Rounded atelectasis after exposure to refractory ceramic fibres (RCF).

BACKGROUND: Refractory Ceramic fibres (RCF) are man-made mineral fibres used in high performance thermal insulation applications. Analogous to asbestos fibres, RCF are respirable, show a pleural drift and can persist in human lung tissue for more than 20 years after exposure. Pleural changes such as localised or diffuse pleural thickening as well as pleural calcification were reported. RESULT: A 45 years old man worked in high performance thermal insulation applications using refractory ceramic fibres (RCF) for almost 20 years. During a occupational medical prophylaxis to ensure early diagnosis of disorders caused by inhalation of aluminium silicate fibres with X-ray including high-resolution computed tomography (HRCT), bilateral pleural thickening was shown and a pleural calcification next to a rounded atelectasis was detected. Asbestos exposure could be excluded. In pulmonary function test a restrictive lung pattern could be revealed. In work samples scanning electron microscopy (SEM) including energy dispersive X-ray analysis (EDX) classified used fibres as aluminium silicate fibres. X-ray powder diffraction (XRD) and transmission electron microscopy (TEM) showed crystalline as well as amorphous fibres. CONCLUSIONS: A comprehensive lung function analysis and in case of restrictive lung disorders additional CT scans are needed in RCF exposed workers in accordance to the guidelines for medical occupational examinations comparable to asbestos exposed workers.

High rate biological contactor system using waste activated sludge from trickling filter/solids contact process.

A high-rate biological contactor process (HRBC) can be used as primary treatment instead of a clarifier to remove particulate, colloidal and soluble fractions of organic matter via biosorption plus flotation and divert it to anaerobic digestion for methane production, simultaneously reducing secondary aeration energy demand. Pilot and bench tests were conducted at a range of contact times (15-60 min) and contactor dissolved oxygen (DO) (0.2-2.0 mg/L) using waste activated sludge (WAS) from a trickling filter/solids contact (TF/SC) process in the HRBC. Biosorption performance was lowest when contact times were <30 min and unstable at DO < 0.5 mg/L. The overall average of 20% sCOD capture was similar to previous findings by others using WAS from conventional AS. The biomethane potential (BMP) of the HRBC float material can be as high as that of primary sludge (340-400 mL CH4/g VS), which is much greater than WAS. Operating the HRBC with a long contact time (>30 min) or with high DO (>1 mg/L) increases the amount of biosorption but reduces the BMP of the float. It was also found that biosorption only effectively occurs when a WAS is paired with the wastewater from the same facility.

Interleukin-6 contributes to the paracrine effects of cardiospheres cultured from human, murine and rat hearts.

Cardiosphere-derived cells (CDCs) were cultured from human, murine, and rat hearts. Diluted supernatant (conditioned-medium) of the cultures improved the contractile behavior of isolated rat cardiomyocytes (CMCs). This effect is mediated by the paracrine release of cytokines. The present study tested the hypothesis, that the cardiovascular state of the donor's heart influences this effect on CMCs and tries to identify the responsible factors. CDCs were cultured from human tissue samples of cardiac surgery and from murine and rat hearts. The supernatants of cultured CDCs from hypertensive humans and rats showed a higher improvement of the contractile behavior of CMCs compared to CDCs of normotensive origin. Subsequently, the cytokine profile of the supernatants was analyzed. Among the cytokines elevated in supernatants originating from hypertensive humans or rats was Interleukin-6. CDCs were also generated from Interleukin-6(-/-) -mice and their wildtype littermates. The supernatant of the cultured Interleukin-6(-/-) -CDCs had no effect on the contractile behavior, whereas the supernatant of the Interleukin-6(+/+) -CDCs showed a positive effect. To confirm the hypothesis that Interleukin-6 contributes to the paracrine effects, CMCs were incubated with Interleukin-6. It improved the contractile function in a concentration dependent way. Finally, the effect of the supernatant of cultured CDCs derived from a hypertensive human sample could be abolished by simultaneous incubation with a specific Interleukin-6 antibody. CDCs release cytokines that improve the contractile behavior of CMCs. This effect is more intense in CDCs from hypertensive donors. Interleukin-6 is involved in this phenomenon.

