Restenosis is a serious occurrence that can lead not only to recurrent angina and repeat revascularisation but also to acute coronary syndromes. Drug-eluting stents revolutionised interventional cardiology owing to their pronounced ability to reduce restenosis compared with bare-metal stents. Attention has now shifted to safety of these devices because of evidence suggesting an association with late stent thrombosis. Findings of randomised clinical trials have not shown that drug-eluting stents result in excess mortality after 4-5 years of follow-up. Current recommendations are that individuals with a drug-eluting stent should receive at least 12 months of uninterrupted dual antiplatelet treatment; patients must understand the importance of this long-term regimen. Patients' assessment should focus on bleeding abnormalities, pre-existing disorders that need anticoagulation treatment, and possible future surgical procedures, since these factors could all contraindicate use of drug-eluting stents. Many people will do well with a bare-metal stent, whereas for individuals with a high likelihood of restenosis and late thrombosis, medical management or surgical revascularisation might be preferred options.

Spinal muscular atrophy is an autosomal recessive neurodegenerative disease characterised by degeneration of spinal cord motor neurons, atrophy of skeletal muscles, and generalised weakness. It is caused by homozygous disruption of the survival motor neuron 1 (SMN1) gene by deletion, conversion, or mutation. Although no medical treatment is available, investigations have elucidated possible mechanisms underlying the molecular pathogenesis of the disease. Treatment strategies have been developed to use the unique genomic structure of the SMN1 gene region. Several candidate treatment agents have been identified and are in various stages of development. These and other advances in medical technology have changed the standard of care for patients with spinal muscular atrophy. In this Seminar, we provide a comprehensive review that integrates clinical manifestations, molecular pathogenesis, diagnostic strategy, therapeutic development, and evidence from clinical trials.

Tobacco use is associated with 5 million deaths per year worldwide and is regarded as one of the leading causes of premature death. Comprehensive programmes for tobacco control can substantially reduce the frequency of tobacco use. An important component of a comprehensive programme is the provision of treatment for tobacco addiction. Treatment involves targeting several aspects of addiction including the underlying neurobiology and behavioural processes. Furthermore, building an infrastructure in health systems that encourages and helps with cessation, as well as expansion of the accessibility of treatments, is necessary. Although pharmacological and behavioural treatments are effective in improving cessation success, the rate of relapse to smoking remains high, emphasising the strong addictive nature of nicotine. The future of treatment resides in improvement in patient matching to treatment, combination or novel drugs, and viewing nicotine addiction as a chronic disorder that might need long-term treatment.

Increasing evidence suggests that induction of mild hypothermia (32-35 degrees C) in the first hours after an ischaemic event can prevent or mitigate permanent injuries. This effect has been shown most clearly for postanoxic brain injury, but could also apply to other organs such as the heart and kidneys. Hypothermia has also been used as a treatment for traumatic brain injury, stroke, hepatic encephalopathy, myocardial infarction, and other indications. Hypothermia is a highly promising treatment in neurocritical care; thus, physicians caring for patients with neurological injuries, both in and outside the intensive care unit, are likely to be confronted with questions about temperature management more frequently. This Review discusses the available evidence for use of controlled hypothermia, and also deals with fever control. Besides discussing the evidence, the aim is to provide information to help guide treatments more effectively with regard to timing, depth, duration, and effective management of side-effects. In particular, the rate of rewarming seems to be an important factor in establishing successful use of hypothermia in the treatment of neurological injuries.

Trachoma is a keratoconjunctivitis caused by ocular infection with Chlamydia trachomatis. Repeated or persistent episodes lead to increasingly severe inflammation that can progress to scarring of the upper tarsal conjunctiva. Trichiasis develops when scarring distorts the upper eyelid sufficiently to cause one or more lashes to abrade the cornea, scarring it in turn and causing blindness. Active trachoma affects an estimated 84 million people; another 7.6 million have end-stage disease, of which about 1.3 million are blind. Trachoma should stand on the brink of extinction thanks to a 1998 initiative launched by WHO--the Global Elimination of Trachoma by 2020. This programme advocates control of trachoma at the community level with four inter-related population-health initiatives that form the SAFE strategy: surgery for trichiasis, antibiotics for active trachoma, facial cleanliness, and environmental improvement. Evidence supports the effectiveness of this approach, and if current world efforts continue, blinding trachoma will indeed be eliminated by 2020.

