bluuebunny/crossref_metadata_2025_split huggingface dataset:
Megaloblastic anaemia and miscellaneous deficiency anaemias
Authors: Hoffbrand A.V. 
Published: February 2020

Abstract
Megaloblastic anaemias are characterized by red blood cell macrocytosis. They arise because of inhibition of DNA synthesis in the bone marrow, usually due to deficiency of one or other of vitamin B12 (cobalamin) or folate, but sometimes as a consequence of a drug or a congenital or acquired biochemical defect that disturbs vitamin B12 or folate metabolism, or affects DNA synthesis independent of vitamin B12 or folate. Acquired pernicious anaemia—antibodies in serum and gastric juice directed against parietal cells (85–90% of cases) and intrinsic factor (50%), and raised serum gastrin are associated with autoimmune gastritis and failure of absorption of vitamin B12. Treatment and prevention of megaloblastic anaemia—vitamin B12 deficiency—may be treated with intramuscular hydroxocobalamin (1-mg doses, six given in the first 2–3 weeks, then every 3 months). Oral therapy is practised by a minority and is unlikely to be useful in pernicious anaemia. Neurological complications are irreversible unless treated early. Folate deficiency—high-dose oral folic acid (5 mg daily) overcomes folate malabsorption, but this should not be given alone where vitamin B12 deficiency coexists because neurological disease may be precipitated or exacerbated (although the haematological abnormalities improve). Where folate metabolism is disturbed by methotrexate, oral or parenteral folinic acid is given to restore DNA synthesis. Prevention—dietary folate fortification is an accepted and highly effective public health measure in many countries (none in Europe) for reducing the incidence of neural tube birth defects.
Anaemias resulting from defective maturation of red cells
Authors: Fuller Stephen J. , Wiley James S. 
Published: February 2020

Abstract
Defective maturation of red cells leads to premature destruction of nucleated red cell precursors before they leave the haematopoietic bone marrow, which results in expansion of the marrow, haemolytic jaundice, peripheral signs of increased erythroid turnover on blood films, and (in long-standing disorders) iron overload due to enhanced absorption. Causes of ineffective erythropoiesis include (1) inhibition of erythroid DNA synthesis (e.g. megaloblastic anaemias (vitamin B12 or folate deficiency), drugs blocking DNA synthesis); (2) clonal disorders of erythropoiesis (e.g. refractory anaemia, acquired idiopathic sideroblastic anaemia, acute erythroleukaemia); (3) genetic disorders of erythropoiesis (e.g. thalassaemia syndromes, hereditary sideroblastic anaemia, congenital dyserythropoietic anaemia); and (4) other causes (e.g. alcohol). Sideroblastic anaemias—these result from defects in haem biosynthesis, with most cases being acquired as a clonal disorder of erythropoiesis, with varying degrees of myelodysplasia. Other causes are (1) hereditary (e.g. inherited deficiency of the erythroid-specific 5-aminolaevulinic acid synthase 2 gene on the X-chromosome causes congenital sideroblastic anaemia); (2) acquired (e.g. due to drugs or toxins such as ethanol, isoniazid, or lead; following chemotherapy or irradiation; or of unknown cause (idiopathic)). Diagnosis, treatment, and prognosis—diagnosis is achieved by finding ring sideroblasts (erythroblasts containing five or more iron-positive granules arranged in a perinuclear location around one-third or more of the nucleus) on bone marrow aspirate stained with Prussian blue iron reagent. Aside from supportive care with blood transfusion and iron chelation, a trial of pyridoxine is generally indicated (25% of hereditary cases—but few acquired cases—show some response). Acquired idiopathic sideroblastic anaemia has a median survival of 42 to 76 months, with 3 to 12% progressing to acute leukaemia.
Disorders of the red cell membrane
Authors: Gallagher Patrick G. 
Published: February 2020

