bluuebunny/crossref_metadata_2025 huggingface dataset:
Guinea worm disease (dracunculiasis)
Authors: Knight Richard
Published: February 2020

Guinea worm disease (dracunculiasis)—now limited to sub-Saharan Africa—is caused by the nematode Dracunculus medinensis, whose life cycle involves aquatic copepod crustaceans. Humans are infected when they drink water containing infective larvae. Adult worms enter subcutaneous tissue and can reach a metre in length. Clinical presentation is usually with a skin blister, most often on the leg, sometimes preceded by allergic prodromal symptoms. Bacterial infection and local scarring with disability are common complications. Most patients in endemic areas recognize their condition, but irrigation of ulcers can reveal larvae. Treatment is by physical removal of the worm; anthelmintics have no role in management. Provision of safe water for drinking is the key to prevention. The disease is now nearing eradication.
Schistosomiasis
Authors: Dunne David , Vennervald Birgitte
Published: February 2020

Schistosomiasis is caused by trematode worms Schistosoma spp., whose life cycle requires a definitive vertebrate host and an intermediate freshwater snail host. Transmission to humans occurs through exposure to fresh water containing infectious larvae, which can penetrate intact skin before developing into blood-dwelling adult worms. The disease is patchily distributed in parts of South America, Africa, the Middle East, China, and Southeast Asia, with about 200 million people infected and 20 million suffering severe consequences of infection. Most infected people living in endemic areas have few (if any) overt symptoms, but clinical manifestations (when present) depend on the stage of infection. Praziquantel is the drug of choice, with corticosteroids added in cases of Katayama fever. Acute schistosomiasis responds well, but chronic disease less so, but rapid re-exposure and reinfection are common (particularly in young children) unless control measures are implemented at the community level.
Podoconiosis (nonfilarial elephantiasis)
Authors: Davey Gail
Published: February 2020

Podoconiosis is the lesser-known of the two major forms of tropical lymphoedema. The disease affects genetically susceptible individuals who go barefoot and whose feet and legs are exposed long term to red clay soils. It is found focally across tropical Africa, Central America, and north India where such soils coexist with high altitude, high rainfall, and low-income populations. Prodromal symptoms include itching and a burning sensation in the foot; early changes include spreading or ‘splaying’ of the forefoot and leakage of colourless ‘lymph’ fluid. Later stages are manifested by lymphoedema, which is usually bilateral and limited to below the knee. Studies examining host immunological and inflammatory responses are currently underway to improve possible future treatment options for the disease.
Minerals and trace elements
Authors: Younger Katherine
Published: February 2020

The essential minerals, calcium, phosphorus, potassium, sulphur, sodium, chlorine, and magnesium (macrominerals) and trace elements chromium, copper, fluorine, iodine, magnesium, manganese, molybdenum, phosphorus, selenium, and zinc, have diverse and critical functions in human metabolism. Dietary sources and the intake requirements for macrominerals and trace elements for optimal physiological well-being have been established, and the upper range of intake has been also been set so that unwanted or even toxic effects can be avoided. Deficiency of certain trace elements contributes importantly to the global burden of illness and mortality, especially in infants under the age of five years. An up-to-date familiarity with the scientific basis of mineral and trace element physiology is therefore critical for maintaining good standards of clinical practice and to inform the best standards of nutritional advice, especially in the treatment of severe illnesses associated with deficiency or toxic excess of one or more macrominerals or trace elements.
The inborn errors of metabolism: General aspects
Authors: Cox Timothy M. , Watts Richard W.E.
Published: February 2020

The inborn errors of metabolism are those inherited diseases in which the phenotype includes a characteristic constellation of biochemical abnormalities related to an alteration in the catalytic activity of a single specific enzyme, activator, or transport protein. Mechanism of diseases—mutations in the proteins giving rise to the inborn errors of metabolism affect primary, secondary, tertiary, or quaternary structure. This can lead to an enormous variety of consequences. Clinical presentation—the manifestations of metabolic disease are protean and may seem nondescript, especially in adults, hence a high level of suspicion may be required to make a correct diagnosis. Prevention and screening—there is a strong case for mass population screening for some inborn errors of metabolism at the presymptomatic stage to allow early detection and introduction of proven treatment before irreversible damage occurs. Management—definitive cure of the underlying abnormality is available for a few disorders, but precise characterization of the biochemical disturbance often permits rational treatment to be organized and provides the basis for further therapeutic endeavours. General approaches include (1) restriction of a substrate that cannot be metabolized including molecules derived from the diet; (2) replacement of a missing metabolic product; (3) removal of poisonous metabolites or rebalancing overproduction of toxic intermediates; (4) administering pharmacological doses of a cofactor, sometimes a vitamin, that may also stabilize a mutant enzyme; (5) replacement of a missing gene product, usually by enzymatic augmentation therapy or pharmacological chaperones, to prevent premature aggregation and denaturation; (6) repression of an overproduced protein or metabolite by stable RNA inhibition; (7) transplantation of cells or organs as a ‘gene replacement therapy’; and (8) activation of a poorly functioning protein.
Protein-dependent inborn errors of metabolism
Authors: Hoffmann Georg F. , Kölker Stefan
Published: February 2020

