[Occupational cancer--burdens of the past or actual threat?].
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Air Pollutants, Occupational↗
Biomedical subjects
K Golka
Publications and source records attributed to K Golka.
[Retroperitoneal leiomyosarcoma. A rare differential diagnosis of an adrenal tumor].
A pararenal mass is a clinical finding that cannot be explored preoperatively regarding its parent organ even nowadays. We report in the following about a patient who was admitted with dull pain located in the flank and upper abdomen. Ultrasound investigation at admission showed a solid homogeneous mass close to the upper pole of the left kidney. Urinalysis and catecholamine levels were normal. Intraoperatively, a sarcoma infiltrating the renal capsule and renal vein was observed. In the case of a mass located in the area of the adrenal gland, an extra-adrenal tumor must be considered especially if there are normal findings for urinalysis and catecholamine levels even if modern imaging techniques had been applied.
Abdominal Pain↗
[The causes of urinary bladder cancer and possibilities of prevention].
Bladder cancer is a malignant disease with exogenous and thus avoidable causative factors. Cigarette smoking is by far the most relevant risk factor and a clear dose-response relationship has been documented. That the bladder cancer risk decreases only a few years after the cessation of smoking is noteworthy. Occupational exposure, particularly to aromatic amines such as benzidine and beta-naphthylamine and to certain azo dyes, represents another important risk factor. At high risk are workers involved in the production of these chemicals and, to a lesser extent, those processing them. The currently known environmental factors seem to play a minor role. Treatment-induced risks causing secondary bladder cancer also have to be considered. Currently, the prevention of bladder cancer mainly involves avoiding exposure to known causative factors and early detection of the disease in high risk populations.
Antineoplastic Agents, Alkylating↗
Expression of cytochrome P450 enzymes CYP1A1, CYP1B1, CYP2E1 and CYP4B1 in cultured transitional cells from specimens of the human urinary tract and from urinary sediments.
Expression of cytochromes P450 CYP1A1, CYP1B1, CYP2E1 and CYP4B1 was analysed on the transcript level in human urothelial cells obtained by various methods. As a source of urothelial cells, exfoliated cells in urine samples were used. Their expression profiles were determined either immediately after centrifugal enrichment (n=4) or after their cultivation and propagation (n=8). Another source of urothelial cells were ureter specimens from surgical subjects (n=4). Generally, expression was most prominent for CYP1B1 and CYP4B1 among the CYP transcripts analysed. CYP1B1 mRNA was detected in all samples investigated except for one ureter specimen. CYP4B1 mRNA was present in cell cultures from three out of eight healthy subjects, in three out of four directly investigated urinary sediments and in the cells of all five ureter specimens of four donors investigated after resection and subsequent cell culture. In most cases, CYP2E1 transcript levels were lower than those of CYP1B1 and CYP4B1. CYP2E1 mRNA was detected in cell cultures of six out of eight healthy subjects, in one out of four urinary sediments and in three out of five ureter specimens. CYP1A1 mRNA was clearly observed only in cells from resected ureters. In cell cultures the relative mRNA expression levels varied with subjects interindividually, intraindividually and also during the time of cell culture. The study demonstrates constitutive mRNA expressions of xenobiotic metabolising CYP enzymes in human urothelial cells obtained by different methods. In particular, transcripts of CYP1B1 and CYP4B1 are present, coding for enzymes which are active in the metabolism of polycyclic aromatic hydrocarbons and arylamines, respectively.
Adult↗
[Occupational and non-occupational risk factors in bladder cancer patients in an industrialized area located in former East-Germany].
