Many studies have shown that screening for breast cancer can reduce mortality from the disease. Mammography has come to be regarded as the screening method of choice, but evidence suggests that physical examination (PE) is at least as effective in reducing mortality. Mammography detects many non-infiltrating and small, non-palpable tumours, but we do not know whether these would ever cause symptoms or threaten the woman's life. It is doubtful whether the time gained by early mammographic detection confers any survival benefit over PE detection. PE has substantial advantages over mammography in terms of human and economic costs. The question we should be asking is not how to refine mammographic screening but whether we need it at all.

The characteristic pathophysiological changes in pre-eclampsia are thought to be related to abnormalities of the maternal vascular endothelium. We suggest that the blood components that affect the risk of such damage are very-low-density lipoproteins (VLDL), which injure the endothelium, and toxicity-preventing activity (the pl 5.6 form of plasma albumin), which protects against VLDL-induced injury.

The Epstein-Barr virus (EBV) has been implicated in the aetiology of many human lymphoid and epithelial malignancies. Although EBV is B lymphotropic in vitro, it has been hypothesised that oropharyngeal epithelium is important in primary EBV infection, replication, and persistence in vivo, and that infection of B lymphocytes is secondary. This hypothesis has been challenged by several recent studies. On the basis of current evidence, we propose that primary EBV infection and virus persistence are mediated through B lymphocytes, and that latent infection of epithelial cells is accidental and irrelevant to virus persistence, although important in the development of certain carcinomas. To what extent T cells are involved in EBV persistence remains uncertain. Clarification of the possible part played by EBV in the development of virus-associated tumours requires a better understanding of the mode of EBV persistence and the identification of the stage in the carcinogenic process at which EBV infection occurs.

Large randomised trials have demonstrated that fibrinolytic therapy can reduce mortality in patients with suspected acute myocardial infarction (AMI). The indications for, and contraindications to, this treatment in some categories of patient are disputed, examples being late presentation, elderly patients, and those in cardiogenic shock. This overview aims to help resolve some of the remaining uncertainties. From all trials of fibrinolytic therapy versus control that randomised more than 1000 patients with suspected AMI, information was sought and checked on deaths during the first 5 weeks and on major adverse events occurring during hospitalisation. The nine trials included 58,600 patients, among whom 6177 (10.5%) deaths, 564 (1.0%) strokes, and 436 (0.7%) major non-cerebral bleeds were reported. Fibrinolytic therapy was associated with an excess of deaths during days 0-1 (especially among patients presenting more than 12 h after symptom onset, and in the elderly) but this was outweighed by a much larger benefit during days 2-35. This "early hazard" should not obscure the very clear overall survival advantage that is produced by fibrinolytic therapy. Benefit was observed among patients presenting with ST elevation or bundle-branch block (BBB)--irrespective of age, sex, blood pressure, heart rate, or previous history of myocardial infarction or diabetes--and was greater the earlier treatment began. Among the 45,000 patients presenting with ST elevation or BBB the relation between benefit and delay from symptom onset indicated highly significant absolute mortality reductions of about 30 per 1000 for those presenting within 0-6 h and of about 20 per 1000 for those presenting 7-12 h from onset, and a statistically uncertain benefit of about 10 per 1000 for those presenting at 13-18 h (with more randomised evidence needed in this latter group to assess reliably the net effects of treatment). Fibrinolytic therapy was associated with about 4 extra strokes per 1000 during days 0-1: of these, 2 were associated with early death and so were already accounted for in the overall mortality reduction, 1 was moderately or severely disabling, and 1 was not. This overview indicates that fibrinolytic therapy is beneficial in a much wider range of patients than is currently given such treatment routinely.

Adult T-cell leukaemia (ATL) was first reported in Japan, where it has a high incidence in the southwest region. The retrovirus human T-lymphotropic virus type I (HTLV-I) is the cause of ATL; and in ATL-endemic areas, the rate of carriage of antibodies to HTLV-I is high. A definite diagnosis of ATL is based on the presence of HTLV-I proviral DNA in the tumour-cell DNA. ATL cells originate from the CD4 subset of peripheral T cells. ATL shows diverse clinical features but can be divided into four subtypes--acute, chronic, smouldering, and lymphoma type. It is resistant to chemotherapy, and the acute and lymphoma types have a poor prognosis. Familial occurrence of ATL is common. HTLV-I infection is caused by transmission of live infected lymphocytes from mother to child, from man to woman, or by transfusion. Infection with HTLV-I can lead to other diseases, including HTLV-I-associated myelopathy/tropical spastic paraparesis and HTLV-I uveitis, possibly via induction of immunodeficiency or hyperreactivity against HTLV-I-infected cells.

