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.     

Intralesional radiolabeled human monoclonal IgM in human tumor xenografts

Sensory-perceptual abnormalities in people with autism are discussed from two perspectives: published firsthand accounts and existing psychological research evidence. A range of abnormalities, including hyper- and hyposensitivity, sensory distortion and overload, and multichannel receptivity and processing difficulties, are described in firsthand accounts and frequently portrayed as central to the autistic experience. A number of dangers are inherent in uncritically accepting these accounts at face value and in any wider generalization to the autistic population as a whole. Evidence from clinical studies suggests that unusual sensory responses are present in a majority of autistic children, that they are manifested very early in development, and that they may be linked with other aspects of autistic behavior. In addition, experimental studies using a range of indices have found evidence of unusual responses to sensory stimuli in autistic subjects. However the clinical and experimental research to date suffers from serious methodological limitations and more systematic investigation is warranted. Key issues for future psychological research in the area are identified.     

A distributed adverse drug reaction detection system using intelligent agents with a fuzzy recognition‐primed decision model

Discovering unknown adverse drug reactions (ADRs) in postmarketing surveillance as early as possible is highly desirable. Nevertheless, current postmarketing surveillance methods largely rely on spontaneous reports that suffer from serious underreporting, latency, and inconsistent reporting. Thus these methods are not ideal for rapidly identifying rare ADRs. The multiagent systems paradigm is an emerging and effective approach to tackling distributed problems, especially when data sources and knowledge are geographically located in different places and coordination and collaboration are necessary for decision making. In this article, we propose an active, multiagent framework for early detection of ADRs by utilizing electronic patient data distributed across many different sources and locations. In this framework, intelligent agents assist a team of experts based on the well‐known human decision‐making model called Recognition‐Primed Decision (RPD). We generalize the RPD model to a fuzzy RPD model and utilize fuzzy logic technology to not only represent, interpret, and compute imprecise and subjective cues that are commonly encountered in the ADR problem but also to retrieve prior experiences by evaluating the extent of matching between the current situation and a past experience. We describe our preliminary multiagent system design and illustrate its potential benefits for assisting expert teams in early detection of previously unknown ADRs. © 2007 Wiley Periodicals, Inc. Int J Int Syst 22: 827–845, 2007.     

A prolog based expert system for the allocation of quality assurance program resources

The worldwide proliferation of fraudulent materials has brought about the need for a new approach to the control of purchased material quality. Nuclear power, defense, aerospace and many other industries are affected by the supply of poor quality clones that presume to be original replacement parts. Safety considerations abound as these highly defective materials are used in systems that are critical to the preservation of human lives. Commonly utilized quality assurance programs have not effectively stopped the influx of fraudulent materials. These programs fail to concentrate inspection efforts on materials and inspection attributes that would effectively prevent the acceptance of fraudulent materials. herein a solution is presented to this problem in the form of an expert system application. Information commonly available in industry is formulated into a knowledge based system wherein advisories are given to the user regarding key purchased material receipt inspection strategies.     

Basic considerations in gastroesophageal reflux disease

The cause of foregut symptoms is often quite uncertain until a comprehensive evaluation has been performed. The critical elements of this evaluation include historic, radiographic, endoscopic, and physiologic data, and most importantly, the insight of a mature diagnostician. Patients who are not evaluated in a comprehensive way are at risk for serious postoperative problems; surgeons who perform interventions without appropriate diagnostic support may have to deal with these unhappy patients. In the long run, a complete workup provides the guidance for treatment and is cost-effective.     

Is electrogastrography a substitute for manometric studies in children with functional gastrointestinal disorders?

