Recombinant granulocyte colony-stimulating factor (rG-CSF) is a glycoprotein hormone which has been produced in mammalian cells and, in a nonglycosylated form, in the bacterium Escherichia coli through recombinant DNA technology. It stimulates proliferation, differentiation and activation of cells of the neutrophil-granulocyte lineage and has been investigated as therapy for patients with various neutropenic conditions, both iatrogenic and disease related. rG-CSF is well tolerated, the most frequently reported adverse effect being mild to moderate bone pain. A major use for rG-CSF therapy will be in ameliorating the neutropenia which follows cytoreductive chemotherapy. rG-CSF accelerates neutrophil recovery after chemotherapy, leading to a reduction in duration of the neutropenic phase. Consequently, infection rate is diminished, as is the associated usage of antibiotics and duration of hospitalisation. The implications are that rG-CSF may allow increased dose intensity and stricter adherence to chemotherapy schedules. The increase in neutrophils produced by rG-CSF renders it a useful treatment for conditions such as congenital, acquired and cyclic neutropenias for which current therapy is not very successful. rG-CSF may be an effective therapy in myelodysplasia, although there is concern about acceleration of the possible rate of conversion of this disease to acute myelogenous leukaemia. It is also likely that rG-CSF will be useful in accelerating the recovery of transplanted bone marrow in patients with leukaemia, lymphoma and solid tumour. Furthermore, there is great potential for expansion of the role of rG-CSF as monotherapy or in combination regimens with other cell factors in various haematological disorders such as aplastic anaemia. In summary, while many aspects of its use remain to be clarified, rG-CSF must be seen as an exciting advance in therapeutics. It should rapidly find an important place as an adjunct to cancer chemotherapy, and also appears to have substantial potential in a number of other neutropenic conditions which are currently difficult to treat.

Formoterol, a long-acting beta 2-selective adrenoceptor agonist, produces dose-proportional bronchodilation in patients with obstructive airways disease with a reversible component. A significant effect occurs within minutes of inhalation of a therapeutic formoterol dose and persists for approximately 12 hours. Oral formoterol has a slower onset of action than the inhaled formulations, but also produces prolonged bronchodilatory effects. Inhaled formoterol has shown a therapeutic efficacy equivalent to or better than comparable dosages of the conventional beta 2-agonists salbutamol, fenoterol and terbutaline in short and long term trials, in both adults and children with asthma. Its prolonged duration of action permits a twice-daily dosage regimen and results in improved control of nocturnal symptoms by reducing the 'morning dip'. Formoterol also compares well with oral slow release theophylline. In addition, significantly more patients with chronic obstructive airways disease (COAD) had an improvement in symptoms when treated with formoterol compared with salbutamol or fenoterol. Noncomparative studies indicate formoterol also provides effective prophylaxis of exercise-induced asthma. Development of tachyphylaxis has not been observed. Formoterol is generally well tolerated. Adverse effects observed represent predictable extensions of its pharmacology. Tremor and palpitations are most frequently reported. The incidence of adverse events is dose-proportional and therefore related to the route of administration, being more frequent following oral than inhalation therapy. The long-acting beta 2-agonists, including formoterol, represent a significant advance over current maintenance or prophylactic bronchodilator therapy with intermediate-acting beta 2-agonists such as salbutamol, fenoterol and terbutaline, predominantly because of the twice daily administration regimen. However, comparisons with other long-acting beta 2-agonists, such as salmeterol, evaluation of its role in improving symptom control in patients failing to respond to prophylactic therapy, and clarification of the optimal role of beta 2-agonists in asthma maintenance therapy are required to fully determine the value of formoterol in the management of obstructive airways disease.

