The ordered transmission disequilibrium test: detection of modifier genes

We consider the problem of detection of modifier genes that lead to variations in a disease‐related continuous variable (DRCV), such as the age of onset or a measure of disease severity, in a strategy of candidate genes. We propose a novel method, the ordered transmission disequilibrium test (OTDT), to test for a relation between the clinical heterogeneity expressed by a DRCV and marker genotypes of a candidate gene. The OTDT applies to trio families with one patients and his parents, all three genotyped at a bi‐allelic marker M. The OTDT aims to find a critical value of the DRCV which separates the sample of families in two subsamples in which the transmission rates are significantly different. We investigate the power of the method by simulations under various genetic models and covariate distributions and compare it with a linear regression analysis. Genet. Epidemiol. 2008. ©2008 Wiley‐Liss, Inc.     

Longitudinal analysis of the relation between moderate long‐term stress and health

The main goal of the present work was to longitudinally examine consequences of long‐term moderately elevated levels of stress for various health outcomes. To address this issue, data covering 10 years was used from the ongoing Swedish population‐based prospective Betula Study. Based on the ratings on a validated self‐reported stress scale, matched subsamples between 40 and 65 years of age were divided into a high (n = 137) and low (n = 211) stress group. The reported incidence of cardiovascular, diabetes, psychiatric, tumour and musculoskeletal diseases was assessed 5 and 10 years after baseline (baseline = 1993–1995) without contaminating effects of past health history. The incidence of diseases 5 years after baseline assessment showed no differences between the groups. After 10 years, there was a significantly higher incidence of psychiatric diseases, mainly depression in the high‐stress group as well as a significant effect for tumours, although the number of cases was low. Although moderately elevated stress level may have a possible impact on psychiatric diseases especially depression and some tumours, it seems that prolonged moderate stress does not appear to be harmful to other stress‐related diseases. Copyright © 2007 John Wiley & Sons, Ltd.     

A case of congenital supratentorial tumor: Atypical teratoid/rhabdoid tumor or primitive neuroectodermal tumor?

Two embryonal CNS tumors, atypical teratoid/rabdoid tumor (AT/RT) and primitive neuroectodermal tumor (PNET), may be confused with each other and misdiagnosed. Here we report an infant with a congenital supratentorial tumor, which was detected by fetal MRI at 37 weeks gestation. On routine histological examination, the tumor was composed mainly of small undifferentiated cells, among which many rhabdoid cells and occasional sickle‐shaped embracing cells were observed. No mesenchymal or epithelial areas were evident. Our impression was that the tumor was an atypical example of AT/RT. Immunohistochemically, almost all the tumor cells were strongly positive for vimentin. However, epithelial membrane antigen was notably negative, and most of the tumor cell nuclei were clearly positive for INI1. In addition, many tumor cells were positive for neurofilament protein. There were also occasional small areas containing many tumor cells positive for glial fibrillary acidic protein. Finally, a diagnosis of PNET, with a rhabdoid phenotype and expression of neuronal and glial markers, was made. In the present case, application of INI1 immunostaining was very helpful for distinguishing PNET from AT/RT.     

ENDOSCOPIC MUCOSAL RESECTION AND SUBMUCOSAL DISSECTION METHOD FOR LARGE COLORECTAL TUMORS

The goal of endoscopic mucosal resection (EMR) is to allow the endoscopist to obtain tissue or resect lesions not previously amenable to standard biopsy or excisional techniques and to remove malignant lesions without open surgery. In this article, we describe the results of conventional EMR and EMR using an insulation‐tipped (IT) electrosurgical knife (submucosal dissection method) for large colorectal mucosal neoplasms and discuss the problems and future prospects of these procedures. At present, conventional EMR is much more feasible than EMR using IT‐knife from the perspectives of time, money, complication, and organ preservation. However, larger lesions tend to be resected in a piecemeal fashion; and it is difficult to confirm whether EMR has been complete. For accurate histopathological assessment of the resected specimen en bloc EMR is desirable although further experience is needed to establish its safety and efficacy. Further improvements of in EMR with special knife techniques are required to simply and safely remove large colorectal neoplasms.