CYP1B1 mRNA inducibility due to benzo(a)pyrene is modified by the CYP1B1 L432V gene polymorphism.

Benzo(a)pyrene (BaP), a primary component of tobacco smoke, is activated by cytochrome P450 1B1 (CYP1B1). Smokers homozygous for the C-allele (*1/*1) at the CYP1B1 Leu432Val polymorphism have shown increased CYP1B1 expression, compared to smokers homozygous for the G-allele *3/*3. Since no difference has been shown in CYP1B1 expression between both genotypes in non-smokers, we assumed that the genetic impact is produced in combination with an exogenous induction (e.g. BaP). To confirm this theory and to quantify the effect, we induced human leucocytes with increasing BaP concentrations and determined CYP1B1 mRNA expression with real-time polymerase chain reaction (PCR). We incubated human leucocytes from 27 healthy donors with BaP concentrations ranging from 2.5 to 250 µM. We identified the CYP1B1 genotypes by melting curve analysis and assessed relative CYP1B1 mRNA expression using real-time PCR. Expression was related to ß-2-microglobulin with the 2(-ΔΔCT) method. Inducibility of CYP1B1 mRNA by BaP was higher in leucocytes carrying the CYP1B1*1/*1 genotype than in leucocytes carrying the CYP1B1*3/*3 genotype (P = 0.012). We revealed significant differences, with BaP concentrations of 2.5 µM (P = 0.0094), 5 µM (P = 0.027), 10 µM (P = 0.0006), 25 µM (P = 0.0007) and 50 µM (P = 0.017). Homozygous carriers of the C-allele (*1/*1) at the CYP1B1 Leu432Val polymorphism show a higher response to environmental factors, such as carcinogenic BaP, than homozygous carriers of the G-allele *3/*3.

Age-dependent improvement of hearing ability in children: an international approach.

OBJECTIVES: Pure-tone auditory thresholds in children are below the standardized hearing threshold levels described by ). The development of hearing ability in Chinese and German children at different ages is analyzed and compared with data in the literature. Extended high frequencies above 8 kHz are included due to their vulnerability to noise. DESIGN: Ninety-one children in China and 197 children at a typical primary school in Germany underwent audiometric tests at 17 frequencies ranging from 125 Hz to 16 kHz. To analyze effects of age the children were assessed in age groups of 6 to 9, 9 to 12, and 13 to 16 years of age. RESULTS: Children in China and Germany have the poorest hearing sensitivity at low frequencies (below 1 kHz) and the best sensitivity at the extended high frequencies above 8 kHz. The mean deviations (both ears) from the standard thresholds for adults 18 to 25 years of age, averaged over all frequencies, are 6.7 dB for Chinese and 7.1 dB for German children in the youngest age groups. In the Chinese age group of 9- to 12-year olds the averaged threshold is 4.5 dB and for the same German age group 3.6 dB. For the Chinese age group of 13- to 16-year olds the averaged threshold is 3.3 dB. The improvements of the older German age group compared with the younger are significant at p < 0.05 and are nearly twice as high compared with the comparable Chinese age groups. CONCLUSIONS: Age-dependent improvements of hearing ability are evident in children and should be considered in evaluating audiometric test results. Audiometric tests in the extended high-frequency range could be used as an early warning system for future degeneration of hearing ability.

Age dependency of oxygen uptake and related parameters in exercise testing: an expert opinion on reference values suitable for adults.

BACKGROUND: Spiroergometry has been established to determine physical capacity. Reference values collected mostly in a younger population can be obtained from a number of studies and therefore may differ. Regression equations are complex and cannot be transferred easily to clinical practice. Our aim was to obtain reference values for spiroergometric parameters in cardiopulmonary exercise in healthy adult populations. METHODS: Eighteen studies of healthy adults (>40 years) that assessed maximal oxygen uptake (VO2max), oxygen uptake in relation to body weight (VO2max/kg), and oxygen pulse (VO2max/heart rate) were included. After data processing, spiroergometric parameters were correlated to age. Regression analysis was performed separately for each study and also weighted with the number of participants. RESULTS: For all spiroergometric parameters, age dependency was detectable for both males and females. After performing regression analysis, the following linear regression equations were determined: VO2max: Males = -28 × age (years) + 4,000; females = -20 × age (years) + 2,700 (ml/min); VO2max/kg: Males = -0.42 × age (years) + 58; females = -0.35 × age (years) + 46 (ml/min/kg); VO2max/heart rate: Males = -0.10 × age (years) + 20.50; females = -0.05 × age (years) + 13 (ml/min/heart rate). CONCLUSIONS: The present study provides practicable reference values for the spiroergometric parameters of adult men and women.

