bluuebunny/crossref_metadata_2025 huggingface dataset:
Science in medicine: when, how, and what
Authors: Bynum W.F.
Published: January 2012

Science has always been part of Western medicine, although what counts as scientific has changed over the centuries, as have the content of medical knowledge, the tools of medical investigation, and the details of medical treatments. This brief overview develops a historical typology of medicine since antiquity. It divides the ‘kinds’ of medicine into five: bedside, library, hospital, social, and laboratory. These categories are still principal headings in modern health budgets, but they also have specific historical resonances. (1) Bedside medicine, developed by the Hippocratic doctors in classical times, has its modern counterpart in primary care. (2) Library medicine, associated with the scholastic mentality of the Middle Ages, still surfaces in the problems of information storage and retrieval in the computer age. (3) Hospital medicine, central to French medicine of the early 19th century, placed the diagnostic and therapeutic functions of the modern hospital centre stage in care and teaching. (4) Social medicine is about prevention, both communal and individual, and is especially visible in our notion of ‘lifestyle’ and its impact on health. (5) Laboratory medicine has its natural home in the research establishment and is a critical site for the creation of medical knowledge, setting the standards for both medical science and scientific medicine. François Magendie (1773–1855) was probably the first truly ‘modern’ medical scientist: he had little sense of medical tradition; instead, he sought to establish medicine on new, scientific foundations....
Bringing the best evidence to the point of care
Authors: Glasziou Paul P.
Published: January 2012

You must always be students, learning and unlearning till your life’s end.

Joseph Lister

Neither our memories nor our textbooks are complete and up to date with all the research relevant to the patients we will see today. The scattering of necessary research across a vast ocean of literature makes it inaccessible at the point of clinical decision. The consequences for patient care have given rise to the discipline of evidence-based medicine (EBM), whose two central concerns are with the quality of research evidence and with its appropriate usage in clinical care....
Evidence-based medicine—does it apply to my particular patient?
Authors: Caplan Louis R.
Published: January 2012

Proponents of evidence-based medicine (EBM) have established a clear, unambiguous requirement for what they consider credible evidence, the randomized controlled trial (RCT), and especially the systematic review of several RCTs. They propose that clinical practice should be dominated by adherence to the ‘evidence’ as they define it....
The future of clinical trials
Authors: Nisen Perry , Vallance Patrick
Published: January 2012

Clinical trials are the bedrock of evidence-based medicine. Introduced in the mid 20th century, they heralded a move away from opinion and anecdote to a more scientific evaluation of new treatments. Indeed, it could be argued that it is the clinical trial and the application of scientific method to determine which treatments work that distinguishes ‘medicine’ from ‘alternative medicine’. The aim of this short section is to outline the way in which clinical trials are likely to evolve over the next few years....
Complementary and alternative medicine
Authors: Ernst E.
Published: January 2012

Complementary and alternative medicine (CAM) can be positively defined as diagnosis, treatment, and/or prevention which complements mainstream medicine by contributing to a common whole, by satisfying a demand not met by orthodoxy, or by diversifying the conceptual frameworks of medicine. It is popular, hence doctors should know about it....
Brainstem syndromes
Authors: Bates David
Published: January 2012

Case History—A 78 yr old woman presenting with brainstem signs following a seizure.

Brainstem syndromes typically cause ipsilateral cranial nerve lesions and contralateral long tract signs. They are commonly due to brainstem ischaemia, but can also be caused by neoplasia, demyelination, infective and hamartomatous lesions. Imaging, ideally with MRI rather than CT, is obligatory and only then—and possibly following other investigations to identify systemic abnormality or cerebrospinal fluid changes—can appropriate therapy be introduced....
Traumatic injuries to the head
Authors: Watkins Laurence , Thomas David G.T.
Published: January 2012

Head injuries cause 1% of all deaths, including 15 to 20% of those in people aged 5 to 35 years, with many survivors facing long-term disability.

Pathophysiology—brain injury may be (1) primary—axonal injury and focal contusions are caused at the moment of impact; or (2) secondary—causes are (a) extracranial—e.g. hypoxia and hypotension, and (b) intracranial—e.g. haematoma, brain swelling, and infection....
Preventive medicine
Authors: Mant David
Published: January 2012

Most deaths before age 80 years are preventable.

Deaths from infectious diseases and trauma usually reflect poverty and political instability. Prevention requires political action to reduce the risk of war and improve the supply of food, clean water, sanitation, and shelter. Preventive medicine can augment, but not replace, this action by controlling spread of infection through vaccination, health education, control of insect vectors, and treatment of disease carriers to prevent onward transmission....
The importance of mass communication in promoting positive health
Authors: Lom Thomas
Published: January 2012

Medical science is enabling an explosion of discovery in diagnostic tools and in the development of new treatments and products. But how do we take advantage if we are not aware? That is where the power of mass communication comes into play.

