Gene therapy is currently used to treat disorders caused by a fault in a single recessive gene, when the defect can remedied by introducing a normal ALLELE. Treating disorders caused by dominant genes is more complicated. CYSTIC FIBROSIS is an example of a disease caused by a recessive gene, and clinical trials are taking place on the e?ectiveness of using LIPOSOMES to introduce the normal gene into the lungs of someone with the disorder. Trials are also underway to test the e?ectiveness of introducing tumour-suppressing genes into cancer cells to check their spread.
Gene therapy was ?rst used in 1990 to treat an American patient. Eleven European medical research councils (including the UK’s) recommended in 1988 that gene therapy should be restricted to correcting disease or defects, and that it should be limited to somatic cells. Interventions in germ-line cells (the sperm and egg) to e?ect changes that would be inherited, though technically feasible, is not allowed (see CLONING; HUMAN GENOME).... gene therapy
Checking a hormone pro?le in the woman’s blood will help in the diagnosis of ovulatory disorders like polycystic ovaries, an early menopause, anorexia or other endocrine illnesses. Ovulation itself is best assessed by ultrasound scan at mid-cycle or by a blood hormone progesterone level in the second half of the cycle.
The FALLOPIAN TUBES may be damaged or blocked in 20–30 per cent of infertile women. This is usually caused by previous pelvic infection or ENDOMETRIOSIS, where menstrual blood is thought to ?ow backwards through the fallopian tubes into the pelvis and seed with cells from the lining of the uterus in the pelvis. This process often leads to scarring of the pelvic tissues; 5–10 per cent of infertility is associated with endometriosis.
To assess the Fallopian tubes adequately a procedure called LAPAROSCOPY is performed. An ENDOSCOPE is inserted through the umbilicus and at the same time a dye is pushed through the tubes to assess their patency. The procedure is performed under a general anaesthetic.
In a few cases the mucus around the cervix may be hostile to the partner’s sperm and therefore prevent fertilisation.
Defective production is responsible for up to a quarter of infertility. It may result from the failure of the testes (see TESTICLE) to descend in early life, from infections of the testes or previous surgery for testicular torsion. The semen is analysed to assess the numbers of sperm and their motility and to check for abnormal forms.
In a few cases the genetic make-up of one partner does not allow the couple ever to achieve a pregnancy naturally.
In about 25 per cent of couples no obvious cause can be found for their infertility.
Treatment Ovulation may be induced with drugs.
In some cases damaged Fallopian tubes may be repaired by tubal surgery. If the tubes are destroyed beyond repair a pregnancy may be achieved with in vitro fertilisation (IVF) – see under ASSISTED CONCEPTION.
Endometriosis may be treated either with drugs or laser therapy, and pregnancy rates after both forms of treatment are between 40–50 per cent, depending on the severity of the disease.
Few options exist for treating male-factor infertility. These are arti?cial insemination by husband or donor and more recently in vitro fertilisation. Drug treatment and surgical repair of VARICOCELE have disappointing results.
Following investigations, between 30 and 40 per cent of infertile couples will achieve a pregnancy usually within two years.
Some infertile men cannot repair any errors in the DNA in their sperm, and it has been found that the same DNA repair problem occurs in malignant cells of some patients with cancer. It is possible that these men’s infertility might be nature’s way of stopping the propagation of genetic defects. With the assisted reproduction technique called intracytoplasmic sperm injection, some men with defective sperm can fertilise an ovum. If a man with such DNA defects fathers a child via this technique, that child could be sterile and might be at increased risk of developing cancer. (See ARTIFICIAL INSEMINATION; ASSISTED CONCEPTION.)... infertility
mm of blood.
The proportion of various white blood cells is measured and the size and shape of red and white cells is noted.
It is the most commonly performed blood test and is important for diagnosing anaemia or confirming the presence of an infection to which the blood has responded.
It is also used to diagnose disorders such as leukaemia and thrombocytopenia.... blood count
Applications of radionuclides to diagnosis The use of radionuclides in diagnosis is based on the fact that it is possible to tag many of the substances normally present in the body with a radioactive label. Certain synthetic radioactive elements, such as technetium, can also be used. Because it is possible to detect minute quantities of radioactive material, only very small doses are needed, making the procedure a safe one. Furthermore the body pool of the material is therefore not appreciably altered, and metabolism is not disturbed. Thus in studies of iodine metabolism the ratio of radioactive atoms administered to stable atoms in the body pool is of the order of 1:1,000 million. By measuring radioactivity in the body, in blood samples, or in the excreta it is possible to gain information about the fate of the labelled substance, and hence of the chemically identical inactive material. Therefore it is theoretically possible to trace the absorption, distribution and excretion of any substance normally present in the body, provided that it can be tagged with a suitable radioactive label.
If the investigation necessitates tracing the path of the material through the body by means of external counting over the body surface, it is obviously essential to use an isotope that emits gamma radiation or positrons. If, however, only measurements on blood sample or excreta are required, it is possible to use pure beta emitters. Whole-body counters measure the total radioactivity in the body, and these are of great value in absorption studies.
Moving images can provide information on body functions such as the movements of the heart, blood ?ow, bile ?ow in the liver, and urine in the kidneys. The development of COMPUTED TOMOGRAPHY or CT scanning has replaced radionuclide scanning for some imaging procedures.
Five main groups of diagnostic uses may be de?ned:
(1) METABOLIC STUDIES The use of radioactive materials in metabolic studies is based on the fundamental property that all isotopes of an element are chemically identical. The radioactive isotope is used as a true isotope tracer – that is, when introduced into the body (in whatever form) it behaves in the same way as the inactive element. For example, isotopes of iodine are used to measure thyroid function (see THYROID GLAND), and isotopes of calcium enable kinetic studies of bone formation and destruction to be performed.... isotope
According to the type of cells that predominate, leukaemia may be classi?ed as acute or chronic lymphoblastic leukaemia or myeloid leukaemia. Acute lymphoblastic leukaemia (ALL) is mostly a disease of childhood and is rare after the age of 25. Acute myeloid leukaemia is most common in children and young adults, but may occur at any age. Chronic lymphatic leukaemia occurs at any age between 35 and 80, most commonly in the 60s, and is twice as common in men as in women. Chronic myeloid leukaemia is rare before the age of 25, and most common between the ages of 30 and 65; men and women are equally affected. Around 2,500 patients with acute leukaemia are diagnosed in the United Kingdom, with a similar number annually diagnosed with chronic leukaemia.
Cause Both types of acute leukaemia seem to arise from a MUTATION in a single white cell. The genetically changed cell then goes through an uncontrolled succession of divisions resulting in many millions of abnormal white cells in the blood, bone marrow and other tissues. Possible causes are virus infection, chemical exposure, radiation and genetic background. The cause of chronic lymphocytic leukaemia is not known; the chronic myeloid version may have a genetic background.
Symptoms In acute cases the patient is pale due to anaemia, may have a purpuric rash due to lack of platelets, and may have enlarged lymphatic glands and spleen. The temperature is raised, and the condition may be mistaken for an acute infection (or may ?rst become apparent because the patient develops a severe infection due to a lack of normal white blood cells).
In the chronic type of the disease the onset is gradual, and the ?rst symptoms which occasion discomfort are either swelling of the abdomen and shortness of breath, due to painless enlargement of the spleen; or the enlargement of glands in the neck, armpits and elsewhere; or the pallor, palpitation, and other symptoms of anaemia which often accompany leukaemia. Occasional bleeding from the nose, stomach, gums or bowels may occur, and may be severe. Generally, there is a slight fever.
When the blood is examined microscopically, not only is there an enormous increase in the number of white cells, which may be multiplied 30- or 60-fold, but various immature forms are also found. In the lymphatic form of the disease, most white cells resemble lymphocytes, which, in healthy blood, are present only in small numbers. In the myeloid form, myelocytes, or large immature cells from the bone marrow, which are never present in healthy blood, appear in large numbers, and there may also be large numbers of immature, nucleated erythrocytes.
Treatment This varies according to the type of leukaemia and to the particular condition of the patient. Excellent results are being obtained in the control of ALL using blood transfusions, CHEMOTHERAPY, RADIOTHERAPY and bone-marrow TRANSPLANTATION. In the case of acute leukaemia, the drugs now being used include MERCAPTOPURINE, METHOTREXATE and CYCLOPHOSPHAMIDE. Blood transfusion and CORTICOSTEROIDS play an important part in controlling the condition during the period before a response to chemotherapy can be expected. Chemotherapy has almost completely replaced radiotherapy in the treatment of chronic leukaemia. For the myeloid form, BUSULFAN is the most widely used drug, replaced by hydroxyurea, mercaptopurine, or one of the nitrogen mustard (see NITROGEN MUSTARDS) derivatives in the later stages of the disease. For the lymphatic form, the drugs used are CHLORAMBUCIL, CYCLOPHOSPHAMIDE, and the nitrogen mustard derivatives.
Prognosis Although there is still no guaranteed cure, the outlook in both acute and chronic leukaemia has greatly improved – particularly for the acute form of the disease. Between 70 and 80 per cent of children with acute lymphoblastic leukaemia may be cured; between 20 and 50 per cent of those with acute myeloid leukaemia now have much-improved survival rates. Prognosis of patients with chronic lymphocytic leukaemia is often good, depending on early diagnosis.... leukaemia
The main function of some cranial nerves is to deliver sensory information from the ears, nose, and eyes to the brain.
These are the vestibulocochlear nerve (hearing and balance), olfactory nerve (smell), and optic nerve (vision). Other cranial nerves carry impulses that move muscles of the head and neck area. These are the oculomotor, trochlear, and abducent nerves (movements of the eye), spinal accessory nerve (head and shoulder movements), and hypoglossal nerve (tongue movements).
Some cranial nerves have both sensory and motor functions. These are the facial nerve (facial expressions, taste, and the secretion of saliva and tears) trigeminal nerve (facial sensation and jaw movements) and glossopharyngeal nerve (taste and swallowing movements). The vagus nerve has branches to all the main digestive organs, the heart, and the lungs, and is a major component of the parasympathetic nervous system, which is concerned with maintaining the body’s automatic functions.
