Association between urinary 1-hydroxypyrene and genotoxic effects in coke oven workers

Methods: Blood and urine samples were collected immediately after a shift at the end of a working week from 50 coke oven workers and 50 control workers not exposed to PAHs. Methods included: (1) biomarkers of exposure: urinary 1-hydroxypyrene (HpU), urinary mutagenicity by the plate Salmonella test with strains TA98 and YG1024 after metabolic activation, expressed as mutagenic rate (MR98 and MR1024, respectively), urinary cotinine; and (2) biomarkers of biological effects in peripheral blood lymphocytes (PBL): sister chromatid exchanges (SCE/cell), cells of high frequency of SCE (% HFC), micronuclei (MN/1000 cells), chromosomal aberrations (CA/100 cells), and DNA damage by the Comet assay.

Results: Occupational exposure to PAH resulted in significantly increased levels of HpU and mutagenic effect of urine. Median values of these biomarkers in coke oven workers were: 9.0 µmol/mol creatinine for HpU, 2.7 for MR98, and 8.2 for MR1024, compared to the controls: HpU = 0.6 µmol/mol creatinine, MR98 = 1.2, and MR1024 = 5.5. Occupational exposure caused significant induction of SCE, HFC, and MN in coke oven workers: median SCE = 5.9, HFC = 12.0%, MN = 6.0 compared to the controls: 3.9, 5.0%, and 3.0, respectively. No effect of occupational exposure was found in relation to CA and DNA damage measured with the Comet assay. HpU concentration was positively associated with SCE and HFC. The concentration of urinary 1-hydroxypyrene corresponding to a 5% probability of increased SCE was 1.0 µmol/mol creatinine.

Conclusions: The occupational exposure to PAHs resulted in measurable biological effects (SCE, HFC, MN). In coke oven workers an increased level of SCE was not observed below the level of 1.0 µmol HpU/mol creatinine.

     

Environmental lead exposure increases micronuclei in children

The objective of this pilot study was to investigate the contribution of environmental exposures to lead in the development of cytogenetic damage detected as the frequency of micronuclei (MN) in children. The other aim was to apply the MN assay in combination with fluorescence in situ hybridization (FISH) using a pan-centromeric chromosome probe to elucidate the formation mechanism of induced MN. The examined population was composed of 9-year-old children (n = 92), living in the region where non-ferrous ores are extracted and processed. The non-exposed group consisted of 49 children of the same age from an unexposed recreational area. Exposure to lead was assessed by determination of lead concentrations in blood (PbB) by atomic absorption spectrophotometry, whereas the level of selenium (Se) in serum was detected by using graphite furnace atomic-absorption spectrometry. The frequency of MN was determined by the cytokinesis-block MN assay and fluorescence in situ hybridization performed using a specific pan-centromeric probe. Environmental exposure to lead resulted in significantly increased levels of PbB (5.29 +/- 2.09 versus 3.45 +/- 1.20 microg/dl in controls), although the average level was much below the value of the biological exposure limit = 10 microg/dl. A negative correlation between lead in blood and Se in serum concentrations (P = 0.006) was found for the pooled study population. The results showed a significant difference (P < 0.0001) in the level of MN between the exposed and control group (standard MN test: 2.96 +/- 2.36 versus 1.16 +/- 1.28; FISH technique: 3.57 +/- 3.02 versus 1.43 +/- 1.69, respectively). The frequencies of both centromere-positive (C+MN) and centromere-negative (C-MN) micronuclei were significantly increased in exposed children; however, the contribution of C+MN in the total number of MN in peripheral blood lymphocytes of exposed children was significantly higher than in the controls what may suggest a pro-aneugenic effect of the exposure to lead. The results of multiple regression analysis indicated that the exposure to lead was an important factor affecting the increase in MN frequency what was confirmed by significant correlation between the PbB and MN levels. In conclusion, our results suggest that the exposure to lead may be associated with an increased frequency of MN, especially of C+MN; however, the influence of other factors (e.g. vitamins and minerals in the diet) cannot be excluded.     

The effect of radiocolloid preference on major parameters in sentinel lymph node biopsy practice in breast cancer

