Occupational exposure and markers of genetic damage, systemic inflammation and lung function: a Danish cross-sectional study among air force personnel

Air force ground crew personnel are potentially exposed to fuels and lubricants, as raw materials, vapours and combustion exhaust emissions, during operation and maintenance of aircrafts. This study investigated exposure levels and biomarkers of effects for employees at a Danish air force military base. We enrolled self-reported healthy and non-smoking employees (n = 79) and grouped them by exposure based on job function, considered to be potentially exposed (aircraft engineers, crew chiefs, fuel operators and munition specialists) or as reference group with minimal occupational exposure (avionics and office workers). We measured exposure levels to polycyclic aromatic hydrocarbons (PAHs) and organophosphate esters (OPEs) by silicone bands and skin wipes (PAHs only) as well as urinary excretion of PAH metabolites (OH-PAHs). Additionally, we assessed exposure levels of ultrafine particles (UFPs) in the breathing zone for specific job functions. As biomarkers of effect, we assessed lung function, plasma levels of acute phase inflammatory markers, and genetic damage levels in peripheral blood cells. Exposure levels of total PAHs, OPEs and OH-PAHs did not differ between exposure groups or job functions, with low correlations between PAHs in different matrices. Among the measured job functions, the UFP levels were higher for the crew chiefs. The exposure level of the PAH fluorene was significantly higher for the exposed group than the reference group (15.9 +/- 23.7 ng/g per 24 h vs 5.28 +/- 7.87 ng/g per 24 h, p = 0.007), as was the OPE triphenyl phosphate (305 +/- 606 vs 19.7 +/- 33.8 ng/g per 24 h, p = 0.011). The OPE tris(1, 3-dichlor-2-propyl)phosphate had a higher mean in the exposed group (60.7 +/- 135 ng/g per 24 h) compared to the reference group (8.89 +/- 15.7 ng/g per 24 h) but did not reach significance. No evidence of effects for biomarkers of systemic inflammation, genetic damage or lung function was found. Overall, our biomonitoring study show limited evidence of occupational exposure of air force ground crew personnel to UFPs, PAHs and OPEs. Furthermore, the OH-PAHs and the assessed biomarkers of early biological effects did not differ between exposed and reference groups

Perinatal determinants of germ-cell testicular cancer in relation to histological subtypes

We aimed to investigate the role of perinatal determinants on the risk for germ-cell testicular cancer, with respect to the aetiological heterogeneity between seminomas and non-seminomas. A case–control study of 628 case patients with testicular cancer (308 seminomas and 320 non-seminomas) and 2309 individually matched controls was nested within a cohort of boys born from 1920 to 1980 in two Swedish regions (Uppsala-Örebro Health Care Region and Stockholm). Cases were diagnosed from 1958 to 1998 and were identified through the Swedish National Cancer Registry. Perinatal information on cases and controls was collected through charts available at maternity wards. Gestational duration, categorised in three categories (<37, 37–41, >41 weeks), was negatively associated with the risk for testicular cancer (P value for linear trend=0.008). A protective effect of long gestational duration and an increased risk for high birth weight were found for seminomas. Non-seminomas were associated with short gestational duration, particularly among those with low birth order (odds ratio: 3.02, 95% confidence intervals: 1.53–5.97) and high maternal age (odds ratio: 2.33, 95% confidence intervals: 1.19–4.55). No significant differences were found in tests for heterogeneity between the two histological groups. Our data support the hypothesis that intrauterine environment affects the risk for germ-cell testicular cancer. Seminomas and non-seminomas seemed to have similar risk patterns, although they are not entirely congruent

Long-term clearance from small airways in subjects with ciliary dysfunction

The objective of this study was to investigate if long-term clearance from small airways is dependent on normal ciliary function. Six young adults with primary ciliary dyskinesia (PCD) inhaled (111 )Indium labelled Teflon particles of 4.2 μm geometric and 6.2 μm aerodynamic diameter with an extremely slow inhalation flow, 0.05 L/s. The inhalation method deposits particles mainly in the small conducting airways. Lung retention was measured immediately after inhalation and at four occasions up to 21 days after inhalation. Results were compared with data from ten healthy controls. For additional comparison three of the PCD subjects also inhaled the test particles with normal inhalation flow, 0.5 L/s, providing a more central deposition. The lung retention at 24 h in % of lung deposition (Ret(24)) was higher (p < 0.001) in the PCD subjects, 79 % (95% Confidence Interval, 67.6;90.6), compared to 49 % (42.3;55.5) in the healthy controls. There was a significant clearance after 24 h both in the PCD subjects and in the healthy controls with equivalent clearance. The mean Ret(24 )with slow inhalation flow was 73.9 ± 1.9 % compared to 68.9 ± 7.5 % with normal inhalation flow in the three PCD subjects exposed twice. During day 7–21 the three PCD subjects exposed twice cleared 9 % with normal flow, probably representing predominantly alveolar clearance, compared to 19 % with slow inhalation flow, probably representing mainly small airway clearance. This study shows that despite ciliary dysfunction, clearance continues in the small airways beyond 24 h. There are apparently additional clearance mechanisms present in the small airways

