bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eosinophilia
Authors: Weller Peter F. 
Published: February 2020

Abstract
Eosinophilia (eosinophil count &gt;0.45 × 109/litre) is associated with some infections, some allergic diseases, and a variety of other conditions, sometimes neoplastic. Parasitic diseases—eosinophilia is a characteristic feature of infection by multicellular helminth parasites (e.g. Strongyloides stercoralis) with diagnosis typically based on geographical/dietary history, serological tests, and examination of stool or tissues for parasite forms. Other diseases—eosinophilia can be caused by the fungal disease coccidioidomycosis, and modest eosinophilia may accompany retroviral infections such as HIV and HTLV-1. Common allergic diseases—asthma, rhinitis, and atopic dermatitis are associated with modest eosinophilia. Drug reactions—these are a frequent cause of eosinophilia, at times in reactions characterized by rashes and pyrexia. More severe reactions may also manifest with (1) pulmonary eosinophilia and lung infiltrates; (2) interstitial nephritis; (3) hepatitis; (4) myocarditis; (5) drug-induced hypersensitivity vasculitis; (6) gastroenterocolitis; and (7) DRESS syndrome. Other conditions—these include (1) eosinophilic granulomatosis with polyangiitis; (2) hyper-IgE syndromes; (3) chronic myeloid leukaemia, acute myeloid leukaemia, and lymphoma; (4) a variety of pulmonary, skin, gastrointestinal, and endocrine diseases. Hypereosinophilic syndromes are defined by (1) eosinophilia (&gt;1.5 × 109/litre) sustained over a month, (2) lack of an identifiable cause precipitating a secondary eosinophilia, and (3) symptoms and signs of organ involvement. About 30% of patients will have either a myeloproliferative condition (chronic eosinophilic leukaemia) or hypereosinophilia mediated by clonal expansion of specific T cells producing interleukin-5 (IL-5). Treatment—patients without organ damage do not require treatment. Aside from supportive care, chronic eosinophilic leukaemia may respond to tyrosine kinase inhibitors (e.g. imatinib), and nonmyeloproliferative hypereosinophilic syndrome may respond to high-dose corticosteroids, with hydroxyurea, interferon-α or anti-IL-5 monoclonal antibody used in refractory cases.
Introduction to lymphopoiesis
Authors: Jacobson Caron A. , Berliner Nancy 
Published: February 2020

Abstract
Lymphoproliferative disorders occur when the normal mechanisms of control of proliferation of lymphocytes break down, resulting in autonomous, uncontrolled proliferation of lymphoid cells and typically leading to lymphocytosis and/or lymphadenopathy, and sometimes to involvement of extranodal sites (e.g. bone marrow). These include (1) malignant—clonal in nature, resulting from the uncontrolled proliferation of a single transformed cell (e.g. lymphoma); (2) nonmalignant—polyclonal lymphoproliferative disorders may result from conditions including (a) infections—lymphocytosis is commonly caused by viral infections (e.g. Epstein–Barr virus (EBV)), lymphadenopathy is a common feature of a very wide variety of infections; and (b) reactive—conditions such as systemic lupus erythematosus and sarcoidosis frequently cause lymphadenopathy. Distinguishing between the lymphoproliferative disorders clinically and pathologically is not always easy. Clinical assessment—when eliciting the history of a patient with suspected lymphoproliferation, particular note should be taken of their general health, the type and duration of any constitutional symptoms, and any episodes of recent infection/exposure to drugs/travel. Thorough examination of all lymph node sites is required, as is careful examination of the oropharynx, tonsils, skin, spleen, and liver. Investigation—whenever a lymphoproliferative disorder is suspected, the key initial investigation is the full blood count and examination of the blood film, sometimes augmented by immunocytochemistry and flow cytometry. Depending on clinical context, other investigations may include (1) serological studies for viral pathogens; (2) serological studies for rheumatological disease; (3) imaging for mediastinal and intra-abdominal lymphadenopathy; (4) bone marrow examination; and—if no diagnosis is apparent—(5) lymph node biopsy.
Acute lymphoblastic leukaemia
Authors: Vormoor H. Josef , Menne Tobias F. , Moorman Anthony V. 
Published: February 2020

