Very low MBL levels are associated with more frequent FN episodes, mainly due to severe bacterial infections. The surprising finding that children with normal MBL levels had more frequent FN episodes than those with low MBL levels needs testing in prospective studies.

A susceptibility gene for Wilms' tumour (WT), designated FWT1, was previously mapped to chromosome 17q12-q21 by linkage analysis of a single family. We now confirm the existence of this gene by analysis of additional cases in the original family (3-point LOD score=5.69), and by detecting strong evidence of linkage to this region in an unrelated pedigree with seven cases of WT (3-point LOD score=2.56). Analysis of 11 smaller WT families confirms that there is genetic heterogeneity in familial WT, as three families exhibit strong evidence against linkage to FWT1. One of these was subsequently found to have a predisposing WT1 mutation. However, the other two families show evidence against both FWT1 and WT1, suggesting that at least one further familial WT gene exists. Analysis of the phenotype of 16 WT cases from the families linked to FWT1 demonstrates that they present at a significantly older age and a significantly later stage than both sporadic WT and the six cases from two families unlinked to either FWT1 or WT1. The results confirm the role of FWT1 in susceptibility to WT, provide strong evidence for genetic heterogeneity in familial WT and suggest there are phenotypic differences between familial WT due to FWT1, familial WT due to other genes and non-familial WT.

Cell proliferation in untreated lymphoid malignancies of children was investigated by an in vitro assessment of the 3H-thymidine labelling index (LI), the growth fraction (GF) with the monoclonal antibody Ki-67, and the duration of the DNA-synthesis phase (ts) with a double labelling technique. Mean cell cycle time (tg) was similar in lymphoid malignancies of precursor B cell and T cell origin (115 h and 102 h, respectively), while B cell neoplasias had a mean tg of only 25 h. A positive correlation between the LI and the GF (r = 0.892) and a negative correlation between the LI and tg (r = -0.908) could be detected in childhood lymphoid malignancies. The proliferation of neoplastic precursor B cells was compared with the proliferation of presumably normal terminal transferase (TdT) positive bone marrow cells that, according to the immunophenotype, correspond mainly to normal precursor B cells. Although mean ts was identical in both cell populations (18-19 h), the neoplastic cell population showed a significantly longer mean tg than the normal counterpart (115 h and 65 h, respectively). However, if malignant and normal precursor B cell populations with a similar LI were compared, the difference in tg disappeared. Therefore, a down-regulation of leukaemic cell proliferation by an increasing cell mass is postulated for most cases of untreated precursor B cell ALL.

Ondansetron-loading doses of 16 mg/m(2) (top, 24 mg) i.v. seem to be safe in infants, children, and adolescents.