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Biomedical subjects

A Hollander

Publications and source records attributed to A Hollander.

At least 19 recordsLinked to original sources

The effect of air pollution on exhaled nitric oxide of atopic and nonatopic subjects.

Levels of exhaled nitric oxide (NO) were determined in well-characterized atopic and nonatopic subjects on 4 days with a different level of outdoor air pollution. The two groups matched well regarding spirometric values, i.e., no difference with regard to FEV(1), FVC, and peak flow. On the 4 test days asymptomatic atopic subjects exhaled 1.5- to 2.4-fold higher levels of NO compared with nonatopic subjects. In both groups the increase in exhaled NO in response to air pollution was similar (2.5 times maximal increase, P < 0.01). In conclusion, atopic subjects exhale higher levels of NO compared with nonatopic subjects, but respond to a similar degree to increased levels of air pollution.

Adult↗

Exposure-response relationships for work-related sensitization in workers exposed to rat urinary allergens: results from a pooled study.

BACKGROUND: Recent studies in a few industries have shown that the likelihood of IgE-mediated sensitization increases with increasing exposure. The shape of the exposure-response relationships and modification by age, sex, and smoking habit has hardly been studied. OBJECTIVE: The purpose of this study was to determine exposure sensitization relationships for rat sensitization and to evaluate the influence of atopy, smoking habits, and sex. METHODS: Data from 3 cross-sectional studies in The Netherlands, the United Kingdom, and Sweden were used and involved 1062 animal laboratory workers. Selection criteria were harmonized, and this resulted in a study population of 650 animal laboratory workers (60.6% female) with less than 4 years of exposure. Air allergen levels were assessed previously and converted on the basis of an interlaboratory allergen analysis comparison. Available sera were analyzed for the presence of specific antibodies against common allergens (house dust mite, cat, dog, and grass and birch pollen) and work-related allergens (rat and mouse urinary proteins). Questionnaire items on work-related respiratory symptoms, hours worked with rats per week, job performed, smoking habits, and sex were used in this analysis RESULTS: The prevalence of work-related sensitization to rat urinary allergens (IgE >0.7 KU/L) was 9.7 % (n = 63). Thirty-six of the sensitized workers had work-related symptoms (asthma or rhinitis). Two hundred forty-eight workers (38.2%) were atopic (defined as specific IgE to 1 of the common allergens). The sensitization rate increased with increasing air allergen exposure. Atopic workers exposed to low levels of allergen had a more than 3-fold increased sensitization risk compared with nonexposed atopic workers. For atopic subjects, the risk increased little with increasing exposure, whereas for nonatopic subjects, a steadily increasing risk was observed. Smoking and sex did not modify the sensitization risk. CONCLUSION: Rat urinary allergen-sensitization risk increased with increasing exposure intensity. Workers who were atopic had a clearly elevated sensitization risk at low allergen exposure levels.

Allergens↗

Comparison of methods to assess airborne rat and mouse allergen levels. I. Analysis of air samples.

Airborne laboratory-animal allergens can be measured by several methods, but little is known about the effects of important differences in methodology. Therefore, methods used in research projects in The Netherlands, the UK, and Sweden were compared. Seventy-four sets of three parallel inhalable dust samples were taken by a single operator in animal facilities in the three countries, and analyzed in parallel by the three institutes for rat and mouse urinary allergen. Rat-allergen levels measured by RAST inhibition (UK) were 3000 and 1700 times higher than levels measured by enzyme immunoassay (EIA)-sandwich methods with polyclonal rabbit (The Netherlands) or monoclonal mouse (Sweden) antibodies, while the difference between the two EIA-sandwich methods was much smaller: a factor of 2.2. For mouse allergen, an inhibition radioimmunoassay (RIA) with rabbit antimouse antibodies (UK) gave 4.6 and 5.9 times higher concentrations than sandwich EIAs with rabbit polyclonal antibodies (Sweden and The Netherlands), while the difference between the two sandwich EIAs was, on average, 1.6-fold. Thus, although levels of rat and mouse aeroallergens are significantly correlated, the assay type gives large differences in absolute concentrations, and interlaboratory technical differences affect even the same assay type. Conversion factors can aid comparison between studies, and, in the long term, assay standardization is desirable.