Abstract
The integrity of the red cell membrane depends on molecular interactions between proteins and the phospholipid membrane: vertical interactions stabilize the membrane lipid bilayer; horizontal interactions provide resistance against shear stress. Hereditary spherocytosis—affects 1 in 25 000 individuals of northern European descent. There is typically a dominant family history, but the condition is genetically heterogeneous: combined spectrin and ankyrin deficiency is the most common defect observed, followed by band 3 deficiency, isolated spectrin deficiency, and protein 4.2 deficiency. These affect vertical membrane interactions with loss of surface area relative to red cell volume. Clinical features—the key clinical manifestations are anaemia and signs of persistent haemolysis, with jaundice and a marked propensity to gallstones. Complications and treatment—parvovirus B19 infection of erythropoietic precursors may cause acute aplastic crises. Megaloblastic anaemia due to folate deficiency occurs in response to increased requirements during growth and pregnancy, but is preventable with supplementation. Splenectomy can alleviate the anaemia in many patients and reduces the risk of gallstones. Hereditary elliptocytosis—occurs with a frequency of 1 in 2000 to 1 in 4000 worldwide, and is more frequent in parts of Africa. The inheritance is usually dominant, with defects in red cell proteins such as α- and β-spectrin causing disturbances in horizontal interactions in the erythrocyte membrane. Clinical features, diagnosis, and treatment—most patients are asymptomatic and are typically diagnosed incidentally during testing for unrelated conditions, but about 10% experience haemolysis, anaemia, splenomegaly, and intermittent jaundice. Diagnosis is based on the presence of elliptocytes on a peripheral blood smear. Treatment is rarely required. Other conditions include hereditary pyropoikilocytosis, South-East Asian (or Melanesian) ovalocytosis, stomatocytosis, and acanthocytosis.
Glucose-6-phosphate dehydrogenase deficiency
Authors: Luzzatto Lucio 
Published: February 2020

Abstract
Deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD) in red blood cells is an inherited abnormality due to mutations of the G6PD gene on the X chromosome that renders the cells vulnerable to oxidative damage. The condition is widespread in many populations living in or originating from tropical and subtropical areas of the world because it confers a selective advantage against Plasmodium falciparum malaria. Clinical features—G6PD deficiency is mostly an asymptomatic trait, but it predisposes to acute haemolytic anaemia in response to exogenous triggers, including (1) ingestion of fava beans—favism; (2) certain bacterial and viral infections; and (3) some drugs—notably some antimalarials (e.g. primaquine), some antibiotics (e.g. sulphanilamide, dapsone, nitrofurantoin), and even aspirin in high doses. Other manifestations include (1) severe neonatal jaundice; and (2) chronic nonspherocytic haemolytic anaemia—the latter is only seen with rare specific genetic variants. The acute haemolytic attack typically starts with malaise, weakness, and abdominal or lumbar pain, followed by the development of jaundice and passage of dark urine (haemoglobinuria). Most episodes resolve spontaneously. Diagnosis relies on the direct demonstration of decreased activity of G6PD in red cells: a variety of screening tests are available, with (ideally) subsequent confirmation by quantitative assay. Prevention is by avoiding exposure to triggering factors of previously screened subjects. Prompt blood transfusion is indicated in severe acute haemolytic anaemia and may be life-saving.
Genetic disorders of coagulation
Authors: Pollak Eleanor S. , High Katherine A. 
Published: February 2020

Abstract
Haemophilia is a familial X-linked disorder due to deficiency of either factor VIII (haemophilia A) or factor IX (haemophilia B), components of the intrinsic enzymatic complex that activates factor X. Clinical features and diagnosis—the main manifestations are bleeding into joints and soft tissues, with haemophilic arthropathy and joint deformity being inevitable complications in untreated patients. Other features include pseudotumours, bleeding into the urinary system, and bleeding following clinical procedures. Laboratory diagnosis is based on a modification of the classic activated partial thromboplastin time (APTT) assay, with inhibitor screening used to exclude other causes of prolonged APTT. Treatment—involves the administration of the deficient factor VIII or factor IX, most commonly ‘on demand’ in response to bleeding, with prophylactic treatment given before surgery. Von Willebrand’s disease is a common autosomal dominant disorder of platelet function caused by a functional deficiency of von Willebrand factor (VWF). VWF, normally synthesized by megakaryocytes, prevents degradation of factor VIII; VWF, also made by endothelial cells, enhances platelet activation and recruitment at sites of tissue damage. Treatment—mild von Willebrand’s disease is treated with desmopressin 1-deamino-8-d-arginine vasopressin (DDAVP), which releases factor VIII and VWF from endothelial cells. Other treatments include ε-aminocaproic acid, oestrogens, and factor VIII concentrates. Other hereditary disorders of coagulation, including (1) hereditary deficiency of the plasma metalloproteinase ADAMTS13; (2) combined deficiency of coagulation factors V and VIII; (3) factor XI deficiency; (4) inherited deficiencies of factors II, V, VII, and X; and (5) deficiency of the contact activating factors, factor XIII, and fibrinogen, and hypercoagulable diseases due to deficiencies of anticoagulants or propensity to thrombosis are discussed in this chapter.
Autoimmune bullous diseases
Authors: Taghipour Kathy , Wojnarowska Fenella 
Published: February 2020