All but 2 of the cranial nerve pairs connect with nuclei in the brainstem (the olfactory and optic nerves link directly with parts of the cerebrum). The nerves emerge through openings in the cranium; many then soon divide into branches.... cranial nerves
A&E Medicine is a relatively new specialty in the UK and there are still inadequate numbers of consultants and trainees, despite an inexorable rise in the number of patients attending A&E departments. With a similar rise in hospital admissions there is often no bed available immediately for casualties, resulting in backlogs of patients waiting for treatment. A major debate in the specialty is about the likely need to centralise services by downgrading or closing smaller units, in order to make the most e?cient use of sta?.
See www.baem.org.uk... accident and emergency medicine
Both HIV-1 and HIV-2 are predominantly sexually transmitted and both are associated with secondary opportunistic infections. However, HIV-2 seems to result in slower damage to the immune system. HIV-1 is known to mutate rapidly and has given rise to other subtypes.
HIV is thought to have occurred in humans in the 1950s, but whether or not it infected humans from another primate species is uncertain. It became widespread in the 1970s but its latency in causing symptoms meant that the epidemic was not noticed until the following decade. Although it is a sexually transmitted disease, it can also be transmitted by intravenous drug use (through sharing an infected needle), blood transfusions with infected blood (hence the importance of e?ective national blood-screening programmes), organ donation, and occupationally (see health-care workers, below). Babies born of HIV-positive mothers can be infected before or during birth, or through breast feeding.
Although HIV is most likely to occur in blood, semen or vaginal ?uid, it has been found in saliva and tears (but not sweat); however, there is no evidence that the virus can be transmitted from these two body ?uids. There is also no evidence that HIV can be transmitted by biting insects (such as mosquitoes). HIV does not survive well in the environment and is rapidly destroyed through drying.
Prevalence At the end of 2003 an estimated 42 million people globally were infected with HIV – up from 40 million two years earlier. About one-third of those with HIV/AIDS are aged 15–24 and most are unaware that they are carrying the virus. During 2003 it is estimated that 5 million adults and children worldwide were newly infected with HIV, and that 3 million adults and children died. In Africa in 2003,
3.4 million people were newly infected and 2.3 million died, with more than 28 million carrying the virus. HIV/AIDS was the leading cause of death in sub-Saharan Africa where over half of the infections were in women and 90 per cent of cases resulted from heterosexual sex. In some southern African countries, one in three pregnant women had HIV.
In Asia and the Paci?c there were 1.2 million new infections and 435,000 deaths. The area with the fastest-growing epidemic is Eastern Europe, especially the Russian Federation where in 2002 around a million people had HIV and there were an estimated 250,000 new infections, with intravenous drug use a key contributor to this ?gure. Seventy-?ve per cent of cases occurred in men, with male-to-male sexual transmission an important cause of infection, though heterosexual activity is a rising cause of infection.
At the end of 2002 the UK had an estimated 55,900 HIV-infected adults aged between 15 and 59. More than 3,600 individuals were newly diagnosed with the infection in 2000, the highest annual ?gure since the epidemic started
– in 1998 the ?gure was 2,817 and in 1999 just over 3,000 (Department of Health and Communicable Disease Surveillance Centre). The incidence of AIDS in the UK has declined sharply since the introduction of highly active antiretroviral therapy (HAART) and HIV-related deaths have also fallen: in 2002 there were 777 reported new AIDS cases and 395 deaths, compared with 1,769 and 1,719 respectively in 1995. (Sources: UNAIDS and WHO, AIDS Epidemic Update, December 2001; Public Health Laboratory Services AIDS and STD Centre Communicable Disease Surveillance and Scottish Centre for Infection and Environmental Health, Quarterly Surveillance Tables.)
Poverty is strongly linked to the spread of AIDS, for various reasons including lack of health education; lack of e?ective public-health awareness; women having little control over sexual behaviour and contraception; and, by comparison with the developed world, little or no access to antiretroviral drugs.
Pathogenesis The cellular target of HIV infection is a subset of white blood cells called T-lymphocytes (see LYMPHOCYTE) which carry the CD4 surface receptor. These so-called ‘helper T-cells’ are vital to the function of cell-mediated immunity. Infection of these cells leads to their destruction (HIV replicates at an enormous rate – 109) and over the course of several years the body is unable to generate suf?cient new cells to keep pace. This leads to progressive destruction of the body’s immune capabilities, evidenced clinically by the development of opportunistic infection and unusual tumours.
Monitoring of clinical progression It is possible to measure the number of viral particles present in the plasma. This gives an accurate guide to the likely progression rate, which will be slow in those individuals with fewer than 10,000 particles per ml of plasma but progressively more rapid above this ?gure. The main clinical monitoring of the immune system is through the numbers of CD4 lymphocytes in the blood. The normal count is around 850 cells per ml and, without treatment, eventual progression to AIDS is likely in those individuals whose CD4 count falls below 500 per ml. Opportunistic infections occur most frequently when the count falls below 200 per ml: most such infections are treatable, and death is only likely when the CD4 count falls below 50 cells per ml when infection is developed with organisms that are di?cult to treat because of their low intrinsic virulence.
Simple, cheap and highly accurate tests are available to detect HIV antibodies in the serum. These normally occur within three months of infection and remain the cornerstone of the diagnosis.
Clinical features Most infected individuals have a viral illness some three weeks after contact with HIV. The clinical features are often non-speci?c and remain undiagnosed but include a ?ne red rash, large lymph nodes, an in?uenza-like illness, cerebral involvement and sometimes the development of opportunistic infections. The antibody test may be negative at this stage but there are usually high levels of virus particles in the blood. The antibody test is virtually always positive within three months of infection. HIV infection is often subsequently asymptomatic for a period of ten years or more, although in most patients progressive immune destruction is occurring during this time and a variety of minor opportunistic infections such as HERPES ZOSTER or oral thrush (see CANDIDA) do occur. In addition, generalised LYMPHADENOPATHY is present in a third of patients and some suffer from severe malaise, weight loss, night sweats, mild fever, ANAEMIA or easy bruising due to THROMBOCYTOPENIA.
The presentation of opportunistic infection is highly variable but usually involves either the CENTRAL NERVOUS SYSTEM, the gastrointestinal tract or the LUNGS. Patients may present with a sudden onset of a neurological de?cit or EPILEPSY due to a sudden onset of a STROKE-like syndrome, or epilepsy due to a space-occupying lesion in the brain – most commonly TOXOPLASMOSIS. In late disease, HIV infection of the central nervous system itself may produce progressive memory loss, impaired concentration and mental slowness called AIDS DEMENTIA. A wide variety of opportunistic PROTOZOA or viruses produces DYSPHAGIA, DIARRHOEA and wasting. In the respiratory system the commonest opportunistic infection associated with AIDS, pneumonia, produces severe shortness of breath and sometimes CYANOSIS, usually with a striking lack of clinical signs in the chest.
In very late HIV infection, when the CD4 count has fallen below 50 cells per ml, infection with CYTOMEGALOVIRUS may produce progressive retinal necrosis (see EYE, DISORDERS OF) which will lead to blindness if untreated, as well as a variety of gastrointestinal symptoms. At this stage, infection with atypical mycobacteria is also common, producing severe anaemia, wasting and fevers. The commonest tumour associated with HIV is Kaposi’s sarcoma which produces purplish skin lesions. This and nonHodgkin’s lymphoma (see LYMPHOMA), which is a hundred times more frequent among HIV-positive individuals than in the general population, are likely to be associated with or caused by opportunistic viral infections.
Prevention There is, as yet, no vaccine to prevent HIV infection. Vaccine development has been hampered
by the large number of new HIV strains generated through frequent mutation and recombination.
because HIV can be transmitted as free virus and in infected cells.
because HIV infects helper T-cells – the very cells involved in the immune response. There are, however, numerous research pro
grammes underway to develop vaccines that are either prophylactic or therapeutic. Vaccine-development strategies have included: recombinant-vector vaccines, in which a live bacterium or virus is genetically modi?ed to carry one or more of the HIV genes; subunit vaccines, consisting of small regions of the HIV genome designed to induce an immune response without infection; modi?ed live HIV, which has had its disease-promoting genes removed; and DNA vaccines – small loops of DNA (plasmids) containing viral genes – that make the host cells produce non-infectious viral proteins which, in turn, trigger an immune response and prime the immune system against future infection with real virus.
In the absence of an e?ective vaccine, preventing exposure remains the chief strategy in reducing the spread of HIV. Used properly, condoms are an extremely e?ective method of preventing exposure to HIV during sexual intercourse and remain the most important public-health approach to countering the further acceleration of the AIDS epidemic. The spermicide nonoxynol-9, which is often included with condoms, is known to kill HIV in vitro; however, its e?ectiveness in preventing HIV infection during intercourse is not known.
Public-health strategies must be focused on avoiding high-risk behaviour and, particularly in developing countries, empowering women to have more control over their lives, both economically and socially. In many of the poorer regions of the world, women are economically dependent on men and refusing sex, or insisting on condom use, even when they know their partners are HIV positive, is not a straightforward option. Poverty also forces many women into the sex industry where they are at greater risk of infection.
Cultural problems in gaining acceptance for universal condom-use by men in some developing countries suggests that other preventive strategies should also be considered. Microbicides used as vaginal sprays or ‘chemical condoms’ have the potential to give women more direct control over their exposure risk, and research is underway to develop suitable products.
Epidemiological studies suggest that male circumcision may o?er some protection against HIV infection, although more research is needed before this can be an established public-health strategy. Globally, about 70 per cent of infected men have acquired the virus through unprotected vaginal sex; in these men, infection is likely to have occurred through the penis with the mucosal epithelia of the inner surface of the foreskin and the frenulum considered the most likely sites for infection. It is suggested that in circumcised men, the glans may become keratinised and thus less likely to facilitate infection. Circumcision may also reduce the risk of lesions caused by other sexually transmitted disease.
Treatment AIDS/HIV treatment can be categorised as speci?c therapies for the individual opportunistic infections – which ultimately cause death – and highly active antiretroviral therapy (HAART) designed to reduce viral load and replication. HAART is also the most e?ective way of preventing opportunistic infections, and has had a signi?cant impact in delaying the onset of AIDS in HIV-positive individuals in developed countries.
