Risks to the public from historical releases of radionuclides and chemicals at the Rocky Flats Environmental Technology Site

This paper summarizes the methods and results of estimating risks of cancer incidence resulting from plutonium, carbon tetrachloride, and beryllium releases from operations at the Rocky Flats Environmental Technology Site, near Denver, Colorado, from 1953 through 1989. The key findings show that people who lived near the facility were exposed to plutonium mainly through inhalation during routine operations, from a major fire in 1957, and from plutonium resuspended from contaminated soil from an outdoor drum storage area, called the 903 Area. Results were presented for five exposure scenarios that were location-independent. Individuals described by the laborer scenario received the highest risk of all scenarios considered. Upper bound (95th percentile) incremental lifetime cancer incidence risks for the laborer scenario were in about the 10(-4) range (1 chance in 10,000) for developing cancer from Rocky Flats plutonium releases during a lifetime. At the 5th percentile level, the maximum cancer risk was about 10(-7) (1 chance in 10 million) for developing cancer during a lifetime. Estimated cancer risks at the 95th percentile level are within the range of for acceptable risks established by the US Environmental Protection Agency of 10(-6) to 10(-4). Carbon tetrachloride was found to be the chemical that presented the highest risk to the public. The 5th and 95th percentile risk values for exposure to carbon tetrachloride were 9.2x10(-7) and 2.5x10(-5), respectively.     

Upper airway malformation associated with partial trisomy 11q

11q trisomy is associated with a recognizable pattern of multiple malformations. Review of the literature reveals the following recurrent themes common to complex and isolated 11q trisomy: mental retardation, pre- and postnatal growth retardation, hypotonia, a distinct pattern of facial features, congenital heart defects, and limb malformations. We report four patients with partial trisomy 11q, none of which arose from the common 11/22 translocation. Three of the four patients had the previously unreported finding of upper airway obstruction secondary to a malformed epiglottis. The critical region for this malformation appears to be 11q21-23.2.     

Respiratory hygiene practices by the public during the 2009 influenza pandemic: an observational study

Please cite this paper as: Barry et al. (2011) Respiratory hygiene practices by the public during the 2009 influenza pandemic: an observational study. Influenza and Other Respiratory Viruses 5(5), 317–320. Aims To describe the public use of respiratory hygiene behaviours during the 2009 influenza pandemic and to test the feasibility of an observational method. Methods Respiratory behaviour was systematically observed at three public settings during August 2009 in the capital city of New Zealand (Wellington). Data on each coughing or sneezing event were collected. Results A total of 384 respiratory events were observed, at a rate of 0·8 cough/sneeze per observed‐person‐hour. Around a quarter of respiratory events (27·3%) were uncovered, and there was infrequent use of the responses recommended by health authorities (i.e., covering with a tissue or handkerchief at 3·4% and covering with elbow or arm at 1·3%). Respiratory event rates were higher in all settings that were ‘high flow’ (for people movement) compared to ‘low flow’ settings. Uncovered events were more common among people at the hospital entrance versus the hospital café [risk ratio (RR) = 7·8, 95% confidence interval (CI): 1·1–52·6] and when a person was located within 1 m of others (RR = 1·5, 95% CI: 1·1–1·9). Observing respiratory hygiene was found to be feasible in all of the selected public locations. There was good agreement between observing pairs about whether or not respiratory events occurred (inter‐observer correlation = 0·81) and for uncovered versus covered events (total Cohen’s kappa score = 0·70). Conclusions It was feasible to document respiratory hygiene behaviour in public urban settings during a influenza pandemic. Respiratory hygiene advice was not being adequately followed by this population towards the end of the first wave of the pandemic.     

Minor role of pregnane-x-receptor for acquired multidrug resistance in head and neck squamous cell carcinoma in vitro

Purpose

Acquired multidrug resistance (MDR) has been linked to overexpression of drug-metabolising and transporting proteins mediated by pregnane-x-receptor (PXR). The aim of this work was to establish the relevance of PXR for MDR in head and neck squamous cell carcinoma (HNSCC).

Methods

Using eight HNSCC cell lines, we determined the efficacy of paclitaxel, cisplatin and 5-fluorouracil (5-FU) via proliferation assays and determined the expression and activity of PXR through quantitative real-time polymerase chain reaction, western blotting and luciferase-based reporter gene assay. PXR knockdown approaches using shRNA-encoding vectors were applied to estimate the role of PXR for native MDR.

Results

Drug resistance ranged between 5.2 and 620 nM for paclitaxel, varied between 4.5 and 58 μM for cisplatin, and varied between 1.1 and 5,467 μM for 5-FU. Lack of PXR mRNA expression was mostly accompanied by the absence of mRNA expression of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp, ABCB1) expression. Neither mRNA nor protein expression of PXR correlated with drug resistance. However, PXR activity tended to correlate with IC₅₀ values of paclitaxel (p = 0.08). Knockdown of PXR in one of the cell lines had a slight but not significant impact on paclitaxel efficacy compared to scrambled sequence control. Surprisingly, only in two cell lines, PXR activity was increased by the well-known inductor rifampicin.

Conclusion

This study suggests a malfunctioning of PXR and thus a minor relevance for iatrogenic chemotherapy resistance in HNSCC.