Expression of microRNAs in leukocytes and serum of asbestosis patients.

BACKGROUND: Although asbestos use is banned in many countries, long latency of asbestos-related diseases like pleural plaques or asbestosis mean it is still a public health issue. People suffering from these diseases have a higher risk of developing mesothelioma or lung cancer, which can progress quickly and aggressively. MicroRNAs were suggested as potential biomarkers in several diseases. However, in asbestosis, blood microRNAs are less explored. Since miR-32-5p, miR-143-3p, miR-145-5p, miR-146b-5p, miR-204-5p and miR-451a are involved in fibrotic processes and in cancer, expression of these microRNAs was analyzed in leukocytes and serum of asbestosis patients. METHODS: MicroRNA expression was analyzed in leukocytes and serum of 36 patients (26 affected by pleural plaques and 10 by asbestosis) and 15 healthy controls by real-time RT-PCR. Additionally, data analyses were performed regarding disease severity based on ILO classification. RESULTS: MicroRNA miR-146b-5p was significantly down-regulated in leukocytes of patients suffering from pleural plaques with a large effect indicated by η2p = 0.150 and Cohen's f = 0.42, a value of difference of 0.725 and a 95% confidence interval of 0.070-1.381. In patients suffering from asbestosis miR-146b-5p was not significantly regulated. However, data analyses considering disease severity only, revealed that miR-146b-5p was significantly down-regulated in leukocytes of mildly diseased patients compared to controls with a large effect indicated by η2p = 0.178 and Cohen's f = 0.465, a value of difference of 0.848 and a 95% confidence interval of 0.097-1.599. Receiver operating characteristic (ROC) curve and an area under the ROC curve value of 0.757 for miR-146b-5p indicated acceptable discrimination ability between patients suffering from pleural plaques and healthy controls. Less microRNAs were detectable in serum than in leukocytes, showing no significant expression differences in all participants of this study. Moreover, miR-145-5p was regulated significantly differently in leukocytes and serum. An R2 value of 0.004 for miR-145-5p indicated no correlation in microRNA expression between leukocytes and serum. CONCLUSION: Leukocytes seem more suitable than serum for microRNA analyses regarding disease and potentially cancer risk assessment of patients suffering from asbestos-related pleural plaques or asbestosis. Long-term studies may reveal whether down-regulation of miR-146b-5p in leukocytes might be an early indicator for an increased cancer risk.

The validity of static lung compliance in asbestos-induced diseases.

BACKGROUND: Pulmonary compliance can be viewed as an indicator of distensibility of the lungs, not only in asbestos-induced pulmonary disorders but also in visceral pleural fibrosis extending into the lung parenchyma. In this study we evaluated static compliance measurements in asbestos-derived diseases, especially in patients with parietal pleura plaques. Lung function analyses, especially static lung compliance, were correlated with high-resolution computer tomography examinations. METHODS: Sixty-three patients with parietal pleural plaques, 10 with visceral pleural fibrosis, 39 with parenchymal pulmonary asbestosis together with parietal pleural plaques, and 42 with parenchymal pulmonary asbestosis together with visceral pleural fibrosis were enrolled in the study. RESULTS: In comparison with patients having only parietal pleural plaques, those having asbestosis and visceral pleural fibrosis showed significant decreases in static lung compliance, diffusing capacity, and vital capacity. Visceral pleural thickening was also associated with significantly reduced FEV(1), MEF(50), and FEV(1)/FVC ratios. Multiple regression analyses indicated that the existence of visceral pleural fibrosis (p = 0.017) is the most important factor accounting for a decrease in static compliance. Reference values of static lung compliance differ notably. In comparison with mean reference values, the sensitivity of detecting reduced lung compliance was calculated to be between 9.7 and 45.5 %. Other respiratory function variables failed to show any significant differences. CONCLUSION: Our data indicate that the measurement of static compliance is not sufficient for early detection of pulmonary function impairment in patients with parietal pleural plaques.

