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.

Regardless of the event that stimulates the aggregation of platelets, the receptor alpha(IIb)beta3--one of a family of adhesion receptors known as integrins--has a key role in the process. The past decade has seen the publication of 10 phase III (randomised) clinical trials of four members of a new class of antiplatelet drugs, the GPIIb-IIIa blockers, targeted at this important receptor. Three (abciximab, eptifibatide, and tirofiban) are licensed for human use. 10 other GbIIb-IIIa blockers are in phase II or III human studies. In all 10 placebo-controlled trials, done in the clinical settings of percutaneous coronary intervention or acute coronary syndrome in patients on aspirin, the endpoints favoured the active drug, with a risk reduction for death or non-fatal myocardial infarction of about 21% overall. With attention to heparin dose the risk of bleeding is not a major concern with these agents. The GPIIb-IIIa blockers are taking the clinician and patient out of the era of aspirin monotherapy when platelet inhibition is required.

Methadone maintenance treatment (MMT) involves the daily administration of the oral opioid agonist methadone as a treatment for opioid dependence-a persistent disorder with a substantial risk of premature death. MMT improves health and reduces illicit heroin use, infectious-disease transmission, and overdose death. However, its effectiveness is compromised if low maintenance doses of methadone (<60 mg) are used and patients are pressured to become prematurely abstinent from methadone. Pregnancy and psychiatric comorbidity are not contraindications for MMT. As an alternative to MMT, other oral opioid agents (eg, naltrexone, buprenorphine) may increase patient choice and avoid some of the more unpleasant aspects of MMT. The public-health challenge for the future is to develop and continue to deliver safe and effective forms of opioid maintenance treatment to as many opioid-dependent individuals as can benefit from them.