed. Nevertheless the rapidly increasing knowledge of cancer biology will almost certainly lead to novel therapeutic approaches – including probably genetic techniques utilising the recent discoveries of oncogenes (genes that can cause cancer). Where cure is not possible, there often remains much that can be done for the cancer-sufferer in terms of control of unpleasant symptoms such as pain. Many of the most important recent advances in cancer care relate to such ‘palliative’ treatment, and include the establishment in the UK of palliative care hospices.
Families and patients can obtain valuable help and advice from Marie Curie Cancer Care, Cancer Relief Macmillan Fund, or the British Association of Cancer United Patients.
www.cancerbacup.org.uk
www.mariecurie.org.uk... cancer
Cause Asthma runs in families, so that parents with asthma have a strong risk of having children with asthma, or with other atopic (see ATOPY) illnesses such as HAY FEVER or eczema (see DERMATITIS). There is therefore a great deal of interest in the genetic basis of the condition. Several GENES seem to be associated with the condition of atopy, in which subjects have a predisposition to form ANTIBODIES of the IgE class against allergens (see ALLERGEN) they encounter – especially inhaled allergens.
The allergic response in the lining of the airway leads to an in?ammatory reaction. Many cells are involved in this in?ammatory process, including lymphocytes, eosinophils, neutrophils and mast cells. The cells are attracted and controlled by a complex system of in?ammatory mediators. The in?amed airway-wall produced in this process is then sensitive to further allergic stimuli or to non-speci?c challenges such as dust, smoke or drying from the increased respiration during exercise. Recognition of this in?ammation has concentrated attention on anti-in?ammatory aspects of treatment.
Continued in?ammation with poor control of asthma can result in permanent damage to the airway-wall such that reversibility is reduced and airway-narrowing becomes permanent. Appropriate anti-in?ammatory therapy may help to prevent this damage.
Many allergens can be important triggers of asthma. House-dust mite, grass pollen and animal dander are the commonest problems. Occupational factors such as grain dusts, hard-metals fumes and chemicals in the plastic and paint industry are important in some adults. Viral infections are another common trigger, especially in young children.
The prevalence of asthma appears to be on the increase in most countries. Several factors have been linked to this increase; most important may be the vulnerability of the immature immune system (see IMMUNITY) in infants. High exposure to allergens such as house-dust mite early in life may prime the immune system, while reduced exposure to common viral infections may delay the maturation of the immune system. In addition, maternal smoking in pregnancy and infancy increases the risk.
Clinical course The major symptoms of asthma are breathlessness and cough. Occasionally cough may be the only symptom, especially in children, where night-time cough may be mistaken for recurrent infection and treated inappropriately with antibiotics.
The onset of asthma is usually in childhood, but it may begin at any age. In childhood, boys are affected more often than girls but by adulthood the sex incidence is equal. Children who have mild asthma are more likely to grow out of the condition as they go through their teenaged years, although symptoms may recur later.
The degree of airway-narrowing, and its change with time and treatment, can be monitored by measuring the peak expiratory ?ow with a simple monitor at home – a peak-?ow meter. The typical pattern shows the peak ?ow to be lowest in the early morning and this ‘morning dipping’ is often associated with disturbance of sleep.
Acute exacerbations of asthma may be provoked by infections or allergic stimuli. If they do not respond quickly and fully to medication, expert help should be sought urgently since oxygen and higher doses of drugs will be necessary to control the attack. In a severe attack the breathing rate and the pulse rate rise and the chest sounds wheezy. The peak-?ow rate of air into the lungs falls. Patients may be unable to talk in full sentences without catching their breath, and the reduced oxygen in the blood in very severe attacks may produce the blue colour of CYANOSIS in the lips and tongue. Such acute attacks can be very frightening for the patient and family.
Some cases of chronic asthma are included in the internationally agreed description CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) – a chronic, slowly progressive disorder characterised by obstruction of the air?ow persisting over several months.
Treatment The ?rst important consideration in the treatment of asthma is avoidance of precipitating factors. When this is a speci?c animal or occupational exposure, this may be possible; it is however more di?cult for house-dust mite or pollens. Exercise-induced asthma should be treated adequately rather than avoiding exercise.
Desensitisation injections using small quantities of speci?c allergens are used widely in some countries, but rarely in the UK as they are considered to have limited value since most asthma is precipitated by many stimuli and controlled adequately with simple treatment.
There are two groups of main drugs for the treatment of asthma. The ?rst are the bronchodilators which relax the smooth muscle in the wall of the airways, increase their diameter and relieve breathlessness. The most useful agents are the beta adrenergic agonists (see ADRENERGIC RECEPTORS) such as salbutamol and terbutaline. They are best given by inhalation into the airways since this reduces the general side-effects from oral use. These drugs are usually given to reverse airway-narrowing or to prevent its onset on exercise. However, longer-acting inhaled beta agonists such as salmeterol and formoterol or the theophyllines given in tablet form can be used regularly as prevention. The beta agonists can cause TREMOR and PALPITATION in some patients.
