bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mycobacteria
Authors: Jarvis Hannah , Kon Onn Min 
Published: February 2020

Abstract
Mycobacteria are Gram-negative, rod-shaped bacilli comprising the Mycobacterium tuberculosis complex (TB) and non-tuberculous mycobacteria. Infection, usually via inhalation, is often asymptomatic but can lead to primary TB or to latent TB infection which can later develop into ‘reactivation’ or ‘post-primary’ active disease. Pulmonary TB is the commonest manifestation, but extrapulmonary disease can affect almost any organ. Definitive diagnosis is by culture. Standard chemotherapy involves the use of rifampicin, isoniazid, pyrazinamide, and ethambutol. Drug resistance is an increasing problem. Around 1.5 million people die from TB each year. Infection tends to present with a worsening of chronic respiratory symptoms in patients with underlying lung diseases. Diagnosis is difficult because these organisms are common in the environment. A long course of treatment with several drugs is required.
Allergic rhinitis
Authors: Durham Stephen R. , Saleh Hesham A. 
Published: February 2020

Abstract
Allergic rhinitis affects more than 20% of the population of Westernized countries and has a significant impact on quality of life and school/work performance. Important environmental factors include tree and grass pollens (seasonal allergic rhinitis); house dust mite and domestic pets, most often cats (perennial allergic rhinitis); and a variety of occupational exposures (occupational rhinitis). Pathogenesis involves activation of type 2 (Th2) lymphocytes resulting in IgE antibody production and tissue eosinophilia. Immediate symptoms (itching, sneezing, and watery nasal discharge) result from allergen cross-linking adjacent IgE molecules on the surface of mast cells in the nasal mucosa, resulting in the release of histamine and tryptase, and generation of bradykinin. Diagnosis is usually straightforward and based on the history, examination, and (when indicated) the results of skin prick tests and/or serum allergen-specific IgE levels.
Sarcoidosis
Authors: Baughman Robert P. , Lower Elyse E. 
Published: February 2020

Abstract
Sarcoidosis is a disease of unknown cause that is characterized by the presence of non-caseating granulomas in at least two organs. It can present in a wide variety of ways. Differential diagnosis is most commonly from tuberculosis or lymphoma. Most patients with sarcoidosis will experience disease resolution within 2–5 years; about 25% will develop residual fibrosis in the lungs or elsewhere; in a few the disease will become chronic and persist for more than 5 years. Most series from referral centres report 5% disease-related mortality, usually from respiratory failure. There is no single treatment for all patients with sarcoidosis. First-line treatment is usually with corticosteroids, although it is not universally accepted that steroids change the course of the disease. If the dose of steroid cannot be reduced to an acceptable level, or if the patient is not responding, then other agents (e.g. chloroquine/hydroxychloroquine, methotrexate, leflunomide, infliximab) are added.
Pneumoconioses
Authors: Reid P.T. 
Published: February 2020

Abstract
Pneumoconiosis describes the pathological reaction of the lung to inhaled dust, most often, but not exclusively, related to exposures occurring at work. It may be defined as a permanent alteration of lung structure due to the inhalation of mineral dust and the tissue reactions of the lung to its presence, excluding bronchitis and emphysema. The causes of pneumoconiosis are many and varied, but coal worker’s pneumoconiosis, asbestosis, and silicosis are most common. Many epidemiological studies have shown an exposure–response relationship between the total mass of respirable dust to which workers have been exposed and their risk of developing disease. These form the basis of regulations specifying limits to permitted levels of exposure. Workers who develop pneumoconiosis as a consequence of their employment may be entitled to compensation in some countries.
Chronic respiratory failure
Authors: Polkey Michael I. , Calverley P.M.A. 
Published: February 2020