Four classes of drugs are currently in use. Nucleoside analogues, including ZIDOVUDINE and DIDANOSINE, interfere with the activity of the unique enzyme of the retrovirus reverse transcriptase which is essential for replication. Nucleotide analogues, such as tenofovir, act in the same way but require no intracellular activation. Non-nucleoside reverse transcriptase inhibitors, such as nevirapine and EFAVIRENZ, act by a di?erent mechanism on the same enzyme. The most potent single agents against HIV are the protease inhibitors, such as lopinavir, which render a unique viral enzyme ineffective. These drugs are used in a variety of combinations in an attempt to reduce the plasma HIV viral load to below detectable limits, which is achieved in approximately 90 per cent of patients who have not previously received therapy. This usually also produces a profound rise in CD4 count. It is likely, however, that such treatments need to be lifelong – and since they are associated with toxicities, long-term adherence is di?cult. Thus the optimum time for treatment intervention remains controversial, with some clinicians believing that this should be governed by the viral load rising above 10,000 copies, and others that it should primarily be designed to prevent the development of opportunistic infections – thus, that initiation of therapy should be guided more by the CD4 count.
It should be noted that the drug regimens have been devised for infection with HIV-1; it is not known how e?ective they are at treating infection with HIV-2.
HIV and pregnancy An HIV-positive woman can transmit the virus to her fetus, with the risk of infection being particularly high during parturition; however, the risk of perinatal HIV transmission can be reduced by antiviral drug therapy. In the UK, HIV testing is available to all women as part of antenatal care. The bene?ts of antenatal HIV testing in countries where antiviral drugs are not available are questionable. An HIV-positive woman might be advised not to breast feed because of the risks of transmitting HIV via breastmilk, but there may be a greater risk associated with not breast feeding at all. Babies in many poor communities are thought to be at high risk of infectious diseases and malnutrition if they are not breast fed and may thus be at greater overall risk of death during infancy.
Counselling Con?dential counselling is an essential part of AIDS management, both in terms of supporting the psychological wellbeing of the individual and in dealing with issues such as family relations, sexual partners and implications for employment (e.g. for health-care workers). Counsellors must be particularly sensitive to culture and lifestyle issues. Counselling is essential both before an HIV test is taken and when the results are revealed.
Health-care workers Health-care workers may be at risk of occupational exposure to HIV, either through undertaking invasive procedures or through accidental exposure to infected blood from a contaminated needle (needlestick injury). Needlestick injuries are frequent in health care – as many as 600,000 to 800,000 are thought to occur annually in the United States. Transmission is much more likely where the worker has been exposed to HIV through a needlestick injury or deep cut with a contaminated instrument than through exposure of mucous membranes to contaminated blood or body ?uids. However, even where exposure occurs through a needlestick injury, the risk of seroconversion is much lower than with a similar exposure to hepatitis C or hepatitis B. A percutaneous exposure to HIV-infected blood in a health-care setting is thought to carry a risk of about one infection per 300 injuries (one in 1,000 for mucous-membrane exposure), compared with one in 30 for hepatitis C, and one in three for hepatitis B (when the source patient is e-antigen positive).
In the event of an injury, health-care workers are advised to report the incident immediately where, depending on a risk assessment, they may be o?ered post-exposure prophylaxis (PEP). They should also wash the contaminated area with soap and water (but without scrubbing) and, if appropriate, encourage bleeding at the site of injury. PEP, using a combination of antiretroviral drugs (in a similar regimen to HAART – see above), is thought to greatly reduce the chances of seroconversion; it should be commenced as soon as possible, preferably within one or two hours of the injury. Although PEP is available, safe systems of work are considered to o?er the greatest protection. Double-gloving (latex gloves remove much of the blood from the surface of the needle during a needlestick), correct use of sharps containers (for used needles and instruments), avoiding the resheathing of used needles, reduction in the number of blood samples taken from a patient, safer-needle devices (such as needles that self-blunt after use) and needleless drug administration are all thought to reduce the risk of exposure to HIV and other blood-borne viruses. Although there have been numerous cases of health-care workers developing HIV through occupational exposure, there is little evidence of health-care workers passing HIV to their patients through normal medical procedures.... aids/hiv
Ancylostoma braziliensis A nematode infection of dogs, which in humans causes local disease (larva migrans) only, generally on the soles of the feet. It is usually acquired by walking on beaches contaminated with dog faeces in places such as the Caribbean.... ancylostomiasis
Patients found to have bacteriuria on SCREENING may never have consulted a doctor but nearly all have a few symptoms, such as frequency or urgency – so-called ‘covert bacteriuria’.
Men have longer urethras and fewer urinary tract infections (UTIs) than women. Risk factors include diabetes mellitus, pregnancy, impaired voiding and genito-urinary malformations. Over 70 per cent of UTIs are due to E. coli, but of UTIs in hospital patients, only 40 per cent are caused by E. coli.
Treatment Patients should be encouraged to drink plenty of water, with frequent urination. Speci?c antibiotic therapy with trimethoprim or amoxicillin may be needed.... bacteriuria
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
Not all sufferers from coeliac disease present with gastrointestinal symptoms: doctors, using screening techniques, have increasingly identi?ed large numbers of such people. This is important because researchers have recently discovered that untreated overt and silent coeliac disease increases the risk of sufferers developing osteoporosis (brittle bone disease – see BONE, DISORDERS OF) and cancer. The osteoporosis develops because the bowel fails to absorb the CALCIUM essential for normal bone growth. Because those with coeliac disease lack the enzyme LACTASE, which is essential for digesting milk, they avoid milk – a rich source of calcium.
The key treatment is a strict, lifelong diet free of gluten. As well as returning the bowel lining to normal, this diet results in a return to normal bone density. People with coeliac disease, or parents or guardians of affected children, can obtain help and guidance from the Coeliac Society of the United Kingdom. (See also MALABSORPTION SYNDROME; SPRUE.)... coeliac disease
See www.cafamily.org.uk... contact a family
Structure of bone Bone is composed partly of ?brous tissue, partly of bone matrix comprising phosphate and carbonate of lime, intimately mixed together. The bones of a child are about two-thirds ?brous tissue, whilst those of the aged contain one-third; the toughness of the former and the brittleness of the latter are therefore evident.
The shafts of the limb bones are composed of dense bone, the bone being a hard tube surrounded by a membrane (the periosteum) and enclosing a fatty substance (the BONE MARROW); and of cancellous bone, which forms the short bones and the ends of long bones, in which a ?ne lace-work of bone ?lls up the whole interior, enclosing marrow in its meshes. The marrow of the smaller bones is of great importance. It is red in colour, and in it red blood corpuscles are formed. Even the densest bone is tunnelled by ?ne canals (Haversian canals) in which run small blood vessels, nerves and lymphatics, for the maintenance and repair of the bone. Around these Haversian canals the bone is arranged in circular plates called lamellae, the lamellae being separated from one another by clefts, known as lacunae, in which single bone-cells are contained. Even the lamellae are pierced by ?ne tubes known as canaliculi lodging processes of these cells. Each lamella is composed of very ?ne interlacing ?bres.
GROWTH OF BONES Bones grow in thickness from the ?brous tissue and lime salts laid down by cells in their substance. The long bones grow in length from a plate of cartilage (epiphyseal cartilage) which runs across the bone about 1·5 cm or more from its ends, and which on one surface is also constantly forming bone until the bone ceases to lengthen at about the age of 16 or 18. Epiphyseal injury in children may lead to diminished growth of the limb.
REPAIR OF BONE is e?ected by cells of microscopic size, some called osteoblasts, elaborating the materials brought by the blood and laying down strands of ?brous tissue, between which bone earth is later deposited; while other cells, known as osteoclasts, dissolve and break up dead or damaged bone. When a fracture has occurred, and the broken ends have been brought into contact, these are surrounded by a mass of blood at ?rst; this is partly absorbed and partly organised by these cells, ?rst into ?brous tissue and later into bone. The mass surrounding the fractured ends is called the callus, and for some months it forms a distinct thickening which is gradually smoothed away, leaving the bone as before the fracture. If the ends have not been brought accurately into contact, a permanent thickening results.
VARIETIES OF BONES Apart from the structural varieties, bones fall into four classes: (a) long bones like those of the limbs; (b) short bones composed of cancellous tissue, like those of the wrist and the ankle; (c) ?at bones like those of the skull; (d) irregular bones like those of the face or the vertebrae of the spinal column (backbone).
The skeleton consists of more than 200 bones. It is divided into an axial part, comprising the skull, the vertebral column, the ribs with their cartilages, and the breastbone; and an appendicular portion comprising the four limbs. The hyoid bone in the neck, together with the cartilages protecting the larynx and windpipe, may be described as the visceral skeleton.
AXIAL SKELETON The skull consists of the cranium, which has eight bones, viz. occipital, two parietal, two temporal, one frontal, ethmoid, and sphenoid; and of the face, which has 14 bones, viz. two maxillae or upper jaw-bones, one mandible or lower jaw-bone, two malar or cheek bones, two nasal, two lacrimal, two turbinal, two palate bones, and one vomer bone. (For further details, see SKULL.) The vertebral column consists of seven vertebrae in the cervical or neck region, 12 dorsal vertebrae, ?ve vertebrae in the lumbar or loin region, the sacrum or sacral bone (a mass formed of ?ve vertebrae fused together and forming the back part of the pelvis, which is closed at the sides by the haunch-bones), and ?nally the coccyx (four small vertebrae representing the tail of lower animals). The vertebral column has four curves: the ?rst forwards in the neck, the second backwards in the dorsal region, the third forwards in the loins, and the lowest, involving the sacrum and coccyx, backwards. These are associated with the erect attitude, develop after a child learns to walk, and have the e?ect of diminishing jars and shocks before these reach internal organs. This is aided still further by discs of cartilage placed between each pair of vertebrae. Each vertebra has a solid part, the body in front, and behind this a ring of bone, the series of rings one above another forming a bony canal up which runs the spinal cord to pass through an opening in the skull at the upper end of the canal and there join the brain. (For further details, see SPINAL COLUMN.) The ribs – 12 in number, on each side – are attached behind to the 12 dorsal vertebrae, while in front they end a few inches away from the breastbone, but are continued forwards by cartilages. Of these the upper seven reach the breastbone, these ribs being called true ribs; the next three are joined each to the cartilage above it, while the last two have their ends free and are called ?oating ribs. The breastbone, or sternum, is shaped something like a short sword, about 15 cm (6 inches) long, and rather over 2·5 cm (1 inch) wide.