The second group of drugs are the antiin?ammatory agents that act to reduce in?ammation of the airway. The main agents in this group are the CORTICOSTEROIDS. They must be taken regularly, even when symptoms are absent. Given by inhalation they have few side-effects. In acute attacks, short courses of oral steroids are used; in very severe disease regular oral steroids may be needed. Other drugs have a role in suppressing in?ammation: sodium cromoglycate has been available for some years and is generally less e?ective than inhaled steroids. Newer agents directed at speci?c steps in the in?ammatory pathway, such as leukotriene receptor-antagonists, are alternative agents.
Treatment guidelines have been produced by various national and international bodies, such as the British Thoracic Society. Most have set out treatment in steps according to severity, with objectives for asthma control based on symptoms and peak ?ow. Patients should have a management plan that sets out their regular treatment and their appropriate response to changes in their condition.
Advice and support for research into asthma is provided by the National Asthma Campaign.
See www.brit-thoracic.org.uk
Prognosis Asthma is diagnosed in 15–20 per cent of all pre-school children in the developed world. Yet by the age of 15 it is estimated that fewer than 5 per cent still have symptoms. A study in 2003 reported on a follow-up of persons born in 1972–3 who developed asthma and still had problems at the age of nine. By the time these persons were aged 26, 27 per cent were still having problems; around half of that number had never been free from the illness and the other half had apparently lost it for a few years but it had returned.... asthma
Dysphasia may come on suddenly and last only for a few hours or days, being due to a temporary block in the circulation of blood to the brain. The effects may be permanent, but although the individual may have di?culty in understanding language and expressing themselves, they will be quite aware of their surroundings and may be very frustrated by their inability to communicate with others.
Further information may be obtained from Speakability.... dysphasia
Pregnancy lasts about 280 days and is calculated from the ?rst day of the last menstrual period – see MENSTRUATION. Pregnancy-testing kits rely on the presence of the hormone beta HUMAN CHORIONIC GONADOTROPHIN (b HCG) which is excreted in the woman’s urine as early as 30 days from the last menstrual period. The estimated date of delivery can be accurately estimated from the size of the developing fetus measured by ULTRASOUND (see also below) between seven and 24 weeks. ‘Term’ refers to the time that the baby is due; this can range from 38 weeks to 41 completed weeks.
Physical changes occur in early pregnancy – periods stop and the abdomen enlarges. The breasts swell, with the veins becoming prominent and the nipples darkening. About two in three women will have nausea with a few experiencing such severe vomiting as to require hospital admission for rehydration.
Antenatal care The aim of antenatal care is to ensure a safe outcome for both mother and child; it is provided by midwives (see MIDWIFE) and doctors. Formal antenatal care began in Edinburgh in the 1930s with the recognition that all aspects of pregnancy – normal and abnormal – warranted surveillance. Cooperation between general practitioners, midwives and obstetricians is now established, with pregnancies that are likely to progress normally being cared for in the community and only those needing special intervention being cared for in a hospital setting.
The initial visit (or booking) in the ?rst half of pregnancy will record the history of past events and the results of tests, with the aim of categorising the patients into normal or not. Screening tests including blood checks and ultrasound scans are a routine part of antenatal care. The ?rst ultrasound scan is done at about 11 weeks to date the pregnancy, with a further one done at 20 weeks – the anomaly scan – to assess the baby’s structure. Some obstetric units will check the growth of the baby with one further scan later in the pregnancy or, in the case of twin pregnancies (see below), many scans throughout. The routine blood tests include checks for ANAEMIA, DIABETES MELLITUS, sickle-cell disease and THALASSAEMIA, as well as for the blood group. Evidence of past infections is also looked for; tests for RUBELLA (German measles) and SYPHILIS are routine, whereas tests for human immunode?ciency virus (see AIDS/ HIV below) and HEPATITIS are being o?ered as optional, although there is compelling evidence that knowledge of the mother’s infection status is bene?cial to the baby.
Traditional antenatal care consists of regular appointments, initially every four weeks until 34 weeks, then fortnightly or weekly. At each visit the mother’s weight, urine and blood pressure are checked, and assessment of fetal growth and position is done by palpating the uterus. Around two-thirds of pregnancies and labours are normal: in the remainder, doctors and midwives need to increase the frequency of surveillance so as to prevent or deal with maternal and fetal problems.
Common complications of pregnancy
Some of the more common complications of pregnancy are listed below.
As well as early detection of medical complications, antenatal visits aim to be supportive and include emotional and educational care. Women with uncomplicated pregnancies are increasingly being managed by midwives and general practitioners in the community and only coming to the hospital doctors should they develop a problem. A small number will opt for a home delivery, but facilities for providing such a service are not always available in the UK.
