Club cell protein (CC16) in serum as an effect marker for small airway epithelial damage caused by diesel exhaust and blasting fumes in potash mining.

OBJECTIVE: The effect marker club cell protein (CC16) is secreted by the epithelium of the small respiratory tract into its lumen and passes into the blood. Increased amounts of CC16 in serum are observed during acute epithelial lung injury due to air pollutants. CC16 in serum was determined as part of this cross-sectional study in underground potash miners on acute and chronic health effects from exposures to diesel exhaust and blasting fumes. METHODS: Nitrogen oxides, carbon monoxide, and diesel particulate matter were measured in 672 workers at a German potash mining site on a person-by-person basis over an early shift or midday shift, together with CC16 serum concentrations before and after the respective shift. CC16 concentrations and CC16 shift-differences were evaluated with respect to personal exposure measurements and other quantitative variables by Spearman rank correlation coefficients. CC16 shift-differences were modeled using multiple linear regression. Above-ground workers as reference group were compared to the exposed underground workers. RESULTS: Serum concentrations of CC16 were influenced by personal characteristics such as age, smoking status, and renal function. Moreover, they showed a circadian rhythm. While no statistically significant effects of work-related exposure on CC16 concentrations were seen in never smokers, such effects were evident in current smokers. CONCLUSION: The small airways of current smokers appeared to be vulnerable to the combination of measured work-related exposures and individual exposure to smoking. Therefore, as health protection of smokers exposed to diesel exhaust and blasting fumes, smoking cessation is strongly recommended.

Underground salt and potash workers exposed to nitrogen oxides and diesel exhaust: assessment of specific effect biomarkers.

PURPOSE: Occupational exposure limits (OEL) for nitrogen oxides (NO, NO2) and diesel exhaust (EC-DPM) were reassessed by the German authorities in 2016/2017. We performed a clinical cross-sectional study among salt and potash underground workers exposed to these substances at relatively high levels to examine possible indicators of acute effects on workers' health. METHODS: We measured post- versus pre-shift differences in cardiovascular, inflammatory, immune, and respiratory effect biomarkers and assessed their associations with personal exposures measured during the same shift. We also compared post- versus pre-shift differences in biomarker levels between exposure groups defined based on work site and job type. RESULTS: None of the above-ground workers exceeded the OEL for NO2 and only 5% exceeded the OEL for EC-DPM exposure. Among underground workers, 33% of miners and 7% underground maintenance workers exceeded the OEL for NO2; the OEL for EC-DPM was exceeded by 56% of miners and 17% of maintenance workers. Some effect biomarkers (thrombocytes, neutrophils, MPO, TNF-α, IgE, FeNO) showed statistically significant differences between pre- versus post-shift measurements; however, there were no consistent associations between pre- and post-shift differences and exposure group or personal exposure measurements during the shift. CONCLUSIONS: We did not find evidence of associations between workplace exposure to NO, NO2 or EC-DPM and clinically relevant indicators of acute cardiovascular, inflammatory and immune, or respiratory effects among salt and potash underground workers in Germany.

Anisotropic Etching of Pyramidal Silica Reliefs with Metal Masks and Hydrofluoric Acid.

This work describes the fabrication of anisotropically etched, faceted pyramidal structures in amorphous layers of silicon dioxide or glass. Anisotropic and crystal-oriented etching of silicon is well known. Anisotropic etching behavior in completely amorphous layers of silicon dioxide in combination with purely isotropic hydrofluoric acid as etchant is an unexpected phenomenon. The work presents practical exploitations of this new process for self-perfecting pyramidal structures. It can be used for textured silica or glass surfaces. The reason for the observed anisotropy, leading to enhanced lateral etch rates, is the presence of thin metal layers. The lateral etch rate under the metal significantly exceeds the vertical etch rate of the non-metallized area by a factor of about 6-43 for liquid and 59 for vapor-based processes. The ratio between lateral and vertical etch rate, thus the sidewall inclination, can be controlled by etchant concentration and selected metal. The described process allows for direct fabrication of shallow angle pyramids, which for example can enhance the coupling efficiency of light emitting diodes or solar cells, can be exploited for producing dedicated silicon dioxide atomic force microscopy tips with a radius in the 50 nm range, or can potentially be used for surface plasmonics.

Impact of diesel exhaust exposure on urinary 1-hydroxypyrene in underground salt and potash workers.

