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1.  Signs of alveolar inflammation in non-smoking Swedish wood trimmers. 
Wood trimmers are periodically exposed to mould and may develop extrinsic allergic alveolitis (EAA). To investigate if there were any signs of EAA in wood trimmers with low exposure, 19 non-smoking wood trimmers underwent bronchoalveolar lavage (BAL), spirometry, and measurement of diffusion capacity (TLCO). The group was subdivided into those with (n = 9) and without serological antibodies against mould. In 14 workers the TLCO was measured both at the beginning and at the end of a week at work. Twenty five healthy non-smokers served as BAL controls and 19 healthy non-smokers as lung function controls. The median exposure of total dust was well below the Swedish threshold value, and the exposure of mould and bacteria was also low. The cell concentrations and the proportions of the various alveolar cells did not differ between the groups. The concentrations of the soluble components albumin, fibronectin, and hyaluronan were, however, significantly increased (p less than 0.001 for all) in the workers. No difference was found in lung function between the workers and the controls, and the TLCO was not impaired during a week at work. The groups of seropositive and seronegative workers did not differ in any of these parameters. The results are interpreted as a low intensity alveolar inflammation. The presence of precipitating antibodies against mould did not predict any greater risk of developing a more intense inflammation. Analysis of soluble non-cellular BAL components seems to reflect a discrete ongoing alveolar inflammation better than cell counts only.
PMCID: PMC1012125  PMID: 1606029
2.  PAS staining of bronchoalveolar lavage cells for differential diagnosis of interstital lung disease 
Diagnostic Pathology  2009;4:13.
Bronchoalveolar lavage (BAL) is a useful diagnostic tool in interstitial lunge diseases (ILD). However, differential cell counts are often non specific and immunocytochemistry is time consuming. Staining of glyoproteins by periodic acid Schiff (PAS) reaction may help in discriminating different forms of ILD. In addition, PAS staining is easy to perform. BAL cells from patients with idiopathic pulmonary fibrosis (IPF) (n = 8), sarcoidosis (n = 9), and extrinsic allergic alveolitis (EAA) (n = 2) were investigated. Cytospins from BAL cells were made and cells were stained using Hemacolor quick stain and PAS staining. Lymphocytic alveolitis was found in sarcoidosis and EAA whereas in IPF both lymphocytes and neutrophils were increased. PAS positive cells were significantly decreased in EAA compared to IPF and sarcoidosis (25.5% ± 0.7% vs 59.8% ± 25.1% and 64.0% ± 19.7%, respectively) (P < 0.05). No significant correlation between PAS positive cells and inflammatory cells was observed. These results suggest that PAS staining of BAL cells may provide additional information in the differential diagnosis of ILD. Further studies ware warranted to evaluate PAS staining in larger numbers of BAL from patients with ILD.
doi:10.1186/1746-1596-4-13
PMCID: PMC2681453  PMID: 19389250
3.  BN 52021 (a platelet activating factor-receptor antagonist) decreases alveolar macrophage-mediated lung injury in experimental extrinsic allergic alveolitis. 
Mediators of Inflammation  1998;7(3):201-210.
Several lines of research indirectly suggest that platelet activating factor (PAF) may intervene in the pathogenesis of extrinsic allergic alveolitis (EAA). The specific aim of our study was to evaluate the participation of PAF on macrophage activation during the acute phase of EAA in an experimental model of this disease developed in guinea pigs. Initially we measured the concentration of PAF in bronchoalvedar lavage fluid, blood and lung tissue. In a second phase we evaluate the participation of PAF on alveolar macrophage activation and parenchymal lung injury. The effect of PAF on parenchymal lung injury was evaluated by measuring several lung parenchymatous lesion indices (lung index, bronchoalvedar lavage fluid (BALF) lactic hydrogenase activity and BALF alkaline phosphatase activity) and parameters of systemic response to the challenge (acute phase reagents). We observed that induction of the experimental EAA gave rise to an increase in the concentration of PAF in blood and in lung tissue. The use of the PAF-receptor antagonist BN52021 decreases the release of lysosomal enzymes (beta-glucuronidase and tartrate-sensitive acid phosphatase) to the extracellular environment both in vivo and in vitro. Furthermore, antagonism of the PAF receptors notably decreases pulmonary parenchymatous lesion. These data suggest that lung lesions from acute EAA are partly mediated by local production of PAF.
