Chromosomal abnormalities Health Dictionary

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Chromosomal Abnormalities: From 1 Different Sources

Variations from normal in the number or structure of chromosomes contained in a person’s cells. The cause is generally a fault in the process of chromosome division, either during the formation of an egg or sperm, or during the first few divisions of a fertilized egg. Chromosomal abnormalities are classified according to whether they involve the 44 autosomes or the 2 X and Y sex chromosomes. A complete extra set of chromosomes per cell is called polyploidy and is lethal.

Autosomal abnormalities cause physical and mental defects of varying severity. Some types of autosomal abnormality, known as trisomy, consist of an extra chromosome on 1 of the 22 pairs of autosomes. The most common trisomy is Down’s syndrome. Sometimes, part of a chromosome is missing, as in cri du chat syndrome. In translocation, a part of a chromosome is joined to another, causing no ill effects in the person but a risk of abnormality in his or her children.

Sex chromosome abnormalities include Turner’s syndrome, in which a girl is born with a single X chromosome in her

cells instead of 2, causing physical abnormalities, defective sexual development, and infertility. A boy with 1 or more extra X chromosomes has Klinefelter’s syndrome, which causes defective sexual development and infertility. The presence of an extra X chromosome in women or an extra Y chromosome in men normally has no physical effect but increases the risk of mild mental handicap.

Chromosomal abnormalities are diagnosed by chromosome analysis in early pregnancy, using amniocentesis or chorionic villus sampling.

Health Source: BMA Medical Dictionary
Author: The British Medical Association

Amniocentesis

A diagnostic procedure for detecting abnormalities of the FETUS. Usually carried out between the 16th and 18th week of pregnancy, amniocentesis is performed by piercing the amniotic sac in the pregnant UTERUS with a hollow needle and withdrawing a sample of AMNIOTIC FLUID for laboratory analysis. As well as checking for the presence of abnormal fetal cells, the procedure can show the sex of the fetus. The risk of early rupture of the fetal membranes or of miscarriage is low (around 0.5 per cent).... amniocentesis

Fetoscopy

Inspection of a FETUS by passing a ?breoptic instrument called a fetoscope through the abdominal wall of a pregnant woman into her UTERUS. The procedure is usually conducted in the 18th to 20th week of pregnancy to assess the fetus for abnormalities and to take blood samples to preclude diseases such as HAEMOPHILIA, DUCHENNE MUSCULAR DYSTROPHY and sickle-cell ANAEMIA. The procedure should be used only if there is a serious possibility of abnormality, the presence of which will usually have been indicated by other screening tests such as ULTRASOUND and tests of blood obtained by (intrauterine) cordocentesis (withdrawal of blood by syringe inserted into the umbilical cord).... fetoscopy

Neural Tube Defects

Congenital abnormalities resulting from the failure of the NEURAL TUBE to form normally. The resulting conditions include SPINA BIFIDA, MENINGOCELE and defects in the bones of the SKULL.... neural tube defects

Neurosurgery

Surgery performed on some part of the NERVOUS SYSTEM, whether brain, spinal cord or nerves. Disorders treated by neurosurgeons include damage to the brain, spinal cord and nerves as a result of injury; tumours in the CENTRAL NERVOUS SYSTEM; abnormalities of blood vessels in or supplying blood to the brain – for example, ANEURYSM; brain abscess; bleeding inside the skull; and certain birth defects such as HYDROCEPHALUS and SPINA BIFIDA.... neurosurgery

Translocation

The term used to describe an exchange of genetic material between CHROMOSOMES. It is an important factor in the etiology, or causation, of certain congenital abnormalities such as, for example, DOWN’S (DOWN) SYNDROME. It is one of the main abnormalities sought for in AMNIOSCOPY.... translocation

Urethrography

Examination of the URETHRA using X-RAYS. A radio-opaque ?uid is injected into the bladder and any abnormalities of the urethra can be observed on the X-ray ?lms.... urethrography

Genetic Disorders

These are caused when there are mutations or other abnormalities which disrupt the code of a gene or set of GENES. These are divided into autosomal (one of the 44 CHROMOSOMES which are not sex-linked), dominant, autosomal recessive, sex-linked and polygenic disorders.

Dominant genes A dominant characteristic is an e?ect which is produced whenever a gene or gene defect is present. If a disease is due to a dominant gene, those affected are heterozygous – that is, they only carry a fault in the gene on one of the pair of chromosomes concerned. A?ected people married to normal individuals transmit the gene directly to one-half of the children, although this is a random event just like tossing a coin. HUNTINGTON’S CHOREA is due to the inheritance of a dominant gene, as is neuro?bromatosis (see VON RECKLINGHAUSEN’S DISEASE) and familial adenomatous POLYPOSIS of the COLON. ACHONDROPLASIA is an example of a disorder in which there is a high frequency of a new dominant mutation, for the majority of affected people have normal parents and siblings. However, the chances of the children of a parent with the condition being affected are one in two, as with any other dominant characteristic. Other diseases inherited as dominant characteristics include spherocytosis, haemorrhagic telangiectasia and adult polycystic kidney disease.

Recessive genes If a disease is due to a recessive gene, those affected must have the faulty gene on both copies of the chromosome pair (i.e. be homozygous). The possession of a single recessive gene does not result in overt disease, and the bearer usually carries this potentially unfavourable gene without knowing it. If that person marries another carrier of the same recessive gene, there is a one-in-four chance that their children will receive the gene in a double dose, and so have the disease. If an individual sufferer from a recessive disease marries an apparently normal person who is a heterozygous carrier of the same gene, one-half of the children will be affected and the other half will be carriers of the disease. The commonest of such recessive conditions in Britain is CYSTIC FIBROSIS, which affects about one child in 2,000. Approximately 5 per cent of the population carry a faulty copy of the gene. Most of the inborn errors of metabolism, such as PHENYLKETONURIA, GALACTOSAEMIA and congenital adrenal hyperplasia (see ADRENOGENITAL SYNDROME), are due to recessive genes.

There are characteristics which may be incompletely recessive – that is, neither completely dominant nor completely recessive – and the heterozygotus person, who bears the gene in a single dose, may have a slight defect whilst the homozygotus, with a double dose of the gene, has a severe illness. The sickle-cell trait is a result of the sickle-cell gene in single dose, and sickle-cell ANAEMIA is the consequence of a double dose.

Sex-linked genes If a condition is sex-linked, affected males are homozygous for the mutated gene as they carry it on their single X chromosome. The X chromosome carries many genes, while the Y chromosome bears few genes, if any, other than those determining masculinity. The genes on the X chromosome of the male are thus not matched by corresponding genes on the Y chromosome, so that there is no chance of the Y chromosome neutralising any recessive trait on the X chromosome. A recessive gene can therefore produce disease, since it will not be suppressed by the normal gene of the homologous chromosome. The same recessive gene on the X chromosome of the female will be suppressed by the normal gene on the other X chromosome. Such sex-linked conditions include HAEMOPHILIA, CHRISTMAS DISEASE, DUCHENNE MUSCULAR

DYSTROPHY (see also MUSCLES, DISORDERS OF – Myopathy) and nephrogenic DIABETES INSIPIDUS.

If the mother of an affected child has another male relative affected, she is a heterozygote carrier; half her sons will have the disease and half her daughters will be carriers. The sister of a haemophiliac thus has a 50 per cent chance of being a carrier. An affected male cannot transmit the gene to his son because the X chromosome of the son must come from the mother; all his daughters, however, will be carriers as the X chromosome for the father must be transmitted to all his daughters. Hence sex-linked recessive characteristics cannot be passed from father to son. Sporadic cases may be the result of a new mutation, in which case the mother is not the carrier and is not likely to have further affected children. It is probable that one-third of haemophiliacs arise as a result of fresh mutations, and these patients will be the ?rst in the families to be affected. Sometimes the carrier of a sex-linked recessive gene can be identi?ed. The sex-linked variety of retinitis pigmentosa (see EYE, DISORDERS OF) can often be detected by ophthalmoscopic examination.

A few rare disorders are due to dominant genes carried on the X chromosome. An example of such a condition is familial hypophosphataemia with vitamin-D-resistant RICKETS.

Polygenic inheritance In many inherited conditions, the disease is due to the combined action of several genes; the genetic element is then called multi-factorial or polygenic. In this situation there would be an increased incidence of the disease in the families concerned, but it will not follow the Mendelian (see MENDELISM; GENETIC CODE) ratio. The greater the number of independent genes involved in determining a certain disease, the more complicated will be the pattern of inheritance. Furthermore, many inherited disorders are the result of a combination of genetic and environmental in?uences. DIABETES MELLITUS is the most familiar of such multi-factorial inheritance. The predisposition to develop diabetes is an inherited characteristic, although the gene is not always able to express itself: this is called incomplete penetrance. Whether or not the individual with a genetic predisposition towards the disease actually develops diabetes will also depend on environmental factors. Diabetes is more common in the relatives of diabetic patients, and even more so amongst identical twins. Non-genetic factors which are important in precipitating overt disease are obesity, excessive intake of carbohydrate foods, and pregnancy.

SCHIZOPHRENIA is another example of the combined effects of genetic and environmental in?uences in precipitating disease. The risk of schizophrenia in a child, one of whose parents has the disease, is one in ten, but this ?gure is modi?ed by the early environment of the child.... genetic disorders

Mosaicism

If non-dysjunction occurs after the formation of a ZYGOTE – that is, during a mitotic cell division and not a meiotic cell division (see MITOSIS; MEIOSIS) – some of the cells will have one chromosome constitution and others another. The term mosaicism describes a condition in which a substantial minority of cells in an individual’s body di?er from the majority in their chromosome content. How substantial this minority is will depend upon how early during cleavage the zygote undergoes nondysjunction. Mosaicism can cause disorders such as DOWN’S (DOWN) SYNDROME and TURNER’S SYNDROME. The proportion and type of abnormal cells affect the physical appearance of the affected individual. This may range from normal to the features typical of people with a chromosomal-abnormality syndrome.... mosaicism

Intravenous Urography

An X-ray procedure, commonly abbreviated to , used to give a clear image of the urinary tract. The procedure involves intravenous infusion of a contrast medium into the arm. The medium is carried in the blood to the urinary system, where it passes through the kidneys, ureters, and bladder to be excreted in the urine. X-rays taken at intervals show outlines of the urinary system. detects abnormalities such as tumours and obstructions, and signs of kidney disease.... intravenous urography

Rubella

Rubella, or German measles, is an acute infectious disease of a mild type, which may sometimes be di?cult to di?erentiate from mild forms of MEASLES and SCARLET FEVER.

Cause A virus spread by close contact with infected individuals. Rubella is infectious for a week before the rash appears and at least four days afterwards. It occurs in epidemics (see EPIDEMIC) every three years or so, predominantly in the winter and spring. Children are more likely to be affected than infants. One attack gives permanent IMMUNITY. The incubation period is usually 14–21 days.

Symptoms are very mild, and the disease is not at all serious. On the day of onset there may be shivering, headache, slight CATARRH with sneezing, coughing and sore throat, with very slight fever – not above 37·8 °C (100 °F). At the same time the glands of the neck become enlarged. Within 24 hours of the onset a pink, slightly raised eruption appears, ?rst on the face or neck, then on the chest, and the second day spreads all over the body. The clinical signs and symptoms of many other viral infections are indistinguishable from rubella so a precise diagnosis cannot be made without taking samples (such as saliva) for antibody testing, but this is rarely done in practice.

An attack of German measles during the early months of pregnancy may be responsible for CONGENITAL defects in the FETUS (for information on fetal abnormalities, see under PREGNANCY AND LABOUR). The incidence of such defects is not precisely known, but probably around 20 per cent of children whose mothers have had German measles in the ?rst three months of the pregnancy are born with congenital defects. These defects take a variety of forms, but the most important ones are: low birth weight with retarded physical development; malformations of the HEART; cataract (see under EYE, DISORDERS OF); and DEAFNESS.

Treatment There is no speci?c treatment. Children who develop the disease should not return to school until they have recovered, and in any case not before four days have passed from the onset of the rash.

In view of the possible dangerous e?ect of the disease upon the fetus, particular care should be taken to isolate pregnant mothers from contact with infected subjects. As the risk is particularly high during the ?rst 16 weeks of pregnancy, any pregnant mother exposed to infection during this period should be given an intramuscular injection of GAMMA-GLOBULIN. A vaccine is available to protect an individual against rubella (see IMMUNISATION).

In the United Kingdom it is NHS policy for all children to have the combined measles, mumps and rubella vaccine (see MMR VACCINE), subject to parental consent. All women of childbearing age, who have been shown by a simple laboratory test not to have had the disease, should be vaccinated, provided that the woman is not pregnant at the time and has not been exposed to the risk of pregnancy during the previous eight weeks.... rubella

Thalassaemia

Also known as Cooley’s anaemia, this is a condition characterised by severe ANAEMIA, due to an abnormal form of HAEMOGLOBIN in the blood. It is an inherited disease which is widely spread across the Mediterranean through the Middle East and into the Far East. It has a particularly high incidence in Greece and in Italy. The abnormal haemoglobin prevents the affected red cells from functioning properly. This results in the anaemia. The SPLEEN enlarges and abnormalities occur in the BONE MARROW. If someone inherits the disease from both parents, he or she is seriously affected but, if only one parent had the abnormal gene (see GENES), the person could well be free of symptoms. The severe form of the disorder is called thalassaemia major and affected individuals need repeated blood transfusions as well as treatment to remove excessive iron from their body. The disease can be diagnosed by prenatal investigation.... thalassaemia

Teratogen

A physical, chemical, or biological agent, such as radiation, the drug thalidomide, and the rubella virus, that causes abnormalities in a developing embryo or fetus.... teratogen

Chorionic Villus Sampling

A method of diagnosing genetic abnormalities in a fetus using a small sample of tissue taken from the chorionic villi at edge of the placenta. Because the cells have the same chromosome makeup as those in the fetus, they can be used to detect genetic abnormalities. Chorionic villus sampling (CVS) is usually performed in the first 3 months of pregnancy in women who are at a higher-than-normal risk of having a child with a chromosomal disorder, such as Down’s syndrome, or a genetic disease, such as thalassaemia. Chromosome analysis of the villi cells takes place in the laboratory. CVS slightly increases the risk of miscarriage. choroid A layer of tissue at the back of the eye, behind the retina. The choroid contains many blood vessels that supply nutrients and oxygen to the retinal cells and to surrounding tissues in the eye. choroiditis Inflammation of the choroid. It is often caused by infections such as toxocariasis or toxoplasmosis, more rarely by sarcoidosis, syphilis, and histoplasmosis. It sometimes has no obvious cause. Treatment includes corticosteroid drugs for the inflammation, and antibiotic drugs for any causative infection.... chorionic villus sampling

Down’s Syndrome

A chromosomal abnormality resulting in a variable degree of learning difficulties and a characteristic physical appearance.

People with Down’s syndrome have an extra chromosome (47 instead of 46). Affected individuals have 3 copies of chromosome number 21 instead of 2; the disorder is also called trisomy 21. In most cases, it is the result of a sperm or egg being formed with an extra chromosome 21. If one of these takes part in fertilization, the baby will also have the extra chromosome. This type of abnormality is more likely if the mother is aged over 35. A less common cause is a chromosomal abnormality known as a translocation, in which part of 1 parent’s own chromosome number 21 has joined with another chromosome. The parent is unaffected but has a high risk of having Down’s children.

Typical physical features of a person with Down’s syndrome include small face and features; sloping eyes with folds of skin that cover their inner corners; large tongue; and short, broad hands. People with Down’s syndrome have a greater than normal risk for certain disorders, such as a heart defect at birth (see heart disease, congenital), intestinal atresia (a narrowing in the intestines), congenital deafness, and acute leukaemia. Down’s syndrome children are especially susceptible to ear infections. A type of Alzheimer’s disease often develops after age 40.

Down’s syndrome is usually recognized soon after birth.

The diagnosis is confirmed by chromosome analysis.

Screening tests during early pregnancy, including ultrasound scanning, indicate those fetuses likely to have the syndrome.

Amniocentesis is then offered.... down’s syndrome

Precocious Puberty

The development of secondary sexual characteristics before age 8 in girls and 9 in boys. It is uncommon and may be caused by various disorders that can result in production of sex hormones at an abnormally early age. Possible underlying causes include a brain tumour or other brain abnormalities; abnormality of the adrenal glands (for example, congenital adrenal hyperplasia); ovarian cysts, and tumours, or a tumour in the testes. In some cases, no underlying cause can be identified.

The hormones may cause a premature growth spurt followed by early fusion of the bones. As a result, affected children may initially be tall but, if untreated, final height is often greatly reduced.

The child’s pattern of pubertal development is assessed by a doctor. Blood tests are performed to measure hormone levels. Ultrasound scanning of the ovaries and testes, and CT scanning of the adrenal glands or brain, may also be carried out, depending on the underlying cause suspected.

Treatment is of the underlying cause, and hormone drugs may be given to delay puberty and increase final height.... precocious puberty

Abortion

Abortion is de?ned as the expulsion of a FETUS before it is normally viable, usually before 24 weeks of pregnancy. (There are exceptional cases nowadays in which fetuses as young as 22 weeks’ gestation have survived.) (See also PREGNANCY AND LABOUR.)

Spontaneous abortion Often called miscarriage, this may occur at any time before 28 weeks; 85 per cent occur in the ?rst 12 weeks of pregnancy. Of all diagnosed pregnancies, 25 per cent end in spontaneous abortion.

Spontaneous abortions occurring in early pregnancy are almost always associated with chromosomal abnormalities of the fetus. Other causes are uterine shape, maternal disorders such as DIABETES MELLITUS, diseases of the thyroid gland (see under ENDOCRINE GLANDS), and problems with the immune system (see IMMUNITY). Recurrent spontaneous abortion (that is, three or more) seems to be a particular problem in women who have an abnormal response of their immune system to pregnancy. Other factors include being older, having had a lot of babies previously, cigarette smoking and spontaneous (but not therapeutic) abortions in the past.

Early ULTRASOUND scans have altered the management of spontaneous abortions. These make it possible to distinguish between threatened abortion, where a woman has had some vaginal bleeding but the fetus is alive; inevitable abortion, where the neck of the uterus has started to open up; incomplete abortion, where part of the fetus or placenta is lost but some remains inside the uterus; and complete abortion. There is no evidence that bed rest is e?ective in stopping a threatened abortion becoming inevitable.

Inevitable or incomplete abortion will usually require a gynaecologist to empty (evacuate) the uterus. (Complete miscarriage requires no treatment.) Evacuation of the uterus is carried out using local or general anaesthetic, usually gentle dilatation of the neck of the uterus (cervix), and curetting-out the remaining products of the pregnancy.

A few late abortions are associated with the cervix opening too early, abnormal structural abnormalities of the uterus, and possibly infection in the mother.

Drugs are often used to suppress uterine contractions, but evidence-based studies show that these do not generally improve fetal salvage. In proven cases of cervical incompetence, the cervix can be closed with a suture which is removed at 37 weeks’ gestation. The evidence for the value of this procedure is uncertain.

Therapeutic abortion In the UK, before an abortion procedure is legally permitted, two doctors must agree and sign a form de?ned under the 1967 Abortion Act that the continuation of the pregnancy would involve risk – greater than if the pregnancy were terminated – of injury to the physical and/or mental health of the mother or any existing child(ren).

Legislation in 1990 modi?ed the Act, which had previously stated that, at the time of the abortion, the pregnancy should not have exceeded the 24th week. Now, an abortion may legally be performed if continuing the pregnancy would risk the woman’s life, or the mental health of the woman or her existing child(ren) is at risk, or if there is a substantial risk of serious handicap to the baby. In 95 per cent of therapeutic terminations in the UK the reason is ‘risk of injury to the physical or mental health of the woman’.

There is no time limit on therapeutic abortion where the termination is done to save the mother’s life, there is substantial risk of serious fetal handicap, or of grave permanent injury to the health of the mother.

About 190,000 terminations are carried out in the UK each year and only 1–1.5 per cent are over 20 weeks’ gestation, with the vast majority of these late abortions being for severe, late-diagnosed, fetal abnormality.

The maternal mortality from therapeutic abortion is less than 1 per 100,000 women and, provided that the procedure is performed skilfully by experienced doctors before 12 weeks of pregnancy, it is very safe. There is no evidence that therapeutic abortion is associated with any reduction in future fertility, increased rates of spontaneous abortion or preterm birth in subsequent pregnancies.

Methods of abortion All abortions must be carried out in premises licensed for doing so or in NHS hospitals. The method used is either surgical or medical, with the latter being used more and the former less as time goes on. Proper consent must be obtained, signed for and witnessed. Women under 16 years of age can consent to termination provided that the doctors obtaining the consent are sure she clearly understands the procedure and its implications. Parental consent in the under-16s is not legally required, but counselling doctors have a duty to record that they have advised young people to inform their parents. However, many youngsters do not do so. The woman’s partner has no legal say in the decision to terminate her pregnancy.

MEDICAL METHODS A combination of two drugs, mifepristone and a prostaglandin (or a prostaglandin-like drug, misoprostol – see PROSTAGLANDINS), may be used to terminate a pregnancy up to 63 days’ gestation. A similar regime can be used between nine and 12 weeks but at this gestation there is a 5 per cent risk of post-treatment HAEMORRHAGE.

An ultrasound scan is ?rst done to con?rm pregnancy and gestation. The sac containing the developing placenta and fetus must be in the uterus; the woman must be under 35 years of age if she is a moderate smoker, but can be over 35 if she is a non-smoker. Reasons for not using this method include women with diseases of the ADRENAL GLANDS, on long-term CORTICOSTEROIDS, and those who have a haemorrhagic disorder or who are on ANTICOAGULANTS. The drugs cannot be used in women with severe liver or kidney disease, and caution is required in those with CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), disease of the cardiovascular system, or prosthetic heart valves (see PROSTHESIS), as well as with those who have had a CAESAREAN SECTION or an ECTOPIC PREGNANCY in the past or who are being treated for HYPERTENSION.

Some clinics use this drug combination for pregnancies older than 12 weeks. In pregnancies approaching viability (20 weeks), pretreatment fetocide (killing of the fetus) with intrauterine drug therapy may be required.

SURGICAL METHODS Vacuum curettage is a method used up to 14–15 weeks. Some very experienced gynaecologists will perform abortions surgically by dilating the cervix and evacuating the uterine contents up to 22 weeks’ gestation. The greater the size of the pregnancy, the higher the risk of haemorrhage and perforation of the uterus. In the UK, illegal abortion is rare but in other countries this is not the case. Where illegal abortions are done, the risks of infection and perforation are high and death a de?nite risk. Legal abortions are generally safe. In the USA, partial-birth abortions are spoken of but, in fact, there is no such procedure recorded in the UK medical journals.... abortion

Amenorrhoea

Absence of MENSTRUATION at the time of life at which it should normally occur. If menstruation has never occurred, the amenorrhoea is termed primary; secondary amenorrhoea is de?ned as menstruation ceasing after a normal cycle has been experienced for a number of years.