Abstract
Autoimmune bullous diseases of the skin are a heterogenous group of blistering diseases that affect the skin and/or mucosal membranes. They are associated with significant morbidity and mortality and may present to several different specialists. They are broadly divided into two groups depending on the location of the blisters formed in the skin, which may be subepidermal (pemphigoids, linear IgA disease, dermatitis herpetiformis, epidermolysis bullosa acquisita) or intraepidermal (pemphigus group). Pathogenic autoantibodies (IgG, IgA) target either the proteins that provide keratinocyte adhesion (intraepidermal disease) or the proteins of hemidesmosomes that attach the basal cell layer to the basement membrane zone (subepidermal disease).
Photosensitivity
Authors: Fassihi Hiva , McGregor Jane 
Published: February 2020

Abstract
Normal human skin is photosensitive in that it reddens following acute sunlight exposure and tans and thickens following chronic sunlight exposure. Skin cancer, particularly non-melanoma skin cancer, is also a consequence of high cumulative sun exposure in genetically predisposed normal individuals (predominantly those with fair skin).
Outside the range of normal photosensitivity, there are several conditions in which patients exhibit diverse abnormal cutaneous reactions to sunlight. These are broadly described together as the photosensitivity disorders, but in fact they comprise a very heterogeneous group of skin conditions. Abnormal cutaneous photosensitive responses range from easy sunburn (as in drug phototoxicity and the DNA repair photodermatoses) and pain (erythropoietic protoporphyria), through to complex inflammatory responses such as urticaria, eczema, or epidermal necrosis induced by specific wavelengths of sunlight, the so-called idiopathic photodermatoses.
Management of skin disease
Authors: Sinclair Rod 
Published: February 2020

Abstract
Topical therapy of skin disease employs a vehicle (ointments, creams, lotions, gels) to deliver an active ingredient to the skin, to provide a protective barrier, or to hydrate and moisturize the skin. There are many types of topical treatments, including antipruritics, are used to relieve itching; keratolytics are used to remove hyperkeratotic skin; tars act by reducing the thickness of the epidermis; corticosteroids have anti-inflammatory and immunosuppressive effects that are useful in treating many skin disorders; calcipotriol reduces epidermal proliferation and is used in local treatment of plaque psoriasis; calcineurin inhibitors for eczema and other diseases; retinoids influence immune function and have some anti-inflammatory activity and are used in acne; immunomodulatory drugs such as imiquimod for some human papillomavirus infections, superficial basal cell carcinomas, and other diseases.
Mind and brain: Building bridges between neurology, psychiatry, and psychology
Authors: Zeman Adam 
Published: February 2020

Abstract
Medicine is traditionally regarded as concerning itself with disorders of the body while psychiatry concerns itself with disorders of the mind—and ‘never the twain shall meet’. But both everyday clinical experience and our growing understanding of the physical basis of mind challenge this view. Patients are always a compound of body and mind; discoveries relating to the mechanisms, phylogeny, ontogeny, and functions of the central nervous system are gradually traversing the mind-body and mind-brain divides. We should take a bio-psycho-social approach in every clinical encounter and seek theories that explain the emergence of mind from life much as life emerges from matter.
Electrophysiology of the central and peripheral nervous systems
Authors: Krarup Christian 
Published: February 2020