Pure-tone auditory threshold in school children.

To determine pure-tone auditory thresholds, 197 screened children at a typical primary school in a German town (~70,000 inhabitants) were examined. All children underwent a tympanometry and an audiometry at 17 frequencies from 125 to 16 kHz. Regarding age effects, two groups (6-8 and 9-12 years) were analyzed. The cross-sectional research was supplemented by a follow-up study with 35 children of the first graders 3 years later. School children have the poorest hearing sensitivity at low frequencies (below 1 kHz) and the best sensitivity at the extended high frequencies above 8 kHz. Hearing thresholds are rising significantly with age. Through all frequencies, averaged improvements were 3.8 dB (right ear) and 3.7 dB (left ear) at the cross-sectional study and 3.7 dB (right ear) and 5.1 dB (left ear) at the longitudinal study. The overall deviation (left and right) from the standard thresholds for adults were 7.4 and 3.6 dB for the younger and older age groups, respectively. The ear canal volume (ECV) measured by tympanometric tests was at mean with 1.06 cm(3) for the 6- to 8-year age group significantly lower (p < 0.001) in comparison with 1.18 cm(3) for the 9- to 12-year age group. Also, girls had significant (p < 0.001) smaller ECV (mean 1.07 cm(3)) than boys (1.17 cm(3)). Auditory performance improves with rising age in school children.

Assessing Energy Expenditure in Female Healthcare Workers in a University Hospital.

INTRODUCTION: The assessment of energy expenditure (EE) at workplaces maintains a central topic in occupational health due to increasing work-related issues. Today 80% of employees in the healthcare system are women. Limited research concerning their physical activity at work is available. The purpose of the study was the investigation of body composition, maximum physical capacity and quantification of physical work activity for female healthcare workers under real-time conditions. METHODS: Occupational physical activity (PA) of 33 female healthcare workers in a university hospital was quantified. Health associate professionals (HAP), health professionals (HP), and females working from cleaners and helpers (CH) department participated. All underwent cardio pulmonary exercise test. For every working task VO2, VCO2 and RER were measured and EE was calculated individually for each task. RESULTS: Forty-two different working tasks were identified and grouped in seven categories to compare physical activity (PA): 'office and laboratory work', 'bedside patient care', 'instrument reprocessing, packing boxes', 'walking with patient, or alone', 'pushing carts or wheelchairs', 'strenuous cleaning in bent posture' and 'lifting heavy boxes, weights or items'. By comparing groups of healthcare workers, CH and HAP spent significant (p < 0.01) more EE (in kcal/min) 3.9 resp. 3.2 than HP 2.5. Light PA e.g. office and laboratory work (2.7 ± 0.6) and bedside patient care (2.9 ± 0.7) were accomplished by HP and HAP while HAP and CH performed moderate PA such as 'packing boxes' (3.6 ± 0.8), 'pushing carts' and 'strenuous cleaning' (4.7 ± 0.9). Work performed by CH and HAP, i.e. 'strenuous cleaning' and 'lifting heavy items' showed highest kcal per kg Fat Free Mass (FFM) per hour with 5.80 [4.05-7.81] and 6.94 [5.18-9.03] kcal/kgFFM/h. CONCLUSION: Our findings lend preliminary support to the hypothesis that the majority of activities in female healthcare workers were of low and moderate PA and can be accomplished by middle aged and even older female workers. CH performed tasks with heavy physical activities (PA) like cleaning and lifting heavy weights. HAP performed light/moderate PA below their maximum physical capacity.

RNA expressions of AHR, ARNT and CYP1B1 are influenced by AHR Arg554Lys polymorphism.

