An International Effort to Improve Methods of Data Collection and Exposure Assessment for Community-based Case-Control Studies of Occupational Disease

In a case of thymoma associated with myasthenia gravis, symptoms of relapse appeared 14 years after thymectomy. Tumour tissue from repeat resection showed the same histologic pattern and aneuploidy as in the original specimen. The case illustrates the necessity of wide surgical exposure to permit maximal thymectomy, though recurrence remains possible.     

Sequential monitoring of survival data with the Wilcoxon statistic

When a spending function is used in sequential data monitoring of a clinical trial, it is important to know the information fraction at the times of interim analysis. In a maximum duration designed study, the information fraction is unknown when data are monitored, and it has to be estimated. The modified Wilcoxon statistic developed by Peto and Peto and modified by Prentice is often used to compare two survival curves in a clinical trial. We give guidelines for estimating the information fraction in a maximum duration trial when this statistic is employed. When there is a relatively low event rate or the survival time is approximately exponential, the information fraction for the Peto-Peto-Prentice Wilcoxon statistic is very close to that of the popular logrank statistic. In other cases, it would be helpful to estimate the information fraction as a function of elapsed calendar time. We discuss both group sequential and continuous monitoring.     

Susceptibility to actively-induced murine experimental allergic encephalomyelitis is not linked to genes of the T cell receptor or CD3 complexes

The role of the T cell receptor (TCR) in the genetic control of susceptibility to autoimmune demyelinating diseases remains shrouded in controversy. We have used the CXD2 series of recombinant inbred lines (RIL) and a (B10.S/DvTe x SJL/J) x B10.S/DvTe backcross (BC1) population to test for linkage between susceptibility to actively-induced EAE and the different TCR and CD3 loci. The two populations were inoculated for induction of EAE, phenotyped for both clinical and histological parameters of disease, and genotyped using markers flanking the loci of interest in the CXD2 RIL and an SJL/J allele-specific TCR V beta assay in the BC1 mice. Comparisons between the CXD2 strain distribution pattern (SDP) for disease and the SDPs for the chromosomal regions containing the TCR alpha, beta, gamma, delta, and CD3 delta, epsilon, gamma and zeta loci showed no linkage to these loci. Additional tests between EAE susceptibility and several other immunologically important loci for which the SDPs were known also showed no linkage to the minor lymphocyte-stimulating antigen gene Mlsl, Hc, the gene encoding complement component C5, Cd8a, or Cd5. Furthermore, our data from the BC1 mice demonstrate that the Tcrb locus segregates independent of disease and does not modulate disease severity. We conclude that while autoreactive TCRs are undoubtedly necessary for disease pathogenesis, the principle non-MHC-linked loci controlling susceptibility to murine EAE in BALB/c mice are not linked to any of the individual TCR-CD3 complex genes. Similarly, the major disease genes in the SJL/J mouse are not linked to TCR V beta. Our data cannot, however, preclude the possibility that TCR/CD3 alleles are involved in epigenetic phenomena or susceptibility in other mouse strains or animal systems.     

A difference in the composition of bronchial mucus between smokers and non-smokers

The effects of the duration of the overall compression cycle and of the duration of the maximum compressive force on tablet strength were studied using an instrumented rotary tablet press. Various direct compression fillers were evaluated. Increasing the overall compression cycle duration to 10 sec resulted in significantly greater tablet tensile strengths with microcrystalline cellulose and compressible starch fillers but not with lactose or compressible sugar. Increasing the duration of the maximum compressive force to 20 sec significantly increased the tensile strength in all cases, but microcrystalline cellulose and compressible starch tablets were affected more than lactose or sugar tablets. The maximum compressive force decayed with time for all fillers but at a greater rate with microcrystalline cellulose and compressible starch. This behavior was attributed to differences in the extent of plastic flow. The decay curves were analyzed using the Maxwell model.