Idarubicin is a 4-demethoxy-anthracycline analogue of daunorubicin which, when administered intravenously in combination with cytarabine, has therapeutic efficacy superior to that of standard induction and salvage treatment regimens in acute myelogenous leukaemia. Idarubicin alone or in combination regimens has also been effective in limited studies in patients with other acute leukaemias, advanced breast cancer, multiple myeloma and non-Hodgkin's lymphoma. Idarubicin is more lipophilic than its parent drug daunorubicin. It intercalates DNA, induces DNA strand breaks and delays cell cycle progression. Leucopenia is often dose-limiting in patients with solid tumours treated with idarubicin, and most other adverse effects are similar in incidence and severity to those experienced with other anthracycline cytotoxic agents, except for alopecia which appears to occur with a reduced incidence and severity. Cardiotoxic effects have been reported with idarubicin as with other anthracyclines, but animal data and preliminary clinical findings suggest the possibility of reduced cardiotoxicity with idarubicin--a potentially important advantage if confirmed on further study. A maximum cumulative dose of idarubicin beyond which the incidence of cardiotoxicity rapidly increases has not been determined. Thus, intravenous idarubicin is a useful alternative to other anthracyclines (particularly in combination with cytarabine) in the treatment of acute myelogenous leukaemia, and there is some evidence that it is less cardiotoxic than other anthracycline drugs. Further studies are required to establish the use of intravenous idarubicin as a replacement for other intravenous anthracyclines, especially its effect on response duration and survival, and to confirm the evidence of reduced cardiotoxic effects. The role of idarubicin as consolidation and maintenance therapy for various malignancies requires further investigation, as does the potential use of oral idarubicin which is currently under development.

The operation of combined heart-lung transplantation results in acute denervation of the heart, lungs, and airways below the level of the trachea. The bronchoconstrictor response to inhaled methacholine of 12 recipients of heart-lung transplants was compared with that of 12 recipients of heart transplants having similar medication and 12 normal subjects. The median dose of methacholine that produced a reduction of at least 20% in the FEV1 (PC20) for the recipients of heart-lung transplants (8 mg/ml) was significantly lower than that for the recipients of heart transplants (64 mg/ml) and normal subjects (> 64 mg/ml). The increased airway reactivity may be related to the effects of chronic pulmonary denervation or subclinical inflammation in the airways. The effect of denervation on the response to full inspiration during bronchoconstriction was studied in six patients with heart-lung transplants by means of partial and maximal forced expiratory manoeuvres. Four showed bronchodilatation after a deep breath, indicating that this response can occur after extrinsic pulmonary denervation in man. The patients with heart-lung transplants described a "tight" sensation in the anterior chest during bronchoconstriction, indicating that this sensation is not dependent on pulmonary innervation.

Bepridil is a calcium antagonist with direct negative chronotropic, dromotropic, inotropic and vasodilatory actions which reduces myocardial oxygen consumption and increases coronary blood flow, leading to a significant anti-ischaemic and antianginal effect in the absence of reflex tachycardia. In contrast to other calcium channel blockers, bepridil produces only modest peripheral vasodilatation and displays weak antihypertensive activity. Its plasma elimination half-life of 1 to 2 days permits once daily administration. Results of short term clinical trials have shown bepridil to be of comparable efficacy to nifedipine, verapamil, diltiazem, propranolol and nadolol in decreasing the frequency of anginal attacks and consumption of nitroglycerin (glyceryl trinitrate) in patients with stable angina. Bepridil is more effective than nifedipine in improving exercise performance in patients with stable angina. Although bepridil proved superior to diltiazem in improving exercise performance in patients refractory to diltiazem, further studies are required to confirm the efficacy of bepridil in patients refractory to, or intolerant of, other antianginal agents. Bepridil in therapeutic doses is well tolerated, and appears to have a similar adverse effect profile to the established calcium antagonists. However, rate-dependent prolongation of the QTc interval and development of torsade de pointes have been associated with the use of bepridil. Therefore, bepridil is contraindicated in patients with hypokalaemia, those receiving other drugs that may prolong the QT interval, and those with congenital QT interval prolongation. Future clinical research will help to further define the position of bepridil as an antianginal treatment relative to the traditional calcium antagonists; in the interim, bepridil is indicated for the treatment of patients with angina refractory to or intolerant of other agents.