bluuebunny/crossref_metadata_2025 huggingface dataset:
Malaria
Authors: White Nicholas J. , Dondorp Arjen M.
Published: February 2020

An estimated 1.1 billion people residing in the tropical world are at high risk for malaria. In 2016, there were an estimated 216 million cases of malaria worldwide causing 445,000 deaths. Africa accounted for 90% of the cases and 91% of deaths; around 70% of the deaths were in children aged less than 5 years. Malaria is transmitted by the female anopheles mosquito and six species of Plasmodium commonly cause malaria in humans: P. falciparum, P. vivax, P. ovale (two species), P. malariae, and P. knowlesi. P. falciparum, the most pathogenic species accounts for 99% of malaria deaths. First line treatment of uncomplicated falciparum malaria is with artemisinin combination therapies (ACTs).
Toxoplasmosis
Authors: Liesenfeld Oliver , Petersen Eskild
Published: February 2020

Toxoplasma gondii is a protozoan parasite with worldwide distribution that infects up to one-third of the world’s population. Human infection is acquired through ingestion in water or food of oocysts shed by cats, or by ingestion of bradyzoites released from cysts contained in uncooked or undercooked meat (e.g. sheep, swine, cattle). Following invasion in the intestine, tachyzoites rapidly disseminate throughout the host. Immune mechanisms mediate the formation of cysts, primarily in the brain, eye, and skeletal and heart muscles, where they persist for the life of the host. Presence of infection can be established by direct detection of the parasite in clinical samples (often by polymerase chain reaction) or by serological techniques.
Cryptosporidium and cryptosporidiosis
Authors: Cacciò Simone M.
Published: February 2020

Parasites within the genus Cryptosporidium infect the mucosal epithelia of a variety of vertebrate hosts, including humans, affecting the health, survival, and economic development of millions of people and animals worldwide. Human infection is mainly caused by two species, Cryptosporidium parvum and C. hominis. The former species is also prevalent in young livestock and has a demonstrated zoonotic potential, whereas the latter species is essentially a human parasite. Direct and indirect (through contaminated water and food) transmission routes exist for both species. Treatment of immunocompetent patients, when necessary, is based on nitazoxanide, a thiazolide drug with broad antiparasitic activities. Nitazoxanide is the only US Food and Drug Administration-approved drug for the treatment of cryptosporidiosis, but it is not licensed in Europe.
Cyclospora and cyclosporiasis
Authors: Kelly Paul , Lainson Ralph
Published: February 2020

Most species of Cyclospora (Protozoa: Apicomplexa: Eimeriidae) are parasites of various reptiles and mammals. C. cayetanensis, which probably infects only humans, is transmitted by way of resistant oocysts voided in the faeces and contaminating food or water. Distribution is worldwide, particularly in regions with a low level of hygiene. Clinical presentation is with explosive outbreaks of acute diarrhoea, with this infection now regarded as an important causative agent of traveller’s diarrhoea. Diagnosis is dependent on detection of oocysts in faeces by direct examination or in stained faecal smears. Aside from supportive care, treatment with trimethoprim–sulfamethoxazole has proved effective in eliminating the parasite in immunocompetent patients, but relapses are common in those with AIDS. Prevention is by ensuring good general hygiene, and in areas of high endemicity water should be boiled before drinking or use in preparation of fruits/vegetables that are to be eaten raw.
Sarcocystosis (sarcosporidiosis)
Authors: Cooper John E.
Published: February 2020

Sarcocystosis is characterized by the invasion of various tissues by protozoa of the genus Sarcocystis. S. hominis (intermediate host domestic cattle) and S. suihominis (domestic pig) are the most significant to humans, to whom they are transmitted by ingestion of uncooked beef or pork. Camel meat can be a significant source of S. cameli in Arabia. Humans and other primates serve as either intermediate or final host: (1) intermediate host—presence of cysts in muscle is usually asymptomatic, but might cause myositis or myopathy; detected on clinical examination or muscle biopsy; (2) final host—can be asymptomatic or cause fever and gastrointestinal upset; oocysts or sporocysts can be detected in faeces. There is no specific treatment. Prevention is by not eating uncooked meat from any animal and by improving food hygiene in poorer countries.
Giardiasis and balantidiasis
Authors: Eckmann Lars , Heyworth Martin F.
Published: February 2020

Infection with Giardia intestinalis, a common flagellate protozoan that colonizes the lumen of the small intestine, is acquired by ingesting environmentally resistant cysts of the parasite, typically in water or food, or after contact with faecal material from infected individuals. Strains of the parasite that can potentially infect humans are also harboured by various mammals, including dogs and cattle. Manifestations include watery diarrhoea, abdominal discomfort, distension and pain, nausea and vomiting, weight loss, and malabsorption, with the infection typically being persistent and severe in individuals with certain immunodeficiencies. Chronic G. intestinalis infection can lead to micronutrient deficiencies, and impairment of growth and cognitive development in children.
Leishmaniasis
Authors: Bryceson Antony D.M. , Lockwood Diana N.J.
Published: February 2020