PURPOSE: Several occupational carcinogens are metabolized by polymorphic enzymes. The distribution of the polymorphic enzymes N-acetyltransferase 2 (NAT2; substrates: aromatic amines), glutathione S-transferase M1 (GSTM1; substrates: e. g., reactive metabolites of polycyclic aromatic hydrocarbons), and glutathione S-transferase T1 (GSTT1; substrates: small molecules with 1 - 2 carbon atoms) were investigated. MATERIAL AND METHODS: At the urological department in Lutherstadt Wittenberg, 136 patients with a histologically proven transitional cell cancer of the urinary bladder were investigated for all occupations performed for more than 6 months. Several occupational and non-occupational risk factors were asked. The genotypes of NAT2, GSTM1, and GSTT1 were determined from leucocyte DNA by PCR. RESULTS: Compared to the general population in Middle Europe, the percentage of GSTT1 negative persons (22.1 %) was ordinary; the percentage of slow acetylators (59.6 %) was in the upper normal range, while the percentage of GSTM1 negative persons (58.8 %) was elevated in the entire group. Shifts in the distribution of the genotypes were observed in subgroups who had been exposed to asbestos (6/6 GSTM1 negative, 5/6 slow acetylators), rubber manufacturing (8/10 GSTM1 negative), and chlorinated solvents (9/15 GSTM1 negative). CONCLUSIONS: The overrepresentation of GSTM1 negative bladder cancer patients also in this industrialized area and more pronounced in several occupationally exposed subgroups points to an impact of the GSTM1 negative genotype in bladder carcinogenesis.
Acetyltransferases↗
Low-cost data transfer from a questionnaire to standard software using a barcode pen.
Computer-aided transfer of questionnaire data simplifies the analysis of questionnaires. We present a solution based on an inexpensive barcode pen and its decoder, the software tool Barcode Wizard included in CorelDRAW, and a self-developed application written using Microsoft Visual Basic for Applications. The barcode may be provided on the questionnaire or on a transparency. Error correction is done by means of two different procedures. The present solution can be applied while looking over the completed questionnaire and thus allows time-saving, economic, and precise data transfer from the completed questionnaire directly into computer software.
Computer Peripherals↗
Physiological and psychological approaches to chemosensory effects of solvents.
Workplace related standard settings for solvents are based in a remarkable extent on information about sensory irritations. However, data from controlled human exposure studies are seldom available. Therefore, the aim of this study was to present the association of self-reported symptoms and physiological processes leading to sensory irritations. Three series of laboratory experiments each with 24 young male subjects were performed. Ethyl benzene (EB), 2-butanone (methyl ethyl ketone or MEK), isopropyl alcohol (IPA), 1-octanol (OCT), and 2-ethylhexanol (EHEX) were investigated in low and high concentrations. Ratings for sensory irritations (eyes and nose), olfactory symptoms, and annoyance were assessed repeatedly before, during and after the 4-h-exposures. The anterior active rhinomanometry (AAR) was employed measuring the nasal flow. The nasal lavage was used for the analysis of the neuropeptide substance P as indicator of nasal chemosensory irritations. Goodness-of-fit was calculated for non-linear regression analyses by fitting the sine function on the data of the ratings given during the 4-h-exposure. In general, ratings for annoyance and odor symptoms were fitted on a higher level than those for sensory irritations. However, a high fit could be shown for nasal irritations due to EHEX. In these experiments, a significant reduction of the nasal flow and a significant increase of substance P could be proved.
Administration, Inhalation↗
[Quality of life following radical prostatectomy].
PURPOSE: To investigate quality of life in prostate cancer patients after radical retropubic prostatectomy. MATERIALS AND METHODS: 401 men who underwent radical prostatectomy between January 1995 and September 1999 at our clinic were asked for information concerning daily life activities, overall satisfaction, voiding ability and sexual activity in standardized questionnaire. RESULTS: The average follow-up was 36 months, 72 % (n = 289) of our patients replied. In 53 (18%) of the men who replied to our questionnaire, the nerve-sparing technique had been used. At the time our patients were questioned, 202 (70%) did not use any pads, and 211 (73%) were satisfied or very satisfied with the outcome. Of these patients 98% would undergo a radical prostatectomy again. 13% (n = 37) of our patients reported limited satisfaction, 14% (n = 41) were not satisfied with their postoperative status. However, 69% of this latter group would nevertheless decide to have a radical prostatectomy again. Of the patients who underwent the nerve-sparing technique, 68% (n = 36) reported sufficient erections for sexual intercourse, four of them under medication with sildenafil. Patients who underwent the nerve-sparing technique reported better results in daily life activities, general health status, IPSS-score and continence. While age at the time of radical prostatectomy did not influence life quality, we found substantial correlation with the postoperative tumor stage. CONCLUSIONS: Our results underline the importance of early prostate cancer detection, not only regarding a lower recurrence rate, but also because of a better postoperative quality of life.