Protein-dependent inborn errors of metabolism are caused by inherited enzyme defects of catabolic pathways or intracellular transport of amino acids. Most result in an accumulation of metabolites upstream of the defective enzyme (amino acids and/or ammonia), causing intoxication. Protein-dependent metabolic diseases usually have a low prevalence except for some high-risk communities with high consanguinity rates. However, the cumulative prevalence of these disorders is considerable (i.e. at least >1:2000 newborns) and represents an important challenge for all public health systems. Types and clinical presentation of protein-dependent inborn errors of metabolism—this chapter discusses amino acid disorders, organic acid disorders, and urea cycle defects. The disease spectrum is broad, but follows a distinct pattern in specific disorders. Investigation and management—every infant presenting with symptoms of unexplained metabolic crisis, intoxication, or encephalopathy requires urgent evaluation of metabolic parameters, including analyses of arterial blood gases, serum glucose and lactate, plasma ammonia and amino acids, acylcarnitine profiling in dried blood spots, and organic acid analysis in urine. This chapter discusses the basic principles of acute emergency therapy and of long-term treatment, which aims principally to mitigate the metabolic consequences of enzyme deficiencies by compensating for them. Successful treatment of affected individuals is often difficult to achieve. Careful supervision in metabolic centres involving an experienced multidisciplinary team is invaluable for the best outcome.
Inborn errors of fructose metabolism
Authors: Cox Timothy M.
Published: February 2020

Most people in developed countries ingest 50 to 100 g fructose equivalents daily in their diet, arising from fructose itself, sucrose, and sorbitol. After rapid carrier-mediated absorption across the intestinal epithelium, fructose is metabolized (mainly in the liver) by the enzymes ketohexokinase (fructokinase), aldolase B, and triokinase, eventually being converted into glucose or glycogen. Dietary sugars—burgeoning constituents in food and drinks worldwide—have undesirable effects on those with limited capacity to metabolize fructose, including severe illness or death in young patients. ‘Fructose malabsorption’ describes incomplete absorption of fructose that is associated with abdominal symptoms and diarrhoea reminiscent of intestinal disaccharidase deficiency. Symptoms occur after ingestion of fructose- or sorbitol-rich foods and drinks such as apple juice, but as yet a convincing genetic cause for this condition has not been found. Symptoms improve when the offending sugars are avoided. Three inborn errors of fructose metabolism are recognized and these disorders are vivid examples of gene–environment interactions: (1) essential or benign fructosuria due to fructokinase deficiency—a very rare disorder with apparently no ill effects; (2) hereditary fructose intolerance (fructosaemia)—an autosomal recessive disease caused by deficiency of aldolase B; and (3) fructose-1,6-diphosphatase deficiency —a very rare disease of infancy and childhood associated with failure of hepatic gluconeogenesis causing bouts of severe hypoglycaemia, ketosis, and lactic acidosis provoked by infection and starvation.
The porphyrias
Authors: Cox Timothy M.
Published: February 2020

The porphyrias are a remarkable family of metabolic disorders characterized biochemically by overproduction of haem precursors, principally in the liver and bone marrow. The acute porphyrias are inborn errors of varying penetrance that affect enzymatic steps in a tightly regulated biosynthetic pathway for haem; nonacute acquired forms also occur in genetically predisposed individuals. Clinical presentation of acute porphyria—life-threatening neurovisceral attacks occur in four of the porphyrias: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and Doss’ porphyria (5-aminolaevulinate dehydratase deficiency). These present with abdominal pain, psychiatric symptoms, and signs of sympathetic and hypothalamic autonomic overactivity, sometimes accompanied by convulsions and motor and sensory deficits. Diagnosis of acute porphyria—this is key to survival of an acute attack of porphyria, which can be suspected on the basis of the past history, in particular of photosensitivity or the intermittent discoloration of urine, and family history, and is confirmed by finding excess water-soluble haem precursors in urine. Management of acute porphyria—treatment of an acute porphyric attack mandates immediate withdrawal of inappropriate drugs and other precipitating factors; infusions of haem arginate or other licensed preparations of haem shorten life-threatening episodes and may be effective prophylaxis for recurrent porphyria in women with periodic attacks. The nonacute porphyrias are photosensitivity syndromes caused by excess photoactive macrocyclic porphyrins triggered especially by visible light in the blue–violet range. In the most severe form, manifestations are of severe blistering lesions on sun-exposed skin, particularly of the hands and face, with the formation of vesicles and bullae that may become infected. Healing may lead to loss of digits, scarring of the eyelids, nose, lips, and scalp, and occasionally blindness due to corneal scarring.
Lipid disorders
Authors: Cegla Jaimini , Scott James
Published: February 2020