AIM: The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that together with Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) controls the expression of Xenobiotic metabolising enzymes (XME) such as CYP1B1. In the absence of exogenous ligands, AHR is supposed to be involved in promotion of cell cycle progression. Polymorphisms of the AHR gene are suggested to be associated with susceptibility to cancer. Because of its critical role in xenobiotic induced toxicity and carcinogenesis as well as its ligand independent relevance we investigated the effects of AHR Arg554Lys Polymorphism on gene expression level of the AHR, ARNT and CYP1B1. METHODS: Detection of the AHR Arg554Lys polymorphism of the AHR gene was performed by rapid capillary PCR with melting curve analysis. The quantitative Real-Time PCR (qRT-PCR) of AHR, ARNT and CYP1B1 mRNAs was carried out in white blood cells from 287 Caucasians. Calculations of expression were made with the 2(-ΔΔCT) method. RESULTS: The relative AHR mRNA expression revealed significant differences between the two homozygote AHR genotypes Arg554Arg (11.0±1.0; n=228) and Lys554Lys (0.6±0.4; n=3; p<0.001). Also significant differences were seen between the heterozygote genotype Arg554Lys (13.0±3.0; n=40) and the homozygote Lys554Lys genotype (0.6±0.4; n=3; p<0.001). These differences above were replicated significantly in the relative mRNA expression of ARNT and CYP1B1. Comparing the determined CT-values, a correlation coefficient of R=0.748 for AHR and ARNT, R=0.626 for ARNT and CYP1B1 as well as R=0.533 for AHR and CYP1B1 was calculated. CONCLUSION: Our findings suggest that the homozygote variant genotype of AHR Lys554Lys is associated with a significantly lower AHR, ARNT and CYP1B1 mRNA expression.

TNF-α -308 genotypes are associated with TNF-α and TGF-ß1 mRNA expression in blood leucocytes of humans.

AIM: Tumor necrosis factor α (TNF-α) influences the pathogenesis of lung-fibrosis and carcinogenesis in normal cells. Polymorphisms of this gene are suggested to be associated with susceptibility to lung-diseases. Additionally TNF-α is postulated to play a significant role in regulating. Transforming growth factor (TGF-ß1) expression Therefore we investigated if the TNF-α or TGF-ß1 gene expression level is different within the -308 TNF-α genotypes. METHODS: Quantitative Real-time PCR of TNF-α and TGF-ß1 was performed in 178 Germans. Calculations of expression were made with the 2(-ΔΔCT) method. Detection of the -308 promoter polymorphism of the TNF-α gene was performed by rapid capillary PCR with melting curve analysis. RESULTS: The relative TNF-α mRNA expression revealed significant differences between the TNF-α -308 homozygote wild-type G/G (0.00079±0.00011; n=113) and the heterozygote genotype G/A (0.0005±0.00008; n=52; p=0.030) as well as between homozygote wild-type G/G and the homozygote mutant A/A (0.00029±0.00009; n=5; p=0.004). The relative TGF-ß mRNA expression showed, similar to TNF-α, the highest mRNA expression was seen within the TNF-α -308 homozygote wild-types, while the lowest mRNA expression lay within the homozygote mutant-types. CONCLUSION: Our findings suggest that the G-allele of TNF-α -308 is associated with a significantly higher TNF-α mRNA expression compared to the A-allele and that this also reflects in TGF-ß expression. Therefore we support the thesis that TGF-ß is regulated by TNF-α.

Physical effort of middle-aged women in a university hospital - Field tests in comparison to standardized cardiopulmonary exercise testing (CPET).

Physical effort of workload of female employees in the healthcare system is perceived to rise. Research focused mainly on physical activity levels of registered nurses (RN). Therefore, we investigated physical strain during daily routine of other hospital workers next to RN. O2uptake, heart rate, breathing frequency and ventilation were measured in 33 female medical (associate) professionals (MAP) and Cleaners&Helpers (Cl&H) using Oxycon Mobile. Physical work load was compared to standardized CPET. Wilcoxon-test and ANOVA were calculated using SPSS 20.0. Cl&H performed heavy-lifting and had the lowest power during CPET. The O2-uptake for heavy-lifting as strong effort, differed significantly from office work (p < 0.001) and bedside-patient-care (p = 0.001). Compared with metabolic equivalent (MET) cleaning, heavy-lifting, and office work are underestimated. Bedside-patient-care, walking, pushing performed by MAP are overestimated. While Cl&H had the lowest maximal power in CPET, their work required the highest O2-uptake. The tasks are underestimated in the MET-tables.