Evidence for the utilisation of substrates by the ischaemic myocardium and its dependence for viability on a critical supply of glucose was established many years ago. It was recognised that an excess of free fatty acids (FFA) could increase the severity of ischaemic damage and possibly be arrhythmogenic. But metabolic intervention to improve survival during acute myocardial infarction was not regarded as a priority, perhaps because of uncertainty about its value and the advent of trials of beta-blocker and antiarrhythmic drugs. There has never been an adequate trial of the benefit to the ischaemic or infarcting myocardium of increasing local glucose concentrations or reducing the availability of FFA. We have taken into account new knowledge of the effects of fatty acids on cation channels and brought up to date the arguments for metabolic intervention with glucose-insulin solutions or antilipolytic drugs sustained ischaemia.

The recommended approach to the increased risk of colorectal carcinoma in ulcerative colitis has been colonoscopic surveillance rather than prophylactic colectomy. This strategy is based on the assumption that dysplastic lesions can be detected before invasive cancer has developed. We have analysed published reports on dysplasia surveillance to find out whether this assumption is valid. Ten prospective studies (1225 patients) satisfied our criteria. Of 40 patients with dysplasia-associated mass or lesion (DALM) detected, 17 (43%) already had cancer at immediate colectomy. The risks of cancer at immediate colectomy were 42% (10 of 24 patients) for high-grade and 19% (3 of 16) for low-grade dysplasia. Of 47 patients found to have high-grade dysplasia after the initial colonoscopy, 15 (32%) had cancer. 16-29% of patients with untreated low-grade dysplasia progressed to DALM, high-grade dysplasia, or cancer. Of patients with indefinite results, 28% progressed to high-grade dysplasia and 9% to cancer, so continued surveillance is essential. The risk of progression to dysplasia was only 2.4% for patients whose initial result was negative, so surveillance could perhaps be less frequent for these patients. Immediate colectomy is essential for all patients diagnosed with high-grade or low-grade dysplasia. A diagnosis of dysplasia does not preclude the presence of invasive cancer. We believe that patients should be informed about the limitations of colonoscopic surveillance so that they can take part rationally in decision-making about their management.

Any hypothesis on the cause of ulcerative colitis must account for genetic influences, geographic and ethnic variations, effects of smoking and oral contraception, anatomical distribution, the relapsing and remitting nature of the disease, and association with primary sclerosing cholangitis. This hypothesis proposes that ulcerative colitis is caused by a reactive xenobiotic metabolite which is conjugated before excretion into bile. The amount of metabolite produced is determined by exposure to its parent compound, by the inherited pattern of metabolism, and by inhibition and induction of enzymes catalysing alternative pathways. Deconjugation by bacteria within the colonic lumen releases the reactive metabolite, damaging the colonic epithelial barrier and exposing the mucosal immune system to luminal contents. Biliary epithelial damage by the metabolite leads to an immune response in those individuals carrying appropriate HLA molecules, thereby initiating an inflammatory process within the biliary tree.

Although 4000 pancreas transplants have now been done, alone or in combination with a kidney transplant, the risk/benefit profile of the procedure has not been established by controlled studies. A solo pancreas transplant abolishes the need for daily insulin but requires chronic immunosuppression, has high failure rates, and is not proved to lessen the chronic complications of diabetes. Thus, it is probably justified only in those diabetic patients with incapacitating disease. For uraemic diabetic patients, combined pancreas and kidney transplantation often removes dependence on both insulin and dialysis, and has lower rejection rates than pancreas transplant alone. However, it needs more immunosuppression than kidney transplant alone, has no proven benefit on chronic complications of diabetes, and carries an increased risk of rejection, infection, and cancer. Living-related-donor kidney transplantation followed by cadaver pancreas transplantation is a possible alternative. Transplantation of pancreatic islets could offer the advantages of strict metabolic control without the drawbacks of immunosuppressive therapy. Thus, research efforts should concentrate on immune-protected islet transplantation. An alternative approach to avoiding long-term immunosuppression is the promotion of allograft tolerance.

Chinese herbal medicines (CHM) and Chinese proprietary medicines (CPM) are widely used by people of Chinese origin throughout the world. Although the use of these medicinal materials rarely causes significant toxic effects, cases of severe and even fatal poisoning have occurred after medication with herbs containing aconitine, podophyllin, and anticholinergic substances. Furthermore, CHM and CPM are often adulterated with substituted herbs, heavy metals, and western medicines; such contamination can have important clinical consequences. In Hong Kong, surveillance and legislation are required to control the use of some of these herbal preparations. In other countries, medical practitioners should also be aware of the possibility that these herbal-medicine-related remedies may cause significant clinical problems in their Chinese patients.