Fecal calprotectin correlates closely with the best invasive measures of colonic and small bowel inflammation in childhood inflammatory bowel disease. As a sensitive objective measure of bowel inflammation that is risk-free and noninvasive, fecal calprotectin lends itself particularly to the monitoring of and assessment of therapeutic interventions in children with inflammatory bowel disease.

Fecal calprotectin seems to reflect bowel inflammation in children with IBD. As a simple, safe, noninvasive test, it has the potential to reduce the number of invasive investigations performed in these children.

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Polymeric cytotoxic conjugates are being developed with the aim of preferential delivery of the anticancer agent to tumour. MAG-CPT comprises the topoisomerase I inhibitor camptothecin linked to a water-soluble polymeric backbone methacryloylglycynamide (average molecular weight 18 kDa, 10% CPT by weight). It was administered as a 30-min infusion once every 4 weeks to patients with advanced solid malignancies. The objectives of our study were to determine the maximum tolerated dose, dose-limiting toxicities, and the plasma and urine pharmacokinetics of MAG-CPT, and to document responses to this treatment. The starting dose was 30 mg m À2 (dose expressed as mg equivalent camptothecin). In total, 23 patients received 47 courses at six dose levels, with a maximum dose of 240 mg m À2 . Dose-limiting toxicities were myelosuppression, neutropaenic sepsis, and diarrhoea. One patient died after cycle 1 MAG-CPT at the maximum dose. The maximum tolerated dose and dose recommended for further clinical study was 200 mg m À2 . The half-lives of both MAG-CPT and released CPT were prolonged (46 days) and measurable levels of MAG-CPT were retrieved from plasma and urine 4 weeks after treatment. However, subsequent pharmacodynamic studies of this agent have led to its withdrawal from clinical development.

In the majority of our subjects with RSV+ve bronchiolitis ECP and LTC4 were detectable in upper airway secretions and were significantly associated with each other. In this clinical setting much of the detected LTC4 within upper airway secretions is likely to originate from the eosinophil, an observation that may have implications for clinical management and for delineation of the underlying mechanisms associated with this illness.

Asthma is a complex inherited disease. The study was undertaken to identify the association of RANTES promoter polymorphisms with atopy and asthma using family-based association tests (FBATs) and generation-specific case-control analyses. We identified 154 nuclear families (453 individuals) in whom we established RANTES promoter status using the RFLP-PCR method. Of the two known promoter polymorphisms À403G/A and À28C/G, only the former appeared with a clinically relevant frequency. A total of 61 families were eligible for assessment of transmission of the allele with asthma and atopy by the pedigree disequilibrium test (PDT). Overall, allele frequency for À403A was 38.3% and 84 of 89 (94.3%) alleles were transmitted with physician diagnosed asthma (PDA) (P ¼ 0.001). All 89 children with atopy received the mutant allele, which was more than expected following Mendelian Laws of transmission (P ¼ 0.0001). In 303 unrelated parents, significant associations of the mutant allele were for atopy with or without asthma (P ¼ 0.001). In 150 unrelated children, significant associations were for atopy alone (P ¼ 0.001) and asthma (P ¼ 0.001). No associations were found for bronchial hyperresponsiveness (BHR). The À403 G-A is transmitted with atopy and atopic asthma, although its contribution appears to relate more to atopy than asthma and BHR.

Background: A number of potential candidate genes have been implicated in the pathogenesis of asthma. A 32 base pair deletion in the CCR5 gene renders this chemokine receptor non-functioning and has been shown to be associated with a reduced prevalence of asthma in childhood. The mechanism may be related to impairment of pathogen entry into cells and modified host inflammatory response. We sought to determine the influence of the CCR5∆32 mutation on asthma and allergy in the transition from childhood to adulthood. Methods: 627 individuals first studied as part of a whole population schoolchildren cohort in 1989 when aged 8-12 years were followed up 10 years later for respiratory and allergy symptoms and laboratory markers of atopy. CCR5∆32 status was also characterised and the association with childhood and adulthood symptoms determined. Results: The follow up sample was representative of the original cohort except for a slightly greater prevalence of symptomatic individuals. As children, none who were homozygous for the CCR5∆32 mutation had a current physician's diagnosis of asthma. In multivariate analysis and controlling for known confounders, the protective effect of carrying the allele in childhood was highly significant (OR 0.31, 95% CI 0.14 to 0.72, p=0.006). There was no protective association with "current asthma" as classified in adulthood within the same population. Subjective or laboratory markers of atopy in childhood or adulthood were not associated with the CCR5∆32 mutation. Methacholine bronchial hyperresponsiveness in adulthood was also unrelated to gene carrier status. Conclusions: In a population with a high allelic frequency for the CCR5∆32 mutation, a significant protection against childhood asthma is evident which is independent of atopy. This protection is lost in the transition between childhood and early adulthood. The contribution of different genetic candidates to the expression of asthma may change with advancing maturity and confound the interpretation of association and linkage studies unless age is taken into account.

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