Leishmaniasis is caused by parasites of the genus Leishmania, which are transmitted to humans from human or animal reservoirs by the bites of phlebotomine sandflies. In places the disease is common and important, with perhaps 500,000 cases of visceral leishmaniasis and 1.5–2 million cases of cutaneous leishmaniasis worldwide each year. Diagnosis is by demonstration of leishmania organisms in tissue smears or biopsy material by microscopy, culture, or detecting leishmaniai DNA by polymerase chain reaction. As an imported disease, cutaneous leishmaniasis is common in travellers, military personnel, and immigrants coming from endemic areas, while the diagnosis of the less common visceral leishmaniasis is frequently overlooked. Prevention is by controlling reservoir hosts and sandfly vectors, or by avoiding bites by vectors. There is no vaccine.
Lymphatic filariasis
Authors: Knight Richard
Published: February 2020

Wuchereria bancrofti, Brugia malayi, and B. timori are mosquito-borne lymphatic-dwelling nematode parasites that are important causes of morbidity, disability, and social stigma in tropical and subtropical countries. The total population at risk is now estimated to be 856 million in some 52 countries where these infections are endemic. In 2000 before systematic control programmes 120 million people were infected, of whom about 40 million had clinical disease and some 80 million had hidden lymphatic damage. Bancroftian filariasis due to W. bancrofti, which has no animal reservoir, accounts for 90% human infections worldwide; it was introduced into the Americas from Africa by the Atlantic slave trade.
Cysticercosis
Authors: Garcia Hector H. , Gilman Robert H.
Published: February 2020

Cysticercosis, infection by larvae of the pork tapeworm Taenia solium, is the most common helminthic infection of the human central nervous system. It accounts for up to 30% of all seizures and epilepsy in endemic countries, and travel and immigration now lead to its more frequent presentation in industrialized countries. Ingestion of raw or undercooked pork can lead to infection with the T. solium cysticercus, formerly known as ‘Cysticercus cellulosae’, which is an encysted immature tapeworm. Once attached to the person’s small intestine, the head, or scolex, evaginates from the cysticercus, anchors in the intestinal mucosa and develops segments (proglottids) to become an adult tapeworm. Only by ingesting T. solium ova can humans develop cysticercosis. The commonest syndromes are late-onset epilepsy or intracranial hypertension. Diagnosis is based on brain imaging studies (CT or MRI) and supported by highly specific serology.
Liver fluke infections
Authors: Andrews Ross H. , Khuntikeo Narong , Sithithaworn Paiboon , Petney Trevor N.
Published: February 2020

Liver flukes, otherwise known as trematodes, are leaf-like hermaphroditic flatworms. In certain parts of the world, the hepatobiliary system of humans is commonly infected by flukes of the genera Clonorchis and Opisthorchis and occasionally by other species. Humans acquire liver fluke infection by the ingestion of viable metacercariae that are found in second intermediate hosts through raw or partially cooked food, predominately cyprinid fish. These infections are usually diagnosed by finding eggs in the faeces. The diseases caused by liver flukes range from asymptomatic, mild disease to fatal bile duct cancer. Currently the drugs of choice for treatment of liver fluke infection are praziquantel and triclabendazole.
Lung flukes (paragonimiasis)
Authors: Silachamroon Udomsak , Vanijanonta Sirivan
Published: February 2020

Paragonimiasis is an infection by flukes of the genus Paragonimus, with foci of disease in Asia, Africa, and Central and South America. Humans acquire infection by eating metacercariae in improperly cooked freshwater crabs or crayfish. Acute inflammatory and allergic symptoms are rarely serious and usually resolve spontaneously. Chronic manifestations may be (1) pulmonary—most remarkably with a chronic, productive cough with jam-like, brownish-red sputum; and (2) extrapulmonary—most importantly in the central nervous system, often presenting with seizures. Diagnosis is by demonstrating ova in sputum, stool, or pleural fluid. Serology can be used to support the diagnosis, especially in extrapulmonary paragonimiasis. Treatment with praziquantel is almost always effective. Prevention is by health education and the mass treatment of infected people in an endemic area.
Intestinal trematode infections
Authors: McGregor Alastair
Published: February 2020

It is notoriously difficult to estimate the prevalence of intestinal trematode infection, but the most widely accepted figures suggest that 40–50 million people worldwide are infected with at least one of these organisms. Most of these infections are found in tropical South and East Asia, mostly as a result of local culinary practice. The most important intestinal flukes are Fasciolopsis buski and members of the families Echinostomatidae and Heterophyidae. Infection is acquired through the ingestion of the second intermediate host—undercooked freshwater fish, molluscs, frogs, or vegetation contaminated with live metacercariae. Fasciolopsis buski, one of the largest (at 20–77 mm) and most important flukes, is acquired by ingestion of contaminated water plants. Heavy infections may cause abdominal discomfort and diarrhoea, but most infections are entirely asymptomatic. Praziquantel is the drug of choice for all of these infections, which can be prevented by thoroughly cooking potentially infected foodstuffs.
Nonvenomous arthropods
Authors: Paul John
Published: February 2020

