Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in vitro and in vivo

The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo.     

Analyses of rhythms of the body temperature in free running in rats

The objective of this study was to determine the disturbances of urea in serum and urine of endurance trained volunteers during prolonged exposure to hypokinesia (decreased number of km/day). The studies during hypokinesia (HK) were performed for 364 days on twenty long-distance runners in the age of 23 to 26 years, with an average peak oxygen uptake, of 66 ml.kg.min-1. All volunteers were divided into two equal groups: Ten volunteers were placed on a continuous regime of exercise 14.8 km/day and served as control subjects (CS). The remaining volunteers were subjected to continuous HK without the use of any preventive measures and were considered as the hypokinetic subjects (HS). For the simulation of the hypokinetic effect, the HS were kept continuously under an average of 2.7 km/day for the duration of the study. Prior to exposure to HK, the HS were on the same exercise regime as the CS. During a 60 day pre-HK period and during the experimental period, urinary excretion of urea, creatinine, sodium, potassium and calcium and concentrations thereof in serum were measured. In the HS the concentrations of urea, creatinine, sodium, potassium and calcium in serum and the rate of excretion thereof in urine increased significantly when compared to the CS. It was concluded that prolonged restriction of muscular activity induces significant disturbances of urea in serum and urine of endurance trained volunteers.     

Online Calculation and Prediction of the Strip Temperature in a Hot Strip Finishing Mill

The paper deals with a physical model for the calculation of the strip temperature in a hot rolling mill. Beside the heat transfer from the strip to the environment in the different mill sections a sub‐model for the material properties of steel including phase transitions is introduced. For the application in a process automation system an online adaptation of the model to the current state of the mill is indispensable. The adaptation is explained in detail.     

Quality of data regarding diagnoses of spinal disorders in administrative databases. A multicenter study

The purpose of the present study was to evaluate the accuracy of data regarding diagnoses of spinal disorders in administrative databases at eight different institutions. The records of 189 patients who had been managed for a disorder of the lumbar spine were independently reviewed by a physician who assigned the appropriate diagnostic codes according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). The age range of the 189 patients was seventeen to eighty-four years. The six major diagnostic categories studied were herniation of a lumbar disc, a previous operation on the lumbar spine, spinal stenosis, cauda equina syndrome, acquired spondylolisthesis, and congenital spondylolisthesis. The diagnostic codes assigned by the physician were compared with the codes that had been assigned during the ordinary course of events by personnel in the medical records department of each of the eight hospitals. The accuracy of coding was also compared among the eight hospitals, and it was found to vary depending on the diagnosis. Although there were both false-negative and false-positive codes at each institution, most errors were related to the low sensitivity of coding for previous spinal operations: only seventeen (28 per cent) of sixty-one such diagnoses were coded correctly. Other errors in coding were less frequent, but their implications for conclusions drawn from the information in administrative databases depend on the frequency of a diagnosis and its importance in an analysis. This study demonstrated that the accuracy of a diagnosis of a spinal disorder recorded in an administrative database varies according to the specific condition being evaluated. It is necessary to document the relative accuracy of specific ICD-9-CM diagnostic codes in order to improve the ability to validate the conclusions derived from investigations based on administrative databases.     

Metaplastic carcinoma of the breast: mammographic appearance with pathologic correlation

OBJECTIVE: The objective of this study was to describe the mammographic appearance with pathologic correlation of metaplastic carcinoma of the breast. CONCLUSION: Metaplastic carcinomas of the breast are masses with mammographic characteristics of low suspicion because of their histologic appearance. Metaplastic carcinoma should be included in the differential assessment of predominately circumscribed, noncalcified masses revealed on mammography. One salient feature that may distinguish metaplastic carcinomas is the occurrence of a circumscribed portion with a spiculated portion, which is seen in carcinomas that have a significant mixture of metaplastic and invasive carcinoma growth patterns.