BACKGROUND: Diesel engine exhaust (DEE) and some of the polycyclic aromatic hydrocarbons (PAH) it contains are carcinogenic to humans (for example benzo(a)pyrene) and can cause lung cancer in workers. The objective of this study was to assess exposures to DEE and its component PAH and the potential associations between these two health hazards in a salt and potash mining population. METHODS: Between 2017 and 2019, 1003 underground workers (mining n = 801, maintenance n = 202) and 243 above-ground facility workers from two German mines participated. Personal exposure to DEE was assessed in air as elemental carbon for diesel particulate matter (EC-DPM), whereas exposure to PAH was assessed in pre- and post-shift urine samples in terms of 1-hydroxypyrene (1-OHP). Associations between EC-DPM and 1-OHP were studied using linear regression models. RESULTS: The highest EC-DPM exposures were measured in mining workers (median 0.06 mg/m³) followed by workers in the maintenance (0.03 mg/m3) and facility areas (<0.02 mg/m3). Exposures above the current German occupational threshold level of 0.05 mg/m3 were observed in 56%, 17%, and 5% of mining, maintenance and facility workers, respectively. 1-OHP increased statistically significantly across a work shift in underground workers but not in facility workers. Regression analyses revealed an increase of post-shift 1-OHP by almost 80% in mining and 40% in maintenance compared with facility workers. 1-OHP increased with increasing EC-DPM among underground workers. However, internal exposure of 1-OHP mainly remained at levels similar to those of the German general population in more than 90% of the urine samples. CONCLUSIONS: While exposures to DEE above the current German OEL for EC-DPM are quite common in the studied population of underground salt and potash miners (39.5% overall), urinary concentrations of 1-OHP did not reflect these findings.

Pathohistological diagnosis and differential diagnosis.

Malignant mesothelioma is a rare aggressive tumour arising from mesothelial cells of the pleural and peritoneal cavity including pericardium and tunica vaginalis testis. Malignant mesothelioma occurs predominantly in men (>90%). Asbestos exposure is the best known and evaluated risk factor with a long latency period between exposure and onset of malignant mesothelioma ranging from 15 to 60 years. Exposure to erionite leads to higher incidences of mesothelioma and play an important role in environmental exposure (Turkey). Other possible risk factors are radiation, recurrent pleuritis/peritonitis and simian virus 40 (SV 40).Malignant pleural mesothelioma is most common, whereas malignant peritoneal mesothelioma accounts only for 6-10%. Infrequent sites of origin are the pericardium and tunica vaginalis in 1-2%.Malignant mesothelioma shows either diffuse growth pattern or occurs as a localised tumour mass. Diffuse type represents an aggressive tumour with poor prognosis and is incurable in most cases.According to the WHO classification, three histological subtypes are distinguished: epithelioid, sarcomatoid and biphasic malignant mesothelioma.Rare variants are desmoplastic type, a subtype of sarcomatoid mesothelioma, undifferentiated type and deciduoid type. Epithelioid type is the most frequent one, but biphasic malignant mesothelioma occurs in 30%. Pure sarcomatoid or biphasic type is seen less frequently in malignant peritoneal mesothelioma than in its pleural counterpart.Well-differentiated papillary mesothelioma is a generally non-invasive mesothelioma with low malignant potential that arises mostly in females in the peritoneal cavity. Histological type is an important prognostic marker. Longest survival is seen in patients with epithelioid malignant mesothelioma. Sarcomatoid subtype has the worst prognosis.Malignant mesothelioma shows macroscopical and microscopical similarities to benign lesions and other malignancies. Therefore, reactive mesothelial proliferations on the one hand and secondary tumours resembling mesothelial cells as well as benign or rare mesothelial tumours on the other hand have to be distinguished. Additional immunohistochemistry is essential in histopathological assessment using a marker panel of antibodies.

Mesothelioma and analysis of tissue fiber content.

The strong relationship between mesothelioma and asbestos exposure is well established. The analysis of lung asbestos burden by light and electron microscopy assisted to understand the increased incidence of mesothelioma in asbestos mining and consuming nations.The data on the occupational exposure to asbestos are important information for the purpose of compensation of occupational disease No. 4105 (asbestos-associated mesothelioma) in Germany.However, in many cases the patients have forgotten conditions of asbestos exposure or had no knowledge about the used materials with components of asbestos. Mineral fiber analysis can provide valuable information for the research of asbestos-associated diseases and for the assessment of exposure. Because of the variability of asbestos exposure and long latency periods, the analysis of asbestos lung content is a relevant method for identification of asbestos-associated diseases. Also, sources of secondary exposure, so called "bystander exposition" or environmental exposure can be examined by mineral fiber analysis.Household contacts to asbestos are known for ten patients (1987-2009) in the German mesothelioma register; these patients lived together with family members working in the asbestos manufacturing industry.Analysis of lung tissue for asbestos burden offers information on the past exposure. The predominant fiber-type identified by electron microscopy in patients with mesothelioma is amphibole asbestos (crocidolite or amosite). Latency times (mean 42.5 years) and mean age at the time of diagnose in patients with mesothelioma are increasing (65.5 years). The decrease of median asbestos burden of the lung in mesothelioma patients results in disease manifestation at a higher age.Lung dust analyses are a relevant method for the determination of causation in mesothelioma. Analysis of asbestos burden of the lung and of fiber type provides insights into the pathogenesis of malignant mesothelioma. The most important causal factor for the development of mesothelioma is still asbestos exposure.