PMCID: PMC1781835  PMID: 9705608
4.  Role of interleukin 4 and its receptor in clinical presentation of chronic extrinsic allergic alveolitis: a pilot study 
Background
Th-2 cytokine milieu including interleukin 4 (IL-4) was detected in fibrotic lung diseases. Chronic extrinsic allergic alveolitis (EAA) may be also accompanied by marked fibrogenesis. The aim of this study was to determine if IL-4 and its receptor (IL-4R-alpha) play any role in the clinical presentation and pathogenesis of chronic EAA.
Methods
Twenty patients originally investigated for interstitial lung disease and finally diagnosed affected with chronic EAA and sarcoidosis were prospectively enrolled into the study. Concentrations of IL-4, IL-4R-aplha and total protein were assessed in the bronchoalveolar lavage fluid (BALF) of all enrolled subjects as well as high resolution computed tomography (HRCT) scores and pulmonary function tests.
Results
BALF IL-4R-alpha and total protein concentrations were significantly higher in chronic EAA patients (p < 0.05). Concentrations of BALF IL-4R-alpha were significantly higher in men than in women (p < 0.05) in EAA group. Total protein BALF levels were significantly elevated in ex-smokers with EAA compared to nonsmokers (p < 0.05). A positive correlation (p < 0.01) between IL-4R-alpha BALF concentrations and HRCT interstitial scores were observed in chronic EAA group; the IL-4R-alpha/total protein ratio showed the same significant positive correlation. A negative correlation between lung function results and IL-4R-alpha, and IL-4R-alpha/total protein as well, was also found (p < 0.05).
Conclusions
We suggest a clinical relevance for the IL-4/IL-4R axis in the etiopathogenesis of chronic EAA. IL-4R-alpha could serve as a potential biomarker of lung fibrogenesis.
doi:10.1186/2049-6958-8-35
PMCID: PMC3682858  PMID: 23721656
Chronic extrinsic allergic alveolitis; High resolution computed tomography score; Interleukin 4; Interleukin 4 receptor; Sarcoidosis
5.  Extrinsic allergic alveolitis in the tobacco industry. 
A total of 57 subjects who had been exposed to mould dust in the tobacco industry were studied. Their working environment showed exposure to spores of different moulds, and 29 subjects (51%) showed antibodies against one or more of the microbes. Fifteen (26%) had work related respiratory symptoms. Eight (14%) showed slight radiographic pulmonary fibrosis. Spirometry showed a tendency toward restriction and obstruction, especially in small airways. Diffusion capacity was decreased in 18% of the workers. Three clinical cases of typical allergic alveolitis were also found. All this suggests that exposure of spores of different moulds (especially Aspergillus fumigatus) in the manufacture of tobacco products may induce symptoms and signs relating to extrinsic allergic alveolitis.
PMCID: PMC1009239  PMID: 6318802
6.  An assessment of dermal exposure to semi-synthetic metal working fluids by different methods to group workers for an epidemiological study on dermatitis 
Background: Assessment of exposure assessment to metal working fluids (MWF) has almost exclusively focused on inhalation exposure.
Aims: To assess levels of, and factors affecting, dermal and inhalation exposure to semi-synthetic MWF, and to identify suitable dermal exposure grouping schemes among metal workers for an epidemiological survey on dermatitis of hands, forearms, and head.
Methods: A cross-sectional survey was conducted in four metal working machining departments of a truck manufacturing plant, estimating dermal and inhalation exposure levels to semi-synthetic metal working fluids (SMWF) in machine operators. Dermal exposure levels to SMWF were estimated by three different methods for dermal exposure assessment (VITAE, surrogate skin pad method, and a semi-quantitative dermal exposure assessment method (DREAM)).
Results: The identified factors affecting dermal exposure were similar for the three methods, although differences were found for estimated variability in dermal exposure levels between groups, within groups (among workers), and from day to day. With the VITAE method differences in exposure levels were detected between workers that were not detected with the surrogate skin pad method, and only partly with the DREAM method.