A few patients with primary amenorrhoea have an abnormality of their CHROMOSOMES or malformation of the genital tract such as absecence of the UTERUS (see TURNER’S SYNDROME). A gynaecological examination will rarely disclose an IMPERFORATE HYMEN in a young girl who may also complain of regular cycles of pain like period pains.

There are many causes of secondary amenorrhoea and management requires dealing with the primary cause. The commonest cause is pregnancy. Disorders of the HYPOTHALAMUS and related psychological factors such as anorexia nervosa (see EATING DISORDERS) also cause amenorrhoea, as can poor nutrition and loss of weight by extreme dieting. It is common in ballet dancers and athletes who exercise a great deal, but can also be triggered by serious illnesses such as tuberculosis or malaria. Excess secretion of prolactin, either due to a micro-adenoma (see ADENOMA) of the PITUITARY GLAND or to various prescription drugs will produce amenorrhoea, and sometimes GALACTORRHOEA as well. Malfunction of other parts of the pituitary gland will cause failure to produce GONADOTROPHINS, thus causing ovarian failure with consequent amenorrhea. In CUSHING’S SYNDROME, amenorrhoea is caused by excessive production of cortisol. Similarly, androgen-production abnormalities are found in the common POLYCYSTIC OVARY SYNDROME. These conditions also have abnormalities of the insulin/glucose control mechanisms. Taking the contraceptive pill is not now considered to provoke secondary amenorrhoea but OBESITY and HYPOTHYROIDISM are potential causes.

When the cause is weight loss, restoring body weight may alone restore menstruation. Otherwise, measuring gonadotrophic hormone levels will help show whether amenorrhoea is due to primary ovarian failure or secondary to pituitary disease. Women with raised concentrations of serum gonadotrophic hormones have primary ovarian failure. When amenorrhoea is due to limited pituitary failure, treatment with CLOMIPHENE may solve the problem.... amenorrhoea

Arachnodactyly

Arachnodactyly, or MARFAN’S SYNDROME, is a congenital condition characterised by extreme length and slenderness of the ?ngers and toes – and, to a lesser extent, of the limbs and trunk; laxity of the ligaments; and dislocation of the lens of the eye. The antero-posterior diameter of the skull is abnormally long, and the jaw is prominent. There may also be abnormalities of the heart.... arachnodactyly

Caesarean Section

The operation used to deliver a baby through its mother’s abdominal wall. It is performed when the risks to mother or child of vaginal delivery are thought to outweigh the problems associated with operative delivery. One of the most common reasons for Caesarean section is ‘disproportion’ between the size of the fetal head and the maternal pelvis. The need for a Caesarean should be assessed anew in each pregnancy; a woman who has had a Caesarean section in the past will not automatically need to have one for subsequent deliveries. Caesarean-section rates vary dramatically from hospital to hospital, and especially between countries, emphasising that the criteria for operative delivery are not universally agreed. The current rate in the UK is about 23 per cent, and in the USA, about 28 per cent. The rate has shown a steady rise in all countries over the last decade. Fear of litigation by patients is one reason for this rise, as is the uncertainty that can arise from abnormalities seen on fetal monitoring during labour. Recent research suggesting that vaginal delivery is becoming more hazardous as the age of motherhood rises may increase the pressure from women to have a Caesarean section – as well as pressure from obstetricians.

The operation is usually performed through a low, horizontal ‘bikini line’ incision. A general anaesthetic in a heavily pregnant woman carries increased risks, so the operation is often performed under regional – epidural or spinal – ANAESTHESIA. This also allows the mother to see her baby as soon as it is born, and the baby is not exposed to agents used for general anaesthesia. If a general anaesthetic is needed (usually in an emergency), exposure to these agents may make the baby drowsy for some time afterwards.

Another problem with delivery by Caesarean section is, of course, that the mother must recover from the operation whilst coping with the demands of a small baby. (See PREGNANCY AND LABOUR.)... caesarean section

Cancer

The general term used to refer to a malignant TUMOUR, irrespective of the tissue of origin. ‘Malignancy’ indicates that (i) the tumour is capable of progressive growth, unrestrained by the capsule of the parent organ, and/or (ii) that it is capable of distant spread via lymphatics or the bloodstream, resulting in development of secondary deposits of tumour known as ‘metastases’. Microscopically, cancer cells appear different from the equivalent normal cells in the affected tissue. In particular they may show a lesser degree of di?erentiation (i.e. they are more ‘primitive’), features indicative of a faster proliferative rate and disorganised alignment in relationship to other cells or blood vessels. The diagnosis of cancer usually depends upon the observation of these microscopic features in biopsies, i.e. tissue removed surgically for such examination.

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

Chocolate

(Cocoa, milk chocolate, sweet chocolate)

Nutritional Profile Energy value (calories per serving): Moderate Protein: Low (cocoa powder) High (chocolate) Fat: Moderate Saturated fat: High Cholesterol: None Carbohydrates: Low (chocolate) High (cocoa powder) Fiber: Moderate (chocolate) High (cocoa powder) Sodium: Moderate Major vitamin contribution: B vitamins Major mineral contribution: Calcium, iron, copper

About the Nutrients in This Food Cocoa beans are high-carbohydrate, high-protein food, with less dietary fiber and more fat than all other beans, excepting soy beans. The cocoa bean’s dietary fiber includes pectins and gums. Its proteins are limited in the essential amino acids lysine and isoleucine. Cocoa butter, the fat in cocoa beans, is the second most highly saturated vegetable fat (coconut oil is number one), but it has two redeeming nutritional qualities. First, it rarely turns rancid. Second, it melts at 95°F, the temperature of the human tongue. Cocoa butter has no cholesterol; neither does plain cocoa powder or plain dark chocolate. Cocoa beans have B vitamins (thiamine, riboflavin, niacin) plus min- erals (iron, magnesium, potassium, phosphorus, and copper). All chocolate candy is made from chocolate liquor, a thick paste pro- duce by roasting and grinding cocoa beans. Dark (sweet) chocolate is made of chocolate liquor, cocoa butter, and sugar. Milk chocolate is made of choc- olate liquor, cocoa butter, sugar, milk or milk powder, and vanilla. White * These values apply to plain cocoa powder and plain unsweetened chocolate. Add- ing other foods, such as milk or sugar, changes these values. For example, there is no cholesterol in plain bitter chocolate, but there is cholesterol in milk chocolate. chocolate is made of cocoa butter, sugar, and milk powder. Baking chocolate is unsweetened dark chocolate. The most prominent nutrient in chocolate is its fat. Fat Content in One Ounce of Chocolate

	Saturated fat (g)	Monounsaturated fat (g)	Polyunsaturated fat (g)	Cholesterol (mg)
Dark (sweet)
chocolate	5.6	3.2	0.3	0
Milk chocolate	5.9	4.5	0.4	6.6
Baking chocolate	9	5.6	0.3	0
White chocolate	5.5	2.6	0.3	0

Source: USDA Nut rient Data Laborator y. Nat ional Nut rient Database for Standard Reference. Available online. UR L : http://w w w.nal.usda.gov/fnic/foodcomp/search /. Because chocolate is made from a bean, it also contains dietary fiber and measurable amounts of certain minerals. For example, one ounce of dark chocolate, the most nutritious “eating” chocolate, has 1.6 g dietary fiber, 0.78 mg iron (4 percent of the R DA for a woman, 10 percent of the R DA for a man), 32 mg magnesium (11 percent of the R DA for a woman, 8 percent of the R DA for a man), and .43 mg zinc (5 percent of the R DA for a woman, 4 percent of the R DA for a man). Cocoa beans, cocoa, and chocolate contain caffeine, the muscle stimulant theobro- mine, and the mood-altering chemicals phenylethylalanine and anandamide (see below).

The Most Nutritious Way to Serve This Food With low-fat milk to complete the proteins without adding saturated fat and cholesterol. NOTE : Both cocoa and chocolate contain oxalic acid, which binds with calcium to form cal- cium oxalate, an insoluble compound, but milk has so much calcium that the small amount bound to cocoa and chocolate hardly matters. Chocolate skim milk is a source of calcium.

Diets That May Restrict or Exclude This Food Antiflatulence diet Low-calcium and low-oxalate diet (to prevent the formation of calcium oxalate kidney stones) Low-calorie diet Low-carbohydrate diet Low-fat diet Low-fat, controlled-cholesterol diet (milk chocolates) Low-fiber diet Potassium-regulated (low-potassium) diet

Buying This Food Look for: Tightly sealed boxes or bars. When you open a box of chocolates or unwrap a candy bar, the chocolate should be glossy and shiny. Chocolate that looks dull may be stale, or it may be inexpensively made candy without enough cocoa butter to make it gleam and give it the rich creamy mouthfeel we associate with the best chocolate. (Fine chocolate melts evenly on the tongue.) Chocolate should also smell fresh, not dry and powdery, and when you break a bar or piece of chocolate it should break cleanly, not crumble. One exception: If you have stored a bar of chocolate in the refrigerator, it may splinter if you break it without bringing it to room temperature first.

Storing This Food Store chocolate at a constant temperature, preferably below 78°F. At higher temperatures, the fat in the chocolate will rise to the surface and, when the chocolate is cooled, the fat will solidif y into a whitish powdery bloom. Bloom is unsightly but doesn’t change the chocolate’s taste or nutritional value. To get rid of bloom, melt the chocolate. The chocolate will turn dark, rich brown again when its fat recombines with the other ingredients. Chocolate with bloom makes a perfectly satisfactory chocolate sauce. Dark chocolate (bitter chocolate, semisweet chocolate) ages for at least six months after it is made, as its flavor becomes deeper and more intense. Wrapped tightly and stored in a cool, dry cabinet, it can stay fresh for a year or more. Milk chocolate ages only for about a month after it is made and holds its peak flavor for about three to six months, depending on how carefully it is stored. Plain cocoa, with no added milk powder or sugar, will stay fresh for up to a year if you keep it tightly sealed and cool.

What Happens When You Cook This Food Chocolate burns easily. To melt it without mishap, stir the chocolate in a bowl over a pot of hot water or in the top of a double boiler or put the chocolate in a covered dish and melt it in the microwave (which does not get as hot as a pot on the store). Simple chemistry dictates that chocolate cakes be leavened with baking soda rather than baking powder. Chocolate is so acidic that it will upset the delicate balance of acid (cream of tartar) and base (alkali = sodium bicarbonate = baking soda) in baking powder. But it is not acidic enough to balance plain sodium bicarbonate. That’s why we add an acidic sour-milk product such as buttermilk or sour cream or yogurt to a chocolate cake. Without the sour milk, the batter would be so basic that the chocolate would look red, not brown, and taste very bitter.

How Other Kinds of Processing Affect This Food Freezing. Chocolate freezes and thaws well. Pack it in a moistureproof container and defrost it in the same package to let it reabsorb moisture it gave off while frozen.

Medical Uses and/or Benefits Mood elevator. Chocolate’s reputation for making people feel good is based not only on its caffeine content—19 mg caffeine per ounce of dark (sweet) chocolate, which is one-third the amount of caffeine in a five-ounce cup of brewed coffee—but also on its naturally occurring mood altering chemicals phenylethylalanine and anandamide. Phenylethylalanine is found in the blood of people in love. Anandamide stimulates areas of your brain also affected by the active ingredients in marijuana. (NOTE : As noted by the researchers at the Neurosci- ences Institute in San Diego who identified anandamide in chocolate in 1996, to get even the faintest hint of marijuana-like effects from chocolate you would have to eat more than 25 pounds of the candy all at once.) Possible heart health benefits. Chocolate is rich in catechins, the antioxidant chemicals that give tea its reputation as a heart-protective anticancer beverage (see tea). In addition, a series of studies beginning with those at the USDA Agricultural Research Center in Peoria, Illinois, suggest that consuming foods rich in stearic acid like chocolate may reduce rather than raise the risk of a blood clot leading to a heart attack. Possible slowing of the aging process. Chocolate is a relatively good source of copper, a mineral that may play a role in slowing the aging process by decreasing the incidence of “protein glycation,” a reaction in which sugar molecules ( gly = sugar) hook up with protein molecules in the bloodstream, twisting the protein molecules out of shape and rendering them unusable. This can lead to bone loss, rising cholesterol, cardiac abnormalities, and a slew of other unpleasantries. In people with diabetes, excess protein glycation may be one factor involved in complications such as loss of vision. Ordinarily, increased protein glyca- tion is age-related. But at the USDA Grand Forks Human Nutrition Research Center in North Dakota, agricultural research scientist Jack T. Saari has found that rats on copper-deficient diets experience more protein glycation at any age than other rats. A recent USDA survey of American eating patterns says that most of us get about 1.2 mg copper a day, considerably less than the Estimated Safe and Adequate Daily Dietary Intake (ESADDI) or 1.5 mg to 3 mg a day. Vegetarians are less likely to be copper deficient because, as Saari notes, the foods highest in copper are whole grains, nuts, seeds, and beans, including the cocoa bean. One ounce of dark chocolate has .25 mg copper (8 –17 percent of the ESADDI).

Adverse Effects Associated with This Food Possible loss of bone density. In 2008, a team of Australian researchers at Royal Perth Hos- pital, and Sir Charles Gairdner Hospital published a report in the American Journal of Clinical Nutrition suggesting that women who consume chocolate daily had 3.1 percent lower bone density than women who consume chocolate no more than once a week. No explanation for the reaction was proposed; the finding remains to be confirmed. Possible increase in the risk of heart disease. Cocoa beans, cocoa powder, and plain dark chocolate are high in saturated fats. Milk chocolate is high in saturated fats and cholesterol. Eating foods high in saturated fats and cholesterol increases the amount of cholesterol in your blood and raises your risk of heart disease. NOTE : Plain cocoa powder and plain dark chocolate may be exceptions to this rule. In studies at the USDA Agricultural Research Center in Peoria, Illinois, volunteers who consumed foods high in stearic acid, the saturated fat in cocoa beans, cocoa powder, and chocolate, had a lower risk of blood clots. In addition, chocolate is high in flavonoids, the antioxidant chemicals that give red wine its heart-healthy reputation. Mild jitters. There is less caffeine in chocolate than in an equal size serving of coffee: A five- ounce cup of drip-brewed coffee has 110 to 150 mg caffeine; a five-ounce cup of cocoa made with a tablespoon of plain cocoa powder ( 1/3 oz.) has about 18 mg caffeine. Nonetheless, people who are very sensitive to caffeine may find even these small amounts problematic. Allergic reaction. According to the Merck Manual, chocolate is one of the 12 foods most likely to trigger the classic food allergy symptoms: hives, swelling of the lips and eyes, and upset stomach.* The others are berries (blackberries, blueberries, raspberries, strawberries), corn, eggs, fish, legumes (green peas, lima beans, peanuts, soybeans), milk, nuts, peaches, pork, shellfish, and wheat (see wheat cer ea ls).

Food/Drug Interactions Monoamine oxidase (MAO) inhibitors. Monoamine oxidase inhibitors are drugs used to treat depression. They inactivate naturally occurring enzymes in your body that metabolize tyra- mine, a substance found in many fermented or aged foods. Tyramine constricts blood vessels and increases blood pressure. Caffeine is a substance similar to tyramine. If you consume excessive amounts of a caffeinated food, such as cocoa or chocolate, while you are taking an M AO inhibitor, the result may be a hypertensive crisis. False-positive test for pheochromocytoma. Pheochromocytoma, a tumor of the adrenal gland, secretes adrenalin, which the body converts to VM A (vanillylmandelic acid). VM A is excreted in urine, and, until recently, the test for this tumor measured the level of VM A in the urine. In the past, chocolate and cocoa, both of which contain VM A, were eliminated from the patient’s diet prior to the test lest they elevate the level of VM A in the urine and produce a false-positive result. Today, more finely drawn tests usually make this unnecessary. * The evidence link ing chocolate to allergic or migraine headaches is inconsistent. In some people, phenylet hylamine (PEA) seems to cause headaches similar to t hose induced by t yramine, anot her pressor amine. The PEA-induced headache is unusual in t hat it is a delayed react ion t hat usually occurs 12 or more hours after t he chocolate is eaten.... chocolate

Dead Space

Gas exchange only occurs in the terminal parts of the pulmonary airways (see LUNGS). That portion of each breath that is taken into the lungs but does not take part in gas exchange is known as dead space. Anatomical dead space describes air in the airways up to the terminal BRONCHIOLES. Physiological dead space also includes gas in alveoli (air sacs) which are unable to take part in gas exchange because of structural abnormalities or disease.... dead space

Diabetes Mellitus

Diabetes mellitus is a condition characterised by a raised concentration of glucose in the blood due to a de?ciency in the production and/or action of INSULIN, a pancreatic hormone made in special cells called the islet cells of Langerhans.

Insulin-dependent and non-insulindependent diabetes have a varied pathological pattern and are caused by the interaction of several genetic and environmental factors.

Insulin-dependent diabetes mellitus (IDDM) (juvenile-onset diabetes, type 1 diabetes) describes subjects with a severe de?ciency or absence of insulin production. Insulin therapy is essential to prevent KETOSIS – a disturbance of the body’s acid/base balance and an accumulation of ketones in the tissues. The onset is most commonly during childhood, but can occur at any age. Symptoms are acute and weight loss is common.

Non-insulin-dependent diabetes mellitus (NIDDM) (maturity-onset diabetes, type 2 diabetes) may be further sub-divided into obese and non-obese groups. This type usually occurs after the age of 40 years with an insidious onset. Subjects are often overweight and weight loss is uncommon. Ketosis rarely develops. Insulin production is reduced but not absent.

A new hormone has been identi?ed linking obesity to type 2 diabetes. Called resistin – because of its resistance to insulin – it was ?rst found in mice but has since been identi?ed in humans. Researchers in the United States believe that the hormone may, in part, explain how obesity predisposes people to diabetes. Their hypothesis is that a protein in the body’s fat cells triggers insulin resistance around the body. Other research suggests that type 2 diabetes may now be occurring in obese children; this could indicate that children should be eating a more-balanced diet and taking more exercise.

Diabetes associated with other conditions (a) Due to pancreatic disease – for example, chronic pancreatitis (see PANCREAS, DISORDERS OF); (b) secondary to drugs – for example, GLUCOCORTICOIDS (see PANCREAS, DISORDERS OF); (c) excess hormone production

– for example, growth hormone (ACROMEGALY); (d) insulin receptor abnormalities; (e) genetic syndromes (see GENETIC DISORDERS).

Gestational diabetes Diabetes occurring in pregnancy and resolving afterwards.

Aetiology Insulin-dependent diabetes occurs as a result of autoimmune destruction of beta cells within the PANCREAS. Genetic in?uences are important and individuals with certain HLA tissue types (HLA DR3 and HLA DR4) are more at risk; however, the risks associated with the HLA genes are small. If one parent has IDDM, the risk of a child developing IDDM by the age of 25 years is 1·5–2·5 per cent, and the risk of a sibling of an IDDM subject developing diabetes is about 3 per cent.

Non-insulin-dependent diabetes has no HLA association, but the genetic in?uences are much stronger. The risks of developing diabetes vary with di?erent races. Obesity, decreased exercise and ageing increase the risks of disease development. The risk of a sibling of a NIDDM subject developing NIDDM up to the age of 80 years is 30–40 per cent.

Diet Many NIDDM diabetics may be treated with diet alone. For those subjects who are overweight, weight loss is important, although often unsuccessful. A diet high in complex carbohydrate, high in ?bre, low in fat and aiming towards ideal body weight is prescribed. Subjects taking insulin need to eat at regular intervals in relation to their insulin regime and missing meals may result in hypoglycaemia, a lowering of the amount of glucose in the blood, which if untreated can be fatal (see below).

Oral hypoglycaemics are used in the treatment of non-insulin-dependent diabetes in addition to diet, when diet alone fails to control blood-sugar levels. (a) SULPHONYLUREAS act mainly by increasing the production of insulin;

(b) BIGUANIDES, of which only metformin is available, may be used alone or in addition to sulphonylureas. Metformin’s main actions are to lower the production of glucose by the liver and improve its uptake in the peripheral tissues.

Complications The risks of complications increase with duration of disease.

Diabetic hypoglycaemia occurs when amounts of glucose in the blood become low. This may occur in subjects taking sulphonylureas or insulin. Symptoms usually develop when the glucose concentration falls below 2·5 mmol/l. They may, however, occur at higher concentrations in subjects with persistent hyperglycaemia – an excess of glucose – and at lower levels in subjects with persistent hypo-glycaemia. Symptoms include confusion, hunger and sweating, with coma developing if blood-sugar concentrations remain low. Re?ned sugar followed by complex carbohydrate will return the glucose concentration to normal. If the subject is unable to swallow, glucagon may be given intramuscularly or glucose intravenously, followed by oral carbohydrate, once the subject is able to swallow.

Although it has been shown that careful control of the patient’s metabolism prevents late complications in the small blood vessels, the risk of hypoglycaemia is increased and patients need to be well motivated to keep to their dietary and treatment regime. This regime is also very expensive. All risk factors for the patient’s cardiovascular system – not simply controlling hyperglycaemia – may need to be reduced if late complications to the cardiovascular system are to be avoided.

Diabetes is one of the world’s most serious health problems. Recent projections suggest that the disorder will affect nearly 240 million individuals worldwide by 2010 – double its prevalence in 1994. The incidence of insulin-dependent diabetes is rising in young children; they will be liable to develop late complications.

Although there are complications associated with diabetes, many subjects live normal lives and survive to an old age. People with diabetes or their relatives can obtain advice from Diabetes UK (www.diabetes.org.uk).

Increased risks are present of (a) heart disease, (b) peripheral vascular disease, and (c) cerebrovascular disease.

Diabetic eye disease (a) retinopathy, (b) cataract. Regular examination of the fundus enables any abnormalities developing to be detected and treatment given when appropriate to preserve eyesight.

Nephropathy Subjects with diabetes may develop kidney damage which can result in renal failure.

Neuropathy (a) Symmetrical sensory polyneuropathy; damage to the sensory nerves that commonly presents with tingling, numbness of pain in the feet or hands. (b) Asymmetrical motor diabetic neuropathy, presenting as progressive weakness and wasting of the proximal muscles of legs. (c) Mononeuropathy; individual motor or sensory nerves may be affected. (d) Autonomic neuropathy, which affects the autonomic nervous system, has many presentations including IMPOTENCE, diarrhoea or constipation and postural HYPOTENSION.

Skin lesions There are several skin disorders associated with diabetes, including: (a) necrobiosis lipoidica diabeticorum, characterised by one or more yellow atrophic lesions on the legs;

(b) ulcers, which most commonly occur on the feet due to peripheral vascular disease, neuropathy and infection. Foot care is very important.