Women requiring more intensive surveillance have their management targeted to the speci?c problems encountered. Cardiologists will see mothers-to-be with heart conditions, and those at risk of diabetes are cared for in designated clinics with specialist sta?. Those women needing more frequent surveillance than standard antenatal care can be looked after in maternity day centres. These typically include women with mildly raised blood pressure or those with small babies. Fetal medicine units have specialists who are highly skilled in ultrasound scanning and specialise in the diagnosis and management of abnormal babies still in the uterus. ECTOPIC PREGNANCY Chronic abdominal discomfort early in pregnancy may be caused by unruptured ectopic pregnancy, when, rarely, the fertilised OVUM starts developing in the Fallopian tube (see FALLOPIAN TUBES) instead of the uterus. The patient needs hospital treatment and LAPAROSCOPY. A ruptured ectopic pregnancy causes acute abdominal symptoms and collapse, and the woman will require urgent abdominal surgery. URINARY TRACT INFECTIONS These affect around 2 per cent of pregnant women and are detected by a laboratory test of a mid-stream specimen of urine. In pregnancy, symptoms of these infections do not necessarily resemble those experienced by non-pregnant women. As they can cause uterine irritability and possible premature labour (see below), it is important to ?nd and treat them appropriately. ANAEMIA is more prevalent in patients who are vegetarian or on a poor diet. Iron supplements are usually given to women who have low concentrations of HAEMOGLOBIN in their blood (less than 10.5 g/dl) or who are at risk of becoming low in iron, from bleeding, twin pregnancies and those with placenta previa (see below). ANTEPARTUM HAEMORRHAGE Early in pregnancy, vaginal bleedings may be due to a spontaneous or an incomplete therapeutic ABORTION. Bleeding from the genital tract between 24 completed weeks of pregnancy and the start of labour is called antepartum haemorrhage. The most common site is where the PLACENTA is attached to the wall of the uterus. If the placenta separates before delivery, bleeding occurs in the exposed ‘bed’. When the placenta is positioned in the upper part of the uterus it is called an abruption. PLACENTA PRAEVIA is sited in the lower part and blocks or partly blocks the cervix (neck of the womb); it can be identi?ed at about the 34th week. Ten per cent of episodes of antepartum bleeding are caused by placenta previa, and it may be associated with bleeding at delivery. This potentially serious complication is diagnosed by ultrasound scanning and may require a caesarean section (see below) at delivery. INCREASED BLOOD PRESSURE, associated with protein in the urine and swelling of the limbs, is part of a condition known as PRE-ECLAMPSIA. This occurs in the second half of pregnancy in about 1 in 10 women expecting their ?rst baby, and is mostly very mild and of no consequence to the pregnancy. However, some women can develop extremely high blood pressures which can adversely affect the fetus and cause epileptic-type seizures and bleeding disorders in the mother. This serious condition is called ECLAMPSIA. For this reason a pregnant woman with raised blood pressure or PROTEIN in her urine is carefully evaluated with blood tests, often in the maternity day assessment unit. The condition can be stopped by delivery of the baby, and this will be done if the mother’s or the fetus’s life is in danger. If the condition is milder, and the baby not mature enough for a safe delivery, then drugs can be used to control the blood pressure. MISCARRIAGE Also called spontaneous abortion, miscarriage is the loss of the fetus. There are several types:
threatened miscarriage is one in which some vaginal bleeding occurs, the uterus is enlarged, but the cervix remains closed and pregnancy usually proceeds.
inevitable miscarriage usually occurs before the 16th week and is typi?ed by extensive blood loss through an opened cervix and cramp-like abdominal pain; some products of conception are lost but the developing placental area (decidua) is retained and an operation may be necessary to clear the womb.
missed miscarriages, in which the embryo dies and is absorbed, but the decidua (placental area of uterine wall) remains and may cause abdominal discomfort and discharge of old blood.
THERAPEUTIC ABORTION is performed on more than 170,000 women annually in England and Wales. Sometimes the woman may not have arranged the procedure through the usual health-care channels, so that a doctor may see a patient with vaginal bleeding, abdominal discomfort or pain, and open cervix – symptoms which suggest that the decidua and a blood clot have been retained; these retained products will need to be removed by curettage.