The use of doping agents, particularly anabolic androgenic steroids (AAS), has changed from being a problem restricted to sports to one of public-health concern. We review the prevalence of misuse, the evidence that some drugs improve performance in sport, their side-effects, and the long-term consequences of AAS misuse for society at large. There is substantial under-reporting of the side-effects of AAS to health authorities. We describe neuropsychiatric side-effects of AAS and their possible neurobiological correlates, with particular emphasis on violent behaviour. Analytical methods and laboratories accredited by the World Anti-Doping Agency can detect the misuse of all doping agents; although the analysis of testosterone requires special techniques, and recently discovered interethnic differences in testosterone excretion should be taken into account. The prevention of misuse of doping agents should include random doping analyses, medical follow-ups, pedagogic interventions, tougher legislation against possession of AAS, and longer disqualifications of athletes who use AAS.

We review the epidemiological and clinical characteristics of tick-borne encephalitis, and summarise biological and virological aspects that are important for understanding the life-cycle and transmission of the virus. Tick-borne encephalitis virus is a flavivirus that is transmitted by Ixodes spp ticks in a vast area from western Europe to the eastern coast of Japan. Tick-borne encephalitis causes acute meningoencephalitis with or without myelitis. Morbidity is age dependent, and is highest in adults of whom half develop encephalitis. A third of patients have longlasting sequelae, frequently with cognitive dysfunction and substantial impairment in quality of life. The disease arises in patchy endemic foci in Europe, with climatic and ecological conditions suitable for circulation of the virus. Climate change and leisure habits expose more people to tick-bites and have contributed to the increase in number of cases despite availability of effective vaccines. The serological diagnosis is usually straightforward. No specific treatment for the disease exists, and immunisation is the main preventive measure.

Individuals with type 2 diabetes mellitus have increased cardiovascular disease risk compared with those without diabetes. Treatment of the residual risk, other than blood pressure and LDL-cholesterol control, remains important as the rate of diabetes increases worldwide. The accelerated atherosclerosis and cardiovascular disease in diabetes is likely to be multifactorial and therefore several therapeutic approaches can be considered. Results of mechanistic studies done in vitro and in vivo--animals and people--can provide important insights with the potential to improve clinical management decisions and outcomes. In this Review, we focus on three areas in which pathophysiological considerations could be particularly informative--ie, the roles of hyperglycaemia, diabetic dyslipidaemia (other than the control of LDL-cholesterol concentrations), and inflammation (including that in adipose tissue) in the acceleration of vascular injury.

Type 1 diabetes is associated with a substantially increased risk of cardiovascular disease that might not always be appreciated in view of the fairly young age of patients with this condition. In fact, in type 1 diabetes, the heart is subject to a variety of pathological insults, including accelerated atherosclerosis, cardiac autonomic neuropathy, and possibly intrinsic cardiomyopathy. Although the relation between hyperglycaemia and microvascular complications has been well established, a direct effect of hyperglycaemia on cardiovascular disease in type 1 diabetes has long been debated. More recently, several studies, most notably the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications, have clarified this issue and provided conclusive evidence that hyperglycaemia is indeed a mediator of cardiovascular risk in type 1 diabetes and that intensive diabetes therapy can reduce cardiovascular disease outcomes. We review current concepts in type 1 diabetes and the heart, focusing on recent insights into the central role of hyperglycaemia.

In developed countries, prostate cancer is the second most frequently diagnosed cancer, and the third most common cause of death from cancer in men. Apart from age and ethnic origin, a positive family history is probably the strongest known risk factor. Clinically, prostate cancer is diagnosed as local or advanced, and treatments range from surveillance to radical local treatment or androgen-deprivation treatment. Androgen deprivation reduces symptoms in about 70-80% of patients with advanced prostate cancer, but most tumours relapse within 2 years to an incurable androgen-independent state. The recorded incidence of prostate cancer has substantially increased in the past two decades, probably because of the introduction of screening with prostate-specific antigen, the use of improved biopsy techniques for diagnosis, and increased public awareness. Trends in mortality from the disease are less clearcut. Mortality changes are not of the same magnitude as the changes in incidence, and in some countries mortality has been stable or even decreased. The disparity between reported incidence and mortality rates leads to the probable conclusion that only a small proportion of diagnosed low-risk prostate cancers will progress to life-threatening disease during the lifetime of the patient.