In a world with increasingly motivated and empowered patients, these go well beyond just the for-profit companies such as the pharmaceutical industry and include payers, governments, health care professionals, and institutions. The motivation for the dissemination of health information is a convergence of public health interest and public health policy with private sector commercial interests....
Human disasters
Authors: Sen Amartya
Published: January 2012

Human disasters, as massive misfortunes long recorded over history, have great importance for medicine, rightly prompting the call for prevention, relief, and practical intervention by medical personnel. But why do human disasters happen? A sharp distinction is sometimes drawn between natural disasters, e.g. earthquakes, and social disasters, e.g. wars, but detailed knowledge often shows that this contrast is not always clear....
Stem cells and regenerative medicine
Authors: Joannides Alexis J. , Pedersen Roger , Chandran Siddharthan
Published: January 2012

There is a great and unmet need for treatments that will deliver restorative solutions to patients with diseases hitherto considered irreparable. The twin properties of self-renewal and specialization common to stem cells offer unprecedented opportunities for regenerative medicine through the generation of unlimited numbers of defined human cells on the scale necessary for experimental study, drug discovery, and disease modelling. The field is fast developing, with the first wave of putative treatments necessarily drawn from autologous and adult stem cells, but the outstanding question remains whether these will lead to meaningful regenerative therapies....
The innate immune system
Authors: Bowness Paul
Published: January 2012

The innate immune system comprises evolutionarily ancient mechanisms that mediate first-line responses against microbial pathogens, and are also important in priming and execution of adaptive immune responses, and in defence against tumours. These responses, which recognize microbial non-self, damaged self, and absent self, are characterized by rapidity of action and lack of plasticity, ‘learning’, or memory, and they involve various different cell types, cell-associated receptors, and soluble factors....
Autoimmunity
Authors: Rosen Antony
Published: January 2012

Autoimmune diseases occur when a sustained, specific, adaptive immune response is generated against self-components, and results in tissue damage or dysfunction. They probably affect more than 3% of Western populations, more commonly women than men, and have peak incidence in the third to sixth decades....
Rat-bite fevers
Authors: Warrell David A.
Published: January 2012

Rat-bite fever is usually attributable to Streptobacillus moniliformis in the Americas, Europe, and Australia; in Asia, Spirillum minus is the commoner cause. Bites are increasingly common among child pet owners and pet-shop and laboratory workers. Both bacteria are commensals of rodents and their predators. After an incubation period less than 1 week, ...
Rickettsioses
Authors: Parola Philippe , Raoult Didier
Published: January 2012

Rickettsioses are zoonoses caused by obligate Gram-negative intracellular bacteria of the order Rickettsiales, comprising (1) rickettsioses due to bacteria of the genus Rickettsia, including spotted fever groups and typhus groups (Rickettsiaceae), (2) ehrlichioses and anaplasmoses due to bacteria of the Anaplasmataceae, and (3) scrub typhus due to ...
Poisonous plants and fungi
Authors: Persson Hans
Published: January 2012

Many plants contain toxic substances heterogeneous in their chemical composition and diverse in their toxic effects. When classifying plant poisonings, a pragmatic approach is to look at the main clinical effects, but it should be emphasized that few plant toxins produce just one type of symptom, and symptomatology is often multiple, although some features predominate....
Occupational and environmental health
Authors: Harrington J. M. , Agius Raymond M.
Published: January 2012

Occupational health is concerned with managing the health of working people. Occupational health physicians deal with the effects of work on health, and the influence of health on work. Other professional groups, including nurses, hygienists, toxicologists, psychologists, and safety engineers, also have important roles to play in keeping people healthy and at work....
Aerospace medicine
Authors: Denison D.M. , Bagshaw M.
Published: January 2012

Travel by air is a safe means of transport, but puts people at various physiological risks and is a potential means of spreading infectious disease.

Physiological risks associated with flying include hypoxia—atmospheric pressure falls with altitude. The minimum cabin pressure in commercial passenger aircraft (565 mmHg, 75.1 kPa) brings a healthy individual’s arterial ...
Artificial nutrition support
Authors: Woodward Jeremy
Published: January 2012

The prevalence and importance of malnutrition in affluent societies is under-recognized, and nutritional status is a major predictor of outcome for most diseases.

Nutrition screening identifies patients at risk of malnutrition and should be performed in all clinical areas: this requires evaluation of events in the past (recent weight loss); present (current body mass index (BMI) and clinical signs of malnutrition); and future (current nutrient intake and foreseeable likely causes of reduced intake). A BMI of less than 18.5 kg/m...
Hereditary disorders of oxalate metabolism—the primary hyperoxalurias
Authors: Danpure Christopher J. , Milliner Dawn S.
Published: January 2012

Oxalate is an end-product of metabolism with no known useful biological function in humans. Anything that increases the body burden of oxalate, or elevates the concentration of oxalate in the urine, increases the risk of calcium oxalate deposition in the kidney and/or urinary tract, resulting in nephrocalcinosis and/or urinary stones....
Principles of hormone action
Authors: Gurnell Mark , Burrin Jacky , Chatterjee V. Krishna
Published: January 2012