High blood cholesterol and high blood triglycerides are causal risk factors for atherosclerotic cardiovascular disease, which remains the leading cause of death in the developed world. Lipid and lipoprotein metabolism—cholesterol, triglycerides, and fat-soluble vitamins are transported with specific proteins in the blood as multimeric complexes called lipoproteins. Lipid and lipoprotein metabolism are effected by three principal physiological processes: (1) intestinal absorption of dietary lipid and transport in the blood of dietary lipid and lipids, principally derived from the liver (as triglyceride-rich lipoproteins) to peripheral tissues for catabolism by skeletal and cardiac muscle or storage in adipose tissue; (2) return of triglyceride-rich lipoprotein remnants to the liver, hepatic synthesis of low-density lipoprotein, and the transport of cholesterol between peripheral tissues and the liver; and (3) reverse cholesterol transport by high-density lipoprotein (HDL) between peripheral tissues and the liver. Dyslipidaemias are disorders of lipoprotein metabolism in which there is elevation of total cholesterol and/or triglycerides, often accompanied by reduced levels of HDL cholesterol. Causes of dyslipidaemia—particular lipid disorders including polygenic hypercholesterolaemia, familial hypercholesterolaemia, combined hypercholesterolaemia and hypertriglyceridaemia, familial combined hyperlipidaemia, familial dysbetalipoproteinaemia (also called type 3 hyperlipoproteinaemia), and severe hypertriglyceridaemia, as well as secondary or aggravating factors. Management of dyslipidaemia—the key questions are: (1) what classes of lipoproteins and lipids are increased or decreased in the patient’s plasma? (2) Does the patient has a primary (genetic) or secondary (acquired) dyslipidaemia (often contributions from both influences)? (3) Is the patient at risk of atherosclerotic cardiovascular disease or acute pancreatitis? (4) What other risk factors (e.g. hypertension or diabetes) are present? (5) What treatments might be used to address these abnormalities?
Hereditary haemochromatosis
Authors: Griffiths William J.H. , Cox Timothy M.
Published: February 2020

Hereditary haemochromatosis syndromes are inherited disorders whereby inappropriate absorption of iron by the small intestine leads to iron deposition in the viscera, endocrine organs, and other sites, causing structural injury and impaired function. The most common form is classical adult (HFE-related) haemochromatosis, but other forms are recognized. Extended genetic platforms are increasingly used for specific diagnosis and noninvasive methods are increasingly used to evaluate hepatic damage. The mainstay of treatment is venesection although iron chelation therapy is an emerging oral alternative. Unravelling the molecular genetics of haemochromatosis is underpinning promising new therapies for disorders of iron homeostasis. Classical adult (HFE-related) haemochromatosis: aetiology and pathogenesis—inherited as a recessive trait and due to mutations in the major histocompatibility complex class I-related HFE gene that appear to reduce liver production of hepcidin. The principal mutant allele of HFE, designated C282Y, is carried by approximately 1 in 10 individuals of European ancestry, hence around 1 in 200 are homozygotes, usually with biochemical abnormalities of iron storage that may lead to full-blown clinical haemochromatosis. Clinical features—expression of disease may range from slight abnormalities of blood parameters that reflect iron metabolism to the established clinical syndrome of cutaneous pigmentation, cardiomyopathy, endocrine failure (especially diabetes mellitus and hypogonadism), arthritis, and pigment cirrhosis. Diagnosis—usually established by demonstrating abnormalities of iron metabolism. Molecular analysis of the HFE gene, in particular for homozygosity for the C282Y allele, is confirmatory. Management and prognosis—this is directed to the removal of iron by phlebotomy until the serum ferritin concentration is reduced to within the low normal range, after which the frequency of phlebotomy is reduced. Family members—first-degree relatives should be offered screening.
Hereditary periodic fever syndromes
Authors: Lachmann Helen J. , Berg Stefan , Hawkins Philip N.
Published: February 2020

The hereditary periodic fever syndromes or hereditary autoinflammatory diseases are disorders of innate immunity that mostly present in childhood and are characterized by recurrent, self-limiting, seemingly unprovoked episodes of fever and systemic inflammation that occur in the absence of autoantibody production or identifiable infection. Disorders include (1) familial Mediterranean fever (FMF), due to mutations in the gene encoding pyrin; (2) tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), due to mutations in a gene for a TNF receptor; (3) mevalonate kinase deficiency and period fever (MKD), caused by mutations in the mevalonate kinase gene; and (4) the cryopyrin-associated periodic syndromes (CAPS), which include (a) familial cold urticarial syndrome, (b) Muckle–Wells syndrome, and (c) chronic infantile neurological, cutaneous, and articular syndrome. With advances in genetics, further syndromes are continually being recognized. These are all extremely rare and in the majority are only known to affect a handful of kindred or individuals. Diagnosis relies on recognition of suggestive clinical features that are almost always accompanied by a substantial acute phase response, and is supported by genetic testing. With the exception of FMF, which is a common disease in certain geographic areas, hereditary periodic fever syndromes are rare and easily overlooked in the differential diagnosis of recurrent fevers. Clinical features and management—attacks can be mild to debilitating and short to prolonged, while their most feared complication is AA amyloidosis. Effective therapies are available for some syndromes, for example: (1) FMF—daily prophylactic colchicine prevents clinical attacks and susceptibility to AA amyloidosis, (2) CAPS—treatment with anti-IL-1 agents produces rapid and often complete clinical and serological remission, and (3) TRAPS—anti-IL therapies are extremely effective.
Disorders of the anterior pituitary gland
Authors: Karavitaki Niki , Wass John A.H.
Published: February 2020

