The autonomic neuropathies are a group of disorders in which the small, lightly myelinated and unmyelinated autonomic nerve fibres are selectively targeted. Autonomic features, which involve the cardiovascular, gastrointestinal, urogenital, sudomotor, and pupillomotor systems, occur in varying combination in these disorders. Diabetes is the most common cause of autonomic neuropathy in more developed countries. Autonomic neuropathies can also occur as a result of amyloid deposition, after acute infection, as part of a paraneoplastic syndrome, and after exposure to neurotoxins including therapeutic drugs. Certain antibodies (eg, anti-Hu and those directed against neuronal nicotinic acetylcholine receptor) are associated with autonomic signs and symptoms. There are several familial autonomic neuropathies with autosomal dominant, autosomal recessive, or X-linked patterns of inheritance. Autonomic dysfunction can occur in association with specific infections. The availability of sensitive and reproducible measures of autonomic function has improved physicians' ability to diagnose these disorders.

Deep vein thrombosis and its sequelae pulmonary embolism and post-thrombotic syndrome are some of the most common disorders. A thrombus either arises spontaneously or is caused by clinical conditions including surgery, trauma, or prolonged bed rest. In these instances, prophylaxis with low-dose anticoagulation is effective. Diagnosis of deep vein thrombosis relies on imaging techniques such as ultrasonography or venography. Only about 25% of symptomatic patients have a thrombus. Thus, clinical risk assessment and D-dimer measurement are used to rule out deep vein thrombosis. Thrombus progression and embolisation can be prevented by low-molecular-weight heparin followed by vitamin K antagonists. Use of these antagonists for 3-6 months is sufficient for many patients. Those with antithrombin deficiency, the lupus anticoagulant, homozygous or combined defects, or with previous deep vein thrombosis can benefit from indefinite anticoagulation. In cancer patients, low-molecular-weight heparin is more effective than and is at least as safe as vitamin K antagonists. Women seem to have a lower thrombosis risk than men, but pregnancy or use of oral contraceptives or hormone replacement therapy represent important risk factors.

Most cases of diarrhoea-associated haemolytic uraemic syndrome (HUS) are caused by Shiga-toxin-producing bacteria; the pathophysiology differs from that of thrombotic thrombocytopenic purpura. Among Shiga-toxin-producing Escherichia coli (STEC), O157:H7 has the strongest association worldwide with HUS. Many different vehicles, in addition to the commonly suspected ground (minced) beef, can transmit this pathogen to people. Antibiotics, antimotility agents, narcotics, and non-steroidal anti-inflammatory drugs should not be given to acutely infected patients, and we advise hospital admission and administration of intravenous fluids. Management of HUS remains supportive; there are no specific therapies to ameliorate the course. The vascular injury leading to HUS is likely to be well under way by the time infected patients seek medical attention for diarrhoea. The best way to prevent HUS is to prevent primary infection with Shiga-toxin-producing bacteria.

Because of the increasing ease and affordability of air travel and mobility of people, airborne, food-borne, vector-borne, and zoonotic infectious diseases transmitted during commercial air travel are an important public health issue. Heightened fear of bioterrorism agents has caused health officials to re-examine the potential of these agents to be spread by air travel. The severe acute respiratory syndrome outbreak of 2002 showed how air travel can have an important role in the rapid spread of newly emerging infections and could potentially even start pandemics. In addition to the flight crew, public health officials and health care professionals have an important role in the management of infectious diseases transmitted on airlines and should be familiar with guidelines provided by local and international authorities.

Asthma is readily diagnosed in most cases and usually responds to inhaled corticosteroids with or without long-acting beta agonists, theophyllines, or leukotriene-receptor antagonists, adjusted stepwise according to symptoms and lung function. However, up to 40% of adult patients with asthma remain symptomatic, and up to 5% have difficult-to-control asthma despite multiple therapies. It is suggested that higher doses of inhaled steroids with long-acting beta2 agonists should be used for total control of symptoms; and anti-IgE therapy is newly licensed in the USA. However, difficult-to-control asthma is complex and multifactorial, and is often not due to severe or therapy-resistant asthma.

The term osteoarthritis describes a common, age-related, heterogeneous group of disorders characterised pathologically by focal areas of loss of articular cartilage in synovial joints, associated with varying degrees of osteophyte formation, subchondral bone change, and synovitis. Joint damage is caused by a mixture of systemic factors that predispose to the disease, and local mechanical factors that dictate its distribution and severity. Various genetic abnormalities have been described, but most sporadic osteoarthritis probably depends on minor contributions from several genetic loci. Osteoarthritic joint damage may be associated with clinical problems, but the severity of joint disease is only weakly related to that of the clinical problem. For this reason the associations and pathogenesis of pain are in as much need of investigation as joint damage. Subchondral bone and synovium may be responsible for nociceptive stimuli, and peripheral neuronal sensitisation is an important feature, and can result in normal activities (such as walking) causing pain. Central pain sensitisation can also occur, and psychosocial factors are important determinants of pain severity. We present a stepwise approach to the management of osteoarthritis.