Septic abortions are now much less common in Britain than before the Abortion Act (1967) permitted abortion in speci?ed circumstances. The cause is the passage of infective organisms from the vagina into the uterus, with Escherichia coli and Streptococcus faecalis the most common pathogenic agents. The woman has abdominal pain, heavy bleeding, usually fever and sometimes she is in shock. The cause is usually an incomplete abortion or one induced in unsterile circumstances. Antibiotics and curettage are the treatment. INTRAUTERINE GROWTH RETARDATION describes a slowing of the baby’s growth. This can be diagnosed by ultrasound scanning, although there is a considerable margin of error in estimates of fetal weight. Trends in growth are favoured over one-o? scan results alone. GESTATIONAL DIABETES is a condition that is more common in women who are overweight or have a family member with diabetes. If high concentrations of blood sugar are found, e?orts are made to correct it as the babies can become very fat (macrosomia), making delivery more di?cult. A low-sugar diet is usually enough to control the blood concentration of sugars; however some women need small doses of INSULIN to achieve control. FETAL ABNORMALITIES can be detected before birth using ultrasound. Some of these defects are obvious, such as the absence of kidneys, a condition incompatible with life outside the womb. These women can be o?ered a termination of their pregnancy. However, more commonly, the pattern of problems can only hint at an abnormality and closer examination is needed, particularly in the diagnosis of chromosomal deformities such as DOWN’S (DOWN) SYNDROME (trisomy 21 or presence of three 21 chromosomes instead of two).
Chromosomal abnormalities can be de?nitively diagnosed only by cell sampling such as amniocentesis (obtaining amniotic ?uid – see AMNION – from around the baby) done at 15 weeks onwards, and chorionic villus sampling (sampling a small part of the placenta) – another technique which can be done from 12 weeks onwards. Both have a small risk of miscarriage associated with them; consequently, they are con?ned to women at higher risk of having an abnormal fetus.
Biochemical markers present in the pregnant woman’s blood at di?erent stages of pregnancy may have undergone changes in those carrying an abnormal fetus. The ?rst such marker to be routinely used was a high concentration of alpha-fetol protein in babies with SPINA BIFIDA (defects in the covering of the spinal cord). Fuller research has identi?ed a range of diagnostic markers which are useful, and, in conjunction with other factors such as age, ethnic group and ultrasound ?ndings, can provide a predictive guide to the obstetrician – in consultation with the woman – as to whether or not to proceed to an invasive test. These tests include pregnancy-associated plasma protein assessed from a blood sample taken at 12 weeks and four blood tests at 15–22 weeks – alphafetol protein, beta human chorionic gonadotrophin, unconjugated oestriol and inhibin A. Ultrasound itself can reveal physical ?ndings in the fetus, which can be more common in certain abnormalities. Swelling in the neck region of an embryo in early pregnancy (increased nuchal thickness) has good predictive value on its own, although its accuracy is improved in combination with the biochemical markers. The e?ectiveness of prenatal diagnosis is rapidly evolving, the aim being to make the diagnosis as early in the pregnancy as possible to help the parents make more informed choices. MULTIPLE PREGNANCIES In the UK, one in 95 deliveries is of twins, while the prevalence of triplets is one in 10,000 and quadruplets around one in 500,000. Racial variations occur, with African women having a prevalence rate of one in 30 deliveries for twins and Japanese women a much lower rate than the UK ?gure. Multiple pregnancies occur more often in older women, and in the UK the prevalence of fertility treatments, many of these being given to older women, has raised the incidence. There is now an o?cial limit of three eggs being transferred to a woman undergoing ASSISTED CONCEPTION (gamete intrafallopian transfer, or GIFT).
Multiple pregnancies are now usually diagnosed as a result of routine ultrasound scans between 16 and 20 weeks of pregnancy. The increased size of the uterus results in the mother having more or worse pregnancy-related conditions such as nausea, abdominal discomfort, backache and varicose veins. Some congenital abnormalities in the fetus occur more frequently in twins: NEURAL TUBE defects, abnormalities of the heart and the incidence of TURNER’S SYNDROME and KLINEFELTER’S SYNDROME are examples. Such abnormalities may be detected by ultrasound scans or amniocentesis. High maternal blood pressure and anaemia are commoner in women with multiple pregnancies (see above).