Abstract
Acute lymphoblastic leukaemia (ALL) is a malignant proliferation of lymphoid blasts, most commonly of B-lineage origin. The clinical symptoms and signs are either a consequence of bone marrow failure (infections, bruising, petechiae, pallor, and tiredness) or a consequence of the uncontrolled proliferation of the blasts (lymphadenopathy, hepatosplenomegaly, and cranial nerve palsies). Its peak incidence is in young children but ALL occurs at all ages. More than 80% of all affected children are cured with modern chemotherapy, but unfortunately the outcome of adults is much worse despite some improvements led by the introduction of paediatric-inspired protocols and tyrosine kinase inhibitors in BCR-ABL1-positive ALL. Standard chemotherapy for ALL consists of several months of intensive multidrug induction, consolidation and intensification chemotherapy (including steroids, vincristine, asparaginase and anthracyclines), intrathecal methotrexate to target blasts in the central nervous system, and low-intensity maintenance therapy (with oral 6-mercaptopurine and methotrexate) for up to 3 years. Treatment is stratified according to the response and other prognostic biomarkers (including genetics). Allogeneic haematopoietic stem cell transplantation is used predominantly in the relapse setting for children but in frontline therapy for adult patients to consolidate chemotherapy. Novel targeted small molecules and, in particular, immunotherapy are promising to offer new treatment options for patients with high-risk or relapsed disease.
Anaemia: pathophysiology, classification, and clinical features
Authors: Weatherall David J. , Hatton Chris 
Published: February 2020

Abstract
Anaemia is defined by the World Health Organization as a reduction of the haemoglobin concentration to less than 130 g/litre (males) or less than 120 g/litre (females). It is a common problem, with a prevalence around 3% for middle-aged men and 14% for middle-aged women in the United Kingdom, and is seen more frequently with age. There is a much greater prevalence in the developing world. Anaemia can be caused by the defective production of red cells or an increased rate of loss of cells, either by bleeding or premature destruction (haemolysis). The causes of defective production of red cells include (1) deficiency of key haematinics, including iron, vitamin B12, or folate; (2) anaemia of chronic disease; (3) reduced erythropoietin production typically seen in chronic kidney disease; and (4) primary diseases of the bone marrow. Haemolytic anaemias may be classified as either genetic or acquired. The key issues are to determine the degree of disability caused by the anaemia and hence how quickly treatment must be started, and the cause of the anaemia. The main causes of anaemia can usefully be classified according to the associated red cell morphological changes: (1) hypochromic, microcytic—including iron deficiency (the commonest cause of anaemia) and thalassaemia (common in some populations); (2) normochromic, macrocytic—vitamin B12 or folate deficiency, alcohol, and myelodysplasia; (3) polychromatophilic, macrocytic—haemolysis; (4) normochromic, normocytic—chronic disorders, renal failure, and diseases of the bone marrow; and (5) leucoerythroblastic—myelofibrosis, leukaemia, and metastatic carcinoma. The reticulocyte count also provides a good way of thinking about the underlying cause of anaemia—whether due to defective production or excess consumption of red cells.
Erythrocyte enzymopathies
Authors: Zanella Alberto , Bianchi Paola 
Published: February 2020

Abstract
Numerous enzymes, including those of the hexose monophosphate and glycolytic pathways, are active in the red cell. They are required for the generation of ATP and the reductants NADH and NADPH. 2,3-Diphosphoglycerate, an intermediate of glucose metabolism, is a key regulator of the affinity of haemoglobin for oxygen, and accessory enzymes are also active for the synthesis of glutathione, disposal of oxygen free radicals, and for nucleotide metabolism. With the exception of heavy metal poisoning and rare cases of myelodysplasia, most red cell enzyme deficiency disorders are inherited. They may cause haematological abnormalities, (most commonly nonspherocytic haemolytic anaemias, but also rarely polycythaemia or methaemoglobinaemia, manifest with autosomal recessive or sex-linked inheritance), and may also be associated with nonhaematological disease when the defective enzyme is expressed throughout the body. Some may mirror important metabolic disorders, without producing haematological problems, making them of diagnostic value. Others are of no known clinical consequence. With rare exceptions, it is impossible to differentiate the enzymatic defects from one another by clinical or routine laboratory methods. Diagnosis depends on the combination of (1) accurate ascertainment of the family history; (2) morphological observations—these can determine whether haemolysis is present, rule out some causes of haemolysis (e.g. hereditary spherocytosis and other red blood cell membrane disorders), and diagnose pyrimidine 5′-nucleotidase deficiency (prominent red cell stippling); (3) estimation of red cell enzyme activity; and (4) molecular analysis. The most common red cell enzyme defects are glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, glucose-6-phosphate isomerase deficiency, pyrimidine 5′-nucleotidase deficiency—which may also induced by exposure to environmental lead—and triosephosphate isomerase deficiency.
The biology of haemostasis and thrombosis
Authors: White Gilbert C. , Roberts Harold R. , Key Nigel S. 
Published: February 2020

