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Nested case-control study of lung cancer among pulp and paper workers in relation to exposure to dusts.

BACKGROUND: Numerous studies have indicated an increased risk of lung cancer in pulp and paper industry workers. In a 1990 survey, standardized mortality ratio (SMR) was found to be 122 (95% CI:96-153) for lung cancer in Polish male workers in the pulp and paper industry, and 166 (95% CI:95-270) among workers engaged in paper production. METHODS: A nested case-control design within a cohort of pulp and paper workers was applied. Seventy-nine lung cancer cases and 237 "healthy" controls were selected from the cohort of 10,460 workers employed during the years 1968-1990, and observed until the end of 1995. Based on personnel files, occupational exposure was reconstructed by experts. Using a questionnaire, data on smoking habits were collected. ORs unadjusted and adjusted for smoking were calculated applying the model of conditional logistic regression. RESULTS: Occupational exposure to inorganic dusts (kaolin, lime, cement, brick, grindstone) adjusted for smoking was a significant lung cancer risk factor, with a 4.0-fold risk (95% CI:1.3-12.6), and a dose-response by cumulative dose index. Among organic dusts only wood dust increased albeit insignificantly the risk for those exposed (adjusted for smoking OR = 2.1, 95% CI:0.9-4.9), but without dose-response relationship. CONCLUSIONS: Exposure to occupational dust with relatively low content of silica, but at high concentrations may be considered as a factor increasing lung cancer risk. However, the observation made in this study should be viewed with caution as it was based on a small number of cases, and further evidence is needed to confirm or refute the authors' hypothesis.

Air Pollutants, Occupational↗

Endotoxins isolated from the air of a Danish paper mill and the relation to change in lung function: an 11-year follow-up.

BACKGROUND: A decline in lung function has been associated with farming, cotton spinning, and work in the animal feed industry. The aim of the study was to reveal if loss of lung function was associated to work at a paper mill. METHODS: Ninety-seven male paper workers (PW), and 55 control workers were examined. Hygiene samples included total dust, endotoxins, and microorganisms. Interview, pulmonary function testing, and skin prick test (SPT) were performed and yearly decline in lung function was calculated. RESULTS: The exposure for endotoxin (LPS) ranged from Median (Max-Min) 69 (370-6) EU/m3, in the wet-end of the paper machines to 6 (19-16) in the pulping area. The lung function decline among the controls was comparable to the decrements among the maintenance and repair workers at the paper factory, around 51-54 and 37-38 ml/year among smokers' and non-smokers, respectively. After adjustment for baseline FEV1, the variables associated to an increased loss of FEV1 were age smoking and cough. For FVC we found an inverse relation between exposure and yearly decline. CONCLUSION: No increase in loss of lung function is seen among workers exposed to up to 200 EU/m3 of LPS.

Air Pollutants, Occupational↗

Pulmonary function and intradermal tests in workers exposed to soft-paper dust.

A survey was carried out in the processing department of a paper mill, consisting of environmental and personal monitoring, a short questionnaire concerning chronic non-specific lung disease (CNSLD), spirometry, and intradermal tests. Spirometry was performed on Monday, Wednesday, and Friday. Exposures to paper dust regularly exceeded the Dutch Maximal Allowable Concentrations (MACs) for total and respirable dust. There were indications of a qualitatively different exposure to molds inside the mill in comparison with the outdoor air. A comparison between a group of workers exposed to paper dust and a control group showed significantly more persons with positive late and delayed intradermal test reactions in the exposed population. The analysis of the spirometric measurements after correction for differences between the groups in age, height, and smoking habits gave evidence of the existence of lower FEV1, MMEF, MEF50, and MEF25 among exposed workers with a positive immediate intradermal reaction on Friday. The same workers showed a decline in pulmonary function over the week compared with the controls. These changes suggest an obstructive airway reaction with an immunologic mechanism to dust exposure in a paper mill.

Humans↗

Application of functional group modified substrate in room-temperature phosphorescence, I--beta-cyclodextrin modified paper substrate for enrichment and determination of fluorene and acenaphthene.