Most arthropods are harmless, but there is a select group of medically significant species. Invertebrates with jointed limbs belong to the phylum Arthropoda. Most of the medically important arthropods are in the classes Insecta (insects) or Arachnida (spiders, ticks, mites, scorpions). Some members of the class Chilopoda (centipedes) may bite humans, and some of the larger members of the Crustacea (crabs, lobsters) may cause injury with pincers or spines. Categories of medical significance include: envenoming by bites or stings; allergic reactions to bites, stings, hairs, or inhaled allergens; transmission of infectious agents; infestation; the pain and trauma from bites or penetrating spines; phobia and delusory parasitosis. Arthropods may cause nuisance by their presence or the noises they may make, or by being perceived as unhygienic. It is helpful to identify the species involved, although this may not always be possible, so generic approaches can help the management of problems.
Pentastomiasis (porocephalosis, linguatulosis/linguatuliasis, or tongue worm infection)
Authors: Warrell David A.
Published: February 2020

Pentastomida are dioecious, obligate parasites that are currently grouped in subclass Branchiura (fish lice and cycloids) of class Maxillopoda, subphylum Crustacea, phylum Arthropoda. Common names are ‘pentastomes’ (referring to two pairs of hooks above the mouth that give the impression of five stomata) or ‘tongue worms’ (alluding to the tongue-like appearance of some, such as adult Linguatula). Adult pentastomes inhabit the upper respiratory tracts of their end hosts (vertebrates such as reptiles, fish, birds, and mammals) where they feed on blood and other tissues. Their larvae infect internal organs of vertebrate or arthropod intermediate hosts. Pentastomes appear to have coevolved with other maxillopodan/branchiuran parasites and their vertebrate hosts. There are about 100 living species in the orders Cephalobaenida (e.g. genus Raillietiella) and Porocephalida (e.g. genera Linguatula, Armillifer, Porocephalus, Leiperia, and Sebekia).
Epidemiology of sexually transmitted infections
Authors: Mabey David , Vas-Falcao Anita
Published: February 2020

Although accurate incidence figures are not available in most countries, sexually transmitted infections (STIs) are a large cause of morbidity worldwide. The burden falls especially heavily on women and infants, with up to half a million perinatal deaths attributable to syphilis annually. Mobile populations, those with many sexual partners, and those whose partners have many partners are at increased risk, and the prevalence of treatable STIs is many times higher in poor populations. Other STIs, especially those that cause genital ulceration, increase the risk of HIV transmission. In Western countries, the reported incidence of many STIs fell during the 1980s and 1990s, probably as a result of changes in sexual behaviour resulting from the HIV epidemic, but has increased subsequently. Although accurate data are not available from most low- and middle-income countries (LMICs), there is no doubt that STIs are more prevalent in the developing world.
Sexual behaviour
Authors: Mercer Catherine H. , Johnson Anne M.
Published: February 2020

Discussion of sexual lifestyle and the ability to take a sexual history are relevant to many types of clinical practice. The age at which people first have sex has decreased and the age at which people start cohabiting has become later in recent decades, increasing the time available to accumulate sexual partners and thus be at risk of sexually transmitted infections (STIs), including human immunodeficiency virus (HIV). While many people have few partners, a small proportion of the population has many. People with many partners are most at risk of STIs, but there are many other influences including the gender, age, and ethnicity of their partners and the type of sexual practice. This chapter covers the adverse consequences of sexual behaviour (including STIs and unintended pregnancy), and initiatives to encourage reducing partner numbers, using condoms and effective contraception, and engaging in less risky practices.
Vaginal discharge
Authors: Nyirjesy Paul
Published: February 2020

Vaginal symptoms are a frequent source of discomfort and distress for many women. Bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis are considered the most common causes in premenopausal women, but atrophic vaginitis and non-infectious disorders seem to occur more often in menopausal women. Self-diagnosis and syndromic management, although increasingly encouraged in many parts of the world, are fraught with inaccuracy. A proper diagnosis depends on a thorough history, examination, and readily available tests in the clinic. Ancillary tests to be considered in selective circumstances include culture for yeast, culture or nucleic acid amplification testing (NAAT) for Trichomonas vaginalis, Neisseria gonorrhoeae, or Chlamydia trachomatis, and Gram stain or (rarely) maturation index. Once a proper diagnosis is obtained, appropriate treatment can be selected.
Pelvic inflammatory disease
Authors: Ross Jonathan D.C.
Published: February 2020

Pelvic inflammatory disease (PID) is an infection of the endometrium, fallopian tubes, and adnexae caused by a wide variety of bacteria, including Chlamydia trachomatis, Neisseria gonorrhoeae, and genital tract bacteria, most notably anaerobes. PID is often asymptomatic but clinical manifestations can range from mild pelvic pain and tenderness to severe peritonitis. Pelvic abscess formation is a serious infectious complication. However, only about 5% of patients with PID have a fever or severe infectious manifestations. An accurate clinical diagnosis of PID is difficult and it is commonly confused with other pelvic conditions, including ectopic pregnancy, appendicitis, and rupture or torsion of an ovarian cyst. Antibiotic therapy is aimed primarily at C. trachomatis, N. gonorrhoeae, and anaerobic bacteria, with prompt identification and treatment of PID recommended in an attempt to reduce the 15% rate of tubal infertility and 40% risk of chronic pelvic pain following this infection.
Principles of contraception
Authors: Haider Zara
Published: February 2020

There are many contraceptive methods available (increasing year on year) which can be classified as: hormonal and non-hormonal, longer lasting, and those with a shorter duration of action, reversible and irreversible. No contraceptive method is 100% effective (apart from abstinence) and where there is potential risk of conception due to unprotected sex or an error with a contraceptive regimen, the patient must be informed about methods of emergency (post-coital) contraception, the most effective being the post-coital intrauterine device (PCIUD). Education of the public about the benefits of contraception is vital and must be done in a timely way (e.g. through school sex education, media, and online resources).
Environmental medicine, occupational medicine, and poisoning—Introduction
Authors: Ayres Jon G.
Published: February 2020