APPENDICULAR SKELETON The upper limb consists of the shoulder region and three segments – the upper arm, the forearm, and the wrist with the hand, separated from each other by joints. In the shoulder lie the clavicle or collar-bone (which is immediately beneath the skin, and forms a prominent object on the front of the neck), and the scapula or shoulder-blade behind the chest. In the upper arm is a single bone, the humerus. In the forearm are two bones, the radius and ulna; the radius, in the movements of alternately turning the hand palm up and back up (called supination and pronation respectively), rotating around the ulna, which remains ?xed. In the carpus or wrist are eight small bones: the scaphoid, lunate, triquetral, pisiform, trapezium, trapezoid, capitate and hamate. In the hand proper are ?ve bones called metacarpals, upon which are set the four ?ngers, each containing the three bones known as phalanges, and the thumb with two phalanges.
The lower limb consists similarly of the region of the hip-bone and three segments – the thigh, the leg and the foot. The hip-bone is a large ?at bone made up of three – the ilium, the ischium and the pubis – fused together, and forms the side of the pelvis or basin which encloses some of the abdominal organs. The thigh contains the femur, and the leg contains two bones – the tibia and ?bula. In the tarsus are seven bones: the talus (which forms part of the ankle joint); the calcaneus or heel-bone; the navicular; the lateral, intermediate and medial cuneiforms; and the cuboid. These bones are so shaped as to form a distinct arch in the foot both from before back and from side to side. Finally, as in the hand, there are ?ve metatarsals and 14 phalanges, of which the great toe has two, the other toes three each.
Besides these named bones there are others sometimes found in sinews, called sesamoid bones, while the numbers of the regular bones may be increased by extra ribs or diminished by the fusion together of two or more bones.... bone
Nutritional Profile Energy value (calories per serving): Moderate Protein: Moderate Fat: Low Saturated fat: Low Cholesterol: None Carbohydrates: High Fiber: High Sodium: Low Major vitamin contribution: Niacin Major mineral contribution: Calcium
About the Nutrients in This Food Carob flour, which is milled from the dried pod of a Mediterranean ever- green tree, Ceratonia siliqua, looks like cocoa but has a starchy, beanlike flavor. It can be mixed with sweeteners to make a cocoalike powder or combined with fats and sweeteners to produce a candy that looks like and has the same rich mouthfeel as milk chocolate but tastes more like honey. Ounce for ounce, carob, which is also known as locust bean gum, has more fiber and calcium but fewer calories than cocoa. Its carbohydrates include the sugars sucrose, D-mannose, and D-galactose. (D-galactose is a simple sugar that links up with other sugars to form the complex indigest- ible sugars raffinose and stachyose.) Carob also contains gums and pectins, the indigestible food fibers commonly found in seeds.
The Most Nutritious Way to Serve This Food As a substitute for cocoa or chocolate for people who are sensitive to chocolate.
Diets That May Restrict or Exclude This Food Low-carbohydrate diet
Buying This Food Look for: Tightly sealed containers that will protect the flour from moisture and insects.
Storing This Food Store carob flour in a cool, dark place in a container that protects it from air, moisture, and insects. Keep carob candy cool and dry.
Preparing This Food Measure out carob flour by filling a cup or tablespoon and leveling it off with a knife. To substitute carob for regular flour, use ¼ cup carob flour plus ¾ cup regular flour for each cup ordinary flour. To substitute for chocolate, use three tablespoons of carob flour plus two tablespoons of water for each ounce of unsweetened chocolate. Carob flour is sweeter than unsweetened chocolate.
What Happens When You Cook This Food Unlike cocoa powder, carob flour contains virtually no fat. It will burn, not melt, if you heat it in a saucepan. When the flour is heated with water, its starch granules absorb moisture and rupture, releasing a gum that can be used as a stabilizer, thickener, or binder in processed foods and cosmetics. In cake batters, it performs just like other flours (see flour).
Medical uses and/or Benefits Adsorbent and demulcent. Medically, carob flour has been used as a soothing skin powder. As a chocolate substitute. People who are sensitive to chocolate can usually use carob instead. Like cocoa beans, carob is free of cholesterol. Unlike cocoa, which contains the cen- tral-nervous-system stimulant caffeine and the muscle stimulant theobromine, carob does not contain any stimulating methylxanthines. Lower cholesterol levels. In 2001, a team of German nutrition researchers from the Institute for Nutritional Science at the University of Potsdam, the German Institute of Human Nutri- tion, Center for Conventional Medicine and Alternative Therapies (Berlin) Nutrinova Nutri- tion Specialties and Food Ingredients GmbH, and PhytoPharm Consulting, Institute for Phytopharmaceuticals GmbH conducted a study to evaluate carob’s effectiveness in lower- ing cholesterol. For a period of eight weeks, 47 volunteers with moderately high cholesterol levels (232– 302 mg/dL) were fed 15 g of carob per day in breakfast cereal, fruit grain bars, and a drink made from powdered carob pulp as supplements to their normal diet. After four weeks, the volunteers’ total cholesterol levels fell an average of 7 percent and their LDL (low density lipoprotein—“bad” cholesterol) levels fell an average 10.6 percent. At six weeks, the numbers were 7.8 percent and 10.6 percent. There was no effect on HDLs (high density lipoproteins, a.k.a. “good” cholesterol).... carob
Adoption declined as the availability of babies fell with the introduction of the Abortion Act 1968, improving contraceptive services and increasing acceptability of single parenthood.
However, with 10 per cent of couples suffering infertility, the demand continued, leading to the adoption of those previously perceived as di?cult to place – i.e. physically, intellectually and/or emotionally disabled children and adolescents, those with terminal illness, and children of ethnic-minority groups.
Recent controversies regarding homosexual couples as adoptive parents, adoption of children with or at high risk of HIV/AIDS, transcultural adoption, and the increasing use of intercountry adoption to ful?l the needs of childless couples have provoked urgent consideration of the ethical dilemmas of adoption and its consequences for the children, their adoptive and birth families and society generally.
Detailed statistics have been unavailable since 1984 but in general there has been a downward trend with relatively more older children being placed. Detailed reasons for adoption (i.e. interfamily, step-parent, intercountry, etc.) are not available but approximately one-third are adopted from local-authority care.
In the UK all adoptions (including interfamily and step-parent adoption) must take place through a registered adoption agency which may be local-authority-based or provided by a registered voluntary agency. All local authorities must act as agencies, the voluntary agencies often providing specialist services to promote and support the adoption of more di?cult-to-place children. Occasionally an adoption allowance will be awarded.
Adoption orders cannot be granted until a child has resided with its proposed adopters for 13 weeks. In the case of newborn infants the mother cannot give formal consent to placement until the baby is six weeks old, although informal arrangements can be made before this time.
In the UK the concept of responsibility of birth parents to their children and their rights to continued involvement after adoption are acknowledged by the Children Act 1989. However, in all discussions the child’s interests remain paramount. The Act also recognises adopted children’s need to have information regarding their origins.
BAAF – British Agencies for Adoption and Fostering – is the national organisation of adoptive agencies, both local authority and voluntary sector. The organisation promotes and provides training service, development and research; has several specialist professional subgroups (i.e. medical, legal, etc.); and produces a quarterly journal.
Adoption UK is an e?ective national support network of adoptive parents who o?er free information, a ‘listening ear’ and, to members, a quarterly newsletter.
National Organisation for Counselling Adoptees and their Parents (NORCAP) is concerned with adopted children and birth parents who wish to make contact.
The Registrar General operates an Adoption Contact Register for adopted persons and anyone related to that person by blood, half-blood or marriage. Information can be obtained from the O?ce of Population Censuses and Surveys. For the addresses of these organisations, see Appendix 2.... child adoption
The two most common causes of death in the UK are diseases of the circulatory system (including strokes and heart disease) and cancer.
Overall annual death rates among women in the UK at the start of the 21st century were
7.98 per 1,000 population, and among men,
5.58 per 1,000. Comparable ?gures at the start of the 20th century were 16.3 for women and
18.4 for men. The death rates in 1900 among infants up to the age of four were 47.9 per 1,000 females and 57 per 1,000 males. By 2003 these numbers had fallen to 5.0 and 5.8 respectively. All these ?gures give a crude indication of how the health of Britain’s population has improved in the past century.
Death rates and ?gures on the causes of deaths are essential statistics in the study of EPIDEMIOLOGY which, along with information on the incidence of illnesses and injuries, provides a temporal and geographical map of changing health patterns in communities. Such information is valuable in planning preventive health measures (see PUBLIC HEALTH) and in identifying the natural history of diseases – knowledge that often contributes to the development of preventive measures and treatments for those diseases.... death, causes of
Since April 1993, local social-services departments have been responsible for assessing what help people need from community-care services: these can include home helps, meals on wheels, sheltered housing, etc. Recipients of such services are means-tested and make variable contributions towards the costs. Policies on charging vary from one area to another and there are wide geographical variations in the range of services provided free and the charges levied for others.
People with complex needs may be assigned a case manager to coordinate the care package and ensure that appropriate responses are made to changing circumstances. The success of community care hinges on e?ective coordination of the services of an often large number of providers from the health and social-services sectors. Poor communication between sectors and inadequate coordination of services have been among the most common complaints about the community-care reforms.
Health care for people being cared for in the community remains largely free under the NHS arrangements, although there are regular debates about where the boundaries should be drawn between free health services and means-tested social care. A distinction has been made between necessary nursing care (funded by the state) and normal personal care (the responsibility of the patient), but the dividing line often proves hard to de?ne.
As care has shifted increasingly into the community, previous hospital facilities have become redundant. Vast numbers of beds in long-stay geriatric hospitals and in-patient psychiatric wards have been closed. There is now concern that too few beds remain to provide essential emergency and respite services. In some areas, patients ?t for discharge are kept in hospital because of delay in setting up community services for the elderly, or because of the inability of the local authority to fund appropriate care in a nursing home or at home with community-care support for other patients; the resulting BED-BLOCKING has an adverse e?ect on acutely ill patients needing hospital admission.
