bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical presentation of respiratory disease
Authors: Kemp Samuel , Hopkin Julian 
Published: February 2020

Abstract
Respiratory disease can present in many ways, with variations attributable to many factors. The clinical presentation directs diagnostic hypothesis making, the choice of diagnostically discriminating investigations, and the most appropriate management. If a detailed history is not taken, the patient not observed carefully and examined diligently, and the information from these sources is not analysed correctly, then inappropriate investigation and management is likely. Common symptoms of respiratory disease are breathlessness, cough, haemoptysis, and pleuritic chest pain, details of which can point to particular diagnoses. An account of environmental exposures at work and home, and of family history, is critically important in some cases. In chronic respiratory disease, where breathlessness and disability are to be assessed, walking with the patient and observing exercise tolerance and distress (and pulse oximetry) can provide valuable information.
Upper airway obstruction
Authors: Hull James H. , Hind Matthew 
Published: February 2020

Abstract
The upper airway is anatomically defined by the carina inferiorly and pharynx superiorly, with pathology predominately arising from the trachea and larynx. Obstruction of the upper airway may arise because of a fixed structural pathology such as tracheal stenosis or malignancy, but can arise following loss of normal function (e.g. inappropriate vocal cord adduction). A high index of suspicion is required to make the diagnosis because the clinical features of upper airway obstruction can mimic other respiratory conditions. Calculation of the ratio of forced expiratory volume in one second to peak expiratory flow (Empey index) may identify patients with unsuspected upper airway obstruction.
Acute upper airway obstruction is a medical emergency and usually caused by aspiration, oedema (allergic, hereditary, and acquired angio-oedema, smoke inhalation), or infection (croup, epiglottitis, quinsy, retropharyngeal abscess). Non-acute causes of upper airway obstruction include malignancy, tracheal stenosis, tracheal compression, dynamic large airway collapse, and laryngeal dysfunction.
Diffuse parenchymal lung disease: An introduction
Authors: Teo F. , Wells A.U. 
Published: February 2020

Abstract
The nomenclature of diffuse parenchymal lung disease (also known as interstitial lung disease) has caused a great deal of confusion, with use of complicated histopathological terms not always corresponding to clinico-radiological entities. Five major groupings are now recognized: idiopathic interstitial pneumonias; diseases associated with systemic conditions, including rheumatological disorders; diseases caused by environmental triggers or drugs; granulomatous diseases; and other diffuse lung diseases. Classification is based on recognition of clinical, radiological, and histopathological patterns, as opposed to the purely histopathological terminology. Diagnosis is complicated by the large number of disorders grouped within the diffuse parenchymal lung diseases. A systematic diagnostic algorithm, based upon careful clinical evaluation and a logical sequence of tests, is essential. Clinical history, clinical examination, chest radiography, pulmonary function tests, and selective blood tests should be followed by high-resolution CT, bronchoalveolar lavage (in some cases), and lung biopsy (in a few cases).
The lung in autoimmune rheumatic disorders
Authors: Kokosi M.A. , Wells A.U. 
Published: February 2020

Abstract
Lung complications occur in all rheumatological disorders, but their frequency and type vary strikingly between different systemic diseases. Interstitial lung disease and pulmonary vascular disease are now increasingly recognized, although the detection of limited abnormalities poses difficulties for clinicians who must now distinguish between subclinical involvement and clinically significant disease. The presence or absence of exertional dyspnoea is often misleading as musculoskeletal limitation may mask respiratory symptoms or, alternatively, may cause exercise intolerance without lung pathology, due to the increased work associated with inefficient locomotion. Furthermore, interstitial lung disease precedes the onset of systemic disease in some cases, although typical autoantibody profiles are often diagnostic.
Lipoid (lipid) pneumonia
Authors: Bourke S. J. 
Published: February 2020

