Cardiovascular disease is the main cause of death in virtually all industrialised countries. The limited information available from developing countries suggests that a similar epidemic is inevitable if current trends go unchecked. Treatment of patients with clinical manifestations is an important element in overall management but on its own is an insufficient and incomplete response. Sudden death is often the first manifestation of cardiovascular disease and, even when treatment of disease is applicable and effective, it is usually palliative rather than curative. Thus treatment and prevention directed at the underlying risk factors, including high blood pressure, constitute a complementary and more fundamental approach to reducing the burden of illness. Epidemiological studies provide the scientific foundation for such an approach by identifying the distribution and determinants of high blood pressure in the general population, by establishing the role of high blood pressure as a risk factor for cardiorenal complications, and by quantifying the potential value of treating and preventing high blood pressure in the general population.

Dehydroepiandrosterone (DHEA), with its sulphate conjugate (DHEAS), is the most abundant steroid hormone in the circulation but its physiological importance is unclear. We propose that DHEA has either oestrogen-like or androgen-like effects depending on the hormonal milieu. In premenopausal women DHEA is either an oestrogen antagonist, perhaps through the competitive binding of its metabolite 5-androstene-3 beta, 17 beta-diol (ADIOL) and oestradiol to the oestrogen receptor, or an androgen through its metabolism to androstenedione and testosterone. In women DHEA contributes to abdominal obesity and insulin resistance: in the premenopausal high oestrogen concentrations may counterbalance the androgenic effects of DHEA but in the postmenopausal metabolism to testosterone may increase the risk of cardiovascular disease, though this effect may be counterbalanced by the age-dependent decline in DHEA and also by the oestradiol-like effects of ADIOL. In some breast cancer cell lines in a low oestrogen milieu DHEA has an oestradiol-like effect, stimulating tumour growth, whereas in oestradiol abundance DHEA antagonises the growth-stimulating effect of oestradiol. In men, with an androgenic milieu, DHEA acts like an oestrogen and protects against cardiovascular disease.

The epidemic of coronary heart disease in the western world followed the introduction of partially hydrogenated fats in food. Exposure to trans fatty acids (TFA) in those foods can explain the observed sex and age differences in serum cholesterol concentrations and coronary heart disease (CHD), the cholesterolaemic response to pregnancy, and national differences in rates of CHD. There is evidence that TFA can be innocuously used for muscular work. I propose that the TFA in partially hydrogenated fats impair lipoprotein receptors during energy surfeit, leading to hypercholesterolaemia, atherogenesis, obesity, and insulin resistance. A series of feasible experiments is proposed to examine this hypothesis.

In the past ten years several research fields have converged to show that the tiny molecule nitric oxide (NO), a reactive gas, functions both as a signalling molecule in endothelial and nerve cells and as a killer molecule by activated immune cells--and it can be used as a new medicine by inhalation. This article reviews the biology of this remarkable molecule and discusses the implications for clinical medicine.

The role of specific human papillomaviruses (HPVs) in the aetiology of cancer of the cervix is firmly established. Progression of an HPV-infected cell clone to invasive growth involves consecutive modifications of a set of host cell genes. Some of these modifications suppress viral oncogene functions post-transcriptionally, and others suppress transcription via a signalling pathway stimulated by activated macrophages and possibly by additional cells. I describe a scheme that tries to unify available data by postulating the existence of two intracellular signalling pathways in the control of latent HPV infections.

The USA and the UK have differed substantially in approaches to health care and especially in intensive care provision. We have compared the health care systems, clinical justification for intensive care, selection of patients likely to benefit from such care, and the performance of the systems. The differences are lessening. Both countries are moving away from clinical autonomy as the driving force of medical decision-making. There is increasing recognition that not all patients will benefit from intensive care and that the doctor's obligation to the patient can be limited by constraints set by society.