Abstract
Chronic respiratory failure describes a clinical state when the arterial Po2 breathing air is less than 8.0 kPa, which may or may not be associated with hypercapnia (defined as Pco2 more than 6.0 kPa (45 mm Hg)). Four processes cause arterial hypoxaemia due to inefficient pulmonary gas exchange—ventilation–perfusion (V/Q) mismatch, hypoventilation, diffusion limitation, and true shunt, with the most important of these being V/Q mismatching. The arterial CO2 is increased by inadequate alveolar ventilation and/or V/Q abnormality. A wide range of disorders can cause chronic respiratory failure, with the commonest being chronic obstructive pulmonary disease, interstitial lung diseases, chest wall and neuromuscular diseases, and morbid obesity.
Disorders of the thoracic cage and diaphragm
Authors: Shneerson John M. , Polkey Michael I. 
Published: February 2020

Abstract
Disorders of the thoracic skeleton can lead to a severe restrictive ventilatory defect, the risk of respiratory failure being highest with (1) scoliosis—particularly if the following characteristics are present: early onset, severe angulation, high in the thorax, respiratory muscle weakness, low vital capacity; (2) kyphosis—but only if of very sharp angulation (gibbus), most commonly seen following tuberculous osteomyelitis; and (3) after thoracoplasty—historically performed as treatment for pulmonary tuberculosis. While not a disorder of the skeleton, a similar pathophysiological pattern is seen in extreme obesity, and this is the fastest growing cause of referral to home ventilation centres. Arterial blood gases and quality of life can both be readily improved with non-invasive ventilation, usually using a nasal or face mask. Survival in most skeletal disorders after starting ventilation leads to apical bullae, pleural thickening/effusions, and cricoarytenoid arthritis, but rarely causes respiratory failure in the absence of other comorbidities.
Pleural tumours
Authors: Lee Y.C. Gary 
Published: February 2020

Abstract
Benign tumours are rare in the pleural cavity, with solitary fibrous tumour of the pleura the most frequent of these rarities. Malignant pleural tumours are common and can arise from the pleura (most commonly mesothelioma) or as metastases from extrapleural malignancies (especially lung and breast cancer). They typically present with breathlessness, chest pain, and a pleural effusion. Diagnosis requires histocytological confirmation of malignant cells from pleural fluid and/or pleural biopsies. Most cases are due to asbestos exposure, characteristically after a latent period of more than 20 years, with risk related to the duration and intensity of asbestos exposure and the fibre type (worst with needle-like amphiboles). Most tumours that have spread to the pleura are incurable.
Spondyloarthritis and related conditions
Authors: Braun Jürgen , Sieper Joachim 
Published: February 2020

Abstract
The spondyloarthritides are a group of common inflammatory rheumatic diseases with predominant involvement of axial and peripheral joints and entheses, together with other characteristic clinical features, including inflammatory back pain, sacroiliitis, peripheral arthritis (mainly in the legs), enthesitis, dactylitis, preceding infection of the urogenital/gastrointestinal tract, psoriatic skin lesions, Crohn-like gut lesions, anterior uveitis, and a family history of spondyloarthritis (SpA). Five subsets can be distinguished on clinical grounds: (1) axial SpA, including ankylosing spondylitis; (2) reactive (spondylo)arthritis/Reiter’s syndrome; (3) psoriatic (spondylo)arthritis; (4) (spondylo)arthritis associated with inflammatory bowel diseases; and (5) undifferentiated peripheral SpA. Prevalence in any population correlates roughly with that of HLA B27, but the relevance of this to pathogenesis is not known. Another more recent approach is to differentiate the SpA on the basis of the predominant clinical manifestation: predominant axial and/or peripheral SpA.
Systemic lupus erythematosus and related disorders
Authors: Rahman Anisur , Isenberg David A. 
Published: February 2020

Abstract
Systemic lupus erythematosus is an autoimmune rheumatic disorder that can present with symptoms in almost any organ or system of the body. It is 10 times commoner in women than men, and commoner in Afro-Caribbeans than in other ethnic groups. Its aetiology is multifactorial, incorporating genetic, hormonal, and environmental elements. No single abnormality of the immune system can be considered responsible, pathogenesis depending on the interplay of several different factors, including autoantibodies, T lymphocytes, cytokines, the complement system, and apoptosis. Common symptoms are constitutional (fatigue, anorexia), musculoskeletal (arthralgia/arthritis, myalgia), dermatological (alopecia, butterfly rash, vasculitic skin lesions, purpura), cardiopulmonary (breathlessness, pleurisy), and neurological (migraine, seizures, depression, psychosis). Treatment for mild disease is NSAID, analgesics and hydroxychloroquine, more severe disease requires corticosteroid and immunosuppressant drugs.
Sjögren’s syndrome
Authors: Ng Wan-Fai 
Published: February 2020

