bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hereditary periodic fever syndromes
Authors: Lachmann Helen J. , Berg Stefan , Hawkins Philip N. 
Published: February 2020

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.