The growth rates of multiple fetuses vary, but the di?erence between them and single fetuses are not that great until the later stages of pregnancy. Preterm labour is commoner in multiple pregnancies: the median length of pregnancy is 40 weeks for singletons, 37 for twins and 33 for triplets. Low birth-weights are usually the result of early delivery rather than abnormalities in growth rates. Women with multiple pregnancies require more frequent and vigilant antenatal assessments, with their carers being alert to the signs of preterm labour occurring. CEPHALOPELVIC DISPROPORTION Disparity between the size of the fetus and the mother’s pelvis is not common in the UK but is a signi?cant problem in the developing world. Disparity is classi?ed as absolute, when there is no possibility of delivery, and relative, when the baby is large but delivery (usually after a dif?cult labour) is possible. Causes of absolute disparity include: a large baby – heavier than 5 kg at birth; fetal HYDROCEPHALUS; and an abnormal maternal pelvis. The latter may be congenital, the result of trauma or a contraction in pelvic size because of OSTEOMALACIA early in life. Disproportion should be suspected if in late pregnancy the fetal head has not ‘engaged’ in the pelvis. Sometimes a closely supervised ‘trial of labour’ may result in a successful, if prolonged, delivery. Otherwise a caesarean section (see below) is necessary. UNUSUAL POSITIONS AND PRESENTATIONS OF THE BABY In most pregnant women the baby ?ts into the maternal pelvis head-?rst in what is called the occipito-anterior position, with the baby’s face pointing towards the back of the pelvis. Sometimes, however, the head may face the other way, or enter the pelvis transversely – or, rarely, the baby’s neck is ?exed backwards with the brow or face presenting to the neck of the womb. Some malpositions will correct naturally; others can be manipulated abdominally during pregnancy to a better position. If, however, the mother starts labour with the baby’s head badly positioned or with the buttocks instead of the head presenting (breech position), the labour will usually be longer and more di?cult and may require intervention using special obstetric forceps to assist in extracting the baby. If progress is poor and the fetus distressed, caesarean section may be necessary. HIV INFECTION Pregnant women who are HIV positive (see HIV; AIDS/HIV) should be taking antiviral drugs in the ?nal four to ?ve months of pregnancy, so as to reduce the risk of infecting the baby in utero and during birth by around 50 per cent. Additional antiviral treatment is given before delivery; the infection risk to the baby can be further reduced – by about 40 per cent – if delivery is by caesarean section. The mother may prefer to have the baby normally, in which case great care should be taken not to damage the baby’s skin during delivery. The infection risk to the baby is even further reduced if it is not breast fed. If all preventive precautions are taken, the overall risk of the infant becoming infected is cut to under 5 per cent.
Premature birth This is a birth that takes place before the end of the normal period of gestation, usually before 37 weeks. In practice, however, it is de?ned as a birth that takes place when the baby weighs less than 2·5 kilograms (5••• pounds). Between 5 and 10 per cent of babies are born prematurely, and in around 40 per cent of premature births the cause is unknown. Pre-eclampsia is the most common known cause; others include hypertension, chronic kidney disease, heart disease and diabetes mellitus. Multiple pregnancy is another cause. In the vast majority of cases the aim of management is to prolong the pregnancy and so improve the outlook for the unborn child. This consists essentially of rest in bed and sedation, but there are now several drugs, such as RITODRINE, that may be used to suppress the activity of the uterus and so help to delay premature labour. Prematurity was once a prime cause of infant mortality but modern medical care has greatly improved survival rates in developing countries.
Labour Also known by the traditional terms parturition, childbirth or delivery, this is the process by which the baby and subsequently the placenta are expelled from the mother’s body. The onset of labour is often preceded by a ‘show’ – the loss of the mucus and blood plug from the cervix, or neck of the womb; this passes down the vagina to the exterior. The time before the beginning of labour is called the ‘latent phase’ and characteristically lasts 24 hours or more in a ?rst pregnancy. Labour itself is de?ned by regular, painful contractions which cause dilation of the neck of the womb and descent of the fetal head. ‘Breaking of the waters’ is the loss of amniotic ?uid vaginally and can occur any time in the delivery process.
Labour itself is divided into three stages: the ?rst is from the onset of labour to full (10 cm) dilation of the neck of the womb. This stage varies in length, ideally taking no more than one hour per centimetre of dilation. Progress is monitored by regular vaginal examinations, usually every four hours. Fetal well-being is observed by intermittent or continuous monitoring of the fetal heart rate in relation to the timing and frequency of the contractions. The print-out is called a cardiotocograph. Abnormalities of the fetal heart rate may suggest fetal distress and may warrant intervention. In women having their ?rst baby (primigravidae), the common cause of a slow labour is uncoordinated contractions which can be overcome by giving either of the drugs PROSTAGLANDIN or OXYTOCIN, which provoke contractions of the uterine muscle, by an intravenous drip. Labours which progress slowly or not at all may be due to abnormal positioning of the fetus or too large a fetus, when prostaglandin or oxytocin is used much more cautiously.
The second stage of labour is from full cervical dilation to the delivery of the baby. At this stage the mother often experiences an irresistible urge to push the baby out, and a combination of strong coordinated uterine contractions and maternal e?ort gradually moves the baby down the birth canal. This stage usually lasts under an hour but can take longer. Delay, exhaustion of the mother or distress of the fetus may necessitate intervention by the midwife or doctor. This may mean enlarging the vaginal opening with an EPISIOTOMY (cutting of the perineal outlet – see below) or assisting the delivery with specially designed obstetric forceps or a vacuum extractor (ventouse). If the cervix is not completely dilated or open and the head not descended, then an emergency caesarean section may need to be done to deliver the baby. This procedure involves delivering the baby and placenta through an incision in the mother’s abdomen. It is sometimes necessary to deliver by planned or elective caesarean section: for example, if the placenta is low in the uterus – called placenta praevia – making a vaginal delivery dangerous.