Community care, if correctly funded and coordinated, is an excellent way of caring for people with long-term needs, but considerable work is still needed in Britain to ensure that all patients have access to high-quality community care when they need it. Problems in providing such are are not con?ned to the UK.... community care
Over the past four decades the ?nancial outlay on NHS dental services has been around 5 per cent of total NHS funding. This contrasts with 10 per cent during the service’s early years, when the NHS was coping with decades of ‘dental neglect’. The population’s dental health has, however, been steadily improving: in 1968 more than one-third of people had no natural teeth; by the late 1990s the proportion had fallen to 13 per cent.
Dentistry is divided into several groupings.
General dental practitioners Concerned with primary dental care, the prevention, diagnosis and treatment of diseases of the gums and teeth – for example, caries (see TEETH, DISORDERS OF). They also deal with diffculties in biting and the effects of trauma, and are aware that oral disorders may re?ect disease elsewhere in the body. They will refer to the hospital dental services, patients who require treatment that cannot be satisfactorily carried out in a primary-care setting.
Most routine dental prevention and treatment is carried out in general dental practitioners’ surgeries, where the dentists also supervise the work of hygienists and dental auxiliaries. Appliances, such as dentures, crowns, bridges and orthodontic appliances are constructed by dental technicians working in dental laboratories.
There are around 18,800 dentists providing general dental services in the UK. These practitioners are free to accept or reject any potential patient and to practise where they wish. Those dentists treating patients under an NHS contract (a mixture of capitation fees and items of service payments) can also treat patients privately (for an appropriate fee). Some dentists opt for full-time private practice, and their numbers are increasing in the wake of changes in 1990 in the contracts of NHS general dental practitioners.
Community dental practitioner Part of the public-health team and largely concerned with monitoring dental health and treating the young and the handicapped.
In the hospitals and dental schools are those who are involved in only one of the specialities.
Around 2,800 dentists work in NHS hospitals and 1,900 in the NHS’s community services. In some parts of the UK, people wanting NHS treatment are having diffculties ?nding dentists willing to provide such care.
Restorative dentist Concerned with the repair of teeth damaged by trauma and caries, and the replacement of missing teeth.
Orthodontist Correction of jaws and teeth which are misaligned or irregular. This is done with appliances which may be removable or ?xed to the teeth which are then moved with springs or elastics.... dental surgeon
– the corpus callosum. Other clefts or ?ssures (sulci) make deep impressions, dividing the cerebrum into lobes. The lobes of the cerebrum are the frontal lobe in the forehead region, the parietal lobe on the side and upper part of the brain, the occipital lobe to the back, and the temporal lobe lying just above the region of the ear. The outer 3 mm of the cerebrum is called the cortex, which consists of grey matter with the nerve cells arranged in six layers. This region is concerned with conscious thought, sensation and movement, operating in a similar manner to the more primitive areas of the brain except that incoming information is subject to much greater analysis.
Numbers of shallower infoldings of the surface, called furrows or sulci, separate raised areas called convolutions or gyri. In the deeper part, the white matter consists of nerve ?bres connecting di?erent parts of the surface and passing down to the lower parts of the brain. Among the white matter lie several rounded masses of grey matter, the lentiform and caudate nuclei. In the centre of each cerebral hemisphere is an irregular cavity, the lateral ventricle, each of which communicates with that on the other side and behind with the third ventricle through a small opening, the inter-ventricular foramen, or foramen of Monro.
BASAL NUCLEI Two large masses of grey matter embedded in the base of the cerebral hemispheres in humans, but forming the chief part of the brain in many animals. Between these masses lies the third ventricle, from which the infundibulum, a funnel-shaped process, projects downwards into the pituitary body, and above lies the PINEAL GLAND. This region includes the important HYPOTHALAMUS.
MID-BRAIN or mesencephalon: a stalk about 20 mm long connecting the cerebrum with the hind-brain. Down its centre lies a tube, the cerebral aqueduct, or aqueduct of Sylvius, connecting the third and fourth ventricles. Above this aqueduct lie the corpora quadrigemina, and beneath it are the crura cerebri, strong bands of white matter in which important nerve ?bres pass downwards from the cerebrum. The pineal gland is sited on the upper part of the midbrain.
PONS A mass of nerve ?bres, some of which run crosswise and others are the continuation of the crura cerebri downwards.
CEREBELLUM This lies towards the back, underneath the occipital lobes of the cerebrum.
MEDULLA OBLONGATA The lowest part of the brain, in structure resembling the spinal cord, with white matter on the surface and grey matter in its interior. This is continuous through the large opening in the skull, the foramen magnum, with the spinal cord. Between the medulla, pons, and cerebellum lies the fourth ventricle of the brain.
Structure The grey matter consists mainly of billions of neurones (see NEURON(E)) in which all the activities of the brain begin. These cells vary considerably in size and shape in di?erent parts of the brain, though all give o? a number of processes, some of which form nerve ?bres. The cells in the cortex of the cerebral hemispheres, for example, are very numerous, being set in layers ?ve or six deep. In shape these cells are pyramidal, giving o? processes from the apex, from the centre of the base, and from various projections elsewhere on the cell. The grey matter is everywhere penetrated by a rich supply of blood vessels, and the nerve cells and blood vessels are supported in a ?ne network of ?bres known as neuroglia.
The white matter consists of nerve ?bres, each of which is attached, at one end, to a cell in the grey matter, while at the other end it splits up into a tree-like structure around another cell in another part of the grey matter in the brain or spinal cord. The ?bres have insulating sheaths of a fatty material which, in the mass, gives the white matter its colour; they convey messages from one part of the brain to the other (association ?bres), or, grouped into bundles, leave the brain as nerves, or pass down into the spinal cord where they end near, and exert a control upon, cells from which in turn spring the nerves to the body.
Both grey and white matter are bound together by a network of cells called GLIA which make up 60 per cent of the brain’s weight. These have traditionally been seen as simple structures whose main function was to glue the constituents of the brain together. Recent research, however, suggests that glia are vital for growing synapses between the neurons as they trigger these cells to communicate with each other. So they probably participate in the task of laying down memories, for which synapses are an essential key. The research points to the likelihood that glial cells are as complex as neurons, functioning biochemically in a similar way. Glial cells also absorb potassium pumped out by active neurons and prevent levels of GLUTAMATE – the most common chemical messenger in the brain – from becoming too high.
The general arrangement of ?bres can be best understood by describing the course of a motor nerve-?bre. Arising in a cell on the surface in front of the central sulcus, such a ?bre passes inwards towards the centre of the cerebral hemisphere, the collected mass of ?bres as they lie between the lentiform nucleus and optic thalamus being known as the internal capsule. Hence the ?bre passes down through the crus cerebri, giving o? various small connecting ?bres as it passes downwards. After passing through the pons it reaches the medulla, and at this point crosses to the opposite side (decussation of the pyramids). Entering the spinal cord, it passes downwards to end ?nally in a series of branches (arborisation) which meet and touch (synapse) similar branches from one or more of the cells in the grey matter of the cord (see SPINAL CORD).
BLOOD VESSELS Four vessels carry blood to the brain: two internal carotid arteries in front, and two vertebral arteries behind. These communicate to form a circle (circle of Willis) inside the skull, so that if one is blocked, the others, by dilating, take its place. The chief branch of the internal carotid artery on each side is the middle cerebral, and this gives o? a small but very important branch which pierces the base of the brain and supplies the region of the internal capsule with blood. The chief importance of this vessel lies in the fact that the blood in it is under especially high pressure, owing to its close connection with the carotid artery, so that haemorrhage from it is liable to occur and thus give rise to stroke. Two veins, the internal cerebral veins, bring the blood away from the interior of the brain, but most of the small veins come to the surface and open into large venous sinuses, which run in grooves in the skull, and ?nally pass their blood into the internal jugular vein that accompanies the carotid artery on each side of the neck.
MEMBRANES The brain is separated from the skull by three membranes: the dura mater, a thick ?brous membrane; the arachnoid mater, a more delicate structure; and the pia mater, adhering to the surface of the brain and containing the blood vessels which nourish it. Between each pair is a space containing ?uid on which the brain ?oats as on a water-bed. The ?uid beneath the arachnoid membrane mixes with that inside the ventricles through a small opening in the fourth ventricle, called the median aperture, or foramen of Magendie.
These ?uid arrangements have a great in?uence in preserving the brain from injury.... divisions
An epidemic disease is usually infectious from person to person, but not necessarily so since many persons in a locality may simply be exposed to the same cause at one time; for example, outbreaks of lead-poisoning are epidemic in this sense.
The conditions which govern the outbreak of epidemics are poorly understood, but include infected food supplies, such as drinking water contaminated by waste from people with CHOLERA or typhoid fever (see ENTERIC FEVER); milk infected with TUBERCLE bacillus; or ‘fast food’ products contaminated with salmonella. The migrations of certain animals, such as rats, are in some cases responsible for the spread of PLAGUE, from which these animals die in great numbers. Certain epidemics occur at certain seasons: for example, whooping-cough occurs in spring, whereas measles produces two epidemics – as a rule, one in winter and one in March. In?uenza, the common cold, and other infections of the upper respiratory tract, such as sore throat, occur predominantly in the winter.
There is another variation, both as regards the number of persons affected and the number who die in successive epidemics: the severity of successive epidemics rises and falls over periods of ?ve or ten years.... epidemic
The Council is funded by doctors’ annual fees and is responsible to the Privy Council. Substantial reforms of the GMC’s structure and functions have been and are still being undertaken to ensure that it operates e?ectively in today’s rapidly evolving medical and social environment. In particular, the Council has strengthened its supervisory and disciplinary functions, and among many changes has proposed the regular revalidation of doctors’ professional abilities on a periodic basis. The Medical Register, maintained by the GMC, is intended to enable the public to identify whom it is safe to approach to obtain medical services. Entry on the Register shows that the doctor holds a recognised primary medical quali?cation and is committed to upholding the profession’s values. Under revalidation requirements being ?nalised, in addition to holding an initial quali?cation, doctors wishing to stay on the Register will have to show their continuing ?tness to practise according to the professional attributes laid down by the GMC.
Once revalidation is fully established, there will be four categories of doctor:
Those on the Register who successfully show their ?tness to practise on a regular basis.
Those whose registration is limited, suspended or removed as a result of the Council’s disciplinary procedures.
Those who do not wish to stay on the Register or retain any links with the GMC.