Diabetic ketoacidosis occurs when there is insu?cient insulin present to prevent KETONE production. This may occur before the diagnosis of IDDM or when insu?cient insulin is being given. The presence of large amounts of ketones in the urine indicates excess ketone production and treatment should be sought immediately. Coma and death may result if the condition is left untreated.

Symptoms Thirst, POLYURIA, GLYCOSURIA, weight loss despite eating, and recurrent infections (e.g. BALANITIS and infections of the VULVA) are the main symptoms.

However, subjects with non-insulindependent diabetes may have the disease for several years without symptoms, and diagnosis is often made incidentally or when presenting with a complication of the disease.

Treatment of diabetes aims to prevent symptoms, restore carbohydrate metabolism to as near normal as possible, and to minimise complications. Concentration of glucose, fructosamine and glycated haemoglobin in the blood are used to give an indication of blood-glucose control.

Insulin-dependent diabetes requires insulin for treatment. Non-insulin-dependent diabetes may be treated with diet, oral HYPOGLYCAEMIC AGENTS or insulin.

Insulin All insulin is injected – mainly by syringe but sometimes by insulin pump – because it is inactivated by gastrointestinal enzymes. There are three main types of insulin preparation: (a) short action (approximately six hours), with rapid onset; (b) intermediate action (approximately 12 hours); (c) long action, with slow onset and lasting for up to 36 hours. Human, porcine and bovine preparations are available. Much of the insulin now used is prepared by genetic engineering techniques from micro-organisms. There are many regimens of insulin treatment involving di?erent combinations of insulin; regimens vary depending on the requirements of the patients, most of whom administer the insulin themselves. Carbohydrate intake, energy expenditure and the presence of infection are important determinants of insulin requirements on a day-to-day basis.

A new treatment for diabetes, pioneered in Canada and entering its preliminary clinical trials in the UK, is the transplantation of islet cells of Langerhans from a healthy person into a patient with the disorder. If the transplantation is successful, the transplanted cells start producing insulin, thus reducing or eliminating the requirement for regular insulin injections. If successful the trials would be a signi?cant advance in the treatment of diabetes.

Scientists in Israel have developed a drug, Dia Pep 277, which stops the body’s immune system from destroying pancratic ? cells as happens in insulin-dependent diabetes. The drug, given by injection, o?ers the possibility of preventing type 1 diabetes in healthy people at genetic risk of developing the disorder, and of checking its progression in affected individuals whose ? cells are already perishing. Trials of the drug are in progress.... diabetes mellitus

Goitre

SIMPLE GOITRE A benign enlargement of the THYROID GLAND with normal production of hormone. It is ENDEMIC in certain geographical areas where there is IODINE de?ciency. Thus, if iodine intake is de?cient, the production of thyroid hormone is threatened and the anterior PITUITARY GLAND secretes increased amounts of thyrotrophic hormone with consequent overgrowth of the thyroid gland. Simple goitres in non-endemic areas may occur at puberty, during pregnancy and at the menopause, which are times of increased demand for thyroid hormone. The only e?ective treament is thyroid replacement therapy to suppress the enhanced production of thyrotrophic hormone. The prevalence of endemic goitre can be, and has been, reduced by the iodinisation of domestic salt in many countries. NODULAR GOITRES do not respond as well as the di?use goitres to THYROXINE treatment. They are usually the result of alternating episodes of hyperplasia and involution which lead to permanent thyroid enlargement. The only e?ective way of curing a nodular goitre is to excise it, and THYROIDECTOMY should be recommended if the goitre is causing pressure symptoms or if there is a suspicion of malignancy. LYMPHADENOID GOITRES are due to the production of ANTIBODIES against antigens (see ANTIGEN) in the thyroid gland. They are an example of an autoimmune disease. They tend to occur in the third and fourth decade and the gland is much ?rmer than the softer gland of a simple goitre. Lymphadenoid goitres respond to treatment with thyroxine. TOXIC GOITRES may occur in thyrotoxicosis (see below), although much less frequently autonomous nodules of a nodular goitre may be responsible for the increased production of thyroxine and thus cause thyrotoxicosis. Thyrotoxicosis is also an autoimmune disease in which an antibody is produced that stimulates the thyroid to produce excessive amounts of hormone, making the patient thyrotoxic.

Rarely, an enlarged gland may be the result of cancer in the thyroid.

Treatment A symptomless goitre may gradually disappear or be so small as not to merit treatment. If the goitre is large or is causing the patient di?culty in swallowing or breathing, it may need surgical removal by partial or total thyroidectomy. If the patient is de?cient in iodine, ?sh and iodised salt should be included in the diet.

Hyperthyroidism is a common disorder affecting 2–5 per cent of all females at some time in their lives. The most common cause – around 75 per cent of cases – is thyrotoxicosis (see below). An ADENOMA (or multiple adenomas) or nodules in the thyroid also cause hyperthyroidism. There are several other rare causes, including in?ammation caused by a virus, autoimune reactions and cancer. The symptoms of hyperthyroidism affect many of the body’s systems as a consequence of the much-increased metabolic rate.

Thyrotoxicosis is a syndrome consisting of di?use goitre (enlarged thyroid gland), over-activity of the gland and EXOPHTHALMOS (protruding eyes). Patients lose weight and develop an increased appetite, heat intolerance and sweating. They are anxious, irritable, hyperactive, suffer from TACHYCARDIA, breathlessness and muscle weakness and are sometimes depressed. The hyperthyroidism is due to the production of ANTIBODIES to the TSH receptor (see THYROTROPHIN-STIMULATING HORMONE (TSH)) which stimulate the receptor with resultant production of excess thyroid hormones. The goitre is due to antibodies that stimulate the growth of the thyroid gland. The exoph-

thalmos is due to another immunoglobulin called the ophthalmopathic immunoglobulin, which is an antibody to a retro-orbital antigen on the surface of the retro-orbital EYE muscles. This provokes in?ammation in the retro-orbital tissues which is associated with the accumulation of water and mucopolysaccharide which ?lls the orbit and causes the eye to protrude forwards.

Although thyrotoxicosis may affect any age-group, the peak incidence is in the third decade. Females are affected ten times as often as males; the prevalence in females is one in 500. As with many other autoimmune diseases, there is an increased prevalence of autoimmune thyroid disease in the relatives of patients with thyrotoxicosis. Some of these patients may have hypothyroidism (see below) and others, thyrotoxicosis. Patients with thyrotoxicosis may present with a goitre or with the eye signs or, most commonly, with the symptoms of excess thyroid hormone production. Thyroid hormone controls the metabolic rate of the body so that the symptoms of hyperthyroidism are those of excess metabolism.

The diagnosis of thyrotoxicosis is con?rmed by the measurement of the circulating levels of the two thyroid hormones, thyroxine and TRIIODOTHYRONINE.

Treatment There are several e?ective treatments for thyrotoxicosis. ANTITHYROID DRUGS These drugs inhibit the iodination of tyrosine and hence the formation of the thyroid hormones. The most commonly used drugs are carbimazole and propylthiouricil: these will control the excess production of thyroid hormones in virtually all cases. Once the patient’s thyroid is functioning normally, the dose can be reduced to a maintenance level and is usually continued for two years. The disadvantage of antithyroid drugs is that after two years’ treatment nearly half the patients will relapse and will then require more de?nitive therapy. PARTIAL THYROIDECTOMY Removal of three-quarters of the thyroid gland is e?ective treatment of thyrotoxicosis. It is the treatment of choice in those patients with large goitres. The patient must however be treated with medication so that they are euthyroid (have a normally functioning thyroid) before surgery is undertaken, or thyroid crisis and cardiac arrhythmias may complicate the operation. RADIOACTIVE IODINE THERAPY This has been in use for many years, and is an e?ective means of controlling hyperthyroidism. One of the disadvantages of radioactive iodine is that the incidence of hypothyroidism is much greater than with other forms of treatment. However, the management of hypothyroidism is simple and requires thyroxine tablets and regular monitoring for hypothyroidism. There is no evidence of any increased incidence of cancer of the thyroid or LEUKAEMIA following radio-iodine therapy. It has been the pattern in Britain to reserve radio-iodine treatment to those over the age of 35, or those whose prognosis is unlikely to be more than 30 years as a result of cardiac or respiratory disease. Radioactive iodine treatment should not be given to a seriously thyrotoxic patient. BETA-ADRENOCEPTOR-BLOCKING DRUGS Usually PROPRANOLOL HYDROCHLORIDE: useful for symptomatic treatment during the ?rst 4–8 weeks until the longer-term drugs have reduced thyroid activity.

Hypothyroidism A condition resulting from underactivity of the thyroid gland. One form, in which the skin and subcutaneous tissues thicken and result in a coarse appearance, is called myxoedema. The thyroid gland secretes two hormones – thyroxine and triiodothyronine – and these hormones are responsible for the metabolic activity of the body. Hypothyroidism may result from developmental abnormalities of the gland, or from a de?ciency of the enzymes necessary for the synthesis of the hormones. It may be a feature of endemic goitre and retarded development, but the most common cause of hypothyroidism is the autoimmune destruction of the thyroid known as chronic thyroiditis. It may also occur as a result of radio-iodine treatment of thyroid overactivity (see above) and is occasionally secondary to pituitary disease in which inadequate TSH production occurs. It is a common disorder, occurring in 14 per 1,000 females and one per 1,000 males. Most patients present between the age of 30 and 60 years.

Symptoms As thyroid hormones are responsible for the metabolic rate of the body, hypothyroidism usually presents with a general sluggishness: this affects both physical and mental activities. The intellectual functions become slow, the speech deliberate and the formation of ideas and the answers to questions take longer than in healthy people. Physical energy is reduced and patients frequently complain of lethargy and generalised muscle aches and pains. Patients become intolerant of the cold and the skin becomes dry and swollen. The LARYNX also becomes swollen and gives rise to a hoarseness of the voice. Most patients gain weight and develop constipation. The skin becomes dry and yellow due to the presence of increased carotene. Hair becomes thinned and brittle and even baldness may develop. Swelling of the soft tissues may give rise to a CARPAL TUNNEL SYNDROME and middle-ear deafness. The diagnosis is con?rmed by measuring the levels of thyroid hormones in the blood, which are low, and of the pituitary TSH which is raised in primary hypothyroidism.

Treatment consists of the administration of thyroxine. Although tri-iodothyronine is the metabolically active hormone, thyroxine is converted to tri-iodothyronine by the tissues of the body. Treatment should be started cautiously and slowly increased to 0·2 mg daily – the equivalent of the maximum output of the thyroid gland. If too large a dose is given initially, palpitations and tachycardia are likely to result; in the elderly, heart failure may be precipitated.

Congenital hypothyroidism Babies may be born hypothyroid as a result of having little or no functioning thyroid-gland tissue. In the developed world the condition is diagnosed by screening, all newborn babies having a blood test to analyse TSH levels. Those found positive have a repeat test and, if the diagnosis is con?rmed, start on thyroid replacement therapy within a few weeks of birth. As a result most of the ill-effects of cretinism can be avoided and the children lead normal lives.

Thyroiditis In?ammation of the thyroid gland. The acute form is usually caused by a bacterial infection elsewhere in the body: treatment with antibiotics is needed. Occasionally a virus may be the infectious agent. Hashimoto’s thyroiditis is an autoimmune disorder causing hypothyroidism (reduced activity of the gland). Subacute thyroiditis is in?ammation of unknown cause in which the gland becomes painful and the patient suffers fever, weight loss and malaise. It sometimes lasts for several months but is usually self-limiting.

Thyrotoxic adenoma A variety of thyrotoxicosis (see hyperthyroidism above) in which one of the nodules of a multinodular goitre becomes autonomous and secretes excess thyroid hormone. The symptoms that result are similar to those of thyrotoxicosis, but there are minor di?erences.

Treatment The ?rst line of treatment is to render the patient euthyroid by treatment with antithyroid drugs. Then the nodule should be removed surgically or destroyed using radioactive iodine.

Thyrotoxicosis A disorder of the thyroid gland in which excessive amounts of thyroid hormones are secreted into the bloodstream. Resultant symptoms are tachycardia, tremor, anxiety, sweating, increased appetite, weight loss and dislike of heat. (See hyperthyroidism above.)... goitre

Heart, Diseases Of

Heart disease can affect any of the structures of the HEART and may affect more than one at a time. Heart attack is an imprecise term and may refer to ANGINA PECTORIS (a symptom of pain originating in the heart) or to coronary artery thrombosis, also called myocardial infarction.

Arrhythmias An abnormal rate or rhythm of the heartbeat. The reason is a disturbance in the electrical impulses within the heart. Sometimes a person may have an occasional irregular heartbeat: this is called an ECTOPIC beat (or an extrasystole) and does not necessarily mean that an abnormality exists. There are two main types of arrhythmia: bradycardias, where the rate is slow – fewer than 60 beats a minute and sometimes so slow and unpredictable (heartblock) as to cause blackouts or heart failure; and tachycardia, where the rate is fast – more than 100 beats a minute. A common cause of arrhythmia is coronary artery disease, when vessels carrying blood to the heart are narrowed by fatty deposits (ATHEROMA), thus reducing the blood supply and damaging the heart tissue. This condition often causes myocardial infarction after which arrhythmias are quite common and may need correcting by DEFIBRILLATION (application of a short electric shock to the heart). Some tachycardias result from a defect in the electrical conduction system of the heart that is commonly congenital. Various drugs can be used to treat arrhythmias (see ANTIARRHYTHMIC DRUGS). If attacks constantly recur, the arrhythmia may be corrected by electrical removal of dead or diseased tissue that is the cause of the disorder. Heartblock is most e?ectively treated with an arti?cial CARDIAC PACEMAKER, a battery-activated control unit implanted in the chest.

Cardiomyopathy Any disease of the heart muscle that results in weakening of its contractions. The consequence is a fall in the e?ciency of the circulation of blood through the lungs and remainder of the body structures. The myopathy may be due to infection, disordered metabolism, nutritional excess or de?ciency, toxic agents, autoimmune processes, degeneration, or inheritance. Often, however, the cause is not identi?ed. Cardiomyopathies are less common than other types of heart diseases, and the incidence of di?erent types of myopathy (see below) is not known because patients or doctors are sometimes unaware of the presence of the condition.

The three recognised groups of cardiomyopathies are hypertrophic, dilated and restrictive.

•Hypertrophic myopathy, a familial condition, is characterised by great enlargement of the muscle of the heart ventricles. This reduces the muscle’s e?ciency, the ventricles fail to relax properly and do not ?ll suf?ciently during DIASTOLE.

In the dilated type of cardiomyopathy, both ventricles overdilate, impairing the e?ciency of contraction and causing congestion of the lungs.

In the restrictive variety, proper ?lling of the ventricles does not occur because the muscle walls are less elastic than normal. The result is raised pressure in the two atria (upper cavities) of the heart: these dilate and develop FIBRILLATION. Diagnosis can be di?cult and treatment is symptomatic, with a poor prognosis. In suitable patients, heart TRANSPLANTATION may be considered. Disorders of the heart muscle may also be

caused by poisoning – for example, heavy consumption of alcohol. Symptoms include tiredness, palpitations (quicker and sometimes irregular heartbeat), chest pain, di?culty in breathing, and swelling of the legs and hands due to accumulation of ?uid (OEDEMA). The heart is enlarged (as shown on chest X-ray) and ECHOCARDIOGRAPHY shows thickening of the heart muscle. A BIOPSY of heart muscle will show abnormalities in the cells of the heart muscle.

Where the cause of cardiomyopathy is unknown, as is the case with most patients, treatment is symptomatic using DIURETICS to control heart failure and drugs such as DIGOXIN to return the heart rhythm to normal. Patients should stop drinking alcohol. If, as often happens, the patient’s condition slowly deteriorates, heart transplantation should be considered.

Congenital heart disease accounts for 1–2 per cent of all cases of organic heart disease. It may be genetically determined and so inherited; present at birth for no obvious reason; or, in rare cases, related to RUBELLA in the mother. The most common forms are holes in the heart (atrial septal defect, ventricular septal defect – see SEPTAL DEFECT), a patent DUCTUS ARTERIOSUS, and COARCTATION OF THE AORTA. Many complex forms also exist and can be diagnosed in the womb by fetal echocardiography which can lead to elective termination of pregnancy. Surgery to correct many of these abnormalities is feasible, even for the most severe abnormalities, but may only be palliative giving rise to major diffculties of management as the children become older. Heart transplantation is now increasingly employed for the uncorrectable lesions.

Coronary artery disease Also known as ischaemic heart disease, this is a common cause of symptoms and death in the adult population. It may present for the ?rst time as sudden death, but more usually causes ANGINA PECTORIS, myocardial infarction (heart attack) or heart failure. It can also lead to a disturbance of heart rhythm. Factors associated with an increased risk of developing coronary artery disease include diabetes, cigarette smoking, high blood pressure, obesity, and a raised concentration of cholesterol in the blood. Older males are most affected.

Coronary thrombosis or acute myocardial infarction is the acute, dramatic manifestation of coronary-artery ischaemic heart disease – one of the major killing diseases of western civilisation. In 1999, ischaemic heart disease was responsible for about 115,000 deaths in England and Wales, compared with 153,000 deaths in 1988. In 1999 more than 55,600 people died of coronary thrombosis. The underlying cause is disease of the coronary arteries which carry the blood supply to the heart muscle (or myocardium). This results in narrowing of the arteries until ?nally they are unable to transport su?cient blood for the myocardium to function e?ciently. One of three things may happen. If the narrowing of the coronary arteries occurs gradually, then the individual concerned will develop either angina pectoris or signs of a failing heart: irregular rhythm, breathlessness, CYANOSIS and oedema.

If the narrowing occurs suddenly or leads to complete blockage (occlusion) of a major branch of one of the coronary arteries, then the victim collapses with acute pain and distress. This is the condition commonly referred to as a coronary thrombosis because it is usually due to the affected artery suddenly becoming completely blocked by THROMBOSIS. More correctly, it should be described as coronary occlusion, because the ?nal occluding factor need not necessarily be thrombosis.

Causes The precise cause is not known, but a wide range of factors play a part in inducing coronary artery disease. Heredity is an important factor. The condition is more common in men than in women; it is also more common in those in sedentary occupations than in those who lead a more physically active life, and more likely to occur in those with high blood pressure than in those with normal blood pressure (see HYPERTENSION). Obesity is a contributory factor. The disease is more common among smokers than non-smokers; it is also often associated with a high level of CHOLESTEROL in the blood, which in turn has been linked with an excessive consumption of animal, as opposed to vegetable, fats. In this connection the important factors seem to be the saturated fatty acids (low-density and very low-density lipoproteins [LDLs and VLDLs] – see CHOLESTEROL) of animal fats which would appear to be more likely to lead to a high level of cholesterol in the blood than the unsaturated fatty acids of vegetable fats. As more research on the subject is carried out, the arguments continue about the relative in?uence of the di?erent factors. (For advice on prevention of the disease, see APPENDIX 2: ADDRESSES: SOURCES OF INFORMATION, ADVICE, SUPPORT AND SELFHELP.)

Symptoms The presenting symptom is the sudden onset, often at rest, of acute, agonising pain in the front of the chest. This rapidly radiates all over the front of the chest and often down over the abdomen. The pain is frequently accompanied by nausea and vomiting, so that suspicion may be aroused of some acute abdominal condition such as biliary colic (see GALLBLADDER, DISEASES OF) or a perforated PEPTIC ULCER. The victim soon goes into SHOCK, with a pale, cold, sweating skin, rapid pulse and dif?culty in breathing. There is usually some rise in temperature.

Treatment is immediate relief of the pain by injections of diamorphine. Thrombolytic drugs should be given as soon as possible (‘rapid door to needle time’) and ARRHYTHMIA corrected. OXYGEN is essential and oral ASPIRIN is valuable. Treatment within the ?rst hour makes a great di?erence to recovery. Subsequent treatment includes the continued administration of drugs to relieve the pain; the administration of ANTIARRHYTHMIC DRUGS that may be necessary to deal with the heart failure that commonly develops, and the irregular action of the heart that quite often develops; and the continued administration of oxygen. Patients are usually admitted to coronary care units, where they receive constant supervision. Such units maintain an emergency, skilled, round-the-clock sta? of doctors and nurses, as well as all the necessary resuscitation facilities that may be required.

The outcome varies considerably. The ?rst (golden) hour is when the patient is at greatest risk of death: if he or she is treated, then there is a 50 per cent reduction in mortality compared with waiting until hospital admission. As each day passes the prognosis improves with a ?rst coronary thrombosis, provided that the patient does not have a high blood pressure and is not overweight. Following recovery, there should be a gradual return to work, care being taken to avoid any increase in weight, unnecessary stress and strain, and to observe moderation in all things. Smoking must stop. In uncomplicated cases patients get up and about as soon as possible, most being in hospital for a week to ten days and back at work in three months or sooner.

Valvular heart disease primarily affects the mitral and aortic valves which can become narrowed (stenosis) or leaking (incompetence). Pulmonary valve problems are usually congenital (stenosis) and the tricuspid valve is sometimes involved when rheumatic heart disease primarily affects the mitral or aortic valves. RHEUMATIC FEVER, usually in childhood, remains a common cause of chronic valvular heart disease causing stenosis, incompetence or both of the aortic and mitral valves, but each valve has other separate causes for malfunction.

Aortic valve disease is more common with increasing age. When the valve is narrowed, the heart hypertrophies and may later fail. Symptoms of angina or breathlessness are common and dizziness or blackouts (syncope) also occur. Replacing the valve is a very e?ective treatment, even with advancing age. Aortic stenosis may be caused by degeneration (senile calci?c), by the inheritance of two valvular leaflets instead of the usual three (bicuspid valve), or by rheumatic fever. Aortic incompetence again leads to hypertrophy, but dilatation is more common as blood leaks back into the ventricle. Breathlessness is the more common complaint. The causes are the same as stenosis but also include in?ammatory conditions such as SYPHILIS or ANKYLOSING SPONDYLITIS and other disorders of connective tissue. The valve may also leak if the aorta dilates, stretching the valve ring as with HYPERTENSION, aortic ANEURYSM and MARFAN’S SYNDROME – an inherited disorder of connective tissue that causes heart defects. Infection (endocarditis) can worsen acutely or chronically destroy the valve and sometimes lead to abnormal outgrowths on the valve (vegetations) which may break free and cause devastating damage such as a stroke or blocked circulation to the bowel or leg.