Hormones, produced by glands or cells, are messengers which act locally or at a distance to coordinate the function of cells and organs. Types of hormone include (1) peptides (e.g hypothalamic releasing factors) and proteins (e.g. insulin, growth hormone)—these generally interact with membrane receptors located on the cell surface, causing activation of downstream signalling pathways leading to alteration in gene transcription or modulation of biochemical pathways to effect a physiological response; (2) steroids (e.g. cortisol, progesterone, testosterone, oestradiol) and other lipophilic substances (e.g. vitamin D, retinoic acid, thyroid hormone)—these act by crossing the plasma membrane to interact with intracellular receptors, with hormone action via nuclear receptors altering cellular gene expression directly....
Sexual dysfunction
Authors: Eardley Ian
Published: January 2012

Erectile dysfunction—the inability to attain or maintain an erection satisfactory for sexual intercourse. It affects about 50% of men over the age of 40 years and can be caused by neurological, vascular, endocrine, and psychiatric diseases, and by drugs, with psychogenic and organic risk factors coexisting in most men. Specific remedies can cure erectile dysfunction in a few patients: the mainstay of treatment in most will be oral therapy using a phosphodiesterase type 5 inhibitor....
Hypoglycaemia
Authors: Marks Vincent
Published: January 2012

Hypoglycaemia is defined as a blood glucose concentration below 3.0 mmol/litre, which is clinically important because of its effect on brain function. Much the commonest cause is excessive (in relation to intake of food and drink) administration of insulin or sulphonylurea drugs to patients known to have diabetes, but there are many rarer causes including insulinoma, toxins (alcohol), organ failure (hepatic), endocrine diseases (adrenal insufficiency, pituitary insufficiency), non-islet cell tumour hypoglycaemia, autoimmune insulin syndrome, factitious or felonious administration of insulin/sulphonylureas, and infections (malaria)....
Physiological changes of normal pregnancy
Authors: Williams David J.
Published: January 2012

Almost every maternal organ system makes a physiological adaptation to pregnancy that is required for optimal pregnancy outcome. An understanding of these adaptations brings insight into the aetiology and management of gestational syndromes, and also helps the clinician to advise women with pre-existing chronic illness about the risks and consequences of a pregnancy....
Nutrition in pregnancy
Authors: Williams David J.
Published: January 2012

Nutritional requirements for healthy pregnancy vary according to a woman’s prepregnancy nutritional state and her access to food during pregnancy: there is no unifying nutritional advice that is appropriate for all pregnant women throughout the world, or even within nations.

The well-nourished mother—maternal adaptation to pregnancy requires few dietary changes during pregnancy. She should eat one or two portions of sea fish per week to -ensure intake of n-3 long-chain polyunsaturated fatty acids sufficient to provide at least 200 mg of docosahexaenoic acid per day, which is needed for the healthy development of the fetal central nervous system. Supplemental folic acid (400 µg/day) during the first trimester reduces the risk of neural tube defects, but with this exception extra vitamins and micronutrients are not necessary for well-nourished, healthy pregnant women who eat a balanced diet, and excessive amounts of some micronutrients can actually be harmful to the fetus. Thiamine replacement is essential for women with hyperemesis gravidarum....
Diabetes in pregnancy
Authors: Hod Moshe , Yogev Yariv
Published: January 2012

Diabetes is one of the most common medical complications in pregnancy: 0.4 to 2% of all births are complicated by pregestational diabetes; about 3% of pregnancies are complicated by gestational diabetes mellitus, with substantially more in some populations.

Preconceptional evaluation—this should include evaluation of glycaemic control, blood pressure, retinal disease, renal status, thyroid function, peripheral and autonomic neuropathy, peripheral vascular disease, and hypoglyacemic symptoms....
Endocrine disease in pregnancy
Authors: Lazarus John H.
Published: January 2012

Endocrine function in the developing fetus is initially almost entirely dependent on the mother, with the fetus becoming less reliant on maternal hormones as the fetal glands develop and mature from the second trimester onwards.

Lymphocytic hypophysitis—typically presents with symptoms of an expanding pituitary tumour; increasingly recognized as a cause of hypopituitarism occurring late in pregnancy and in the postpartum period....
Neurological disease in pregnancy
Authors: Lennox G.G. , Firth John D.
Published: January 2012

Thiamine deficiency—caused by the combination of the nutritional demands of pregnancy and hyperemesis gravidarum, presenting as a subacute sensory neuropathy or (less commonly) acute Wernicke’s encephalopathy.

Chorea—all types are exacerbated in pregnancy, an effect termed chorea gravidarum.