The third stage occurs when the placenta (or afterbirth) is delivered, which is usually about 10–20 minutes after the baby. An injection of ergometrine and oxytocin is often given to women to prevent bleeding.
Pain relief in labour varies according to the mother’s needs. For uncomplicated labours, massage, reassurance by a birth attendant, and a warm bath and mobilisation may be enough for some women. However, some labours are painful, particularly if the woman is tired or anxious or is having her ?rst baby. In these cases other forms of analgesia are available, ranging from inhalation of NITROUS OXIDE GAS, injection of PETHIDINE HYDROCHLORIDE or similar narcotic, and regional local anaesthetic (see ANAESTHESIA).
Once a woman has delivered, care continues to ensure her and the baby’s safety. The midwives are involved in checking that the uterus returns to its normal size and that there is no infection or heavy bleeding, as well as caring for stitches if needed. The normal blood loss after birth is called lochia and generally is light, lasting up to six weeks. Midwives o?er support with breast feeding and care of the infant and will visit the parents at home routinely for up to two weeks.
Some complications of labour All operative deliveries in the UK are now done in hospitals, and are performed if a spontaneous birth is expected to pose a bigger risk to the mother or her child than a specialist-assisted one. Operative deliveries include caesarean section, forceps-assisted deliveries and those in which vacuum extraction (ventouse) is used. CAESAREAN SECTION Absolute indications for this procedure, which is used to deliver over 15 per cent of babies in Britain, are cephalopelvic disproportion and extensive placenta praevia, both discussed above. Otherwise the decision to undertake caesarean section depends on the clinical judgement of the specialist and the views of the mother. The rise in the proportion of this type of intervention (from 5 per cent in the 1930s to its present level of over 23 per cent
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of the 600,000 or so annual deliveries in England) has been put down to defensive medicine
– namely, the doctor’s fear of litigation (initiated often because the parents believe that the baby’s health has suffered because the mother had an avoidably di?cult ‘natural’ labour). In Britain, over 60 per cent of women who have had a caesarean section try a vaginal delivery in a succeeding pregnancy, with about two-thirds of these being successful. Indications for the operation include:
absolute and relative cephalopelvic disproportion.
placenta previa.
fetal distress.
prolapsed umbilical cord – this endangers the viability of the fetus because the vital supply of oxygen and nutrients is interrupted.
malpresentation of the fetus such as breech or transverse lie in the womb.
unsatisfactory previous pregnancies or deliveries.
a request from the mother.
Caesarean sections are usually performed using regional block anaesthesia induced by a spinal or epidural injection. This results in loss of feeling in the lower part of the body; the mother is conscious and the baby not exposed to potential risks from volatile anaesthetic gases inhaled by the mother during general anaesthesia. Post-operative complications are higher with general anaesthesia, but maternal anxiety and the likelihood that the operation might be complicated and di?cult are indications for using it. A general anaesthetic may also be required for an acute obstetric emergency. At operation the mother’s lower abdomen is opened and then her uterus opened slowly with a transverse incision and the baby carefully extracted. A transverse incision is used in preference to the traditional vertical one as it enables the woman to have a vaginal delivery in any future pregnancy with a much smaller risk of uterine rupture. Women are usually allowed to get up within 24 hours and are discharged after four or ?ve days. FORCEPS AND VENTOUSE DELIVERIES Obstetric forceps are made in several forms, but all are basically a pair of curved blades shaped so that they can obtain a purchase on the baby’s head, thus enabling the operator to apply traction and (usually) speed up delivery. (Sometimes they are used to slow down progress of the head.) A ventouse or vacuum extractor comprises an egg-cup-shaped metal or plastic head, ranging from 40 to 60 mm in diameter with a hollow tube attached through which air is extracted by a foot-operated vacuum pump. The instrument is placed on the descending head, creating a negative pressure on the skin of the scalp and enabling the operator to pull the head down. In mainland Europe, vacuum extraction is generally preferred to forceps for assisting natural deliveries, being used in around 5 per cent of all deliveries. Forceps have a greater risk of causing damage to the baby’s scalp and brain than vacuum extraction, although properly used, both types should not cause any serious damage to the baby.
Episiotomy Normal and assisted deliveries put the tissues of the genital tract under strain. The PERINEUM is less elastic than the vagina and, if it seems to be splitting as the baby’s head
moves down the birth canal, it may be necessary to cut the perineal tissue – a procedure called an episiotomy – to limit damage. This is a simple operation done under local anaesthetic. It should be done only if there is a speci?c indication; these include:
to hasten the second stage of labour if the fetus is distressed.
to facilitate the use of forceps or vacuum extractor.
to enlarge a perineum that is restricted because of unyielding tissue, perhaps because of a scar from a previous labour. Midwives as well as obstetricians are trained
to undertake and repair (with sutures) episiotomies.