Abstract
Lipoid pneumonia is an unusual form of lung disease resulting from the accumulation of lipids in the alveoli, where they provoke a foreign body reaction with associated inflammation and sometimes local fibrosis. The lipids may be endogenous or exogenous in origin, and the clinical mechanisms and circumstances differ accordingly. Exogenous lipoid pneumonia occurs when animal, vegetable, or mineral oils are aspirated or inhaled into the lungs, provoking a foreign body reaction with chronic inflammation. Typical symptoms are cough and breathlessness. The chest radiograph and CT may show interstitial thickening, with areas of consolidation that may coalesce into a mass (paraffinoma) which simulates carcinoma. Bronchoalveolar lavage and biopsy show lipid-laden macrophages. In endogenous lipoid pneumonia the lipids are derived from surfactant and cholesterol released from decaying cells distal to bronchial obstruction.
Pulmonary alveolar microlithiasis
Authors: Bourke S. J. 
Published: February 2020

Abstract
Pulmonary alveolar microlithiasis is characterized by the deposition of calcium phosphate in the alveolar air spaces as a result of mutations of the SLC34A2 gene. The diagnosis is often made before symptoms have developed when a chest radiograph is performed for other reasons, and shows a dramatic typical ‘sandstorm’ pattern of diffuse bilateral calcified micronodules. The patient is often symptom-free when the diagnosis is made after a chest radiograph is taken incidentally and reveals calcified micronodules, but typically the disease progresses to respiratory failure over about 10–20 years. Etidronate has led to improvement in some cases that have been detected early. Lung transplantation is the main option in advanced disease. The severity of the disease and prognosis are variable, and this may be influenced by the specific type of gene mutation. Survival of 10–20 years from the onset of symptoms is typical.
Radiation pneumonitis
Authors: Bourke S. J. 
Published: February 2020

Abstract
The lungs can be injured by radiation used in the treatment of cancer, with the rapidly dividing endothelial cells and type II pneumocytes most affected. Immediate injury is followed by an inflammatory response and at a later stage by fibrosis. Chest radiography detects asymptomatic changes in about 50% of patients after radiotherapy. Acute radiation pneumonitis presents with cough, breathlessness, and fever about 2 months after exposure; corticosteroids are usually effective in relieving symptoms but do not prevent the subsequent development of fibrosis. Fibrosis typically develops about 6 months later, may progress for 6–24 months, but has usually stabilized by 2 years. Prevention depends on refining techniques for giving radiotherapy.
Mediastinal tumours and cysts
Authors: Lee Y.C. Gary , Davies Helen E. 
Published: February 2020

Abstract
Mediastinal masses are most conveniently categorized by their anatomical site in the anterior, middle, or posterior mediastinum. Most present as a radiographic abnormality alone, or in association with symptoms arising from compression of other mediastinal structures. Systemic symptoms such as fever or weight loss are more likely with malignant tumours such as lymphomas or thymomas. Detailed knowledge of normal mediastinal anatomy is a prerequisite to the interpretation of both normal and abnormal chest radiographs. Lymph nodes are present in all three compartments thereby knowledge of their anatomical relationships, together with sites of drainage, is important when interpreting radiographic mediastinal enlargement. The most important group of visceral nodes lie in the middle mediastinum and are predominantly subcarinal and paratracheal. Bronchopulmonary and hilar nodes are numerous but not visible radiographically unless pathologically enlarged.
ANCA-associated vasculitis
Authors: Jayne David 
Published: February 2020

Abstract
The ANCA-associated vasculitides (AAV) are a grouping of three syndromes of acute and chronic inflammation characterized by their clinical and histological phenotypes, which are associated with circulating antineutrophil cytoplasm autoantibodies (ANCA). They comprise: granulomatosis with polyangiitis (GPA, formerly Wegener’s granulomatosis); microscopic polyangiitis (MPA); and eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome). The defining histological lesion is a microscopic vasculitis affecting arterioles, capillaries, or venules associated with few or no deposits of immunoglobulin or complement. Granulomata, involving or close by blood vessels, are commonly present in GPA. These diseases involve multiple organ systems with considerable heterogeneity in extent and severity of organ involvement between patients, and overlapping clinical and histological features between syndromes.
Osteonecrosis, osteochondrosis, and osteochondritis dissecans
Authors: Clunie Gavin 
Published: February 2020