A novel method for the determination of fluorene and acenaphthene on solid phase extraction-room-temperature phosphorescence (SPE-RTP) was studied. beta-cyclodextrin (beta-CD) was chemically bonded onto chromatography paper by reaction with epichorohydrin in an ultrasonic bath. The RTP signal of fluorene and acenaphthene included on the beta-CD-modified paper was increased more than 10 times compared with non-modified filter paper, indicating the formation of the inclusion complex. The conditions for the of RTP of compounds were studied in detail. The linear ranges of fluorene and acenaphthene concentrations to the RTP intensity were over two orders of magnitude (8.0 x 10(-7)-4.0 x 10(-5) mol/L for fluorene) with a correlation coefficient of 0.999. The concentration limits of detection for fluorene and acenaphthene were 1.11 x 10(-8) mol/L and 3.8 x 10(-7) mo/L, respectively. When the sampling volume was 10 microL, the absolute LODs for fluorene and acenaphthene were 18.4 pg/spot and 0.58 ng/spot, respectively. The modified filter paper was used for solid phase extraction (SPE) and the retention behaviour of fluorene and acenaphthene was examined. The enrichment efficiency of the analytes was higher than 100-fold. The SPE-RTP coupling technique was applied directly to the determination of fluorene and acenaphthnene in environmental water samples.

Acenaphthenes↗

Application of functional group modified substrate in room temperature phosphorescence, II--heavy atom-chelated filter paper for selective determination of alpha-naphthalene acetic acid.

Heavy atom-chelated filter paper was synthesized and used as the substrate for room-temperature phosphorescence (RTP). The synthesis conditions for chelated paper were studied. The Pb-chelated filter paper could selectively induce the RTP of alpha-naphthalene acetic acid (alpha-NAA). The excitation and emission wavelengths of RTP of alpha-NAA were 300 nm and 521 nm, respectively. The concentration of alpha-NAA was linear with the RTP intensity in the range 2 x 10(-6)-6 x 10(-4) mol/L (correlation coefficient, 0.9999). The concentration detection limit was 1.35 x 10(-7) mol/L and the absolute detection limit was 0.25 ng/spot. The RSD (n = 10) was 1.7%. The method was applied to the analysis of water and vegetable samples with satisfactory results. Because the heavy atom was directly chelated onto the filter paper, the heavy-atom effect on the RTP of NAA was further increased and the analysis procedure was simple, fast and economical.

Aspartic Acid↗

Enhanced detection sensitivity of "fluorescence reduction" by shifting the analyte absorbance spectrum and use of a fluorescent paper with higher signal/noise ratio.

Nonfluorescing protein bands can be detected by the fluorescence optics of the commercial gel electrophoresis apparatus with automated scanning of the migration path (HPGE-1000, LabIntelligence, Belmont CA), taking advantage of the decrease of emission from a fluorescent paper placed below the gel by the absorbance of proteins ("fluorescence reduction"). That decrease of fluorescence gives rise to an inverted protein peak. Nonfluorescent colorless proteins appear to reduce the intensity of light emitted from the fluorescent paper due to absorbance of incident and emitted light. When the absorbance spectrum only slightly overlaps with the excitation and emission spectra of the fluorescent paper, that reduction is weak, and detection sensitivity in that application is consequently only 1/30 of that of fluorescent proteins. By contrast, when the protein is colored so that its absorbance spectrum overlaps widely with the excitation and emission spectra of the fluorescent paper, the sensitivity of "fluorescence reduction" equals 1/4 to 1/5 of that obtained for fluorescent proteins. Bands detected by "fluorescence reduction" provide a quantitative measure of protein load and mobility. The area of the inverted bands is proportional to protein loads up to 16 microg/lane of the gel tray. A theory of "fluorescence reduction" is presented which accounts for the existence of a linear relationship between band area and load.

Animals↗

Use of micro samples of finger prick blood dried on filter paper for a quick and simple dipstick dot-EIA for diagnosis of amebic liver abscess (ALA).

Filter paper was used as a support to absorb micro samples of finger prick blood for detection of antibodies to Entamoeba histolytica (causative organism of amebiasis) by a rapid dipstick dot-EIA technique; 8 microliters of blood was sufficient to saturate discs (diameter 6 mm) of Whatman paper No. 3. Conditions of elution of blood from the discs were optimized and the best results were obtained when 0.4 ml of buffer was used for elution for 30 minutes at room temperature. The filter paper technique is extremely useful for field use and for diagnosis of amebic liver abscess on a large scale since it does not involve centrifugation of blood and use of sterile vials because blood dried on paper can be stored in polythene bags at room temperature for up to 3 months and for a week at 42 degrees C without significant loss of antibody activity, thereby eliminating the need of refrigeration of samples for storage or transportation to a reference laboratory. Elution of blood from different discs of the same patient was found to be highly reproducible without appreciable loss of sensitivity or specificity. Twenty-four confirmed ALA, 29 non-ALA, and 25 apparently normal healthy controls, with no previous history of amebiasis, were tested. Sensitivity and specificity of the test was found to be 96% and 92%, respectively.