Conclusions: Considering the additional effort and costs that use of the VITAE method entailed, the observational semi-quantitative DREAM method appeared to be more efficient for grouping of dermal exposure levels for the epidemiological study on dermatitis.
doi:10.1136/oem.2004.015396
PMCID: PMC1741081  PMID: 16109820
7.  Clinical and immunological reactions to Aspergillus niger among workers at a biotechnology plant. 
The workforce at a biotechnology plant producing citric acid by fermentation of molasses with a strain of Aspergillus niger was studied. A combination of a respiratory questionnaire and clinical assessment identified 18 subjects (4.9% of the workforce) with work related bronchospasm. In nine of these evidence of sensitisation to A niger was obtained by skin prick tests and radioallergosorbent test (RAST) using as an antigen an extract of the A niger culture fluid from the process. Of the 325 subjects without work related bronchospasm, only nine (2.7%) had a positive prick test. There were no subjects with symptoms of extrinsic allergic alveolitis. Investigation into the source of the antigen showed that whereas, in some areas of the plant, A niger spores were present, in others there were no detectable spores. In these areas, however, extracts of filters from air samplers were shown by RAST inhibition to contain A niger antigens, indicating that the culture fluid was generating airborne antigen. RAST inhibition studies showed that the A niger culture fluid used in the process contained antigens that were not present in a commercially available A niger extract, thus emphasising the importance in this type of investigation of using antigens prepared from material to which the workers are exposed.
PMCID: PMC1007478  PMID: 3986142
8.  Bagassosis: An Epidemiological, Environmental, and Clinical Survey 
An epidemiological and environmental survey of 170 bagasse workers employed by a raw sugar producing company in Trinidad was carried out in order to assess the prevalence of respiratory symptoms and to determine if exposure to bagasse was associated with alterations in ventilatory capacity.
The epidemiological survey failed to reveal a significantly increased prevalence of respiratory symptoms in the more exposed group but showed that the group of Indian workers who were regularly and continuously exposed to bagasse had a significantly lower ventilatory capacity than the control group. This diminished ventilatory capacity was demonstrated despite negligible dust concentrations in the plant. However, the possibility that persistent exposure to low concentrations of bagasse may be the cause must be considered.
During a five-year period, 17 patients with bagassosis were seen, the clinical picture being similar to that described in extrinsic allergic alveolitis from other causes.
The systematic variations demonstrated in some indices of ventilatory function in different racial groups are discussed.
Images
PMCID: PMC1008810  PMID: 5723350
9.  Extrinsic Allergic Alveolitis (Hypersensitivity Pneumonitis) Caused by Sphingobacterium spiritivorum from the Water Reservoir of a Steam Iron 
Journal of Clinical Microbiology  2005;43(9):4908-4910.
A case of extrinsic allergic alveolitis (EAA) caused by Sphingobacterium spiritivorum is described. The symptoms were associated with the use of a steam iron. The water reservoir was heavily contaminated with S. spiritivorum (106 CFU ml−1). This is the first report of S. spiritivorum as a causative agent of EAA.
doi:10.1128/JCM.43.9.4908-4910.2005
PMCID: PMC1234114  PMID: 16145174
10.  Airway Symptoms and Biological Markers in Nasal Lavage Fluid in Subjects Exposed to Metalworking Fluids 
PLoS ONE  2013;8(12):e83089.
Backgrounds
Occurrence of airway irritation among industrial metal workers was investigated. The aims were to study the association between exposures from water-based metal working fluids (MWF) and the health outcome among the personnel, to assess potential effects on the proteome in nasal mucous membranes, and evaluate preventive actions.
Methods
The prevalence of airway symptoms related to work were examined among 271 metalworkers exposed to MWF and 24 metal workers not exposed to MWF at the same factory. At the same time, air levels of potentially harmful substances (oil mist, morpholine, monoethanolamine, formaldehyde) generated from MWF was measured. Nasal lavage fluid was collected from 13 workers and 15 controls and protein profiles were determined by a proteomic approach.