Malignancies—choriocarcinoma (see Chapter 14.17) can cause brain or spine metastases, the former giving rise to strokes through infarction or haemorrhage, and the latter to cord or cauda equina compression....
Prescribing in pregnancy
Authors: Rubin Peter
Published: January 2012

Only prescribe if it is essential to do so—the guiding principle when prescribing in pregnancy, or in a woman who may become pregnant, is to use no drug at all if possible. If it is necessary to prescribe, then use the smallest number of drugs in the lowest possible doses, balancing the benefits of treatment for the mother against what (if anything) is known about its risks to the developing baby. Prepregnancy evaluation is invaluable for chronic conditions....
Benefits and risks of hormone replacement therapy
Authors: Stevenson J.C.
Published: January 2012

Hormone replacement therapy (HRT) comprises oestrogen with or without progestogen.

Benefits—HRT is the most effective treatment for the relief of menopausal symptoms and for the primary prevention of postmenopausal osteoporosis. There are also possible benefits for coronary heart disease, colorectal cancer, and neurocognitive function, but these are yet to be established....
Symptomatology of gastrointestinal disease
Authors: Neale Graham
Published: January 2012

The skilful analysis of symptoms indicating disorders of the digestive system is an integral part of the practice of internal medicine. Many patients with abdominal symptoms do not have easily defined organic conditions. The traditional skills of taking a careful history and examining the patient thoroughly are invaluable in managing patients who have functional disorders such as ‘irritable bowel’, nonulcer dyspepsia, nonspecific diarrhoea, recurrent abdominal pain, and somatization disorder....
Upper gastrointestinal endoscopy
Authors: Hatfield Adrian R.W.
Published: January 2012

Flexible fibre optic endoscopes were developed in the mid-1960s, leading to the growth of gastrointestinal endoscopy as we now know it. The recent availability of cheaper, miniaturized colour chips has led to the development of video endoscopes, providing an excellent clear view that does not deteriorate with age (as it does with fibre optic devices). With improvements in software, the endoscopic video image can be magnified: modern instruments will zoom up to 25 × magnification, and mucosal detail can also be enhanced electronically so that small lesions a few millimetres in size can be seen quite clearly. The modern video endoscope image can be instantly printed out and archived digitally on a computer system....
The mouth and salivary glands
Authors: Lehner T. , Challacombe S.J.
Published: January 2012

Stomatology is the branch of medicine that deals with oral diseases of both hard and soft tissues. For historical reasons and due to the rather technical aspects of treatment of teeth, dentistry has been separated from the main body of teaching medicine. This has created a curious anomaly in the training of doctors, namely that oral diseases receive low priority in teaching, and yet many systemic diseases are associated with oral symptoms and signs....
Irritable bowel syndrome and functional bowel disorders
Authors: Thompson D.G.
Published: January 2012

Case History—A 42 yr old woman presenting with increased bowel frequency, loose stools and urgency after treatment of Campylobacter sp..

Symptoms suggestive of disturbed lower gastrointestinal function without adequate explanation are very common in adults in the Western world, up to 15% of whom experience such symptoms at any one time, although most do not seek medical advice. It is not clear whether the symptoms of those individuals who do seek medical help have a different pathophysiological basis from those who do not, and whether the seeking of medical advice is more an indication of a worried individual than of disturbed gut function....
Liver tumours—primary and secondary
Authors: Griffiths William J.H. , Rushbrook Simon M.
Published: January 2012

A number of benign and malignant tumours may arise in the liver, the most important of which are:

HCC is the fifth most common cancer worldwide, but with great geographical variation in incidence, ranging from around 2 per 100 000 population in western Europe to 100 per 100 000 population in some parts of Africa. Most tumours arise on the background of cirrhosis, commonly due to hepatitis B, hepatitis C, or alcohol....
Cardiac arrhythmias
Authors: Ginks S.M. , Lip Gregory Y.H. , Lane D. , Cobbe S.M. , McGavigan A.D. , Rankin A.C.
Published: January 2012

The term cardiac arrhythmia (or dysrhythmia) is used to describe any abnormality of cardiac rhythm. The spectrum of cardiac arrhythmias ranges from innocent extrasystoles to immediately life-threatening conditions such as asystole or ventricular fibrillation.

The key to the successful diagnosis of cardiac arrhythmias is the systematic analysis of an ECG (see ...
Structure and function of the pulmonary circulation
Authors: Morrell Nicholas W.
Published: January 2012

The normal pulmonary circulation distributes deoxygenated blood at low pressure and high flow to the pulmonary capillaries for the purposes of gas exchange. The structure of pulmonary blood vessels varies with their function—from large elastic conductance arteries, to small muscular arteries, to thin-walled vessels involved in gas exchange....
Discontinuing treatment of the critically ill patient
Authors: Lindop M.J.
Published: January 2012

A patient may have made an advance directive before the moment of decision about life-prolonging treatments, and their view is paramount. However, many patients have not made such a directive, and in this circumstance the responsibility for such decisions remains with the doctor.