Abstract
Haemostasis—a component of the wound defence mechanism—is a process by which vessel wall components and platelets act in concert with procoagulant and anticoagulant proteins to form a plug of cells and cross-linked fibrin. The plug is later remodelled and replaced by new tissue as part of wound healing. These processes are very complex and involve highly controlled pathways of interaction between cells, glycans, and membrane-bound and soluble proteins of coagulation and fibrinolysis, as well as their cognate inhibitors. Thrombosis—this is an abnormal state leading to formation of a clot that partially or completely obstructs the flow of blood within the blood vessel; dislodgement leads to thromboembolism. To understand the biology of haemostasis and thrombosis, it is necessary to know the roles of the vessel wall, the platelets, the coagulation and fibrinolytic systems, and their respective inhibitors. Fibrinolysis and coagulation are interrelated: fibrin clots are normally lysed by plasmin locally released from plasminogen by the action of tissue plasminogen activator, and this process can be enhanced by some procoagulant factors (e.g. activated factor XII, and protein C). This system, so delicately controlled and normally maintained in a dynamic equilibrium, is strongly influenced by components involved in inflammatory and other defence mechanisms in the host. An integrated understanding of these processes offers the potential for improved means to predict the adverse complications of many diseases and ultimately to prevent their occurrence.
Evaluation of the patient with a bleeding tendency
Authors: Baglin Trevor 
Published: February 2020

Abstract
An apparent bleeding tendency is a common clinical problem, with presentation varying from acute unexpected bleeding during or immediately after surgery or dental extraction, to spontaneous unusual or excessive bruising, purpura, epistaxis, or a chronic haemorrhagic tendency. Long-standing bleeding symptoms suggest a lifelong condition, whereas recent-onset bleeding suggests an acquired disorder. If a bleeding disorder has been diagnosed and characterized in another family member, then the cause of bleeding may be easily identified, but the absence of a family history does not exclude a heritable disorder. The commonest cause of an acquired bleeding disorder is antithrombotic therapy. Investigations for bleeding disorder include full blood count and film (severe bleeding rarely occurs in the absence of trauma with a platelet count of more than 20 to 30 × 109/litre), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen level, reptilase time (useful for determining if a prolonged APTT is due to heparin), individual factor assays, mixing studies (can indicate if prolongation of PT or APTT is likely due to a factor deficiency or an inhibitor), platelet function analysis, and (rarely) bleeding time. Aside from general supportive care, specific therapy can be given when a defined haemostatic abnormality is identified. Drugs that cause bleeding should be stopped. Overanticoagulation due to a vitamin K antagonist can be reversed with vitamin K and/or prothrombin complex concentrate; dabigatran and be reversed with idarucizumab; it will soon be possible to reverse factor Xa-inhibitors (e.g. with andexanet alfa). Vitamin K should also be given to critically ill patients and those with liver disease. Early and sufficient blood product support should be given to those with massive blood loss and/or dilutional coagulopathy.
Thrombocytopenia and disorders of platelet function
Authors: Curry Nicola , Shapiro Susie 
Published: February 2020

