25 years after the first HIV/AIDS cases emerged in 1981, the disease continues to spread worldwide, with about 15 000 new infections every day. Although highly active antiretroviral therapy (HAART) has greatly reduced the rate of HIV infection, and the spread of the epidemic, this effect has largely been seen in developed countries. More than 90% of HIV-infected people live in developing countries, most of whom do not have access to this treatment. The development of efficient, widely available, and low-cost microbicides (gels and creams can be applied topically before sex) to prevent sexually transmitted HIV infections should be given high priority. We review different categories of microbicide drugs and lead compounds, their mechanism of action, current status of development, and progress in phase III trials.

Increases in international funding for health have been accompanied by accelerating demand for more and better statistics, which are needed to track performance and ensure accountability. Worldwide interest in the monitoring of development, as exemplified in the Millennium Development Goals (MDGs), generates pressure for high-quality and timely data for reporting on country progress. This rapid escalation of demand has exposed major gaps in the supply of health statistics for developing countries but also provides major opportunities to increase the supply and use of sound health statistics. First, the emphasis on monitoring and evaluation is leading to proliferation of indicators and excessive reporting requirements, and needs to be refocused on systematic investments in data generation and analysis. Second, the risk of inadequate or poorly targeted investments can be kept to a minimum by understanding the causes of poor availability of health statistics, including lack of accurate measurement instruments, application of suboptimum methods of data collection, and inadequate use of methods and analyses to produce comparable estimates. Third, the preoccupation with MDGs does not take into account the rapid health transition, which implies that health statistics should systematically include a much wider array of health issues from acute infectious diseases to chronic non-communicable diseases and injuries, disaggregated by socioeconomic position. Fourth, the growing number of national household surveys, which are the main source of most population health statistics, need to be streamlined into cohesive and comprehensive country health survey programmes. Now is the time to accelerate the production and use of accurate, complete, and timely health statistics for decision-making by investing in country health information systems that should be based on an efficient and effective mix of standardised methods of data collection and analysis that meet country and international needs.

Juvenile idiopathic arthritis is a broad term that describes a clinically heterogeneous group of arthritides of unknown cause, which begin before 16 years of age. This term encompasses several disease categories, each of which has distinct methods of presentation, clinical signs, and symptoms, and, in some cases, genetic background. The cause of disease is still poorly understood but seems to be related to both genetic and environmental factors, which result in the heterogeneity of the illness. Although none of the available drugs has a curative potential, prognosis has greatly improved as a result of substantial progresses in disease management. The most important new development has been the introduction of drugs such as anticytokine agents, which constitute a valuable treatment option for patients who are resistant to conventional antirheumatic agents. Further insights into the disease pathogenesis and treatment will be provided by the continuous advances in understanding of the mechanisms connected to the immune response and inflammatory process, and by the development of new drugs that are able to inhibit selectively single molecules or pathways.

Four factors have driven China's response to the HIV/AIDS pandemic: (1) existing government structures and networks of relationships; (2) increasing scientific information; (3) external influences that underscored the potential consequences of an HIV/AIDS pandemic and thus accelerated strategic planning; and (4) increasing political commitment at the highest levels. China's response culminated in legislation to control HIV/AIDS-the AIDS Prevention and Control Regulations. Three major initiatives are being scaled up concurrently. First, the government has prioritised interventions to control the epidemic in injection drug users, sex workers, men who have sex with men, and plasma donors. Second, routine HIV testing is being implemented in populations at high risk of infection. Third, the government is providing treatment for infected individuals. These bold programmes have emerged from a process of gradual and prolonged dialogue and collaboration between officials at every level of government, researchers, service providers, policymakers, and politicians, and have led to decisive action.

Endocrine disease frequently interrupts sexual function, and sexual dysfunction may signal serious endocrine disease. Diabetic autonomic neuropathy and endothelial dysfunction impair erectile function, and phosphodiesterase inhibition produces only moderate benefit. The effect of diabetes on women's sexual function is complex: the most consistent finding is a correlation between sexual dysfunction and depression. Reductions in testosterone level in men are associated with low sexual desire and reduced nocturnal erections and ejaculate volume, all of which improve with testosterone supplementation. The age-dependent decline in testosterone production in men is not associated with precise sexual symptoms, and supplementation has not been shown to produce sexual benefit. In women, sexual dysfunction has not been associated with serum testosterone, but this may be confounded by limitations of assays at low concentrations and by the greater importance of intracellular production of testosterone in women than in men. Testosterone supplementation after menopause does improve some aspects of sexual function in women, but long-term outcome data are needed. More research on the sexual effects of abnormal adrenal and thyroid function, hyperprolactinaemia, and metabolic syndrome should also be prioritised. We have good data on local management of the genital consequences of oestrogen lack, but need to better understand the potential role of systemic oestrogen supplementation from menopause onwards in sexually symptomatic women.

