Effect of rosuvastatin on risk markers for venous thromboembolism in cancer.

Essentials Statins lower venous thromboembolism risk in general but have not been studied in cancer patients. We completed a randomized trial of rosuvastatin vs. placebo among cancer patients on chemotherapy. Rosuvastatin did not significantly lower prothrombotic biomarkers including D-dimer. The role of statins in venous thrombosis prevention in cancer patients remains unknown. SUMMARY: Background Statin therapy is associated with lower risk of venous thromboembolism (VTE) but has not been prospectively evaluated in patients with advanced cancer. Objectives We determined if statin administration in this high-risk population reduces the risk of VTE, based on established and emerging biomarkers. Patients/Methods This double-blind, crossover, randomized controlled trial among patients with advanced cancer receiving systemic therapy allocated participants to rosuvastatin 20 mg daily or placebo for 3-4 weeks prior to crossover to the alternative therapy, with a 3-5-week washout. D-dimer, C-reactive protein (CRP), soluble (s)P-selectin, factor VIII (FVIII), thrombin generation and exploratory biomarkers focusing on endogenous thrombin potential, including tissue factor (TF), activated factor IX (FIXa) and activated factor XI (FXIa), were measured at the start and end of both treatment periods. The primary outcome was change in D-dimer with rosuvastatin compared with placebo. Results Of 38 enrolled participants, 24 (63%) completed the study. Rosuvastatin did not cause statistically significant changes in D-dimer levels or any other biomarker. CRP levels decreased by 40%; 4.3 mg L-1 (95% confidence interval, -11.0 to +2.5 mg L-1 ) compared with placebo. In post-hoc analysis, participants who received rosuvastatin initially during their first line of treatment had a 13% decrease in D-dimer. Circulating TF, FIXa and FXIa were detected in 26%, 68% and 71% of cancer patients despite not being found in healthy individuals. Conclusions Rosuvastatin did not cause favorable changes in biomarkers of VTE risk in advanced cancer patients receiving chemotherapy. The role of statin therapy as thromboprophylaxis in the cancer population remains uncertain.

Methodology validation, intra-subject reproducibility and stability of exhaled volatile organic compounds.

Robust methods for breath sampling and analysis are required for potential clinical applications. We have evaluated an improved sampling and experimental design, assessing instrumental and biological variability within and across breath measurements. Calibration curves for selected relevant volatile organic compounds (VOCs) were produced to look at the dynamic range and stability of analysis by gas chromatography/time-of-flight mass spectrometry. Linear responses were observed with R(2) > 95% and limits of detection in mid-range pg/µl. Overall experimental design, visualized by means of principal component analysis, demonstrated good clustering on quality control samples, background air and blanks, with dispersion observed as expected across human breath samples. Serial sampling while breathing VOC-filtered air for up to 30 min demonstrated marked variation in reproducibility of VOCs, with median intraclass correlation coefficient of 0.29 (interquartile range 0.16-0.71), with no apparent effect of disease status. We have shown that we can reliably detect VOCs at very low concentrations in exhaled breath samples, and that the reproducibility depends on (a) compound of interest; (b) length of time breathing VOC-filtered air. These parameters will require investigation in studies of potential breath biomarkers, and must be standardized if tests are to become clinically useful.

Metabolism of 2-fluoro-4-iodoaniline in earthworm Eisenia veneta using (19)F-NMR spectroscopy, HPLC-MS, and HPLC-ICPMS ((127)I).

A combination of (19)F-NMR spectroscopy, HPLC-MS/MS, HPLC-MS with constant neutral loss scanning of 127, and HPLC-ICPMS with iodine detection has enabled the profiling, quantification, and limited characterization of the metabolites produced in the earthworm Eisenia veneta, following exposure to 2-fluoro-4-iodoaniline. Mass spectrometric analysis of the worm tissue and coelomic fluid afforded the identification of two Phase II metabolites, N-glutamyl and N-glucoside conjugates, indicating the importance of these pathways in the detoxification of xenobiotics for earthworms. Several further metabolites were observed and quantified by (19)F-NMR spectroscopy and HPLC-(127)I-ICPMS, although these were of low abundance and their structures were not unequivocally identified. The parent compound and the glutamyl conjugate were found to be the major xenobiotic components of both the coelomic fluid and the worm tissue, representing approximately 23 and approximately 35%, respectively, of the dose that was recovered from the earthworm tissue extract.

Variations in the estimation of the contribution of environmental tobacco smoke (ETS) to respirable (< or = 5 microns) indoor air particulates obtained by the use of different analytical methods.

Several methods are in use for the identification of the contribution of particulate associated environmental tobacco smoke (ETS) and sidestream smoke to an atmosphere. These include the measurement of respirable suspended particulates (RSP), measurements of the total UV absorption and total fluorescence emission of a methanol extract of collected particulates and the use of specific marker compounds such as solanesol and scopoletin. Use of these methods gave values for the contribution of particulate ETS to total respirable (< or = 5 microns) particulates in the ranges 8.3-124.7% for smokers' houses and 9.6-121.2% for smokers' offices, respectively. However, using what we consider to be the most reliable methodology, based on the measurement of solanesol, the average contribution of particulate ETS to total respirable (< or = 5 microns) particulates for smokers' houses was 21.7% and for smokers' offices was 23.3%.

Cryptosporidium plus Campylobacter: an outbreak in a semi-rural population.

An outbreak of cryptosporidiosis in a circumscribed semi-rural population is described; some cases were infected concurrently with campylobacter. The results of a detailed case-control study and environmental surveillance are discussed.