Coronary heart disease is still highly prevalent worldwide, and stable angina pectoris is one of its more common presentations. Three major controversies are risk factor management, drug therapy, and intervention. As well as the major risk factors stated by the Framingham study and European guidelines, other factors include abdominal obesity, metabolic syndrome, and psychological stress. How should these additional factors be rated? With respect to drug therapy, apart from aspirin, all patients with stable angina should be assessed for statin treatment. Although statins will reduce coronary events by about one third in patients with vascular disease, the absolute benefit depends on the absolute risk. Non-controversially, all patients should be considered for angiotensin-converting-enzyme inhibitors. The concept that beta blockers are protective from future coronary events can be disputed. Percutaneous coronary intervention can relieve symptoms without extending lifespan beyond medical therapy. However, strong mortality data favour coronary-artery bypass grafting in individuals with triple-vessel or even double-vessel disease. Thus, effort angina needs comprehensive assessment, lifestyle changes, and treatment tailored to the individual patient.

Urinary incontinence is common in women, but is under-reported and under-treated. Urine storage and emptying is a complex coordination between the bladder and urethra, and disturbances in the system due to childbirth, aging, or other medical conditions can lead to urinary incontinence. The two main types of incontinence in women, stress urinary incontinence and urge urinary incontinence, can be evaluated by history and simple clinical assessment available to most primary care physicians. There is a wide range of therapeutic options, but the recent proliferation of new drug treatments and surgical devices for urinary incontinence have had mixed results; direct-to-consumer advertising has increased public awareness of the problem of urinary incontinence, but many new products are being introduced without long-term assessment of their safety and efficacy.

Sex work is an extremely dangerous profession. The use of harm-reduction principles can help to safeguard sex workers' lives in the same way that drug users have benefited from drug-use harm reduction. Sex workers are exposed to serious harms: drug use, disease, violence, discrimination, debt, criminalisation, and exploitation (child prostitution, trafficking for sex work, and exploitation of migrants). Successful and promising harm-reduction strategies are available: education, empowerment, prevention, care, occupational health and safety, decriminalisation of sex workers, and human-rights-based approaches. Successful interventions include peer education, training in condom-negotiating skills, safety tips for street-based sex workers, male and female condoms, the prevention-care synergy, occupational health and safety guidelines for brothels, self-help organisations, and community-based child protection networks. Straightforward and achievable steps are available to improve the day-to-day lives of sex workers while they continue to work. Conceptualising and debating sex-work harm reduction as a new paradigm can hasten this process.

In early breast cancer, variations in local treatment that substantially affect the risk of locoregional recurrence could also affect long-term breast cancer mortality. To examine this relationship, collaborative meta-analyses were undertaken, based on individual patient data, of the relevant randomised trials that began by 1995.

The pathogenesis of the acute Charcot foot of diabetes remains unclear. All patients with this condition have evidence of peripheral neuropathy, with loss of protective sensation and abnormal foot biomechanics. However, the acute Charcot foot is also characterised by a pronounced inflammatory reaction and the pathogenic significance of this inflammation has received little attention. We suggest that an initial insult--which may or may not be detected--is sufficient to trigger an inflammatory cascade through increased expression of proinflammatory cytokines, including TNFalpha and interleukin 1beta. This cascade then leads to increased expression of the nuclear transcription factor, NF-kappaB, which results in increased osteoclastogenesis. Osteoclasts cause progressive bone lysis, leading to further fracture, which in turn potentiates the inflammatory process. The potential role of proinflammatory cytokines suggests the possibility of new treatments for this sometimes devastating complication of diabetes.

A consensus has emerged that angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-II receptor blockers (ARBs) have specific renoprotective effects. Guidelines specify that these are the drugs of choice for the treatment of hypertension in patients with renal disease. We sought to determine to what extent this consensus is supported by the available evidence.

Marfan's syndrome is a systemic disorder of connective tissue caused by mutations in the extracellular matrix protein fibrillin 1. Cardinal manifestations include proximal aortic aneurysm, dislocation of the ocular lens, and long-bone overgrowth. Important advances have been made in the diagnosis and medical and surgical care of affected individuals, yet substantial morbidity and premature mortality remain associated with this disorder. Progress has been made with genetically defined mouse models to elucidate the pathogenetic sequence that is initiated by fibrillin-1 deficiency. The new understanding is that many aspects of the disease are caused by altered regulation of transforming growth factor beta (TGFbeta), a family of cytokines that affect cellular performance, highlighting the potential therapeutic application of TGFbeta antagonists. Insights derived from studying this mendelian disorder are anticipated to have relevance for more common and non-syndromic presentations of selected aspects of the Marfan phenotype.