The environment, both occupational and beyond, can affect health in many ways, adversely as well as beneficially. While to date many of these effects have been well understood, most specifically for the work environment, the importance of the wider environment as a cause of ill health has been less well studied on the basis that there is not much one can do about general exposures, such as the weather, or specific events, such as volcanic eruptions, apart from deal with the direct effects. However, increasing awareness of the importance of the environment on health, such as exposure to air pollution (both indoor and outdoor) and the short-, medium-, and long-term effects of climate change, has resulted in better understanding of interventions that can improve health or at least abrogate deleterious effects. This section discusses these aspects in detail.
Occupational and environmental health
Authors: Agius Raymond , Sen Debasish
Published: February 2020

Occupational diseases are those for which work or, specifically, exposures in the workplace are necessary causes. The most prevalent occupational diseases in developed countries today are musculoskeletal and psychological disorders (usually stress-related conditions), but generally occupationally related malignancies (e.g. mesothelioma related to asbestos exposure) have the most serious outcomes. The proportion of all cancers attributable to occupational exposures is about 4%, with occupationally related cancers almost exclusively concentrated in manual workers aged 20 or over in sectors such as mining, agriculture, and industry. When presented with a patient whose illness might possibly have been caused or aggravated by work or by other environmental factors, the physician can usefully adopt an approach similar to that used for determining causation in epidemiological studies; the key issues being the temporality, reversibility, exposure-response, strength of association, and specificity of the illness with exposure to the factor in question.
Aviation medicine
Authors: Bagshaw Michael
Published: February 2020

Travel by air is a safe means of transport, but puts people at various physiological risks and is a potential means of spreading infectious disease. Physiological risks associated with flying include hypoxia, as atmospheric pressure falls with altitude. The minimum cabin pressure in commercial passenger aircraft (565 mm Hg, 75.1 kPa) brings a healthy individual’s arterial P along the plateau of the oxyhaemoglobin dissociation curve until just at the top of the steep part, but does not cause desaturation. By contrast, people with respiratory disease and a low arterial oxygen pressure may desaturate, which can be overcome by administering 30% oxygen, this being equivalent to breathing air at ground level. There is no evidence that the pressurized aircraft cabin itself encourages transmission of disease, and recirculation of cabin air is not a risk factor for contracting symptoms of upper respiratory tract infection.
Heat
Authors: Stroud Michael A.
Published: February 2020

Rising body temperature triggers behavioural and physiological responses including reduction in physical activity, alterations of clothing, skin vasodilatation, and sweating. Heat-related illness is relatively common, especially with high humidity or prolonged physical activity. Risk can be reduced by acclimatization with repeated heat exposure, but some individuals seem to be particularly susceptible. Clinical presentations of heat-related illness include (1) ‘heat exhaustion’—the commonest manifestation, with symptoms including nausea, weakness, headache, and thirst. Patients appear dehydrated, complain of being hot, and are flushed and sweaty. Treatment requires rest and fluids, given orally or (in severe cases) intravenously. (2) ‘Heat stroke’ victims often complain of headache, may be drowsy or irritable, and may claim to feel cold. Core temperature is usually 38–41°C, but the patient is shivering with dry, vasoconstricted skin. Treatment requires (a) aggressive rapid cooling; (b) close biochemical monitoring; (c) supportive care for organ failure. There is significant mortality.
Radiation
Authors: Meara Jill
Published: February 2020

Ionizing radiation has sufficient energy to break chemical bonds and produce charged ions in living tissue. These changes might cause cell death, but breaks of both strands of a DNA molecule that do not kill a cell can be a precursor of cancer. Excluding medical exposures, natural radiation accounts for most human exposure, which produces health effects that might be (1) stochastic, where the probability of manifesting the effect depends on the radiation dose, including carcinogenesis and induction of heritable defects; (2) psychological, especially following accidental exposures; and (3) tissue reactions, occurring when sufficient cells are killed after exposure to radiation doses above a certain threshold, including the acute radiation syndrome (radiation sickness) and radiation burns.
Injuries, envenoming, poisoning, and allergic reactions caused by animals
Authors: Warrell David A.
Published: February 2020

Attacks by wild and domesticated animals are increasing worldwide. They are best prevented by taking local advice about minimizing exposure. Injuries usually occur in places remote from medical care. They may involve extensive trauma, haemorrhagic shock, and a high risk of bacterial contamination. First aid consists of resuscitation, control of bleeding and perforating injuries, intravenous fluid replacement, and rapid evacuation to hospital for emergency surgery and treatment of infection. In hospital, specific antivenom (hyperimmune equine or ovine immunoglobulins) is given if there is evidence of systemic or severe local envenoming. Early anaphylactic or pyrogenic reactions and late serum sickness antivenom reactions are common but not predictable by hypersensitivity tests.
Poisonous fungi
Authors: Persson Hans , Warrell David A.
Published: February 2020