The pituitary gland or hypophysis cerebri was first described by Galen of Pergamon in the 2nd century ad, and is considered to be the ‘master gland’ integrating hormonal signals that control numerous endocrine and metabolic functions. Since the demonstration of the hypothalamic control of pituitary function by Harris in Oxford in the 1950s, our understanding of the physiology and pathophysiology of the pituitary gland has broadened. The development of radioimmunoassays in the 1960s, the extraction of hypothalamic factors principally by Schally and Guillemin in the 1970s, the advances in immunocytochemistry, electron microscopy, and in situ hybridization methods, as well as the expansion of molecular biology have increased this understanding. Finally, the advances in modern imaging techniques and in pituitary surgery combined with the development of medical treatments for pituitary tumours have greatly expanded the therapeutic possibilities, providing successful and safe outcomes in most patients.
The thyroid gland and disorders of thyroid function
Authors: Weetman Anthony P. , Boelaert Kristien
Published: February 2020

The iodine-containing thyroid hormones triiodothyronine (T3) and thyroxine (T4) have diverse effects on metabolism and are essential for normal development, particularly of the fetal brain. The active principle, T3, binds to nuclear receptor isoforms and serves as a transcriptional regulatory factor, thus explaining the protean actions. Thyroid hormone release is regulated by thyrotropin (TSH) from the anterior pituitary, which is itself modulated by the hypothalamic tripeptide, thyrotropin-releasing hormone. A normal TSH level rules out primary thyroid dysfunction, but when TSH levels are abnormal, or when pituitary or hypothalamic abnormalities are possible, it is essential to confirm thyroid status by measuring circulating thyroid hormone levels, which is best achieved by immunoassay of free T3 and free T4. Thyroid-antibody measurement and imaging by scintiscanning are useful in determining the aetiology of thyroid disease when this is not obvious clinically.
Thyroid cancer
Authors: Boelaert Kristien , Weetman Anthony P.
Published: February 2020

Thyroid cancers are the most common endocrine malignancies and their incidence is rising globally, largely due to significant increases in small, incidentally detected low-risk tumours. Follicular epithelial cell cancer is the commonest type; this usually presents with usually well differentiated tumours and has an excellent prognosis, but occasionally highly undifferentiated; it may be induced by exposure to ionizing radiation. Medullary thyroid carcinoma arises from parafollicular C cells; it comprises 3–5% of all thyroid cancers; usually hereditary autosomal dominant forms associated with germline point mutations in the RET proto-oncogene. Rare thyroid tumours include anaplastic carcinomas, which present as a rapidly enlarging and fixed thyroid masses, sometimes with local pain; they are rapidly fatal; sarcomas; and primary lymphomas—these usually present as a rapidly enlarging thyroid mass in a patient with Hashimoto’s thyroiditis.
Normal growth and its disorders
Authors: Butler Gary
Published: February 2020

Normal growth has three phases: rapid in infancy and adolescence, steady during mid childhood. Height should always be interpreted within the context of the family: short or tall stature is often familial; idiopathic short stature occurs when the height of a normal child is below their target range. Constitutional growth delay is a common normal variant, but poor growth and/or weight gain may be associated with recognized and unrecognized chronic disease, and also with psychosocial deprivation. Investigation must exclude conditions including hypothyroidism, coeliac disease, inflammatory bowel disease, and chronic kidney disease. Turner syndrome (karyotype 45,X) should be suspected in all girls presenting with growth failure, and skeletal dysplasia when a child is either short for their family or has one parent of significant short stature.
Chest diseases in pregnancy
Authors: Pugh Meredith , Hartert Tina
Published: February 2020

Respiratory changes in pregnancy include an increase in tidal volume and minute ventilation, leading to a primary respiratory alkalosis. This chapter examines the various chest conditions arising in pregnancy—these include: amniotic fluid embolism—unique to pregnancy; venous air embolism—a rare condition that can occur in pregnancy; venous and pulmonary thromboembolism—pregnancy is a risk factor; pulmonary oedema—this can be caused by heart disease, as in the non-pregnant state, but it can also be associated with pre-eclampsia or HELPP syndrome and be induced by tocolysis; aspiration; varicella pneumonia—a potentially devastating complication of primary varicella-zoster virus infection; and influenza, which is associated with increased maternal morbidity.
Contraception for women with medical diseases
Authors: Mohan Aarthi R.
Published: February 2020

All women with underlying medical disorders should be given correct advice regarding adequate contraception so that they can make informed choices regarding potential future pregnancies. There are several important factors to consider when deciding upon the most appropriate form of contraception to use. These include the risk of pregnancy for the woman, the effect of the contraceptive method on the medical disease, the failure rates associated with the contraceptive method, the consequences of an unplanned pregnancy, and the compliance and preferences of the individual woman. There are a small number of very high-risk conditions where pregnancy is not recommended due to high mortality rates, and the most reliable contraceptive methods should be recommended for these women.
Investigation of gastrointestinal function
Authors: Andreyev Jervoise
Published: February 2020

