A phase I study of intravenous liposomal daunorubicin (DaunoXome) in paediatric patients with relapsed or resistant solid tumours.

Anthracyclines are widely used in paediatric oncology, but their use is limited by the risk of cumulative cardiac toxicity. Encapsulating anthracyclines in liposomes may reduce cardiac toxicity and possibly increase drug availability to tumours. A phase I study in paediatric patients was designed to establish the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) after a single course of liposomal daunorubicin, 'DaunoXome', as a 1 h infusion on day 1 of a 21 day cycle. Patients were stratified into two groups according to prior treatment: Group A (conventional) and group B (heavily pretreated patients). Dose limiting toxicity was expected to be haematological, and a two-step escalation was planned, with and without G-CSF support. Pharmacokinetic studies were carried out in parallel. In all, 48 patients aged from 1 to 18 years were treated. Dose limiting toxicity was neutropenia for both groups. Maximum tolerated dose was defined as 155 mg m(-2) for Group A and 100 mg m(-2) for Group B. The second phase with G-CSF was interrupted because of evidence of cumulative cardiac toxicity. Cardiac toxicity was reported in a total of 15 patients in this study. DaunoXome shares the early cardiotoxicity of conventional anthracyclines in paediatric oncology. This study has successfully defined a haematological MTD for DaunoXome, but the significance of this is limited given the concerns of delayed cardiac toxicity. The importance of longer-term follow-up in patients enrolled into phase I studies has been underestimated previously, and may lead to an under-recognition of important adverse events.

Quantitative PCR of the immunoglobulin heavy chain gene using genomic DNA.

Techniques currently available enable the detection of clonal rearrangements of the immunoglobulin heavy chain gene using fluorescent PCR technology. It is possible to use this technique to analyse minimal residual disease throughout patient treatment: however, without the development of a quantitative assay, only the presence or absence of a clonal population can be determined. We describe here the development of a quantitative competitive PCR technique using genomic DNA which enables the rate of clearance of disease to be measured. In future, the ability to detect and also quantitate minimal residual disease may enhance the application of molecular investigations in the clinical management of patients.

Faecal contamination on children's hands and environmental surfaces in primary schools in Leeds.

Gastro-intestinal diseases continue to be a major health problem in primary schools in the UK. This study, which took place in 20 primary schools in the Leeds area, investigated the presence of faecal indicator bacteria on children's hands and environmental surfaces. Faecal streptococci were used as an indicator of faecal contamination. A handwashing knowledge score was developed for each child. Those children with good hygiene knowledge had less faecal contamination on their hands (relative risk: 1.4, 95% CI = 1.09-1.81, P = 0.005). Those schools with higher hand counts were more likely to have had a reported outbreak of gastroenteritis in the past. Values of the Townsend Deprivation Index, an indicator of deprivation, were compared with the hand results and those schools in high deprivation areas had higher hand counts. Of the swabs taken from surfaces in the toilet areas and classrooms, the carpets in the classrooms were the most frequently contaminated surfaces.