Injuries resulting from falls in elderly people are a major public-health concern, representing one of the main causes of longstanding pain, functional impairment, disability, and death in this population. The problem is going to worsen, since the rates of such injuries seem to be rising in many areas, as is the number of elderly people in both the developed and developing world. Many methods and programmes to prevent such injuries already exist, including regular exercise, vitamin D and calcium supplementation, withdrawal of psychotropic medication, cataract surgery, professional environment hazard assessment and modification, hip protectors, and multifactorial preventive programmes for simultaneous assessment and reduction of many of the predisposing and situational risk factors. To receive broader-scale effectiveness, these programmes will need systematic implementation. Care must be taken, however, to rigorously select the right actions for those people most likely to benefit, such as vitamin D and calcium supplementation and hip protectors for elderly people living in institutions.

Total lymphocyte count has been proposed as an alternative to the percentage of CD4+ T-cells to indicate when antiretroviral therapy should be started in children with HIV in resource-poor settings. We aimed to assess thresholds of total lymphocyte count at which antiretroviral therapy should be considered, and compared monitoring of total lymphocyte count with monitoring of CD4-cell percentage.

The periodontal diseases are highly prevalent and can affect up to 90% of the worldwide population. Gingivitis, the mildest form of periodontal disease, is caused by the bacterial biofilm (dental plaque) that accumulates on teeth adjacent to the gingiva (gums). However, gingivitis does not affect the underlying supporting structures of the teeth and is reversible. Periodontitis results in loss of connective tissue and bone support and is a major cause of tooth loss in adults. In addition to pathogenic microorganisms in the biofilm, genetic and environmental factors, especially tobacco use, contribute to the cause of these diseases. Genetic, dermatological, haematological, granulomatous, immunosuppressive, and neoplastic disorders can also have periodontal manifestations. Common forms of periodontal disease have been associated with adverse pregnancy outcomes, cardiovascular disease, stroke, pulmonary disease, and diabetes, but the causal relations have not been established. Prevention and treatment are aimed at controlling the bacterial biofilm and other risk factors, arresting progressive disease, and restoring lost tooth support.

Optimum healing of a cutaneous wound requires a well-orchestrated integration of the complex biological and molecular events of cell migration and proliferation, and of extracellular matrix deposition and remodelling. Cellular responses to inflammatory mediators, growth factors, and cytokines, and to mechanical forces, must be appropriate and precise. However, this orderly progression of the healing process is impaired in chronic wounds, including those due to diabetes. Several pathogenic abnormalities, ranging from disease-specific intrinsic flaws in blood supply, angiogenesis, and matrix turnover to extrinsic factors due to infection and continued trauma, contribute to failure to heal. Yet, despite these obstacles, there is increasing cause for optimism in the treatment of diabetic and other chronic wounds. Enhanced understanding and correction of pathogenic factors, combined with stricter adherence to standards of care and with technological breakthroughs in biological agents, is giving new hope to the problem of impaired healing.

People with diabetes develop foot ulcers because of neuropathy (sensory, motor, and autonomic deficits), ischaemia, or both. The initiating injury may be from acute mechanical or thermal trauma or from repetitively or continuously applied mechanical stress. Patients with clinically significant limb ischaemia should be assessed by a vascular surgeon to determine the need for angioplasty, stenting, or femorodistal bypass. When infection complicates a foot ulcer, the combination can be limb or life-threatening. Infection is defined clinically, but wound cultures reveal the causative pathogens. Tissue specimens are strongly preferred to wound swabs for wound cultures. Antimicrobial therapy should be guided by culture results, and should aim to cure the infection, not to heal the wound. Alleviation of the mechanical load on ulcers (off-loading) should always be a part of treatment. Neuropathic ulcers typically heal in 6 weeks with total contact casting, because it effectively relieves pressure at the ulcer site and enforces patient compliance. The success of other approaches to off-loading similarly depends on the patients' adherence to the effectiveness of pressure relief. Surgery to heal ulcers and prevent recurrence can include tenotomy, tendon lengthening, reconstruction, or removal of bony prominences. However, these procedures may result in secondary ulceration and other complications. Ulcer recurrence rates are high, but appropriate education for patients, the provision of posthealing footwear, and regular foot care can reduce rates of re-ulceration.