(For organisations which o?er advice and information on various aspects of childbirth, including eclampsia, breast feeding and multiple births, see APPENDIX 2: ADDRESSES: SOURCES OF INFORMATION, ADVICE, SUPPORT AND SELF-HELP.)... pregnancy and labour
Habitat: Parasitic on the Oak, Hawthorn, Apple and many other trees.
Features ? This familiar evergreen is a true parasite, receiving no nourishment from the soil, nor even from the decaying bark. The leaves are obtuse lance-shaped, broader towards the end, sessile, and grow from a smooth-jointed stem about a foot high. The flower-heads are yellowish and the berries white. The plant is tasteless and without odour.Part used ? Leaves.Action: Highly valued as a nervine and antispasmodic.
Mistletoe leaves are given in hysteria, epilepsy, chorea and other diseases of the nervous system. As an anti-spasmodic and tonic it is used in cardiac dropsy.Culpeper is at his most "Culpeperish" in discussing this plant, as witness:"The birdlime doth mollify hard knots, tumours and imposthumes, ripeneth and discuteth them; and draweth thick as well as thin humours from remote parts of the body, digesting and separating them. And being mixed with equal parts of resin and wax, doth mollify the hardness of the spleen, and healeth old ulcers and sores. Being mixed with Sandarack and Orpiment, it helpeth to draw off foul nails; and if quicklime and wine lees be added thereunto it worketh the stronger. Both the leaves and berries of Mistletoe do heat and dry, and are of subtle parts."While some truth may be hidden behind all this quaint terminology, it is feared that the modern herbal consultant would encounter serious difficulties if he attempted to follow the Culpeperian procedure too literally—although certain people still believe, or affect to believe, that he does so!The birdlime mentioned in the quotation and also in the synonyms is the resin viscin, from the Latin viscum, birdlime.MOUNTAIN FLAX.Linum cartharticum. N.O. LinaceaeSynonym: Purging Flax.Habitat: Heaths, moorlands; occasionally meadows and pastures.
Features ? Stem simple, up to eight inches high. Leaves opposite, small, lower obovate, higher lanceolate, entire. Flowers small, white (June to September), five-parted with serrate sepals, pointed petals. Taste, bitter and acrid.Part used ? Herb.Action: Laxative, cathartic.
In constipation, action similar to Senna, and sometimes preferred to the latter; rarely gripes. Occasionally prescribed with diuretics, etc., for gravel and dropsy. Combined with tonics and stomachics such as Gentian and Calumba root, makes a first-rate family medicine. Dose, wineglass of the ounce to pint infusion.... mistletoeThe incidence of silicosis is steadily being reduced by various measures which diminish the risk of inhaling silica dust. These include adequate ventilation to draw o? the dust; the suppression of dust by the use of water; the wearing of respirators where the risk is particularly great and it is not possible to reduce the amount of dust – for example, in sand-blasting; and periodic medical examination of work-people exposed to risk. Fewer than 100 new cases a year are diagnosed now in the United Kingdom. (See also OCCUPATIONAL HEALTH, MEDICINE AND DISEASES.)... silicosis
Symptoms: dry throat, eye irritation, headache, fatigue, wheezy chest and flu-like colds may be a product of modern ventilating systems. The headache may come on in the afternoon and improve on leaving work. Humidifier fever. Passive inhalation of cigarette smoke a factor.
Alternatives. Treatment. Ginseng, Iceland Moss, Irish Moss, German Chamomile tea. ... building sickness syndrome
The traditional repellent is Sweet Bay (Laurus nobilis) which is also used as external treatment for bite.
To prevent infection: Tincture Echinacea, 10-15 drops in water every 2 hours. See: SALMONELLA. INFECTIVE HEPATITIS.
Many asthma patients are allergic to presence of cockroaches. ... cockroach, the
It can be a reaction of tissue to infection, injury, surgery, radiation, chemicals, heat or cold, cancer or auto-immune disease.
Every medical student has to commit to memory four classical symptoms: heat, redness, pain and swelling.
As inflammation is a natural process, its progress should not be hindered by too much interference. Invading micro-organisms are destroyed by antibodies and white blood cells. During the encounter white cells may also be destroyed and expelled from the body in the form of pus. They are assisted in their action by an Anti-inflammatory. Most anti-inflammatories are also antiseptics. An external injury should be washed and treated with one.
Selection of remedies varies according to area and degree of inflammation. When occurring in the colon, it was known as ‘colicon’ by Celsus, Roman physician, in the 1st century. His prescription is as apt today:– Aniseed, Parsley, Pepper, few drops Castor oil and a pinch of powdered Myrrh.