Animals↗

Lung function and respiratory symptoms among workers in a soft paper mill.

The aim of the present cross-sectional study was to investigate whether long-term exposure to soft paper dust causes impairment of lung function. Exposed workers (n = 287) and referents (n = 79) were investigated, using spirometry and questionnaires. Personal samplings of total dust showed that the actual mean concentrations did not exceed 3 mg/m3. The exposed subjects were divided into three categories according to historical and present exposure to paper dust; low exposure, moderate exposure and high exposure. The study did not show any lung function impairment due to exposure to paper dust. However, the exposed subjects had a significantly increased prevalence of symptoms from both the upper and lower airways as well as an increased prevalence of reported asthma. On the basis of our study, we conclude that lung function impairment does not occur among workers exposed to mean levels of soft paper dust below 5 mg/m3.

Cross-Sectional Studies↗

A simple filter-paper technique allows detection of mucosal cytokine levels in vivo in ulcerative colitis. Interleukin-1 and interleukin-1-receptor antagonist.

A simple filter-paper method for in vivo assessment of cytokines in intestinal mucosa of patients with ulcerative colitis (UC) was developed and evaluated. Twenty-eight patients were included. Twenty-three patients had ulcerative colitis (UC) and five irritable bowel syndrome (IBS). Inflammation was assessed endoscopically. Through a rectoscope, filter paper was applied to the macroscopically most inflamed area of the rectal mucosa until soaked. The filter paper was transferred to a buffer solution, and IL-1 beta and IL-1ra were assessed using ELISA. Positive correlations between endoscopic grading and In(IL-1 beta) (P < 0.0001) and In(IL-1ra) (P < 0.001) and a negative correlation between endoscopic grading and In(IL-1ra /IL-1 beta) (P < 0.02) were found. In measurements during and after a flare-up no significant change in IL-1ra but a significant decrease in IL-1 beta was detected, which is in agreement with investigations on biopsies. In conclusion, the filter-paper technique is an easily applicable, low-risk method that provides a means of monitoring cytokines in vivo in UC.

Colitis, Ulcerative↗

Paper and pulp mill effluent-induced immunotoxicity in freshwater fish Channa punctatus (Bloch).

The influence of temperature variation on the humoral immune response using the plaque-forming cell (PFC) assay in freshwater fish Channa punctatus (Bloch) was investigated. The fish was exposed to 1% concentration (v/v in water) of paper and pulp mill effluent under standard laboratory conditions in glass aquaria. Effect of effluent exposure on the organ weight and organ cellularity was also evaluated. In general, lower temperature in winter produced a subdued response in control as well as experimental group. At higher temperature of summer and rainy seasons, an elevated response was observed. It was revealed that though suppressive effect of effluent was evident during all the seasons, in summer, extent of suppression was greater as compared to winter. Paper and pulp mill effluent exposure resulted in a decrease in the splenic and pronephric (head kidney) cellularity, with more pronounced effect in the summer season. We also studied the effects of the length of exposure on various parameters. Fish were exposed for 15, 30, 60, and 90 days to effluent. Short-term exposure for 15 days induced an elevated PFC response, but change was not statistically significant. Conversely, the exposure for 30, 60, and 90 days significantly reduced (p < 0.05-0.001) the PFC response. Long-term exposure also caused significant reduction (p < 0.05-0.01) in the weights of lymphoid organs (spleen, head kidney, and total kidney). These results show a suppressive effect of chemical constituents of paper and pulp mill effluent on the immune functions. Furthermore, results demonstrated that though modulatory effect of the temperature on immune functions is recognized, it was not a major contributory factor to the elevated immunotoxicity of paper and pulp mill effluent in the seasons of high temperature.

Animals↗

Nasal symptoms among workers exposed to soft paper dust.