[Skin and Soft Tissue Infections Due to Corynebacterium ulcerans - Case Reports]. / Haut- und Weichteilinfektionen durch Corynebacterium ulcerans ­ Fallberichte.

History and clinical findings We report on three patients suffering from skin and soft tissue infections of the legs due to toxigenic Corynebacterium ulcerans strains. In all three patients, there was a predisposition due to chronic diseases. Three patients had domestic animals (cat, dog) in their households. Investigations and diagnosis A mixed bacterial flora including Corynebacterium ulcerans was found in wound swab samples. Diphtheric toxin was produced by the Corynebacterium ulcerans strains in all three cases. Treatment and course In all three patients, successful handling of the skin and soft tissue infections was possible by combining local treatment with antibiotics. Diphtheria antitoxin was not administered in any case. Conclusion Based on a review of the recent literature pathogenesis, clinical symptoms and signs, diagnostics and therapy of skin and soft tissue infections due to Corynebacterium ulcerans are discussed. Corynebacterium ulcerans should be considered as a potential cause of severe skin and soft tissue infections. Occupational or domestic animal contacts should be evaluated.

Inter-comparison of personal monitors for nanoparticles exposure at workplaces and in the environment.

Personal monitors based on unipolar diffusion charging (miniDiSC/DiSCmini, NanoTracer, Partector) can be used to assess the individual exposure to nanoparticles in different environments. The charge acquired by the aerosol particles is nearly proportional to the particle diameter and, by coincidence, also nearly proportional to the alveolar lung-deposited surface area (LDSA), the metric reported by all three instruments. In addition, the miniDiSC/DiSCmini and the NanoTracer report particle number concentration and mean particle size. In view of their use for personal exposure studies, the comparability of these personal monitors was assessed in two measurement campaigns. Altogether 29 different polydisperse test aerosols were generated during the two campaigns, covering a large range of particle sizes, morphologies and concentrations. The data provided by the personal monitors were compared with those obtained from reference instruments: a scanning mobility particle sizer (SMPS) for LDSA and mean particle size and a ultrafine particle counter (UCPC) for number concentration. The results indicated that the LDSA concentrations and the mean particle sizes provided by all investigated instruments in this study were in the order of ±30% of the reference value obtained from the SMPS when the particle sizes of the test aerosols generated were within 20-400nm and the instruments were properly calibrated. Particle size, morphology and concentration did not have a major effect within the aforementioned limits. The comparability of the number concentrations was found to be slightly worse and in the range of ±50% of the reference value obtained from the UCPC. In addition, a minor effect of the particle morphology on the number concentration measurements was observed. The presence of particles >400nm can drastically bias the measurement results of all instruments and all metrics determined.

Malignant pleural mesothelioma: incidence, etiology, diagnosis, treatment, and occupational health.

BACKGROUND: The incidence of malignant mesothelioma in Germany is about 20 cases per million persons per year. Its association with asbestos exposure, usually occupational, has been unequivocally demonstrated. Even though the industrial use of asbestos was forbidden many years ago, new cases of mesothelioma continue to appear because of the long latency of the disease (median, 50 years). Its diagnosis and treatment still present a major challenge for ambulatory and in-hospital care and will do so for years to come. METHODS: This article is based on a selective review of the literature, along with data from the German Mesothelioma Register. RESULTS: 1397 people died of mesothelioma in Germany in 2010. A plateau in the incidence of the disease is predicted between 2015 and 2030. Most mesotheliomas arise from the pleura. The histological subtype and the Karnofsky score are the main prognostic factors. Only limited data are now available to guide treatment with a combination of the available methods (chemotherapy, surgery, radiotherapy). The prognosis is still poor, with a median survival time of only 12 months. Symptom control and the preservation of the patient's quality of life are the main aspects of care for patients with mesothelioma. CONCLUSION: The incidence of mesothelioma is not expected to drop in the next few years. The available treatments are chemotherapy, surgery, and radiotherapy. Specialized treatment centers now increasingly provide multimodal therapy for treatment of mesothelioma.

Folylpoly-glutamate synthetase expression is associated with tumor response and outcome from pemetrexed-based chemotherapy in malignant pleural mesothelioma.