Abstract
The platelet is the smallest circulating blood cell. In health, it plays a vital role in haemostasis, and in disease contributes to problems of bleeding and/or thrombosis. The number of platelets produced is under tight homeostatic control, regulated by the cytokine thrombopoietin. A normal platelet count lies within the range 150 to 450 × 109/litre. Thrombocytopenia is defined as a reduction in the number of circulating platelets to fewer than the normal reference range (typically &lt;150 × 109/litre). Spontaneous bleeding is uncommon unless the platelet count falls below 10 to 20 × 109/litre or unless there is abnormal platelet function. Thrombocytopenia can be classified according to three main pathologies: (1) increased platelet destruction, (2) reduced platelet production, and (3) increased platelet sequestration. Disorders of increased platelet destruction may be immune mediated or nonimmune. Primary immune thrombocytopenia (ITP) is an acquired disorder affecting both adults and children, characterized by an isolated thrombocytopenia (platelet count &lt;100 × 109 /litre) for which no precipitant can be found. Primary ITP is a diagnosis of exclusion. Corticosteroids are the main first-line therapy for adult ITP, commonly prednisolone. Nonimmune causes of platelet destruction include microangiopathic haemolytic disorders such as thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome, and disseminated intravascular coagulation. Decreased platelet production—most cases are acquired, with common or important causes being toxins (drugs, alcohol), nutritional deficiencies (folate or vitamin B12), bone marrow infiltration, and myelodysplastic syndrome. Disorders of platelet distribution and platelet sequestration include splenomegaly and hypersplenism, haemodilution, and extracorporeal circulation. Disorders of platelet function are usually acquired. The most common causes are medications and toxins, systemic disorders, and haematological diseases. Congenital disorders are a rare cause of symptomatic bleeding.
Imaging in neurological diseases
Authors: Molyneux Andrew J. , Renowden Shelley , Bradley Marcus 
Published: February 2020

Abstract
The modern imaging techniques of computed tomography and magnetic resonance imaging for the demonstration of structural neurological disease have developed rapidly since their first introduction in the 1970s and 1980s, respectively. They have undergone further technological evolution, particularly in the last 10 years, and continue to do so. A variety of both computed tomography- and magnetic resonance imaging-based techniques can provide anatomical, angiographic, and functional information. In addition, biochemical data may be obtained using magnetic resonance spectroscopy and microstructural information can be obtained using diffusion tensor imaging. The choice between computed tomography or magnetic resonance imaging depends on several factors. This chapter explains the various applications of both techniques and the situations that can call for either, or both.
Movement disorders other than Parkinson’s disease
Authors: Balint Bettina , Bhatia Kailash 
Published: February 2020

Abstract
Hyperkinetic movement disorders are characterized by involuntary (and excessive) movements. The five main forms are chorea, tics, myoclonus, dystonia, and tremor, which can sometimes occur in combination. Some movement disorders are defined by their paroxysmal occurrence (paroxysmal movement disorders) or by their presence only during sleep, and there are other conditions that lie outside the conventional list but are part of the spectrum of movement disorders, for example, stiff person syndrome. It is important to remember that drugs can cause a variety of movement disorders, including some very distinct presentations, and also that all organic movement disorders can be mimicked by so-called psychogenic or functional movement disorders.
Ataxic disorders
Authors: Wood Nicholas 
Published: February 2020

Abstract
Ataxia is a feature of disorders of the cerebellum and its connections. It may be found in a large range of neurological conditions, in some of which it is the principal or main feature, but clinical assessment is complicated by the fact that few ataxic patients have disease restricted to the cerebellum alone. The term ataxia derived from the Greek means ‘irregularity’ or ‘disorderliness’. Unsteadiness can result from several causes, including poor vision, impairment of postural reflexes, or due to a deficiency of sensory input (i.e. sensory ataxia). This chapter focuses on the symptoms, signs, and the pathological and clinical features of the disorders of the cerebellum (and its connections).
Bacterial infections
Authors: van de Beek Diederik , Thwaites Guy E. 
Published: February 2020

Abstract
Bacterial meningitis occurs in many clinical situations, including spontaneous (the most important category), post-traumatic, and device-associated (relating to cerebrospinal fluid shunts and drains). Each of these is associated with a particular pattern of infecting organisms, clinical presentation, and outcome, but overall there is high morbidity and mortality. Spontaneous meningitis is the most important category. It can be divided into neonatal meningitis and meningitis of childhood and adulthood. Post-traumatic meningitis follows neurosurgery or fractures of the skull. Device-associated meningitis complicates the use of cerebrospinal fluid shunts and drains. Infection may also be considered as community acquired or nosocomial (hospital acquired or physician associated).
Human prion diseases
Authors: Mead Simon , Will R.G. 
Published: February 2020