Transient lower esophageal sphincter relaxation and esophageal motor response.

BACKGROUND: Gastroesophageal reflux is caused by transient lower esophageal sphincter relaxations (TLESRs) in healthy individuals and in most patients with gastroesophageal reflux disease (GERD). Refluxate is normally propelled by pharyngeally induced swallowing events, but TLESRs may also be accompanied by retrograde esophageal motor responses (EMRs). These contractions have not previously been investigated and their effect on esophageal clearance is not known. The aim of this study was to assess the frequency of EMRs after TLESR in healthy individuals and GERD patients and to develop an animal model for further investigation of EMRs. MATERIALS AND METHODS: The frequency of TLESRs and esophageal body contractions after TLESRs was assessed using ambulatory manometry in five healthy individuals and five GERD patients. An animal model was developed for reproducible provocation of TLESRs and subsequent EMRs. RESULTS: Patients with GERD have significantly more TLESRs than healthy individuals. However, post-TLESR EMRs were not more frequent in the GERD group. All post-TLESR EMRs presented as simultaneous contractions of the esophagus. The feline model allowed reproducible initiation of the esophageal motor response after TLESR, showing that EMRs can be induced by external mechanoreceptor stimulation simultaneously with LES relaxation. This experimental design imitates the conditions after fundoplication in humans. CONCLUSIONS: The study demonstrated that GERD patients have significantly more TLESRs in comparison with healthy individuals, but these were only incidental to EMRs. Further research is needed to improve our understanding of esophageal motility disorders. The animal model presented offers a feasible tool for investigating TLESR-induced esophageal motility.

Tumour necrosis factor-alpha gene polymorphisms in asbestos-induced diseases.

BACKGROUND: Tumour necrosis factor (TNF)-alpha influences the pathogenesis of lung fibrosis and carcinogenesis in normal cells. Polymorphisms of this gene have been suggested to be associated with susceptibility to lung diseases. METHODS: Association studies were performed in German subjects, using control subjects (n = 177), pulmonary fibrosis patients (n = 612) and bronchial carcinoma patients (n = 374). RESULTS: Compared with a healthy (control) group, a significant result could be obtained for the asbestosis (patient) group (crude odds ratio (OR(crude)) = 1.57; 95% confidence interval (CI) 1.05-2.36; p = 0.03), especially with severe lung asbestosis (OR(crude) = 4.15; 95% CI 1.06-16.16; p = 0.04). A significant association was revealed when comparing asbestosis patients (OR(crude) = 4.08; 95% CI 1.53-10.54; p = 0.004 and OR(adjusted) = 3.89; 95% CI 1.49-10.17; p = 0.006) with asbestos-induced lung cancer patients. CONCLUSION: The results confirm the hypothesis that TNF-alpha polymorphisms are associated with asbestos-induced fibrotic or malignant lung diseases in Germans.

Cyp1B1 mRNA expression in correlation to cotinine levels with respect to the Cyp1B1 L432V gene polymorphism.