Air Pollutants↗

Comparison of methods to assess airborne rat and mouse allergen levels. II. Factors influencing antigen detection.

Potential factors influencing antigen detection in immunoassays for measuring rat or mouse aeroallergen (i.e., assay setup, antigen specificities, standard extracts used, and antigen decay) were investigated in a three-country study (the UK, The Netherlands, Sweden). An inhibition enzyme immunoassay (EIA) setup gave nominal rat urinary allergen (RUA) sample values seven times higher than a sandwich EIA setup utilizing identical antibodies and standards. In immunoblotting experiments, pooled patient serum and polyclonal rabbit antibodies partly detected different rat antigens; monoclonal antibody specificity could not be determined. Immunoblot detection of mouse urinary antigens (MUA) by the polyclonal rabbit antibodies from all laboratories was similar. In both the RUA and the MUA assays, urinary antigen standards were detected with similar potency, except purified Rat n 1, which was an inefficient inhibitor in the RUA RAST inhibition. In the sandwich EIA RUA assays, a rat room-dust extract was detected with 700800-fold less sensitivity than rat urine, whereas in the RAST RUA assay, dust inhibited equally with rat urine. Simulated decay did not decrease the potency of urinary antigen in any assay. Thus, assay setup and choice of detection antibodies strongly influence the nominal allergen levels. We recommend the use of standardized and characterized antibodies and standard extracts in sandwich EIAs to measure airborne rodent urinary allergens.

Air Pollutants↗

Interferon-ribavirin for chronic hepatitis C with and without cirrhosis: analysis of individual patient data of six controlled trials. Eurohep Study Group for Viral Hepatitis.

BACKGROUND & AIMS: The aim of this study was to compare interferon (IFN)-ribavirin combination therapy with IFN monotherapy in chronic hepatitis C with particular focus on its efficacy in cirrhosis. METHODS: A multivariate analysis of individual patient data of all randomized controlled trials using an IFN-ribavirin arm, reported between 1991 and March 1998, was performed. Centers included 1 Asian and 5 European university-based referral centers for liver disease. A total of 197 patients with chronic hepatitis C received IFN-alpha (3 MU three times weekly) and ribavirin (1-1.2 g daily) for 6 months, and 147 patients received IFN-alpha (3 MU three times weekly) for 6 months. Patients were characterized according to previous IFN therapy, presence of cirrhosis, and genotype 1. Efficacy of therapy was evaluated by assessing the sustained response rate by logistic regression analysis. RESULTS: Patients without cirrhosis treated with IFN-ribavirin had a significantly higher sustained response rate than those treated with IFN, approximately 3-fold for previously untreated patients (IFN-ribavirin: genotype 1, 33%; genotype 2/3, 65%; IFN: genotype 1, 8%; genotype 2/3, 24%). In cirrhosis, sustained response rates with IFN-ribavirin (previously untreated: genotype 1, 7%; genotype 2/3, 24%) were also significantly higher than those with IFN (previously untreated: genotype 1, 1%; genotype 2/3, 5%). Clinical relevant superiority of combination therapy over IFN monotherapy was also observed for relapse; the same trend was observed for nonresponders. Tolerance for IFN-ribavirin was similar for patients with or without cirrhosis. CONCLUSIONS: Combination with ribavirin significantly enhances the sustained response rate of IFN therapy in major patient types (cirrhosis, genotype 1) with chronic hepatitis C. Thus, IFN-ribavirin combination is likely to become the antiviral therapy of choice for cirrhosis caused by hepatitis C.

Adult↗

Acute lung function changes and low endotoxin exposures in the potato processing industry.