This chapter covers poisoning by members of the fungal subkingdom Dikarya that includes most of the ‘higher fungi’. The phylum Ascomycota contains the medically important toxic fungi Claviceps purpurea, the cause of ergotism, Aspergillus flavus, a source of hepatotoxic and carcinogenic aflatoxins, the edible but potentially toxic morel mushrooms (Morchella species), Gyromitra species, and Podostroma cornudamae that has caused multisystem symptoms and signs. The phylum Basidiomycota includes the order Agaricales (gilled mushrooms/toadstools or agarics) to which most of the medically important larger fungi belong. ‘Mushroom’ and ‘toadstool’ may suggest ‘edible’ and ‘poisonous’ respectively, but these terms are not strictly applied. Poisonous species must be distinguished from field (Agaricus campestris) and cultivated (A. bisporus) mushrooms and from the many other mushrooms that are considered to be delicious and are passionately sought after by mycophiles worldwide.
Nutrition: Macronutrient metabolism
Authors: Frayn Keith N. , Evans Rhys D.
Published: February 2020

Food intake is sporadic and, in many cultures, occurs in three daily boluses. At the same time, energy expenditure is continuous and can vary to a large extent independently of the pattern of energy intake, although fixed or predictable demands (e.g. through occupation) means that in most persons food intake and energy expenditure are soon balanced. The body has developed complex systems that direct excess nutrients into storage pools; as they are needed, they also regulate the mobilization of nutrients from these pools. Carbohydrate, lipid, and protein (the latter a source of amino acids) are the three types of energy supply that are stored variably and assimilated from food each day. That we can carry on our daily lives without thinking about whether to store or mobilize fuels, and which to use, attests to the remarkable efficiency and refinement of these systems of metabolic control.
Artificial nutrition support
Authors: Woodward Jeremy
Published: February 2020

The prevalence and relevance of undernutrition in affluent societies is often unrecognized, but nutritional status significantly impacts outcomes in all disease states. Nutrition screening identifies patients at risk of undernutrition and should be carried out in hospitals and community: its components comprise past weight loss, current body mass index, and likely foreseeable nutritional challenges. A body mass index less than 18.5 kg/m2; weight loss of more than 10% over 6 months; or BMI of less than 20 kg/m2 with weight loss of more than 5% over 6 months, are all indicative of undernutrition. Nutrition support is indicated for malnourished patients or those at risk of undernutrition in view of inadequate oral intake or malabsorption. Timing of the intervention depends on the pre-existing nutritional status and the likelihood of restoring adequate intake.
Glycogen storage diseases
Authors: Lachmann Robin H. , Cox Timothy M.
Published: February 2020

Glycogen is a highly branched glucose polymer with a compacted structure found predominantly in liver and muscle. Liver glycogen is important in the maintenance of euglycaemia during fasting; muscle glycogen is an immediate source of glucose for energy production during exercise. Genetic disorders affecting proteins that regulate glycogen metabolism and transport, as well as those which catalyse its biosynthesis and breakdown, cause marked accumulation of glycogen in diverse tissues, and pathological glycogen often has an abnormal macromolecular structure. Depending on the enzyme system involved, diseases of glycogen metabolism principally affect liver and muscle. Clinical features are related to pathological glycogen in tissues and/or failure to release glucose. Glycogen storage is associated with organomegaly and tissue injury. Fasting hypoglycaemia occurs where hepatic breakdown of glycogen is impaired. Glycogen diseases that affect muscle usually present with rhabdomyolysis, exercise intolerance, and muscle pain or weakness. Formerly, diseases of glycogen metabolism were diagnosed by showing excess storage of glycogen in the tissue of interest, accompanied by reduced activity of particular glycogen-metabolizing enzymes. Currently, where available, molecular analysis of genomic DNA is the preferred method for providing a definitive diagnosis. The mainstay of treatment of glycogen diseases affecting the liver is dietary, including pre-emptive management of hypoglycaemia that is readily provoked by fasting. Dietary interventions may also ameliorate some of the glycogen diseases that affect muscle, and weakness and pain after exertion can be improved by graduated exercise programmes in some patients.
Inherited diseases of copper metabolism: Wilson’s disease and Menkes’ disease
Authors: Schilsky Michael L. , Mistry Pramod K.
Published: February 2020

Copper is an essential metal that is an important cofactor for many proteins and enzymes. Two related genetic defects in copper transport have been described, each with distinct phenotypes. Wilson’s disease—an uncommon disorder (1 in 30 000) caused by autosomal recessive loss-of-function mutations in a metal-transporting P-type ATPase (ATP7B) that result in defective copper excretion into bile and hence copper toxicity. Typical presentation is in the second and third decade of life with liver disease (ranging from asymptomatic to acute fulminant hepatic failure or chronic end-stage liver disease) or neurological or psychiatric disorder (dystonia, dysarthria, parkinsonian tremor, movement disorder, a spectrum of psychiatric ailments). While no single biochemical test or clinical finding is sufficient for establishing the diagnosis, typical findings include low serum ceruloplasmin, high urinary copper excretion, and elevated liver copper content. Corneal Kayser–Fleischer rings may be seen. Treatment is with copper chelating agents and zinc. Liver transplantation is required for fulminant hepatic failure and decompensated liver disease unresponsive to medical therapy. Menkes’ disease—a rare disorder (1 in 300 000) caused by X-linked loss-of-function mutations in a P-type ATPase homologous to ATP7B (ATP7A) that result in defective copper transport across intestine, placenta, and brain and hence cellular copper deficiency. Clinical presentation is in infancy with facial dimorphism, connective tissue disorder, hypopigmentation, abnormal hair, seizures, and failure to thrive, usually followed by death by age 3 years (although some variants with a milder phenotype result from milder mutations, e.g. occipital horn syndrome). Treatment, which is only effective when presymptomatic diagnosis is made in a sibling after florid presentation in a previous affected sibling, is with intravenous copper histidine.
A physiological approach to acid–base disorders: The roles of ion transport and body fluid compartments
Authors: Seifter Julian
Published: February 2020