Systemic lupus erythematosus is an autoimmune connective-tissue disorder with a wide range of clinical features, which predominantly affects women, especially from certain ethnic groups. Diagnosis is based on clinical assessment supported by investigations, including the finding of autoantibodies. Treatments range from antimalarial agents to corticosteroids and immunosuppressive agents. This Seminar draws attention to advances in the epidemiology, genetics, cardiovascular risks, lupus nephritis, CNS disease, the antiphospholipid syndrome, assessment of disease activity and damage, and pregnancy related and quality of life issues. New therapeutic approaches, such as biological agents and mycophenolate mofetil, will also be discussed.

The advent of non-invasive functional brain imaging has clarified which regions of the brain are recruited during sexual arousal. Injuries to those regions, and to the spinal cord and peripheral nerves that link genitalia to limbic and cognitive centres, can profoundly influence sexual wellbeing. In epilepsy, expressions of hypersexuality and hyposexuality interact with the location of epileptogenic foci in the temporolimbic circuitry, and are tempered by the sexual effects of drug treatments. We outline the sexual consequences of epilepsy, stroke, multiple sclerosis, Parkinson's disease, and other common neurological disorders. Management of sexual dysfunction from both disease and treatment is discussed. Nerve-sparing techniques could mitigate the substantial sexual dysfunction in both men and women through surgical disruption of the autonomic nerves during radical pelvic surgery.

Narcolepsy with cataplexy is a disabling sleep disorder affecting 0.02% of adults worldwide. It is characterised by severe, irresistible daytime sleepiness and sudden loss of muscle tone (cataplexy), and can be associated with sleep-onset or sleep-offset paralysis and hallucinations, frequent movement and awakening during sleep, and weight gain. Sleep monitoring during night and day shows rapid sleep onset and abnormal, shortened rapid-eye-movement sleep latencies. The onset of narcolepsy with cataplexy is usually during teenage and young adulthood and persists throughout the lifetime. Pathophysiological studies have shown that the disease is caused by the early loss of neurons in the hypothalamus that produce hypocretin, a wakefulness-associated neurotransmitter present in cerebrospinal fluid. The cause of neural loss could be autoimmune since most patients have the HLA DQB1*0602 allele that predisposes individuals to the disorder. Treatment is with stimulant drugs to suppress daytime sleepiness, antidepressants for cataplexy, and gamma hydroxybutyrate for both symptoms. Because narcolepsy is an under-recognised disease, it is important that general practitioners and other primary health-care workers identify abnormal daytime sleepiness early.

Hypertension has a range of effects on the eye. Hypertensive retinopathy refers to retinal microvascular signs that develop in response to raised blood pressure. Signs of hypertensive retinopathy are frequently seen in adults 40 years and older, and are predictive of incident stroke, congestive heart failure, and cardiovascular mortality--independently of traditional risk factors. Hypertension is also a major risk factor for the development of other retinal vascular diseases, such as retinal vein and artery occlusion, and ischaemic optic neuropathy. High blood pressure increases the risk of both development of diabetic retinopathy and its progression. Adequate control of blood pressure has been proven in randomised clinical trials to reduce vision loss associated with diabetic retinopathy. Finally, hypertension has been implicated in the pathogenesis of glaucoma and age-related macular degeneration. Recognition of the ocular effects of blood pressure could allow physicians to better manage patients with hypertension, and to monitor its end-organ effects.

That sexual symptoms can signal serious underlying disease confirms the importance of sexual enquiry as an integral component of medical assessment. Data on sexual function are sparse in some medical specialties. However, increased scientific understanding of the central and peripheral physiology of sexual response could help to identify the pathophysiology of sexual dysfunction from disease and medical interventions, and also to ameliorate or prevent some dysfunctions. Many common general medical disorders have negative effects on desire, arousal, orgasm, ejaculation, and freedom from pain during sex. Chronic disease also interferes indirectly with sexual function, by altering relationships and self-image and causing fatigue, pain, disfigurement, and dependency. Current approaches to assessment of sexual dysfunction are based on models that combine psychological and biological aspects.