Most people agree that prolongation of life itself is not necessarily a benefit: it is only valuable if that life is of adequate quality. Continuing aggressive treatment of a patient who is severely ill may not be kind or sensible....
Brainstem death and organ donation
Authors: Lindop M.J.
Published: January 2012

Brain death in the United States of America is defined as the ‘irreversible cessation of all functions of the entire brain, including the brainstem … that are clinically ascertainable’; in the United Kingdom the definition focuses on brainstem function. Half of those who fulfil the necessary clinical criteria will have a cardiac arrest despite intensive treatment within 24 h, and this happens to almost all within 72 h....
Sleep-related disorders of breathing
Authors: Stradling J.R. , Craig S.E.
Published: January 2012

Case History—A 52 yr old man referred for assessment of snoring.

Obstructive sleep apnoea (OSA) and other sleep-related breathing problems significantly impair the functioning of about 0.5 to 1% of the population and are becoming increasingly common.

OSA in adults is commoner in men than women (3–5:1) and usually caused by obesity (BMI typically >30 kg/m...
Idiopathic pulmonary fibrosis
Authors: Wells A.U. , Nicholson A.G. , Hirani N.
Published: January 2012

The synonymous terms idiopathic pulmonary fibrosis (IPF) and cryptogenic fibrosing alveolitis (CFA) refer to a relentlessly progressive fibrotic lung disorder that is the underlying diagnosis in over one-half of patients presenting with typical clinical features of the ‘CFA clinical syndrome’ (see Chapter 18.11.1). Incidence is about 10 to 15 per 100 000, men are more often affected than women, and it most commonly presents in the seventh and eighth decades. Aetiology remains uncertain....
The lung in autoimmune rheumatic disorders
Authors: Wells A.U. , Branley H.R.
Published: January 2012

Lung complications occur in all rheumatological disorders, but their frequency and type vary strikingly between different systemic diseases. Greater routine use of high-resolution CT and echocardiography means that interstitial lung disease and pulmonary vascular disease are increasingly recognized, which can create clinical difficulty in distinguishing between subclinical involvement and significant disease....
Pulmonary alveolar microlithiasis
Authors: Hendrick D.J.
Published: January 2012

Pulmonary alveolar microlithiasis is caused by mutations of the type IIb sodium phosphate cotransporter gene, which by an unknown mechanism leads to the accretion of calcified microliths in the lungs. Almost invariably the patient is symptom free when the diagnosis is made after a chest radiograph is taken incidentally (or during family screening) and reveals profuse small calcified nodules. Patients usually survive 10–20 years from diagnosis, lung transplantation being the only effective treatment in severe cases....
Chronic respiratory failure
Authors: Calverley P.M.A.
Published: January 2012

Chronic respiratory failure describes a clinical state when the arterial P
o
2 breathing air is less than 8.0 kPa, which may or may not be associated with hypercapnia (defined as P
co
2 more than 6.0 kPa (45 mmHg)). Four processes cause arterial hypoxaemia due to inefficient pulmonary gas exchange—ventilation–perfusion (...
Ankylosing spondylitis, other spondyloarthritides, and related conditions
Authors: Braun J. , Sieper J.
Published: January 2012

The spondyloarthritides are a group of 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. They are the second most frequent inflammatory rheumatic diseases after rheumatoid arthritis....
Kawasaki’s disease
Authors: McCrindle Brian W.
Published: January 2012

Kawasaki’s disease is an acute, self-limited, inflammatory vasculitis of unknown aetiology, with a peak incidence under 5 years of age.

Clinical features—the diagnosis is made in the presence of persistent fever for 5 days or more and at least four of the following five clinical signs: (1) nonpurulent conjunctivitis, (2) oropharyngeal inflammation, (3) cervical lymphadenopathy, (4) polymorphous exanthem, and (5) erythema of the palms and soles with subsequent desquamation. Incomplete presentations occur in approximately 25% of patients. The primary complications are cardiac, with coronary artery dilation and aneurysms evident in approximately 15 to 25% of untreated patients....
Miscellaneous conditions presenting to the rheumatologist
Authors: O’Gradaigh Donncha
Published: January 2012

Musculoskeletal symptoms may occur in a very wide range of diseases, or as a drug side effect. If the clinical picture is unusual, it is important that the physician keeps an open mind and reviews the history, signs, and investigation results carefully, looking for findings incongruent with ‘common diagnoses’. Some of the more distinctive and important miscellaneous conditions that are likely to present to rheumatologists are the following....
Structure and function of the kidney
Authors: Phillips A.O. , Riley Steve
Published: January 2012

The kidney is responsible for control of water, electrolyte (particularly sodium and potassium), and acid–base balance and for excretion of metabolic wastes, and it has important functions as an endocrine organ, including key roles in renin, vitamin D, and erythropoietin production or metabolism.

