Ian C. Marschner

The effect of heterogeneity on the spread of disease

In the formulations of standard epidemic models it is usually assumed that, as far as the spread of the disease is concerned, the community consists of homogeneous individuals who mix uniformly with one another. This is a simplifying assumption which helps to make the mathematics tractable. Empirical evidence suggests that in real world epidemics there is often variability among individuals. It is therefore important to determine how the introduction of heterogeneity among individuals is likely to affect any conclusions arrived at from consideration of the standard epidemic models.

Clinical application of a rapid, functional assay for multidrug resistance based on accumulation of the fluorescent dye, fluo-3

A rapid and simple functional assay for P-glycoprotein (Pgp) using flow cytometry to measure the accumulation of the flurophore fluo-3 has been applied to samples from patients with B-cell chronic lymphocytic leukaemia (B-CLL). Peripheral blood lymphocytes from 37 patients with B-CLL were studied for Pgp. Pgp expression, using MRK-16, a monoclonal antibody recognising an external surface epitope of Pgp, was detected in 92% of patients with B-CLL. The functional assays for Pgp expression were positive in 78 and 59% of patients using the fluo-3 and doxorubicin (dox) assays, respectively. When compared with the MRK-16 assay, the fluo-3 assay had a sensitivity of 82% compared to a sensitivity of 56% for the dox assay (P = 0.004). The specificity of the fluo-3 and dox assays could not be evaluated because of the low number of MRK-16 negative CLL cells.

Differential effects of estrogen, tamoxifen and the pure antiestrogen ICI 182,780 in human drug-resistant leukemia cell lines

ICI 182,780, a potent, new steroidal antiestrogen without apparent agonist activity, appears to be a potent modulator of the classic multidrug resistance (MDR) phenotype in the CEM/A7, CEM/VLB100 and K562/VIN100 MDR cell lines. This reagent had no effect on the respective parental CCRF-CEM and K562 cell lines. The use of 1.25 μM ICI 182,780 resulted in a 6- to 7-fold decrease in doxorubicin resistance in the CEM/A7 and CEM/VLB100 cell lines. A dose-response effect was observed at ICI 182,780 concentrations of up to 5 μM. As compared with tamoxifen (TAM), ICI 182,780 was 2 and 4 times more effective in the K562/VIN100 and CEM/A7 cell lines, respectively. ICI 182,780 at 0.625 μM increased [3H]-daunomycin uptake (P<0.0001) as effectively as 5 μM TAM in the resistant CEM/A7 line. Drug-efflux studies showed that 5 μM ICI 182,780 significantly decreased drug efflux as compared with 5 μM TAM (P<0.0001). Estradiol (EST) at 10 μM increased doxorubicin resistance by 1.2–1.3 times in the CEM/A7 and CEM/VLB100 cell lines and significantly decreased drug accumulation (P=0.002) and retention (P<0.001) in the CEM/A7 cell line. However, the addition of 10 μM EST to 1–2 μM ICI 182,780 did not inhibit the ability of ICI 182,780 to modulate doxorubicin resistance in the two resistant cell lines. Using reverse-phase high-performance liquid chromatography (HPLC) to measure lipophilicity, we found no apparent association between the ability of ICI 182,780, TAM or EST to modulate resistance and their relative hydrophobicity.

The effect of preferential mixing on the growth of an epidemic.

The spread of infection in a community stratified into classes, where individuals have a preference for either within- or between-class contact, is discussed. The effect of such classification is assessed through the comparison of heterogeneous epidemic models with corresponding homogeneous models. Stratification of the community is modeled via a multitype branching process approximation to the epidemic. This allows us to conveniently study its effect through such quantities as the epidemic threshold parameter and the probability of a major outbreak. Attention is focused on the model of May and Anderson; however, a number of other heterogeneous structures reflecting preferential mixing are also studied.