Primary open-angle glaucoma is a progressive optic neuropathy and, perhaps, the most common form of glaucoma. Because the disease is treatable, and because the visual impairment caused by glaucoma is irreversible, early detection is essential. Early diagnosis depends on examination of the optic disc, retinal nerve fibre layer, and visual field. New imaging and psychophysical tests can improve both detection and monitoring of the progression of the disease. Recently completed long-term clinical trials provide convincing evidence that lowering intraocular pressure prevents progression at both the early and late stages of the disease. The degree of protection is related to the degree to which intraocular pressure is lowered. Improvements in therapy consist of more effective and better-tolerated drugs to lower intraocular pressure, and more effective surgical procedures. New treatments to directly treat and protect the retinal ganglion cells that are damaged in glaucoma are also in development.

Preimplantation genetic diagnosis (PGD) was introduced at the beginning of the 1990s as an alternative to prenatal diagnosis, to prevent termination of pregnancy in couples with a high risk for offspring affected by a sex-linked genetic disease. At that time, embryos obtained in vitro were tested to ascertain their sex, and only female embryos were transferred. Since then, techniques for genetic analysis at the single-cell level, involving assessment of first and second polar bodies from oocytes or blastomeres from cleavage-stage embryos, have evolved. Fluorescence in-situ hybridisation (FISH) has been introduced for the analysis of chromosomes and PCR for the analysis of genes in cases of monogenic diseases. In-vitro culture of embryos has also improved through the use of sequential media. Here, we provide an overview of indications for, and techniques used in, PGD, and discuss results obtained with the technique and outcomes of pregnancies. A brief review of new technologies is also included.

Cerebral palsy, a range of non-progressive syndromes of posture and motor impairment, is a common cause of disability in childhood. The disorder results from various insults to different areas within the developing nervous system, which partly explains the variability of clinical findings. Management options include physiotherapy, occupational and speech therapy, orthotics, device-assisted modalities, pharmacological intervention, and orthopaedic and neurosurgical procedures. Since 1980, modification of spasticity by means of orally administered drugs, intramuscular chemodenervation agents (alcohol, phenol, botulinum toxin A), intrathecally administered drugs (baclofen), and surgery (neurectomy, rhizotomy) has become more frequent. Family-directed use of holistic approaches for their children with cerebral palsy includes the widespread adoption of complementary and alternative therapies; however, the prevalence of their use and the cost of these options are unknown. Traditional medical techniques (physiotherapy, bracing, and orthopaedic musculoskeletal surgery) remain the mainstay of treatment strategies at this time. This seminar addresses only the musculoskeletal issues associated with cerebral palsy and only indirectly discusses the cognitive, medical, and social issues associated with this diagnosis.

Adherence difficulties and psychological problems are associated with poor glycaemic control in diabetes. We undertook a systematic review and meta-analysis of psychological therapies to assess their effectiveness in improving glycaemic control in type 2 diabetes.

Use of illicit drugs, particularly cannabis, by young people is widespread and is associated with several types of psychological and social harm. These relations might not be causal. Causal relations would suggest that recreational drug use is a substantial public health problem. Non-causal relations would suggest that harm-reduction policy based on prevention of drug use is unlikely to produce improvements in public health. Cross-sectional evidence cannot clarify questions of causality; longitudinal or interventional evidence is needed. Past reviews have generally been non-systematic, have often included cross-sectional data, and have underappreciated the extent of methodological problems associated with interpretation.

Many human diseases are the result of autoimmune attack, presumably related to a loss of tolerance to self. Autoimmune disease can be divided into either organ-specific illnesses, such as thyroid disease, type 1 diabetes, and mysasthenia gravis, or systemic illnesses, such as rheumatoid arthritis and systemic lupus erythematosus. The pathogenesis of autoimmune damage also segregates autoimmune disease in that some diseases or manifestations are mainly induced by autoantibodies. Pathogenesis may be mainly mediated by autoimmune T lymphocytes. Notwithstanding the underlying mechanism of disease, virtually all autoimmune diseases are associated with circulating autoantibodies, which bind self-protein. Furthermore, for many diseases these autoantibodies are found in serum samples many years before disease onset.