During the past three to four decades, the incidence of acquired sensorineural hearing loss (SNHL) in children living in more developed countries has fallen, as a result of improved neonatal care and the widespread implementation of immunisation programmes. The overall decrease has been accompanied by a relative increase in the proportion of inherited forms of SNHL. The contribution made by one gene in particular, GJB2, to the genetic load of SNHL has strongly affected the assessment and care of children with hearing loss. These changes in the incidence of SNHL have not been seen in children living in less developed countries, where the prevalence of consanguinity is high in many areas, and both genetic and acquired forms of SNHL are more common, particularly among children who live in poverty. Focused genetic counselling and health education might lead to a decrease in the prevalence of inherited SNHL in these countries. Establishment of vaccination programmes for several vaccine-preventable infectious diseases would reduce rates of acquired SNHL. Although the primary purpose of such programmes is the prevention of serious and in many cases fatal infections, a secondary benefit would be a reduction in disease-related complications such as SNHL that cause permanent disability in survivors.

Glucocorticoids are frequently and successfully used drugs that mediate important immunosuppressive and anti-inflammatory effects. These drugs are also relatively inexpensive, but it is their broad range of adverse reactions that continuously stimulate efforts to optimise glucocorticoid treatment.

Pre-eclampsia is a major cause of maternal mortality (15-20% in developed countries) and morbidities (acute and long-term), perinatal deaths, preterm birth, and intrauterine growth restriction. Key findings support a causal or pathogenetic model of superficial placentation driven by immune maladaptation, with subsequently reduced concentrations of angiogenic growth factors and increased placental debris in the maternal circulation resulting in a (mainly hypertensive) maternal inflammatory response. The final phenotype, maternal pre-eclamptic syndrome, is further modulated by pre-existing maternal cardiovascular or metabolic fitness. Currently, women at risk are identified on the basis of epidemiological and clinical risk factors, but the diagnostic criteria of pre-eclampsia remain unclear, with no known biomarkers. Treatment is still prenatal care, timely diagnosis, proper management, and timely delivery. Many interventions to lengthen pregnancy (eg, treatment for mild hypertension, plasma-volume expansion, and corticosteroid use) have a poor evidence base. We review findings on the diagnosis, risk factors, and pathogenesis of pre-eclampsia and the present status of its prediction, prevention, and management.

We aimed to assess evidence of efficacy and effectiveness of live attenuated and inactivated influenza vaccines in children up to 16 years of age.

There is continuing debate on the extent of the effects of media violence on children and young people, and how to investigate these effects. The aim of this review is to consider the research evidence from a public-health perspective. A search of published work revealed five meta-analytic reviews and one quasi-systematic review, all of which were from North America. There is consistent evidence that violent imagery in television, film and video, and computer games has substantial short-term effects on arousal, thoughts, and emotions, increasing the likelihood of aggressive or fearful behaviour in younger children, especially in boys. The evidence becomes inconsistent when considering older children and teenagers, and long-term outcomes for all ages. The multifactorial nature of aggression is emphasised, together with the methodological difficulties of showing causation. Nevertheless, a small but significant association is shown in the research, with an effect size that has a substantial effect on public health. By contrast, only weak evidence from correlation studies links media violence directly to crime.

Episodic exposure of fair-skinned individuals to intense sunlight is thought to be responsible for the steadily increasing melanoma incidence worldwide over recent decades. Rarely, melanoma susceptibility is increased more than tenfold by heritable mutations in the cell cycle regulatory genes CDKN2A and CDK4. Effective treatment requires early diagnosis followed by surgical excision with adequately wide margins. Sentinel lymph node biopsy provides accurate staging, but no published results are yet available from clinical trials designed to assess the therapeutic efficacy of early complete regional node dissection in those with metastatic disease in a sentinel node. Magnetic resonance spectroscopy is one technique under investigation for non-invasive, in-situ assessment of sentinel nodes. Localised metastatic disease is best treated surgically. No postoperative adjuvant therapy is of proven value for improving overall survival, although numerous clinical trials of vaccines and cytokines are in progress. Medical therapies have contributed little to the control of established metastatic disease, but molecular pathways recently identified as being central to melanoma growth and apoptosis are under intense investigation for their potential as therapeutic targets.

Type 2 diabetes and attendant cardiovascular morbidity are becoming major health concerns globally. Obesity-related type 2 diabetes is rapidly rising in prevalence, probably largely because of increased longevity and sedentary lifestyles. Insulin resistance and type 2 diabetes are associated with increased coronary heart disease, but the severity of glycaemia during the diabetic phase can only to a minor extent explain the increased risk. Increased levels of the acute-phase inflammatory marker, C-reactive protein (CRP), are related to insulin resistance and the metabolic syndrome, suggesting a role for chronic low-grade inflammation. CRP levels might predict the development of type 2 diabetes.