Abstract
Sjögren’s syndrome is an autoimmune connective tissue disease characterized by dryness of the eyes and mouth and lymphocytic infiltrates in the salivary, lachrymal, and other exocrine glands. Its cause is not known, but it may be primary or associated with other autoimmune diseases (secondary) and it affects women more than men (ratio 9–15:1). The aetiology of SS remains elusive, although genetic susceptibility and environmental triggers both play a role. Genome-wide association studies have identified several disease-susceptibility loci. Infections with various viruses have been associated with an SS-like syndrome. Current evidence suggests that environmental or endogenous antigen triggers immune cell activation and autoantibody production, leading to a self-perpetuating inflammatory response in genetically susceptible individuals, and resulting in destruction of exocrine glands.
Skeletal disorders—general approach and clinical conditions
Authors: Wordsworth B. Paul , Javaid M.K. 
Published: February 2020

Abstract
Bone is made up of (1) cells—osteoblasts, osteoclasts, and ostoecytes; and (2) extracellular mineralized matrix—roughly one-third organic (90% type 1 collagen) and two-thirds inorganic (mainly hydroxyapatite). Common presentations of bone disease include (1) deformity and short stature; (2) bone pain and fracture; (3) myopathy—in osteomalacia and rickets; (4) features of underlying disease (e.g. renal failure, myeloma). Many generalized disorders of the skeleton, such as osteoporosis, have entirely normal routine biochemical values. Radiographic imaging can be diagnostic in some cases, but MRI and CT are increasingly employed in addition to conventional (‘plain’) radiographs and bisphosphonate-labelled isotope scans. Bone biopsy is required for diagnosis in some circumstances. This chapter emphasizes those disorders in which impact on the skeleton is a substantial feature of the underlying condition.
Membranoproliferative glomerulonephritis
Authors: Turner-Stokes Tabitha , Little Mark A. 
Published: February 2020

Abstract
The key histological features of membranoproliferative glomerulonephritis (MPGN) are mesangial hypercellularity, endocapillary proliferation, and capillary wall remodelling. There are two main types: (1) immune complex-mediated disease—caused by chronic infection causing persistent antigenaemia (notably hepatitis C), autoimmune disease, or monoclonal immunoglobulin production by plasma cell dyscrasia, and a few ‘idiopathic’ cases; and (2) complement-mediated disease—caused by dysregulation of the alternative pathway of complement, including by C3 nephritic factor (C3Nef), an autoantibody that stabilizes the alternative pathway C3 convertase. Clinical presentation is varied, including nephrotic syndrome, episodic visible haematuria, hypertension/rapidly progressive glomerulonephritis, asymptomatic nonvisible haematuria, and chronic kidney disease. Treatment depends on the underlying disease. All patients should receive appropriate conservative measures (blood pressure control, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker). Underlying infection or monoclonal gammopathy should be treated, when possible, in those with immune complex-mediated MPGN. Eculizumab may have a role in treatment of some patients with complement-mediated MPGN. Steroids and cyclophosphamide or mycophenolate mofetil are used in patients with severe idiopathic MPGN.
Chronic tubulointerstitial nephritis
Authors: De Broe Marc E. , Jayasumana Channa , D’Haese Patrick C. , Elseviers Monique M. , Vervaet Benjamin 
Published: February 2020