Meningiomas are by far the most common tumours arising from the meninges. Progressive enlargement of the tumour leads to focal or generalised seizure disorders or neurological deficits caused by compression of adjacent neural tissue. Surgery remains the primary treatment of choice, although the use of fractionated radiotherapy or stereotactic single-dose radiosurgery is increasing for meningiomas that are incompletely excised, surgically inaccessible, or recurrent and either atypical or anaplastic. Although most meningiomas have good long-term prognosis after treatment, there are still controversies over management in a proportion of cases. We review various features of meningioma biology, diagnosis, and treatment and provide an overview of the current rationale and evidence base for the various therapeutic approaches.

The clinically and pathophysiologically distinct entities of portopulmonary hypertension and hepatopulmonary syndrome occur in a substantial proportion of patients who have advanced liver disease of different causes. These disorders are notoriously underdiagnosed, but they have a substantial impact on survival and require focused treatment. Abnormal intrapulmonary vascular dilatation, the hallmark of hepatopulmonary syndrome, can cause profound hypoxaemia that can be very difficult to treat. By contrast, portopulmonary hypertension results from excessive pulmonary vasoconstriction and vascular remodelling that eventually leads to right-heart failure. Insights into the pathogeneses of these syndromes have led to novel therapeutic approaches. However, in severely affected patients, effective treatment remains a difficult task. In selected patients, liver transplantation represents the only treatment option, but the decision to do isolated liver transplantation is particularly challenging in patients who have severe pulmonary disease involvement. Data from several centres have contributed to provide criteria that allow improved prediction of which patients may, or may not, benefit from liver transplantation alone.

Developmental dyslexia, or specific reading disability, is a disorder in which children with normal intelligence and sensory abilities show learning deficits for reading. Substantial evidence has established its biological origin and the preponderance of phonological disorders even though important phenotypic variability and comorbidity have been recorded. Diverse theories have been proposed to account for the cognitive and neurological aspects of dyslexia. Findings of genetic studies show that different loci affect specific reading disability although a direct relation has not been established between symptoms and a given genomic locus. In both children and adults with dyslexia, results of neuroimaging studies suggest defective activity and abnormal connectivity between regions crucial for language functions--eg, the left fusiform gyrus for reading--and changes in brain activity associated with performance improvement after various remedial interventions.

Malaria accounts for 1-3 million deaths yearly worldwide, mostly in children under 5 years of age in sub-Saharan Africa. Laboratory and clinical studies show an association between acute malaria and a decreased response to diphtheria and tetanus toxoids and to meningococcal, salmonella, and Haemophilus influenzae type b vaccinations. Malaria treatment, chemoprophylaxis, or other forms of parasite suppression might improve the immune response to childhood vaccinations. However, the antimalarial 4-aminoquinolones are immunodepressive, such that antimalarial drugs might depress the vaccine response.

Osteogenesis imperfecta is a genetic disorder of increased bone fragility, low bone mass, and other connective-tissue manifestations. The most frequently used classification outlines four clinical types, which we have expanded to seven distinct types. In most patients the disorder is caused by mutations in one of the two genes encoding collagen type 1, but in some individuals no such mutations are detectable. The most important therapeutic advance is the introduction of bisphosphonate treatment for moderate to severe forms of osteogenesis imperfecta. However, at present, the best treatment regimen and the long-term outcomes of bisphosphonate therapy are unknown. Although this treatment does not constitute a cure, it is an adjunct to physiotherapy, rehabilitation, and orthopaedic care. Gene-based therapy presently remains in the early stages of preclinical research.

Insulin-like growth factor (IGF)-I and its main binding protein, IGFBP-3, modulate cell growth and survival, and are thought to be important in tumour development. Circulating concentrations of IGF-I might be associated with an increased risk of cancer, whereas IGFBP-3 concentrations could be associated with a decreased cancer risk.

Questions concerning the safety of selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression in children led us to compare and contrast published and unpublished data on the risks and benefits of these drugs.

Research into myocardial regeneration has an exciting future, shown by the results of experimental and clinical work challenging the dogma that the heart is a postmitotic non-regenerating organ. Such studies have initiated a lively debate about the feasibility of novel treatment approaches leading to the recovery of damaged myocardial tissue. The possibility of reconstituting dead myocardium by endogenous cardiomyocyte replication, transplantation, or activation of stem cells--or even cloning of an artificial heart--is being advanced, and will be a major subject of future research. Although health expenditure for heart failure in the industrial world is high, we are still a long way from being able to treat the cause of reduced myocardial contractility. Despite the hopes of some people, conventional treatment for heart failure does not achieve myocardial regeneration. We present a virtual case report of a patient with acute myocardial infarction; we discuss treatment options, including strategies aimed at organ regeneration.

