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.     

Pharmacokinetics of SPECT radiopharmaceuticals for imaging hypoxic tissues

Low back pain (LBP), a common illness that may progress to chronic disability, costs many billions for care, lost work, and compensation. Conventional medicine does not effectively restore chronic LBP patients to work; multidisciplinary rehabilitation does, but limited or delayed access risks unnecessary costs, additional morbidity, and permanent disability. The authors examine costs of delayed treatment for 23 disabled LBP patients in a rehabilitation program. Compensation costs average $26,159 per patient, a sum covering treatment for 3 patients. Additional medical and societal costs are estimated. Factors causing delay, such as economic incentives and ignorance about pain, and policies to remediate these problems, are discussed.     

On the logic of preference and judgment aggregation

Agents that must reach agreements with other agents need to reason about how their preferences, judgments, and beliefs might be aggregated with those of others by the social choice mechanisms that govern their interactions. The emerging field of judgment aggregation studies aggregation from a logical perspective, and considers how multiple sets of logical formulae can be aggregated to a single consistent set. As a special case, judgment aggregation can be seen to subsume classical preference aggregation. We present a modal logic that is intended to support reasoning about judgment aggregation scenarios (and hence, as a special case, about preference aggregation): the logical language is interpreted directly in judgment aggregation rules. We present a sound and complete axiomatisation. We show that the logic can express aggregation rules such as majority voting; rule properties such as independence; and results such as the discursive paradox, Arrow’s theorem and Condorcet’s paradox—which are derivable as formal theorems of the logic. The logic is parameterised in such a way that it can be used as a general framework for comparing the logical properties of different types of aggregation—including classical preference aggregation. As a case study we present a logical study of, including a formal proof of, the neutrality lemma, the main ingredient in a well-known proof of Arrow’s theorem.     

Health practices and hardiness as mediators in the stress-illness relationship.

Two stress and illness models that included the joint mediating effects of health practices and hardiness were tested prospectively over a 2-mo period. 86 undergraduates completed 5 subscales indexing hardiness. Stress, health practices, and illness for the prior month were assessed at this time as well as 1 and 2 mo later. In the 1st model, illness was measured by the severity of physical symptoms. In the 2nd model, it was measured by the number of symptoms reported. In both models, path analyses revealed that stress acted directly to affect illness as well as indirectly by changing health practices. Hardiness also had a direct effect on illness as well as an indirect effect through health practices. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of a behavioral self-regulation intervention on patient adherence in hemodialysis.

The present study examined the efficacy of a behavioral intervention designed to increase adherence to fluid-intake restrictions among hemodialysis patients. Twenty intervention-group patients were compared with 20 matched control patients on an indicator of fluid-intake adherence at 3 time points. The Group X Time interaction was significant, indicating that patients in the 2 groups exhibited a differential pattern of change in fluid-intake adherence across the follow-up period. The intervention and control groups did not differ significantly in terms of adherence at the initial postintervention period but did differ at the 8-week follow-up. The observed group differences were, in part, due to a trend toward increasingly better adherence in the intervention group and poorer adherence in the control group across the follow-up period. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recovery of alicyclobacillus from inhibitory fruit juice concentrates

Growth of Alicyclobacillus in low-pH fruit juices may result in off-odors and off-flavors due to the production of compounds such as guaiacol (2-methoxy phenol). An important step in preventing Alicyclobacillus contamination of fruit juices is the screening of incoming ingredients. Many fruit juice concentrates contain compounds that inhibit Alicyclobacillus growth, but beverages produced from the concentrates may not contain sufficient amounts of the active component to prevent spoilage. Therefore, accurate screening of juice concentrates is essential to prevent false-negative test results and product spoilage. The objective of this study was to evaluate isolation methods for detection of Alicyclobacillus in inhibitory juice concentrates. Recovery of Alicyclobacillus spores from inoculated and naturally contaminated concentrates was compared by using pour plate, spread plate, and filtration methods. Pour plates consistently recovered the lowest number of spores from inoculated concentrates. Spread plating was the most effective method used to recover spores from inoculated apple and pomegranate juice concentrates, while filtration resulted in the highest recovery from cranberry concentrate. When tested on naturally contaminated concentrates, the pour plate method failed to detect Alicyclobacillus in many samples. Filtration was much more effective. The filtration method increased the likelihood of detecting Alicyclobacillus contamination of fruit juice concentrates containing inhibitory compounds.