Results
Airway symptoms were reported in 39% of the workers exposed to MWF although the measured levels of MWF substances in the work place air were low. Highest prevalence was found among workers handling the MWF machines but also those working in the same hall were affected. Improvement of the ventilation to reduce MWF exposure lowered the prevalence of airway problems. Protein profiling showed significantly higher levels of S100-A9 and lower levels of SPLUNC1, cystatin SN, Ig J and β2-microglobulin among workers with airway symptoms.
Conclusions
This study confirms that upper airway symptoms among metal workers are a common problem and despite low levels of MWF-generated substances, effects on airway immune proteins are found. Further studies to clarify the role of specific MWF components in connection to airway inflammation and the identified biological markers are warranted.
doi:10.1371/journal.pone.0083089
PMCID: PMC3877012  PMID: 24391738
11.  Extrinsic allergic alveolitis: comparative study of the bronchoalveolar lavage profiles and radiological presentation 
Postgraduate Medical Journal  2006;82(971):598-601.
Introduction
Extrinsic allergic alveolitis (EAA) is an immunologically mediated interstitial lung disease. The abnormalities in the bronchoalveolar lavage (BAL) fluid cell counts are almost always seen in patients with EAA according to the stage of the disease. The aim of this retrospective study was to find out how the BAL lymphocyte count, percentage of lymphocytes expressing HLA‐DR, CD4/CD8 T cell ratio in BAL fluid, and the concentration of immunoglobulin G in serum correspond to the inflammatory activity of the disease.
Methods
The study included 14 patients with EAA. BAL fluid samples were obtained and processed for cytological and cytometric analysis. Immunoglobulin G serum concentrations were measured. High resolution computed tomography (HRCT) scoring system modified by Gay was used for establishing the alveolar and interstitial score in each patient.
Conclusions
It was found that subjects with normal value of CD4/CD8 ratio in BAL fluid had higher interstitial HRCT score. Clinical presentation, continuous exposure to the causative antigens, and BAL lymphocyte count positively correlated with the alveolar HRCT score. It is proposed that the increased BAL lymphocyte count could be the predictor of the inflammatory activity of the disease, especially in people with lasting exposure to the offending antigen.
doi:10.1136/pgmj.2005.044735
PMCID: PMC2585727  PMID: 16954458
extrinsic allergic alveolitis; bronchoalveolar lavage; HRCT scoring system
12.  Expression of the Fc-receptor for IgE (Fc epsilon RII, CD23) on alveolar macrophages in extrinsic allergic alveolitis 
The Journal of Experimental Medicine  1990;171(4):1163-1169.
Expression of the Fc receptor for IgE (Fc epsilon R) was analyzed on alveolar macrophages (AM) in 10 patients with extrinsic allergic alveolitis (EAA) compared with 10 patients with sarcoidosis and to 6 apparently healthy controls. By using the anti-Fc epsilon RII mAb M-L25 in immunocytochemistry experiments, we found that greater than 60% of AM in 10 of 10 patients with EAA were strongly positive, as evidenced by visual analysis in light microscopy and by cytometry. By contrast, no significant staining was detected in sarcoidosis or in controls with either method. Similar results were obtained when Fc epsilon R were identified with preformed immune complexes consisting of NIP-specific human/mouse chimeric IgE antibody plus NIP-ovalbumin. Furthermore, greater than 60% of AM in patients with EAA stained positive for IgE, demonstrating that endogenous IgE is bound to the AM. Our data suggest that IgE antibodies bound to Fc epsilon RII on AM may be involved in pathophysiology of extrinsic allergic alveolitis by activation of the AM after binding of allergen to the cell surface IgE. Furthermore, with the clearcut pattern of Fc epsilon RII expression in extrinsic allergic alveolitis it may be possible to use CD23 antibodies for differential diagnosis of inflammatory lung disease.