Work-related respiratory symptoms, acute lung function changes and personal endotoxin exposure were studied in 61 workers from a potato processing plant. According to their job title mean endotoxin exposure level, workers were divided into low (AM = 21 EU/m3) and high (AM = 56 EU/m3) exposure categories. Shortness of breath and chest tightness during work were reported by 18% and 16% of the workers, respectively, mainly in the low endotoxin exposure category. A total of 148 across-shift lung function changes were measured during three consecutive afternoon shifts. The mean FEV1 and MMEF showed a decrease over the work shift, being largest on the first working day after a 3-day absence from work. Workers exposed to high endotoxin levels showed a larger across-shift decrease in lung function than workers exposed to low endotoxin exposures, the effect being most pronounced on the first day after a 3-day absence from work. At the start of the second work shift, FVC, FEV1 and MMEF were lower than at the start of the first work shift. This difference was larger for high exposed workers. High exposed workers with work-related respiratory symptoms showed an 8-10% across-shift change in FVC, FEV1 and MMEF We conclude that significant across-shift decreases in lung function of potato processing workers is related to endotoxin exposure levels above 53 EU/m3 over 8 hr.

Acute Disease↗

Work-related changes in peak expiratory flow among laboratory animal workers.

Laboratory animal workers are at risk of developing allergic symptoms, of which asthmatic symptoms are the most severe. The aim was to study the relationship between allergic symptoms due to working with rats and variability and changes in peak expiratory flow (PEF). Several indices were used on the basis of the amplitude of the PEF or the differences in PEF between days with and without exposure to rat aeroallergens. Of the 398 rat workers, 73% completed PEF readings on at least 9 days, of whom 208 had PEF readings on working days with and without contact with animals. The overall prevalence rate of allergic symptoms (asthmatic, eye, nose and/or skin) among rat workers during the handling of rats was 17.3%. Asthmatic symptoms were reported by 6.7%. The PEF of the workers who reported asthmatic symptoms due to working with rats decreased significantly on days working with the animals (difference between the minimum PEF averaged over working days with animals and over days without animals (deltaPEFmin-min) = -73 L x min(-1)), compared to the workers without symptoms (2.2 L x min(-1)). This effect was more pronounced among workers with a late asthmatic response, i.e. the presence of asthmatic symptoms several hours after working with rats (deltaPEFmin-min = -11.6 L x min(-1)). Multiple regression analyses showed that only those with asthmatic symptoms several hours after working with rats and those with allergic symptoms had an increased deltaPEFmin-min. In addition, workers with asthmatic symptoms were also more likely to have a higher PEF variability than workers without asthmatic symptoms. However, no difference in PEF variability between days with and without animals contact was observed. This study shows that the peak expiratory flow of workers who reported asthmatic symptoms due to working with rats decreased significantly on days working with laboratory animals.

Adult↗

Determinants of airborne rat and mouse urinary allergen exposure.

OBJECTIVES: The purpose of this study was to determine the factors affecting exposure to rat and mouse urinary allergens. METHODS: Ambient and personal air sampling was performed on a large scale in 7 laboratory animal facilities. RESULTS: Allergens were mainly present as large particles (>5.8 microm). The higher the number of animals in a room, the higher the allergen concentrations. Allergen levels were twice as high on Mondays as on other days due to the tasks performed on Mondays. Filter tops on animal cages were associated with 6-17 times lower ambient allergen levels. An inverse day-night rhythm for rats produced > or = 10 times higher rat urinary allergen levels. Personal exposure to rat and mouse urinary allergens differed between job titles but especially between facilities, probably because of differences in task performance and technology. Task-specific sampling revealed that the highest personal exposure levels occurred when contaminated bedding and high numbers of conscious animals were handled. The proportion of time spent on these tasks determined the degree of allergen exposure to a large extent. CONCLUSIONS: This study showed that the number of animals present in the room, use of filter top cages, and an inverse day-night rhythm were important determinants of rat and mouse urinary allergens in ambient air. Personal exposure to rat and mouse urinary allergens was predominantly determined by the task and site and, to a limited extent, by ambient exposure levels. The presented determinants can be used to develop exposure reduction strategies and also to aid epidemiologic studies of laboratory animal allergy.

Air Pollution, Indoor↗

Respiratory allergy in laboratory animal workers: a retrospective cohort study using pre-employment screening data.