We performed simultaneous fasting and fed antroduodenal manometry and EGG in 25 children with functional bowel disorders. Three patients (12%) had an uninterpretable EGG. The manometric studies showed severe neuropathy in six patients; milder neuropathic changes in five patients; postprandial hypomotility in one patient; myopathy in four patients, and normal motility in the remaining six patients. The percentage of tachygastria time (frequency > 3.5 cycles/min) was higher in the patiens with mild (44.1 +/- 15.8%) and severe (48 +/- 19.1%) neuropathy than in the patients with myopathy (20 +/- 16.2%, P < 0.05) or with normal motility (23 +/- 13.3%, P < 0.05). There was a considerable overlap in the percentage of tachygastria and total arrhythmia time among the different study groups. The ratio of post- to preprandial power was significantly higher (2.5 +/- 0.07) in children with normal motility than in the other patients groups. Every child with total arrhythmia time < 35% and a ratio of post- to preprandial power > 2.4 had normal manometry. In summary, EGG differentiated groups of children with normal manometry from others with neuropathic or myopathic changes, but in a minority of patients the study was not interpretable and there was overlap in EGG results between children with normal and abnormal manometry.     

Symptom correlates of attentional improvement following hospitalization for a first episode of affective psychosis

BACKGROUND: This study examined patients with a first-episode of affective psychosis during acute and compensated states in order to determine whether changes in attentional functioning over time were accompanied by changes in the severity of psychotic or affective symptoms. METHODS: Attentional performance was measured in patients (n = 27) using the degraded-stimulus continuous Performance Test (CPT) and symptoms were assessed at the time of index hospitalization, and 2 months after discharge. A comparison group of normal volunteers (n = 31) also performed the CPT two months apart. RESULTS: Patients performed significantly worse than controls at the initial testing but not at follow-up. The improvement in attentional performance significantly correlated with decreased severity of manic symptoms. CONCLUSIONS: Results suggest attentional dysfunction is a state-dependent characteristic of mania, and may provide an additional measure of clinical improvement following treatment.     

Results of selective venous site-specific catheterization in occult C-cell carcinoma of the thyroid gland

Ileal pouch-anal anastomosis is a surgical procedure used for the treatment of people with chronic ulcerative colitis and familial adenomatous polyposis. The surgery is intended to preserve anal sphincter function, but it carries a risk for certain complications, including pouchitis and anastomotic stricture. The purpose of this article is to review the clinical manifestations, causes, and treatment of anastomotic stricture and pouchitis after ileal pouch-anal anastomosis.     

Wooden sticks as the source of a pseudoepidemic of infection with Rhizopus microsporus var. rhizopodiformis among immunocompromised patients

Wooden sticks used to suspend feces obtained for surveillance cultures were found to be the source of Rhizopus microsporus var. rhizopodiformis causing a pseudo-outbreak among 17 immunocompromised patients cared for in three different wards. Nonsterile wooden products should therefore not be used for collecting, handling, and processing specimens for microbiological examination.     

The L5178Y/tk+/- mouse lymphoma specific gene and chromosomal mutation assay a phase III report of the U.S. Environmental Protection Agency Gene-Tox Program

The L5178Y/tk+/- (-)3.7.2C mouse lymphoma assay (MLA) which detects mutations affecting the heterozygous thymidine kinase (tk) locus is capable of responding to chemicals acting as clastogens as well as point mutagens. Improvements in the assay to enhance detection of this spectrum of genetic events are summarized, and criteria for evaluating the data are defined. Using these criteria, the Phase III Work Group reviewed and evaluated literature containing MLA results published from 1976 through 1993. The data base included 602 chemicals of which 343 were evaluated as positive, 44 negative, 18 equivocal, 54 apparently inappropriate for evaluation in this test system with the published protocols, and 142 that were inadequately tested, and thus a definitive call could not be made. The overall performance of the assay is summarized by chemical class, and the outcome of testing 260 chemicals in the MLA is compared with Gene-Tox and National Toxicology Program evaluations of rodent carcinogenesis bioassay results for the same chemicals. Based on the Work Group's evaluation of published MLA data for chemicals that were considered adequately tested, it is concluded that for most chemicals the L5178Y/tk+/- mouse lymphoma assay is eminently well suited for genotoxicity testing and for predicting the potential for carcinogenicity.