PMCID: PMC2187838  PMID: 2139100
13.  Respiratory symptoms, immunological responses, and aeroallergen concentrations at a sawmill. 
After identification of a case of extrinsic allergic alveolitis due to exposure to wood dust at a sawmill, all employees at the sawmill where he worked were studied with an occupational, environmental, and symptom questionnaire, spirometry, skin prick tests, and serum specific IgG measurements. Ninety five of current and 14 of 17 ex-sawmill workers were studied. As a basis for comparison, a group of 58 workers from a nearby light engineering factory were also studied. Few women (6) were employed and they were excluded from the analysis. Workers at the sawmill were stratified into high and low exposure groups depending on their place of work. This division was supported both by their subjective assessment of the dustiness of their environment and the results of personal dust samples. There were no significant differences between the three groups in age, height, smoking habits, exposure to other causes of extrinsic allergic alveolitis, forced expiratory volume in one second, forced vital capacity, atopic state, or cutaneous reactivity to moulds. In the high exposure group the prevalence of work related cough and nasal and eye symptoms was higher than in the low exposure and comparison groups. The prevalence of work related wheeze was similar in both the high exposure and comparison groups, but was lower in the low exposure group. The prevalences of chronic bronchitis and symptomatic bronchial hyper-reactivity were similar in the high and low exposure groups but were lower in the comparison group. Serum concentrations of specific IgG against extracts of sawdust and Trichoderma koningii were significantly higher in the high exposure group than in the other two groups. The prevalence of symptoms suggestive of extrinsic allergic alveolitis was 4.4% in the high exposure group, greater than in the low exposure group (0%), and the comparison group (1.9%). In conclusion extrinsic allergic alveolitis probably occurs in British sawmills, and among the exposed population its prevalence may be as high as that reported in Sweden. The allergen responsible is likely to be from mould growing on the wood and may be from Trichoderma koningii.
PMCID: PMC1127934  PMID: 8130844
14.  Risk of upper aerodigestive tract cancers in a case-cohort study of autoworkers exposed to metalworking fluids 
Aims: To re-examine aerodigestive cancer risk in a cohort of autoworkers exposed to metal working fluids (MWF), using improved case definition and more recently diagnosed cases.
Methods: The autoworker cohort included 31 100 hourly workers alive on 1 January 1985 who worked at three automobile plants in Michigan. A case-cohort design was carried out that included incident cases of cancers of the larynx, oesophagus, and stomach, and a 10% sample of the cohort. A Cox proportional hazards model was used to estimate MWF exposure effects. The smoothing method of penalised splines was used to explore the shape of the underlying exposure-response curves.
Results: The most important finding was the association between larynx cancer incidence and cumulative straight MWF exposure. The results for oesophageal cancer were less consistent. For stomach cancer there was no evidence of excess risk.
Conclusion: This association between larynx cancer and straight MWF exposures was consistent with a previous finding in this cohort, providing further support for a causal relation.
doi:10.1136/oem.2003.010157
PMCID: PMC1740767  PMID: 15090663
15.  Different Levels of Transcriptional Regulation Due to Trophic Constraints in the Reduced Genome of Buchnera aphidicola APS▿ †  
Applied and Environmental Microbiology  2006;72(12):7760-7766.
Symbiotic associations involving intracellular microorganisms and animals are widespread, especially for species feeding on poor or unbalanced diets. Buchnera aphidicola, the obligate intracellular bacterium associated with most aphid species, provides its hosts with essential amino acids (EAAs), nutrients in short supply in the plant phloem sap. The Buchnera genome has undergone severe reductions during intracellular evolution. Genes for EAA biosynthesis are conserved, but most of the transcriptional regulatory elements are lost. This work addresses two main questions: is transcription in Buchnera (i) regulated and (ii) scaled to aphid EAA demand? Two microarray experiments were designed for profiling the gene expression in Buchnera. The first one was characterized by a specific depletion of tyrosine and phenylalanine in the aphid diet, and the second experiment combined a global diminution of EAAs in the aphid diet with a sucrose concentration increase to manipulate the aphid growth rate. Aphid biological performance and budget analysis (the balance between EAAs provided by the diet and those synthesized by Buchnera) were performed to quantify the nutritional demand from the aphids toward their symbiotic bacteria. Despite the absence of known regulatory elements, a significant transcriptional regulation was observed at different levels of organization in the Buchnera genome: between genes, within putative transcription units, and within specific metabolic pathways. However, unambiguous evidence for transcriptional changes underpinning the scaling of EAA biosynthesis to aphid demand was not obtained. The phenotypic relevance of the transcriptional response from the reduced genome of Buchnera is addressed.
doi:10.1128/AEM.01118-06
PMCID: PMC1694209  PMID: 17041159
16.  Endotoxemia in critically ill patients: why a reliable test could be beneficial 
Critical Care  2002;6(4):289-290.