There are two main reasons for investigating the gastrointestinal (GI) tract: first, to identify diseases at an early stage (e.g. endoscopic screening for neoplasia); second, to diagnose and manage symptoms. A pathological process can potentially affect any part of the GI tract, but apart from mass lesions, pathological change per se hardly ever causes symptoms directly. Symptoms depend on whether critical physiological change has been triggered by the pathological insult. Individual symptoms or clusters of symptoms are not a reliable indicator of the underlying cause, and different physiological changes can produce identical symptoms. Critical symptoms indicative of significant GI tract pathology include ‘red flag’ symptoms (e.g. a palpable mass, rectal bleeding, weight loss) and other symptoms that are frequently missed by patients and clinicians alike (e.g. steatorrhoea, nocturnal waking to defecate). Dietary intake requires systematic assessment. Routine investigation should usually include thyroid function testing, vitamin B12 and vitamin D status, coeliac screen, iron studies, and inflammatory markers. Endoscopy and cross-sectional radiology provide excellent anatomical visualization but provide little information about the dynamic function and physiology of the GI tract, for which various tests for specific physiological functions can be used. Failure to investigate adequately misses easily treated diagnoses and means ongoing symptoms for patients. For many patients with multiple comorbidities, there is often more than one cause for their GI symptoms, which will not improve unless all causes are identified and treated.
The acute abdomen
Authors: Buczacki Simon J.A. , Davies R. Justin
Published: February 2020

The term ‘acute abdomen’ describes abdominal pain of rapid onset requiring urgent surgical assessment. No firm pathological diagnosis is made in many patients initially presenting in this way, but those that do, require rapid diagnosis and treatment to avoid potentially life-threatening complications. Patients may present directly to medical specialties with an acute abdomen, or abdominal pain may occur in patients already residing on medical wards. These patients are often old and their acute abdomen is likely to present on a background of other comorbidities. Understanding the interaction between risk factors and underlying pathological diagnosis is key to preventing misdiagnosis in such cases. Although not eliminating the need for a sound focused history and examination, spiral CT scanning allows rapid diagnosis of most causes. However, management of the diagnosed acute abdomen in medical patients can be extremely difficult, and there is no substitute for an experienced physician working together with a thoughtful surgeon supported by anaesthetists and intensivists. The key question is often ‘Does this patient need an operation?’, a decision which depends on many factors. It may be necessary to proceed straight to surgery without any supportive imaging in very sick patients who may be bleeding or who are profoundly septic.
Gastrointestinal bleeding
Authors: Brown Vanessa , Rockall T.A.
Published: February 2020

Gastrointestinal bleeding (GIB) is a common emergency, which can be subdivided into upper and lower, and acute or chronic, with acute upper GIB further subdivided into variceal (11%) and nonvariceal (89%) bleeding. Risk stratification in acute upper GIB can be performed using simple clinical and endoscopic criteria that can be used to estimate the risk of mortality, but there are no validated systems for use in acute lower GIB. The immediate management of the hypovolaemic patient is first directed towards resuscitation and then to identification of the site and cause of bleeding. Most patients will stop bleeding spontaneously and should then be investigated with either upper gastrointestinal endoscopy or colonoscopy as appropriate. Patients with acute ongoing upper GIB require urgent investigation by oesophagogastroduodenoscopy with a view to applying endoscopic haemostatic therapy, which is efficacious in up to 95% of patients. High-dose proton pump inhibitor treatment should be given following successful endoscopic therapy to patients with major ulcer bleeding. If these techniques fail to arrest bleeding, then either selective mesenteric angiography with embolization or surgery is indicated. Patients who are unstable with acute lower GIB require early oesophagogastroduodenoscopy (to exclude an upper gastrointestinal cause) and then an interventional radiological procedure to embolize the bleeding vessel(s); surgery is generally a last resort.
The mouth and salivary glands
Authors: Gibson John , Robertson Douglas
Published: February 2020

Many systemic diseases are associated with oral symptoms or signs, hence thorough examination of the lips, gums, teeth, tongue, and oropharynx should be part of any complete physical examination of a patient. Dental caries, caused by bacterial action, is one of the commonest human diseases and a cause of considerable misery. Chronic periodontal disease is the most important cause of dental loss in adults. In addition to describing these conditions, this chapter also covers potentially malignant lesions of the oral mucosa and oral cancer; viral, fungal, and bacterial infections; oral ulceration; oral manifestations of dermatological, gastroenterological, haematological, and multisystem disorders; orofacial pain syndromes; and salivary gland disorders.
Gastrointestinal lymphomas
Authors: Naresh Kikkeri N.
Published: February 2020