The normal pH of human extracellular fluid is maintained within the range of 7.35 to 7.45. The four main types of acid–base disorders can be defined by the relationship between the three variables, pH, Pco2, and HCO3–. Respiratory disturbances begin with an increase or decrease in pulmonary carbon dioxide clearance which—through a shift in the equilibrium between CO2, H2O, and HCO3–—favours a decreased hydrogen ion concentration (respiratory alkalosis) or an increased hydrogen ion concentration (respiratory acidosis) respectively. Metabolic acidosis may result when hydrogen ions are added with a nonbicarbonate anion, A−, in the form of HA, in which case bicarbonate is consumed, or when bicarbonate is removed as the sodium or potassium salt, increasing hydrogen ion concentration. Metabolic alkalosis is caused by removal of hydrogen ions or addition of bicarbonate. Laboratory tests usually performed in pursuit of diagnosis, aside from arterial blood gas analysis, include a basic metabolic profile with electrolytes (sodium, potassium, chloride, bicarbonate), blood urea nitrogen, and creatinine. Calculation of the serum anion gap, which is determined by subtracting the sum of chloride and bicarbonate from the serum sodium concentration, is useful. The normal value is 10 to 12 mEq/litre. An elevated value is diagnostic of metabolic acidosis, helpful in the differential diagnosis of the specific metabolic acidosis, and useful in determining the presence of a mixed metabolic disturbance. Acid–base disorders can be associated with (1) transport processes across epithelial cells lining transcellular spaces in the kidney, gastrointestinal tract, and skin; (2) transport of acid anions from intracellular to extracellular spaces—anion gap acidosis; and (3) intake.
Disorders of the adrenal cortex
Authors: Sherlock Mark , Gurnell Mark
Published: February 2020

Three classes of steroid hormone are produced by the adrenal cortex after uptake of precursor cholesterol from the plasma—mineralocorticoids, glucocorticoids, and sex steroids—with classical endocrine feedback loops controlling their secretion. Glucocorticoids have more diverse and extensive roles than mineralocorticoids, regulating sodium and water homeostasis, glucose and carbohydrate metabolism, inflammation, and stress. These effects are mediated by the interaction of cortisol with ubiquitous glucocorticoid receptors, and the induction or repression of target gene transcription (via glucocorticoid response elements, GREs). Adrenocortical diseases are relatively uncommon, but they have detrimental clinical consequences and can be treated effectively. Hormonal deficiency or excess is usually the result of abnormal secretion.
Congenital adrenal hyperplasia
Authors: Krone Nils P. , Hughes Ieuan A.
Published: February 2020

Congenital adrenal hyperplasia (CAH) results from enzymatic defects in the pathways of adrenal steroidogenesis, with over 90% of cases being due to 21-hydroxylase deficiency caused by autosomal recessive mutations in the CYP21A2 gene. Management requires glucocorticoid and mineralocorticoid replacement sufficient to replenish salt balance and control ACTH hyperstimulation without incurring steroid side effects. In the adolescent and young adult, attention is focused on continuing optimal steroid replacement, with clinical endpoints being potential reproductive function rather than linear growth. Fertility in women is compromised by scarring effects of surgery following genitoplasty in childhood, inadequate adrenal suppression that leads to anovulation, and an overall reduced maternal desire in women with congenital adrenal hyperplasia. Men with congenital adrenal hyperplasia should be screened for testicular adrenal rest tumours after puberty, and semen preservation should be considered in young adulthood.
Ovarian disorders
Authors: Franks Stephen , Hardy Kate , Webber Lisa J.
Published: February 2020

Ovarian disorders are very common. Involuntary infertility affects an estimated 15% of couples and disorders of ovulation account for 25–30% of the causes of infertility. In most cases, disorders of ovulation are attributable to a treatable, endocrine abnormality. Indeed, polycystic ovary syndrome, a major contributor to endocrine-related infertility, is the commonest endocrine disorder in women, with a prevalence in excess of 5% in the female population of reproductive age. Disorders of ovarian function usually manifest themselves as irregular, infrequent, or absent menses. Hirsutism, or excess, male-pattern body hair is another common manifestation of ovarian (and, less often adrenal) dysfunction. In this chapter, ovarian development, the physiology of the hypothalamic–pituitary–gonadal axis, and the hormonal changes of the normal menstrual cycle will be described as a preface to the description of disorders of ovulation, their investigation, and management. The causes, investigation, and management of hirsutism will also be elucidated.
Benign breast disease
Authors: MacLean Gael M.
Published: February 2020