Mitral valve disease leading to stenosis is rheumatic in origin. Mitral incompetence may be rheumatic but in the absence of stenosis can be due to ISCHAEMIA, INFARCTION, in?ammation, infection and a congenital weakness (prolapse). The valve may also leak if stretched by a dilating ventricle (functional incompetence). Infection (endocarditis) may affect the valve in a similar way to aortic disease. Mitral symptoms are predominantly breathlessness which may lead to wheezing or waking at night breathless and needing to sit up or stand for relief. They are made worse when the heart rhythm changes (atrial ?brillation) which is frequent as the disease becomes more severe. This leads to a loss of e?ciency of up to 25 per cent and a predisposition to clot formation as blood stagnates rather than leaves the heart e?ciently. Mitral incompetence may remain mild and be of no trouble for many years, but infection must be guarded against (endocarditis prophylaxis).

Endocarditis is an infection of the heart which may acutely destroy a valve or may lead to chronic destruction. Bacteria settle usually on a mild lesion. Antibiotics taken at vulnerable times can prevent this (antibiotic prophylaxis) – for example, before tooth extraction. If established, lengthy intravenous antibiotic therapy is needed and surgery is often necessary. The mortality is 30 per cent but may be higher if the infection settles on a replaced valve (prosthetic endocarditis). Complications include heart failure, shock, embolisation (generation of small clots in the blood), and cerebral (mental) confusion.

PERICARDITIS is an in?ammation of the sac covering the outside of the heart. The sac becomes roughened and pain occurs as the heart and sac rub together. This is heard by stethoscope as a scratching noise (pericardial rub). Fever is often present and a virus the main cause. It may also occur with rheumatic fever, kidney failure, TUBERCULOSIS or from an adjacent lung problem such as PNEUMONIA or cancer. The in?ammation may cause ?uid to accumulate between the sac and the heart (e?usion) which may compress the heart causing a fall in blood pressure, a weak pulse and circulatory failure (tamponade). This can be relieved by aspirating the ?uid. The treatment is then directed at the underlying cause.... heart, diseases of

Hypoproteinaemia

A fall in the amount of PROTEIN in the blood. This may be caused by malnutrition, loss of protein from kidney disorders, or faulty production of protein which occurs in some liver disorders. Hypoproteinaemia causes OEDEMA because ?uid accumulates in the tissues as a consequence of the metabolic abnormalities. Patients’ resistance to infections is also impaired.... hypoproteinaemia

Asparagus

Asparagus racemosus

Liliaceae

San, Mar, Hin, Mal: Satavari;

Ben: Shatamuli,

Guj: Ekalkanto,

Tel: Pilligadalu, Philithaga

Tam: Ammaikodi, Kilwari,

Kan: Aheruballi, Ori: Manajolo

Importance: Asparagus is a climbing undershrub with widespread applications as diuretic, cooling agent and an excellent safe herbal medicine for ante-natal care. It is useful in nervous disorders, dyspepsia, diarrhoea, tumours, inflammations, vitiated conditions of vata and pitta, burning sensation, hyperdipsia, ophthalmopathy, nephropathy, hepatopathy, strangury, scalding of urine, throat infections, tuberculosis, cough, bronchitis, gleet, gonorrhoea, leucorrhoea, leprosy, epilepsy, fatigue, hyperacidity, colic haemorrhoids, hypertension, abortion, agalactia, cardiac and general debility (Warrier et al, 1993).

Shatavari is described in Rigveda and Atharvaveda. In Ayurvedic classics it is prescribed as a cooling agent and uterine tonic. It is the main ingredient in ayurvedic medicines like shatavari gulam and shatavari ghrtam. Besides quenching thirst, its root juice helps in cooling down the body from summer heat, curing hyper-acidity and peptic ulcer. It contains good amount of mucilage which soothes the inner cavity of stomach. It relieves burning sensation while passing urine and is used in urinary tract infections. It contains an anticancer agent asparagin which is useful against leukaemia. It also contains active antioxytocic saponins which have got antispasmodic effect and specific action on uterine musculature. It is very good relaxant to uterine muscles, especially during pregnancy and is used to prevent abortion and pre-term labour on the place of progesterone preparations. Its powder boiled with milk is generally used to prevent abortion. It increases milk production in cows and buffaloes. Its preparations in milk helps in increasing breast milk in lactating women. Its proper use helps in avoiding excessive blood loss during periods. It clears out infections and abnormalities of uterine cavity and hence it is used to rectify infertility in women. The leaves are used to prepare toilet soaps. The plant has also ornamental value both for indoor and out door decorations (Syamala, 1997).

Distribution: The plant is found wild in tropical and subtropical India including Andaman and Nicobar Islands. It is distributed from mean sea level upto 1500m in the Himalayas from Kashmi r eastwards. The crop is cultivated in Kerala, Tamil Nadu, Andhra Predesh and northern states in India. However, most of the requirement of the industry is met through wild collections from forests. It is also grown in gardens.

Botany: Satavari, Asparagus racemosus Willd. belongs to the lily family, Liliaceae. Asparagus adscendens Roxb., A. filicinus Lam., A. gonoclados Baker, A. officinalis Linn. and A. sarmentosus Willd. are the other important medicinal plant species of the genus. A. racemosus Willd. is an armed climbing undershrub with woody terete stems and recurved or rarely straight spines. The tuberous succulent roots are 30cm to 100cm or more in length, fascicled at the stem base, smooth tapering at both ends. Young stems are very delicate, brittle and smooth. Leaves are reduced to minute chaffy scales and spines; cladodes triquetrous, curved in tufts of 2-6. Flowers are white fragrant in simple or branched recemes on the naked nodes of the main shoots or in the axils of the thorns. Fruits are globular or obscurely 3-lobed, pulpy berries, purplish black when ripe; seeds with hard and brittle testa.

Agrotechnology: The plant comes up well under a wide range of tropical and subtropical climate. Fertile moist sandy loam soils are ideal for its cultivation though it grows in a wide range of soils. Better root development is observed in soils in increased proportion of sand. However, a decline in the yield of the crop is noticed in soils containing previous year’s residue of the roots. Asparagus plant is best grown from its tuberous roots even though it can be successfully propagated through seeds. Since root tubers are of commercial value seed propagation provides economic advantage to the farmers. Seeds usually start germinating after 40 days and average germination is 70% (Tewari and Misra, 1996).

For the cultivation of the crop, the land is ploughed well with pre-monsoon showers and seed nurseries are raised on seed beds of approximately 1m width, 15cm height and suitable length. Seed nursery should be irrigated regularly and kept weed free. With the onset of monsoon in June-July the main field is ploughed thoroughly and pits of size 30cm cube are dug at a spacing of 60-100cm. Tiwari and Misra (1996) have reported that irrespective of more number of roots and higher fresh weight per plant under wider spacings, the per hectare yields were highest in the closer spacing of 30cm x 30cm. The pit is filled with a mixture of top soil and well decomposed FYM or compost applied at 10 - 15 t/ha and the seedlings are transplanted. Application of N, P2O5 and K2O at 60:30:30 kg/ha increases the root yield. Regular irrigation and weeding are required to realize higher yields. Standards are to be provided for training the plant (Sharma et al, 1992). Few pests and diseases are observed on this crop. Harvesting the crop after two years provided higher root yield than annual harvests in pots as well as in field experiments. Irrigating the field prior to harvest enables easy harvesting of the root tubers. The average yield is 10 - 15 t/ha of fresh root tubers though yields over 60t/ha have been reported.

Properties and activity: Asparagus roots contain protein 22%, fat 6.2%, Carbohydrate 3.2%, Vitamin B 0.36%, Vitamin C 0.04% and traces of Vitamin A. It contains several alkaloids. Alcoholic extract yields asparagin- an anticancer agent. It also contains a number of antioxytocic saponins, viz. Shatavarisn - I to IV (Syamala, 1997). Leaves contain rutin, diosgenin and a flavonoid glycoside identified as quercetin - 3 - glucuronide. Flowers contain quercetin hyperoside and rutin. Fruits contain glycosides of quercetin, rutin and hyperoside while fully ripe fruits contain cyanidin - 3 - galactoside and cyanidin - 3 - glucorhamnoside.

Root is demulcent, diuretic, aphrodisiac, tonic, alterative, antiseptic, antidiarrhoeal, glalctogogue and antispasmodic. Aerial part is spasmolytic, antiarrhythmic and anticancer. Bark is antibacterial and antifungal.... asparagus

Bundle Branch Block

An abnormality of the conduction of electrical impulses through the ventricles of the HEART, resulting in delayed depolarisation of the ventricular muscle. The electrocardiograph (see ELECTROCARDIOGRAM (ECG)) shows characteristic widening of the QRS complexes. Abnormalities of the right and left bundle branches cause delayed contraction of the right and left ventricles respectively.... bundle branch block

Immunodeficiency

Impaired IMMUNITY resulting from inherited or acquired abnormalities of the immune system. This leads to increased vulnerability to infection. Important inherited examples of immunode?ciency are defects in function of GRANULOCYTES and the COMPLEMENT SYSTEM. Common acquired forms of immunode?ciency are defective function of B-type lymphocytes and hence antibody de?ciency in ‘common variable hypogammaglobulinaemia’, and grossly de?cient CD4 T-cell function – malfunctioning T-type lymphocytes – in AIDS, secondary to HIV infection (see AIDS/HIV).... immunodeficiency

Carbon Monoxide (co)

This is a colourless, odourless, tasteless, nonirritating gas formed on incomplete combustion of organic fuels. Exposure to CO is frequently due to defective gas, oil or solid-fuel heating appliances. CO is a component of car exhaust fumes and deliberate exposure to these is a common method of suicide. Victims of ?res often suffer from CO poisoning. CO combines reversibly with oxygen-carrying sites of HAEMOGLOBIN (Hb) molecules with an a?nity 200 to 300 times greater than oxygen itself. The carboxyhaemoglobin (COHb) formed becomes unavailable for oxygen transportation. In addition the partial saturation of the Hb molecule results in tighter oxygen binding, impairing delivery to the tissues. CO also binds to MYOGLOBIN and respiratory cytochrome enzymes. Exposure to CO at levels of 500 parts per million (ppm) would be expected to cause mild symptoms only and exposure to levels of 4,000 ppm would be rapidly fatal.

Each year around 50 people in the United Kingdom are reported as dying from carbon monoxide poisoning, and experts have suggested that as many as 25,000 people a year are exposed to its effects within the home, but most cases are unrecognised, unreported and untreated, even though victims may suffer from long-term effects. This is regrettable, given that Napoleon’s surgeon, Larrey, recognised in the 18th century that soldiers were being poisoned by carbon monoxide when billeted in huts heated by woodburning stoves. In the USA it is estimated that 40,000 people a year attend emergency departments suffering from carbon monoxide poisoning. So prevention is clearly an important element in dealing with what is sometimes termed the ‘silent killer’. Safer designs of houses and heating systems, as well as wider public education on the dangers of carbon monoxide and its sources, are important.

Clinical effects of acute exposure resemble those of atmospheric HYPOXIA. Tissues and organs with high oxygen consumption are affected to a great extent. Common effects include headaches, weakness, fatigue, ?ushing, nausea, vomiting, irritability, dizziness, drowsiness, disorientation, incoordination, visual disturbances, TACHYCARDIA and HYPERVENTILATION. In severe cases drowsiness may progress rapidly to COMA. There may also be metabolic ACIDOSIS, HYPOKALAEMIA, CONVULSIONS, HYPOTENSION, respiratory depression, ECG changes and cardiovascular collapse. Cerebral OEDEMA is common and will lead to severe brain damage and focal neurological signs. Signi?cant abnormalities on physical examination include impaired short-term memory, abnormal Rhomberg’s test (standing unsupported with eyes closed) and unsteadiness of gait including heel-toe walking. Any one of these signs would classify the episode as severe. Victims’ skin may be coloured pink, though this is very rarely seen even in severe incidents. The venous blood may look ‘arterial’. Patients recovering from acute CO poisoning may suffer neurological sequelae including TREMOR, personality changes, memory impairment, visual loss, inability to concentrate and PARKINSONISM. Chronic low-level exposures may result in nausea, fatigue, headache, confusion, VOMITING, DIARRHOEA, abdominal pain and general malaise. They are often misdiagnosed as in?uenza or food poisoning.

First-aid treatment is to remove the victim from the source of exposure, ensure an e?ective airway and give 100-per-cent oxygen by tight-?tting mask. In hospital, management is largely suppportive, with oxygen administration. A blood sample for COHb level determination should be taken as soon as practicable and, if possible, before oxygen is given. Ideally, oxygen therapy should continue until the COHb level falls below 5 per cent. Patients with any history of unconsciousness, a COHb level greater than 20 per cent on arrival, any neurological signs, any cardiac arrhythmias or anyone who is pregnant should be referred for an expert opinion about possible treatment with hyperbaric oxygen, though this remains a controversial therapy. Hyperbaric oxygen therapy shortens the half-life of COHb, increases plasma oxygen transport and reverses the clinical effects resulting from acute exposures. Carbon monoxide is also an environmental poison and a component of cigarette smoke. Normal body COHb levels due to ENDOGENOUS CO production are 0.4 to

0.7 per cent. Non-smokers in urban areas may have level of 1–2 per cent as a result of environmental exposure. Smokers may have a COHb level of 5 to 6 per cent.... carbon monoxide (co)

Chest, Deformities Of

The healthy chest is gently rounded all over, its contour being more rounded in women by the breast tissue. In cross-section it is oval-shaped with a longer dimension from side to side than from back to front.

Barrel chest is found in long-standing ASTHMA or chronic BRONCHITIS and EMPHYSEMA, when the lungs are chronically enlarged. The anterio-posterior dimension of the chest is increased and the ribs are near horizontal. In this position they can produce little further expansion of the chest, and breathing often relies on accessory muscles in the neck lifting up the whole thoracic cage on inspiration.

Pigeon chest is one in which the cross-section of the chest becomes triangular with the sternum forming a sort of keel in front. It may be related to breathing problems in early life.

Rickety chest is uncommon now and is caused by RICKETS in early life. There is a hollow down each side caused by the pull of muscles on the softer ribs in childhood. The line of knobs produced on each side where the ribs join their costal cartilages is known as the rickety rosary.

Pectus excavatum, or funnel chest, is quite a common abnormality where the central tendon of the diaphragm seems to be too short so that the lower part of the sternum is displaced inwards and the lower ribs are prominent. When severe, it may displace the heart further to the left side.

Local abnormalities in the shape of the chest occur when there is a deformity in the spine such as scoliosis which alters the angles of the ribs. The chest wall may be locally ?attened when the underlying lung is reduced in size locally over a prolonged period. (See SPINE AND SPINAL CORD, DISEASES AND INJURIES OF.) This may be seen over a scarred area of lung such as that observed in pulmonary TUBERCULOSIS.... chest, deformities of

Impairment

Any loss or abnormality of psychological, physiological or anatomical structure or function. It is concerned with abnormalities of body structure and appearance, organ or system resulting from any cause. In principle, impairments represent disturbances at the organ level. See also “handicap”; “disability”.... impairment

Impression

In dentistry, a mould (using a rubber or alginate compound) of the teeth and gums from which a plaster-of-Paris model is prepared. This model provides a base on which to construct a denture, bridge or dental inlay. A similar process is used in ORTHODONTICS to make dental appliances to correct abnormalities in the positioning of teeth.... impression

Child Health

Paediatrics is the branch of medicine which deals with diseases of children, but many paediatricians have a wider role, being employed largely outside acute hospitals and dealing with child health in general.

History Child health services were originally designed, before the NHS came into being, to ?nd or prevent physical illness by regular inspections. In the UK these were carried out by clinical medical o?cers (CMOs) working in infant welfare clinics (later, child health clinics) set up to ?ll the gap between general practice and hospital care. The services expanded greatly from the mid 1970s; ‘inspections’ have evolved into a regular screening and surveillance system by general practitioners and health visitors, while CMOs have mostly been replaced by consultant paediatricians in community child health (CPCCH).

Screening Screening begins at birth, when every baby is examined for congenital conditions such as dislocated hips, heart malformations, cataract and undescended testicles. Blood is taken to ?nd those babies with potentially brain-damaging conditions such as HYPOTHYROIDISM and PHENYLKETONURIA. Some NHS trusts screen for the life-threatening disease CYSTIC FIBROSIS, although in future it is more likely that ?nding this disease will be part of prenatal screening, along with DOWN’S (DOWN) SYNDROME and SPINA BIFIDA. A programme to detect hearing impairment in newborn babies has been piloted from 2001 in selected districts to ?nd out whether it would be a useful addition to the national screening programme. Children from ethnic groups at risk of inherited abnormalities of HAEMOGLOBIN (sickle cell disease; thalassaemia – see under ANAEMIA) have blood tested at some time between birth and six months of age.

Illness prevention At two months, GPs screen babies again for these abnormalities and start the process of primary IMMUNISATION. The routine immunisation programme has been dramatically successful in preventing illness, handicap and deaths: as such it is the cornerstone of the public health aspect of child health, with more potential vaccines being made available every year. Currently, infants are immunised against pertussis (see WHOOPING COUGH), DIPHTHERIA, TETANUS, POLIOMYELITIS, haemophilus (a cause of MENINGITIS, SEPTICAEMIA, ARTHRITIS and epiglottitis) and meningococcus C (SEPTICAEMIA and meningitis – see NEISSERIACEAE) at two, three and four months. Selected children from high-risk groups are o?ered BCG VACCINE against tuberculosis and hepatitis vaccine. At about 13 months all are o?ered MMR VACCINE (measles, mumps and rubella) and there are pre-school entry ‘boosters’ of diphtheria, tetanus, polio, meningococcus C and MMR. Pneumococcal vaccine is available for particular cases but is not yet part of the routine schedule.

Health promotion and education Throughout the UK, parents are given their child’s personal health record to keep with them. It contains advice on health promotion, including immunisation, developmental milestones (when did he or she ?rst smile, sit up, walk and so on), and graphs – called centile charts – on which to record height, weight and head circumference. There is space for midwives, doctors, practice nurses, health visitors and parents to make notes about the child.

Throughout at least the ?rst year of life, both parents and health-care providers set great store by regular weighing, designed to pick up children who are ‘failing to thrive’. Measuring length is not quite so easy, but height measurements are recommended from about two or three years of age in order to detect children with disorders such as growth-hormone de?ciency, malabsorption (e.g. COELIAC DISEASE) and psychosocial dwar?sm (see below).

All babies have their head circumference measured at birth, and again at the eight-week check. A too rapidly growing head implies that the infant might have HYDROCEPHALUS – excess ?uid in the hollow spaces within the brain. A too slowly growing head may mean failure of brain growth, which may go hand in hand with physically or intellectually delayed development.

At about eight months, babies receive a surveillance examination, usually by a health visitor. Parents are asked if they have any concerns about their child’s hearing, vision or physical ability. The examiner conducts a screening test for hearing impairment – the so-called distraction test; he or she stands behind the infant, who is on the mother’s lap, and activates a standardised sound at a set distance from each ear, noting whether or not the child turns his or her head or eyes towards the sound. If the child shows no reaction, the test is repeated a few weeks later; if still negative then referral is made to an audiologist for more formal testing.

The doctor or health visitor will also go through the child’s developmental progress (see above) noting any signi?cant deviation from normal which merits more detailed examination. Doctors are also recommended to examine infants developmentally at some time between 18 and 24 months. At this time they will be looking particularly for late walking or failure to develop appropriate language skills.... child health

Intravenous Pyelogram (urogram)

A procedure for getting X-ray pictures of the URINARY TRACT. A radio-opaque medium is injected into a vein and, when it is excreted by the kidneys, the substance can be identi?ed on X-rays. Any abnormalities in structure or foreign bodies such as calculi are outlined by the dye (see KIDNEYS, DISEASES OF).... intravenous pyelogram (urogram)

Laparoscopy

Also called peritoneoscopy, this is a technique using an instrument called an ENDOSCOPE for viewing the contents of the ABDOMEN. The instrument is inserted via an incision just below the UMBILICUS and air is then pumped into the peritoneal (abdominal) cavity. Visual inspection may help in the diagnosis of cancer, APPENDICITIS, SALPINGITIS, and abnormalities of the LIVER, GALL-BLADDER, OVARIES or GASTROINTESTINAL TRACT. A BIOPSY can be taken of tissue suspected of being abnormal, and operations such as removal of the gall-bladder or appendix may be carried out. (See also MINIMALLY INVASIVE SURGERY (MIS).)... laparoscopy

Maculopapular

A skin rash that is made up of macules (discoloration of the skin) and papules (raised abnormalities of the skin).... maculopapular

Menstruation

A periodic change occurring in (female) human beings and the higher apes, consisting chie?y in a ?ow of blood from the cavity of the womb (UTERUS) and associated with various slight constitutional disturbances. It begins between the ages of 12 and 15, as a rule – although its onset may be delayed until as late as 20, or it may begin as early as ten or 11. Along with its ?rst appearance, the body develops the secondary sex characteristics: for example, enlargement of the BREASTS, and characteristic hair distribution. The duration of each menstrual period varies in di?erent persons from 2– 8 days. It recurs in the great majority of cases with regularity, most commonly at intervals of 28 or 30 days, less often with intervals of 21 or 27 days, and ceasing only during pregnancy and lactation, until the age of 45 or 50 arrives, when it stops altogether – as a rule ceasing early if it has begun early, and vice versa. The ?nal stoppage is known as the MENOPAUSE or the CLIMACTERIC.

Menstruation depends upon a functioning ovary (see OVARIES) and this upon a healthy PITUITARY GLAND. The regular rhythm may depend upon a centre in the HYPOTHALAMUS, which is in close connection with the pituitary. After menstruation, the denuded uterine ENDOMETRIUM is regenerated under the in?uence of the follicular hormone, oestradiol. The epithelium of the endometrium proliferates, and about a fortnight after the beginning of menstruation great development of the endometrial glands takes place under the in?uence of progesterone, the hormone secreted by the CORPUS LUTEUM. These changes are made for the reception of the fertilised OVUM. In the absence of fertilisation the uterine endometrium breaks down in the subsequent menstrual discharge.

Disorders of menstruation In most healthy women, menstruation proceeds regularly for 30 years or more, with the exceptions connected with childbirth. In many women, however, menstruation may be absent, excessive or painful. The term amenorrhoea is applied to the condition of absent menstruation; the terms menorrhagia and metrorrhagia describe excessive menstrual loss – the former if the excess occurs at the regular periods, and the latter if it is irregular. Dysmenorrhoea is the name given to painful menstruation. AMENORRHOEA If menstruation has never occurred, the amenorrhoea is termed primary; if it ceases after having once become established it is known as secondary amenorrhoea. The only value of these terms is that some patients with either chromosomal abnormalities (see CHROMOSOMES) or malformations of the genital tract fall into the primary category. Otherwise, the age of onset of symptoms is more important.