Primary gastrointestinal lymphoma is the most common extranodal lymphoma and is almost exclusively of non-Hodgkin type. It is defined as lymphoma that has presented with the main bulk of disease in the gastrointestinal tract, with or without involvement of contiguous lymph nodes. MALT lymphoma is an indolent B-cell lymphoma whose histology recapitulates the features of mucosa-associated lymphoid tissue (MALT). It most commonly affects the stomach, presenting with nonspecific dyspepsia. Most cases appear to be driven by Helicobacter pylori, with 75% regressing following eradication of the organism with appropriate antibiotics. Deeply invasive lymphomas and those with adverse histological or cytogenetic features are unlikely to respond. Mantle cell lymphoma and follicular lymphoma are adult B-cell lymphomas that can present as gastrointestinal lymphomas. Diffuse large B-cell lymphoma is an aggressive lymphoma that is relatively frequently encountered in gastrointestinal locations. Burkitt’s lymphoma is also an aggressive B-cell lymphoma, and is the most frequent childhood gastrointestinal lymphoma. Enteropathy-associated T-cell lymphoma is an intestinal lymphoma of intraepithelial T lymphocytes that occurs most commonly in the jejunum or ileum and is associated with coeliac disease. It presents with abdominal pain, often due to intestinal perforation. The prognosis is usually poor, with death frequently resulting from abdominal complications in patients already weakened by uncontrolled malabsorption.
Disaccharidase deficiency
Authors: Cox Timothy M.
Published: February 2020

Disaccharidases are abundant enzymes expressed on the microvillous membrane of the small intestine: apart from free glucose and fructose, disaccharidases are required for the complete assimilation of nearly all carbohydrate present in food and drinks. The enzymes cleave disaccharides such as sucrose, maltose, and lactose, as well as dextrins derived from starch, into their component monosaccharides. Their activity is reduced in hereditary conditions or in generalized intestinal diseases. Disaccharidase deficiency causes dietary intolerance of carbohydrate induced by the fermentation of undigested sugars in the distal small intestine and colon. Abdominal symptoms are usually noticed within an hour of the ingestion of foods containing the offending sugars. By far the most common symptomatic disaccharidase deficiency is lactose intolerance. Lactase activity is high in healthy infants when milk is the principal food, but in most humans the activity declines after weaning and remains low (lactase nonpersistence), which greatly reduces the capacity to break down lactose. In contrast, those inheriting a Mendelian dominant trait that leads to sustained high intestinal lactase expression throughout life (lactase persistence) digest and tolerate large quantities. The distribution of lactase activity in adult populations is subject to great variation. Intestinal lactase phenotypes can be identified by assay of mucosal biopsy samples or appropriate sugar tolerance tests, as can other (much rarer) genetically determined disaccharidase variants. The most convenient diagnostic screen involves hydrogen breath testing after oral loading. Disaccharide intolerance is readily treated by institution of a strict exclusion diet; oral enzymatic supplementation may benefit patients with severe enzymatic deficiency. Innovative and early phase clinical trials suggest that modulation of the host intestinal microbiome with a pure short-chain galacto-oligosaccharide may be beneficial in symptom control and in favouring the outgrowth of lactose-fermenting flora.
Malabsorption syndromes in the tropics
Authors: Ahuja Vineet , Makharia Govind K.
Published: February 2020

Causes of secondary malabsorption that are most common in the tropics include (1) progressive wasting in people infected with HIV, which is known as ‘slim disease’; (2) various infections—protozoal (e.g. Giardia lamblia, Cryptosporidium parvum), helminthic (e.g. Capillaria philippinensis, Strongyloides stercoralis), and bacterial (Mycobacterium tuberculosis); (3) immunoproliferative small intestinal disease; and (4) hypolactasia. Coeliac disease and Crohn’s disease also occur. When patients with conditions that can cause secondary malabsorption are excluded, a group remains who have chronic diarrhoea, malabsorption, and its nutritional sequelae. This primary or idiopathic malabsorption syndrome is called ‘tropical sprue’, which occurs against the background of tropical enteropathy (describing the fact that the morphology of the mucosa of normal gut is different in tropical preindustrialized countries from that in temperate-zone industrialized countries). The aetiology of tropical sprue is not known: epidemiological data suggests an infective cause, but no causal agent has been identified. Presentation is typically with loose or watery stools lasting for several weeks or months, and with symptoms and signs of nutritional deficiency. Management involves symptomatic relief from diarrhoea, and correction of fluid and electrolyte abnormalities and nutritional deficiencies. Attempts at specific curative measures—folic acid and tetracyclines—are usually given for up to 6 months.
Drug-induced liver disease
Authors: Aithal Guruprasad P.
Published: February 2020

Drug-induced liver disease encompasses a wide range of pathology including idiosyncratic drug-induced liver injury (DILI), acute fatty liver, autoimmune hepatitis, sclerosing cholangitis, granulomatous hepatitis, and nodular regenerative hyperplasia, as well as drug-associated fatty liver disease, cirrhosis, and liver tumours. The vast majority of commonly used drugs are reported to be associated with DILI, including over-the-counter preparations, herbal remedies, and dietary supplements. It is important to consider drug therapy as an aetiology when assessing patients presenting with hepatocellular or cholestatic patterns of liver injury. Systematic evaluation and prompt diagnosis followed by discontinuation of the particular medication is crucial to prevent the development of acute liver failure and to avoid inappropriate investigations. Both candidate gene and genome-wide association studies have identified the critical role of the adaptive immune system in the pathogenesis of idiosyncratic DILI. Human leucocyte antigen alleles that are strongly associated with DILI have the potential to assist in the clinical investigation of patients suspected to have DILI in particular circumstances.
Cardiac investigations: Nuclear, MRI, and CT
Authors: Sabharwal Nikant , Kelion Andrew , Karamitos Theodoros , Neubauer Stefan
Published: February 2020

Myocardial perfusion scintigraphy provides physiological information about the coronary circulation, in contrast to the anatomical information provided by angiography.

