bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artificial nutrition support
Authors: Woodward Jeremy 
Published: February 2020

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
High blood pressure (BP &gt;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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.
Peptic ulcer disease
Authors: Sung Joseph 
Published: February 2020

Abstract
Helicobacter pylori infection, use of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin, and smoking are the most important causes of peptic ulcer disease. Peptic ulcer disease is characterized by a history of waxing and waning symptoms of localized, dull, aching pain in the upper abdomen. Bleeding is the most common complication; free perforation of the stomach or duodenum into the peritoneal cavity is uncommon but serious. The diagnosis of peptic ulcer disease is made by endoscopy, which offers an opportunity for biopsy of gastric ulcers (which may be malignant) and reveals important prognostic indicators in patients with bleeding ulcers. A single daily dose of a proton pump inhibitor gives quick relief of symptoms and effective healing of peptic ulcers in 4 to 6 weeks. The management of patients with upper gastrointestinal haemorrhage requires a multidisciplinary medical and surgical approach. Early risk stratification based on clinical and endoscopic criteria allows delivery of appropriate care, with endoscopic intervention now widely accepted as the first line of therapy. This should be followed by administration of a high dose of an intravenous proton pump inhibitor to further reduce recurrent bleeding. Treatment of H. pylori is a cure for peptic ulcer disease in most patients. This usually requires at least two antimicrobial agents, with the most popular triple therapy combining a proton pump inhibitor with any two of amoxicillin, metronidazole, and clarithromycin for 7 to 14 days. Eradication of H. pylori infection, avoidance of high-dose NSAIDs or aspirin, and the maintenance use of proton pump inhibitors in high-risk individuals are the best ways to prevent recurrence of ulcer and ulcer complications.