Abstract
This chapter examines the bone conditions of osteonecrosis, osteochondrosis, and osteochondritis dissecans. Osteonecrosis is ischaemia of bone caused by a range of conditions, including trauma, which cause intravascular or extravascular obstruction of blood flow to bone. Many cases are associated with pro-thrombotic conditions. Osteonecrosis can be asymptomatic, but if progressive often leads to secondary (adjacent) joint destruction. Diagnosis is made by magnetic resonance imaging. Aside from treatment of any underlying cause, treatment options include analgesics, vasodilators, and surgery. The osteochondritides are trauma-induced focal disturbances of cartilage, either in joints (articular) or at a periarticular epiphyseal plate or at a tendon or ligament insertion (apophysis/enthesis). Lesions typically occur in active children and adolescents and respond to biomechanical modifications and pain relief.
Clinical investigation of renal disease
Authors: Davenport Andrew 
Published: February 2020

Abstract
An accurate history and careful examination will determine the sequence and spectrum of clinical investigations required to make a diagnosis or decide on prognosis or treatment for renal disease. Midstream urine (MSU) sample—this standard investigation requires consideration of (1) macroscopic appearance, (2) stick testing, and (3) microscopy. Quantification of proteinuria—this is important because the risk for progression of underlying kidney disease to endstage renal failure is related to the amount of protein in the urine. Low molecular weight proteinuria is caused by proximal tubular injury and can be detected with markers. Knowledge of the glomerular filtration rate (GFR) is of crucial importance in the management of patients, not only for detecting the presence of renal impairment, but also in the monitoring of all patients with or at risk of renal impairment, and in determining appropriate dosing of those drugs cleared by the kidney. Measurement of plasma creatinine remains the standard biochemical test used to assess renal function. The simplified Modification of Diet in Renal Disease (sMDRD) formula is explained, along with a revised version (CKD-EPI). Investigations of tubular function, including the proximal tubule, distal tubule, and renal-induced electrolyte and acid–base imbalances are discussed in this chapter. Renal imaging covered in this chapter includes ultrasonography, ultrafast multislice CT scanning, magnetic resonance imaging, nuclear medicine scanning, and fluorodeoxyglucose positron emission tomography. Invasive techniques including antegrade or retrograde ureteropyelography and angiography are discussed. A renal biopsy should be considered in any patient with disease affecting the kidney when the clinical information and other laboratory investigations have failed to establish a definitive diagnosis or prognosis, or when there is doubt as to the optimal therapy.
Renal transplantation
Authors: Torpey Nicholas , Firth John D. 
Published: February 2020

Abstract
Renal transplantation is the preferred option for the treatment of endstage chronic renal failure in patients for whom there are no major medical contraindications. In well-selected recipients, both life expectancy and quality of life are superior to treatment with long-term dialysis. However, as the dialysis population continues to grow, the gap between supply and demand for renal transplantation is widening. Immunosuppression—excepting for transplants between HLA-identical twins, immunosuppression is required to prevent rejection, but there is no clear consensus on the best immunosuppressive regimen. Most centres use an induction antibody directed against CD25 or a T-lymphocyte-depleting antibody (thymoglobulin or alemtuzumab), followed by what is now called standard triple therapy—comprising a calcineurin inhibitor (almost always tacrolimus), combined with either mycophenolate mofetil or azathioprine, and steroids. Steroids are not infrequently tailed off rapidly in the early post-transplant period. Transplant rejection can be classified into four main categories: (1) hyperacute, (2) accelerated, (3) acute cellular, and (4) humoral. Complications of renal transplantation—this chapter discusses specific and nonspecific side effects of immunosuppressive agents, infective complications (including viral, bacterial, fungal, and parasitic infections), malignant complications, and other complications (including hypertension, accelerated atherosclerosis, and electrolyte, musculoskeletal, haematological, gastrointestinal, and cosmetic disorders) in detail. Prognosis—first-year transplant losses from rejection have been dramatically reduced from about 40% in the 1970s to 5%. However, the rate of chronic graft loss remains at about 4% per year. The commonest cause of insidious late graft failure is probably chronic antibody-mediated rejection, frequently associated with poor adherence to immunosuppression. Calcineurin toxicity may also contribute. A major focus of research is to identify non-nephrotoxic immunosuppressive agents able to suppress antibody-mediated rejection.
Minimal-change nephropathy and focal segmental glomerulosclerosis
Authors: Saleem Moin , Willcocks Lisa 
Published: February 2020