Three radionuclide-labelled perfusion tracers are routinely used in single photon emission computed tomography (SPECT) imaging: thallium-201 and the technetium-99m-labelled complexes sestamibi and tetrofosmin. Imaging is performed following tracer injection during stress (exercise or pharmacological) and at rest; comparison allows determination of whether regional perfusion is normal, or if there is inducible hypoperfusion or infarction/scar. Myocardial perfusion imaging is minimally invasive, and—in contrast to other methods of investigation—can be performed regardless of overall exercise capacity, abnormalities of the resting electrocardiogram, pacemakers, obesity, claustrophobia, renal dysfunction, iodine allergy, or acoustic windows.
Cardiorenal syndrome
Authors: Green Darren , Kalra Philip A.
Published: February 2020

Concurrent renal and cardiovascular disease is common. Renal disease is a potent cardiovascular risk factor and consequently cardiovascular disease is the most important cause of mortality in patients with end-stage renal disease. This increased risk is mediated by vascular disease (coronary calcification, endothelial dysfunction, dyslipidaemia, and others), left ventricular hypertrophy, risk of arrhythmias, and left ventricular systolic and diastolic dysfunction. These interactions are further complicated by the presence of anaemia in advanced renal disease. The coexistence of renal disease and heart failure presents a major therapeutic challenge and requires careful attention to fluid status and renal function. Diuretic resistance is common and the important prognostic benefit of angiotensin-converting enzyme inhibition in this high-risk group is often neglected. Cardiovascular drugs, particularly antiarrhythmic agents such as digoxin, sotalol, and flecainide, should be used with caution in patients with renal disease.
Valvular heart disease
Authors: Henein Michael
Published: February 2020

Rheumatic valve disease remains prevalent in developing countries, but over the last 50 years there has been a decline in the incidence of rheumatic valve disease and an increase in the prevalence of degenerative valve pathology in northern Europe and North America. In all forms of valve disease, the most appropriate initial diagnostic investigation is almost always the echocardiogram. The most common cause is rheumatic valve disease. Other causes include mitral annular calcification, congenital mitral stenosis, infective endocarditis (very rarely), and systemic lupus erythematosus (Liebman–Sachs endocarditis). The important consequences of mitral stenosis are its effect on left atrial pressure, size, and the pulmonary vasculature; it commonly causes atrial fibrillation. Presenting symptoms are typically exertional fatigue and breathlessness; systemic embolism can occur. Characteristic physical signs are irregular pulse, tapping apex beat, loud first heart sound, opening snap, and an apical low-pitched rumbling mid-diastolic murmur.
Endocarditis
Authors: Harrison James L. , Klein John L. , Littler William A. , Prendergast Bernard D.
Published: February 2020

Endocarditis predominantly affects the aortic and mitral valves; involvement of the tricuspid valve occurs in approximately one-fifth of cases and pulmonary valve involvement is rare. In the developing world rheumatic heart disease is the most common predisposing factor. In developed countries endocarditis is more common in older people with native valve disease and in patients with prosthetic valves and intracardiac devices (pacemakers and defibrillators). In these countries up to 50% of cases have no predisposing cardiac lesion and more cases are related to intravenous drug abuse and nosocomial infection related to invasive procedures. Mortality remains high (30%) despite advances in antimicrobial therapy and surgery, and at least 50% of cases require valve surgery. Early diagnosis, specialist management, and timely intervention are key to successful outcome.
Cardiovascular syphilis
Authors: Somers Krishna
Published: February 2020

Clinicians need to be aware of cardiovascular syphilis in patients at risk of infection, with the time taken from initial infection to clinical manifestation ranging from 10 to 25 years, although this is accelerated in patients with HIV infection. Inadequate or interrupted antibiotic therapy may confound the development of cardiovascular syphilis and make diagnosis difficult. In diagnosis, serological testing is the mainstay: latent or inadequately treated syphilis should be suspected with the finding of a positive non-specific treponemal serological test (e.g. rapid plasma reagin) and a positive specific treponemal antibody test (e.g. Treponema pallidum haemagglutination), but negative serology does not absolutely exclude infection with T. pallidum, particularly in an immunocompromised host. Parenteral penicillin remains the treatment of choice for cardiovascular syphilis: the World Health Organization and European and United States guidelines recommend benzathine benzylpenicillin 2.4 × 106 units administered once weekly for 3 weeks by the intramuscular route.
Tumours of the heart
Authors: Traill Thomas A.
Published: February 2020

Cardiac myxomas are rare benign tumours that grow in the lumen of the atria, usually the left. Most are sporadic, but they can be associated with the Carney complex, where unusual freckling is typically the most obvious clinical clue. Symptoms and signs most commonly mimic those of mitral stenosis. Systemic emboli occur in about 40% of cases. However, the most common tumour seen in adult patients is the benign papillary fibroelastoma, which should be surgically removed only if it has been discovered in the search for a source of otherwise unexplained embolism. Primary cardiac sarcomas are found more often in the right heart than in the left. Microscopic secondary deposits within the myocardium can often be found in patients who die of metastatic cancer, but these are rarely of clinical importance.
Biology and pathology of atherosclerosis
Authors: Choudhury Robin P. , Chai Joshua T. , Fisher Edward A.
Published: February 2020

