Elder abuse has received increasing attention over the past decade as a common problem with serious consequences for the health and wellbeing of old people. Our aim is to assist clinicians by summarising recent international research and clinical findings about elder abuse, and to assess their quality, relevance, and feasibility for health-care providers in clinical practice. This seminar includes issues of definition and frequency of elder abuse and a summary of major known risk factors. The advantages and disadvantages of screening for elder abuse are discussed. We review clinical manifestations and diagnosis of elder abuse, and propose a protocol for medical assessment of a patient with confirmed or suspected abuse. Suggestions for treatment are offered on the basis that elder abuse is multifactorial and needs individual medical and social intervention strategies, preferably in the context of a multidisciplinary team.

Oxidative stress can cause cancer. Our aim was to establish whether antioxidant supplements reduce the incidence of gastrointestinal cancer and mortality.

The incidence of malignant pleural mesothelioma is increasing throughout most of the world. This cancer is uniformly fatal, and characterised by progressive breathlessness and unremitting pain in the chest wall. From the onset of symptoms, survival is from a few weeks to a few years. Desperation by patients and doctors has driven a search for effective treatments. Clinical benefits are marginal and evidence of a good quality is lamentably lacking.

Superficial fungal infections arise from a pathogen that is restricted to the stratum corneum, with little or no tissue reaction. In this Seminar, three types of infection will be covered: tinea versicolor, piedra, and tinea nigra. Tinea versicolor is common worldwide and is caused by Malassezia spp, which are human saprophytes that sometimes switch from yeast to pathogenic mycelial form. Malassezia furfur, Malassezia globosa, and Malassezia sympodialis are most closely linked to tinea versicolor. White and black piedra are both common in tropical regions of the world; white piedra is also endemic in temperate climates. Black piedra is caused by Piedraia hortae; white piedra is due to pathogenic species of the Trichosporon genus. Tinea nigra is also common in tropical areas and has been confused with melanoma.

No currently available treatments have been shown to slow the progression of chronic obstructive pulmonary disease (COPD) or suppress the inflammation in small airways and lung parenchyma. However, several new treatments are in clinical development; some target the inflammatory process and others are directed against structural cells. A group of specific therapies are directed against the influx of inflammatory cells into the airways and lung parenchyma that occurs in COPD; these include agents directed against adhesion molecules and chemokines, as well as therapies to oppose tumour necrosis factor alpha and increase interleukin 10. Broad-range anti-inflammatory drugs are now in phase III development for COPD; they include inhibitors of phosphodiesterase 4. Other drugs that inhibit cell signalling include inhibitors of p38 mitogen-activated protein kinase, nuclear factor kappaB, and phosphoinositide-3-kinase gamma. More specific approaches are to give antioxidants, inhibitors of inducible nitric oxide synthase, and antagonists of leukotriene B4 receptor. Inhibitors of epidermal-growth-factor-receptor kinase and calcium-activated chloride channels have the potential to prevent overproduction of mucus. Therapy to inhibit fibrosis is being developed against transforming growth factor beta1 and protease-activated receptor 2. There is also a search for inhibitors of serine proteinases and matrix metalloproteinases to prevent lung destruction and the development of emphysema, as well as drugs such as retinoids that might even reverse this process. Effective delivery of drugs to the sites of disease in the peripheral lung is an important consideration, and there is a need for validated biomarkers and monitoring techniques in early clinical studies with new therapies for COPD.

The Atkins diet books have sold more than 45 million copies over 40 years, and in the obesity epidemic this diet and accompanying Atkins food products are popular. The diet claims to be effective at producing weight loss despite ad-libitum consumption of fatty meat, butter, and other high-fat dairy products, restricting only the intake of carbohydrates to under 30 g a day. Low-carbohydrate diets have been regarded as fad diets, but recent research questions this view.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide, and the burden of the disorder will continue to increase over the next 20 years despite medical intervention. Apart from smoking cessation, no approach or agent affects the rate of decline in lung function and progression of the disease. Especially in the later phase, COPD is a multicomponent disorder, and various integrated intervention strategies are needed as part of the optimum management programme. This seminar describes largely non-pharmacological interventions aimed at improving health status and function of disabled patients. Exacerbations become progressively more troublesome as baseline lung function declines, commonly necessitating hospital admission and associated with the development of acute respiratory failure.

The imperative to undertake randomised trials in children arises from extraordinary advances in basic biomedical sciences, needing a matching commitment to translational research if child health is to reap the benefits from this new knowledge. Unfortunately, many prescribed treatments for children have not been adequately tested in children, sometimes resulting in harmful treatments being given and beneficial treatments being withheld. Government, industry, funding agencies, and clinicians are responsible for research priorities being adult-focused because of the greater burden of disease in adults, coupled with financial and marketing considerations. This bias has meant that the equal rights of children to participate in trials has not always been recognised. This is changing, however, as the need for clinical trials in children has been increasingly recognised by the scientific community and broader public, leading to new legislation in some countries making trials of interventions mandatory in children as well as adults before drug approval is given. Trials in children are more challenging than those in adults. The pool of eligible children entering trials is often small because many conditions are uncommon in children, and the threshold for gaining consent is often higher and more complex because parents have to make decisions about trial participation on behalf of their child. Uncertain about what is best, despite supporting the notion of trials in principle, parents and paediatricians generally opt for the new intervention or for standard care rather than trial participation. In this review, we explore issues relating to trial participation for children and suggest some strategies for improving the conduct of clinical trials involving children.

