It is too soon for a verdict on the health risks from cellular telephones, especially in view of changing technology. From the Interphone project and some other large studies in progress, better information may emerge. Based on the epidemiological evidence available now, the main public-health concern is clearly motor vehicle collisions, a behavioural effect rather than an effect of radiofrequency exposure as such. Neither the several studies of occupational exposure to radiofrequencies nor the few of cellular telephone users offer any clear evidence of an association with brain tumours or other malignancies. Even if the studies in progress were to find large relative effects for brain cancer, the absolute increase in risk would probably be much smaller than the risk stemming from motor vehicle collisions. Cellular telephones affect the quality of our lives in myriad ways, for good and ill; the health risk is just one part of a picture that is slowly coming into focus.

Although safety guidelines--to which mobile telephones and their base-stations conform--do protect against excessive microwave heating, there is evidence that the low intensity, pulsed radiation currently used can exert subtle non-thermal influences. If these influences entail adverse health consequences, current guidelines would be inadequate. This review will focus on this possibility. The radiation used is indeed of very low intensity, but an oscillatory similitude between this pulsed microwave radiation and certain electrochemical activities of the living human being should prompt concern. However, being so inherently dependent on aliveness, non-thermal effects cannot be expected to be as robust as thermal ones, as is indeed found; nor can everyone be expected to be affected in the same way by exposure to the same radiation. Notwithstanding uncertainty about whether the non-thermal influences reported do adversely affect health, there are consistencies between some of these effects and the neurological problems reported by some mobile-telephone users and people exposed longterm to base-station radiation. These should be pointers for future research.

Proteomics-based approaches, which examine the expressed proteins of a tissue or cell type, complement the genome initiatives and are increasingly being used to address biomedical questions. Proteins are the main functional output, and the genetic code cannot always indicate which proteins are expressed, in what quantity, and in what form. For example, post-translational modifications of proteins, such as phosphorylation or glycosylation, are very important in determining protein function. Similarly, the effects of environmental factors or multigenic processes such as ageing or disease cannot be assessed simply by examination of the genome alone. This review describes the underlying technology and illustrates several areas of biomedical research, ranging from pathogenesis of neurological disorders to drug and vaccine design, in which potential clinical applications are being explored.

Polymorphisms in the genes that code for drug-metabolising enzymes, drug transporters, drug receptors, and ion channels can affect an individual's risk of having an adverse drug reaction, or can alter the efficacy of drug treatment in that individual. Mutant alleles at a single gene locus are the best studied individual risk factors for adverse drug reactions, and include many genes coding for drug-metabolising enzymes. These genetic polymorphisms of drug metabolism produce the phenotypes of "poor metabolisers" or "ultrarapid metabolisers" of numerous drugs. Together, such phenotypes make up a substantial proportion of the population. Pharmacogenomic techniques allow efficient analysis of these risk factors, and genotyping tests have the potential to optimise drug therapy in the future.

No one can question the remarkable contribution of US public health to understanding the causes and consequences of illness, disability, and death. However, some commentators question the agenda: the endless pursuit of individual risk factors and the cursory attention to social determinants of disease. We attempt to illustrate some limitations of US public health by focusing on type-2 diabetes (adult-onset non-insulin-dependent diabetes)--an increasingly prevalent but still poorly understood medical condition with devastating complications and implications for quality of life. A more theoretically based multilevel approach to diabetes, outlined for the 21st century, has an almost exclusive downstream curative focus, that ranges from midstream preventive programmes to upstream healthy public policy.

Cardiogenic shock remains the major cause of death among patients with all types of acute coronary syndromes. Thus, there is a growing interest in the identification of patients who are at risk for developing cardiogenic shock, in the exploration of different therapeutic approaches to preventing its development, and in the improvement of outcome when it occurs. This article reviews the aetiology and pathophysiology of cardiogenic shock, its epidemiology, its treatment (including pharmaceutical agents, counterpulsation, and revascularisation), and its outcome. Algorithms are presented that predict its occurrence in both ST-segment-elevation myocardial infarction and unstable angina or non-ST-elevation myocardial infarction, and that predict its mortality in patients with ST-segment-elevation acute myocardial infarction. Such new areas as metabolic therapy and glycoprotein IIb/IIIa inhibitors are discussed, as are the economic implications of shock.

Idiosyncratic drug reactions are unpredictable reactions that can result in significant morbidity and mortality. Severe reactions are often characterised by fever and internal organ involvement. Despite progress in the identification of reactive metabolites believed to be the cause of idiosyncratic reactions, the basic mechanisms remain elusive. Furthermore, because of the lack of consensus regarding definition of these syndromes, reporting, and therefore epidemiological data, are often unreliable. Research is needed to explore further the pathophysiology of these reactions, so that better diagnostic tests and treatment methods can be developed.

Adverse reactions are a potential concern for physicians when they prescribe or recommend drugs. Epidemiological principles, when combined with clinical judgment, can be of help in this situation, starting with an appreciation of the strengths and weaknesses of different sources of information on adverse reactions--clinical trials, case reports, and formal epidemiological studies. The latter studies generally provide the most comprehensive information on the risks of serious adverse drug reactions. An understanding of the different types of risk estimates, relative and absolute, is also needed--we stress the value of the absolute risk as the best measure of the impact of an adverse reaction. Rare serious reactions, although striking, have little impact on individual risk, whereas more common reactions, even with much lower fatality rates, are more likely to lead to adverse outcomes for patients. The importance of balancing risks and benefits, taking into account all the information about an individual patient's risk profile, is also highlighted.