Abstract
This chapter looks at electrophysiological studies of the central nervous system and peripheral nervous system—the core investigations in clinical neurophysiology. These include electroencephalography, which is of value to diagnose epilepsy caused by focal or diffuse brain diseases, electromyography and nerve conduction studies, which are of value to diagnose diseases in nerves and muscles, and evoked potentials, which are of value to diagnose diseases of white matter in the brain and spinal cord.
Subcortical structures: The cerebellum, basal ganglia, and thalamus
Authors: Edwards Mark J. , Talelli Penelope 
Published: February 2020

Abstract
Less is known of the function of the cerebellum, thalamus, and basal ganglia than of other structures in the brain, but there is an increasing appreciation of their complex role in motor and non-motor functions of the entire nervous system. These structures exercise functions that far exceed their previously assumed supporting parts as simple ‘relay stations’ between cortex and spinal cord. The subcortical structures receive massive different inputs from the cerebral cortex and peripheral sense organs and stretch receptors. Through recurrent feedback loops this information is integrated and shaped to provide output which contributes to scaling, sequencing, and timing of movement, as well as learning and automatization of motor and non-motor behaviours.
Parkinsonism and other extrapyramidal diseases
Authors: Sokolov Elisaveta , Metta Vinod K. , Chaudhuri K. Ray 
Published: February 2020

Abstract
The human basal ganglia is a complex functional organization, with important interconnections with the nigrostriatal pathway, which dominates the dopaminergic innervation of the striatum (caudate nucleus and the putamen). The principal clinical syndromes affecting it are Parkinson’s disease; other syndromes with parkinsonian features (including drug-induced parkinsonism); progressive supranuclear palsy; multisystem atrophy; dementia with Lewy bodies; neuroacanthosis; torsion dystonia; and chorea. Apart from the use of dopaminergic agents, several drugs have beneficial effects in the management of parkinsonism and other extrapyramidal diseases. Parkinson’s disease affects about 0.2% of the population, including 2% of those over 80 years of age. The main pathological feature is degeneration of neuromelanin-containing neurons and Lewy body inclusions in the pars compacta of the substantia nigra, which leads directly and indirectly to excessive inhibition of the thalamus and consequent bradykinesia.
Headache
Authors: Goadsby Peter J. 
Published: February 2020

Abstract
Headache is among the most common of human maladies. So much so that it is generally (and often incorrectly) assumed to be understood, especially by doctors. The classification of headache, with formal definitions of different diagnostic entities, by the International Headache Society into (1) primary—occurring in the absence of external causes, and (2) secondary—some of which may have sinister cause, has greatly simplified the description, understanding, and management of this often challenging symptom. It also allows those headaches with serious or life-threatening consequences to be distinguished from other forms. This chapter examines the various types of headache, from primary headaches and migraine, and tension-type to secondary headache and other forms.
Stroke: Cerebrovascular disease
Authors: van Gijn J. , Rothwell Peter M. 
Published: February 2020

Abstract
Cerebrovascular diseases include many pathological conditions but the principal categories are (1) infarction—through occlusion of major arteries, small arteries or venous sinuses; and (2) haemorrhage—most often through rupture of small arteries, arterial aneurysms, or capillaries. Strokes are common, with annual incidence rates for subjects aged over 55 ranging from 420 to over 1,000 per 100,000. They are the most important case of disability in developed Western nations and the second most frequent cause of death after coronary heart disease. About 80% of strokes are caused by cerebral infarcts, with the remainder due to haemorrhage, with 20% of these attributable to a bleeding cerebral aneurysm. The annual incidence of transient ischaemic attacks (TIAs) is about 50–100 per 100,000.
Idiopathic intracranial hypertension
Authors: Sinclair Alexandra 
Published: February 2020

Abstract
Idiopathic intracranial hypertension (IIH) (also called pseudotumour cerebri and, previously, benign intracranial hypertension) is a syndrome of raised intracranial pressure in the absence of an intracranial mass lesion, enlargement of the cerebral ventricles, or venous sinus thrombosis. IIH affects predominantly obese women of childbearing age (&gt;90%). The condition has considerable morbidity from permanent visual loss (up to 25% of cases) and chronic disabling headaches, which result in poor quality of life. Patients presenting acutely with papilloedema must be evaluated urgently for secondary causes of raised intracranial pressure (e.g. space occupying lesion and venous thrombosis). After this, the priority is to assess accurately the threat to vision. In most patients, the condition becomes chronic and the disease burden is mostly from chronic headaches, which need active management, alongside visual monitoring. This chapter does not cover paediatric IIH.
Neurosyphilis and neuro-AIDS
Authors: Manji Hadi 
Published: February 2020