The nephron—beginning at the glomerulus, the functional unit of the kidney is the nephron, through which glomerular filtrate passes to be finally excreted as urine. The nephron is divided into anatomically and functionally distinct sections that work together to maintain homeostasis....
Haemodialysis
Authors: Farrington Ken , Greenwood Roger
Published: January 2012

Over the past four decades, maintenance haemodialysis has proved to be a highly successful treatment for patients with endstage renal disease. In the developed world, the haemodialysis population continues to increase and is becoming more elderly and dependent. However, despite considerable advances in haemodialysis technology and other significant improvements, such as those in renal anaemia management, the long-term clinical outcomes for patients remain much less good than those of other people with comparable characteristics but without renal failure....
Renal transplantation
Authors: Sweny P.
Published: January 2012

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. Attempts to bridge this gap have included (1) relaxation of the criteria for a suitable deceased donor (expanded/extended criteria or ‘marginal donors’); (2) reversion to the procurement of kidneys from donors with cardiac death (DCD donors, previously known as non-heart beating donors); and (3) encouragement of living donation—including techniques for desensitization of recipients, also paired exchanges, both to circumvent blood group incompatibilities or preformed antibodies that would otherwise bar transplantation....
The kidney in rheumatological disorders
Authors: Tse Wai Y. , Adu Dwomoa
Published: January 2012

Epidemiology and clinical features of renal disease—10 to 20% of patients with SLE have evidence of renal involvement at presentation, with this subsequently developing in about 40 to 50% of cases, typically during the first 5 years after diagnosis. Presentation is with proteinuria (causing nephrotic syndrome in ...
Urinary tract infection
Authors: Tomson Charles , Armitage Alison
Published: January 2012

Urinary tract infection (UTI) is a common condition, accounting for 1 to 3% of all primary care consultations in the United Kingdom. It affects patients of both sexes and all ages. The commonest organism causing uncomplicated community-acquired bacterial UTI is Escherichia coli.

The occurrence and course of a UTI is influenced by the integrity of the host defence and by bacterial virulence factors. Disruption of the highly specialized transitional cell epithelium which lines the urinary tract, incomplete bladder emptying, anatomical abnormalities, and the presence of a foreign body, such as a urinary catheter, can all contribute to disruption of the host defence and increase the likelihood of infection. Sexual intercourse, use of condoms, and use of spermicides all increase the risk, and genetic factors influence the susceptibility of some people, e.g. girls with the P1 blood group are at increased risk of acute pyelonephritis. Bacterial characteristics that determine their ability to cause infection include specific mechanisms to adhere to the uroepithelium (‘pili’ or ‘fimbrias’ in the case of certain ...
Myelodysplasia
Authors: Gardner Lawrence B. , Dang Chi V.
Published: January 2012

Myelodysplasia is a common haematological disorder that may occur at any age, although prevalence increases with age and most patients are over 60 years old. It is associated with a wide variety of acquired clonal abnormalities that may affect all lineages of blood cells and frequently lead to the development of leukaemia. Some particular chromosomal abnormalities are characteristic, and in a few cases functional studies of candidate genes implicated in the chromosomal abnormalities suggest cause–effect relationships, e.g. an activating mutation in the JAK2 kinase....
Thrombocytosis
Authors: Ciurea Stefan O. , Hoffman Ronald
Published: January 2012

Thrombocytosis describes 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, malignancy.

Platelets are released from megakaryocytes, whose development is principally regulated by thrombopoietin. This is chiefly produced in the liver and binds to its receptor (c-Mpl) to cause activation via the JAK-STAT signalling pathway at different levels of the platelet production pathway, ranging from the proliferation and survival of haematopoietic stem cell/progenitor cells to megakaryocyte maturation. Thrombopoietin production is increased by a wide variety of stimuli, which explains the many causes of secondary thrombocytosis....
Histiocytoses
Authors: Webb D.K.H
Published: January 2012

The histiocytoses are characterized by the infiltration of affected tissues with cells of monocyte/macrophage lineage.

Langerhans’ cell histiocytosis—may present with (1) disease affecting a single organ—typically skin (rash) or bone (pain and soft tissue swelling, or asymptomatic radiographic lesions); or (2) multisystem disease—characteristic features include ear discharge, diabetes insipidus, and lung involvement (diffuse micronodular shadowing on chest radiography, with progression to cyst formation and a honeycomb lung appearance). Diagnosis requires identification of Langerhans’ cells within lesional inflammatory cell infiltrate, with demonstration of either the CD1a surface antigen on immunohistochemistry or the presence of Birbeck granules on electron microscopy. Most cases eventually resolve spontaneously. Immunosuppressive and/or cytotoxic drugs are given when there is progressive organ injury, but the most effective and least toxic approach to treatment is not known....
Haemolytic anaemia—congenital and acquired
Authors: Powers Amy , Silberstein Leslie , Strobl Frank J.
Published: January 2012

Premature destruction of red cells occurs through two primary mechanisms: (1) decreased erythrocyte deformability that leads to red-cell sequestration and extravascular haemolysis in the spleen and other components of the reticuloendothelial system—may be caused by membrane defects, metabolic abnormalities, exogenous oxidizing agents, or pathological antibodies; (2) red-cell membrane damage and intravascular haemolysis—may be caused by exposure to pathological antibodies, activated complement, mechanical forces, chemicals, and infectious agents....
Disorders of the red cell membrane
Authors: Gallagher Patrick G.
Published: January 2012

The integrity of the red-cell membrane depends on molecular interactions between proteins and protein–lipid interactions: vertical interactions stabilize the membrane lipid bilayer; horizontal interactions provide resistance against shear stress.