Chronic obstructive pulmonary disease (COPD) is a readily diagnosable disorder that responds to treatment. Smoking cessation can reduce symptoms and prevent progression of disease. Bronchodilator therapy is key in improvement of lung function. Three classes of bronchodilators-beta agonists, anticholinergics, and theophylline-are available and can be used individually or in combination. Inhaled glucocorticoids can also improve airflow and can be combined with bronchodilators. Inhaled glucocorticoids, in addition, might reduce exacerbation frequency and severity as might some bronchodilators. Effective use of pharmacotherapy in COPD needs integration with a rehabilitation programme and successful treatment of co-morbidities, including depression and anxiety. Treatment for stable COPD can improve the function and quality of life of many patients, could reduce admissions to hospital, and has been suggested to improve survival.

The cause and pathogenesis of Parkinson's disease remain unknown; mitochondrial dysfunction, oxidative damage, environmental factors, and genetic predisposition might all be involved. Identification of the causative genes for familial Parkinson's diseases allow study of the pathogenesis of the disease at the molecular level.

The airflow limitation that defines chronic obstructive pulmonary disease (COPD) is the result of a prolonged time constant for lung emptying, caused by increased resistance of the small conducting airways and increased compliance of the lung as a result of emphysematous destruction. These lesions are associated with a chronic innate and adaptive inflammatory immune response of the host to a lifetime exposure to inhaled toxic gases and particles. Processes contributing to obstruction in the small conducting airways include disruption of the epithelial barrier, interference with mucociliary clearance apparatus that results in accumulation of inflammatory mucous exudates in the small airway lumen, infiltration of the airway walls by inflammatory cells, and deposition of connective tissue in the airway wall. This remodelling and repair thickens the airway walls, reduces lumen calibre, and restricts the normal increase in calibre produced by lung inflation. Emphysematous lung destruction is associated with an infiltration of the same type of inflammatory cells found in the airways. The centrilobular pattern of emphysematous destruction is most closely associated with cigarette smoking, and although it is initially focused on respiratory bronchioles, separate lesions coalesce to destroy large volumes of lung tissue. The panacinar pattern of emphysema is characterised by a more even involvement of the acinus and is associated with alpha1 antitrypsin deficiency. The technology needed to diagnose and quantitate the individual small airway and emphysema phenotypes present in people with COPD is being developed, and should prove helpful in the assessment of therapeutic interventions designed to modify the progress of either phenotype.

Faecal incontinence can affect individuals of all ages and in many cases greatly impairs quality of life, but incontinent patients should not accept their debility as either inevitable or untreatable. Education of the general public and of health-care providers alike is important, because most cases are readily treatable. Many cases of mild incontinence respond to simple medical therapy, whereas patients with more advanced incontinence are best cared for after complete physiological assessment. Recent advances in therapy have led to promising results, even for patients with refractory incontinence. Health-care providers must make every effort to communicate fully with incontinent patients and to help restore their self-esteem, eliminate their self-imposed isolation, and allow them to resume an active and productive lifestyle.

Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality and represents a substantial economic and social burden throughout the world. It is the fifth leading cause of death worldwide and further increases in its prevalence and mortality are expected in the coming decades. The substantial morbidity associated with COPD is often underestimated by health-care providers and patients; likewise, COPD is frequently underdiagnosed and undertreated. COPD develops earlier in life than is usually believed. Tobacco smoking is by far the major risk for COPD and the prevalence of the disease in different countries is related to rates of smoking and time of introduction of cigarette smoking. Contribution of occupational risk factors is quite small, but may vary depending on a country's level of economic development. Severe deficiency for alpha-1-antitrypsin is rare and the impact of other genetic factors on the prevalence of COPD has not been established. COPD should be considered in any patient presenting with cough, sputum production, or dyspnoea, especially if an exposure to risk factors for the disease has been present. Clinical diagnosis needs to be confirmed by standardised spirometric tests in the presence of not-fully-reversible airflow limitation. COPD is generally a progressive disease. Continued exposure to noxious agents promotes a more rapid decline in lung function and increases the risk for repeated exacerbations. Smoking cessation is the only intervention shown to slow the decline. If exposure is stopped, the disease may still progress due to the decline in lung function that normally occurs with aging, and some persistence of the inflammatory response.

Kawasaki syndrome is an acute, self-limited vasculitis that occurs in children of all ages and presents a challenge for the clinician: the disorder can be difficult to recognise; there is no diagnostic laboratory test; there is an extremely effective therapy; and there is a 25% chance of serious cardiovascular damage if the treatment is not given early in the course of the disease. This review includes discussion of the history of the syndrome, the diagnostic challenges, epidemiology, aetiology, pathology, immunopathogenesis, therapy, genetic influences, and the long-term cardiovascular sequelae.