The causes of amenorrhoea are numerous and treatment requires dealing with the primary cause. The commonest cause is pregnancy; psychological stress or eating disorders can cause amenorrhoea, as can poor nutrition or loss of weight by dieting, and any serious underlying disease such as TUBERCULOSIS or MALARIA. The excess secretion of PROLACTIN, whether this is the result of a micro-adenoma of the pituitary gland or whether it is drug induced, will cause amenorrhoea and possibly GALACTORRHOEA as well. Malfunction of the pituitary gland will result in a failure to produce the gonadotrophic hormones (see GONADOTROPHINS) with consequent amenorrhoea. Excessive production of cortisol, as in CUSHING’S SYNDROME, or of androgens (see ANDROGEN) – as in the adreno-genital syndrome or the polycystic ovary syndrome – will result in amenorrhoea. Amenorrhoea occasionally follows use of the oral contraceptive pill and may be associated with both hypothyroidism (see under THYROID GLAND, DISEASES OF) and OBESITY.

Patients should be reassured that amenorrhoea can often be successfully treated and does not necessarily affect their ability to have normal sexual relations and to conceive. When weight loss is the cause of amenorrhoea, restoration of body weight alone can result in spontaneous menstruation (see also EATING DISORDERS – Anorexia nervosa). Patients with raised concentration of serum gonadotrophin hormones have primary ovarian failure, and this is not amenable to treatment. Cyclical oestrogen/progestogen therapy will usually establish withdrawal bleeding. If the amenorrhoea is due to mild pituitary failure, menstruation may return after treatment with clomiphene, a nonsteroidal agent which competes for oestrogen receptors in the hypothalamus. The patients who are most likely to respond to clomiphene are those who have some evidence of endogenous oestrogen and gonadotrophin production. IRREGULAR MENSTRUATION This is a change from the normal monthly cycle of menstruation, the duration of bleeding or the amount of blood lost (see menorrhagia, below). Such changes may be the result of an upset in the balance of oestrogen and progesterone hormones which between them control the cycle. Cycles may be irregular after the MENARCHE and before the menopause. Unsuspected pregnancy may manifest itself as an ‘irregularity’, as can an early miscarriage (see ABORTION). Disorders of the uterus, ovaries or organs in the pelvic cavity can also cause irregular menstruation. Women with the condition should seek medical advice. MENORRHAGIA Abnormal bleeding from the uterus during menstruation. A woman loses on average about 60 ml of blood during her period; in menorrhagia this can rise to 100 ml. Some women have this problem occasionally, some quite frequently and others never. One cause is an imbalance of progesterone and oestrogen hormones which between them control menstruation: the result is an abnormal increase in the lining (endometrium) of the uterus, which increases the amount of ‘bleeding’ tissue. Other causes include ?broids, polyps, pelvic infection or an intrauterine contraceptive device (IUD – see under CONTRACEPTION). Sometimes no physical reason for menorrhagia can be identi?ed.

Treatment of the disorder will depend on how severe the loss of blood is (some women will become anaemic – see ANAEMIA – and require iron-replacement therapy); the woman’s age; the cause of heavy bleeding; and whether or not she wants children. An increase in menstrual bleeding may occur in the months before the menopause, in which case time may produce a cure. Medical or surgical treatments are available. Non-steroidal anti-in?ammatory drugs may help, as may tranexamic acid, which prevents the breakdown of blood clots in the circulation (FIBRINOLYSIS): this drug can be helpful if an IUD is causing bleeding. Hormones such as dydrogesterone (by mouth) may cure the condition, as may an IUD that releases small quantities of a PROGESTOGEN into the lining of the womb.

Traditionally, surgical intervention was either dilatation and curettage of the womb lining (D & C) or removal of the whole uterus (HYSTERECTOMY). Most surgery is now done using minimally invasive techniques. These do not require the abdomen to be cut open, as an ENDOSCOPE is passed via the vagina into the uterus. Using DIATHERMY or a laser, the surgeon then removes the whole lining of the womb. DYSMENORRHOEA This varies from discomfort to serious pain, and sometimes includes vomiting and general malaise. Anaemia is sometimes a cause of painful menstruation as well as of stoppage of this function.

In?ammation of the uterus, ovaries or FALLOPIAN TUBES is a common cause of dysmenorrhoea which comes on for the ?rst time late in life, especially when the trouble follows the birth of a child. In this case the pain exists more or less at all times, but is aggravated at the periods. Treatment with analgesics and remedying the underlying cause is called for.

Many cases of dysmenorrhoea appear with the beginning of menstrual life, and accompany every period. It has been estimated that 5–10 per cent of girls in their late teens or early 20s are severely incapacitated by dysmenorrhoea for several hours each month. Various causes have been suggested for the pain, one being an excessive production of PROSTAGLANDINS. There may be a psychological factor in some sufferers and, whether this is the result of inadequate sex instruction, fear, family, school or work problems, it is important to o?er advice and support, which in itself may resolve the dysmenorrhoea. Symptomatic relief is of value.... menstruation

Mitosis

The classic four-phased cellular division of somatic cells, wherein (when the dust settles) two new daughter cells contain full chromosomal information of the parent, complete nuclei, and half the cytoplasm. This is distinct from cloning (as in the bone morrow) and the chromosome splitting of miosis (ovum and sperm).... mitosis

Collagen

The most abundant protein in the body. It is the major structural component of many parts of the body and occurs in many di?erent forms. Thus it exists as thick ?bres in skin and tendons. It is also an important constituent of the heart and blood vessels. With calcium salts it provides the rigid structure of bone. It also occurs as a delicate structure in the cornea of the eye, and in what is known as the basement membrane of many tissues including the glomeruli of the kidneys and the capsule of the lens of the eye. It plays a part in many diseases, hereditary and otherwise. Among the inherited abnormalities of collagen are those responsible for aneurysms of the CIRCLE OF WILLIS and for OSTEOGENESIS IMPERFECTA. On boiling it is converted into gelatin.... collagen

Diabetes Insipidus

Diabetes insipidus is a relatively rare condition and must be di?erentiated from DIABETES MELLITUS which is an entirely di?erent disease.

It is characterised by excessive thirst and the passing of large volumes of urine which have a low speci?c gravity and contain no abnormal constituents. It is either due to a lack of the antidiuretic hormone normally produced by the HYPOTHALAMUS and stored in the posterior PITUITARY GLAND, or to a defect in the renal tubules which prevents them from responding to the antidiuretic hormone VASOPRESSIN. When the disorder is due to vasopressin insu?ciency, a primary or secondary tumour in the area of the pituitary stalk is responsible for one-third of cases. In another one-third of cases there is no apparent cause, and such IDIOPATHIC cases are sometimes familial. A further one-third of cases result from a variety of lesions including trauma, basal MENINGITIS and granulomatous lesions in the pituitary-stalk area. When the renal tubules fail to respond to vasopressin this is usually because of a genetic defect transmitted as a sex-linked recessive characteristic, and the disease is called nephrogenic diabetes insipidus. Metabolic abnormalities such as HYPERCALCAEMIA and potassium depletion render the renal tubule less sensitive to vasopressin, and certain drugs such as lithium and tetracycline may have a similar e?ect.

If the disease is due to a de?ciency of vasopressin, treatment should be with the analogue of vasopressin called desmopressin which is more potent than the natural hormone and has less pressor activity. It also has the advantage in that it is absorbed from the nasal mucosa and so does not need to be injected.

Nephrogenic diabetes insipidus cannot be treated with desmopressin. The urine volume can, however, usually be reduced by half by a thiazide diuretic (see THIAZIDES).... diabetes insipidus

Dwarfism

Dwar?sm, or short stature, refers to underdevelopment of the body. The condition, which has various causes, is not common. All children who by the age of ?ve years are at least what is technically known as ‘three standard deviations below the mean’ – well below average size for children of that age – should be referred for specialist advice. Among the causes are:

•genetic: familial; abnormalities of chromosomes, for example, TURNER’S SYNDROME; abnormal skeletal development; and failure of primary growth.

intrauterine growth retardation: maternal disorders; placental abnormalities; multiple fetuses.

constitutional delay in normal growth.

systemic conditions: nutritional de?ciencies; gastrointestinal absorption disorders; certain chronic diseases; psychosocial deprivation; endocrine malfunctions, including HYPOTHYROIDISM, CUSHING’S SYNDROME, RICKETS, dysfunction of the PITUITARY GLAND which produces growth hormone, the endocrine growth controller. Treatment of short stature is, where possible,

to remedy the cause: for example, children with hypothyroidism can be given THYROXINE. Children who are not growing properly should be referred for expert advice to determine the diagnosis and obtain appropriate curative or supportive treatments.... dwarfism

Encephalitis

Encephalitis means in?ammation or infection of the brain, usually caused by a virus; it may also be the result of bacterial infection. It occurs throughout the world and affects all racial groups and ages. Rarely it occurs as a complication of common viral disease such as measles, mumps, glandular fever, or chickenpox. It may occur with no evidence of infection elsewhere, such as in HERPES SIMPLEX encephalitis, the most common form seen in Europe and America. RABIES is another form of viral encephalitis, and the HIV virus which causes AIDS invades the brain to cause another form of encephalitis (see AIDS/HIV). In some countries – North and South America, Japan and east Asia and Russia

– there may be epidemics spread by the bite of mosquitoes or ticks.

The clinical features begin with in?uenza-like symptoms – aches, temperature and wretchedness; then the patient develops a headache with drowsiness, confusion and neck sti?ness. Severely ill patients develop changes in behaviour, abnormalities of speech, and deterioration, sometimes with epileptic seizures. Some develop paralysis and memory loss. CT (see COMPUTED TOMOGRAPHY) and MRI brain scans show brain swelling, and damage to the temporal lobes if the herpes virus is involved. ELECTROENCEPHALOGRAPHY (EEG), which records the brainwaves, is abnormal. Diagnosis is possible by an examination of the blood or other body ?uids for antibody reaction to the virus, and modern laboratory techniques are very speci?c.

In general, drugs are not e?ective against viruses – antibiotics are of no use. Herpes encephalitis does respond to treatment with the antiviral agent, aciclovir. Treatment is supportive: patients should be given painkillers, and ?uid replacement drugs to reduce brain swelling and counter epilepsy if it occurs. Fortunately, most sufferers from encephalitis make a complete recovery, but some are left severely disabled with physical defects, personality and memory disturbance, and epileptic ?ts. Rabies is always fatal and the changes found in patients with AIDS are almost always progressive. Except in very speci?c circumstances, it is not possible to be immunised against encephalitis.

Encephalitis lethargica is one, now rare, variety that reached epidemic levels after World War I. It was characterised by drowsiness and headache leading on to COMA. The disease occasionally occurs as a complication after mumps and sometimes affected individuals subsequently develop postencephalitic PARKINSONISM.... encephalitis

Eating Disorders

The term ‘eating disorders’ covers OBESITY, feeding problems in childhood, anorexia nervosa, and bulimia nervosa. The latter two are described here.

Anorexia nervosa Often called the slimmer’s disease, this is a syndrome characterised by the loss of at least a quarter of a person’s normal body weight; by fear of normal weight; and, in women, by AMENORRHOEA. An individual’s body image may be distorted so that the sufferer cannot judge real weight and wants to diet even when already very thin.

Anorexia nervosa usually begins in adolescence, affecting about 1–2 per cent of teenagers and college students at any time. It is 20 times more common among women than men. Up to 10 per cent of sufferers’ sisters also have the syndrome. Anorexia may be linked with episodes of bulimia (see below).

The symptoms result from secretive self-starvation, usually with excessive exercise, self-induced vomiting, and misuse of laxatives. An anorexic (or anorectic) person may wear layers of baggy clothes to keep warm and to hide the ?gure. Starvation can cause serious problems such as ANAEMIA, low blood pressure, slow heart rate, swollen ankles, and osteoporosis. Sudden death from heart ARRHYTHMIA may occur, particularly if the sufferer misuses DIURETICS to lose weight and also depletes the body’s level of potassium.

There is probably no single cause of anorexia nervosa. Social pressure to be thin seems to be an important factor and has increased over the past 20–30 years, along with the incidence of the syndrome. Psychological theories include fear of adulthood and fear of losing parents’ attention.

Treatment should start with the general practitioner who should ?rst rule out other illnesses causing similar signs and symptoms. These include DEPRESSION and disorders of the bowel, PITUITARY GLAND, THYROID GLAND, and OVARIES.

If the diagnosis is clearly anorexia nervosa, the general practitioner may refer the sufferer to a psychiatrist or psychologist. Moderately ill sufferers can be treated by COGNITIVE BEHAVIOUR THERAPY. A simple form of this is to agree targets for daily calorie intake and for acceptable body weight. The sufferer and the therapist (the general practitioner or a member of the psychiatric team) then monitor progress towards both targets by keeping a diary of food intake and measuring weight regularly. Counselling or more intensely personal PSYCHOTHERAPY may help too. Severe life-threatening complications will need urgent medical treatment in hospital, including rehydration and feeding using a nasogastric tube or an intravenous drip.

About half of anorectic sufferers recover fully within four years, a quarter improve, and a quarter remain severely underweight with (in the case of women) menstrual abnormalities. Recovery after ten years is rare and about 3 per cent die within that period, half of them by suicide.

Bulimia nervosa is a syndrome characterised by binge eating, self-induced vomiting and laxative misuse, and fear of fatness. There is some overlap between anorexia nervosa and bulimia but, unlike the former, bulimia may start at any age from adolescence to 40 and is probably more directly linked with ordinary dieting. Bulimic sufferers say that, although they feel depressed and guilty after binges, the ‘buzz’ and relief after vomiting and purging are addictive. They often respond well to cognitive behaviour therapy.

Bulimia nervosa does not necessarily cause weight loss because the binges – for example of a loaf of bread, a packet of cereal, and several cans of cold baked beans at one sitting – are cancelled out by purging, by self-induced vomiting and by brief episodes of starvation. The full syndrome has been found in about 1 per cent of women but mild forms may be much more common. In one survey of female college students, 13 per cent admitted to having had bulimic symptoms.

Bulimia nervosa rarely leads to serious physical illness or death. However, repeated vomiting can cause oesophageal burns, salivary gland infections, small tears in the stomach, and occasionally dehydration and chemical imbalances in the blood. Inducing vomiting using ?ngers may produce two tell-tale signs – bite marks on the knuckles and rotten, pitted teeth.

Those suffering from this condition may obtain advice from the Eating Disorders Association.... eating disorders

Infant Mortality Rate (imr)

The number of deaths of infants under one year of age. The IMR in any given year is calculated as the number of deaths in the ?rst year of life in proportion to every 1,000 registered live births in that year. Along with PERINATAL MORTALITY, it is accepted as one of the most important criteria for assessing the health of the community and the standard of the social conditions of a country.

The improvement in the infant mortality rate has occurred mainly in the period from the second month of life. There has been much less improvement in the neonatal mortality rate – that is, the number of infants dying during the ?rst four weeks of life, expressed as a proportion of every 1,000 live births. During the ?rst week of life the main causes of death are asphyxia, prematurity, birth injuries and congenital abnormalities. After the ?rst week the main cause of death is infection.

Social conditions also play an important role in infant mortality. In England and Wales the infant mortality rate in 1930–32 was: Social Class I (professional), 32·7; Social Class III (skilled workers), 57·6; Social Class V (unskilled workers), 77·1. Many factors come into play in producing these social variations, but overcrowding is undoubtedly one of the most important.

1838–9 146 1950–52 30 1851–60 154 1960–62 22 1900–02 142 1970–72 18 1910–12 110 1980–82 12 1920–22 82 1990–92 7 1930–32 67 1996 6·2 1940–42 59 1999 5.8 2000 5.6

It is thus evident that for a reduction of the infant mortality rate to the minimum ?gure, the following conditions must be met. Mothers and potential mothers must be housed adequately in healthy surroundings, particularly with regard to safe water supplies and sewage disposal. The pregnant and nursing mother must be ensured an adequate diet. E?ective antenatal supervision must be available to every mother, as well as skilled supervision during labour (see PREGNANCY AND LABOUR). The newborn infant must be adequately nursed and fed and mothers encouraged to breast feed. Environmental and public-health measures must be taken to ensure adequate housing, a clean milk supply and full availability of medical care including such protective measures as IMMUNISATION against diphtheria, measles, poliomyelitis and whooping-cough. (See also PERINATAL MORTALITY.)... infant mortality rate (imr)

Pregnancy And Labour

Pregnancy The time when a woman carries a developing baby in her UTERUS. For the ?rst 12 weeks (the ?rst trimester) the baby is known as an EMBRYO, after which it is referred to as the FETUS.

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

P

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

Respiratory Therapy

The diagnostic evaluation, management and treatment of the care of older persons with deficiencies and abnormalities of the cardiopulmonary (heart lung) system.... respiratory therapy

Emblica Officinalis

Gaertn.

Synonym: Phyllanthus emblica Linn.

Family: Euphorbiaceae.

Habitat: Native to tropical Southeast Asia; distributed throughout India; also planted in public parks.

English: Emblic, Indian gooseberry.

Ayurvedic: Aaamalaki, Aaamalaka, Dhaatri, Kaayasthaa, Amoghaa, Amritaphala, Amla, Aaamalaa, Dhaatriphala, Vayasyaa, Vrshya, Shiva, Hattha.

Unani: Aamalaa, Amlaj.

Siddha/Tamil: Nellikkaai, Nelli.

Action: Fruit—antianaemic, anabolic, antiemetic, bechic, astringent, antihaemorrhagic, antidiarrhoeal, diuretic, antidiabetic, carminative, antioxidant. Used in jaundice, dyspepsia, bacillary dysentery, eye trouble and as a gastrointestinal tonic. Juice with turmeric powder and honey is prescribed in diabetes insipidus. Seed—antibilious, antiasthmatic. Used in bronchitis. Bark—astringent. Leaf—juice is given in vomiting.

A decoction of powdered pericarp is prescribed for paptic ulcer.

Key application: As an antacid. (Indian Herbal Pharmacopoeia.).

The fruit is an important source of vitamin C, minerals and amino acids. The edible fruit tissue contains protein concentration threefold and vitamin C (ascorbic acid) concentration 160-fold than those of apple. The fruit also contains considerably higher concentration of most minerals and amino acids than apple.

The fruit gave cytokinine-like substances identified as zeatin, zeatin ribo- side and zeatin nucleotide; suspension culture gave phyllembin. Phyllem- bin exhibits CNS depressant and spasmolytic activity, potentiates action of adrenaline and hypnotic action of Nembutal.

The leaves contain gallic acid (10.8 mg/g dry basis), besides ascorbic and music acid. The methanol extract of the leaves is found to be effective in rat paw inflammation.

The bark contains tannin identified as mixed type of proanthocyanidin.

The fruit contains superoxide dis- mutase 482.14 units/g fresh weight and exhibits antisenescent (anti-aging) activity. Fruit, juice, its sediment and residue are antioxidant due to gallic acid. EtOH (50%) extract—antiviral.

Aqueous extract of the fruit increases cardiac glycogen level and decreases serum GOT, GPT and LDH in rats having induced myocardial necrosis.

Preliminary evidence suggests that the fruit and its juice may lower serum cholesterol, LDL, triglycerides and phospholipids without affecting HDL levels and may have positive effect on atherosclerosis. (Eur J clin Nutr, 42, 1988, 939-944; PhytotherRes, 14, 2000, 592-595.)

An aqueous extract of the fruit has been reported to provide protection against radiation-induced chromosomal damage in both pre-and postirradiation treatment. The fruit is reported to enhance natural killer cell activity and antibody dependent cellular cytotoxicity in mice bearing Dalton's lymphoma ascites tumour. The extract of the fruit and ascorbic acid prevented hepatotoxic and nephrotoxic effects induced by lead and aluminium. The toxicity could be counteracted to a great extent by the fruit extract than by an amount of ascorbic acid alone equivalent to that contained in fruits. (The fruit can be used as a dietary supplement to counteract prolonged exposure to metals in population in industrial areas.)

The fruits are reported to activate trypsin (proteolytic enzyme) activity.

The fruits can be used as coagulant in the treatment of water and can purify low turbidity water.

The fruits can be consumed safely all round the year.

Dosage: Fresh fruit—10-20 g; pulp juice—5-10 ml. (API Vol. I.)... emblica officinalis

Intersexuality

Intersexuality is a state of indeterminate sexuality of an individual, and may present in many di?erent forms. A characteristic is that only one type of gonad – testis or ovary – is present; in a HERMAPHRODITE both types are present. Intersexuality may be due to a fault in the genetic mechanism of sex determination as early as conception, or to later errors in sexual di?erentiation of the embryo and fetus, or after birth. Some cases may result from abnormal metabolism of the sex hormones, or may be drug-induced (for example, women given androgens [see ANDROGEN] or PROGESTERONE for repeated miscarriages may give birth to girls with some genital VIRILISATION). Abnormalities of the sex chromosomes may be associated with delayed (or failure of) sexual development, so that the individual shows some of the characteristics (often underdeveloped) of both sexes. Some of the more common presentations of the condition include HYPOGONADISM, CRYPTORCHIDISM, and primary AMENORRHOEA.

Intersexuality inevitably leads to considerable psychological disturbance as the child grows up. It is therefore important to reach an early decision as to the child’s sex – or at least, the sex that he or she is to be brought up as. Surgical or hormonal means should then be employed, when appropriate, to develop the attributes of that sex and diminish those of the other, together with psychological counselling.... intersexuality

Teeth

Hard organs developed from the mucous membranes of the mouth and embedded in the jawbones, used to bite and grind food and to aid clarity of speech.

Structure Each tooth is composed of enamel, dentine, cement, pulp and periodontal membrane. ENAMEL is the almost translucent material which covers the crown of a tooth. It is the most highly calci?ed material in the body, 96–97 per cent being composed of calci?ed salts. It is arranged from millions of long, six-sided prisms set on end on the dentine (see below), and is thickest over the biting surface of the tooth. With increasing age or the ingestion of abrasive foods the teeth may be worn away on the surface, so that the dentine becomes visible. The outer sides of some teeth may be worn away by bad tooth-brushing technique. DENTINE is a dense yellowish-white material from which the bulk and the basic shape of a tooth are formed. It is like ivory and is harder than bone but softer than enamel. The crown of the tooth is covered by the hard protective enamel and the root is covered by a bone-like substance called cement. Decay can erode dentine faster than enamel (see TEETH, DISORDERS OF – Caries of the teeth). CEMENT or cementum is a thin bone-like material which covers the roots of teeth and helps hold them in the bone. Fibres of the periodontal membrane (see below) are embedded in the cement and the bone. When the gums recede, part of the cement may be exposed and the cells die. Once this has happened, the periodontal membrane can no longer be attached to the tooth and, if su?cient cement is destroyed, the tooth-support will be so weakened that the tooth will become loose. PULP This is the inner core of the tooth and is

composed of a highly vascular, delicate ?brous tissue with many ?ne nerve-?bres. The pulp is very sensitive to temperature variation and to touch. If the pulp becomes exposed it will become infected and usually cannot overcome this. Root-canal treatment or extraction of the tooth may be necessary. PERIODONTAL MEMBRANE This is a layer of ?brous tissue arranged in groups of ?bres which surround and support the root of a tooth in a bone socket. The ?bres are interspersed with blood vessels and nerves. Loss of the membrane leads to loss of the tooth. The membrane can release and re-attach the ?bres to allow the tooth to move when it erupts, or (to correct dental deformities) is being moved by orthodontic springs.