Abstract
Prion protein (for proteinacious infectious particle) is a membrane-associated glycoprotein present in all mammalian species. Its normal function is unknown, but in prion diseases (also known as transmissible spongiform encephalopathies) a misfolded polymer form of the protein, partially resistant to protease digestion, is deposited in the brain and associated—typically after long incubation periods—with neuronal dysfunction and death. Prion diseases have become the subject of intense scientific and public interest because they are caused by a biologically distinct disease mechanism and because of the implications for public health following the identification of a new human prion disease, variant Creutzfeldt–Jakob disease (vCJD), and the evidence that it is caused by the transmission to humans of a cattle prion disease, bovine spongiform encephalopathy (BSE).
Acquired metabolic disorders and the nervous system
Authors: Scolding Neil 
Published: February 2020

Abstract
Metabolic diseases and their neurological complications require a knowledge of both general internal medicine and of neurology - one reason why they are often poorly handled clinically. They range from the neurological complications of hypercalcaemia to dramatic, serious, and not uncommon neurological picture of central pontine myelinolysis and its still uncertain metabolic cause(s); from the emergence of new(-ish) disorders such as superficial siderosis and E-induced water intoxication to the changing face and context of iatrogenic Cushing’s syndrome, chemotherapy-induced nutritional and metabolic disruption. This brief and partial list helps to emphasize the importance and impact of acquired neurometabolic diseases. This chapter aims to deal with these, or to point elsewhere in this text to where they are covered.
Autoimmune encephalitis and Morvan’s syndrome
Authors: Buckley Camilla , Vincent Angela 
Published: February 2020

Abstract
Since its first recognition in 2001, hundreds of patients have been identified with autoimmune limbic encephalitis (LE) associated with antibodies that immunoprecipitate voltage-gated potassium channel (VGKC)-complex proteins. Preliminary epidemiology suggests that it is more common in men (2:1) and that the median age at onset is 65 years. The phenotype has been recognized mainly in patients over the age of 18 years at onset. The classic presentation is with subacute onset of short-term memory loss, seizures, disorientation, with psychological disturbance or hallucinations. Additional features that may occur are sleep disturbance, autonomic dysfunction, and neuromyotonia, but these would be more typical of Morvan’s syndrome.
Substance misuse
Authors: Potts Stephen 
Published: February 2020

Abstract
Many chemical substances are taken for their psychoactive properties, even if prescribed for other purposes. Such use and misuse of psychoactive substances is so highly prevalent that it inevitably impinges on medical practice. All physicians therefore need a general understanding of the ways in which substance misuse may interrelate with medical needs, as well as a specific understanding of the inter-relationships most relevant to their own area of medical practice. Use of psychoactive substances may lead to acute intoxication and its consequences, or the effects of chronic use and dependence. Acute intoxication is associated with accidents and with acute psychiatric and medical illness. Chronic misuse may cause medical harm, which is often linked to the route of administration. Injection of substances poses particular hazards.
Anxiety disorders
Authors: Liao Ted , Epstein Steve 
Published: February 2020

Abstract
Anxiety is a common feeling, but also the central symptom of several psychiatric disorders: generalized anxiety disorder, panic disorder, phobias, and obsessive-compulsive disorder. Anxiety disorders are common and important in general medical practice as they often manifest with physical symptoms such as palpitations, chest pain, and dizziness that can be misdiagnosed as medical conditions and lead to unnecessary investigation and treatment. Anxiety disorder, especially phobic anxiety, can also lead to inability to adhere to medical treatments, for example, because of needle phobia interfering with blood tests and/or injected drugs treatment. Both pharmacological and psychological treatments are effective. For chronic anxiety, selective serotonin reuptake inhibitors are the drugs of choice, with benzodiazepines being reserved for short-term use. If available, cognitive behaviour therapy is similarly effective. Anxiety disorders usually respond to treatment but often recur.