Those, placed on a supplementary list, who do not wish to stay on the main Register but who want to retain a formal link with the medical profession through the Council. Such doctors will not be able to practise or prescribe.... general medical council (gmc)
Symptoms These depend upon whether the anaemia is sudden in onset, as in severe haemorrhage, or gradual. In all cases, however, the striking sign is pallor, the depth of which depends upon the severity of the anaemia. The colour of the skin may be misleading, except in cases due to severe haemorrhage, as the skin of many Caucasian people is normally pale. The best guide is the colour of the internal lining of the eyelid. When the onset of the anaemia is sudden, the patient complains of weakness and giddiness, and loses consciousness if he or she tries to stand or sit up. The breathing is rapid and distressed, the pulse is rapid and the blood pressure is low. In chronic cases the tongue is often sore (GLOSSITIS), and the nails of the ?ngers may be brittle and concave instead of convex (koilonychia). In some cases, particularly in women, the Plummer-Vinson syndrome is present: this consists of di?culty in swallowing and may be accompanied by huskiness; in these cases glossitis is also present. There may be slight enlargement of the SPLEEN, and there is usually some diminution in gastric acidity.
CHANGES IN THE BLOOD The characteristic change is a diminution in both the haemoglobin and the red cell content of the blood. There is a relatively greater fall in the haemoglobin than in the red cell count. If the blood is examined under a microscope, the red cells are seen to be paler and smaller than normal. These small red cells are known as microcytes.
Treatment consists primarily of giving suf?cient iron by mouth to restore, and then maintain, a normal blood picture. The main iron preparation now used is ferrous sulphate, 200 mg, thrice daily after meals. When the blood picture has become normal, the dosage is gradually reduced. A preparation of iron is available which can be given intravenously, but this is only used in cases which do not respond to iron given by mouth, or in cases in which it is essential to obtain a quick response.
If, of course, there is haemorrhage, this must be arrested, and if the loss of blood has been severe it may be necessary to give a blood transfusion (see TRANSFUSION – Transfusion of blood). Care must be taken to ensure that the patient is having an adequate diet. If there is any underlying metabolic, oncological, toxic or infective condition, this, of course, must be adequately treated after appropriate investigations.
Megaloblastic hyperchromic anaemia There are various forms of anaemia of this type, such as those due to nutritional de?ciencies, but the most important is that known as pernicious anaemia.
PERNICIOUS ANAEMIA An autoimmune disease in which sensitised lymphocytes (see LYMPHOCYTE) destroy the PARIETAL cells of the stomach. These cells normally produce INTRINSIC FACTOR, the carrier protein for vitamin B12 (see APPENDIX 5: VITAMINS) that permits its absorption in the terminal part of the ILEUM. Lack of the factor prevents vitamin B12 absorption and this causes macrocytic (or megaloblastic) anaemia. The disorder can affect men and women, usually those over the age of 40; onset is insidious so it may be well advanced before medical advice is sought. The skin and MUCOSA become pale, the tongue is smooth and atrophic and is accompanied by CHEILOSIS. Peripheral NEUROPATHY is often present, resulting in PARAESTHESIA and numbness and sometimes ATAXIA. A rare complication is subacute combined degeneration of the SPINAL CORD.
In 1926 two Americans, G R Minot and W P Murphy, discovered that pernicious anaemia, a previously fatal condition, responded to treatment with liver which provides the absent intrinsic factor. Normal development requires a substance known as extrinsic factor, and this depends on the presence of intrinsic factor for its absorption from the gut. The disease is characterised in the blood by abnormally large red cells (macrocytes) which vary in shape and size, while the number of white cells (LEUCOCYTES) diminishes. A key diagnostic ?nd is the presence of cells in the BONE MARROW.
Treatment consists of injections of vitamin B12 in the form of hydroxocobalamin which must be continued for life.
Aplastic anaemia is a disease in which the red blood corpuscles are very greatly reduced, and in which no attempt appears to be made in the bone marrow towards their regeneration. It is more accurately called hypoplastic anaemia as the degree of impairment of bone-marrow function is rarely complete. The cause in many cases is not known, but in rather less than half the cases the condition is due to some toxic substance, such as benzol or certain drugs, or ionising radiations. The patient becomes very pale, with a tendency to haemorrhages under the skin and mucous membranes, and the temperature may at times be raised. The red blood corpuscles diminish steadily in numbers. Treatment consists primarily of regular blood transfusions. Although the disease is often fatal, the outlook has improved in recent years: around 25 per cent of patients recover when adequately treated, and others survive for several years. In severe cases promising results are being reported from the use of bone-marrow transplantation.
Haemolytic anaemia results from the excessive destruction, or HAEMOLYSIS, of the red blood cells. This may be the result of undue fragility of the red blood cells, when the condition is known as congenital haemolytic anaemia, or of acholuric JAUNDICE.
Sickle-cell anaemia A form of anaemia characteristically found in people of African descent, so-called because of the sickle shape of the red blood cells. It is caused by the presence of the abnormal HAEMOGLOBIN, haemoglobin S, due to AMINO ACID substitutions in their polypeptide chains, re?ecting a genetic mutation. Deoxygenation of haemoglobin S leads to sickling, which increases the blood viscosity and tends to obstruct ?ow, thereby increasing the sickling of other cells. THROMBOSIS and areas of tissue INFARCTION may follow, causing severe pain, swelling and tenderness. The resulting sickle cells are more fragile than normal red blood cells, and have a shorter life span, hence the anaemia. Advice is obtainable from the Sickle Cell Society.... inadequate intake of iron
Café au lait spots are usually oval in shape and may measure several centimetres across.
Generally, a few spots are not significant; larger numbers may be a sign of neurofibromatosis.... café au lait spots
Water, for example, has the formula H2O, indicating that each molecule is composed of 2 atoms of hydrogen (H2) and 1 of oxygen (O).... formula, chemical
The lymph is derived, initially, from the blood, the watery constituents of which exude through the walls of the CAPILLARIES into the tissues, conveying material for the nourishment of the tissues and absorbing waste products.
The spaces in the tissues communicate with lymph capillaries, which have a structure similar to that of the capillaries of the blood-vessel system, being composed of delicate ?at cells joined edge to edge. These unite to form ?ne vessels, resembling minute veins in structure, called lymphatics, which ramify throughout the body, passing through lymphatic glands and ultimately discharging their contents into the jugular veins in the root of the neck. Other lymph vessels commence in great numbers as minute openings on the surface of the PLEURA and PERITONEUM, and act as drains for these otherwise closed cavities. When ?uid is e?used into these cavities – as in a pleural e?usion, for example – its absorption takes place through the lymphatic vessels. The course of these vessels is described under the entry on GLAND.
Lymph circulates partly by reason of the pressure at which it is driven through the walls of the blood capillaries, but mainly in consequence of incidental forces. The lymph capillaries and vessels are copiously provided with valves, which prevent any back ?ow of lymph, and every time these vessels are squeezed (as by the contraction of a muscle, or movement of a limb) the lymph is pumped along.
The term lymph is also applied to the serous ?uid contained in the vesicles which develop as the result of vaccination, and used for the purpose of vaccinating other individuals.... lymph
(See also thought disorders.)... thought
During registration, information from the sense organs and the cerebral cortex is put into codes for storage in the short-term memory system. The codes are usually acoustic (based on the sounds and words that would be used to describe the information) but may use any of the ?ve senses. This system can take only a few chunks of information at a time: for example, only about seven longish numbers can be retained and recalled at once – the next new number displaces an earlier one that is then forgotten. And if a subject is asked to describe a person just met, he or she will recall only seven or so facts about that person. This depends on attention span and can be improved by concentration and rehearsal – for example, by reciting the list of things that must be remembered.
Material needing storage for several minutes stays in the short-term memory. More valuable information goes to the long-term memory where it can be kept for any period from a few minutes to a lifetime. Storage is more reliable if the information is in meaningful codes – it is much easier to remember people’s names if their faces and personalities are memorable too. Using techniques such as mnemonics takes this into account.
The ?nal stage is retrieval. Recognising and recalling the required information involves searching the memory. In the short-term memory, this takes about 40-thousandths of a second per item – a rate that is surprisingly consistent, even in people with disorders such as SCHIZOPHRENIA.
Most kinds of forgetting or AMNESIA occur during retrieval. Benign forgetfulness is usually caused by interference from similar items because the required information was not clearly coded and well organised. Retrieval can be improved by recreating the context in which the information was registered. This is why the police reconstruct scenes of crimes, and why revision for exams is more e?ective if facts are learnt in the form of answers to mock questions.
Loss of memory or amnesia mainly affects long-term memory (information which is stored inde?nitely) rather than short-term memory which is measured in minutes. Short-term memory may, however, be affected by unconsciousness caused by trauma. Drivers involved in an accident may be unable to recall the event or the period leading up to it. The cause of amnesia is disease of or damage to the parts of the brain responsible for memory. Degenerative disorders such as ALZHEIMER’S DISEASE, brain tumours, infections (for example, ENCEPHALITIS), STROKE, SUBARACHNOID HAEMORRHAGE and alcoholism all cause memory loss. Some psychiatric illnesses feature loss of memory and AGEING is usually accompanied by some memory loss, although the age of onset and severity vary greatly.... memory
(2) An internationally agreed unit (see SI UNITS) for measuring the quantity of a substance at molecular level.... mole
The symptoms depend upon the site of the infection. General symptoms such as fever, weight loss and night sweats are common. In the most common form of pulmonary tuberculosis, cough and blood-stained sputum (haemoptysis) are common symptoms.
The route of infection is most often by inhalation, although it can be by ingestion of products such as infected milk. The results of contact depend upon the extent of the exposure and the susceptibility of the individual. Around 30 per cent of those closely exposed to the organism will be infected, but most will contain the infection with no signi?cant clinical illness and only a minority will go on to develop clinical disease. Around 5 per cent of those infected will develop post-primary disease over the next two or three years. The rest are at risk of reactivation of the disease later, particularly if their resistance is reduced by associated disease, poor nutrition or immunosuppression. In developed countries around 5 per cent of those infected will reactivate their healed tuberculosis into a clinical problem.
Immunosuppressed patients such as those infected with HIV are at much greater risk of developing clinical tuberculosis on primary contact or from reactivation. This is a particular problem in many developing countries, where there is a high incidence of both HIV and tuberculosis.