This disorder 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....
The biology of haemostasis and thrombosis
Authors: Roberts Harold R. , White Gilbert C.
Published: January 2012

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....
Evaluation of the patient with a bleeding tendency
Authors: Baglin Trevor
Published: January 2012

An apparent bleeding tendency is a common clinical problem, with presentation varying from acute unexpected bleeding during or immediately after surgery, to spontaneous unusual or excessive bruising, purpura, epistaxis, or a chronic haemorrhagic tendency. The following are important aspects of the assessment of the patient....
Disorders of platelet number and function
Authors: Webert Kathryn E. , Kelton John G.
Published: January 2012

Platelets are released from megakaryocytes in the bone marrow and circulate for 5 to 10 days before being cleared by the cells of the reticuloendothelial system. They play a critical role in haemostasis, with key features being (1) adhesion—when the wall of a blood vessel is damaged, platelets adhere to exposed collagen and other components of the subendothelium via the glycoprotein Ib receptor and other adhesive receptors; followed by (2) activation—release of thrombin, adenosine diphosphate, and arachidonic acid, which is converted by a cascade of enzymes into platelet activating agents including thromboxane A...
Sebaceous and sweat gland disorders
Authors: Layton Alison
Published: January 2012

Cutaneous glands in humans include holocrine or sebaceous glands and merocrine or sweat glands. Merocrine glands are subdivided into apocrine, eccrine, and apoeccrine glands. Disorders of each of these cutaneous glands have been associated with disease.

Apocrine glands in adults are found predominantly in the axillae and anogenital regions, with a few located in the ear canal (ceruminous glands) and eyelids (Moll’s glands). Associated disorders include hidradenitis suppurativa, Fox–Fordyce disease, bromhidrosis, trimethylaminuria, and chromhidrosis....
Blood and lymphatic vessel disorders
Authors: Mortimer Peter S.
Published: January 2012

Bleeding into the skin may occur for local reasons or as part of a systemic disorder. The distribution of lesions is important: widespread lesions suggest a systemic problem, whereas regional lesions suggest that local factors predominate.

Widespread flat purpura without erythema should prompt a search for underlying haematological abnormalities such as platelet disorders. Larger (>1 cm) areas of purpura or bruising usually result from coagulation dysfunction. Palpable purpuric lesions, or those with a blanching component, suggest an associated inflammation as can be seen with vasculitis....
The unconscious patient
Authors: Bates David
Published: January 2012

Prolonged loss of consciousness (coma, defined as a Glasgow Coma Score of 8 or less) is seen commonly: (1) following head injury, (2) after an overdose of sedating drugs, and (3) in the situation of ‘nontraumatic coma’, where there are many possible diagnoses, but the most common are postanoxic, postischaemic, systemic infection, and metabolic derangement, e.g. hypoglycaemia....
Brain death and the vegetative state
Authors: Hutchinson P.J. , Pickard J.D.
Published: January 2012

Death can be defined as the irreversible loss of the capacity for consciousness and brain stem function, combined with irreversible loss of the capacity to breathe. The irreversible cessation of brainstem function, whether caused by a primary intracranial catastrophe (e.g. trauma, haemorrhage) or the result of extracranial cranial events (e.g hypoxia), will result in the same clinical state, hence brain stem death is the same as death of the patient....
Eavesdropping and signal matching in visual courtship displays of spiders
Authors: Clark David L. , Roberts J. Andrew , Uetz George W.
Published: January 2012

Eavesdropping on communication is widespread among animals, e.g. bystanders observing male–male contests, female mate choice copying and predator detection of prey cues. Some animals also exhibit signal matching, e.g. overlapping of competitors' acoustic signals in aggressive interactions. Fewer studies have examined male eavesdropping on conspecific courtship, although males could increase mating success by attending to others' behaviour and displaying whenever courtship is detected. In this study, we show that field-experienced male
Schizocosa ocreata
wolf spiders exhibit eavesdropping and signal matching when exposed to video playback of courting male conspecifics. Male spiders had longer bouts of interaction with a courting male stimulus, and more bouts of courtship signalling during and after the presence of a male on the video screen. Rates of courtship (leg tapping) displayed by individual focal males were correlated with the rates of the video exemplar to which they were exposed. These findings suggest male wolf spiders might gain information by eavesdropping on conspecific courtship and adjust performance to match that of rivals. This represents a novel finding, as these behaviours have previously been seen primarily among vertebrates.
Computational modelling of cell chain migration reveals mechanisms that sustain follow-the-leader behaviour
Authors: Wynn Michelle L. , Kulesa Paul M. , Schnell Santiago
Published: January 2012