OBJECTIVES: To clarify whether occupational exposure to paper-dust is associated with an increased risk of non-infectious rhinitis. METHODS: Thirty-seven workers exposed to paper-dust in a soft-paper mill were compared with 36 unexposed controls. The study was performed under normal working conditions during the non-pollen season. Medical and occupational history was taken down in a comprehensive questionnaire and nasal symptoms were scored on a visual analogue scale (VAS). Pulmonary and nasal function was assessed by spirometry, acoustic rhinometry and peak nasal inspiratory flow. Nasal lavage was analysed for interleukin-8 (IL-8) and nasal transit time was monitored with the saccharine test. Concentrations of inhalable dust for each exposed subject during the day of the clinical study were measured with personal sampling devices. RESULTS: There was an increased prevalence of nasal blockage and crust formation among the exposed workers. However, there was no difference with regard to acoustic rhinometry, nasal transit time or nasal peak inspiratory flow. In the whole population, IL-8 in nasal lavage was higher among men than among women, 193 ng/l vs 132 ng/l, P = 0.006. There was also a positive trend (P = 0.01) with increasing nasal IL-8 going from non-smokers (122 ng/l), ex-smokers (126 ng/l) to current smokers (235 ng/l). CONCLUSIONS: We have found that occupational exposure to paper-dust is associated with symptoms of nasal blockage and nasal crusting. We find no objective signs of nasal inflammation, even among the subgroup with the highest current exposure.

Adult↗

Detection and quantitation of colored deposit-forming Meiothermus spp. in paper industry processes and end products.

Colored biofilms cause problems in paper industry. In this work we used real-time PCR to detect and to quantitate members of the genus Meiothermus from the process samples and end products from 24 machines manufacturing pulp, paper and board in four countries. The results obtained from 200 samples showed the importance of members of the genus Meiothermus as ubiquitous biofoulers in paper machines. This genus was the dominant biofouler in some mills. From < or =10(4) to 10(11) copies of Meiothermus 16S rRNA genes were found per gram of process deposit (wet weight). Meiothermus spp. were found in paper and board products with colored defects and connection between deposit-forming microbes and end-product spots was shown. 16S rRNA gene sequences of 29 biofilm producing bacterial isolates from different mills were determined. Based on sequence data, 25 of the isolates were assigned to the genus Meiothermus, with Meiothermus silvanus and M. ruber as the most frequent species.

DNA Primers↗

A new system for washing ion-exchange paper disks used in radiochemical enzyme assays.

A new device has been developed for the removal of radioactive substrate from ion-exchange paper disks, leaving ionized product bound to the paper. It has a number of important advantages over older methods of washing the ion-exchange paper: (1) It is much more thorough and efficient; background absorption of unionized material is reduced to relatively low levels. (2) Fragile media such as DEAE-substituted paper (DE81) are not subjected to the erosive effects of stirrers or agitators. (3) The disks remain organized throughout the sample application and washing procedure, eliminating need for time-consuming sorting of wet radioactive disks after washing. A larger number of assays can therefore be processed conveniently at one time. (4) Radioactive nucleosides and other adsorbable substrates are collected in a cartridge, eliminating the handling and sink-disposal of large volumes or excessive quantities of radioactive materials.

Chromatography, Ion Exchange↗

Use of cyanuric chloride-activated paper for detection of subpicogram quantities of specific DNA sequences and its application to linked restriction fragment length polymorphism analysis in a Duchenne muscular dystrophy affected family.

Conditions for the optimal use of cyanuric chloride-activated (CCA) paper in Southern transfer hybridization experiments of genomic DNA were investigated. They depend critically on pH and ionic strength during transfer and on the composition of the hybridization solution. Simplified hybridization conditions using a SSC/dextran sulfate system at 65 degrees C without sodium dodecyl sulfate and the complex Denhardt's solution are applied. CCA paper allows repeated use in hybridization experiments. Under optimized conditions CCA paper allows a more sensitive detection of single-copy gene sequences in the subpicogram range than do nylon membranes. Application of these transfer and hybridization conditions with our newly developed CCA paper to carrier determination and prediction of the healthy male haplotype demonstrates its usefulness for prenatal counseling of a Duchenne muscular dystrophy family.

DNA↗

Detection of cellulose-binding proteins in electrophoresis gels by filter paper affinity blotting.

