The peroxisome proliferator-activated receptor gamma (PPARgamma) and its partner the retinoid X receptor (RXR) are two nuclear receptors that are expressed mainly in adipose tissue and which have a role in lipid metabolism and insulin sensitisation. New sites of PPARgamma/RXR expression have been described, especially in the intestinal tract, pancreas, and liver. Concomitantly, new functions have been attributed to this heterodimer in regulation of inflammation, by its inhibition of nuclear factor (NF)-kappaB and via stress-kinase pathways. These new sites and functions of PPARgamma/RXR have led to novel ideas about pathophysiology of different inflammatory digestive diseases and to development of innovative treatment strategies with PPARgamma activators.

The pharmaceutical industry spends more time and resources on generation, collation, and dissemination of medical information than it does on production of medicines. This information is essential as a resource for development of medicines, but is also needed to satisfy licensing requirements, protect patents, promote sales, and advise patients, prescribers, and dispensers. Such information is of great commercial value, and most of it is confidential, protected by regulations about intellectual property rights. Through their generation and dissemination of information, transnational companies can greatly influence clinical practice. Sometimes, their commercially determined goals represent genuine advances in health-care provision, but most often they are implicated in excessive and costly production of information that is largely kept secret, often duplicated, and can risk undermining the best interests of patients and society.

Reliable and comparable analysis of risks to health is key for preventing disease and injury. Causal attribution of morbidity and mortality to risk factors has traditionally been in the context of individual risk factors, often in a limited number of settings, restricting comparability. Our aim was to estimate the contributions of selected major risk factors to global and regional burden of disease in a unified framework.

Asthma is one of the commonest chronic diseases of affluent societies. The striking increase in prevalence of asthma over recent decades and the rarity of this disease in less affluent populations confirms the importance of environmental factors in the cause of asthma--although which environmental factors are responsible is still not clear. Family studies show that genetic factors are also important in determining individual susceptibility to asthma, with results of genetic studies suggesting that there are many genes with moderate effects rather than a few major genes. Asthmatic airways show inflammation and remodelling, with CD4+ helper cells, mast cells, and eosinophils characterising the inflammatory response. Inhaled corticosteroids remain the cornerstone of treatment with the addition of long-acting beta agonists as the next step if symptoms continue. Leukotriene antagonists, the only new drugs to reach the market in the past decade, have modest effects. However, a better understanding of the mechanisms underlying asthma and the genetic and environmental factors that predispose individuals to asthma should lead to better preventative strategies and new therapeutic approaches.

The health effects of air pollution have been subject to intense study in recent years. Exposure to pollutants such as airborne particulate matter and ozone has been associated with increases in mortality and hospital admissions due to respiratory and cardiovascular disease. These effects have been found in short-term studies, which relate day-to-day variations in air pollution and health, and long-term studies, which have followed cohorts of exposed individuals over time. Effects have been seen at very low levels of exposure, and it is unclear whether a threshold concentration exists for particulate matter and ozone below which no effects on health are likely. In this review, we discuss the evidence for adverse effects on health of selected air pollutants.

The human cytochrome P450 (CYP) superfamily comprises 57 genes. These genes code for enzymes that can have a role in: metabolism of drugs, foreign chemicals, arachidonic acid and eicosanoids; cholesterol metabolism and bile-acid biosynthesis; steroid synthesis and metabolism; vitamin D(3) synthesis and metabolism; retinoic acid hydroxylation; and those of still unknown function. Cytochrome P450 was once believed to be mainly a hepatic drug detoxication system, but is now understood to include a myriad of enzymic reactions implicated in important life processes. Mutations in many CYP genes cause inborn errors of metabolism and contribute to many clinically relevant diseases.

In 1996, the World Health Assembly declared violence a major public health issue. To follow up on this resolution, on Oct 3 this year, WHO released the first World Report on Violence and Health. The report analyses different types of violence including child abuse and neglect, youth violence, intimate partner violence, sexual violence, elder abuse, self-directed violence, and collective violence. For all these types of violence, the report explores the magnitude of the health and social effects, the risk and protective factors, and the types of prevention efforts that have been initiated. The launch of the report will be followed by a 1-year Global Campaign on Violence Prevention, focusing on implementation of the recommendations. This article summarises some of the main points of the world report.