Cytochrome P450 1B1 (CYP1B1) is involved in the activation of a broad spectrum of procarcinogens. An association of the Cyp1B1 Leu432Val polymorphism with cancer as well as an impact on the enzyme activity has been described. To study gene-environmental interactions we investigated the quantitative Cyp1B1 mRNA expression in smokers (N = 102) and non-smokers (N = 192) with regards to the Cyp1B1 L432V gene polymorphism. Tobacco smoke exposure was assessed by serum cotinine levels. Genotypes were analysed by melting curve analysis and quantification of Cyp1B1 mRNA by real-time PCR. In comparing Cyp1B1 expression, significant differences between the two homozygote genotypes *1/*1 and *3/*3 (0.105 ± 0.019; n = 26 vs. 0.051 ± 0.017; n = 14; P = 0.039) and between the heterozygote genotype *1/*3 and *3/*3 (0.121 ± 0.029; n = 55 vs. 0.051 ± 0.017; n = 14; P = 0.039) of smokers were revealed. According to the serum cotinine levels, three subgroups (low; medium; high) were build. The group "high" (0.248 ± 0.089; n = 32) showed proportionally high Cyp1B1 mRNA expression compared to "medium" (0.101 ± 0.024; n = 33), "low" (0.086 ± 0.015; n = 32) and non-smokers (0.084 ± 0.007; n = 176). This result was reflected in the homozygote *1/*1 and the heterozygote *1/*3 genotypes. In contrast the homozygote *3/*3 genotype was missing the high Cyp1B1 mRNA expression in the cotinine subgroup "high". Our results suggest that genotypes carrying the C-allele (*1/*1 and *1/*3) at Cyp1B1 Leu432Val polymorphism show a higher response to environmental factors, such as tobacco smoke than homozygote *3/*3 genotypes.

Meta- and pooled analysis of GSTP1 polymorphism and lung cancer: a HuGE-GSEC review.

Lung cancer is the most common cancer worldwide. Polymorphisms in genes associated with carcinogen metabolism may modulate risk of disease. Glutathione S-transferase pi (GSTP1) detoxifies polycyclic aromatic hydrocarbons found in cigarette smoke and is the most highly expressed glutathione S-transferase in lung tissue. A polymorphism in the GSTP1 gene, an A-to-G transition in exon 5 (Ile105Val, 313A --> 313G), results in lower activity among individuals who carry the valine allele. The authors present a meta- and a pooled analysis of case-control studies that examined the association between this polymorphism in GSTP1 and lung cancer risk (27 studies, 8,322 cases and 8,844 controls and 15 studies, 4,282 cases and 5,032 controls, respectively). Overall, the meta-analysis found no significant association between lung cancer risk and the GSTP1 exon 5 polymorphism. In the pooled analysis, there was an overall association (odds ratio = 1.11, 95% confidence interval: 1.03, 1.21) between lung cancer and carriage of the GSTP1 Val/Val or Ile/Val genotype compared with those carrying the Ile/Ile genotype. Increased risk varied by histologic type in Asians. There appears to be evidence for interaction between amount of smoking, the GSTP1 exon 5 polymorphism, and risk of lung cancer in whites.

Influence of the Cyp1B1 L432V gene polymorphism and exposure to tobacco smoke on Cyp1B1 mRNA expression in human leukocytes.

Cytochrome P450 1B1 (CYP1B1), a phase I enzyme, is involved in the activation of a broad spectrum of procarcinogens. An association of the Cyp1B1 L432V polymorphism with diverse types of cancer, as well as an impact on the catalytic activity of the enzyme, has been described. To show the functional impact of the allelic variant Cyp1B1*3, we investigated the quantitative Cyp1B1 mRNA expression in a population of smokers, nonsmokers, and ex-smokers and determined their genotypes. Detection of the L432V polymorphism in exon 3 of the Cyp1B1 gene was performed by rapid capillary polymerase chain reaction (PCR) with melting curve analysis. For quantitative comparison of Cyp1B1 mRNA levels, real-time PCR was performed using SYBR Green fluorescence in a LightCycler system. Calculations of expression were made with the 2(-DeltaDeltaCT) method. In comparing relative Cyp1B1 mRNA expression, highly significant differences between the two homozygote genotypes *1/*1 and *3/*3 (0.185 +/- 0.027, n = 118 versus 0.071 +/- 0.013, n = 56; p = 0.000), as well as between the heterozygote genotype *1/*3 and the homozygote genotype *3/*3 (0.178 +/- 0.025, n = 171 versus 0.071 +/- 0.013, n = 56; p = 0.000), were revealed. Significant differences between the genotypes were also detected within the subgroups of smokers, nonsmokers, and ex-smokers. No significant differences were determined in comparing the relative Cyp1B1 mRNA expression with regard to tobacco smoke exposure. Our results suggest that genotypes carrying the C allele (*1/*1 and *1/*3) at Cyp1B1 L432V polymorphism have a significantly higher Cyp1B1 mRNA expression compared with the genotype without the C allele (*3/*3). Gene expression of Cyp1B1 mRNA cannot be used as a biomarker for exposure of tobacco smoke.