Most head and neck cancers are squamous cell carcinomas that develop in the upper aerodigestive epithelium after exposure to carcinogens such as tobacco and alcohol. Human papillomavirus has also been strongly implicated as a causative agent in a subset of these cancers. The complex anatomy and vital physiological role of the tumour-involved structures dictate that the goals of treatment are not only to improve survival outcomes but also to preserve organ function. Major improvements have been accomplished in surgical techniques and radiotherapy delivery. Moreover, systemic therapy including chemotherapy and molecularly targeted agents--namely, the epidermal growth factor receptor inhibitors--has been successfully integrated into potentially curative treatment of locally advanced squamous-cell carcinoma of the head and neck. In deciding which treatment strategy would be suitable for an individual patient, important considerations include expected functional outcomes, ability to tolerate treatment, and comorbid illnesses. The collaboration of many specialties is the key for optimum assessment and decision making. We review the epidemiology, molecular pathogenesis, diagnosis and staging, and the latest multimodal management of squamous cell carcinoma of the head and neck.

Arginine-vasopressin is a hormone that plays an important part in circulatory and water homoeostasis. The three arginine-vasopressin-receptor subtypes--V1a, V1b, and V2--all belong to the large rhodopsin-like G-protein-coupled receptor family. The vaptans are orally and intravenously active non-peptide vasopressin receptor antagonists that are in development. Relcovaptan is a selective V1a-receptor antagonist, which has shown initial positive results in the treatment of Raynaud's disease, dysmenorrhoea, and tocolysis. SSR-149415 is a selective V1b-receptor antagonist, which could have beneficial effects in the treatment of psychiatric disorders. V2-receptor antagonists--mozavaptan, lixivaptan, satavaptan, and tolvaptan--induce a highly hypotonic diuresis without substantially affecting the excretion of electrolytes (by contrast with the effects of diuretics). These drugs are all effective in the treatment of euvolaemic and hypervolaemic hyponatraemia. Conivaptan is a V1a/V2 non-selective vasopressin-receptor antagonist that has been approved by the US Food and Drug Administration as an intravenous infusion for the inhospital treatment of euvolaemic or hypervolaemic hyponatraemia.

Stroke is the second most common cause of death and major cause of disability worldwide. Because of the ageing population, the burden will increase greatly during the next 20 years, especially in developing countries. Advances have occurred in the prevention and treatment of stroke during the past decade. For patients with acute stroke, management in a stroke care unit, intravenous tissue plasminogen activator within 3 h or aspirin within 48 h of stroke onset, and decompressive surgery for supratentorial malignant hemispheric cerebral infarction are interventions of proven benefit; several other interventions are being assessed. Proven secondary prevention strategies are warfarin for patients with atrial fibrillation, endarterectomy for symptomatic carotid stenosis, antiplatelet agents, and cholesterol reduction. The most important intervention is the management of patients in stroke care units because these provide a framework within which further study might be undertaken. These advances have exposed a worldwide shortage of stroke health-care workers, especially in developing countries.

Although carotid bruits are deemed to be markers of generalised atherosclerosis, they are poor predictors of cerebrovascular events. We investigated whether a carotid bruit predicts myocardial infarction and cardiovascular death.

Peanut allergy has become a major health concern worldwide, especially in developed countries. However, the reasons for this increasing prevalence over the past several decades are not well understood. Because of the potentially severe health consequences of peanut allergy, those suspected of having had an allergic reaction to peanuts deserve a thorough evaluation. All patients with peanut allergy should be given an emergency management plan, as well as epinephrine and antihistamines to have on hand at all times. Patients and families should be taught to recognise early allergic reactions to peanuts and how to implement appropriate peanut-avoidance strategies. It is imperative that severe, or potentially severe, reactions be treated promptly with intramuscular epinephrine and oral antihistamines. Patients who have had such a reaction should be kept under observation in a hospital emergency department or equivalent for up to 4 h because of the possible development of the late-phase allergic response. This Seminar looks at the changing epidemiology of this allergy--and theories as to the rise in prevalence, diagnosis, and management of the allergy, and potential new treatments and prevention strategies under development.

Adolescent idiopathic scoliosis (AIS) affects 1-3% of children in the at-risk population of those aged 10-16 years. The aetiopathogensis of this disorder remains unknown, with misinformation about its natural history. Non-surgical treatments are aimed to reduce the number of operations by preventing curve progression. Although bracing and physiotherapy are common treatments in much of the world, their effectiveness has never been rigorously assessed. Technological advances have much improved the ability of surgeons to safely correct the deformity while maintaining sagittal and coronal balance. However, we do not have long-term results of these changing surgical treatments. Much has yet to be learned about the general health, quality of life, and self-image of both treated and untreated patients with AIS.

Few studies have assessed the extent and distribution of the blood-pressure burden worldwide. The aim of this study was to quantify the global burden of disease related to high blood pressure.