Abstract
Minimal-change nephrotic syndrome (MCNS) is an immune-mediated condition, usually of unknown cause. On light microscopy the glomeruli appear normal, and on electron microscopy there is effacement of epithelial cell foot processes over the outer surface of the glomerular basement membrane. MCNS is the cause of about 75% of cases of nephrotic syndrome in children and 17% in adults.
Management and prognosis—treatment in adults is with prednisolone at an initial dose of 80 mg/day, then tapering. This leads to complete remission in 90 to 95% of patients, but 50 to 75% of glucocorticoid-responsive adults will have a relapse. Progression to renal failure is not expected and would call the diagnosis of MCNS into question. Focal segmental glomerulosclerosis (FSGS) is not a specific disease entity but a histological lesion, often of unknown aetiology, which is characterized by segmental areas of glomerular sclerosis. It may be (1) primary—either due to genetic mutation, or associated with an unknown circulating protein factor that causes an increase in glomerular permeability; or (2) secondary—the end product of a variety of pathological processes including glomerular hyperfiltration, healed glomerulonephritis, viral (including HIV) infection, or parasitic infection. Management and prognosis—corticosteroid and immunosuppressive therapy should be considered only in patients with primary FSGS and nephrotic syndrome. The steroid regimen is as used for MCNS, but with lesser success. Steroid-resistant cases are treated with ciclosporin (for which there is most published evidence), mycophenolate mofetil, or cyclophosphamide. Prognosis depends on histology and response to treatment.
Membranous nephropathy
Authors: De Vriese An S. , Fervenza Fernando C. 
Published: February 2020

Abstract
Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in Caucasians adults. It may also present with asymptomatic proteinuria. Its defining feature is the presence of subepithelial immune deposits, localized between the podocyte and the glomerular basement membrane. Aetiology—primary MN (80% of cases) is caused in most cases by antibodies against the M-type phospholipase A2 receptor (PLA2R). Secondary MN occurs as a consequence of drugs, malignancy, or autoimmune disease. Prognosis—the clinical course of primary MN is variable: spontaneous complete remission of proteinuria occurs in 20 to 30% and progressive kidney failure develops in 20 to 40% over 5 to 15 years. Patients with gross proteinuria (&gt;8 g/day) are at high risk of progression, as are those with a high and rising anti-PLA2R antibody level. Management—patients at low risk of progression have an excellent long-term prognosis and should be treated conservatively without immunosuppression. Patients at medium and high risk for progression benefit from immunosuppression in addition to conservative treatment. Corticosteroid monotherapy is ineffective in primary MN and should not be used. Standard treatment regimens include corticosteroids with alkylating agents (chlorambucil, cyclophosphamide), corticosteroids with mycophenolate mofetil, and calcineurin inhibitors (ciclosporin, tacrolimus). Early experience with rituximab has given some promising results.
The renal tubular acidoses
Authors: Sayer John A. , Karet Fiona E. 
Published: February 2020

Abstract
Renal tubular acidosis (RTA) arises when the kidneys either fail to excrete sufficient acid, or are unable to conserve bicarbonate, with both circumstances leading to metabolic acidosis of varying severity with altered serum potassium. Proximal and distal types of RTA can be differentiated according to which nephron segment is malfunctioning. Proximal RTA: aetiology and diagnosis—the condition may be (1) secondary to generalized proximal tubular dysfunction (part of the renal Fanconi’s syndrome), or rarely (2) due to an inherited mutation of a single transporter (NBC1) located at the basolateral surface of the proximal tubular epithelium. The combination of normal anion gap acidosis with other features of proximal tubular dysfunction such as renal phosphate wasting (and hypophosphataemia), renal glycosuria, hypouricaemia (due to uricosuria), aminoaciduria, microalbuminuria, and other low molecular weight proteinuria suggests the diagnosis. Management—this requires large quantities of oral alkali with (in most cases) potassium supplements to prevent severe hypokalaemia. Distal RTA: aetiology/diagnosis—two main classes are differentiated by whether (1) the acid-handling cells in the collecting ducts are themselves functioning inadequately, in which case there is associated hypokalaemia (this is ‘classic’ distal RTA); or (2) the main abnormality is of the salt-handling principal cells in the same nephron segment, in which case hyperkalaemia occurs and the acidosis is a secondary phenomenon—this is hyperkalaemic distal RTA. The combination of normal anion gap acidosis with a urine pH higher than 5.5 suggests classic distal RTA. Management—(1) classic distal RTA—1 to 3 mg/kg per day of oral alkali; (2) hyperkalaemic distal RTA—treatment is with sodium bicarbonate, but fludrocortisone and/or potassium-lowering measures may also be necessary. Precipitating drugs should be stopped.
Thrombocytosis and essential thrombocythaemia
Authors: Aruch Daniel , Hoffman Ronald 
Published: February 2020