Activities of Daily Living↗
Two extrapulmonary neoplasms in a uranium miner.
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Aged↗
Experiments on the effects of a continuous 16.7 Hz magnetic field on melatonin secretion, core body temperature, and heart rates in humans.
The present study investigated the hypothesis that a strong extremely low frequency magnetic field partially suppresses the synthesis of melatonin and subsequently elevates the core body temperature. Seven healthy young men (16-22 years) took part in a control and in an exposure session. Three men experienced first the control and then the exposure session, four men experienced the sessions in reverse order. Control sessions were performed as constant routines, where the participants spent 24 hour periods continuously in bed while air temperature was 18 degrees C, illumination less than 30 lux, and the sound pressure level 50 dBA. The exposure sessions differed from that protocol only between 6 pm and 2 am when a strong extremely low frequency magnetic field was continuously applied (16.7 Hz, 0.2 mT). Assuming that the participants were unable to perceive the field consciously, they were blind against the actual condition. Salivary melatonin levels were determined hourly; body core temperatures and heart rates were registered continuously throughout. Neither of these parameters revealed alterations that can be related to the influence of the magnetic field. The present results, taken together with other investigations using that particular field, lead to the hypothesis that the effects most likely, occur, only after repetitive exposures to intermittent fields.
Adolescent↗
Dependence of papanicolaou gradings of exfoliated urothelial cells upon GSTM1 and GSTT1 polymorphism in benzidine-exposed workers of the Shanghai dye industry.
The distribution of the polymorphic alleles of the genes coding for glutathione S-transferases (GSTs) M1 and T1 was compared with the results of cytological grading of exfoliated urothelial cells (Pap test) in a non-diseased high-risk group of workers formerly exposed to benzidine in the Shanghai dyestuff industry (n = 317). All subjects were genotyped for GSTT1 and M1 gene polymorphism by allele-specific PCR. Individuals were stratified according to their job and duration of exposure. A subgroup of 78 individuals with cytological gradings of grade III or higher in the Pap test showed a significant under-representation of the combination of GSTT1 0/0 and M1 0/0 genotypes compared with 238 subjects with a cytological classification lower than grade III (OR 0.55, 95% CI 0.31-0.98. P=0.04). These results suggest that neither the GSTM1 0/0 or GSTT1 0/ 0 genotype alone nor their combination had a clear association with cytopathological changes in exfoliated urothelial cells from individuals previously exposed to benzidine in Shanghai. This contradicts the results of studies indicating that the GSTM1 0/0 genotype is associated with an increased risk for bladder cancer in the general population, mostly outside China.
Adult↗
Polymorphic methyl group metabolism genes in patients with transitional cell carcinoma of the urinary bladder.
Because polymorphisms in the methyl group metabolism genes methylene-tetrahydrofolate reductase (MTHFR), methionine synthase (MS), and cystathione beta-synthetase (CBS) affect plasma homocysteine levels and intracellular concentrations of S-adenosylmethionine (SAM), they modify the susceptibility to cardiovascular diseases and cancer. Specifically, genome-wide decreased DNA methylation ('hypomethylation') in human cancers might be a consequence of decreased SAM levels. Because hypomethylation is particularly prevalent in transitional cell carcinoma of the urinary bladder (TCC), the genotype distributions for the two each most prevalent MTHFR, MS, and CBS alleles were compared between 165 TCC patients and 150 population controls. The distributions of the MTHFR 677A/V and the MS 919G/D alleles were not significantly different between cancer patients and controls, even after stratification according to age, gender, tumor stage or grade. The CBS 844INS68 allele was slightly less frequent in TCC patients than in controls (q=0.07 versus 0.10), but was rarer among males in both groups. Among the TCC patients, this gender difference was highly significant (Mantel-Haenszel and chi(2)-test P=0.007). No significant difference between TCC patients and controls was found for any combined genotype. Likewise, the extent of DNA hypomethylation determined in 62 carcinoma specimens was not related to the respective genotypes. Thus, on their own, the MTHFR, MS and CBS genotypes do not appear to act upon susceptibility to TCC or influence the extent of DNA hypomethylation in this cancer.
5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
N-acetyltransferase 2 phenotype in painters with bladder cancer and controls.