Pulmonary embolism (PE) is a common illness that can cause death and disability. It is difficult to detect because patients present with a wide array of symptoms and signs. The clinical setting can raise suspicion, and certain inherited and acquired risk factors predispose susceptible individuals. D-dimer concentration in blood is the best laboratory screening test, and chest CT has become the most widespread imaging test. Treatment requires rapid and accurate risk stratification before haemodynamic decompensation and the development of cardiogenic shock. Anticoagulation is the foundation of therapy. Right-ventricular dysfunction on echocardiography and higher than normal concentrations of troponin identify high-risk patients who might need escalation of therapy with thrombolysis or embolectomy even if the blood pressure is normal on presentation. When patients are admitted to medical wards or when patients undergo surgery, their physicians should prescribe prophylactic measures to prevent PE. After hospital discharge, prophylaxis should continue for about a month for patients at high risk of thromboembolism.

Membrane-protein ion channels control electrical activity in the nervous system. Voltage-gated channels have four-fold symmetry, with a central pore domain surrounded by voltage-sensor regions. Each voltage-sensor region has a positively charged transmembrane helix, S4, which carries gating charges through the membrane on opening or closing. How S4 moves at gating is debated: either S4 moves in a helical screw or in a helical twist pattern. In both cases S4 is assumed to move inside the densely packed channel protein. The pore region was visualised when Roderick MacKinnon's group crystallised a bacterial K+ channel in 1998. The voltage-sensor region and the S4 movement are more difficult to visualise, because voltage-gated channels are harder to crystallise.

Leprosy remains an important health problem worldwide. The disease is caused by a chronic granulomatous infection of the skin and peripheral nerves with Mycobacterium leprae. The clinical range from tuberculoid to lepromatous leprosy is a result of variation in the cellular immune response to the mycobacterium. The resulting impairment of nerve function causes the disabilities associated with leprosy. This review summarises recent advances in understanding of the biology of leprosy, clinical features of the disease, the current diagnostic criteria, and the new approaches to treatment of the infection and the immune-mediated complications. Supervised multi-drug therapy (MDT) for fixed durations is highly effective for all forms of the disease. The widespread implementation of MDT has been associated with a fall in the prevalence of the leprosy but as yet no reduction in the case-detection rate globally. Thus, leprosy control activities must be maintained for decades to interrupt transmission of infection.

Migraine is a very common neurobiological headache disorder that is caused by increased excitability of the CNS. It ranks among the world's most disabling medical illnesses. Diagnosis is based on the headache's characteristics and associated symptoms. The economic and societal effect of migraine is substantial: it affects patients' quality of life and impairs work, social activities, and family life. There are many acute and preventive migraine treatments. Acute treatment is either specific (triptans and ergots) or non-specific (analgesics). Disabling migraine should be treated with triptans. Increased headache frequency is an indication for preventive treatment. Preventive treatment decreases migraine frequency and improves quality of life. More treatments are being developed, which provides hope to the many patients whose migraines remain uncontrolled.

Stroke-unit care can be valuable for stroke patients in hospital, but effectiveness of outpatient care is less certain. We aimed to assess the effects of therapy-based rehabilitation services targeted at stroke patients resident in the community within 1 year of stroke onset or discharge from hospital.

Late-onset sporadic Alzheimer's disease is a heterogeneous disorder. In elderly patients, increasing evidence suggests a link between this neurodegenerative disease, and vascular risk factors and atherosclerosis. The nature of this link remains speculative. Some investigators have suggested that the disease arises as a secondary event related to atherosclerosis of extracranial or intracranial vessels. A toxic effect of vascular factors on the microvasculature of susceptible brain regions has also been argued. An alternative explanation is that atherosclerosis and Alzheimer's disease are independent but convergent disease processes. This hypothesis is lent support by observations of shared epidemiology, pathophysiological elements, and response to treatment in both disorders. It provides a potential framework for an improved understanding of the pathogenesis of Alzheimer's disease, especially in elderly patients with vascular risk factors, and offers some promise toward the search for preventive and therapeutic treatments.