Benign conditions of the breast are very common, but they cause great anxiety, often leading the patient to be concerned that she has breast cancer. Symptoms may include: a mass in the breast, commonly due to fibroadenoma, benign cystic change, or macrocysts; discharge from the nipple, which may be caused by hyperprolactinaemia, intraduct papilloma, or duct ectasia; and mastalgia. Management involves exclusion of malignancy, often by triple assessment of any palpable abnormality (clinical examination, radiological and pathological assessment), followed by reassurance, with appropriate specific treatment if required. Suspicious features such as a hard, rugged lump in the breast should prompt triple assessment to exclude malignancy. Other benign conditions of the male breast are very rare and male breast cancers account for less than 1% of all breast cancers in the United Kingdom.
Normal puberty and its disorders
Authors: Ryan Fiona , Patel Sejal
Published: February 2020

Puberty is the physiological sequence of events when secondary sexual characteristics develop, reproductive capacity is achieved, and final adult stature reached. The outward signs usually develop over 3 to 5 years, with significant variation both in the age that puberty starts and the pace at which development proceeds. The events that lead to the triggering of puberty remain uncertain, but clinical presentations may arise because the process is abnormally early (precocious puberty) or abnormally late (delayed or absent puberty). Several variants of the normal processes may also present for clinical assessment, for example, premature isolated thelarche (breast development) or adrenarche (pubic and axillary hair development), which do not require treatment.
Pancreatic endocrine disorders and multiple endocrine neoplasia
Authors: Khoo B. , Tan T.M. , Bloom S.R.
Published: February 2020

Pancreatic neuroendocrine tumours (islet-cell tumours) are rare and usually sporadic, but they may be associated with complex familial endocrine cancer syndromes. Recognized types of pancreatic neuroendocrine tumours are those that are non-functioning (often advanced at diagnosis and presenting with mass effects due to the absence of symptoms attributable to hormone hypersecretion), insulinoma (the most frequent type), and others including gastrinoma, VIPoma, and glucagonoma. The following should be considered in addition to the symptomatic treatments: surgical resection—the only curative treatment, but not possible in many cases; tyrosine kinase inhibitors which inhibit specific kinases involved in tumour cell proliferation, growth, and angiogenesis; mammalian Target of Rapamycin (mTOR) inhibitors; peptide-receptor radionuclide therapy (radiolabelled somatostatin analogues).
Hypoglycaemia
Authors: Evans Mark , Challis Ben
Published: February 2020

Hypoglycaemia is a low blood glucose concentration, clinically important because glucose is the main fuel supporting brain metabolism and function. The commonest causes are as a consequence of insulin or sulphonylurea drugs used to treat diabetes, but there are many rarer causes including insulinoma, toxins (alcohol), organ failure (hepatic), endocrine diseases (adrenal insufficiency, pituitary insufficiency), non-islet cell tumour hypoglycaemia (large mesenchymal tumours and other malignancies), post bariatric surgery (non-insulinoma pancreatogenous hypoglycaemia syndrome), autoimmune insulin syndrome, factitious or felonious administration of insulin/sulphonylureas, and infections (malaria). Typical features include ‘autonomic’ symptoms (e.g. tachycardia, tremor, and sweating), hunger and neuroglycopenic symptoms related to brain glucose deprivation (e.g. impaired cognitive function, blurred vision, drowsiness, and irritation).
Hormonal manifestations of nonendocrine disease
Authors: Barber Thomas M. , Wass John A.H.
Published: February 2020

Tumours (usually but not invariably malignant), other ‘non-endocrine conditions’ and drugs can be associated with a wide variety of endocrine syndromes. ‘Ectopic’ hormone secretion, defined as the release of a hormone from a site different from the gland that normally produces it, has classically been recognized in the context of neoplasia, but it is now apparent that many hormones are synthesized by ‘non-endocrine’ tissue. Although a particular endocrinopathy may be associated with a specific type of tumour in a particular organ, the relationship is not invariable, and many neoplasms elaborate more than one hormonal substance at the same or at different times and thus produce a mixed endocrine picture.
Hypertension in pregnancy
Authors: McCarthy Fergus
Published: February 2020

High blood pressure (BP >140/90 mm Hg) complicates approximately 10% of pregnancies and may be due to white coat hypertension, chronic hypertension, gestational hypertension, or pre-eclampsia (de novo or superimposed on chronic hypertension).

Pre-eclampsia occurs in 2–8% of pregnancies and remains a common cause of fetal and maternal death in developing countries. Maternal symptoms include headache/visual disturbances, breathlessness, epigastric pain, and seizures (eclampsia); signs include pulmonary oedema, liver tenderness, hyper-reflexia/clonus, and papilloedema.