AIM: This study was designed to evaluate the impact of N-acetyltransferase 2 (NAT2, substrate: aromatic amines) in painters with bladder cancer and controls. BACKGROUND: Until the beginning of the 1960s, painters in Germany have used, among others, azo dyes based on carcinogenic aromatic amines. MATERIALS AND METHODS: Sixteen painters with bladder cancer and 26 healthy painters (controls) who were from the same area in Germany and in the same age group (+/-5 years) were recruited into the study. All subjects were phenotyped for NAT2 by the molar ratio of two caffeine metabolites in the urine which was determined by the high performance liquid chromatography (HPLC) method. The number of years working as a painter, age at first exposure to paints and the life-time smoking habits of subjects were noted. RESULTS: Fourteen cases and 23 controls had been exposed to paints before 1960. Age at first exposure to paint was 15.5 years (SD 5.3) in cases and 16.3 (SD 4.9) years in controls. Cases had worked 31.1 years (SD 15.0) and controls had worked 44.8 years (SD 7.2) as painters. Four cases and 7 controls were non-smokers. In this study, 88% of cases and 65% of controls were of the "slow" acetylation and phenotype, CONCLUSION: The result point to and impact of the slow acetylation status as an individual risk factor for bladder cancer in persons occupationally exposed to amounts of carcinogenic aromatic amines released from water-soluble azo dyes.
Acetylation↗
Current smoking, occupation, N-acetyltransferase-2 and bladder cancer: a pooled analysis of genotype-based studies.
The aim of this study was to investigate the association of NAT2 gene polymorphism with bladder cancer using the data derived from the International Project on Genetic Susceptibility to Environmental Carcinogens. Four case control studies conducted in four European countries, plus two case series, one from England and one from Germany, for a total of 1530 cases and 731 controls (all Caucasian) were included. The interaction between NAT2 and bladder cancer considering smoking habits and occupational exposure was studied. There was a significant association between NAT2 and bladder cancer (odds ratio: 1.42, 95% confidence interval: 1.14-1.77), with a slightly significant heterogeneity among studies. However, heterogeneity disappeared when smokers were divided into current and ex-smokers. The risk of cancer was elevated in smokers and occupationally exposed subjects, with the highest risk among slow acetylators. The increase in risk was limited, in fact, to current smokers (odds ratio = 1.74, 95% confidence interval: 0.96-3.15). This analysis confirms that the NAT2 genotype is a risk factor for bladder cancer by interacting with smoking or occupational exposures. Our observation suggests that NAT2 is not a risk factors per se but modulates the effect of carcinogens contained in tobacco smoke (probably arylamines) or associated with occupational exposures.
Adult↗
Methyl group metabolism gene polymorphisms and susceptibility to prostatic carcinoma.
BACKGROUND: Alterations of DNA methylation are very frequent in prostatic carcinoma. A possible cause underlying altered DNA methylation could be an insufficient level of S-adenosylmethionine as a consequence of nutritional imbalances or of weaker alleles of genes for its synthesis, i.e., encoding methylene-tetrahydrofolate reductase (MTHFR), methionine synthase (MS), and beta-cystathione synthetase (CBS). Therefore, homozygosity or heterozygosity for such weaker alleles may underlie susceptibility to prostatic carcinoma. METHODS: The distribution of the two most frequent MTHFR, MS, and CBS alleles was determined in 132 prostatic carcinoma patients and 150 population controls by restriction fragment length polymorphism-(RFLP) PCR. RESULTS: In the controls, a Hardy-Weinberg equilibrium was observed for each allele pair. No significant differences were observed with respect to age or gender. No significant differences for single genes or combinations were found between prostatic carcinoma patients and controls, although the MTHFR Val allele was slightly overrepresented among the tumor patients. Neither did the allele distribution significantly differ among the prostatic carcinoma patients stratified according to age, clinical stage, or presence of metastases. However, the MTHFR Val allele tended to be associated with higher tumor grade. CONCLUSIONS: In general, the data do not support the hypothesis that weaker alleles in methyl group metabolism genes constitute a major factor in the high prevalence of DNA methylation alterations found in prostatic carcinoma. However, a potential association with the MTHFR genotype deserves further study.
5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
Reversible ageusia as an effect of clopidogrel treatment.