Diabetic foot problems are common throughout the world, resulting in major economic consequences for the patients, their families, and society. Foot ulcers are more likely to be of neuropathic origin, and therefore eminently preventable, in developing countries, which will experience the greatest rise in the prevalence of type 2 diabetes in the next 20 years. People at greatest risk of ulceration can easily be identified by careful clinical examination of the feet: education and frequent follow-up is indicated for these patients. When assessing the economic effects of diabetic foot disease, it is important to remember that rates of recurrence of foot ulcers are very high, being greater than 50% after 3 years. Costing should therefore include not only the immediate ulcer episode, but also social services, home care, and subsequent ulcer episodes. A broader view of total resource use should include some estimate of quality of life and the final outcome. An integrated care approach with regular screening and education of patients at risk requires low expenditure and has the potential to reduce the cost of health care.

The scientific knowledge to achieve a new global goal for the prevention of chronic diseases--a 2% yearly reduction in rates of death from chronic disease over and above projected declines during the next 10 years--already exists. However, many low-income and middle-income countries must deal with the practical realities of limited resources and a double burden of infectious and chronic diseases. This paper presents a novel planning framework that can be used in these contexts: the stepwise framework for preventing chronic diseases. The framework offers a flexible and practical public health approach to assist ministries of health in balancing diverse needs and priorities while implementing evidence-based interventions such as those recommended by the WHO Framework Convention on Tobacco Control and the WHO Global Strategy on Diet, Physical Activity and Health. Countries such as Indonesia, the Philippines, Tonga, and Vietnam have applied the stepwise planning framework: their experiences illustrate how the stepwise approach has general applicability to solving chronic disease problems without sacrificing specificity for any particular country.

Guillain-Barré syndrome consists of at least four subtypes of acute peripheral neuropathy. Major advances have been made in understanding the mechanisms of some of the subtypes. The histological appearance of the acute inflammatory demyelinating polyradiculoneuropathy (AIDP) subtype resembles experimental autoimmune neuritis, which is predominantly caused by T cells directed against peptides from the myelin proteins P0, P2, and PMP22. The role of T-cell-mediated immunity in AIDP remains unclear and there is evidence for the involvement of antibodies and complement. Strong evidence now exists that axonal subtypes of Guillain-Barré syndrome, acute motor axonal neuropathy (AMAN), and acute motor and sensory axonal neuropathy (AMSAN), are caused by antibodies to gangliosides on the axolemma that target macrophages to invade the axon at the node of Ranvier. About a quarter of patients with Guillain-Barré syndrome have had a recent Campylobacter jejuni infection, and axonal forms of the disease are especially common in these people. The lipo-oligosaccharide from the C jejuni bacterial wall contains ganglioside-like structures and its injection into rabbits induces a neuropathy that resembles acute motor axonal neuropathy. Antibodies to GM1, GM1b, GD1a, and GalNac-GD1a are in particular implicated in acute motor axonal neuropathy and, with the exception of GalNacGD1a, in acute motor and sensory axonal neuropathy. The Fisher's syndrome subtype is especially associated with antibodies to GQ1b, and similar cross-reactivity with ganglioside structures in the wall of C jejuni has been discovered. Anti-GQ1b antibodies have been shown to damage the motor nerve terminal in vitro by a complement-mediated mechanism. Results of international randomised trials have shown equivalent efficacy of both plasma exchange and intravenous immunoglobulin, but not corticosteroids, in hastening recovery from Guillain-Barré syndrome. Further research is needed to discover treatments to prevent 20% of patients from being left with persistent and significant disability.

35 million people will die in 2005 from heart disease, stroke, cancer, and other chronic diseases. Only 20% of these deaths will be in high-income countries--while 80% will occur in low-income and middle-income countries. The death rates from these potentially preventable diseases are higher in low-income and middle-income countries than in high-income countries, especially among adults aged 30-69 years. The impact on men and women is similar. We propose a new goal for reducing deaths from chronic disease to focus prevention and control efforts among those concerned about international health. This goal-to reduce chronic disease death rates by an additional 2% annually--would avert 36 million deaths by 2015. An additional benefit will be a gain of about 500 million years of life over the 10 years from 2006 to 2015. Most of these averted deaths and life-years gained will be in low-income and middle-income countries, and just under half will be in people younger than 70 years. We base the global goal on worldwide projections of deaths by cause for 2005 and 2015. The data are presented for the world, selected countries, and World Bank income groups.