The differential diagnosis of glomerulonephritis without systemic disease includes poststreptococcal glomerulonephritis, IgA nephropathy, rapidly progressive glomerulonephritis (RPGN), and membranoproliferative glomerulonephritis (MPGN). Glomerular inflammation is probably induced directly by a nephritogenic streptococcal protein in poststreptococcal glomerulonephritis, and by mesangial deposition of abnormally glycosylated IgA1-containing immune aggregates in IgA nephropathy. In crescentic RPGN the role of cellular rather than humoral immune mechanisms is now becoming clear. Many patients with MPGN have chronic hepatitis C infection. There is no effective disease-specific therapy for poststreptococcal glomerulonephritis or IgA nephropathy. RPGN benefits from high-dose steroids and cytotoxic drug therapy with the addition of plasma exchange in disease induced by antibody to glomerular basement membrane. Antiviral therapies reduce the severity of MPGN due to hepatitis C virus. However, various new therapies directed at specific cytokines, growth factors, fibrin deposition, and other mediators of injury are being developed, as well as more specific and less toxic forms of immunotherapy.

The development of new antithrombotic agents has been stimulated by clinical needs and by advances in biotechnology that have made it possible to produce drugs that target specific steps in thrombogenesis. Heparin has pharmacokinetic and biophysical limitations that are overcome by new anticoagulants. Of these, low-molecular-weight heparin and direct inhibitors of thrombin have been evaluated clinically. Coumarins require careful laboratory monitoring because of concerns about safety. Orally active direct inhibitors of thrombin and factor Xa may replace coumarins. Aspirin is of limited efficacy because it inhibits only one pathway of platelet activation. Inhibitors of adenosine diphosphate receptor and glycoprotein IIb/IIIa antagonists are more effective than aspirin and are used in the clinic.

Schizophrenia is among the most severe and debilitating of psychiatric disorders. Diagnosis is currently by criterion-based systems, including positive (eg, hallucinations and delusions) and negative (eg, avolition and alogia) symptoms. The importance of negative symptoms in the course and outcome of the illness is increasingly being studied. Current research seeks to detect causal mechanisms in schizophrenia through studies of neural connectivity and function, as well as models of genetic transmission, such as polygenic models of inheritance in genetic research. Potential genes have been identified that may confer vulnerability to the illness, perhaps in conjunction with environmental factors. Neuroimaging research with magnetic resonance imaging and positron emission tomography has investigated differences in volumes and functional dysregulation in specific neural subregions. Areas studied include the frontal and temporal cortex, the hippocampus, the thalamus, and the cerebellum. Despite these advances, treatment of symptoms and psychosocial and cognitive impairments remains only partially successful for many patients.

Antiphospholipid antibodies are associated with arterial and venous thrombosis, recurrent pregnancy loss, and thrombocytopenia. Although the antibodies have not been conclusively shown to be causal in thrombosis and miscarriage, they are useful laboratory markers for the antiphospholipid syndrome. The identification of the syndrome is clinically important because of the risk of recurrent thrombosis and the need for antithrombotic therapy in many cases. Diagnosis and treatment of antiphospholipid syndrome is difficult, however, because of the protean clinical manifestations and associations, limitations of existing laboratory tests for antiphospholipid antibodies, and the absence of evidence-based guidance on best management.

Hypertension with hypokalaemia and suppression of plasma renin activity is known as mineralocorticoid hypertension. Although mineralocorticoid hypertension accounts for a small number of patients labelled as having "essential" hypertension, it is a potentially reversible cause of high blood pressure. The most common cause of mineralocorticoid hypertension is probably primary aldosteronism; controlled posture studies to measure plasma renin activity and aldosterone concentrations, followed by adrenal imaging, will ensure the differential diagnosis between an aldosterone-producing adenoma and idiopathic adrenal hyperplasia in most cases. Three monogenic forms of mineralocorticoid hypertension have been described: glucocorticoid-suppressible hyperaldosteronism, Liddle's syndrome, and apparent mineralocorticoid excess, which have provided new insights into mineralocorticoid hormone action. Many patients with mineralocorticoid-based hypertension are now known to have normal serum potassium concentrations. Until the true prevalence of primary aldosteronism and monogenic forms of mineralocorticoid hypertension are defined, a high index of suspicion is needed in every hypertensive patient. Hypertensive patients with hypokalaemia, together with those with severe hypertension or a family history of hypertension or stroke, should be screened for mineralocorticoid excess.

Pulmonary thromboembolism is the main cause of maternal death in the UK and current trends show an increase. Deep-vein thrombosis underlies this disorder. Important issues include pathophysiology, diagnosis, and management of thrombosis in pregnancy, especially the use of anticoagulants. Congenital and acquired thrombophilias contribute to the pathophysiological processes that underlie miscarriage, intrauterine growth restriction, and pre-eclampsia, and raises new possibilities for intervention. The high prevalence of thrombophilic defects in the population, the association of defects with maternal and fetal disorders, and special considerations for management make it essential for obstetricians to understand this area.

Hepatocellular carcinoma (HCC) for most patients is a terminal complication of chronic inflammatory and fibrotic liver disease. With regrettably few exceptions, treatment is largely palliative, and long-term survival is rare. However, the major causes of HCC worldwide are known and preventable. Hepatitis B and C exist only in man; the viruses have no known non-human reservoirs. Transmission of the viruses can be interrupted by vaccination against hepatitis B virus infection and improvements in medical techniques for hepatitis C, for which no vaccine has yet been developed.

The risk factors for venous thrombosis differ from those for arterial vascular disease. During the past 5 years, knowledge about the aetiology of venous thrombosis has advanced with the discovery of several factors that contribute to the incidence of thrombosis, particularly the role of coagulation abnormalities. These abnormalities are common in the general population and therefore will be present simultaneously in some individuals. The resultant gene-gene and gene-environment interactions between risk factors are the key to the understanding of why a certain person develops thrombosis at a specific point in time.

Delayed presentation of symptomatic breast cancer is associated with lower survival. Understanding of the factors that influence delay is important for the development of strategies to shorten delays. We did a systematic review to assess the quality and strength of evidence on risk factors for delays by patients and providers.

Most patients with breast cancer are detected after symptoms occur rather than through screening. The impact on survival of delays between the onset of symptoms and the start of treatment is controversial and cannot be studied in randomised controlled trials. We did a systematic review of observational studies (worldwide) of duration of symptoms and survival.