In two patients we observed a loss of taste during clopidogrel treatment which was reversible.
Aged↗
Glutathione transferase isozyme genotypes in patients with prostate and bladder carcinoma.
Genotype distributions for GSTP1, GSTM1, and GSTT1 were determined in 91 patients with prostatic carcinoma and 135 patients with bladder carcinoma and compared with those in 127 abdominal surgery patients without malignancies. None of the genotypes differed significantly with respect to age or sex among controls or cancer patients. In the group of prostatic carcinoma patients, GSTT1 null allele homozygotes were more prevalent (25% in carcinoma patients vs. 13% in controls, Fisher P =0.02, chi2 P=0.02, OR=2.31, CI = 1.17-4.59) and the combined M1-/T1 -null genotype was also more frequent (9% vs. 3%, chi2 P=0.02, Fisher P = 0.03). Homozygosity for the GSTM1 null allele was more frequent among bladder carcinoma patients (59% in bladder carcinoma patients vs 45% in controls, Fisher P=0.03, chi2 P=0.02, OR=1.76, CI=1.08-2.88). In contrast to a previous report, no significant increase in the frequency of the GSTP1b allele was found in the tumor patients. Except for the combined GSTM1-/ T1-null genotype in prostatic carcinoma, none of the combined genotypes showed a significant association with either of the cancers. These findings suggest that specific single polymorphic GST genes, that is GSTM1 in the case of bladder cancer and GSTT1 in the case of prostatic carcinoma, are most relevant for the development of these urological malignancies among the general population in Central Europe.
Aged↗
Cultures of exfoliated epithelial cells from different locations of the human urinary tract and the renal tubular system.
Exfoliated human urinary tract epithelial cells and renal tubular cells from urinary sediments of healthy adults, of urological patients and of internal patients were isolated and cultured. Cells started proliferating within 1 week after seeding a sediment. Proliferating cells formed colonies of different morphologies, designated as type-1 or type-2 cell colonies. Type-1 cell colonies showed irregular contours and spindle-like cells within the colonies. Subcultivation of type-1 cells for up to six passages was possible. Type-2 cell colonies showed smooth-edged contours and subcultivation was not possible. The epithelial character of type-1 cells was demonstrated by positive immunohistochemical staining for cytokeratin-7. In contrast to carbonic anhydrase-positive stained Madin Darby canine kidney cells (MDCK), which were used as positive controls for renal tubular cells, type-1 cells were carbonic anhydrase-negative on staining with the cobalt phosphate method. This indicates that type-1 cells were not of renal tubular origin. Type-2 cells were positively stained for carbonic anhydrase, indicating that type-2 cells were renal tubular cells. Type-2 cell colonies could be assigned to two subgroups with different cell forms. Colonies of cobblestone-like cells more often occurred than type-2 cell colonies with spindle-like cells, which are described in this study for the first time. Colonies with cobblestone-like cells formed domes (hemicysts), whereas spindle-like type-2 cell colonies did not. Cultures of urinary sediments from healthy adults, elderly multimorbid patients treated with furosemide, and urological patients with urolithiasis treated with sulfamethoxazole/trimethoprim and/or with a percutaneous nephrostomy catheter were compared. In 52% of all cultured sediments from healthy adults, in 30% of those from multimorbid patients, and in 75-80% of those from urological patients cells proliferated to colonies. The ratios of type-1 to type-2 cell colonies were 3.3:1 (healthy adults), 1.4:1 (urological patients with urolithiasis), and 1.8:1 (urological patients with urolithiasis, urine was directly collected from the renal pelvis with a percutaneous nephrostomy catheter). Successful cultures of the urinary sediments from these three groups revealed means of 3 or 4 colonies, 14 colonies, and 21 colonies, respectively. Differences in the number of colonies in relation to sex were observed only for the group of urological patients. It was shown that type-1 cells were urothelial cells, which did not show morphological differences due to their locations of origin within the urinary tract, whereas type-2 cells were probably renal tubular cells. These findings offer new aspects in the culturing of human urothelial or kidney epithelial cells with a method based on noninvasive collecting of specimens and requiring only minimal culture effort. The cultures obtained by this method can be used for in vitro studies in toxicological and clinical research.
Adolescent↗