We determined if soy isoflavones have dose-related estrogenic and methylation effects. Thirty-four healthy premenopausal women were randomized to 40 mg or 140 mg isoflavones daily through one ...menstrual cycle. Breast specific and systemic estrogenic effects were assessed measuring the estrogenic marker complement (C)3 and changes in cytology, whereas methylation assessment of 5 cancer related genes (p16, RASSF1A, RAR β 2, ER, and CCND2) was performed on intraductal specimens. Serum genistein significantly increased after consuming both isoflavone doses. Cytology did not significantly change at either isoflavone dose. Serum C3 levels posttreatment were inversely related to change in serum genistein (r =-0.76, P = 0.0045) in women consuming low but not high dose isoflavones. The RAR β 2 hypermethylation increase posttreatment correlated with the posttreatment genistein level considering the entire group (r = 0.67, P = 0.0017) and those receiving high-dose isoflavones (r = 0.68, P = 0.021). At the low but not the high isoflavone dose, CCND2 hypermethylation increase correlated with posttreatment genistein levels (r = 0.79, P = 0.011). In summary, the inverse correlation between C3 and genistein suggests an antiestrogenic effect. Isoflavones induced dose-specific changes in RAR β 2 and CCND2 gene methylation, which correlated with genistein levels. This work provides novel insights into estrogenic and methylation effects of dietary isoflavones.
Since the Institute of Medicine (IOM) reports on medical errors and quality, national attention has focused on improving patient safety through changes in "systems" of care. These reports resulted in ...a new paradigm that, rather than centering on individual errors, focuses on the "systems" necessary to facilitate and enhance quality and protect patients.
To assess the status of hospital patient safety systems since the release of the IOM reports and to identify changes over time in 2 states that collaborated on a patient safety project funded by the Agency for Healthcare Research and Quality.
Survey of all acute care hospitals in Missouri and Utah at 2 points in time, in 2002 and 2004, using a 91-item comprehensive questionnaire (n = 126 for survey 1 and n = 128 for survey 2). To assess changes over time, we also studied the cohort of 107 hospitals that responded to both surveys.
Responses to the 91-question survey as well as changes in responses to the survey questions over an 18-month period. Seven latent variables were constructed to represent the most important patient safety constructs studied: computerized physician order entry systems, computerized test results, and assessments of adverse events; specific patient safety policies; use of data in patient safety programs; drug storage, administration, and safety procedures; manner of handling adverse event/error reporting; prevention policies; and root cause analysis. For each hospital, the 7 latent variables were summed to give an overall measure of the patient safety status of the hospital.
Development and implementation of patient safety systems is at best modest. Self-reported regression in patient safety systems was also found. While 74% of hospitals reported full implementation of a written patient safety plan, nearly 9% reported no plan. The area of surgery appears to have the greatest level of patient safety systems. Other areas, such as medications, with a long history of efforts in patient safety and error prevention, showed improvements, but the percentage of hospitals with various safety systems was already high at baseline for many systems. Some findings are surprising, given the overall trends; for example, while a substantial percentage of hospitals have medication safety systems, only 34.1% corrected reported full implementation at survey 2 of computerized physician order entry systems for medications, despite the growth of computer technology in general and in hospital billing systems in particular.
The current status of hospital patient safety systems is not close to meeting IOM recommendations. Data are consistent with recent reports that patient safety system progress is slow and is a cause for great concern. Efforts for improvement must be accelerated.
The assessment of DNA had demonstrated altered methylation in malignant compared to benign breast tissue. The purpose of our study was to (i) confirm the predictive ability of methylation assessment ...in breast tissue, and (ii) use the genes found to be cancer predictive in tissue to evaluate the diagnostic potential of hypermethylation assessment in nipple aspirate fluid (NAF) and mammary ductoscopic (MD) samples. Quantitative methylation specific (qMS)‐PCR was conducted on three specimen sets: 44 malignant (CA) and 34 normal (NL) tissue specimens, 18 matched CA, adjacent normal (ANL) tissue and NAF specimens, and 119 MD specimens. Training and validation tissue sets were analyzed to determine the optimal group of cancer predictive genes for NAF and MD analysis. NAF and MD cytologic review were also performed. Methylation of CCND‐2, p16, RAR‐β and RASSF‐1a was significantly more prevalent in tumor than in normal tissue specimens. Receiver operating characteristic curve analysis demonstrated an area under the curve of 0.96. For the 18 matched CA, ANL and NAF specimens, the four predictive genes identified in cancer tissue contained increased methylation in CA vs. ANL tissue; NAF samples had higher methylation than ANL specimens. Methylation frequency was higher in MD specimens from breasts with cancer than benign samples for p16 and RASSF‐1a. In summary, i) routine quantitative DNA methylation assessment in NAF and MD samples is possible, and ii) genes hypermethylated in malignant breast tissue are also altered in matched NAF and in MD samples, and may be useful to assist in early breast cancer detection.
To evaluate and compare the efficacy of pharmacological and nonpharmacological treatments of fibromyalgia syndrome (FMS).
This meta-analysis of 49 fibromyalgia treatment outcome studies assessed the ...efficacy of pharmacological and nonpharmacological treatment across four types of outcome measures-physical status, self-report of FMS symptoms, psychological status, and daily functioning.
After controlling for study design, antidepressants resulted in improvements on physical status and self-report of FMS symptoms. All nonpharmacological treatments were associated with significant improvements in all four categories of outcome measures with the exception that physically-based treatment (primarily exercise) did not significantly improve daily functioning. When compared, nonpharmacological treatment appears to be more efficacious in improving self-report of FMS symptoms than pharmacological treatment alone. A similar trend was suggested for functional measures.