Abstract
The term thrombocytosis refers to a platelet count elevated above 450 × 109/litre, which can be (1) primary—including essential thrombocythaemia, chronic myeloid leukaemia, polycythaemia vera, and myelodysplastic syndromes; or (2) secondary—including iron deficiency, infection, blood loss, and malignancy. Essential thrombocythaemia: aetiology—the JAK2 V617F missense mutation typical of polycythaemia vera is found in about 50% of cases. In addition, 10% of patients have a mutation in the thrombopoietin receptor gene, MPL, and 30% have a mutation in calreticulin (CALR). Approximately 10% of patients have none of these mutations and are referred to as ‘triple negative’ essential thrombocythaemia. Diagnosis requires all of the following four major criteria: (1) platelet count greater than 450 × 109/litre; (2) bone marrow biopsy showing proliferation mainly of the megakaryocyte lineage with increased numbers of enlarged, mature megakaryocytes with hyperlobulated nuclei without a significant increase or left shift in neutrophil granulopoiesis or erythropoiesis and very rarely minor (grade 1) increase in reticulin fibres; (3) failure to meet the criteria for other myeloproliferative neoplasms; and (4) presence of JAK2, CALR, or MPL mutations. Alternatively, diagnosis can be met when the first three major criteria are present and the one minor criterion, namely the presence of another clonal marker or absence of evidence for reactive thrombocytosis. Treatment requires risk stratification based on the age of the patient and any prior history of thrombosis, with treatment being reserved for those at a high risk of developing complications and not introduced simply on the basis of platelet counts alone unless there is extreme thrombocytosis (&gt;1500 × 109/litre). Therapies include low-dose aspirin and cytoreduction.
Non-Hodgkin lymphoma
Authors: Bhatt Vijaya Raj , Armitage James O. 
Published: February 2020

Abstract
Non-Hodgkin’s lymphomas comprise precursor lymphoid neoplasms, mature B-cell neoplasms, and mature T-cell neoplasms. The aetiology of most cases is unknown, but increased risk is associated with immune deficiencies, agricultural chemicals, autoimmune disorders, treated Hodgkin’s disease, and some infectious agents. Incidence varies from 10 to 22 cases per 100 000 per year in different populations. Patients with non-Hodgkin’s lymphoma most commonly present with lymphadenopathy, but other presentations include systemic symptoms or those attributable to mediastinal or retroperitoneal masses or involvement. Diagnosis is typically based on expert evaluation of an adequate lymph node biopsy. Staging depends largely on determining the anatomical extent of disease, with FDG positron emission tomography/CT scanning generally the preferable imaging modality. For most patients, the goal of therapy is to achieve a complete remission. Patients with definitely curable lymphomas, such as diffuse large B-cell lymphoma and Burkitt’s lymphoma, are almost always treated promptly with intensive regimens, for example, chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone) plus the anti-CD20 monoclonal antibody rituximab. By contrast, follicular lymphoma is often not curable and the best treatment is not clear, with many physicians favouring no initial therapy in an asymptomatic patient. Patients who are not cured with initial therapy are candidates for what has been termed ‘salvage therapy’. For most patients, the only curative approach in this setting is haematopoietic stem cell transplantation, the toxicity of which means that it is only sensibly offered to carefully selected patients. Various new agents, such as small molecule kinase and BCL-2 inhibitors, and immune checkpoint inhibitors, offer hope for the future.