Arrangement and form Teeth are present in most mammals and nearly all have two sets: a temporary or milk set, followed by a permanent or adult set. In some animals, like the toothed whale, all the teeth are similar; but in humans there are four di?erent shapes: incisors, canines (eye-teeth), premolars (bicuspids), and molars. The incisors are chisel-shaped and the canine is pointed. Premolars have two cusps on the crown (one medial to the other) and molars have at least four cusps. They are arranged together in an arch in each jaw and the

cusps of opposing teeth interdigitate. Some herbivores have no upper anterior teeth but use a pad of gum instead. As each arch is symmetrical, the teeth in an upper and lower quadrant can be used to identify the animal. In humans, the quadrants are the same: in other words, in the child there are two incisors, one canine and two molars (total teeth 20); in the adult there are two incisors, one canine, two premolars and three molars (total 32). This mixture of tooth-form suggests that humans are omnivorous. Anatomically the crown of the tooth has mesial and distal surfaces which touch the tooth next to it. The mesial surface is the one nearer to the centre line and the distal is the further away. The biting surface is called the incisal edge for the anterior teeth and the occlusal surface for the posteriors.

Development The ?rst stage in the formation of the teeth is the appearance of a down-growth of EPITHELIUM into the underlying mesoderm. This is the dental lamina, and from it ten smaller swellings in each jaw appear. These become bell-shaped and enclose a part of the mesoderm, the cells of which become specialised and are called the dental papillae. The epithelial cells produce enamel and the dental papilla forms the dentine, cement and pulp. At a ?xed time the teeth start to erupt and a root is formed. Before the deciduous teeth erupt, the permanent teeth form, medial to them. In due course the deciduous roots resorb and the permanent teeth are then able to push the crowns out and erupt themselves. If this process is disturbed, the permanent teeth may be displaced and appear in an abnormal position or be impacted.

Eruption of teeth is in a de?nite order and at a ?xed time, although there may be a few months’ leeway in either direction which is of no signi?cance. Excessive delay is found in some congenital disorders such as CRETINISM. It may also be associated with local abnormalities of the jaws such as cysts, malformed teeth and supernumerary teeth.

The usual order of eruption of deciduous teeth is:

Middle incisors 6–8 months Lateral incisors 8–10 months First molars 12–16 months Canines (eye-teeth) 16–20 months Second molars 20–30 months

The usual order of eruption of permanent teeth is:

First molars 6–7 years Middle incisors 6–8 years Lateral incisors 7–9 years Canines 9–12 years First and second premolars 10–12 years Second molars 11–13 years Third molars (wisdom teeth) 17–21 years

The permanent teeth of the upper (top) and lower (bottom) jaws.

Teeth, Disorders of

Teething, or the process of eruption of the teeth in infants, may be accompanied by irritability, salivation and loss of sleep. The child will tend to rub or touch the painful area. Relief may be obtained in the child by allowing it to chew on a hard object such as a toy or rusk. Mild ANALGESICS may be given if the child is restless and wakens in the night. A serious pitfall is to assume that an infant’s symptoms of ill-health are due to teething, as the cause may be more serious. Fever and ?ts (see SEIZURE) are not due to teething.

Toothache is the pain felt when there is in?ammation of the pulp or periodontal membrane of a tooth (see TEETH – Structure). It can vary in intensity and may be recurring. The commonest cause is caries (see below) when the cavity is close to the pulp. Once the pulp has become infected, this is likely to spread from the apex of the tooth into the bone to form an abscess (gumboil – see below). A lesser but more long-lasting pain is felt when the dentine is unprotected. This can occur when the enamel is lost due to decay or trauma or because the gums have receded. This pain is often associated with temperature-change or sweet foods. Expert dental advice should be sought early, before the decay is extensive. If a large cavity is accessible, temporary relief may be obtained by inserting a small piece of cotton wool soaked, for example, in oil of cloves.

Alveolar abscess, dental abscess or gumboil This is an ABSCESS caused by an infected tooth. It may be present as a large swelling or cause trismus (inability to open the mouth). Treatment is drainage of the PUS, extraction of the tooth and/or ANTIBIOTICS.

Caries of the teeth or dental decay is very common in the more a?uent countries and is most common in children and young adults. Increasing awareness of the causes has resulted in a considerable improvement in dental health, particularly in recent years; this has coincided with a rise in general health. Now more than half of ?ve-year-old children are caries-free and of the others, 10 per cent have half of the remaining carious cavities. Since the start of the National Health Service, the emphasis has been on preventive dentistry, and now edentulous patients are mainly found among the elderly who had their teeth removed before 1948.

The cause of caries is probably acid produced by oral bacteria from dietary carbohydrates, particularly re?ned sugar, and this dissolves part of the enamel; the dentine is eroded more quickly as it is softer (see TEETH – Structure). The exposed smooth surfaces are usually protected as they are easily cleaned during normal eating and by brushing. Irregular and overcrowded teeth are more at risk from decay as they are di?cult to clean. Primitive people who chew coarse foods rarely get caries. Fluoride in the drinking water at about one part per million is associated with a reduction in the caries rate.

Prolonged severe disease in infancy is associated with poor calci?cation of the teeth, making them more vulnerable to decay. As the teeth are formed and partly calci?ed by the time of birth, the diet and health of the mother are also important to the teeth of the child. Pregnant mothers and children should have a good balanced diet with su?cient calcium and vitamin

D. A ?brous diet will also aid cleansing of the teeth and stimulate the circulation in the teeth and jaws. The caries rate can be reduced by regular brushing with a ?uoride toothpaste two or three times per day and certainly before going to sleep. The provision of sweet or sugary juices in an infant’s bottle should be avoided.

Irregularity of the permanent teeth may be due to an abnormality in the growth of the jaws or to the early or late loss of the deciduous set (see TEETH – Development). Most frequently it is due to an imbalance in the size of the teeth and the length of the jaws. Some improvement may take place with age, but many will require the help of an orthodontist (specialist dentist) who can correct many malocclusions by removing a few teeth to allow the others to be moved into a good position by means of springs and elastics on various appliances which are worn in the mouth.

Loosening of the teeth may be due to an accident or in?ammation of the GUM. Teeth loosened by trauma may be replaced and splinted in the socket, even if knocked right out. If the loosening is due to periodontal disease, the prognosis is less favourable.

Discoloration of the teeth may be intrinsic or extrinsic: in other words, the stain may be in the calci?ed structure or stuck on to it. Intrinsic staining may be due to JAUNDICE or the antibiotic tetracycline. Extrinsic stain may be due to tea, co?ee, tobacco, pan (a mixture of chuna and betel nuts wrapped in a leaf), iron-containing medicines or excess ?uoride.

Gingivitis or in?ammation of the gum may occur as an acute or chronic condition. In the acute form it is often part of a general infection of the mouth, and principally occurs in children or young adults – resolving after 10–14 days. The chronic form occurs later in life and tends to be progressive. Various microorganisms may be found on the lesions, including anaerobes. Antiseptic mouthwashes may help, and once the painful stage is past, the gums should be thoroughly cleaned and any calculus removed. In severe conditions an antibiotic may be required.

Periodontal disease is the spread of gingivitis (see above) to involve the periodontal membrane of the tooth; in its ?orid form it used to be called pyorrhoea. In this, the membrane becomes damaged by the in?ammatory process and a space or pocket is formed into which a probe can be easily passed. As the pocket becomes more extensive, the tooth loosens. The loss of the periodontal membrane also leads to the loss of supporting bone. Chronic in?ammation soon occurs and is di?cult to eradicate. Pain is not a feature of the disease but there is often an unpleasant odour (halitosis). The gums bleed easily and there may be DYSPEPSIA. Treatment is largely aimed at stabilising the condition rather than curing it.

Dental abscess is an infection that arises in or around a tooth and spreads to involve the bone. It may occur many years after a blow has killed the pulp of the tooth, or more quickly after caries has reached the pulp. At ?rst the pain may be mild and intermittent but eventually it will become severe and a swelling will develop in the gum over the apex of the tooth. A radiograph of the tooth will show a round clear area at the apex of the tooth. Treatment may be by painting the gum with a mild counter-irritant such as a tincture of aconite and iodine in the early stages, but later root-canal therapy or apicectomy may be required. If a swelling is present, it may need to be drained or the o?ending teeth extracted and antibiotics given.

Injuries to teeth are common. The more minor injuries include crazing and the loss of small chips of enamel, and the major ones include a broken root and avulsion of the entire tooth. A specialist dental opinion should be sought as soon as possible. A tooth that has been knocked out can be re-implanted if it is clean and replaced within a few hours. It will then require splinting in place for 4–6 weeks.

Prevention of dental disease As with other disorders, prevention is better than cure. Children should be taught at an early age to keep their teeth and gums clean and to avoid re?ned sugars between meals. It is better to ?nish a meal with a drink of water rather than a sweetened drink. Fluoride in some of its forms is useful in the reduction of dental caries; in some parts of the UK natural water contains ?uoride, and in some areas where ?uoride content is low, arti?cial ?uoridation of the water supply is carried out. Overcrowding of the teeth, obvious maldevelopment of the jaw and persistent thumbsucking into the teens are all indications for seeking the advice of an orthodontist. Generally, adults have less trouble with decay but more with periodontal disease and, as its onset is insidious, regular dental inspections are desirable.... teeth

Urination

The act of voiding URINE through the URETHRA. Abnormalities in urination such as di?culty in starting or stopping, greater than normal frequency, unusually small amounts of urine passed, a constant feeling of wanting to urinate or a sudden hard-to-control urge to urinate are all symptoms that suggest possible disorders of the urinary tract which merit investigation.... urination

Uterus, Diseases Of

Absence or defects of the uterus

Rarely, the UTERUS may be completely absent as a result of abnormal development. In such patients secondary sexual development is normal but MENSTRUATION is absent (primary amennorhoea). The chromosomal make-up of the patient must be checked (see CHROMOSOMES; GENES): in a few cases the genotype is male (testicular feminisation syndrome). No treatment is available, although the woman should be counselled.

The uterus develops as two halves which fuse together. If the fusion is incomplete, a uterine SEPTUM results. Such patients with a double uterus (uterus didelphys) may have fertility problems which can be corrected by surgical removal of the uterine septum. Very rarely there may be two uteri with a double vagina.

The uterus of most women points forwards (anteversion) and bends forwards (ante?exion). However, about 25 per cent of women have a uterus which is pointed backwards (retroversion) and bent backwards (retro?exion). This is a normal variant and very rarely gives rise to any problems. If it does, the attitude of the uterus can be corrected by an operation called a ventrosuspension.

Endometritis The lining of the uterine cavity is called the ENDOMETRIUM. It is this layer that is partially shed cyclically in women of reproductive age giving rise to menstruation. Infection of the endometrium is called endometritis and usually occurs after a pregnancy or in association with the use of an intrauterine contraceptive device (IUCD – see CONTRACEPTION). The symptoms are usually of pain, bleeding and a fever. Treatment is with antibiotics. Unless the FALLOPIAN TUBES are involved and damaged, subsequent fertility is unaffected. Very rarely, the infection is caused by TUBERCULOSIS. Tuberculous endometritis may destroy the endometrium causing permanent amenorrhoea and sterility.

Menstrual disorders are common. Heavy periods (menorrhagia) are often caused by ?broids (see below) or adenomyosis (see below) or by anovulatory cycles. Anovulatory cycles result in the endometrium being subjected to unopposed oestrogen stimulation and occasionally undergoing hyperplasia. Treatment is with cyclical progestogens (see PROGESTOGEN) initially. If this form of treatment fails, endoscopic surgery to remove the endometrium may be successful. The endometrium may be removed using LASER (endometrial laser ablation) or electrocautery (transcervical resection of endometrium). Hysterectomy (see below) will cure the problem if endoscopic surgery fails. Adenomyosis is a condition in which endometrial tissue is found in the muscle layer (myometrium) of the uterus. It usually presents as heavy and painful periods, and occasionally pain during intercourse. Hysterectomy is usually required.

Oligomenorhoea (scanty or infrequent periods) may be caused by a variety of conditions including thyroid disease (see THYROID GLAND, DISEASES OF). It is most commonly associated with usage of the combined oral contraceptive pill. Once serious causes have been eliminated, the patient should be reassured. No treatment is necessary unless conception is desired, in which case the patient may require induction of ovulation.

Primary amenorrhoea means that the patient has never had a period. She should be investigated, although usually it is only due to an inexplicable delay in the onset of periods (delayed menarche) and not to any serious condition. Secondary amenorrhoea is the cessation of periods after menstruation has started. The most common cause is pregnancy. It may be also caused by endocrinological or hormonal problems, tuberculous endometritis, emotional problems and severe weight loss. The treatment of amenorrhoea depends on the cause.

Dysmenorrhoea, or painful periods, is the most common disorder; in most cases the cause is unknown, although the disorder may be due to excessive production of PROSTAGLANDINS.

Irregular menstruation (variations from the woman’s normal menstrual pattern or changes in the duration of bleeding or the amount) can be the result of a disturbance in the balance of OESTROGENS and PROGESTERONE hormone which between them regulate the cycle. For some time after the MENARCHE or before the MENOPAUSE, menstruation may be irregular. If irregularity occurs in a woman whose periods are normally regular, it may be due to unsuspected pregnancy, early miscarriage or to disorders in the uterus, OVARIES or pelvic cavity. The woman should seek medical advice.

Fibroids (leiomyomata) are benign tumours arising from the smooth muscle layer (myometrium) of the uterus. They are found in 80 per cent of women but only a small percentage give rise to any problems and may then require treatment. They may cause heavy periods and occasionally pain. Sometimes they present as a mass arising from the pelvis with pressure symptoms from the bladder or rectum. Although they can be shrunk medically using gonadorelin analogues, which raise the plasma concentrations of LUTEINISING HORMONE and FOLLICLE-STIMULATING HORMONE, this is not a long-term solution. In any case, ?broids only require treatment if they are large or enlarging, or if they cause symptoms. Treatment is either myomectomy (surgical removal) if fertility is to be retained, or a hysterectomy.

Uterine cancers tend to present after the age of 40 with abnormal bleeding (intermenstrual or postmenopausal bleeding). They are usually endometrial carcinomas. Eighty per cent present with early (Stage I) disease. Patients with operable cancers should be treated with total abdominal hysterectomy and bilateral excision of the ovaries and Fallopian tubes. Post-operative RADIOTHERAPY is usually given to those patients with adverse prognostic factors. Pre-operative radiotherapy is still given by some centres, although this practice is now regarded as outdated. PROGESTOGEN treatment may be extremely e?ective in cases of recurrence, but its value remains unproven when used as adjuvant treatment. In 2003 in England and Wales, more than 2,353 women died of uterine cancer.

Disorders of the cervix The cervix (neck of the womb) may produce an excessive discharge due to the presence of a cervical ectopy or ectropion. In both instances columnar epithelium – the layer of secreting cells – which usually lines the cervical canal is exposed on its surface. Asymptomatic patients do not require treatment. If treatment is required, cryocautery – local freezing of tissue – is usually e?ective.

Cervical smears are taken and examined in the laboratory to detect abnormal cells shed from the cervix. Its main purpose is to detect cervical intraepithelial neoplasia (CIN) – the presence of malignant cells in the surface tissue lining the cervix – since up to 40 per cent of women with this condition will develop cervical cancer if the CIN is left untreated. Women with abnormal smears should undergo colposcopy, a painless investigation using a low-powered microscope to inspect the cervix. If CIN is found, treatment consists of simply removing the area of abnormal skin, either using a diathermy loop or laser instrument.

Unfortunately, cervical cancer remains the most common of gynaecological cancers. The most common type is squamous cell carcinoma and around 4,000 new cases (all types) are diagnosed in England and Wales every year. As many as 50 per cent of the women affected may die from the disease within ?ve years. Cervical cancer is staged clinically in four bands according to how far it has extended, and treatment is determined by this staging. Stage I involves only the mucosal lining of the cervix and cone BIOPSY may be the best treatment in young women wanting children. In Stage IV the disease has spread beyond the cervix, uterus and pelvis to the URINARY BLADDER or RECTUM. For most women, radiotherapy or radical Wertheim’s hysterectomy – the latter being preferable for younger women – is the treatment of choice if the cancer is diagnosed early, both resulting in survival rates of ?ve years in 80 per cent of patients. Wertheim’s hysterectomy is a major operation in which the uterus, cervix, upper third of vagina and the tissue surrounding the cervix are removed together with the LYMPH NODES draining the area. The ovaries may be retained if desired. Patients with cervical cancer are treated by radiotherapy, either because they present too late for surgery or because the surgical skill to perform a radical hysterectomy is not available. These operations are best performed by gynaecological oncologists who are gynaecological surgeons specialising in the treatment of gynaecological tumours. The role of CHEMOTHERAPY in cervical and uterine cancer is still being evaluated.

Prolapse of the uterus is a disorder in which the organ drops from its normal situation down into the vagina. First-degree prolapse is a slight displacement of the uterus, second-degree a partial displacement and third-degree when the uterus can be seen outside the VULVA. It may be accompanied by a CYSTOCOELE (the bladder bulges into the front wall of the vagina), urethrocoele (the urethra bulges into the vagina) and rectocoele (the rectal wall bulges into the rear wall of the vagina). Prolapse most commonly occurs in middle-aged women who have had children, but the condition is much less common now than in the past when prenatal and obstetric care was poor, women had more pregnancies and their general health was poor. Treatment is with pelvic exercises, surgical repair of the vagina or hysterectomy. If the woman does not want or is not ?t for surgery, an internal support called a pessary can be ?tted – and changed periodically.

Vertical section of female reproductive tract (viewed from front) showing sites of common gynaecological disorders.

Hysterectomy Many serious conditions of the uterus have traditionally been treated by hysterectomy, or removal of the uterus. It remains a common surgical operation in the UK, but is being superseded in the treatment of some conditions, such as persistent MENORRHAGIA, with endometrial ablation – removal of the lining of the uterus using minimally invasive techniques, usually using an ENDOSCOPE and laser. Hysterectomy is done to treat ?broids, cancer of the uterus and cervix, menorrhagia, ENDOMETRIOSIS and sometimes for severely prolapsed uterus. Total hysterectomy is the usual type of operation: it involves the removal of the uterus and cervix and sometimes the ovaries. After hysterectomy a woman no longer menstruates and cannot become pregnant. If the ovaries have been removed as well and the woman had not reached the menopause, hormone replacement therapy (HRT – see MENOPAUSE) should be considered. Counselling helps the woman to recover from the operation which can be an emotionally challenging event for many.... uterus, diseases of

Von Recklinghausen’s Disease

An inherited disease, now called neuro?bromatosis. About one case occurs every 3,000 live births. The disease is characterised by tumours along the course of nerves which can be felt beneath the skin. Soft tumours may also develop beneath the skin. The condition may have other associated abnormalities such as SCOLIOSIS, decalci?cation of the bones due to overactivity of the PARATHYROID glands, and ?brosis in the lungs. Surgery may be needed for cosmetic reasons or to relieve pressure on the nervous system.... von recklinghausen’s disease

Blood-clotting Tests

Tests to screen for and diagnose bleeding disorders, usually resulting from deficiencies or abnormalities of blood coagulation factors or of platelets (see blood clotting). Tests are also used to monitor treatment with anticoagulant drugs.... blood-clotting tests

Cervical Intraepithelial Neoplasia

Also known as , abnormalities in the cells of the cervix which may become cancerous.

The grading system is used to distinguish levels of change in the surface cells of the cervix in biopsy samples taken during colposcopy, a procedure usually performed following an abnormal cervical smear test.

Grades 1–3 broadly correspond to mild to severe cervical dysplasia in cells obtained from a smear.... cervical intraepithelial neoplasia

Intracytoplasmic Sperm Injection

Intracytoplasmic sperm injection (ICSI) is the most signi?cant therapeutic advance in male INFERTILITY treatment in the past 30 years. The technique is used when in vitro fertilisation (IVF – see under ASSISTED CONCEPTION) is not possible because the man has very few, motile, normal sperm (see SPERMATOZOON), or when previous attempts at IVF have not produced a fertilised EMBRYO. ICSI requires a single sperm which is injected directly into the cytoplasm of an egg previously retrieved from the woman. Once fertilised, the embryo is transferred to her UTERUS. For men with no sperm in the semen, it may be possible to retrieve sperm by needle aspiration of the EPIDIDYMIS under local anaesthetic (see ANAESTHESIA). Other techniques involve microsurgical retrieval from the epididymis or TESTICLE under a general anaesthetic. Potential complications include scrotal pain, bruising, HAEMATOMA formation and infection. ICSI and surgical sperm-retrieval require extensive training and expertise and is currently available in only a few selected

infertility units. Safety concerns relate to a higher-than-expected rate of abnormalities in the SEX CHROMOSOMES after ICSI, and also the potential risk of transmitting paternal genetic defects in the Y chromosome to sons born after ICSI.... intracytoplasmic sperm injection

Klinefelter’s Syndrome

The original syndrome described by Klinefelter consisted of GYNAECOMASTIA, testicular ATROPHY and INFERTILITY. Intelligence was unimpaired. Patients have been described who have associated mental defects and striking tallness of stature, but the only constant feature of the syndrome is testicular atrophy with resulting azoospermia and infertility.

The atrophy of the testis is the result of ?brosis, which begins to appear in childhood and progresses until all the seminiferous tubules are replaced by ?brous tissue. Gynaecomastia, mental retardation and eunuchoidism (see EUNUCH; loss of male secondary sexual characteristics – small penis, loss of body hair and a high-pitched voice) may be present. Most patients with Klinefelter’s syndrome have 47 chromosomes instead of the normal 46. The extra chromosome is an X chromosome, so that the sex chromosome constitution is XXY instead of XY. Klinefelter’s syndrome is one of the most common chromosome abnormalities and occurs in 1 in 300 of the male population. Patients with this syndrome show that the Y chromosome is strongly sex-determining: thus, a patient who has an XXY chromosome constitution may have the appearance of a normal male, with infertility the only incapacity, while the loss of a Y chromosome leads to the development of a bodily form which is essentially feminine (see TURNER’S SYNDROME).... klinefelter’s syndrome

Larynx, Disorders Of

Obstruction of the larynx is potentially dangerous in adults but can sometimes be life-threatening in infants and children. Stridor – noisy, di?cult breathing – is a symptom of obstruction. There are several causes, including congenital abnormalities of the larynx. Others are in?ammatory conditions such as acute laryngitis (see below), acute EPIGLOTTITIS and laryngo-tracheo-bronchitis (croup – see below); neurological abnormalities; trauma; and inhalation of foreign bodies.

