In vitro and in vivo activity and cross resistance profiles of novel ruthenium (II) organometallic arene complexes in human ovarian cancer.

Ruthenium complexes offer the potential of reduced toxicity, a novel mechanism of action, non-cross resistance and a different spectrum of activity compared to platinum containing compounds. Thirteen novel ruthenium(II) organometallic arene complexes have been evaluated for activity (in vitro and in vivo) in models of human ovarian cancer, and cross-resistance profiles established in cisplatin and multi-drug-resistant variants. A broad range of IC50 values was obtained (0.5 to >100 microM) in A2780 parental cells with two compounds (RM175 and HC29) equipotent to carboplatin (6 microM), and the most active compound (HC11) equipotent to cisplatin (0.6 microM). Stable bi-dentate chelating ligands (ethylenediamine), a more hydrophobic arene ligand (tetrahydroanthracene) and a single ligand exchange centre (chloride) were associated with increased activity. None of the six active ruthenium(II) compounds were cross-resistant in the A2780cis cell line, demonstrated to be 10-fold resistant to cisplatin/carboplatin by a mechanism involving, at least in part, silencing of MLH1 protein expression via methylation. Varying degrees of cross-resistance were observed in the P-170 glycoprotein overexpressing multi-drug-resistant cell line 2780AD that could be reversed by co-treatment with verapamil. In vivo activity was established with RM175 in the A2780 xenograft together with non-cross-resistance in the A2780cis xenograft and a lack of activity in the 2780AD xenograft. High activity coupled to non cross-resistance in cisplatin resistant models merit further development of this novel group of anticancer compounds

Measuring body composition in overweight individuals by dual energy x-ray absorptiometry

BACKGROUND: Dual energy x-ray absorptiometry (DXA) is widely used for body composition measurements in normal-weight and overweight/obese individuals. The limitations of bone densitometers have been frequently addressed. However, the possible errors in assessing body composition in overweight individuals due to incorrect positioning or limitations of DXA to accurately assess both bone mineral density and body composition in obese individuals have not received much attention and are the focus of this report. DISCUSSION: We discuss proper ways of measuring overweight individuals and point to some studies where that might not have been the case. It appears that currently, the most prudent approach to assess body composition of large individuals who cannot fit under the scanning area would be to estimate regional fat, namely the regions of thigh and/or abdomen. Additionally, using two-half body scans, although time consuming, may provide a relatively accurate measurement of total body fat, however, more studies using this technique are needed to validate it. SUMMARY: Researchers using bone densitometers for body composition measurements need to have an understanding of its limitations in overweight individuals and address them appropriately when interpreting their results. Studies on accuracy and precision in measurements of both bone and soft tissue composition in overweight individuals using available densitometers are needed

Accuracy of responses from postal surveys about continuing medical education and information behavior: experiences from a survey among German diabetologists

BACKGROUND: Postal surveys are a popular instrument for studies about continuing medical education habits. But little is known about the accuracy of responses in such surveys. The objective of this study was to quantify the magnitude of inaccurate responses in a postal survey among physicians. METHODS: A sub-analysis of a questionnaire about continuing medical education habits and information management was performed. The five variables used for the quantitative analysis are based on a question about the knowledge of a fictitious technical term and on inconsistencies in contingency tables of answers to logically connected questions. RESULTS: Response rate was 52%. Non-response bias is possible but seems not very likely since an association between demographic variables and inconsistent responses could not be found. About 10% of responses were inaccurate according to the definition. CONCLUSION: It was shown that a sub-analysis of a questionnaire makes a quantification of inaccurate responses in postal surveys possible. This sub-analysis revealed that a notable portion of responses in a postal survey about continuing medical education habits and information management was inaccurate

Raloxifene: Mechanism of Action, Effects on Bone Tissue, and Applicability in Clinical Traumatology Practice

Raloxifene, a member of the class of selective estrogen receptor modulators (SERM), reproduces the beneficial effects of estrogens on the skeletal systems, without the negative effects estrogens on breast and endometrium

Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia.

Introduction: The change in bone turnover markers (BTM) in response to osteoporosis therapy can be assessed by a decrease beyond the least significant change (LSC) or below the mean of the reference interval (RI). We compared the performance of these two approaches in women treated with raloxifene. Methods: Fifty postmenopausal osteopenic women, (age 51-72y) were randomised to raloxifene or no treatment for 2 years. Blood samples were collected for the measurement of BTM. The LSC for each marker was calculated from the untreated women and the RI obtained from healthy premenopausal women (age 35-40y). Bone mineral density (BMD) was measured at the spine and hip. Results: There was a decrease in BTM in response to raloxifene treatment; percentage change at 12 weeks, CTX -39% (95% CI -48 to -28) and PINP -32% (95% CI -40 to -23) P<0.001. The proportion of women classified as responding to treatment using LSC at 12 weeks was: CTX 38%, PINP 52%, at 48 weeks CTX 60%, PINP 65%. For the RI approach; at 12 weeks CTX and PINP 38%, at 48 weeks CTX 40%, PINP 45%. There was a significant difference in the change in spine BMD in the raloxifene treated group compared to the no-treatment group at week 48; difference 0.031 g/cm2, (95% CI 0.016 to 0.046, P<0.001). Conclusions: The two approaches identified women that reached the target for treatment using BTM. Both LSC and RI criteria appear useful in identifying treatment response but the two approaches do not fully overlap and may be complementary

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table

Search for New Physics in e mu X Data at D0 Using Sleuth: A Quasi-Model-Independent Search Strategy for New Physics

We present a quasi-model-independent search for the physics responsible for electroweak symmetry breaking. We define final states to be studied, and construct a rule that identifies a set of relevant variables for any particular final state. A new algorithm ("Sleuth") searches for regions of excess in those variables and quantifies the significance of any detected excess. After demonstrating the sensitivity of the method, we apply it to the semi-inclusive channel e mu X collected in 108 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV at the D0 experiment during 1992-1996 at the Fermilab Tevatron. We find no evidence of new high p_T physics in this sample.Comment: 23 pages, 12 figures. Submitted to Physical Review

Search For Heavy Pointlike Dirac Monopoles

We have searched for central production of a pair of photons with high transverse energies in $p\bar p$ collisions at $\sqrt{s} = 1.8$ TeV using $70 pb^{-1}$ of data collected with the D\O detector at the Fermilab Tevatron in 1994--1996. If they exist, virtual heavy pointlike Dirac monopoles could rescatter pairs of nearly real photons into this final state via a box diagram. We observe no excess of events above background, and set lower 95% C.L. limits of $610, 870, or 1580 GeV/c^2$ on the mass of a spin 0, 1/2, or 1 Dirac monopole.Comment: 12 pages, 4 figure

The Dijet Mass Spectrum and a Search for Quark Compositeness in bar{p}p Collisions at sqrt{s} = 1.8 TeV

Using the DZero detector at the 1.8 TeV pbarp Fermilab Tevatron collider, we have measured the inclusive dijet mass spectrum in the central pseudorapidity region |eta_jet| < 1.0 for dijet masses greater than 200 Gev/c^2. We have also measured the ratio of spectra sigma(|eta_jet| < 0.5)/sigma(0.5 < |eta_jet| < 1.0). The order alpha_s^3 QCD predictions are in good agreement with the data and we rule out models of quark compositeness with a contact interaction scale < 2.4 TeV at the 95% confidence level.Comment: 11 pages, 4 figures, 2 tables, submitted to Phys. Rev. Let