OBJECTIVES: To study the role of exposure, atopy, and smoking in the development of laboratory animal allergy (LAA) in a retrospective cohort study. METHODS: Between 1977 and 1993, 225 people received a pre-employment screening when they started a job at a Dutch research institute where they were going to work with laboratory animals. After active follow up 136 of them (60.4%) could be traced and were sent a questionnaire with extensive questions on allergic symptoms, smoking habits, and job history. 122 people (89.7%) sent back a completed questionnaire. Those who were accepted for a job at the institute and did not have allergic symptoms at the start of the job were selected as cohort members. After selecting people with complete data on start and end date of jobs, exposure intensity, atopy, and smoking, the cohort consisted of 99 people with an average time of follow up of 9.7 years. LAA was defined as a positive response to a set of questions in the questionnaire. The mean number of hours a week a person was exposed to laboratory animals at entry of the cohort was used as a surrogate for exposure, and was divided into four categories. RESULTS: 19 cohort members (19.2%) reported LAA. More people with asthmatic symptoms were found in the high exposure categories. More atopic than non-atopic people reported asthmatic symptoms (13% v 6%). The mean time until development of symptoms of LAA was about 109 months in non-atopic people (n = 9), and 45 months in atopic people (n = 10) (t test; P < 0.05). Time until development of symptoms of LAA was shorter at a higher intensity of exposure, except for those exposed for less than two hours a week. A proportional hazard regression analysis showed that exposure and atopy were significant determinants of LAA. An increased relative risk (RR) was found for non-atopic people exposed to laboratory animal allergens for more than two hours a week. Atopic people had an even higher risk when exposed to laboratory animals for more than two hours a week (RR above 7.3). Sex, smoking, and age were not risk factors. More atopic than non-atopic people were absent from work or transferred because of allergies. CONCLUSIONS: This study showed that exposure and atopy are significant predictors of LAA and that the risk of developing LAA remained present for a much longer period (> 3 y) than considered before.

Animal Technicians↗

Respiratory allergy to rats: exposure-response relationships in laboratory animal workers.

Laboratory animal workers are at high risk of developing occupational allergy. Little is known about the relationship between levels of exposure and the risk of developing laboratory animal allergy. A cross-sectional study was performed in 540 workers at eight facilities to quantify the exposure-response relationship for allergy to rats, while controlling for determinants like atopy, gender, and smoking. All participants completed a questionnaire, underwent skin prick testing with common and occupational allergens, and total IgE as well as occupational allergen-specific IgE antibodies were serologically measured. Personal air dust samples were taken during full-shift periods to estimate the rat urinary aeroallergen exposure levels. In the whole study population no clear exposure-response relationship was observed. However, in the group of workers with less than 4 yr of working experience with laboratory animals the prevalence rate of sensitization to rat allergens was clearly associated with exposure levels. The exposure-response relationship was steepest for workers with atopy-associated risk factors, i.e., self-reported allergy or sensitization to cats or dogs, or elevated total serum IgE. The prevalence rates of sensitization to rat allergens for these workers were about 15, 9.5, and 7.3 times higher in the high, medium, and low exposure group, respectively, compared with internal reference group.

Adult↗

Exposure of laboratory animal workers to airborne rat and mouse urinary allergens.

BACKGROUND: Laboratory animal workers are at high risk of developing occupational allergy. Little is known about the relationship between levels of exposure and the risk of developing laboratory animal allergy. Since laboratory animal work comprises a large number of different-often short lasting-tasks, it is of interest to assess which activities are associated with high, low or intermediate levels of allergen exposure. OBJECTIVE: To develop and evaluate highly sensitive immunoassays in order to quantify rat and mouse urinary allergens in airborne dust sampled during short-lasting tasks. METHODS: Personal air dust samples were taken during full-shift periods as well as during specific tasks in seven laboratory animal facilities. Two sandwich enzyme immunoassays were developed, using rabbit antisera against rat and mouse urinary proteins. The rabbit antibodies were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting and compared with IgE antibodies from sensitized laboratory animal workers. RESULTS: The rabbit antibodies were highly specific for rat and mouse urinary proteins and reacted with all IgE-binding allergens in either urinary protein preparation. The assays for rat and mouse urine were very sensitive, with detection limits of 0.075 ng/mL. The coefficient of variation of the analysis was 12.9% for both assays. Animal caretakers appeared to experience the highest exposure to aeroallergens. A large variation in exposure within jobs was found, due to differences between tasks performed during the sampling day and the facility worked at. The highest exposure levels were found during removal of contaminated bedding from the cages. However, rat and mouse allergen exposure levels during this task varied enormously between facilities, 1.1-158 ng eq/m3 and 0.63-2000 ng eq/m3, respectively. CONCLUSION: Both sandwich immunoassays are highly specific and sensitive and are able to identity tasks of relatively short duration with high, medium and low exposure to airborne rat and mouse urinary allergens.