Abstract
Chronic tubulointerstitial nephritis is usually asymptomatic, presenting with slowly progressive renal impairment. Urinalysis may be normal or show low-grade proteinuria (&lt;1.5 g/day) and/or pyuria. Diagnosis depends on renal biopsy, which reveals variable cellular infiltration of the interstitium, tubular atrophy, and fibrosis. There are many causes including sarcoidosis, drugs (prescribed and nonprescribed), irradiation, toxins, and metabolic disorders. Analgesic nephropathy—characterized by renal papillary necrosis and chronic interstitial nephritis and caused by the prolonged and excessive consumption of combinations of analgesics, mostly including phenacetin. Nonsteroidal anti-inflammatory drugs—the most frequent cause of permanent renal insufficiency after acute interstitial nephritis. Aristolochic acid nephropathy—(1) Chinese herb nephropathy—caused in most cases (but perhaps not all) by aristolochic acid, and is associated with a high incidence of urothelial malignancy. (2) Balkan endemic nephropathy—a chronic, familial, noninflammatory tubulointerstitial disease of the kidneys that is associated with a high frequency of urothelial atypia, occasionally culminating in tumours of the renal pelvis and urethra. 5-Aminosalicylic acid—used in the treatment of chronic inflammatory bowel disease and causes clinical nephrotoxicity in approximately 1 in 4000 patients/year. Chronic interstitial nephritis in agricultural communities (CINAC) —nonproteinuric chronic kidney disease that presents in young, agricultural workers in Central America and Sri Lanka in the absence of any clear aetiology. Lithium—the most common renal side effect is to cause nephrogenic diabetes insipidus. Radiation nephropathy—preventive shielding of the kidneys in patients receiving radiation therapy generally prevents radiation nephropathy, but total body irradiation preceding bone marrow transplantation leads 20% to develop chronic renal failure in the long term. Nephropathies induced by toxins (including lead and cadmium) or by metabolic disorders (chronic hypokalaemia and chronic urate nephropathy).
Renal diseases in the tropics
Authors: Jha Vivekanand 
Published: February 2020

Abstract
Kidney diseases encountered in tropical areas are a mix of conditions that have a worldwide distribution and those that are secondary to factors unique to the tropics (e.g. climatic conditions, infectious agents, nephrotoxic plants, envenomations, and chemical toxins). Cultural factors, illiteracy, superstitions, living conditions, level of access to health care, and nutritional status also affect the nature and course of disease. Knowledge of such conditions and issues is important for medical professionals in all parts of the globe, as ease of travel means that individuals and practices are exported with increasing frequency. Glomerular diseases—there is a high prevalence of infection-related glomerulonephritis (e.g. quartan malarial, schistosomal, and filarial nephropathies) throughout the tropics, with the pattern of injury dependent upon the nature of the prevalent endemic infection in that region. Once established, the course of disease is rarely modified by treatment of underlying infection. Acute kidney injury (AKI)—there is a higher prevalence of community-acquired AKI in the tropics than elsewhere. Medical causes predominate, with diarrhoeal diseases, intravascular haemolysis due to glucose-6-phosphate dehydrogenase deficiency, ingestion of toxic plants, snake bites, insect stings, and locally prevalent infections being responsible for most cases. Falciparum malaria and leptospirosis are the most important infectious aetiologies. Use of indigenous herbs and chemicals by traditional healers (‘witch doctors’) are the most important toxic causes of AKI in sub-Saharan Africa. Chronic kidney disease (CKD)—although the contributions of diabetes and hypertension are growing, many cases are secondary to glomerular diseases, likely infection related, or have CKD of undetermined aetiology. Many of the latter are agriculture or farm workers presenting with chronic tubulointerstitial nephritis of unknown cause.
Drugs and the kidney
Authors: Burns Aine , Ashley Caroline 
Published: February 2020

