This paper charts the development of haemodialysis, the cornerstone of renal replacement therapy (RRT). It has enabled patients with end-stage renal failure to survive for years, in many cases with a surprisingly good quality of life. Through technological advances, RRT can be offered to patients who are older and more frail. Many have intercurrent comorbid illness. Such patients can have good quality of life, but their survival is shorter since they are likely to succumb early to comorbid illnesses. The challenge to nephrologists is to provide treatment based on exacting standards for all those patients who can benefit, yet to maintain cost-effectiveness. There is increasing recognition that, however good the technology underpinning dialysis, what justifies the cost and commitment that dialysis entails is the provision for the patient of a satisfactory quality of life.

Leprosy is an ancient disease which is still poorly understood and often feared by the general public and even by some healthcare professionals. Fortunately, improvements in the management of leprosy over the past three decades have diminished the stigma and greatly altered the outlook for patients. Public understanding of the disease has benefited from WHO's goal of eliminating leprosy as a public health problem by the year 2000. Unfortunately that goal has also led many to believe that leprosy has been or will soon be eradicated. This will not happen in the near future because, despite a fall in registered cases, the incidence of the disease has changed very little, and eradication of a bacterial infectious disease such as this is unlikely with chemotherapy alone. Nevertheless, as a result of the WHO's efforts, patients nearly everywhere should have access to care, and the incidence may begin to diminish if adequate control efforts are maintained beyond the year 2000. Given the mobility of patients today a physician anywhere may occasionally see a case or be asked about the disease so a basic understanding of leprosy and its management should prove useful.

Menopause is diagnosed after 12 months of amenorrhoea resulting from the permanent cessation of ovarian function. The mean age at menopause is 51 years. The perimenopause, a time of changing ovarian function, precedes the final menses by several years. The physiology and clinical manifestations of this transition to menopause are not well understood; however, some symptoms, such as hot flashes, certainly begin in the perimenopause. Causal associations between menopause and several symptoms and diseases are proposed. The evidence for these associations varies and is reviewed. Hormone replacement therapy can be directed at symptom relief or at prevention or treatment of chronic diseases. Doses and routes of hormone replacement therapy vary by indication. Complications of hormone replacement therapy depend on the regimen used. Knowing the expected vaginal bleeding pattern for each hormone replacement therapy regimen is important, since unexpected bleeding may signal endometrial hyperplasia. Postmenopausal hormone therapy is a complex intervention that produces positive and negative specific health effects. Overall, based on observational studies, postmenopausal women who use hormones have a 30-50% lower all-cause mortality rate than those who do not use hormones. It is important to recognise that the value that individual women place on various health outcomes associated with hormone replacement therapy may differ. Thus, the decision to use hormone replacement therapy should be made jointly by each woman and her health-care provider, after careful consideration of possible benefits, risks, and her personal preferences.

Leukotriene-receptor antagonists are the first novel class of antiasthma drugs to become available over the past three decades. They have an unique profile in that they are a hybrid of an anti-inflammatory and bronchodilator drug, and they can be taken as a tablet once or twice daily. The published data with leukotriene-receptor antagonists such as montelukast or zafirlukast show good antiasthmatic activity over a wide spectrum of asthma severity either as monotherapy or with inhaled steroids. Another potential spin-off of leukotriene-receptor antagonists is that they also seem to be effective in treating allergic rhinitis, which commonly coexists in patients with asthma. Here I overview the clinical pharmacology of leukotriene antagonists and appraise the published data from clinical trials, and look at the appropriate position of these agents in asthma management guidelines.

During the 1990s the focus of group B streptococcus (GBS) disease research has shifted to prevention. Increased use of intrapartum antimicrobial prophylaxis in North America and Australia has led to substantial declines in perinatal disease. Vaccine development (initiated two decades earlier) has yielded results--for example, polysaccharide-protein conjugate vaccines given to women of reproductive age proved to be highly immunogenic and well tolerated. Also economic evaluations have assessed the cost-effectiveness of prevention strategies in different populations. Although GBS has traditionally been considered a perinatal pathogen, the burden of invasive GBS disease among nonpregnant adults has been measured. Adverse outcomes of pregnancy attributable to GBS were addressed through a multicentre study which confirmed the important role of heavy colonisation with GBS in preterm low-birthweight deliveries. Finally, the pathogen itself has continued to evolve: new capsular serotypes described in the past decade are now causing an important proportion of clinical infections.

The very potent endogenous vasoconstrictor endothelin was discovered in 1988. We know now that there are three isoforms (1, 2, and 3) and two receptor subtypes (A and B). A whole range of peptide and non-peptide antagonists has been developed, some selective for A or B receptors and others with non-selective A/B antagonistic activity. So far the main application of these agents has been experimental--ie, endothelin blockers are used to throw light on disease mechanisms, most notably cardiovascular and renal. However, the non-selective antagonist bosentan and a few other agents have been studied clinically. Evidence so far from preclinical studies and healthy volunteers and from the limited number of investigations in patients permits a listing of the potential areas of clinical interest. These are mainly cardiovascular (eg, hypertension, cerebrovascular damage, and possibly heart failure) and renal. Clouds on the horizon are the need to show that these new agents are better than existing drugs; the possibility of conflicting actions if mixed A/B antagonists are used; and animal evidence hinting that endothelin blockade during development could be dangerous.

Deep-vein thrombosis is an important complication of several inherited and acquired disorders, but may also occur spontaneously. Prevention of recurrent venous thrombosis and pulmonary embolism is the main reason for accurate diagnosis and adequate treatment. This seminar discusses only symptomatic deep-vein thrombosis. The diagnosis can be confirmed by objective tests in only about 30% of patients with symptoms. Venous thromboembolic complications happen in less than 1% of untreated patients in whom the presence of venous thrombosis is rejected on the basis of serial ultrasonography or ultrasonography plus either D-dimer or clinical score. Initial anticoagulant treatment (intravenous or subcutaneous heparin) should continue until oral anticoagulant treatment, started concurrently, increases the international normalised ratio above 2.0 for more than 24 h. The optimum duration of oral anticoagulant treatment is unresolved, but may be guided by the presence of temporary or persistent risk factors or presentation with recurrent venous thromboembolism.

Colorectal cancer is a leading cause of morbidity and mortality with about 300,000 new cases and 200,000 deaths in Europe and the USA each year. Published trials have established a role for chemotherapy in colorectal cancer, in the adjuvant setting for Dukes C colon cancer, with an absolute survival benefit of about 5% and in advanced colorectal cancer, for which it improves quality of life and increases survival by 6-12 months. For rectal cancer, radiotherapy decreases rates of local recurrence and, in locally advanced disease, successfully palliates pain, tenesmus, and bleeding. The evolving understanding of colorectal carcinogenesis, in particular recognition of vital genes that may be mutated or lost during tumour development, has been translated into innovative gene therapy techniques. Finally it is increasingly apparent that surgical site specialisation and a multidisciplinary approach (including surgeons, pathologists, and oncologists) may lead to optimum outcomes for patients with colorectal cancer.