Diagnosis This depends upon identi?cation of mycobacteria on direct staining of sputum or other secretions or tissue, and upon culture of the organism. Culture takes 4–6 weeks but is necessary for di?erentiation from other non-tuberculous mycobacteria and for drug-sensitivity testing. Newer techniques involving DNA ampli?cation by polymerase chain reaction (PCR) can detect small numbers of organisms and help with earlier diagnosis.
Treatment This can be preventative or curative. Important elements of prevention are adequate nutrition and social conditions, BCG vaccination (see IMMUNISATION), an adequate public-health programme for contact tracing, and chemoprophylaxis. Radiological screening with mass miniature radiography is no longer used.
Vaccination with an attenuated organism (BCG – Bacillus Calmette Guerin) is used in the United Kingdom and some other countries at 12–13 years, or earlier in high-risk groups. Some studies show 80 per cent protection against tuberculosis for ten years after vaccination.
Cases of open tuberculosis need to be identi?ed; their close contacts should be reviewed for evidence of disease. Adequate antibiotic chemotherapy removes the infective risk after around two weeks of treatment. Chemoprophylaxis – the use of antituberculous therapy in those without clinical disease – may be used in contacts who develop a strong reaction on tuberculin skin testing or those at high risk because of associated disease.
The major principles of antibiotic chemotherapy for tuberculosis are that a combination of drugs needs to be used, and that treatment needs to be continued for a prolonged period – usually six months. Use of single agents or interrupted courses leads to the development of drug resistance. Serious outbreaks of multiply resistant Mycobacterium tuberculosis have been seen mainly in AIDS units, where patients have greater susceptibility to the disease, but also in developing countries where maintenance of appropriate antibacterial therapy for six months or more can be di?cult.
Streptomycin was the ?rst useful agent identi?ed in 1944. The four drugs used most often now are RIFAMPICIN, ISONIAZID, PYRAZINAMIDE and ETHAMBUTOL. Three to four agents are used for the ?rst two months; then, when sensitivities are known and clinical response observed, two drugs, most often rifampicin and isoniazid, are continued for the rest of the course. Treatment is taken daily, although thrice-weekly, directly observed therapy is used when there is doubt about the patient’s compliance. All the antituberculous agents have a range of adverse effects that need to be monitored during treatment. Provided that the treatment is prescribed and taken appropriately, response to treatment is very good with cure of disease and very low relapse rates.... nature of the disease tuberculosis has
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
(2) A public o?cial responsible for registering births, deaths, and marriages.... registrar
Typically the patient complains of widespread severe itching, worse when the body is warm after a bath or in bed. Burrows are visible as wavy black lines 3–5 mm long in the skin of the hands, wrists or sides of the feet. The intensity of the rash depends on the immune response. Papules, pustules, crusts and excoriations are seen on the hands and there may be a widespread eczematous (see DERMATITIS) or urticarial (see URTICARIA) rash elsewhere. Papules or even nodules on the PENIS and SCROTUM are characteristic. In infants, burrows occur on the palms and soles. Diminished immune response in old age, DOWN’S (DOWN) SYNDROME, etc. lead to a type of scabies which is less itching and more scaly. Rarely, absence of immune response causes a mite-saturated, generalised scaly dermatitis (Norwegian scabies). Admission of such a patient to hospital may result in an outbreak of scabies in other patients, sta? and visitors caused by mite-infested airborne scale.
Treatment MALATHION 0·5 per cent aqueous lotion, or PERMETHRIN 5 per cent cream, applied to the whole body, except the head, for 24 hours and then washed o? cures the infection. In infants the head and neck should be included. The secondary eruption may take 2– 3 weeks to settle completely and 10 per cent crotamiton cream is used during this period. It is essential that all intimate contacts be treated simultaneously. FOMITES need not be treated.... scabies
The concept of the dose-response is important for understanding the risk of exposure to a particular substance. This is embodied in a statement by Paracelsus (c.1493–1541): ‘All substances are poisons; there is none which is not a poison. The right dose di?erentiates a poison and a remedy.’
Poisoning may occur in a variety of ways: deliberate – SUICIDE, substance abuse or murder; accidental – including accidental overdose of medicines; occupational; and environmental
– including exposure during ?re.
Ingestion is the most common route of exposure, but poisoning may also occur through inhalation, absorption through the skin, by injection and through bites and stings of venomous animals. Poisoning may be described as acute, where a single exposure produces clinical effects with a relatively rapid onset; or chronic, where prolonged or repeated exposures may produce clinical effects which may be insidious in onset, cumulative and in some cases permanent.
Diagnosis of poisoning is usually by circumstantial evidence or elimination of other causes of the clinical condition of the patient. Some substances (e.g. opioids) produce a characteristic clinical picture in overdose that can help with diagnosis. In some patients laboratory analysis of body ?uids or the substance taken may be useful to determine or con?rm the o?ending agent. Routine assays are not necessary. For a very small number of poisons, such as paracetamol, aspirin, iron and lead, the management of the patient may depend on measuring the amount of poison in the bloodstream.
Accurate statistics on the incidence of poisoning in the UK are lacking. Mortality ?gures are more reliable than morbidity statistics; annually, well over 100,000 cases of poisoning are admitted to hospital. The annual number of deaths from poisoning is relatively small – about 300 – and in most cases patients die before reaching hospital. Currently, CARBON MONOXIDE (CO) is by far the most common cause of death due to poisoning. The most common agents involved in intentional or accidental poisoning are drugs, particularly ANALGESICS, ANTIDEPRESSANT DRUGS and SEDATIVES. Alcohol is also commonly taken by adults, usually in combination with drugs. Children frequently swallow household cleaners, white spirit, plant material – such as belladonna (deadly nightshade) and certain mushrooms; for example, death cap and ?y agaric – aftershave and perfume as well as drugs. If possible, the suspect container, drug or plant should be taken with the victim to the hospital or doctor. The use of child-resistant containers has reduced the number of admissions of children to hospital for treatment. Bixtrex® is an intensely bitter-tasting agent which is often added to products to discourage ingestion; however, not everybody is able to taste it, nor has any bene?cial e?ect been proven.
Treatment of poisoning usually begins with decontamination procedures. For ingested substances this may involve making the patient sick or washing the stomach out (GASTRIC LAVAGE): this is usually only worthwhile if performed soon after ingestion. It should be emphasised that salt (sodium chloride) water must never be given to induce vomiting, since this procedure is dangerous and has caused death. For substances spilt on the skin, the affected area should immediately be thoroughly washed and all contaminated clothing removed. Following eye exposure, the affected eye/s should be thoroughly irrigated with saline or water.
Treatment thereafter is generally symptomatic and supportive, with maintenance of the victim’s respiratory, neurological and cardiovascular systems and, where appropriate, monitoring of their ?uid and electrolyte balance and hepatic and renal function. There are speci?c antidotes for a few substances: the most important of these are PARACETAMOL, iron, cyanide (see CYANIDE POISONING), opioids (see OPIOID), DIGOXIN, insecticides and some heavy metals. Heavy-metal poisoning is treated with CHELATING AGENTS – chemical compounds that form complexes by binding metal ions: desferrioxamine and pencillinamine are two such agents. The number of people presenting with paracetamol overdose – a common drug used for attempted suicide – has fallen sharply since restrictions were placed on its over-thecounter sales.
When a patient presents with an illness thought to be caused by exposure to substances at work, further exposure should be limited or prevented and investigations undertaken to determine the source and extent of the problem. Acutely poisoned workers will usually go to hospital, but those suffering from chronic exposure may attend their GP with non-speci?c symptoms (see OCCUPATIONAL HEALTH, MEDICINE AND DISEASES).
In recent years, legislation has been enacted in the UK to improve safety in the workplace and to ensure that data on the hazardous constituents and effects of chemicals are more readily available. These o?cial controls include the Control of Substances Hazardous to Health (COSHH) and the Chemicals (Hazard Information and Packaging) Regulations (CHIP) and are UK legislation in response to European Union directives.
The National Poisons Information Service is a 24-hour emergency telephone service available to the medical profession and provides information on the likely effects of numerous agents and advice on the management of the poisoned patient. The telephone numbers are available in the medical literature. In the UK this is not a public-access service. People who believe they, or their relatives, have been poisoned should seek medical advice from their GPs or attend their local hospital.
Toxbase The National Poisons Information Service provides a primary clinical toxicology database on the Internet: www.spib.axl.co.uk. This website provides information about routine diagnosis, treatment and management of people exposed to drugs, household products and industrial and agricultural products.
(See also APPENDIX 1: BASIC FIRST AID.)... poisons
In Britain, for instance, preventive medicine is usually taken to encompass a range of activities whose purpose is:
to reduce the chance of a person contracting a disease or becoming disabled.
to identify either an increased susceptibility to develop a disease, or an early manifestation of a disease at a stage which will still allow treatment to be e?ective. The American College of Preventive Medi
cine (1983) de?ned it as ‘a specialised ?eld of medical practice composed of distinct disciplines which utilise skills focusing on the health of de?ned populations in order to promote and maintain health and well-being and to prevent disease, disability and premature death’.
However de?ned, the spectrum of activities encompassed by preventive medicine is wide and includes actions, such as counselling about lifestyle, where there may not be a clear cut-o? between a preventive and a curative act. For example, advice about smoking and exercise to a recent victim of a myocardial infarction (see under HEART, DISEASES OF) is both essential to treatment and preventive against a future attack. Action aimed at a whole population – such as the addition of ?uoride to drinking-water to protect against dental caries (see under TEETH, DISORDERS OF) – is part of a population-based public-health strategy but would also be widely regarded as preventive medicine.
A common and widely accepted classi?cation of preventive medicine is as follows:
Primary prevention which aims at the complete avoidance of a disease (for example, by immunising a child against an infectious disease – see IMMUNISATION).
Secondary prevention which aims at detecting and curing a disease at an early stage before it has caused any symptoms. This requires ‘screening’ procedures to detect either the early pre-symptomatic condition, or a risk factor which may lead to it. (An example of the former is cervical cytology, where a sample of cells is scraped from the cervix of the UTERUS and examined microscopically for abnormality.
An example of the latter is CHOLESTEROL measurement as part of assessing an individual’s risk of developing ischaemic heart disease (see under HEART, DISEASES OF). If it is signi?cantly raised, dietary or drug treatment can be advised.)
Tertiary prevention aims at minimising the consequences for a patient who already has the disease (e.g. advising people to take more exercise and stop smoking after a heart attack).