Risk of testicular germ-cell tumours in relation to childhood physical activity

The US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) case–control study of testicular germ-cell tumours (TGCTs) enrolled participants and their mothers in 2002–2005. Hours of sports or vigorous childhood physical activity per week were ascertained for three time periods; 1st–5th grades, 6th–8th grades and 9th–12th grades. Son- and mother-reports were analysed separately and included 539 control son–mother pairs and 499 case son–mother pairs. Odds ratios and 95% confidence intervals were produced. The analysis of the sons' responses found no relationship between childhood physical activity and TGCT, while the mothers' analysis found an inverse association, which was solely due to nonseminoma. Future studies should seek to validate responses further using recorded information sources such as school records

An unusual case of chronic meningitis

BACKGROUND: Chronic meningitis is defined as symptoms and signs of meningeal inflammation and persisting cerebrospinal fluid abnormalities such as elevated protein level and pleocytosis for at least one month. CASE PRESENTATION: A 62-year-old woman, of unremarkable past medical history, was admitted to hospital for investigation of a four-week history of vomiting, malaise an associated hyponatraemia. She had a low-grade pyrexia with normal inflammatory markers. A CT brain was unremarkable and a contrast MRI brain revealed sub-acute infarction of the right frontal cortex but with no evidence of meningeal enhancement. Due to increasing confusion and patient clinical deterioration a lumbar puncture was performed at 17 days post admission. This revealed gram-negative coccobacilli in the CSF, which was identified as Neisseria meningitidis group B. The patient made a dramatic recovery with high-dose intravenous ceftriaxone antibiotic therapy for meningococcal meningitis. CONCLUSIONS: 1) Chronic bacterial meningitis may present highly atypically, particularly in the older adult. 2) There may be an absent or reduced febrile response, without a rise in inflammatory markers, despite a very unwell patient. 3) Early lumbar puncture is to be encouraged as it is essential to confirm the diagnosis.4) Despite a delayed diagnosis appropriate antibiotic therapy can still lead to a good outcome

Estimate of overdiagnosis of breast cancer due to mammography after adjustment for lead time. A service screening study in Italy

INTRODUCTION: Excess of incidence rates is the expected consequence of service screening. The aim of this paper is to estimate the quota attributable to overdiagnosis in the breast cancer screening programmes in Northern and Central Italy. METHODS: All patients with breast cancer diagnosed between 50 and 74 years who were resident in screening areas in the six years before and five years after the start of the screening programme were included. We calculated a corrected-for-lead-time number of observed cases for each calendar year. The number of observed incident cases was reduced by the number of screen-detected cases in that year and incremented by the estimated number of screen-detected cases that would have arisen clinically in that year. RESULTS: In total we included 13,519 and 13,999 breast cancer cases diagnosed in the pre-screening and screening years, respectively. In total, the excess ratio of observed to predicted in situ and invasive cases was 36.2%. After correction for lead time the excess ratio was 4.6% (95% confidence interval 2 to 7%) and for invasive cases only it was 3.2% (95% confidence interval 1 to 6%). CONCLUSION: The remaining excess of cancers after individual correction for lead time was lower than 5%

Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours

The carcinoma in situ (CIS) cell is the common precursor of nearly all testicular germ cell tumours (TGCT). In a previous study, we examined the gene expression profile of CIS cells and found many features common to embryonic stem cells indicating that initiation of neoplastic transformation into CIS occurs early during foetal life. Progression into an overt tumour, however, typically first happens after puberty, where CIS cells transform into either a seminoma (SEM) or a nonseminoma (N-SEM). Here, we have compared the genome-wide gene expression of CIS cells to that of testicular SEM and a sample containing a mixture of N-SEM components, and analyse the data together with the previously published data on CIS. Genes showing expression in the SEM or N-SEM were selected, in order to identify gene expression markers associated with the progression of CIS cells. The identified markers were verified by reverse transcriptase–polymerase chain reaction and in situ hybridisation in a range of different TGCT samples. Verification showed some interpatient variation, but combined analysis of a range of the identified markers may discriminate TGCT samples as SEMs or N-SEMs. Of particular interest, we found that both DNMT3B (DNA (cytosine-5-)-methyltransferase 3 beta) and DNMT3L (DNA (cytosine-5-)-methyltransferase 3 like) were overexpressed in the N-SEMs, indicating the epigenetic differences between N-SEMs and classical SEM

A comparative population-based study of prostate cancer incidence and mortality rates in Singapore, Sweden and Geneva, Switzerland from 1973 to 2006

10.1186/1471-2407-12-222BMC Cancer12-BCMA

Maternal hormone levels among populations at high and low risk of testicular germ cell cancer

Ethnic differences in maternal oestrogen levels have been suggested as explaining the significantly higher risk of testicular germ cell tumours (TGCT) of white men than black men in the United States. We therefore examined levels of maternal oestrogens, as well as testosterone and alphafetoprotein (AFP), in 150 black and 150 white mothers in the Collaborative Perinatal Project. Serum levels of estradiol (total, free and bioavailable), estriol, testosterone (total, free and bioavailable), sex hormone binding globulin (SHBG), and AFP were examined during first and third trimesters. We found that the black mothers, rather than the white mothers, had significantly higher estradiol levels in first trimester (P=0.05). Black mothers also had significantly higher levels of all testosterone (P<0.001) and AFP (P<0.001) in both trimesters. In addition, the ratios of sex hormones (estradiol/testosterone) were significantly lower among black mothers. These findings provide little support to the oestrogen hypothesis, but are consistent with higher levels of testosterones and/or AFP being associated with reduced risk of TGCT; alternatively, lower oestrogen/androgen ratios may be associated with reduced risk