Cataract, opacification of the lens, is one of the commonest causes of loss of useful vision, with an estimated 16 million people worldwide affected. Several risk factors have been identified in addition to increasing age--genetic composition, exposure to ultraviolet light, and diabetes. However, no method to halt the formation of a cataractous lens has been shown to be effective. Nevertheless, advances in surgical removal of cataracts, including small-incision surgery, use of viscoelastics, and the development of intraocular lenses, have made treatment very effective and visual recovery rapid in most cases. Despite these advances, cataract continues to be a leading public-health issue that will grow in importance as the population increases and life expectancy is extended worldwide.

Alcoholic beverages, and the problems they engender, have been familiar fixtures in human societies since the beginning of recorded history. We review advances in alcohol science in terms of three topics: the epidemiology of alcohol's role in health and illness; the treatment of alcohol use disorders in a public health perspective; and policy research and options. Research has contributed substantially to our understanding of the relation of drinking to specific disorders, and has shown that the relation between alcohol consumption and health outcomes is complex and multidimensional. Alcohol is causally related to more than 60 different medical conditions. Overall, 4% of the global burden of disease is attributable to alcohol, which accounts for about as much death and disability globally as tobacco and hypertension. Treatment research shows that early intervention in primary care is feasible and effective, and a variety of behavioural and pharmacological interventions are available to treat alcohol dependence. This evidence suggests that treatment of alcohol-related problems should be incorporated into a public health response to alcohol problems. Additionally, evidence-based preventive measures are available at both the individual and population levels, with alcohol taxes, restrictions on alcohol availability, and drinking-driving countermeasures among the most effective policy options. Despite the scientific advances, alcohol problems continue to present a major challenge to medicine and public health, in part because population-based public health approaches have been neglected in favour of approaches oriented to the individual that tend to be more palliative than preventative.

Mitral valve prolapse is a common valvular abnormality that is the most common cause of severe non-ischaemic mitral regurgitation in the USA. The overall prognosis of patients with mitral valve prolapse is excellent, but a small subset will develop serious complications, including infective endocarditis, sudden cardiac death, and severe mitral regurgitation. We present a comprehensive review of mitral valve prolapse, examining normal mitral anatomy, the clinical and echocardiographic features of mitral valve prolapse, and the pathophysiology and genetics of the disorder. We discuss the contemporary management of both asymptomatic and symptomatic prolapse, with particular attention to the timing and technique of surgical repair. We conclude that echocardiography is the method of choice for diagnosing mitral valve prolapse, that clinical and echocardiographic features can predict which patients with prolapse are at highest risk for complications, and that mitral valve repair is the treatment of choice for symptomatic prolapse.

This seminar covers the most recent information on definition, epidemiology, and clinical causes of acute renal failure. The mechanisms of acute prerenal failure and the potential interference by commonly used drugs of autoregulation of renal blood flow are discussed. We summarise some basic and recent insights into the haemodynamic and cellular pathophysiological mechanisms, mainly of postischaemic acute renal failure. Recent findings on the repair mechanisms of renal injury and the potential future therapeutic possibilities are discussed. We provide some differential diagnostic approaches for patients with acute renal failure and summarise prevention of the disorder and management of critically ill patients by dialysis and by other means. Finally, some information on the influence of gene polymorphisms on the prognosis of acute renal failure is given.

The worldwide rise in the number of patients with chronic kidney disease (CKD) and consequent end-stage renal failure necessitating renal replacement therapy is threatening to reach epidemic proportions over the next decade, and only a small number of countries have robust economies able to meet the challenges posed. A change in global approach to CKD from treatment of end-stage renal disease (ESRD) to much more aggressive primary and secondary prevention is therefore imperative. In this Seminar, we examine the epidemiology of CKD worldwide, with emphasis on early detection and prevention, and the feasibility of methods for detection and primary prevention of CKD. We also review the risk factors and markers of progressive CKD. We explore current understanding of the mechanisms underlying renal scarring leading to ESRD to inform on current and future interventions as well as evidence relating to interventions to slow the progression of CKD. Finally, we make strategic recommendations based on future research to stem the worldwide growth of CKD. Consideration is given to health economics. A global and concerted approach to CKD must be adopted in both more and less developed countries to avoid a major catastrophe.

The frequency of asthma varies between countries, and may also vary between ethnic groups in more geographically confined areas. We sought evidence of such ethnic variations in the UK for asthma frequency, morbidity, and health-services use, and to understand possible reasons for any differences.

Polymicrobial diseases, caused by combinations of viruses, bacteria, fungi, and parasites, are being recognised with increasing frequency. In these infections, the presence of one micro-organism generates a niche for other pathogenic micro-organisms to colonise, one micro-organism predisposes the host to colonisation by other micro-organisms, or two or more non-pathogenic micro-organisms together cause disease.