Allergens↗

Cat and dog allergy and total IgE as risk factors of laboratory animal allergy.

BACKGROUND: Laboratory animal workers are at high risk of developing occupational allergy. In many cases the severity of allergy symptoms makes further work with laboratory animals impossible. OBJECTIVE: This study was designed to estimate prevalence rates of sensitization and symptoms of allergy in a population of laboratory animal workers and to determine the association between various host factors and these prevalence rates. METHODS: A cross-sectional survey was undertaken in 540 workers at eight facilities in the Netherlands. All participants completed a questionnaire and underwent skin prick testing with common and occupational allergens. In addition, total and specific IgE measurements were obtained. RESULTS: Prevalence rates of allergy symptoms caused by working with rats and mice were 19% and 10%, respectively. Symptoms, especially chest tightness, were strongly related to sensitization. Rat and mouse allergy, defined as symptoms of allergy accompanied by specific atopic sensitization, were highly associated with elevated total IgE, reported adverse reactions, and positive skin prick test responses to common allergens. This relationship could be explained by a response to cat or dog allergens. CONCLUSIONS: Allergy to cats or dogs seemed to be an important risk factor for laboratory animal allergy, whereas allergy to pollen or house dust mite, in the absence of cat and dog allergy, appeared to be insignificant. More conclusive evidence about cat and dog allergy preceding laboratory animal allergy can only be provided after analysis of follow-up data.

Allergens↗

Enzyme immunoassays for total and allergen specific IgE in population studies.

OBJECTIVE: Extensive IgE serology in occupational or environmental health studies is often hampered by a lack of technical facilities and finance. The use in population studies of relatively simple and inexpensive enzyme immunoassays (EIAs) was therefore evaluated for the assessment of total serum immunoglobulin E (IgE), and of specific IgE reactions with various common (house dust mites, grass and birch pollen, and cat) or occupational (fungal alpha-amylase and rat urinary protein) allergens. METHODS: Total IgE was measured with a sandwich EIA, calibrated with commercially available IgE standards. Reproducibility was studied by testing pooled normal human serum samples in each of a large series of test plates. A panel of 156 children's serum samples with known IgE values was used to compare the assay with other total IgE assays. A previously developed EIA for anti-yeast IgE was adapted for the measurement of IgE reacting with various common and occupational allergens. Binding of IgE to microwells coated with commercially available allergen extracts, or allergen preparations from our own laboratory, was measured with a monoclonal anti-human IgE antibody and subsequent incubations with biotinylated rabbit anti-mouse Ig and avidin-peroxidase. Panels of serum samples from school children (n = 116), bakery workers (n = 126), and laboratory animal workers (n = 52) were used to study sensitivity and specificity, with reference to skin prick tests as the standard, and to compare the EIAs with commercially available test kits. RESULTS: The detection limit of the EIA for total IgE was 0.5-1 kU/l for undiluted serum samples, and the coefficient of variation between assays was less than 15% at serum concentrations between 1 and 150 kU/l. Results obtained with the panel of 156 children's serum samples were strongly correlated (r2 = 0.86) with IgE concentrations measured previously by radioimmunoassay. The results of the EIA for various occupational allergens correlated very well, both qualitatively and quantitatively, with the results of commercial test kits. Sensitivity and specificity of the EIA results as a predictor of skin prick test reactivity towards common allergens (house dust mite, grass pollen, birch pollen, and cat) were remarkably high (> 80%-90%) in the series of 116 children's serum samples. In a population of bakery workers the specificity of the EIAs was also very high (> 90%). The sensitivity was notably lower (30%-70%) in this adult population, which is, however, in agreement with results reported for conventional IgE tests. CONCLUSION: As the costs were estimated to be at least five to 10-fold lower than those of commercial test kits, the EIAs for total and specific IgE may be very useful tools in epidemiological studies of atopic respiratory or other disorders.