Abstract
The kidney plays a critical role in the elimination of many drugs from the body, hence consideration should be given to a patient’s renal function whenever any drug is prescribed. Much kidney disease is unrecognized, but the widespread reporting of estimated glomerular filtration rates (eGFR) has brought greater awareness of the prevalence of chronic kidney disease (CKD), thereby encouraging medical practitioners to take account of reduced renal function when prescribing. CKD is very often one of many coexisting comorbid conditions, especially in elderly patients, when particularly careful thought must be given to appropriate drug dosing and the possibility of drug interactions. A reduced GFR is the primary reason for reduced excretion of drugs in renal failure, but drug absorption, distribution, protein binding, metabolism, and pharmacodynamics may all be affected. Key general points—both filtration and secretion of drugs appear to fall in parallel and in proportion to the GFR. The clinical significance of a reduction in GFR and increased drug half-life depends on the relative importance of renal excretion and metabolism as a mode of elimination, and the therapeutic ratio of the drug. If nonrenal clearance accounts for elimination of more than 50% of a drug, then no adjustment needs be made to dose/frequency of administration. Dosages of drugs which are mainly excreted in active form by the kidney may need to be modified to avoid accumulation. Potentially toxic drugs should only be used in patients with renal failure if there is a specific indication for their use and if therapy can be monitored appropriately. If dose adjustment is required, then dose, dose interval, or both can be adjusted to achieve the desired therapeutic profile.
Cellular and molecular basis of haematopoiesis
Authors: Vyas Paresh , Jakobsen N. Asger 
Published: February 2020

Abstract
Haematopoiesis involves a regulated set of developmental stages from haematopoietic stem cells (HSCs) that produce haematopoietic progenitor cells that then differentiate into more mature haematopoietic lineages, which provide all the key functions of the haematopoietic system. Definitive HSCs first develop within the embryo in specialized regions of the dorsal aorta and umbilical arteries and then seed the fetal liver and bone marrow. At the single-cell level, HSCs have the ability to reconstitute and maintain a functional haematopoietic system over extended periods of time in vivo. They (1) have a self-renewing capacity during the life of an organism, or even after transplantation; (2) are multipotent, with the ability to make all types of blood cells; and (3) are relatively quiescent, with the ability to serve as a deep reserve of cells to replenish short-lived, rapidly proliferation progenitors. Haematopoietic progenitor cells are unable to maintain long-term haematopoiesis in vivo due to limited or absent self-renewal. Rapid proliferation and cytokine responsiveness enables increased blood cell production under conditions of stress. Lineage commitment means limited cell type production. The haematopoietic stem cell niche is an anatomically and functionally defined regulatory environment for stem cells modulates self-renewal, differentiation, and proliferative activity of stem cells, thereby regulating stem cell number. Haematopoietic reconstitution during bone marrow transplantation is mediated by a succession of cells at various stages of development. More mature cells contribute to repopulation immediately following transplantation. With time, cells at progressively earlier stages of development are involved, with the final stable repopulation being provided by long-lived, multipotent HSCs. Long-term haematopoiesis is sustained by a relatively small number of HSCs.
Acute myeloid leukaemia
Authors: Russell Nigel , Burnett Alan 
Published: February 2020

Abstract
Acute myeloblastic leukaemia arises in a haematopoietic stem cell as a result of mutations which promote growth or inhibit apoptosis in association with mutations that inhibit differentiation. There is usually no obvious cause, but exposure to chemical and ionizing radiation may be relevant, including previous chemotherapy for solid tumours. This leukaemia arises particularly in older patients, often in the context of antecedent haematological disorders such as myelodysplastic syndromes or myeloproliferative neoplasms. Clinical features are of marrow failure, with anaemia, bleeding (petechiae, purpura, from mucous membranes), and infection. Acute promyelocytic leukaemia should be viewed as a medical emergency characterized by disseminated intravascular coagulation which requires urgent treatment to avoid haemorrhagic death. Aside from providing appropriate supportive care, the first clinical decision to be made is whether to give conventional intensive chemotherapy aiming for disease eradication, or to adopt a more palliative approach. Intensive chemotherapy is the norm up to age 65 to 70 years. Above this age, the biology of the disease tends to be less favourable and patients may have significant comorbidities limiting treatment tolerance. In patients under 60 years, 75 to 80% will achieve initial remission and about 45 to 50% will survive. In older patients given intensive treatment, 50 to 60% will enter remission but only 15 to 20% will survive 2 years. With nonintensive treatments, remissions are seen in 15 to 25% with the median survival being 6 to 9 months. Relapsed disease—more than 50% of patients will ultimately relapse and their overall outcome is generally very poor. The best curative option is allogeneic stem cell transplantation if a second complete remission can be achieved with reinduction chemotherapy.