BACKGROUND: Pemetrexed-based chemotherapy represents the standard of care in first-line treatment of advanced malignant pleural mesothelioma (MPM). However, there are no established predictors of clinical benefit. Pemetrexed inhibits multiple enzymes involved in pyrimidine and purine synthesis, but the main target is thymidylate synthase (TS). After cellular uptake pemetrexed is converted into more effective polyglutamated forms by folylpoly-γ-glutamate synthetase (FPGS). We hypothesized that FPGS and TS protein expressions are associated with clinical outcome after pemetrexed-based chemotherapy. METHODS: Pretreatment tumor samples from 84 patients with histologically confirmed MPM, who received pemetrexed combined with platinum (79 of 84) or single-agent pemetrexed (5 of 84) as first-line treatment, were retrospectively analyzed. FPGS and TS protein expressions were semiquantitatively assessed by using the Hybrid (H)-scoring system (range, 0-300). H-scores were correlated with radiological response according to modified Response Evaluation Criteria in Solid Tumors, progression-free survival (PFS) and overall survival (OS). RESULTS: Median H-score of the entire cohort was 230 for FPGS (range, 100-300), and 210 for TS (range, 100-300). High FPGS protein expression was significantly associated with longer PFS (pCOX = 0.0337), better objective tumor response (partial response versus stable disease + progressive disease; pKW = 0.003), and improved disease-control rate (partial response + stable disease versus progressive disease; pKW = 0.0208), but not with OS. In addition, high TS protein expression was associated with progressive disease under pemetrexed-based therapy (p = 0.0383), and shorter OS (pCOX = 0.0071), but no association with PFS was observed. CONCLUSION: FPGS and TS expressions were associated with clinical response and outcome to pemetrexed-based first-line chemotherapy in MPM. Prospective evaluation of FPGS and TS expressions and their prognostic/predictive power in MPM patients is warranted.

Nodular hemangiomatosis of pleura and peritoneum.

Multiple, simultaneously occurring hemangiomas in one or more organs are known as hemangiomatosis syndromes in the context of phacomatosis manifesting in childhood. Nevertheless, hemangiomas of the serous membranes are extremely rare and often present as solitary lesions. We report the case of an elderly patient who suffered from diffuse hemangiomatosis of the visceral peritoneum and pleura and deceased due to acute respiratory distress syndrome following persistent and unmanageable pulmonary hemorrhage. We present an unusual case of a disseminated but histologically benign appearing hemangiomatosis of the serous membranes.

Cancer mortality in a surveillance cohort of German males formerly exposed to asbestos.

The objective of this analysis was the estimation of the cancer risks of asbestos and asbestosis in a surveillance cohort of high-exposed German workers. A group of 576 asbestos workers was selected for high-resolution computer tomography of the chest in 1993-1997. A mortality follow-up was conducted through 2007. Standardised mortality ratios (SMRs) were calculated and Poisson regression was performed to assess mesothelioma risks. A high risk was observed for pleural mesothelioma (SMR 28.10, 95% CI 15.73-46.36) that decreased after cessation of exposure (RR 0.1; 95% CI 0.0-0.6 for > or =30 vs. <30 years after last exposure). Asbestosis was a significant risk factor for mesothelioma (RR 6.0, 95% CI 2.4-14.7). Mesothelioma mortality was still in excess in former asbestos workers although decreasing after cessation of exposure. Fibrosis was associated with subsequent malignancy.

[Medical insurance aspects of peritoneal tumors with particular attention to peritoneal mesotheliomas]. / Versicherungsmedizinische Aspekte bei peritonealen Mesotheliomen und sonstigen peritonealen Tumoren.

Malignant peritoneal mesotheliomas arise mainly in male patients and the median age of initial diagnosis is about 56 years. Epitheloid subtype predominates in peritoneal mesotheliomas. Asbestos exposure is the best-known and most common risk factor associated with the development of both pleural and peritoneal mesotheliomas and, therefore, about 90% of cases can be assessed as asbestos-associated. Patients with peritoneal mesotheliomas have distinctly higher asbestos burden of the lungs than patients with pleural mesotheliomas. The mean latency period between exposure and diagnosis of peritoneal mesothelioma ranges from 35 to 40 years and is comparable to that of pleural mesothelioma. Mesothelioma of the tunica vaginalis testis also belongs to the group of peritoneal mesotheliomas. No significant evidence exists for the classification of well-differentiated papillary mesothelioma, solitary fibrous tumor, adenomatoid tumor, primary peritoneal serous borderline tumor, and benign multicystic mesothelioma as asbestos-associated tumors. Except malignant mesotheliomas, the induction of other abdominal tumors is independent of an exposure to asbestos dust.