Progressive hepatolenticular degeneration, or Wilson's disease, is a genetic disorder of copper metabolism. Knowledge of the clinical presentations and treatment of the disease are important both to the generalist and to specialists in gastroenterology and hepatology, neurology, psychiatry, and paediatrics. Wilson's disease invariably results in severe disability and death if untreated. The diagnosis is easily overlooked but if discovered early, effective treatments are available that will prevent or reverse many manifestations of this disorder. Studies have identified the role of copper in disease pathogenesis and clinical, biochemical, and genetic markers that can be useful in diagnosis. There are several chelating agents and zinc salts for medical therapy. Liver transplantation corrects the underlying pathophysiology and can be lifesaving. The discovery of the Wilson's disease gene has opened up a new molecular diagnostic approach, and could form the basis of future gene therapy.

Treatments for acute ischaemic stroke continue to evolve. Experimental approaches to restore cerebral perfusion include techniques to augment recanalising therapies, including combination of antiplatelet agents with intravenous thrombolysis, bridging therapy of combining intravenous with intra-arterial thrombolysis, and trials of new thrombolytic agents. Trials with MRI selection criteria are underway to expand the window of opportunity for thrombolysis. Sonothrombolysis and novel endovascular mechanical devices to retrieve or dissolve acute cerebral occlusions are being tested. Approaches to improve cerebral perfusion with other devices and induced hypertension are also being considered. Although numerous neuroprotective agents have not shown benefit, trials of hypothermia, magnesium, caffeinol, high doses of statins, and albumin are continuing. The findings of these randomised trials are anticipated to allow improved treatment of patients with acute stroke.

This article reviews the recommended management of patients presenting to accident and emergency departments with acute ischaemic stroke, and focuses on thrombolysis. The review includes initial management, recommended clinical, laboratory, and radiographic examinations. Appropriate general medical care, consisting of monitoring of oxygenation, fever, blood pressure, and blood glucose concentrations are examined. Criteria for thrombolysis with intravenous recombinant tissue plasminogen activator (rt-PA) are discussed. Complications of rt-PA therapy, such as haemorrhagic transformation and angio-oedema, are reviewed. An approach to management of rt-PA complications is outlined. Only a small percentage of acute ischaemic stroke patients meet criteria for rt-PA; therefore, alternative acute treatment strategies are also discussed. Acute medical and neurological complications in stroke patients are analysed, along with recommendations for treatment.

Subarachnoid haemorrhage accounts for only 5% of strokes, but occurs at a fairly young age. Sudden headache is the cardinal feature, but patients might not report the mode of onset. CT brain scanning is normal in most patients with sudden headache, but to exclude subarachnoid haemorrhage or other serious disorders, a carefully planned lumbar puncture is also needed. Aneurysms are the cause of subarachnoid haemorrhage in 85% of cases. The case fatality after aneurysmal haemorrhage is 50%; one in eight patients with subarachnoid haemorrhage dies outside hospital. Rebleeding is the most imminent danger; a first aim is therefore occlusion of the aneurysm. Endovascular obliteration by means of platinum spirals (coiling) is the preferred mode of treatment, but some patients require a direct neurosurgical approach (clipping). Another complication is delayed cerebral ischaemia; the risk is reduced with oral nimodipine and probably by maintaining circulatory volume. Hydrocephalus might cause gradual obtundation in the first few hours or days; it can be treated by lumbar puncture or ventricular drainage, dependent on the site of obstruction.

This paper is the third in the Child Development Series. The first paper showed that more than 200 million children under 5 years of age in developing countries do not reach their developmental potential. The second paper identified four well-documented risks: stunting, iodine deficiency, iron deficiency anaemia, and inadequate cognitive stimulation, plus four potential risks based on epidemiological evidence: maternal depression, violence exposure, environmental contamination, and malaria. This paper assesses strategies to promote child development and to prevent or ameliorate the loss of developmental potential. The most effective early child development programmes provide direct learning experiences to children and families, are targeted toward younger and disadvantaged children, are of longer duration, high quality, and high intensity, and are integrated with family support, health, nutrition, or educational systems and services. Despite convincing evidence, programme coverage is low. To achieve the Millennium Development Goals of reducing poverty and ensuring primary school completion for both girls and boys, governments and civil society should consider expanding high quality, cost-effective early child development programmes.

Huntington's disease is an autosomal-dominant, progressive neurodegenerative disorder with a distinct phenotype, including chorea and dystonia, incoordination, cognitive decline, and behavioural difficulties. Typically, onset of symptoms is in middle-age after affected individuals have had children, but the disorder can manifest at any time between infancy and senescence. The mutant protein in Huntington's disease--huntingtin--results from an expanded CAG repeat leading to a polyglutamine strand of variable length at the N-terminus. Evidence suggests that this tail confers a toxic gain of function. The precise pathophysiological mechanisms of Huntington's disease are poorly understood, but research in transgenic animal models of the disorder is providing insight into causative factors and potential treatments.