Pre-eclampsia is associated with significant morbidity and mortality for mother and baby, but it resolves completely post partum. Despite a steady reduction in maternal mortality from the disorder in more developed countries, it remains one of the most common reasons for a woman to die during pregnancy. The disorder starts with a placental trigger followed by a maternal systemic response. Because both this systemic response and the woman's reaction to it are inconsistent, the clinical presentation varies in time and substance, with many different organ systems affected. With the increasing understanding of the disease process, there have been advances in management, such as antihypertensive therapy, magnesium sulphate, and fluid restriction.

Epilepsy is the most common serious neurological disorder affecting an estimated 50 million people worldwide. Particular focus should be placed on a safe diagnosis, seizure and syndrome classification, and choice of pharmacological and surgical options for a range of patient populations with different health-care requirements. Eight new antiepileptic drugs were licensed in the 1990s with more to come. These new drugs along with earlier resective surgery have led to a better outcome for many more people with this condition.

Antiretroviral toxicity is an increasingly important issue in the management of HIV-infected patients. With the sustained major declines in opportunistic complications, HIV infection is a more chronic disease, and so more drugs are being used in more patients for longer periods. This review focuses on the pathogenesis, clinical features, and management of the principal toxicities of the 15 licensed antiretroviral drugs, including mitochondrial toxicity, hypersensitivity, and lipodystrophy, as well as more drug-specific adverse effects and special clinical settings.

Concern about upper-genital-tract infection related to intrauterine devices (IUDs) limits their wider use. In this systematic review I summarise the evidence concerning IUD-associated infection and infertility. Choice of an inappropriate comparison group, overdiagnosis of salpingitis in IUD users, and inability to control for the confounding effects of sexual behaviour have exaggerated the apparent risk. Women with symptomless gonorrhoea or chlamydial infection having an IUD inserted have a higher risk of salpingitis than do uninfected women having an IUD inserted; however, the risk appears similar to that of infected women not having an IUD inserted. A cohort study of HIV-positive women using a copper IUD suggests that there is no significant increase in the risk of complications or viral shedding. Similarly, fair evidence indicates no important effect of IUD use on tubal infertility. Contemporary IUDs rival tubal sterilisation in efficacy and are much safer than previously thought.

The effectiveness of surgery for colorectal cancer depends on it being carried out safely, which allows most patients to return to productive lives, with an improved postoperative life expectancy, or at least one that is not diminished by the surgery. Because colorectal cancer is a major cause of morbidity and mortality in elderly people, we have examined how the outcomes of surgery in elderly patients differ from those in younger patients.

The advent of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) has revolutionised the treatment of hypercholesterolaemia. Statin treatment, by lowering the atherogenic lipoprotein profile, reduces morbidity and mortality in patients with cardiovascular disease. Treatment with simvastatin causes a reduction of events of new-onset heart failure, but this may be attributable to properties other than its lipid-lowering effects. There is some evidence that lower serum cholesterol concentrations (as a surrogate for the totality of lipoproteins) relate to impaired survival in patients with chronic heart failure (CHF). Inflammation is a feature in patients with CHF and increased lipopolysaccharide may contribute substantially. We postulate that higher concentrations of total cholesterol are beneficial in these patients. This is potentially attributable to the property of lipoproteins to bind lipopolysaccharide, thereby preventing its detrimental effects. We hypothesise there is an optimum lipoprotein concentration below which lipid reduction would, on balance, be detrimental. We also propose that, in patients with CHF, a non-lipid-lowering statin (with ancillary properties such as immune modulatory and anti-inflammatory actions) could be as effective or even more beneficial than a lipid-lowering statin.

The decrease in mortality and improved outcome for patients with severe traumatic brain injury over the past 25 years can be attributed to the approach of "squeezing oxygenated blood through a swollen brain". Quantification of cerebral perfusion by monitoring of intracranial pressure and treatment of cerebral hypoperfusion decrease secondary injury. Before the patient reaches hospital, an organised trauma system that allows rapid resuscitation and transport directly to an experienced trauma centre significantly lowers mortality and morbidity. Only the education of medical personnel and the institution of trauma hospital systems can achieve further improvements in outcome for patients with traumatic brain injuries.

Selective serotonin-reuptake inhibitors (SSRIs) are increasingly being used as first-line therapy for severe premenstrual syndrome (PMS). We undertook a meta-analysis on the efficacy of SSRIs in this disorder.

Poverty not only excludes people from the benefits of health-care systems but also restricts them from participating in decisions that affect their health. The resulting health inequalities are well documented, and the search for greater equity attracts many concerned players and initiatives. Fundamental to the success of these efforts, however, is the need for people to be able to negotiate their own inclusion into health systems and demand adequate health care. This calls for a restatement of the centrality of people in public health and its practice. New forms of communication and cooperation are required at all levels of society, nationally, and internationally, to ensure equitable exchange of views and knowledge to formulate appropriate action to redress inequalities and improve people's health and wellbeing.