Proteins separated in electrophoresis gels were tested for the ability to bind cellulose by a simple blotting procedure. Proteins were blotted onto Whatman No. 1 filter paper by diffusion or by electrophoretic transfer and detected by Coomassie blue staining. Certain proteins released into culture supernatant by Bacteroides succinogenes NR9 (ATCC 43854) adhered strongly to cellulose, but were not found to have carboxymethylcellulose activity. Boiling of samples prior to electrophoresis eliminated the ability of proteins to bind to cellulose. Proteins that did not adhere to filter paper cellulose were detected on a nitrocellulose membrane placed behind the filter paper during electrophoretic transfer. The technique, referred to as filter paper affinity blotting, detects cellulose-binding proteins with great sensitivity.

Bacterial Proteins↗

Xerographic paper as a transfer medium for western blots: quantification of bovine alpha S1-casein by western blot.

We have found that xerographic paper (regular photocopy or laser printer paper) can be used as a transfer medium for protein blots for the immunodetection of low concentrations (a few nanograms) of bovine alpha S1-casein. With paper blotting, we could detect the protein with three times more sensitivity than with polyvinylidene difluoride. Blotting was achieved by transfer from sodium dodecyl sulfate-polyacrylamide gel electrophoresis to the methanol-wet paper. The blot was incubated with chicken anti-casein antibodies, sequentially peroxidase-labeled rabbit anti-chicken antibodies, and diaminobenzidine substrate. The blots were directly scanned and the pixel intensity of the band areas was integrated. An analysis of the scanned blots showed that the log of protein concentration was linearly related with the square root of an integrated pixel intensity (r2 greater than 0.96). This linear relationship was observed in a wide range of protein concentration from 5 ng to 15 micrograms. The coefficients of variation were 12.4% for intraassay and 15.7% for interassay. This new analytical procedure can be applied to estimate the concentration of proteins by immunological blotting.

Animals↗

Amino acid profiles by HPLC after filter paper sampling: 'appropriate technology' for monitoring of nutritional status.

This paper describes a rapid analysis of free amino acid levels in capillary blood samples using a modified HPLC system. Capillary whole blood (25 microliters) is dried on a filter paper, extracted and the equivalent of 0.25 microliter of the initial blood sample is used for each amino acid analysis. Nineteen free amino acid levels are determined with a reproducibility of better than +/- 10% for the entire procedure of sampling, preparation and analysis, with the exception of ornithine (+/- 19%) and lysine (+/- 12%). Cystine and proline cannot easily be determined by this method. Alanine, tyrosine, methionine, valine, phenylalanine, isoleucine and leucine concentrations on the filter paper are unaltered after 1, 2 and 21 wk. Storage at room temperature should not be for longer than 2 wk, but storage at +4 degrees C, -18 degrees C and -70 degrees C is acceptable for 21 wk. This new micromethod seems to be a practical and reliable tool. Because of its simplicity and, above all, the need for a minimal amount of capillary blood, it is a valid means for the routine monitoring of amino acid profiles in sick preterm infants on different protein regimens. The sampling and storage methods are also examples of 'appropriate technology' for field studies of nutritional adequacy in population samples derived from infants. This is because centrifugation is not necessary and the fact that the relevant amino acids on the dried filter paper samples display high stability.

Adult↗

High-performance liquid chromatographic method for the simultaneous determination of mefloquine and its carboxylic metabolite in 100-microliters capillary blood samples dried on paper.

A reversed-phase high-performance liquid chromatographic method is described for the analysis of mefloquine and its carboxylic metabolite in 100-microliters capillary blood spots dried on chromatographic paper. Each spot was cut into small pieces, and mefloquine and its metabolite were eluted with an ammonia-water solution (10:90, v/v). The compounds were extracted simultaneously after alkalization at pH 9.5 using tetrabutylammonium as ion-pairing agent and then separated on a C18 column with ultraviolet detection at 227 nm. The recovery of the drugs from spiked blood applied to paper and dried was 70-80%, and the inter-assay precision at 1.0-5.0 mumol/l (therapeutic range) was less than 10%. The correlation between extractions from venous whole blood and capillary blood applied to chromatographic paper was more than 0.94. The analytes were stable in dried blood spots for at least fifty days at -20 degrees C. The decrease of concentration was less than 10%, when the paper was stored at 37 degrees C for fifty days. The assay is reliable and easy to use for therapeutic monitoring of mefloquine with a lower limit of determination of 0.3-0.5 mumol/l.

Chromatography, High Pressure Liquid↗