Mounting evidence suggests that the early dissemination of HIV in human beings evokes an immune response that is responsible for containment of the infection during the long symptom-free period. Loss of this immune control coincides with a final escalation of the viraemia and the terminal failure of the immune system. Other studies imply that pre-emptive vaccination of monkeys with attenuated forms of simian immunodeficiency virus (SIV) produces a substantial degree of resistance to superinfection with fully virulent viruses. Here we consider how observations from natural and experimental systems might influence thought as to what is required to produce safe induced immunity against HIV. We concentrate on three questions: what is the nature of the immune response that contains the infection? How does this response fail? How could a vaccine enhance protective immunity so that it exceeds the efficacy of this natural response?

Rotaviruses are responsible for more diarrhoeal disease-associated mortality than any other single agent. Vaccination may therefore hold the key to combating diarrhoeal disease worldwide. Natural immunity to rotavirus infection indicates that rather than protection from reinfection such immunity gives rise to less severe and less frequent attacks of diarrhoea. Early attempts to design a rotavirus vaccine with bovine rotavirus failed because of poor efficacy in some developing countries. Research into rhesus rotavirus, particularly the high-titre rhesus rotavirus tetravalent (RRV-TV) vaccine, has given slightly better results. A stumbling block to truly effective oral vaccines seems to be immunogenicity in developing countries. If efficacy can be ensured by trials in the developing countries, money spent on rotavirus vaccines will be well spent.

Silicone-gel-filled breast implants have been widely used for breast augmentation and reconstruction after mastectomy. The rate of implant rupture and its sequelae are not known. We review the frequency, causes, sequelae, and detection of implant rupture. Materials testing of removed implants provides evidence that as implants age in vivo, they weaken and may rupture. Sequelae of rupture include migration of gel accompanied by inflammation and silicone granuloma formation. The role of free silicone gel in relation to idiopathic or atypical connective tissue disease is not clear. Magnetic resonance imaging is substantially more sensitive in the detection of rupture than is mammography or ultrasonography.

A major challenge for vaccine design and development, and for trials of new vaccines, is to tackle antigenically variable infectious agents. Here we outline a few general conceptual issues and then discuss new frameworks that are being developed to help understand how vaccination might change the distribution, abundance, and type of strains in a population. Herd Immunity is a key concept in population-based immunisation programmes and has to be considered in vaccine design and use even though it may cause a conflict between the needs of the individual versus those of the community. This issue is of increasing importance since once common infections are becoming rare due to effective vaccination. Concomitantly, adverse effects arising from immunisation are becoming more apparent as infection-induced morbidity declines to very low levels. Efficacy is widely regarded as a key criterion in vaccine design but duration of protection is of equal importance. Whether it is possible to produce effective vaccines to antigenically diverse pathogens remains uncertain but progress towards this goal will be enhanced by a better understanding of the population genetics of the target infectious agent facilitated by molecular epidemiological studies to assess the genetic constitution of pathogen populations and changes therein over time.

The development, implementation, and continued use of new vaccines depends on several factors. Although disease burden seems like an obvious quantitative measure for setting priorities for new vaccine development and use, resources are not always allocated proportionately. This is particularly evident for diseases that are unique (or largely limited) to people in developing countries. Public pressure based on perceptions of the risks associated with a disease or vaccine, the cost of new vaccines, and the ability to incorporate them into existing vaccination programmes also need to be considered in the decision to introduce new vaccines. Vaccine manufacturers play an important part in development of new vaccines, and therefore, the issues that are important to them, namely, production, intellectual property rights, and product liability, must be addressed. By advocating rational decisions, supported by accurate information, scientists and public-health professionals can have an important role in transforming the potential of new vaccines into the reality of new vaccine-preventable diseases.

Most public-health assessments of climate-control policies have focused on long-term impacts of global change. Our interdisciplinary working group assesses likely short-term impacts on public health.

The first abnormality leading to sodium and water retention in cirrhosis is the renal tubular defect that is related to deteriorating liver function and hyperaldosteronism. With progression of liver disease and portal hypertension, renal blood flow declines because of the hepatorenal reflex, and is then maintained by the vasoactive hormonal systems. With increasing peripheral vasodilatation, intrarenal factors for maintenance of renal perfusion cause intense cortical vasoconstriction. The systemic vasoactive factors are predominantly compensatory; any attempts to counteract their action risk circulatory collapse. Future studies should be directed at intrarenal factors. The ideal drug for the treatment of portal hypertension would reduce portal pressure, increase renal blood flow, and produce insignificant changes in arterial pressure.

There is much evidence that people who had low birthweight tend to have higher blood pressure in later life. However, the mechanisms that mediate this relation are unknown. We argue that, in fetuses whose growth is impaired, synthesis of elastin in the walls of the aorta and large arteries may be deficient, and that this deficiency would lead to permanent changes in the mechanical properties of these vessels. Over a lifetime, such changes could predispose an individual to higher blood pressure, increased left-ventricular mass, and cardiovascular disease.