Follow-the-leader chain migration is a striking cell migratory behaviour observed during vertebrate development, adult neurogenesis and cancer metastasis. Although cell–cell contact and extracellular matrix (ECM) cues have been proposed to promote this phenomenon, mechanisms that underlie chain migration persistence remain unclear. Here, we developed a quantitative agent-based modelling framework to test mechanistic hypotheses of chain migration persistence. We defined chain migration and its persistence based on evidence from the highly migratory neural crest model system, where cells within a chain extend and retract filopodia in short-lived cell contacts and move together as a collective. In our agent-based simulations, we began with a set of agents arranged as a chain and systematically probed the influence of model parameters to identify factors critical to the maintenance of the chain migration pattern. We discovered that chain migration persistence requires a high degree of directional bias in both lead and follower cells towards the target. Chain migration persistence was also promoted when lead cells maintained cell contact with followers, but not vice-versa. Finally, providing a path of least resistance in the ECM was not sufficient alone to drive chain persistence. Our results indicate that chain migration persistence depends on the interplay of directional cell movement and biased cell–cell contact.
Force-enhancing vortex equilibria for two parallel plates in uniform flow
Authors: Sakajo Takashi
Published: January 2012

A two-dimensional potential flow in an unbounded domain with two parallel plates is considered. We examine whether two free point vortices can be trapped near the two plates in the presence of a uniform flow and observe whether these stationary point vortices enhance the force on the plates. The present study is an extension of previously published work in which a free point vortex over a single plate is investigated. The flow problem is motivated by an airfoil design problem for the double wings. Moreover, it also contributes to a design problem for an efficient wind turbine with vertical blades. In order to obtain the point-vortex equilibria numerically, we make use of a linear algebraic algorithm combined with a stochastic process, called the Brownian ratchet scheme. The ratchet scheme allows us to capture a family of stationary point vortices in multiply connected domains with ease. As a result, we find that stationary point vortices exist around the two plates and they enhance the downward force and the counter-clockwise rotational force acting on the two plates.
How do communication systems emerge?
Authors: Scott-Phillips Thomas C. , Blythe Richard A. , Gardner Andy , West Stuart A.
Published: January 2012

Communication involves a pair of behaviours—a signal and a response—that are functionally interdependent. Consequently, the emergence of communication involves a chicken-and-egg problem: if signals and responses are dependent on one another, then how does such a relationship emerge in the first place? The empirical literature suggests two solutions to this problem: ritualization and sensory manipulation; and instances of ritualization appear to be more common. However, it is not clear from a theoretical perspective why this should be the case, nor if there are any other routes to communication. Here, we develop an analytical model to examine how communication can emerge. We show that: (i) a state of non-interaction is evolutionarily stable, and so communication will not necessarily emerge even when it is in both parties' interest; (ii) the conditions for sensory manipulation are more stringent than for ritualization, and hence ritualization is likely to be more common; and (iii) communication can arise by a third route, when the intention to communicate can itself be communicated, but this may be limited to humans. More generally, our results demonstrate the utility of a functional approach to communication.
The role of robustness in phenotypic adaptation and innovation
Authors: Wagner Andreas
Published: January 2012

Phenotypes that vary in response to DNA mutations are essential for evolutionary adaptation and innovation. Therefore, it seems that robustness, a lack of phenotypic variability, must hinder adaptation. The main purpose of this review is to show why this is not necessarily correct. There are two reasons. The first is that robustness causes the existence of genotype networks—large connected sets of genotypes with the same phenotype. I discuss why genotype networks facilitate phenotypic variability. The second reason emerges from the evolutionary dynamics of evolving populations on genotype networks. I discuss how these dynamics can render highly robust phenotypes more variable, using examples from protein and RNA macromolecules. In addition, robustness can help avoid an important evolutionary conflict between the interests of individuals and populations—a conflict that can impede evolutionary adaptation.
Diversification and the adaptive radiation of the vangas of Madagascar
Authors: Reddy S. , Driskell A. , Rabosky D. L. , Hackett S. J. , Schulenberg T. S.
Published: January 2012

The vangas of Madagascar exhibit extreme diversity in morphology and ecology. Recent studies have shown that several other Malagasy species also are part of this endemic radiation, even as the monophyly of the clade remains in question. Using DNA sequences from 13 genes and representatives of all 15 vanga genera, we find strong support for the monophyly of the Malagasy vangids and their inclusion in a family along with six aberrant genera of shrike-like corvoids distributed in Asia and Africa. Biogeographic reconstructions of these lineages include both Asia and Africa as possible dispersal routes to Madagascar. To study patterns of speciation through time, we introduce a method that can accommodate phylogenetically non-random patterns of incomplete taxon sampling in diversification studies. We demonstrate that speciation rates in vangas decreased dramatically through time following the colonization of Madagascar. Foraging strategies of these birds show remarkable congruence with phylogenetic relationships, indicating that adaptations to feeding specializations played a role in the diversification of these birds. Vangas fit the model of an ‘adaptive radiation’ in that they show an explosive burst of speciation soon after colonization, increased diversification into novel niches and extraordinary ecomorphological diversity.