Atherosclerotic plaques are not randomly distributed, but tend to form at the inner curvatures and branch points of arteries, where laminar flow is either disturbed or insufficient to support the normal, quiescent state of the endothelium (the lining of endothelial cells that separates the circulating blood from the arterial wall). This is an inflammatory process that involves the contribution of endothelial cells, lymphocytes, monocytes, and smooth muscle cells in conjunction with the deposition of atherogenic lipoproteins in the intimal layer of the vascular wall. The initial stage involves activation of the endothelium at regions of non-laminar flow in vessels resulting in increased permeability to Apo B-containing lipoproteins. Inflammatory cells, in particular monocytes, are recruited into the intimal layer of the vessel wall via the action of chemokines and adhesion molecules mobilized by activated endothelium.
Management of acute coronary syndrome
Authors: Kharbanda Rajesh K. , Fox Keith A.A.
Published: February 2020

Acute coronary syndrome (ACS) is precipitated by an abrupt change in an atheromatous plaque and/or thrombotic occlusion. This results in increased obstruction to perfusion and ischaemia or infarction in the territory supplied by the affected vessel. The clinical consequences of plaque rupture can range from a clinically silent episode, through to unstable symptoms of ischaemia without infarction, to profound ischaemia complicated by progressive infarction, heart failure, arrhythmia, and risk of sudden death. Clinical presentation with an ACS identifies a patient at high risk of further cardiovascular events requiring a defined acute and long-term management strategy. Prompt relief of pain is important, not only for humanitarian reasons, but also because pain is associated with sympathetic activation, vasoconstriction, and increased myocardial work. The management of prehospital cardiac arrest requires special attention: at least as many lives can be saved by prompt resuscitation and defibrillation as by reperfusion.
Peripheral arterial disease
Authors: Powell Janet , Davies Alun
Published: February 2020

The most common presentations of peripheral arterial disease are intermittent claudication and abdominal aortic aneurysm. In patients under 50 years of age the cause of disease is most likely to be genetic, congenital, immunological, infectious, or traumatic; over 50 years of age the principal risk factor is smoking. The main diagnostic method used to confirm the diagnosis of peripheral arterial disease is Doppler ultrasonography, in particular to estimate the ratio of systolic blood pressure at the ankle and in the arm, the ankle–brachial pressure index. Presents as a painful, pale, and pulseless limb, and is usually caused by thrombosis at the site of an atherosclerotic stenosis.
Essential hypertension: Definition, epidemiology, and pathophysiology
Authors: Williams Bryan , Firth John D.
Published: February 2020

‘Essential hypertension’ is high blood pressure for which there is no clearly defined aetiology. From a practical perspective, it is best defined as that level of blood pressure at which treatment to lower blood pressure results in significant clinical benefit—a level which will vary from patient to patient depending on their absolute cardiovascular risk.

Historically, most guidelines define ‘hypertension’ as an office blood pressure greater than or equal to 140/90 mm Hg, but some recent recommendations prefer home or ambulatory blood pressure (blood pressure) averages. When using 24 h ambulatory blood pressure or home blood pressure averages to define hypertension, the diagnostic thresholds are lower than those used with office measurement, with a value of 135/85 mm Hg typically used for both daytime ambulatory blood pressure and home measurements.
Essential hypertension: Diagnosis, assessment, and treatment
Authors: Williams Bryan , Firth John D.
Published: February 2020

Essential hypertension is invariably symptomless and usually detected by routine screening or opportunistic measurement of blood pressure. However, once a patient has been labelled as ‘hypertensive’ it is not uncommon for them to associate preceding symptoms to their elevated blood pressure. Some patients will claim that they can recognize when their blood pressure is elevated, usually on the basis of symptoms such as plethoric features, palpitations, dizziness, or a feeling of tension. Screening surveys have demonstrated that these symptoms occur no more commonly in untreated hypertensive patients than they do in the normotensive population. However, there are two important caveats to the symptomless nature of essential hypertension: (1) symptoms may develop as a consequence of target organ damage, (2) headache may be a feature of severe hypertension.
Idiopathic oedema of women
Authors: Firth John D.
Published: February 2020

Idiopathic oedema is an unsatisfactory label that is applied to women who complain of swelling, typically variable, with diagnosis requiring exclusion of known causes of oedema and (most authors would agree) demonstration of weight gain, from morning to evening, of more than 1.4 kg. The cause of idiopathic oedema is (by definition) unknown: hypotheses include abnormal capillary permeability/leakage, re-feeding oedema, and diuretic-induced oedema. There is no clear relationship to the menstrual cycle. Even if not a primary cause, the use and abuse of diuretics can complicate and exacerbate the problem. Management is difficult, but patients can be helped by a sympathetic approach from the physician and (1) encouragement to lose weight if they are obese; (2) avoidance of excess dietary salt; and (3) weaning from consumption of high doses of diuretics that can cause or exacerbate the tiredness, lethargy, weakness, and dizziness that are suffered by many.