The optimal intervention for FMS would include nonpharmacological treatments, specifically exercise and cognitive-behavioral therapy, in addition to appropriate medication management as needed for sleep and pain symptoms.
The goal of this prospective study was to determine (a) concentrations of the carbohydrate biomarkers Thomsen Friedenreich (TF) antigen and its precursor, Tn antigen, in nipple discharge (ND) ...collected from women requiring biopsy because of a suspicious breast lesion; and (b) if concentration levels predicted pathologic diagnosis.
Adult women requiring biopsy to exclude breast cancer were enrolled and ND obtained. The samples from 124 women were analyzed using an anti-TF and anti-Tn monoclonal antibodies in direct immunoassay.
The highest median concentration in ND for TF and Tn was in women with ductal carcinoma in situ (DCIS). TF was higher in women with 1) cancer (DCIS or invasive) vs. either no cancer (atypia or benign pathology, p = .048), or benign pathology (p = .018); and 2) abnormal (atypia or cancer) versus benign pathology (p = .016); and was more predictive of atypia or cancer in post- compared to premenopausal women. Tn was not predictive of disease. High TF concentration and age were independent predictors of disease, correctly classifying either cancer or abnormal vs. benign pathology 83% of the time in postmenopausal women.
TF concentrations in ND were higher in women with precancer and cancer compared to women with benign disease, and TF was an independent predictor of breast atypia and cancer. TF may prove useful in early breast cancer detection.
ABSTRACT
This is the second in a series of papers presenting a new calculation of the mass of the Galaxy based on radial velocities and distances for a sample of faint 16 < B < 21.3 field blue ...horizontal‐branch (BHB) stars. We present accurate BV CCD photometry and spectra for 142 candidate A‐type stars selected from ubjr photometry of UK Schmidt telescope plates in six high‐Galactic‐latitude fields. Classification of these candidates produces a sample of 60 BHB stars at distances of 11–52 kpc from the Sun (mean 28 kpc), with heliocentric line‐of‐sight velocities accurate to 15 km s−1, and distance errors <10 per cent. We provide a summary table listing coordinates and velocities of these stars. The measured dispersion of the radial component of the Galactocentric velocity for this sample is 108 ± 10 km s−1, in agreement with a recent study of the distant halo by Sirko and coworkers. Measurements of the Ca ii K line indicate that nearly all the stars are metal‐poor with a mean Fe/H=−1.8 with dispersion 0.5. Subsequent papers will describe a second survey of BHBs to heliocentric distances 70 < R < 125 kpc and present a new estimate of the mass of the Galaxy.
We present FOcal Reducer/low dispersion Spectrograph-1 spectra (from the European Southern Observatory's Very Large Telescope) of a sample of 34 faint 20.0 < g* < 21.1 A-type stars selected from the ...Sloan Digital Sky Survey Early Data Release, with the goal of measuring the velocity dispersion of blue horizontal branch (BHB) stars in the remote Galactic halo, R∼ 80 kpc. We show that colour selection with 1.08 < u*−g* < 1.40 and −0.2 < g*−r* < −0.04 minimizes contamination of the sample by less luminous blue stragglers. In classifying the stars we confine our attention to the 20 stars with spectra of signal-to-noise ratio >15 Å−1. Classification produces a sample of eight BHB stars at distances 65–102 kpc from the Sun (mean 80 kpc), which represents the most distant sample of Galactic stars with measured radial velocities. The dispersion of the measured radial component of the velocity with respect to the centre of the Galaxy is 58 ± 15 km s−1. This value is anomalously low in comparison with measured values for stars at smaller distances, as well as for satellites at similar distances. Seeking an explanation for the low measured velocity dispersion, further analysis reveals that six of the eight remote BHB stars are plausibly associated with a single orbit. Three previously known outer halo carbon stars also appear to belong to this stream. The velocity dispersion of all nine stars relative to the orbit is only 15 ± 4 km s−1. Further observations along the orbit are required to trace the full extent of this structure on the sky.
Celecoxib inhibits PGE2 production in cancerous tissue. We previously reported that PGE2 levels in nipple aspirate fluid (NAF) and plasma were not decreased in women at increased breast cancer risk ...who received celecoxib 200 mg twice daily (bid). The endpoints of the current study were to determine if a short course of celecoxib 400 mg bid would decrease PGE2 levels in women 1) at increased breast cancer risk, and 2) with established breast cancer.
NAF and plasma samples were collected before, 2 weeks after taking celecoxib 400 mg bid, and two weeks after washout from 26 women who were at increased breast cancer risk. From 13 women with newly diagnosed breast cancer, NAF from the incident breast and plasma were collected before and on average 2 weeks after taking celecoxib. Additionally, in nine of the 13 women with breast cancer, NAF was collected from the contralateral breast.
No consistent change in NAF or plasma PGE2 levels was noted in high risk premenopausal women. NAF PGE2 levels decreased after celecoxib administration in postmenopausal high risk women (p = 0.02), and in both the NAF (p = 0.02) and plasma (p = 0.03) of women with breast cancer.
Celecoxib 400 mg bid taken on average for 2 weeks significantly decreased NAF, but not plasma, PGE2 levels in postmenopausal high risk women, and decreased both NAF and plasma PGE2 levels in women with newly diagnosed breast cancer. PGE2 levels may predict celecoxib breast cancer prevention and treatment efficacy. Our observations are preliminary, and larger studies to confirm and extend these findings are warranted.
PDF