Many prefer to limit the term ‘preventive medicine’ to primary and secondary prevention, emphasising the focus on risk-reducing interventions targeted at ‘well’ individuals. Others prefer the wider emphasis because of the importance of a preventive approach in reducing further disability by recognising and treating symptoms early. This can be particularly important in older people, where, for example, vigorous treatment of an orthopaedic problem can enable the patient to maintain physical mobility with all the bene?ts to health that brings. Whether primary, secondary or tertiary prevention, some form of screening question or test is normally necessary to identify a problem.
The range and extent of opportunities for prevention are expanding as research identi?es the causes of diseases and more e?ective treatment becomes feasible. Inevitably there is economic and political debate about the cost-e?ectiveness of prevention versus cure, as well as about the ETHICS. The situation varies in relation to the natural history of the speci?c disease. Some conditions can easily be prevented but once contracted cannot be cured
(e.g. RABIES); others are easily cured but are not yet preventable.
Screening Screening involves carrying out tests either to identify a treatable disease at a very early stage, before it has caused symptoms or damage; or to identify a risk factor which can lead to a disease. The tests might be by simple questioning (e.g. ‘Do you smoke cigarettes?’ – this predicts a considerable increase in the risk of chronic bronchitis, heart disease, bronchial cancer and many other diseases, and enables targeted advice and help to stop smoking to be given). Other screening tests involve carrying out complex special investigations such as blood tests or the microscopic investigations of cells – for example, for precancerous changes.
Many conditions can be identi?ed at an early stage before they cause symptoms or signs of disease and in time for e?ective treatment to be carried out. Inevitably, some of the screening tests proposed can be expensive (particularly if used in large populations), painful or inaccurate and may not improve the results of treatment. Screening can also provoke considerable anxiety in those waiting for tests or results. Therefore, over the years considerable research has been carried out into the appropriateness and ethics of screening, and the World Health Organisation in 1968 identi?ed a set of rules for evaluating screening tests:
The condition sought should be an important health problem, for which there should be an accepted treatment for patients with recognised disease.
Facilities for diagnosis and treatment should be available if a case is found.
The screening test or examination must be suitable and valid. A false positive test will cause massive anxiety and also considerable expense in proving that there is no disease. Similarly, false negatives can lead people to be reassured and to ignore serious symptoms until too late. If large numbers of positive tests or false positives occur during a screening programme, health services can be swamped.
The test, and any treatment as a possible result, should be acceptable. For example, there is little point in screening for a fetal abnormality which, if found, would lead to a recommendation for termination if the mother will refuse it on religious or moral grounds.
Screening tests also need to be considered from an economic perspective and the cost of case-?nding (including diagnosis and treatment of patients diagnosed) balanced in relation to possible expenditure on medical care as a whole.
Finally the programme should re?ect the natural history of the disease, and case-?nding should normally be a continuing process and not a ‘once for all’ project. If these rules are followed, considerable
bene?ts can result from well-planned and well-managed screening programmes, and they form an important part of any health-care system. The extent to which manipulation of genetic material will be added to more traditional approaches such as counselling, immunisation and drug treatment cannot yet be predicted but, as time goes by, it is often likely to be ethical and social controls which limit developments rather than technical and scienti?c limits.... preventive medicine
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
Structure
CORIUM The foundation layer. It overlies the subcutaneous fat and varies in thickness from 0·5–3.0 mm. Many nerves run through the corium: these have key roles in the sensations of touch, pain and temperature (see NEURON(E)). Blood vessels nourish the skin and are primarily responsible for regulating the body temperature. Hairs are bedded in the corium, piercing the epidermis (see below) to cover the skin in varying amounts in di?erent parts of the body. The sweat glands are also in the corium and their ducts lead to the surface. The ?brous tissue of the corium comprises interlocking white ?brous elastic bundles. The corium contains many folds, especially over joints and on the palms of hands and soles of feet with the epidermis following the contours. These are permanent throughout life and provide unique ?ngerprinting identi?cation. HAIR Each one has a root and shaft, and its varying tone originates from pigment scattered throughout it. Bundles of smooth muscle (arrectores pilorum) are attached to the root and on contraction cause the hair to stand vertical. GLANDS These occur in great numbers in the skin. SEBACEOUS GLANDS secrete a fatty substance and sweat glands a clear watery ?uid (see PERSPIRATION). The former are made up of a bunch of small sacs producing fatty material that reaches the surface via the hair follicle. Around three million sweat or sudoriparous glands occur all over the body surface; sited below the sebaceous glands they are unconnected to the hairs. EPIDERMIS This forms the outer layer of skin and is the cellular layer covering the body surface: it has no blood vessels and its thickness varies from 1 mm on the palms and soles to 0·1 mm on the face. Its outer, impervious, horny layer comprises several thicknesses of ?at cells (pierced only by hairs and sweat-gland openings) that are constantly rubbed o? as small white scales; they are replaced by growing cells from below. The next, clear layer forms a type of membrane below which the granular stratum cells are changing from their origins as keratinocytes in the germinative zone, where ?ne sensory nerves also terminate. The basal layer of the germinative zone contains melanocytes which produce the pigment MELANIN, the cause of skin tanning.
Nail A modi?cation of skin, being analagous to the horny layer, but its cells are harder and more adherent. Under the horny nail is the nail bed, comprising the well-vascularised corium (see above) and the germinative zone. Growth occurs at the nail root at a rate of around 0·5 mm a week – a rate that increases in later years of life.
Skin functions By its ability to control sweating and open or close dermal blood vessels, the skin plays a crucial role in maintaining a constant body temperature. Its toughness protects the body from mechanical injury. The epidermis is a two-way barrier: it prevents the entry of noxious chemicals and microbes, and prevents the loss of body contents, especially water, electrolytes and proteins. It restricts electrical conductivity and to a limited extent protects against ultraviolet radiation.
The Langerhans’ cells in the epidermis are the outposts of the immune system (see IMMUNITY), just as the sensory nerves in the skin are the outposts of the nervous system. Skin has a social function in its ability to signal emotions such as fear or anger. Lastly it has a role in the synthesis of vitamin D.... skin
Idiopathic stammering begins at some time between the onset of speech and puberty, mostly between 2–5 years of age. Acquired stammering at a later age due to brain damage is rare. The prevalence of stammering (the percentage of the population actually stammering at any point in time) is approximately 0·9 per cent. Three times as many boys as girls stammer. About 70 per cent of stammering children recover with little or no therapy. Stammerers have not been shown to demonstrate di?erences in personality from non-stammerers; there are, however, indications that at least some stammerers show minimal di?erences from ?uent speakers in cerebral processing of verbal material.
There is a genetic predisposition towards stammering. The risk of stammering among ?rst-degree relatives of stammerers is more than three times the population risk. In 77 per cent of identical twins, either both stammer or both are ?uent. Only 33 per cent of non-identical twins agree in this way. As there are identical twins who di?er for stammering, environmental factors must be important for some stammerers. There are relatively large numbers of stammerers in highly competitive societies, where status and prestige are important and high standards of speech competence are valued.
Di?erent treatments have been demonstrated to produce considerable bene?t, their basic outline being similar. A long period of time is spent in training stammerers to speak in a di?erent way (?uency-shaping techniques). This may include slowing down the rate of speech, gentle onset of utterance, continuous ?ow with correct juncturing, etc. When the targets have been achieved within the clinic, a series of planned speech assignments outside the clinic is undertaken. In these assignments, and initially in everyday situations, the ?uency-enchancing techniques have to be used conscientiously. Gradually speech is shaped towards normality requiring less and less e?ort. Therapy may also include some work on attitude change (i.e. helping the client to see him or herself as a ?uent speaker) and possibly general communicative skills training.
For information about organisations concerned with stammering, see Appendix 2.... stammering
The human backbone is about 70 cm (28
inches) in length, and varies little in full-grown people; di?erences in height depend mainly upon the length of the lower limbs. The number of vertebrae is 33 in children, although in adult life ?ve of these fuse together to form the sacrum, and the lowest four unite in the coccyx, so that the number of separate bones is reduced to 26. Of these there are seven in the neck, known as cervical vertebrae; 12 with ribs attached, in the region of the thorax known as thoracic or dorsal vertebrae; ?ve in the loins, called lumbar vertebrae; ?ve fused to form the sacrum; and four joined in the coccyx. These numbers are expressed in a formula thus: C7, D12, L5, S5, Coc4=33.
Although the vertebrae in each of these regions have distinguishing features, all the vertebrae are constructed on the same general plan. Each has a thick, rounded, bony part in front, known as the body, and these bodies form the main thickness of the column. Behind the body of each is a ring of bone, the neural ring, these rings placed one above another forming the bony canal which lodges the spinal cord. From each side of the ring a short process of bone known as the transverse process stands out, and from the back of the ring a larger process, the spinous process, projects. These processes give attachment to the strong ligaments and muscles which unite, support, and bend the column. The spines can be seen or felt beneath the skin of the back lying in the centre of a groove between the muscular masses of the two sides, and they give to the column its name of the spinal column. One of these spines, that of the seventh cervical vertebra, is especially large and forms a distinct bony prominence, where the neck joins the back. Between the bodies of the vertebrae lies a series of thick discs of ?brocartilage known as intervertebral discs. Each disc consists of an outer portion, known as the annulus ?brosus, and an inner core, known as the nucleus pulposus. These 23 discs provide the upper part of the spine with pliability and resilience.
The ?rst and second cervical vertebrae are specially modi?ed. The ?rst vertebra, known as the atlas, is devoid of a body, but has a specially large and strong ring with two hollows upon which the skull rests, thus allowing forward and backward movements (nodding). The second vertebra, known as the axis, has a pivot on its body which ?ts into the ?rst vertebra and thus allows free rotation of the head from side to side. The spinal column has four natural curves (see diagram) which help to cushion the shocks of walking and running.
The neural rings of the vertebrae form a canal, which is wide in the neck, smaller and almost round in the dorsal region, and wide again in the lumbar vertebrae. Down the canal runs the spinal cord, and the nerves leaving the cord do so through openings between the vertebrae which are produced by notches on the upper and lower margins of each ring. The intervertebral foramina formed by these notches are so large in comparison with the nerves passing through them that there is no chance of pressure upon the latter, except in very serious injuries which dislocate and fracture the spine.... spinal column
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