Laryngitis In?ammation of the mucous membrane of the larynx and vocal chords may be acute or chronic. The cause is usually an infection, most commonly viral, although it may be the result of secondary bacterial infection, voice abuse or irritation by gases or chemicals. ACUTE LARYNGITIS may accompany any form of upper-respiratory-tract infection. The main symptom is hoarseness and often pain in the throat. The voice becomes husky or it may be lost. Cough, breathing diffculties and sometimes stridor may occur. Acute airway obstruction is unusual following laryngitis but may occasionally occur in infants (see laryngotracheo-bronchitis, below).

Treatment Vapour inhalations may be soothing and reduce swelling. Usually all that is needed is rest and analgesics such as paracetamol. Rarely, airway intervention – either ENDOTRACHEAL INTUBATION or TRACHEOSTOMY – may be necessary if severe airway obstruction develops (see APPENDIX 1: BASIC FIRST AID). A?ected patients should rest their voice and avoid smoking.

Chronic laryngitis can result from repeated attacks of acute laryngitis; excessive use of the voice – loud and prolonged, singing or shouting; tumours, which may be benign or malignant; or secondary to diseases such as TUBERCULOSIS and SYPHILIS.

Benign tumours or small nodules, such as singer’s nodules, may be surgically removed by direct laryngoscopy under general anaesthetic; while cancer of the larynx may be treated either by RADIOTHERAPY or by SURGERY, depending on the extent of the disease. Hoarseness may be the only symptom of vocal-chord disturbance or of laryngeal cancer: any case which has lasted for six weeks should be referred for a specialist opinion.

Laryngectomy clubs are being established

A laryngoscopic view of the interior of the larynx.

throughout the country to support patients following laryngectomy. Speech therapists provide speech rehabilitation.... larynx, disorders of

Clubbing

Thickening and broadening of the tips of the fingers and toes, usually with increased curving of the nails.

It is associated with chronic lung diseases, such as lung cancer, bronchiectasis, and fibrosing alveolitis; with certain heart abnormalities; and, occasionally, with Crohn’s disease and ulcerative colitis.... clubbing

Congenital

Present at birth. Congenital abnormalities (sometimes called birth defects) are either inherited or result from damage or infection occurring in the uterus or at the time of birth.... congenital

Cri Du Chat Syndrome

A rare, congenital condition of severe mental handicap, abnormal facial appearance, low birth weight, and short stature, which is characterized by a cat-like cry in infancy. The syndrome is caused by a chromosomal abnormality. There is no treatment. (See also genetic counselling.)... cri du chat syndrome

Cystometry

A procedure used to assess bladder function and to detect abnormalities of the nerves supplying the bladder or bladder muscle.

Cystometry is used to investigate urinary incontinence or poor bladder emptying caused by damage to bladder muscles or disrupted nerve control of these muscles.... cystometry

Cytology

The study of individual cells. Cytology’s main use in medicine is to detect abnormal cells. It is widely used to screen for cancer (as in the cervical smear test) or to confirm a diagnosis of cancer, and increasingly in antenatal screening for certain fetal abnormalities (using amniocentesis or chorionic villus sampling to obtain the sample of cells).

Examination of cells in a sample of fluid also helps to determine the cause of conditions such as pleural effusion and ascites.

Fine-needle aspiration biopsy of internal organs also involves cytology.... cytology

Learning Disability

Learning disability, previously called mental handicap, is a problem of markedly low intellectual functioning. In general, people with learning disability want to be seen as themselves, to learn new skills, to choose where to live, to have good health care, to have girlfriends or boyfriends, to make decisions about their lives, and to have enough money to live on. They may live at home with their families, or in small residential units with access to work and leisure and to other people in ordinary communities. Some people with learning disabilities, however, also have a MENTAL ILLNESS. Most can be treated as outpatients, but a few need more intensive inpatient treatment, and a very small minority with disturbed behaviour need secure (i.e. locked) settings.

In the United Kingdom, the 1993 Education Act refers to ‘learning diffculties’: generalised (severe or moderate), or speci?c (e.g. DYSLEXIA, dyspraxia [or APRAXIA], language disorder). The 1991 Social Security (Disability Living Allowance) Regulations use the term ‘severely mentally impaired’ if a person suffers from a state of arrested development or incomplete physical development of the brain which results in severe impairment of intelligence and social functioning. This is distinct from the consequences of DEMENTIA. Though ‘mental handicap’ is widely used, ‘learning disability’ is preferred by the Department of Health.

There is a distinction between impairment (a biological de?cit), disability (the functional consequence) and handicap (the social consequence).

People with profound learning disability are usually unable to communicate adequately and may be seriously movement-impaired. They are totally dependent on others for care and mobility. Those with moderate disability may achieve basic functional literacy (recognition of name, common signs) and numeracy (some understanding of money) but most have a life-long dependency for aspects of self-care (some fastenings for clothes, preparation of meals, menstrual hygiene, shaving) and need supervision for outdoor mobility.

Children with moderate learning disability develop at between half and three-quarters of the normal rate, and reach the standard of an average child of 8–11 years. They become independent for self-care and public transport unless they have associated disabilities. Most are capable of supervised or sheltered employment. Living independently and raising a family may be possible.

Occurrence Profound learning disability affects about 1 in 1,000; severe learning disability 3 in 1,000; and moderate learning disability requiring special service, 1 per cent. With improved health care, survival of people with profound or severe learning disability is increasing.

Causation Many children with profound or severe learning disability have a diagnosable biological brain disorder. Forty per cent have a chromosome disorder – see CHROMOSOMES (three quarters of whom have DOWN’S (DOWN) SYNDROME); a further 15 per cent have other genetic causes, brain malformations or recognisable syndromes. About 10 per cent suffered brain damage during pregnancy (e.g. from CYTOMEGALOVIRUS (CMV) infection) or from lack of oxygen during labour or delivery. A similar proportion suffer postnatal brain damage from head injury – accidental or otherwise – near-miss cot death or drowning, cardiac arrest, brain infection (ENCEPHALITIS or MENINGITIS), or in association with severe seizure disorders.

Explanations for moderate learning disability include Fragile X or other chromosome abnormalities in a tenth, neuro?bromatosis (see VON RECKLINGHAUSEN’S DISEASE), fetal alcohol syndrome and other causes of intra-uterine growth retardation. Genetic counselling should be considered for children with learning disability. Prenatal diagnosis is sometimes possible. In many children, especially those with mild or moderate disability, no known cause may be found.

Medical complications EPILEPSY affects 1 in 20 with moderate, 1 in 3 with severe and 2 in 3 with profound learning disability, although only 1 in 50 with Down’s syndrome is affected. One in 5 with severe or profound learning disability has CEREBRAL PALSY.

Psychological and psychiatric needs Over half of those with profound or severe – and many with moderate – learning disability show psychiatric or behavioural problems, especially in early years or adolescence. Symptoms may be atypical and hard to assess. Psychiatric disorders include autistic behaviour (see AUTISM) and SCHIZOPHRENIA. Emotional problems include anxiety, dependence and depression. Behavioural problems include tantrums, hyperactivity, self-injury, passivity, masturbation in public, and resistance to being shaved or helped with menstrual hygiene. There is greater vulnerability to abuse with its behavioural consequences.

Respite and care needs Respite care is arranged with link families for children or sta?ed family homes for adults where possible. Responsibility for care lies with social services departments which can advise also about bene?ts.

Education Special educational needs should be met in the least restrictive environment available to allow access to the national curriculum with appropriate modi?cation and support. For older children with learning disability, and for young children with severe or profound learning disability, this may be in a special day or boarding school. Other children can be provided for in mainstream schools with extra classroom support. The 1993 Education Act lays down stages of assessment and support up to a written statement of special educational needs with annual reviews.

Pupils with learning disability are entitled to remain at school until the age of 19, and most with severe or profound learning disability do so. Usually those with moderate learning disability move to further education after the age of 16.

Advice is available from the Mental Health Foundation, the British Institute of Learning Disabilities, MENCAP (Royal Society for Mentally Handicapped Children and Adults), and ENABLE (Scottish Society for the Mentally Handicapped).... learning disability

Dysplasia

Any abnormality of growth. The term applies to deformities in structures such as the skull and to abnormalities of single cells. Abnormal cell features include the size, shape, and rate of multiplication of cells.... dysplasia

Embolization

The deliberate obstruction of a blood vessel in order to stop

internal bleeding or to cut off the blood supply to a tumour. In the latter case, the technique can relieve pain; cause the tumour to shrivel, making surgical removal easier; or stop the tumour from spreading. Embolization can also be used to block flow through vascular abnormalities such as haemangiomas both in the skin and the internal organs. A catheter is introduced into a blood vessel near the one to be blocked and the embolus that will block the vessel is released through the catheter. Emboli are made of materials such as bloodclotting agents or silicone.... embolization

Lipid

A substance which is insoluble in water, but soluble in fat solvents such as alcohol and ether. The main lipid groups are the triglycerides, phospholipids, and glycolipids. They play an important role in nutrition, health (particularly in the functioning of the cell membranes, and the immune response), and disease (notably cardiovascular disease). There is a strong correlation between the concentration of CHOLESTEROL in the blood (transported as lipoproteins) and the risk of developing ATHEROMA and coronary heart disease (see HEART, DISEASES OF). Lipoproteins are classi?ed by their density and mobility, the chief groups being low-density (LDL) and high-density (HDL). High SERUM concentrations of LDL increase the risk of cardiovascular disease, while HDL is thought to protect the vessel wall by removing cholesterol, and has an inverse relationship to risk. The various serum lipid abnormalities have been classi?ed into ?ve groups, according to the cause and particular lipoprotein raised. Most important are type II (increased LDL, genetically determined) and type IV (increased VLDL, associated with obesity, diabetes, and excess alcohol). Various lipid-lowering drugs are available, but any drug treatment must be combined with a strict diet, reduction of blood pressure, and cessation of smoking.... lipid

Mammography

The special technique whereby X-rays are used to show the structure of the breast or any abnormalities in it (see BREASTS; BREASTS, DISEASES OF). It is an e?ective way of distinguishing benign from malignant tumours, and can detect tumours that are not palpable. In a multi-centre study in the USA, called the Breast Cancer Detection Demonstration Project and involving nearly 300,000 women in the 40–49 age group, 35 per cent of the tumours found were detected by mammography alone, 13 per cent by physical examination, and 50 per cent by both methods combined. The optimum frequency of screening is debatable: the American College of Radiologists recommends a baseline mammogram at the age of 40 years, with subsequent mammography at one- to two-year intervals up to the age of 50; thereafter, annual mammography is recommended. In the United Kingdom a less intensive screening programme is in place, with women over 50 being screened every three years. As breast cancer is the commonest malignancy in western women and is increasing in frequency, the importance of screening for this form of cancer is obvious.... mammography

Metoclopramide

This drug antagonises the actions of DOPAMINE. Given orally, intramuscularly, or intravenously, it is used to treat nausea and vomiting, particularly in gastrointestinal disorders, or when associated with cytotoxics or radiotherapy. It is useful in the early treatment of MIGRAINE.

Caution is indicated in prescribing metoclopramide for elderly and young patients, and whenever hepatic or renal impairment is present, and it should be avoided in pregnancy or cases of PORPHYRIAS. Adverse effects include extrapyramidal effects (see under EXTRAPYRAMIDAL SYSTEM) and HYPERPROLACTINAEMIA with occasional TARDIVE DYSKINESIA on prolonged administration. There have also been occasional reports of drowsiness, restlessness, diarrhoea, depression and neuroleptic malignant syndrome, with rare cardiac conduction abnormalities following intravenous administration.... metoclopramide

Mri

MRI, or magnetic resonance imaging, is a noninvasive method of imaging the body and its organs. It may also be used to study tissue metabolism. The body is placed in a magnetic ?eld which causes certain atomic nuclei to align in the direction of the ?eld. Pulses of radio-frequency radiation are then applied; interpretation of the frequencies absorbed and re-emitted allows an image in any body plane to be built up. Di?erent tissues – for example, fat and water – can be separately identi?ed and, if the resonance signal for the fat is suppressed, then only the signal from any abnormalities in the fat can be identi?ed. Many diseases result in a rise in the water content of tissues,so MRI is a valuable test for identifying disease, and the operating radiologist is skilled in interpreting the meaning of altered signals.... mri

Evoked Responses

The tracing of electrical activity in the brain in response to a specific external stimulus. The procedure is similar to that for an EEG.

The technique is used to check the functioning of various sensory systems (such as sight, hearing, or touch). The information obtained can be used to reveal abnormalities caused by inflammation, pressure from a tumour, or other disorders, and to help confirm a diagnosis of multiple sclerosis.... evoked responses

Fanconi’s Syndrome

A rare kidney disorder that occurs most commonly in childhood. Various important chemicals, such as amino acids, phosphate, calcium, and potassium, are lost in the urine, leading to failure to thrive, stunting of growth, and bone disorders such as rickets. Possible causes of the syndrome include several rare inherited abnormalities of body chemistry and an adverse reaction to certain drugs.

The child may resume normal growth if an underlying chemical abnormality can be corrected. Alternatively, a kidney transplant may be possible.... fanconi’s syndrome

Genitalia, Ambiguous

A group of conditions in which the external sex organs are not clearly male or female, or in which they appear to be those of the opposite chromosomal sex.

This may result from an abnormality of the sex chromosomes or a hormonal disorder (see hermaphroditism; sex determination; adrenal hyperplasia, congenital).... genitalia, ambiguous

Homocystinuria

A rare, inherited condition caused by an enzyme deficiency. Homocystinuria is a type of inborn error of metabolism (see metabolism, inborn errors of) in which there is an abnormal presence of homocystine (an amino acid) in the blood and urine. Affected people are very tall, with long limbs and fingers. Some have skeletal deformities and abnormalities of the eye lens. The condition is incurable but may be improved by a special diet.... homocystinuria

Neonatal Mortality

Neonatal mortality is the mortality of infants under one month of age. In England and Wales this has fallen markedly in recent decades: from more than 28 per 1,000 live births in 1939 to 3.6 in 2002. This improvement can be attributed to various factors: better antenatal supervision of expectant mothers; care to ensure that expectant mothers receive adequate nourishing food; improvements in the management of the complications of pregnancy and of labour; and more skilled resuscitation at birth for those who need it.

Nearly three-quarters of neonatal deaths occur during the ?rst week of life. For this reason, increasing emphasis is being laid on this initial period of life. In Britain, in the last four decades of the 20th century, the number of deaths in the ?rst week of life fell dramatically from 13.2 to just over 2.7 per 1,000 live births. The chief causes of deaths in this period are extreme prematurity (less than 28 weeks’ gestation), birth asphyxia with oxygen lack to the brain, and congenital abnormalities. After the ?rst week the commonest cause is infection.... neonatal mortality

Palate, Malformations Of

The commonest deformity of the PALATE is cleft palate, which is a result of faulty embryonic development in which the two sides of the palate fail to fuse or only fuse in part. If the cleft extends the full length with bilateral clefts at the front of the MAXILLA, it may be accompanied by a cleft lip (also called hare-lip) and disruption in the development of the front teeth. About 1 in 500 babies is born with a cleft lip and 1 in 1,000 has a cleft palate. If the parents are affected, the risk is three times that of the normal population; if one child has a deformity, the risk for a subsequent child is higher. Associated abnormalities include tongue tie, malpositioning of the MANDIBLE and ?uid in the middle EAR.

Cleft palate and hare-lip should be recti?ed by operation, because both are a serious drawback to feeding in early life – while later, harelip is a great dis?gurement, and the voice may be affected. The lip may be dealt with at any time from the neonatal period to a few weeks, depending on the individual surgeon’s view of when the best result is likely to be achieved. Prior to operation, special techniques may be necessary to ensure adequate feeding such as the use of special teats in formula-fed babies. The closure of a large cleft in the palate is a more formidable operation and is better performed when the face has grown somewhat, perhaps at 6–12 months. The operations performed vary greatly in details, but all consist in paring the edges of the gap and drawing the soft parts together across it.

Further operations may be required over the years to improve the appearance of the nose and lip, to make sure that teeth are even, and to improve speech.

Parents of such children can obtain help and advice from the Cleft Lip and Palate Association (CLAPA).... palate, malformations of

Paracetamol Poisoning

Paracetamol is one of the safest drugs when taken in the correct dosage, but overdose may occur inadvertently or deliberately. Initially there may be no symptoms or there may be nausea, vomiting, abdominal pain and pallor. Then, 16–24 hours after ingestion, liver damage becomes evident and by 72–120 hours the patient may have JAUNDICE, COAGULATION abnormalities, hepatic failure (see LIVER, DISEASES OF), renal failure (see KIDNEYS, DISEASES OF), ENCEPHALOPATHY and COMA. Treatment involves the administration of antidotes such as METHIONINE (within 8 hours) orally or intravenous ACETYLCYSTEINE.

An overdose of paracetamol is a common choice of those attempting to commit suicide. Since the government restricted the number of paracetamol tablets an individual may purchase over the counter, the incidence of people taking the drug in overdose with the intention of taking their lives has fallen sharply.... paracetamol poisoning

Parenteral Nutrition

In severely ill patients – especially those who have had major surgery or those with SEPSIS, burns, acute pancreatitis (see PANCREAS, DISORDERS OF) and renal failure – the body’s reserves of protein become exhausted. This results in weight loss; reduction in muscle mass; a fall in the serum albumin (see ALBUMINS) and LYMPHOCYTE count; and an impairment of cellular IMMUNITY. Severely ill patients are unable to take adequate food by mouth to repair the body protein loss so that enteral or parenteral nutrition is required. Enteral feeding is through the gastrointestinal tract with the aid of a nasogastric tube; parenteral nutrition involves the provision of carbohydrate, fat and proteins by intravenous administration.

The preferred route for the infusion of hyperosmolar solutions is via a central venous catheter (see CATHETERS). If parenteral nutrition is required for more than two weeks, it is advisable to use a long-term type of catheter such as the Broviac, Hickman or extra-corporeal type, which is made of silastic material and is inserted via a long subcutaneous tunnel; this not only helps to ?x the catheter but also minimises the risk of ascending infection.

Dextrose is considered the best source of carbohydrate and may be used as a 20 per cent or 50 per cent solution. AMINO ACIDS should be in the laevo form and should contain the correct proportion of essential (indispensable) and non-essential amino acids. Preparations are available with or without electrolytes and with or without fat emulsions.

The main hazards of intravenous feeding are blood-borne infections made possible by continued direct access to the circulation, and biochemical abnormalities related to the composition of the solutions infused. The continuous use of hypertonic solutions of glucose can cause HYPERGLYCAEMIA and glycosuria and the resultant POLYURIA may lead to dehydration. Treatment with INSULIN is needed when hyper-osmolality occurs, and in addition the water and sodium de?cits will require to be corrected.... parenteral nutrition

Hurler’s Syndrome

A rare, inherited condition caused by an enzyme defect. The syndrome is a type of inborn error of metabolism (see metabolism, inborn errors of) in which there is an abnormal accumulation of substances known as mucopolysaccharides in the tissues.

Affected children may appear normal at birth but, at 6–12 months of age, they develop cardiac abnormalities, umbilical hernia, skeletal deformities, and enlargement of the tongue, liver, and spleen.

Growth is limited and mental development slows.

If the condition is diagnosed in early infancy, a bone marrow transplant may be curative.... hurler’s syndrome

Infiltrate

Build-up of substances or cells within a tissue that are either not normally found in it or are usually present only in smaller amounts.

Infiltrate may refer to a drug (such as a local anaesthetic) that has been injected into a tissue, or to the build-up of a substance within an organ (for example, fat in the liver caused by excessive alcohol consumption).

Radiologists use the term to refer to the presence of abnormalities, most commonly on a chest X-ray, due to conditions such as infection.... infiltrate

Perinatal Mortality

Perinatal mortality consists of deaths of the FETUS after the 28th week of pregnancy and deaths of the newborn child during the ?rst week of life. Today, more individuals die within a few hours of birth than during the following 40 years. It is therefore not surprising that the perinatal mortality rate, which is the number of such deaths per 1,000 total births, is a valuable indicator of the quality of care provided for the mother and her newborn baby. In 2002, the perinatal mortality rate was 7.87 in the United Kingdom compared with 11.4 in 1982 – and over 30 in the early 1960s.

The causes of perinatal mortality include extreme prematurity, intrapartum anoxia (that is, di?culty in the birth of the baby, resulting in lack of oxygen), congenital abnormalities of the baby, and antepartum anoxia (that is, conditions in the terminal stages of pregnancy preventing the fetus from getting su?cient oxygen).

The most common cause of perinatal death is some complication of placenta, cord or membranes. The next most common is congenital abnormality. Intrauterine hypoxia and birth asphyxia comprise the third most common cause.... perinatal mortality

Perspiration

Commonly called sweat, it is an excretion from the SKIN, produced by microscopic sweat-glands, of which there are around 2·5 million, scattered over the surface. There are two di?erent types of sweat-glands, known as eccrine and apocrine. Insensible (that is unnoticed) perspiration takes place constantly by evaporation from the openings of the sweat-glands, well over a litre a day being produced. Sensible perspiration (that is, obvious) – to which the term ‘sweat’ is usually con?ned – occurs with physical exertion and raised body temperature: up to 3 litres an hour may be produced for short periods. Normal sweating maintains the body within its customary temperature range and ensures that the skin is kept adequately hydrated – for example, properly hydrated skin of the palm helps the e?ectiveness of a person’s normal grip.

The chief object of perspiration is to maintain an even body temperature by regulating the heat lost from the body surface. Sweating is therefore increased by internally produced heat, such as muscular activity, or external heat. It is controlled by two types of nerves: vasomotor, which regulate the local blood ?ow, and secretory (part of the sympathetic nervous system) which directly in?uence secretion.

Eccrine sweat is a faintly acid, watery ?uid containing less than 2 per cent of solids. The eccrine sweat-glands in humans are situated in greatest numbers on the soles of the feet and palms of the hands, and with a magnifying glass their minute openings or pores can be seen in rows occupying the summit of each ridge in the skin. Perspiration is most abundant in these regions, although it also occurs all over the body.

Apocrine sweat-glands These start functioning at puberty and are found in the armpits, the eyelids, around the anus in association with the external genitalia, and in the areola and nipple of the breast. (The glands that produce wax in the ear are modi?ed apocrine glands.) The ?ow of apocrine sweat is evoked by emotional stimuli such as fear, anger, or sexual excitement.