Treatment of pre-eclampsia is by timely delivery of the fetus (and placenta) to minimize maternal complications and maximize fetal gestational age, while avoiding morbidity and mortality. Pharmacological treatment to control hypertension is generally given when BP consistently exceeds 150 mm Hg (systolic) or 90 mm Hg (diastolic). Commonly used agents include labetalol, nifedipine, amlodipine, and α-methyldopa. ACEi, ARBs, and diuretics should not be used in pregnancy. Intravenous magnesium sulphate is given to women at risk of eclampsia.
Thrombosis in pregnancy
Authors: MacCallum Peter K. , Bowles Louise
Published: February 2020

Pregnancy and the puerperium are associated with a 10-fold increase in the risk of venous thromboembolism, comprising deep vein thrombosis and pulmonary embolism, compared to the non-pregnant state. Pulmonary embolism has been the leading direct cause of maternal mortality in most of the United Kingdom’s triennial Confidential Enquiries into Maternal Deaths over the past 30 years, attesting to the importance of prevention and prompt diagnosis and treatment of venous thromboembolism during pregnancy and following delivery. The diagnosis of venous thromboembolism is challenging in pregnancy because it can be difficult to distinguish features of venous thromboembolism, such as leg swelling and breathlessness, from those of normal pregnancy, and there are no validated clinical scoring systems. All women should undergo risk assessment for venous thromboembolism in early pregnancy, at the time of hospital admission or change in clinical condition, and after delivery.
Endocrine disease in pregnancy
Authors: Carty David
Published: February 2020

During pregnancy, there are several diseases of the endocrine system that can affect women. This chapter looks at a few of these. Many pregnant women will develop goitre. Gestational thyrotoxicosis needs to be differentiated from Grave’s disease, which requires treatment with propylthiouracil in early pregnancy and carbimazole in later pregnancy. Overt hypothyroidism is associated with adverse maternal and fetal outcomes and should be treated to maintain thyroid-stimulating hormone within the trimester-specific reference range. The diagnosis of both Addison’s disease and Cushing’s syndrome can be challenging in pregnancy. Patients with adrenal insufficiency require higher replacement steroid doses in the first and third trimesters. Prolactinomas are commonly encountered in pregnancy, with dopamine agonists the treatment of choice. Women with macroprolactinomas should have visual field monitoring throughout pregnancy. Lymphocytic hypophysitis is increasingly recognized as a cause of hypopituitarism arising in late pregnancy and in the post-partum period.
The skin in pregnancy
Authors: Kirtschig Gudula , Wojnarowska Fenella
Published: February 2020

Dermatoses in pregnancy are common, they may be very itchy and may influence the life of a pregnant woman dramatically. There are four classical dermatoses of pregnancy, which this chapter will examine. It is particularly important to recognize these as they may have serious health implications for mother and child. Intrahepatic cholestasis of pregnancy occurs in 1/40 to 1/500 pregnancies and is the most serious cause of itch in pregnancy, with potentially substantial effects on mother and fetus. Meanwhile, atopic eruption of pregnancy affects 1/300 pregnancies, typically with an eczematous eruption over abdomen and limbs. Pemphigoid gestationis occurs in 1/50,000 pregnancies and is due to circulating antibodies against the skin basement membrane zone. The eruption often begins around the umbilicus and spreads to the whole trunk, limbs, hands, and feet. If potent topical steroids fail systemic steroids are required. Transplacental transmission to the fetus may also occur. Recurrence in future pregnancies is to be expected.
Fetal effects of maternal infection
Authors: Impey Lawrence
Published: February 2020

This chapter looks at the fetal effects of maternal infection. Immunity is mildly suppressed in pregnancy, and the fetal immune system is developmentally immature. Infections in pregnancy can therefore be devastating both for the mother, as is occasionally seen with varicella, and for the fetus, as exemplified by congenital infections such as those caused by rubella, cytomegalovirus, syphilis, and toxoplasmosis. The fetal effects of maternal infection in pregnancy can be broadly categorized as follows (these are not mutually exclusive): transplacental infection causing fetal malformation (e.g. treponema pallidum, rubella); transplacental infection causing severe in utero illness (e.g. parvovirus); neonatal infection/carrier status as a result of transplacental or intrapartum infection (e.g. HIV, herpes zoster); such neonatal infection may be severe; preterm delivery, late miscarriage, perinatal death, and cerebral palsy at term delivery are more common in the presence of in utero and placental infection (chorioamnionitis) (e.g. group B streptococcus).
Maternal critical care
Authors: Gauntlett Rupert
Published: February 2020

Critical illness during pregnancy or after giving birth is rare: in the United Kingdom 0.29% of maternities involve admission to a critical care unit, and the maternal death rate is 0.01%. Over 80% of obstetric admissions to critical care occur in the post-partum phase, mainly due to complications relating to massive haemorrhage. Other pregnancy specific conditions that may require critical care support include pre-eclampsia (typically when diagnosis and treatment have been delayed), amniotic fluid embolism, peri-partum cardiomyopathy, and acute fatty liver of pregnancy. Puerperal sepsis remains a major problem in resource-poor parts of the world. Pregnant women who survive critical illness may be particularly prone to long-term psychological morbidity. It is vital that, once physiological stability has been achieved, no time is wasted before a mother is reunited with her baby.
Structure and function of the gastrointestinal tract
Authors: FitzPatrick Michael E.B. , Keshav Satish
Published: February 2020

The gastrointestinal tract is a hollow tube stretching from the oral cavity through the oesophagus, stomach, small intestine, colon, and rectum to the anal sphincter. Its function is the transport, digestion, and elimination of ingested material to supply nutrients, vitamins, minerals, and electrolytes that are essential for life, together with the protection of the rest of the body from injurious or allergenic material. The stomach acts as a storage, sterilizing, and digestive tank; the small intestine is the major site of digestion and absorption; the colon’s function is to salvage water and electrolytes from the small intestinal effluent; and the rectum provides a storage function, enabling the elimination of colonic residue (defecation) to be restricted to times of personal convenience.