Treatment for inflammation would be appropriate to the disease or condition, i.e. inflammation of the inner lining of the heart requires specific treatment as appears in entry for ENDOCARDITIS. For simple external inflammation, a tea of Chickweed, Comfrey or Marshmallow root may be indicated. See: ANTI- INFLAMMATORIES.
Treatment by or in liaison with a general medical practitioner. ... inflammation
The term innate immunity is given to the protection that we are born with, such as the skin and the mucous membranes that line the mouth, nose, throat, intestines, and vagina. It also includes antibodies, or immunoglobulins (protective proteins), that have been passed to the child from the mother. If microorganisms penetrate these defences, they encounter “cell-devouring” white blood cells called phagocytes, and other types of white cells, such as natural cellkilling (cytotoxic) cells. Microorganisms may also meet naturally produced substances (such as interferon) or a group of blood proteins called the complement system, which act to destroy the invading microorganisms.The 2nd part of the immune system, adaptive immunity, comes into play when the body encounters organisms that overcome the innate defences. The adaptive immune system responds specifically to each type of invading organism, and retains a memory of the invader so that defences can be rallied instantly in the future.
The adaptive immune system first must recognize part of an invading organism or tumour cell as an antigen (a protein that is foreign to the body). One of 2 types of response – humoral or cellular – is then mounted against the antigen.
Humoral immunity is important in the defence against bacteria. After a complex recognition process, certain B-lymphocytes multiply and produce vast numbers of antibodies that bind to antigens. The organisms bearing the antigens are then engulfed by phagocytes. Binding of antibody and antigen may activate the complement system, which increases the efficiency of the phagocytes.
Cellular immunity is particularly important in the defence against viruses, some types of parasites that hide within cells, and, possibly, cancer cells. It involves 2 types of T-lymphocyte: helper cells, which play a role in the recognition of antigens and activate the killer cells (the 2nd type of T-lymphocyte), which destroy the cells that have been invaded.
Disorders of the immune system include immunodeficiency disorders and allergy, in which the immune system has an inappropriate response to usually innocuous antigens such as pollen.
In certain circumstances, such as after tissue transplants, immunosuppressant drugs are used to suppress the immune system and thus prevent rejection of the donor tissue as a foreign organism.... immune system
Allergic reactions occur only on 2nd or subsequent exposure to the allergen, once 1st contact has sensitized the body. The function of the immune system is to recognize antigens (foreign proteins) on the surfaces of microorganisms and to form antibodies (also called immunoglobulins) and sensitized lymphocytes (white blood cells). When the immune system next encounters the same antigens, the antibodies and sensitized lymphocytes interact with them, leading to destruction of the microorganisms.
A similar immune response occurs in allergies, except that the immune system forms antibodies or sensitized lymphocytes against harmless substances because these allergens are misidentified as potentially harmful antigens.
The inappropriate or exaggerated reactions seen in allergies are termed
Allergen hypersensitivity reactions and can have any of four different mechanisms (termed Types I to hypersensitivity reactions).
Most well known allergies are caused by Type I (also known as anaphylactic or immediate) hypersensitivity in which allergens cause immediate symptoms by provoking the immune system to produce specific antibodies, belonging to a type called immunoglobulin E
(IgE), which coat cells (called mast cells or basophils). When the allergen is encountered for the second time, it binds to the IgE antibodies and causes the granules in mast cells to release various chemicals, which are responsible for the symptoms of the allergy.
Among the chemicals released is histamine, which causes widened blood vessels, leakage of fluid into tissues, and muscle spasm. Symptoms can include itching, swelling, sneezing, and wheezing. Particular conditions associated with Type I reactions include asthma, hay fever, urticaria (nettle rash), angioedema, anaphylactic shock (a severe, generalized allergic reaction), possibly atopic eczema, and many food allergies.
Types to hypersensitivity reactions are less often implicated in allergies. However, contact dermatitis, in which the skin reacts to substances such as nickel, is due to a Type hypersensitivity reaction.
It is not known why certain individuals and not others get allergies, but about 1 in 8 people seem to have an inherited predisposition to them (see atopy).
Whenever possible, the most effective treatment for allergy of any kind is avoidance of the relevant allergen.
Drug treatment for allergic reactions includes the use of antihistamine drugs, which relieve the symptoms. Some antihistamine drugs have a sedative effect, which is useful in treating itching at night due to eczema. Many antihistamines do not cause drowsiness, making them more suitable for daytime use.
Other drugs, such as sodium cromoglicate and corticosteroid drugs, can be used regularly to prevent symptoms from developing.
Hyposensitization can be valuable for a minority of people who suffer allergic reactions to specific allergens such as bee stings. Treatment involves gradually increasing doses of the allergen, but it must be carried out under close supervision because a severe allergic reaction can result.... allergy