Results from a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) study suggest that angiotensin-converting-enzyme (ACE) inhibitors may be less effective in patients receiving aspirin. We aimed to confirm or refute this theory.

The BRCA1 gene was cloned in 1994 as one of the genes that conferred genetic predisposition to early-onset breast and ovarian cancer. Since then, a genetic test for identification of high-risk individuals has been developed. Despite being implicated in many important cellular pathways, including DNA repair and regulation of transcription, the exact mechanism by which inactivation of BRCA1 might lead to malignant transformation of cells remains unknown. We examine the mechanisms that underlie inactivation of BRCA1 and assess how they affect management of patients, in terms of both primary and secondary cancer prevention strategies. Furthermore, we look at the potential usefulness of BRCA1 as a prognostic tool and as a predictive marker of response to different classes of drugs. Finally, throughout this review, we draw links between the functional consequences of BRCA1 inactivation, in terms of key cellular signalling pathways, and how they might explain specific clinical observations in individuals who carry mutations in the gene.

Over the past few decades hormone replacement therapy (HRT) has been used increasingly by post-menopausal women in western countries. The need for objective data on long-term effects prompted the setting up of randomised trials to compare cancer and cardiovascular disease endpoints in HRT users and non-users. With the early termination of part of the Women's Health Initiative trial (JAMA 2002; 288: 321-33), it is timely to review the evidence from such studies.

The discovery of Helicobacter pylori has greatly changed our approach to peptic ulcer disease. Bacterial, host, and environmental factors all have a role in peptic-ulcer disease. Although the prevalence of uncomplicated peptic ulcers is falling, hospital admissions for ulcer complications associated with non-steroidal anti-inflammatory drugs (NSAIDs) are rising. Evidence suggests that prescription of NSAIDs along with potent antiulcer agents and the use of highly selective cyclo-oxygenase-2 inhibitors reduce gastroduodenal ulceration. Whether these therapeutic advances will translate into clinical benefits remains to be seen. The interaction between H pylori and NSAIDs is one of the most controversial issues in peptic ulcer disease. With the fall in rates of H pylori infection, the proportion of ulcers not related to this organism and NSAIDs has risen, which will affect the management of peptic ulcer.

Diet-related factors are thought to account for about 30% of cancers in developed countries. Obesity increases the risk of cancers in the oesophagus, colorectum, breast, endometrium, and kidney. Alcohol causes cancers of the oral cavity, pharynx, larynx, oesophagus, and liver, and causes a small increase in the risk of breast cancer. Adequate intakes of fruit and vegetables probably lower the risk for several types of cancer, especially cancers of the gastrointestinal tract. The importance of other factors, including meat, fibre, and vitamins, is not yet clear. Prudent advice is to eat a varied diet including plenty of fruit, vegetables, and cereals to maintain a healthy bodyweight with the help of regular physical activity and to restrict consumption of alcohol.

New therapies have evolved from our improved understanding of the biology of sickle cell disease (SCD) and the availability of a useful transgenic animal model. Several therapeutic options are available that interrupt the sickling process at various key pathways. Nitric oxide (NO)is a critical factor in the pathophysiology of SCD and is a promising antisickling agent with vasodilation properties. NO regulates blood vessel tone, endothelial adhesion, and the severity of ischaemia-reperfusion injury and anaemia in SCD. Although NO is difficult to administer, its precursor, L-arginine, is an oral supplement.

Infrared ear thermometry is frequently used in children, because this is a quick method of taking temperature and the ear is easily accessible. Our aim was to evaluate agreement between temperature measured at the rectum and ear in children.

Food allergy encompasses a range of disorders that result from adverse immune responses to dietary antigens. This group of conditions includes acute, potentially fatal reactions, and a host of chronic diseases that mainly affect the skin and gastrointestinal tract. Tools for diagnosis and management have not changed much in the past two decades, and include the clinical history, physical examination, tests for specific IgE antibody to suspected foods, elimination diets, oral food challenges, and provision of medications such as epinephrine for emergency treatment. However, much research in the past few years has enhanced our understanding of the clinical, epidemiological, and immunological aspects of these disorders. In this review I will discuss these advances and incorporate them into an improved diagnostic and management scheme. Additionally, emergent diagnostic, treatment, and prevention strategies are reviewed.