Abnormalities of perspiration Decreased sweating may occur in the early stages of fever, in diabetes, and in some forms of glomerulonephritis (see KIDNEYS, DISEASES OF). Some people are unable to sweat copiously, and are prone to HEAT STROKE. EXCESSIVE SWEATING, OR HYPERIDROSIS, may be caused by fever, hyperthyroidism (see THYROID GLAND, DISEASES OF), obesity, diabetes mellitus, or an anxiety state. O?ensive perspiration, or bromidrosis, commonly occurs on the hands and feet or in the armpits, and is due to bacterial decomposition of skin secretions. A few people, however, sweat over their whole body surface. For most of those affected, it is the palmar and/or axillary hyperhidrosis that is the major problem.

Conventional treatment is with an ANTICHOLINERGIC drug. This blocks the action of ACETYLCHOLINE (a neurotransmitter secreted by nerve-cell endings) which relaxes some involuntary muscles and tightens others, controlling the action of sweat-glands. But patients often stop treatment because they get an uncomfortably dry mouth. Aluminium chloride hexahydrate is a topical treatment, but this can cause skin irritation and soreness. Such antiperspirants may help patients with moderate hyperhidrosis, but those severely affected may need either surgery or injections of BOTULINUM TOXIN to destroy the relevant sympathetic nerves to the zones of excessive sweating.... perspiration

Prenatal Screening Or Diagnosis

Prenatal screening of fetal abnormalities may be the result of screening tests carried out on most or all pregnant women, or as the result of speci?c diagnostic tests performed to detect speci?c conditions. Prenatal diagnosis is important as it will identify babies who might need medical or surgical treatment before or soon after birth. In addition, it may also detect severe abnormalities for which parents might decide to have a therapeutic ABORTION.

ULTRASOUND scanning is probably the most widely used diagnostic tool in obstetric practice. It can detect structural abnormalities such as SPINA BIFIDA and CLEFT PALATE and even cardiac and renal problems. A series of scans can assess whether the baby is growing at a normal rate; ultrasound may also be used to assist with other diagnostic tests (e.g. AMNIOCENTESIS – see below).

Tests on the mother’s blood can also diagnose fetal abnormalities. Alphafetoprotein (AFP) is produced by babies and ‘leaks’ into the AMNIOTIC FLUID and is absorbed by the mother. In spina bi?da and other neural-tube defects there is increased leakage of AFP, and a blood test at 16 weeks’ gestation can detect a raised level which suggests the presence of these abnormalities.

The triple test, also performed at 16 weeks, measures AFP and two hormones – HUMAN CHORIONIC GONADOTROPHIN and unconjugated OESTRADIOL – and is used in diagnosing DOWN’S (DOWN) SYNDROME.

Amniocentesis involves inserting a needle through the mother’s abdominal wall into the uterus to remove a sample of amniotic ?uid at 16–18 weeks. Examination of the ?uid and the cells it contains is used in the diagnosis of Down’s syndrome and other inherited disorders. The test carries a small risk of miscarriage.

Chorionic villus sampling may be used to diagnose various inherited conditions. A small amount of tissue from the developing PLACENTA is removed for analysis: this test has the advantages of having a lower incidence of miscarriage than amniocentesis and is carried out at an earlier stage (9–13 weeks).

Analysis of a blood sample removed from the umbilical cord (cordocentesis) may diagnose infections in the uterus, blood disorders or inherited conditions.

Direct observation of the fetus via a viewing instrument called a fetoscope is also used diagnostically and will detect structural abnormalities.

Most tests have a recognised incidence of false positive and negative results and are therefore usually cross-checked with another test. Counselling of the parents about prenatal tests is important. This allows them to make an informed choice which may not necessarily involve terminating the pregnancy if an abnormality is found. (See PREGNANCY AND LABOUR.)... prenatal screening or diagnosis

Pneumonia

Pneumonia is an in?ammation of the lung tissue (see LUNGS) caused by infection. It can occur without underlying lung or general disease, or in patients with an underlying condition that makes them susceptible.

Pneumonia with no predisposing cause – community-acquired pneumonia – is caused most often by Streptococcus pneumoniae (PNEUMOCOCCUS). The other most common causes are viruses, Mycoplasma pneumoniae and Legionella species (Legionnaire’s disease). Another cause, Chlamydia psittaci, may be associated with exposure to perching birds.

In patients with underlying lung disease, such as CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) or BRONCHIECTASIS as in CYSTIC FIBROSIS, other organisms such as Haemophilus in?uenzae, Klebsiella, Escherichia coli and Pseudomonas aeruginosa are more prominent. In patients in hospital with severe underlying disease, pneumonia, often caused by gram-negative bacteria (see GRAM’S STAIN), is commonly the terminal event.

In patients with an immune system suppressed by pregnancy and labour, infection with HIV, CHEMOTHERAPY or immunosuppressive drugs after organ transplantation, a wider range of opportunistic organisms needs to be considered. Some of these organisms such as CYTOMEGALOVIRUS (CMV) or the fungus Pneumocystis carinii rarely cause disease in immunocompetent individuals – those whose body’s immune (defence) system is e?ective.

TUBERCULOSIS is another cause of pneumonia, although the pattern of lung involvement and the more chronic course usually di?erentiate it from other causes of pneumonia.

Symptoms The common symptoms of pneumonia are cough, fever (sometimes with RIGOR), pleuritic chest pain (see PLEURISY) and shortness of breath. SPUTUM may not be present at ?rst but later may be purulent or reddish (rusty).

Examination of the chest may show the typical signs of consolidation of an area of lung. The solid lung in which the alveoli are ?lled with in?ammatory exudate is dull to percussion but transmits sounds better than air-containing lung, giving rise to the signs of bronchial breathing and increased conduction of voice sounds to the stethoscope or palpating hand.

The chest X-ray in pneumonia shows opacities corresponding to the consolidated lung. This may have a lobar distribution ?tting with limitation to one area of the lung, or have a less con?uent scattered distribution in bronchopneumonia. Blood tests usually show a raised white cell (LEUCOCYTES) count. The organism responsible for the pneumonia can often be identi?ed from culture of the sputum or the blood, or from blood tests for the speci?c ANTIBODIES produced in response to the infection.

Treatment The treatment of pneumonia involves appropriate antibiotics together with oxygen, pain relief and management of any complications that may arise. When treatment is started, the causative organism has often not been identi?ed so that the antibiotic choice is made on the basis of the clinical features, prevalent organisms and their sensitivities. In severe cases of community-acquired pneumonia (see above), this will often be a PENICILLIN or one of the CEPHALOSPORINS to cover Strep. pneumoniae together with a macrolide such as ERYTHROMYCIN. Pleuritic pain will need analgesia to allow deep breathing and coughing; oxygen may be needed as judged by the oxygen saturation or blood gas measurement.

Possible complications of pneumonia are local changes such as lung abscess, pleural e?usion or EMPYEMA and general problems such as cardiovascular collapse and abnormalities of kidney or liver function. Appropriate treatment should result in complete resolution of the lung changes but some FIBROSIS in the lung may remain. Pneumonia can be a severe illness in previously ?t people and it may take some months to return to full ?tness.... pneumonia

Respiratory Distress Syndrome

This may occur in adults as ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS), or in newborn children, when it is also known as HYALINE MEMBRANE DISEASE. The adult syndrome consists of PULMONARY OEDEMA of non-cardiac origin. The process begins when tissue damage stimulates the autonomic nervous system, releases vasoactive substances, precipitates complement activation, and produces abnormalities of the clotting cascade – the serial process that leads to clotting of the blood (see COAGULATION). The activation of complement causes white cells to lodge in the pulmonary capillaries where they release substances which damage the pulmonary endothelium.

Respiratory distress syndrome is a complication of SHOCK, systemic SEPSIS and viral respiratory infections. It was ?rst described in 1967, and – despite advances with assisted ventilation

– remains a serious disease with a mortality of more than 50 per cent. The maintenance of adequate circulating blood volume, peripheral PERFUSION, acid-base balance and arterial oxygenation is important, and assisted ventilation should be instituted early.

In newborns the mechanism is diferent, being provoked by an inability of the lungs to manufacture SURFACTANT.... respiratory distress syndrome

Intersex

A group of abnormalities in which the affected person has ambiguous genitalia (abnormal external sex organs) or external genitalia that have the opposite appearance to the chromosomal sex of the individual (see sex determination).... intersex

Liver Imaging

Techniques that produce images of the liver, gallbladder, bile ducts, and blood vessels supplying the liver, to aid the detection of disease.

Ultrasound scanning, CT scanning, and MRI are commonly used.

Radionuclide scanning may reveal cysts and tumours and show bile excretion.

X–ray techniques include cholangiography, cholecystography, and ERCP (endoscopic retrograde cholangiopancreatography).

In these procedures, a contrast medium, which is opaque to X-rays, is introduced to show abnormalities in the biliary system.

Angiography reveals the blood vessels in the liver.... liver imaging

Lymphangiography

A diagnostic procedure that involves injecting a contrast medium into lymph vessels (see lymphatic system) so that these vessels and lymph nodes, and any abnormalities, can be seen on X-ray film. Lymphangiography has largely been superseded by CT scanning and MRI.... lymphangiography

Rheumatic Fever

An acute febrile illness, usually seen in children, which may include ARTHRALGIA, ARTHRITIS, CHOREA, carditis (see below) and rash (see ERUPTION). The illness has been shown to follow a beta-haemolytic streptococcal infection (see STREPTOCOCCUS).

Rheumatic fever is now extremely uncommon in developed countries, but remains common in developing areas. Diagnosis is based on the presence of two or more major manifestations – endocarditis (see under HEART, DISEASES OF), POLYARTHRITIS, chorea, ERYTHEMA marginatum, subcutaneous nodules – or one major and two or more minor ones – fever, arthralgia, previous attacks, raised ESR, raised white blood cell count, and ELECTROCARDIOGRAM (ECG) changes. Evidence of previous infection with streptococcus is also a criterion.

Clinical features Fever is high, with attacks of shivering or rigor. Joint pain and swelling (arthralgia) may affect the knee, ankle, wrist or shoulder and may migrate from one joint to another. TACHYCARDIA may indicate cardiac involvement. Subcutaneous nodules may occur, particularly over the back of the wrist or over the elbow or knee. Erythema marginatum is a red rash, looking like the outline of a map, characteristic of the condition.

Cardiac involvement includes PERICARDITIS, ENDOCARDITIS, and MYOCARDITIS. The main long-term complication is damage to the mitral and aortic valves (see HEART).

The chief neurological problem is chorea (St Vitus’s dance) which may develop after the acute symptoms have subsided.

Chronic rheumatic heart disease occurs subsequently in at least half of those who have had rheumatic fever with carditis. The heart valve usually involved is the mitral; less commonly the aortic, tricuspid and pulmonary. The lesions may take 10–20 years to develop in developed countries but sooner elsewhere. The heart valves progressively ?brose and ?brosis may also develop in the myocardium and pericardium. The outcome is either mitral stenosis or mitral regurgitation and the subsequent malfunction of this or other heart valves affected is chronic failure in the functioning of the heart. (see HEART, DISEASES OF).

Treatment Eradication of streptococcal infection is essential. Other features are treated symptomatically. PARACETAMOL may be preferred to ASPIRIN as an antipyretic in young children. One of the NON-STEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDS) may bene?t the joint symptoms. CORTICOSTEROIDS may be indicated for more serious complications.

Patients who have developed cardiac-valve abnormalities require antibiotic prophylaxis during dental treatment and other procedures where bacteria may enter the bloodstream. Secondary cardiac problems may occur several decades later and require replacement of affected heart valves.... rheumatic fever

Marfan’s Syndrome

A rare genetic disorder of connective tissue (material that holds body structures together) that results in skeletal, heart, and eye abnormalities. Features of Marfan’s syndrome usually appear after age 10. Affected people are very tall and thin, with long, spidery fingers and weak ligaments and tendons. The chest and spine are often deformed and the lens of the eye may be dislocated. The heart or aorta is often abnormal.... marfan’s syndrome

Mitochondrial Dna

Mitochondria have their own DNA. In human mitochondria, the is a double-helical circle that codes for 13 proteins. Mitochondria have a distinctive genetic code, and their genomes are not changed by meiosis during reproduction, making the useful in genetic studies.

The significance of mitochondria having their own is that diseases can be inherited via abnormalities of mitochondrial , and inheritance of the is maternal, directly from the egg.... mitochondrial dna

Myocarditis

Inflammation of the heart muscle, usually due to infection by the coxsackievirus. Myocarditis is a characteristic feature of rheumatic fever.

There are often no symptoms. Rarely, there may be a serious disturbance of the heartbeat, breathlessness, chest pain, and heart failure. In severe cases, death may result from cardiac arrest.Myocarditis may be suspected from the patient’s history and from a physical examination. An ECG will show characteristic abnormalities of the heartbeat. Diagnosis also involves echocardiography and blood tests.

There is no specific treatment.

Bed rest is usually recommended and corticosteroid drugs may be prescribed.... myocarditis

Sex Chromosomes

In humans there are 23 pairs of CHROMOSOMES. Male and female di?er in respect of one pair. In the nucleus of female cells, the two members of the pair are identical and are called X chromosomes. In the male nucleus there is one X chromosome paired with a dissimilar, di?erently sized chromosome called the Y chromosome. In the sex cells, after MEIOSIS, all cells in the female contain a single X chromosome. In the male, half will contain an X chromosome and half a Y chromosome. If a sperm with an X chromosome fertilises an ovum (which, as stated, must have an X chromosome) the o?spring will be female; if a sperm with a Y chromosome fertilises the ovum the o?spring will be male. It is the sex chromosomes which determine the sex of an individual.

Sometimes during cell division chromosomes may be lost or duplicated, or abnormalities in the structure of individual chromosomes may occur. The surprising fact is the infrequency of such errors. About one in 200 live-born babies has an abnormality of development caused by a chromosome, and two-thirds of these involve the sex chromosomes. There is little doubt that the frequency of these abnormalities in the early embryo is much higher, but because of the serious nature of the defect, early spontaneous ABORTION occurs.

Chromosome studies on such early abortions show that half have chromosome abnormalities, with errors of autosomes being three times as common as sex chromosome anomalies. Two of the most common abnormalities in such fetuses are triploidy with 69 chromosomes and trisomy of chromosome 16. These two anomalies almost always cause spontaneous abortion. Abnormalities of chromosome structure may arise because of:

Deletion Where a segment of a chromosome is lost.

Inversion Where a segment of a chromosome becomes detached and re-attached the other way around. GENES will then appear in the wrong order and thus will not correspond with their opposite numbers on homologous chromosomes.

Duplication Where a segment of a chromosome is included twice over. One chromosome will have too little nuclear material and one too much. The individual inheriting too little may be non-viable and the one with too much may be abnormal.

Translocation Where chromosomes of different pairs exchange segments.

Errors in division of centromere Sometimes the centromere divides transversely instead of longitudinally. If the centromere is not central, one of the daughter chromosomes will arise from the two short arms of the parent chromosome and the other from the two long arms. These abnormal daughter chromosomes are called isochromosomes.

These changes have important bearings on heredity, as the e?ect of a gene depends not only upon its nature but also upon its position on the chromosome with reference to other genes. Genes do not act in isolation but against the background of other genes. Each gene normally has its own position on the chromosome, and this corresponds precisely with the positon of its allele on the homologous chromosome of the pair. Each member of a pair of chromosomes will normally carry precisely the same number of genes in exactly the same order. Characteristic clinical syndromes, due to abnormalities of chromosome structure, are less constant than those due to loss or gain of a complete chromosome. This is because the degree of deletion, inversion and duplication is inconstant. However, translocation between chromosomes 15 and 21 of the parent is associated with a familial form of mongolism (see DOWN’S (DOWN) SYNDROME) in the o?spring, and deletion of part of an X chromosome may result in TURNER’S SYNDROME.

Non-disjunction Whilst alterations in the structure of chromosomes arise as a result of deletion or translocation, alterations in the number of chromosomes usually arise as a result of non-disjunction occurring during maturation of the parental gametes (germ cells). The two chromosomes of each pair (homologous chromosomes) may fail to come together at the beginning of meiosis and continue to lie free. If one chromosome then passes to each pole of the spindle, normal gametes may result; but if both chromosomes pass to one pole and neither to the other, two kinds of abnormal gametes will be produced. One kind of gamete will contain both chromosomes of the pair, and the other gamete will contain neither. Whilst this results in serious disease when the autosomes are involved, the loss or gain of sex chromosomes seems to be well tolerated. The loss of an autosome is incompatible with life and the malformation produced by a gain of an autosome is proportional to the size of the extra chromosome carried.

Only a few instances of a gain of an autosome are known. An additional chromosome 21 (one of the smallest autosomes) results in mongolism, and trisomy of chromosome 13 and 18 is associated with severe mental, skeletal and congenital cardiac defects. Diseases resulting from a gain of a sex chromosome are not as severe. A normal ovum contains 22 autosomes and an X sex chromosome. A normal sperm contains 22 autosomes and either an X or a Y sex chromosome. Thus, as a result of nondisjunction of the X chromosome at the ?rst meiotic division during the formation of female gametes, the ovum may contain two X chromosomes or none at all, whilst in the male the sperm may contain both X and Y chromosomes (XY) or none at all. (See also CHROMOSOMES; GENES.)... sex chromosomes

Neurocutaneous Disorders

A group of conditions characterized by abnormalities of the skin and of the nerves and/or the central nervous system.

The best known of these neurocutaneous disorders is neurofibromatosis, in which there are brown patches on the skin and numerous fibrous nodules on the skin and nerves. Another example is tuberous sclerosis, which is characterized by small skin-coloured swellings over the cheeks and nose, mental deficiency, and epilepsy.... neurocutaneous disorders

Nickel

A metallic element that is present in the body in minute amounts. Nickel is thought to activate certain enzymes (substances that promote biochemical reactions), and it may also play a part in stabilizing chromosomal material in the nuclei of cells.

Exposure to nickel may cause dermatitis (inflammation of the skin). Lung cancer has been reported in workers in nickel refineries.... nickel

Nuchal Thickness Scan

Ultrasound scanning performed in early pregnancy in order to identify fetuses at high risk of chromosomal abnormalities such as Down’s syndrome. The scan investigates the nuchal fold, an area of skin at the back of the neck. Excessive thickness of the skin is an indicator of possible chromosomal abnormalities.... nuchal thickness scan

Oncogenes

Genes found in every cell that control growth, repair, and replacement.

Abnormalities of oncogenes are known to be a factor in the development of cancerous cells.

Mutations in oncogenes, resulting from damage by carcinogens, can cause a cell to grow unrestrainedly and infiltrate and destroy normal tissues (see cancer).

Factors known to cause cancer include ultraviolet light, radioactivity, tobacco, alcohol, asbestos, some chemicals, and certain viruses.... oncogenes

Spina Bifida

This is one of the most common of the congenital (present at birth) malformations. It is one of the three types of neural-tube anomaly, the other two being ANENCEPHALY and cranium bi?dum. It takes two main forms – spina bi?da occulta being much the commoner. There is a de?cit in the posterior part of the SPINAL COLUMN, usually in the LUMBAR region, and it is generally asymptomatic unless the underlying spinal cord is affected. Occasionally it is associated with a hairy patch or birthmark on the back, and a few children develop a mild spastic gait or bladder problems.

Much more serious is spina bi?da cystica, in which the spinal-wall defect is accompanied by a protrusion of the spinal cord. This may take two forms: a meningocele, in which the MENINGES, containing CEREBROSPINAL FLUID, protrude through the defect; and a meningomyelocele, in which the protrusion contains spinal cord and nerves.

Meningocele is less common and has a good prognosis. HYDROCEPHALUS and neurological problems affecting the legs are rare, although the bladder may be affected. Treatment consists of surgery which may be in the ?rst few days of life or much later depending upon the precise situation; long-term follow-up is necessary to pick up any neurological problems that may develop during subsequent growth of the spine.

Meningomyelocele is much more serious and more common, accounting for 90 per cent of all cases. Usually affecting the lumbo-sacral region, the range of severity may vary considerably and, while early surgery with careful attention in a minor case may achieve good mobility, normal bladder function and intellect, a more extensive protrusion may cause complete ANAESTHESIA of the skin, with increased risk of trauma; extensive paralysis of the trunk and limbs, with severe deformities; and paralysis and insensitivity of the bladder and bowel. Involuntary movements may be present, and hydrocephalus occurs in 80 per cent of cases. The decision to operate can only be made after a full examination of the infant to determine the extent of the defect and any co-existent congenital abnormalities. The child’s potential can then be estimated, and appropriate treatment discussed with the parents. Carefully selected patients should receive long-term treatment in a special centre, where full attention can be paid to all their various problems.

There is growing evidence of the value of vitamin supplements before and during pregnancy in reducing the incidence of spina bi?da. Parents of affected infants may obtain help, advice, and encouragement from the Association for Spina Bi?da and Hydrocephalus which has branches throughout the country, or the Scottish Spina Bi?da Association.... spina bifida

Strongyloidiasis

This infection is caused by nematode worms of the genus Strongyloides spp. – the great majority being from S. stercoralis. This helminth is present throughout most tropical and subtropical countries; a single case report has been made in England – about an individual who had not been exposed to such an environment. Larvae usually penetrate intact skin, especially the feet (as with hookworm infection). Unlike hookworm infection, eggs mature and hatch in the lower gastrointestinal tract; thus larvae can immediately re-enter the circulation in the colo-rectum or perianal region, setting up an auto-infection cycle. Therefore, infection can continue for the remaining lifespan of the individual. Severe malnutrition may be a predisposing factor to infection, as was the case in prisoners of war in south-east Asia during World War II.

Whilst an infected patient is frequently asymptomatic, heavy infection can cause jejunal mucosal abnormalities, and an absorptive defect, with weight loss. During the migratory phase an itchy linear rash (larva currens) may be present on the lower abdomen, buttocks, and groins; this gives rise to recurrent transient itching. In an immunosuppressed individual, the ‘hyperinfection syndrome’ may ensue; migratory larvae invade all organs and tissues, including the lungs and brain. Associated with this widespread infection, the patient may develop an Enterobacteriacae spp. SEPTICAEMIA; this, together with S. stercoralis larvae, produces a MENINGOENCEPHALITIS. There is no evidence that this syndrome is more common in patients with HIV infection.

Diagnosis consists of visualisation of S. stercoralis (larvae or adults) in a jejunal biopsy-section or aspirate. Larvae may also be demonstrable in a faecal sample, especially following culture. Eosinophilia may be present in peripheral blood, during the invasive stage of infection. Chemotherapy consists of albendazole. The formerly used benzimidazole compound, thiabendazole, is now rarely prescribed in an uncomplicated infection due to unpleasant side-effects; even so, in the ‘hyperinfection syndrome’ it probably remains the more e?ective of the two compounds.... strongyloidiasis

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