Adult↗

Influence of various dust sampling and extraction methods on the measurement of airborne endotoxin.

The influence of various filter types and extraction conditions on the quantitation of airborne endotoxin with the Limulus amebocyte lysate test was studied by using airborne dusts sampled in a potato processing plant. Samples were collected with an apparatus designed to provide parallel samples. Data from the parallel-sampling experiment were statistically evaluated by using analysis of variance. In addition, the influence of storage conditions on the detectable endotoxin concentration was investigated by using commercially available lipopolysaccharides (LPS) and endotoxin-containing house dust extracts. The endotoxin extraction efficiency of 0.05% Tween 20 in pyrogen-free water was seven times higher than that of pyrogen-free water only. Two-times-greater amounts of endotoxin were extracted from glass fiber, Teflon, and polycarbonate filters than from cellulose ester filters. The temperature and shaking intensity during extraction were not related to the extraction efficiency. Repeated freeze (-20 degrees C)-and-thaw cycles with commercial LPS reconstituted in pyrogen-free water had a dramatic effect on the detectable endotoxin level. A 25% loss in endotoxin activity per freeze-thaw cycle was observed. Storage of LPS samples for a period of 1 year at 7 degrees C had no effect on the endotoxin level. House dust extracts showed a decrease of about 20% in the endotoxin level after they had been frozen and thawed for a second time. The use of different container materials (borosilicate glass, "soft" glass, and polypropylene) did not result in different endotoxin levels. This study indicates that the assessment of endotoxin exposure may differ considerably between groups when different sampling, extraction, and storage procedures are employed.

Air Pollutants↗

Acute respiratory effects in the potato processing industry due to a bioaerosol exposure.

The relation between bioaerosol exposure in the potato starch industry and work related respiratory symptoms is described. One group of workers was exposed to high dust concentrations (geometric mean up to 56.0 mg/m3) with low endotoxin and antigen concentrations (geometric mean up to 12.6 ng/m3 and 90 relative antigen units (RAU) per m3). A second group was exposed to low dust concentrations (geometric mean up to 3.9 mg/m3), but the endotoxin and antigen concentrations were high (geometric means of environmental samples up to 72 ng/m3 and 2.9.10(2)RAU/m3). Twenty of the 48 workers had specific IgG4 titres to dust extract. Of these 20 workers, 14 showed an increase in IgG4 titre during the first month of the potato processing season. No specific IgE antibodies to dust extracts were found. Twenty two workers were equipped with a Mini-Wright peak flow meter during a four week period. Two workers showed a work related decline in peak flow values. It was concluded that exposure to dust made airborne during the refining process of potato starch may cause work related respiratory symptoms.

Aerosols↗

Inhibition and enhancement in the analysis of airborne endotoxin levels in various occupational environments.

Inhibition and enhancement effects on the Limulus Amebocyte Lysate (LAL) assay were studied in a series of endotoxin exposure samples from various occupational environments. Two types of analyses were performed, with various dilutions and with spiked samples. Results showed that inhibition and enhancement occurred in some samples, leading to respective underestimation and overestimation of the endotoxin concentration. When inhibition or enhancement is present, the result of this study shows that large differences in endotoxin concentration may be found, depending on the dilution at which the sample is analyzed. False conclusions about exposure levels and their potential health effects might be introduced. Results show that quality control procedures need to become standard practice when endotoxins are analyzed in occupational environments and development of a validated, generally accepted protocol should be encouraged.

Air Pollutants↗

Potentially allergenic airborne particles in the vicinity of a yeast and penicillin production plant.

Potential health risks of exposure to emissions of a yeast and penicillin production plant were investigated by measuring viable particles and protein contents of particles in ambient air. The results showed a clear decrease of the downwind number of yeast colony-forming units with increasing distance from the source. Upwind the number of yeast colony-forming units was zero. Identification showed that nearly all yeast were of the species Saccharomices cerevisiae. Such a trend could not be found for the total number of colony-forming units (yeasts, molds, and bacteria) although the upwind concentration was slightly lower than the downwind concentration. The downwind protein concentration was significantly elevated compared to the upwind concentration.

Air Pollutants, Occupational↗