Morbid obesity and subsequent pancreatic cancer: pylorus-preserving pancreatoduodenectomy after laparoscopic sleeve gastrectomy.

Morbid obesity is a recognized risk factor for gastrointestinal cancer. Little is known about pancreatic cancer developing after gastric bypass surgery or about surgery for this type of tumor following bariatric surgery. This report describes a case of pancreatic head cancer identified 3 months after laparoscopic sleeve gastrectomy for morbid obesity. During routine follow-up, mild abdominal pain and elevated pancreatic enzymes prompted computed tomography, which revealed mild edematous pancreatitis. Hyperbilirubinemia developed, and magnetic resonance imaging showed a pancreatic head tumor. CA19-9 was elevated. After a pylorus-preserving pancreatic head resection, the postoperative course was uneventful. The patient received adjuvant chemotherapy. Unfortunately, at the time of writing (9 months postoperatively), a local recurrence and hepatic metastases were diagnosed. Patients treated with bariatric surgery who develop new symptoms or report constant mild symptoms should be evaluated using endoscopy and radiomorphological imaging. Interdisciplinary obesity treatment can then offer significant benefits for the patient, particularly in the case of pancreatic cancer, which is still difficult to diagnose. In addition, there is a need for epidemiological studies of patients who undergo bariatric surgery and subsequently develop cancer.

Association of transforming growth factor beta1 gene polymorphisms and asbestos-induced fibrosis and tumors.

AIM: Inhaled asbestos fibers are known to cause progressive lung or pleural fibrosis and malignancies such as lung cancer or diffuse malignant mesothelioma. Transforming growth factor beta1 (TGF-beta1), a multifunctional cytokine, regulates the proliferation and differentiation of cells. Transforming growth factor beta1 is known to promote the pathogenesis of lung fibrosis and acts as a tumor suppressor in normal cells. Two genetic polymorphisms in codons 10 (Leu10Pro) and 25 (Arg25Pro) of the TGF-beta1 gene are suggested to be associated with a different TGF-beta1 protein production. Therefore, we examined an association between the 2 TGF-beta1 gene polymorphisms and asbestos-induced lung fibrosis and lung cancer. METHODS: Detection of the 2 polymorphisms was performed by rapid capillary polymerase chain reaction, with melting curve analysis, using fluorescence-labeled hybridization probes. To investigate the association between TGF-beta1 gene polymorphisms in codons 10 and 25 and the susceptibility to asbestos-induced diseases, association studies were performed with healthy control subjects (n = 83), patients with pulmonary fibrosis (n = 591), and patients with bronchial carcinoma (n = 147). RESULTS: Compared with a healthy control group, odds ratio (OR) analysis revealed an inverse relationship for the proline allele at codon 10 or 25 with pulmonary fibrosis (higher risk) and lung cancer (lower risk). The proline allele at codon 10 or 25 is significantly associated with a higher risk for fibrotic lung diseases (ORcrude, 1.46; 95% confidence interval [CI], 1.01-2.11; P = 0.045 and ORadjusted, 1.76; 95% CI, 1.14-2.72; P = 0.011, respectively, for codon 10; OR, 2.13; 95% CI, 1.33-3.99; P = 0.019 and ORadjusted, 2.27; 95% CI, 1.14-4.52; P = 0.02, respectively, for codon 25) when compared with patients with lung cancer. A significant association for the proline allele is also revealed when comparing patients with asbestosis (ORcrude, 3.01; 95% CI, 1.44-6.29; P = 0.003 and ORadjusted, 3.72; 95% CI, 1.56-8.85; P = 0.011) with patients with asbestos-induced lung cancer. CONCLUSIONS: In summary, the results confirm the hypothesis that TGF-beta1 polymorphisms are associated with asbestos-induced fibrotic or malignant lung diseases in whites.