IntroductionThe possible effects of radiocolloid preference on sentinel lymph node biopsy (SLNB) were investigated.MethodsA total of 200 patients with T1-2N0M0 breast cancer were evaluated. The first 100 patients underwent SLNB using ^99mTc tin colloid (TC) and the next 100 using ^99mTc nanocolloid (NC). Radiocolloid was injected intradermally at four quadrants of the periareolar region the day before surgery. All patients underwent lymphoscintigraphy 1 h after injection. All nodes having fourfold activity of the background were harvested using gamma probe.ResultsSentinel lymph node (SLN) identification rate by gamma probe was 98% in each group. The number of SLNs identified by lymphoscintigraphy, gamma probe and pathological evaluation was 1.39±0.7, 1.70±1.0 and 2.23±1.70 in the TC and 2.03±0.94, 2.60±1.36 and 3.05±1.90 in the NC group, respectively (P<.05). Metastatic SLN was found in 24 (24.4%) of 98 patients in the TC group and 41 (41.8%) of 98 patients in the NC group (P=.04). None of the patients showed dispersion to internal mammarian lymph nodes. Lymphatic vessel visualization was observed in eight (8.1%) of 98 TC patients and in 47 (47.9%) of 98 NC patients (P=.000). SLNs were the only metastatic node(s) in 54.1% of TC and 73.1% of NC patients.ConclusionThe periareolar intradermal injection technique gives a high detection rate in the localization of SLNs independently from the choice of the tracer. Mean SLN numbers and lymphatic vessel visualization frequency were significantly higher using a smaller albumin Tc-99m nanocolloid as compared to a stannous fluoride Tc-99m tin colloid. The results of our study support the idea that the influence of increased number of SLNs on positive SLN frequency is critical.     

Measuring performance directly using the veterans health administration electronic medical record: a comparison with external peer review

BACKGROUND: Electronic medical records systems (EMR) contain many directly analyzable data fields that may reduce the need for extensive chart review, thus allowing for performance measures to be assessed on a larger proportion of patients in care. OBJECTIVE: This study sought to determine the extent to which selected chart review-based clinical performance measures could be accurately replicated using readily available and directly analyzable EMR data. METHODS: A cross-sectional study using full chart review results from the Veterans Health Administration's External Peer Review Program (EPRP) was merged to EMR data. RESULTS: Over 80% of the data on these selected measures found in chart review was available in a directly analyzable form in the EMR. The extent of missing EMR data varied by site of care (P<0.01). Among patients on whom both sources of data were available, we found a high degree of correlation between the 2 sources in the measures assessed (correlations of 0.89-0.98) and in the concordance between the measures using performance cut points (kappa: 0.86-0.99). Furthermore, there was little evidence of bias; the differences in values were not clinically meaningful (difference of 0.9 mg/dL for low-density lipoprotein cholesterol, 1.2 mm Hg for systolic blood pressure, 0.3 mm Hg for diastolic, and no difference for HgbA1c). CONCLUSIONS: Directly analyzable data fields in the EMR can accurately reproduce selected EPRP measures on most patients. We found no evidence of systematic differences in performance values among these with and without directly analyzable data in the EMR.     

Down-regulation of endothelial TLR4 signalling after apo A-I gene transfer contributes to improved survival in an experimental model of lipopolysaccharide-induced inflammation

The protective effects of high-density lipoprotein (HDL) under lipopolysaccharide (LPS) conditions have been well documented. Here, we investigated whether an effect of HDL on Toll-like receptor 4 (TLR4) expression and signalling may contribute to its endothelial-protective effects and to improved survival in a mouse model of LPS-induced inflammation and lethality. HDL cholesterol increased 1.7-fold (p<0.005) and lung endothelial TLR4 expression decreased 8.4-fold (p<0.005) 2 weeks after apolipoprotein (apo) A-I gene transfer. Following LPS administration in apo A-I gene transfer mice, lung TLR4 and lung MyD88 mRNA expression, reflecting TLR4 signalling, were 3.0-fold (p<0.05) and 2.1-fold (p<0.05) lower, respectively, than in LPS control mice. Concomitantly, LPS-induced lung neutrophil infiltration, lung oedema and mortality were significantly attenuated following apo A-I transfer. In vitro, supplementation of HDL or apo A-I to human microvascular endothelial cells-1 24 h before LPS administration reduced TLR4 expression, as assessed by fluorescent-activated cell sorting, and decreased the LPS-induced MyD88 mRNA expression and NF-κB activity, independently of LPS binding. In conclusion, HDL reduces TLR4 expression and signalling in endothelial cells, which may contribute significantly to the protective effects of HDL in LPS-induced inflammation and lethality.     

Advantages of Wordless Instructions on How to Complete a Fecal Immunochemical Test: Lessons from Patient Advisory Council Members of a Federally Qualified Health Center

Some patients face difficulty understanding instructions for completing the fecal immunochemical test (FIT), a self-administered test to screen for colorectal cancer. We sought to develop and test low-literacy instructions for completing the FIT. Working in partnership with a Latino-serving Federally Qualified Health Center (FQHC) in the Portland Metro area, we developed and tested low-literacy instructions for completing the FIT; the instructions contained seven words (mail within 3 days; Devolver dentro de 3 dias). We conducted focus groups of Spanish-speaking patients on the advisory council of our partnering FQHC organization, and we gathered feedback from the project's advisory board members and clinic staff. We mailed a FIT kit to each patient, along with either (a) instructions written in English and Spanish, consisting of 415 words; or (b) low-literacy “wordless” instructions. We asked patients to complete the test before providing feedback. Our qualitative assessment showed that the wordless instructions were preferred over instructions consisting of words. Wordless instructions might aid efforts to raise the rates of colorectal cancer screening among low-literacy and non-English-speaking populations.