Abstract
Invasion of the central nervous system occurs early in the course of syphilis infection. Neurosyphilis causes a meningitis, a myeloradiculopathy due to pachymeningitis, gummatous (granulomatous) cord and brain lesions; endarteritis may cause infarction and a low-grade meningoencephalitis affecting the brain results in dementia (general paralysis of the insane) and in the spinal cord, a sensory ataxic syndrome (tabes dorsalis). The introduction of highly active antiretroviral therapies has greatly reduced the frequency of these complications in patients with access to these treatments. However, newer complications are now increasingly recognized such as neurological immune reconstitution inflammatory syndrome, a compartmentalization syndrome (cerebrospinal fluid escape). This chapter looks at these and other important issues regarding the background, diagnosis, treatment, and outlook for neurosyphilis and neuro-AIDS.
Disorders of cranial nerves
Authors: Hadden Robert D.M. 
Published: February 2020

Abstract
The 12 cranial nerves are peripheral nerves except for the olfactory and optic nerves which are central nervous system tracts. Disorders of each nerve are discussed in turn, summarising the complex anatomy and many causes. The commonest single nerve disorders are anosmia due to head injury, eye movement disorders due to microvascular ischaemia of the oculomotor or abducens nerve, trigeminal neuralgia, and Bell's facial palsy. Multiple cranial nerves may be affected simultaneously by structural lesions at key locations such as skull foramina, and various inflammatory, neoplastic or infective causes.
Muscular dystrophy
Authors: Bushby Kate , Marini-Bettolo Chiara 
Published: February 2020

Abstract
Muscular dystrophy is not a single disease. Many different types of muscular dystrophy can be recognized: all are primary, genetically determined disorders of muscle and all cause muscle weakness and wasting, which is usually progressive. Muscular dystrophies are primary, genetically determined disorders of muscle. All cause muscle weakness, which is usually progressive. They are challenging to classify, but clinical characteristics can be combined with genetic and molecular information to obtain a useful operational nomenclature for prognosis and family counselling. In general, diagnosis is guided by the age at which clinical manifestations appear, the distribution of weakness, and the rate at which muscle function is lost, but unusual features such as muscle pain and rhabdomyolysis may also contribute to the identification of a particular hereditary muscle disorder.
Myotonia
Authors: Hilton-Jones David 
Published: February 2020

Abstract
Myotonia is defined at an electrical level as repetitive discharge of the muscle fibre membrane after initial activation, which occurs due to dysfunction of the membrane’s ion channels, most commonly the chloride channel, less commonly the sodium channel. This manifests clinically as stiffness of the muscle and delayed relaxation after voluntary contraction (e.g. difficulty relaxing the grip after clenching the fingers, and stiffness in the thigh muscles and difficulty walking on first moving after rest). Disabling myotonia may respond to carbamazepine, phenytoin or, often most effectively, mexiletine, although supplies are now limited. This chapter takes a closer look at the condition, its symptoms, presentations, diagnosis, and treatment.
Medically unexplained symptoms
Authors: Sharpe Michael 
Published: February 2020

Abstract
Physical symptoms are not always associated with disease. In secondary medical care as many as a third of patients present with symptoms unexplained by disease. Such ‘medically unexplained symptoms’ pose a challenge for clinical services that focus on identifying and treating disease. The principles of effective management are to: (a) avoid overinvestigation and giving speculative treatment for disease; (b) take a positive approach with the patient, accepting the reality of the symptoms while explaining clearly that they do not indicate disease; (c) identify and provide treatment for associated depression and anxiety disorders; (d) refer for psychiatric or psychological treatment when required. Complex cases with multiple persistent medically unexplained symptoms are at particular risk of iatrogenic harm and require active multidisciplinary management. Psychological treatments such as cognitive behaviour therapy may be effective.