Child sexual abuse is a worldwide concern. It is an insidious, persistent, and serious problem that, depending on the population studied and definition used, affects 2-62% of women and 3-16% of men as victims. Pain and tissue injury from child sexual abuse can completely heal in time, but psychological and medical consequences can persist through adulthood. Associated sexually transmitted diseases (such as HIV) and suicide attempts can be fatal. All physicians who treat children should be aware of the manifestations and consequences of child sexual abuse, and should be familiar with normal and abnormal genital and anal anatomy of children. This aim is best accomplished through training and routine examination of the anus and genitalia of children. Because as many as 96% of children assessed for suspected sexual abuse will have normal genital and anal examinations, a forensic interview by a trained professional must be relied on to document suspicion of abuse.

Borderline personality disorder is characterised by a pervasive pattern of instability in affect regulation, impulse control, interpersonal relationships, and self-image. Clinical signs of the disorder include emotional dysregulation, impulsive aggression, repeated self-injury, and chronic suicidal tendencies, which make these patients frequent users of mental-health resources. Causal factors are only partly known, but genetic factors and adverse events during childhood, such as physical and sexual abuse, contribute to the development of the disorder. Dialectical behaviour therapy and psychodynamic partial hospital programmes are effective treatments for out-of-control patients, and drug therapy can reduce depression, anxiety, and impulsive aggression. More research is needed for the understanding and management of this disabling clinical condition. Current strategies are focusing on the neurobiological underpinnings of the disorder and the development and dissemination of better and more cost-effective treatments to clinicians.

Bone and joint infections are painful for patients and frustrating for both them and their doctors. The high success rates of antimicrobial therapy in most infectious diseases have not yet been achieved in bone and joint infections owing to the physiological and anatomical characteristics of bone. The key to successful management is early diagnosis, including bone sampling for microbiological and pathological examination to allow targeted and long-lasting antimicrobial therapy. The various types of osteomyelitis require differing medical and surgical therapeutic strategies. These types include, in order of decreasing frequency: osteomyelitis secondary to a contiguous focus of infection (after trauma, surgery, or insertion of a joint prosthesis); that secondary to vascular insufficiency (in diabetic foot infections); or that of haematogenous origin. Chronic osteomyelitis is associated with avascular necrosis of bone and formation of sequestrum (dead bone), and surgical debridement is necessary for cure in addition to antibiotic therapy. By contrast, acute osteomyelitis can respond to antibiotics alone. Generally, a multidisciplinary approach is required for success, involving expertise in orthopaedic surgery, infectious diseases, and plastic surgery, as well as vascular surgery, particularly for complex cases with soft-tissue loss.

Klinefelter's syndrome is the most common genetic cause of human male infertility, but many cases remain undiagnosed because of substantial variation in clinical presentation and insufficient professional awareness of the syndrome itself. Early recognition and hormonal treatment of the disorder can substantially improve quality of life and prevent serious consequences. Testosterone replacement corrects symptoms of androgen deficiency but has no positive effect on infertility. However, nowadays patients with Klinefelter's syndrome, including the non-mosaic type, need no longer be considered irrevocably infertile, because intracytoplasmic sperm injection offers an opportunity for procreation even when there are no spermatozoa in the ejaculate. In a substantial number of azoospermic patients, spermatozoa can be extracted from testicular biopsy samples, and pregnancies and livebirths have been achieved. The frequency of sex chromosomal hyperploidy and autosomal aneuploidies is higher in spermatozoa from patients with Klinefelter's syndrome than in those from normal men. Thus, chromosomal errors might in some cases be transmitted to the offspring of men with this syndrome. The genetic implications of the fertilisation procedures, including pretransfer or prenatal genetic assessment, must be explained to patients and their partners.

The genetic code in the DNA of virtually every somatic cell can produce the entire complement of encoded proteins. Acetylation of histones and methylation of histones and DNA cytosine residues are part of the complex epigenetic regulatory process determining lineage-specific gene expression by altering the local structure of chromatin. After fertilisation, sperm DNA exchanges protamines for histones recruited from oocyte cytoplasm, reconfiguring both parental genomes into an epigenetic state conducive to activating the embryonic developmental programme. The identification of epigenetic reprogramming mechanisms is a major interest, rekindled by the ability of at least some somatic cells to acquire totipotency after somatic-cell nuclear transfer.

Curative therapy for diabetes mellitus mainly implies replacement of functional insulin-producing pancreatic beta cells, with pancreas or islet-cell transplants. However, shortage of donor organs spurs research into alternative means of generating beta cells from islet expansion, encapsulated islet xenografts, human islet cell-lines, and stem cells. Stem-cell therapy here implies the replacement of diseased or lost cells from progeny of pluripotent or multipotent cells. Both embryonic stem cells (derived from the inner cell mass of a blastocyst) and adult stem cells (found in the postnatal organism) have been used to generate surrogate beta cells or otherwise restore beta-cell functioning.