The detection of endotoxemia may provide a clue to the cause of sepsis or may indicate translocation of endotoxin from the gastrointestinal tract. A reliable endotoxin activity assay (EAA) offers the potential to determine Gram-negative infections in critically ill patients. In addition, a reliable EAA may indicate the adequacy of gastrointestinal tract perfusion, as well as potentially help to predict morbidity and mortality. A recent study by Marshall and colleagues, published in the present issue of Critical Care, evaluated the use of a whole blood EAA in a medical–surgical intensive care unit and found that 58% of the patients had positive endotoxin assays. However, only 13.5% of the population had a documented Gram-negative infection. This discrepancy and the observation that translocation and other causes of endotoxemia may not reflect true Gram-negative infection might severely limit the clinical utility of this EAA. Further study may better define the potential role of this technique in the diagnostic evaluation of the critically ill patient.
PMCID: PMC137306  PMID: 12225599
endotoxemia; Gram-negative infection; prognosis; sepsis; translocation
17.  Q Fever Outbreak in Industrial Setting 
Emerging Infectious Diseases  2004;10(7):1282-1289.
An outbreak of Q fever was likely caused by renovation work that aerosolized contaminated straw board.
An outbreak of Q fever occurred in South Wales, United Kingdom, from July 15 through September 30, 2002. To investigate the outbreak a cohort and nested case-control study of persons who had worked at a cardboard manufacturing plant was conducted. The cohort included 282 employees and subcontractors, of whom 253 (90%) provided blood samples and 214 (76%) completed questionnaires. Ninety-five cases of acute Q fever were identified. The epidemic curve and other data suggested an outbreak source likely occurred August 5–9, 2002. Employees in the factory's offices were at greatest risk for infection (odds ratio 3.46; 95% confidence interval 1.38–9.06). The offices were undergoing renovation work around the time of likely exposure and contained straw board that had repeatedly been drilled. The outbreak may have been caused by aerosolization of Coxiella burnetii spore-like forms during drilling into contaminated straw board.
doi:10.3201/eid1007.030536
PMCID: PMC3323322  PMID: 15324550
Q fever; Coxiella burnetii; disease outbreak; straw; construction materials; Wales; research
18.  Coccidioidomycosis among Workers at an Archeological Site, Northeastern Utah 
Emerging Infectious Diseases  2004;10(4):637-642.
In 2001, an outbreak of acute respiratory disease occurred among persons working at a Native American archeological site at Dinosaur National Monument in northeastern Utah. Epidemiologic and environmental investigations were undertaken to determine the cause of the outbreak. A clinical case was defined by the presence of at least two of the following symptoms: self-reported fever, shortness of breath, or cough. Ten workers met the clinical case definition; 9 had serologic confirmation of coccidioidomycosis, and 8 were hospitalized. All 10 were present during sifting of dirt through screens on June 19; symptoms began 9–12 days later (median 10). Coccidioidomycosis also developed in a worker at the site in September 2001. A serosurvey among 40 other Dinosaur National Monument workers did not find serologic evidence of recent infection. This outbreak documents a new endemic focus of coccidioidomycosis, extending northward its known geographic distribution in Utah by approximately 200 miles.
doi:10.3201/eid1004.030446
PMCID: PMC3323065  PMID: 15200853
Coccidioidomycosis; pulmonary; epidemiology; outbreak; Coccidioides immitis
19.  Outbreak of Infections Caused by Group A Streptococcus after Modified Radical Mastectomy 
Surgical Infections  2013;14(4):385-388.
Abstract
Background
Eight infections occurred after modified radical mastectomies in a tertiary-care hospital. Group A streptococci (GAS) were isolated from three of the eight patients.
Methods
To control the outbreak, an epidemiologic investigation was conducted, and healthcare workers were screened for pathogens. Strains isolated from healthcare workers were compared with patient strains by emm typing.
Results
One surgeon attended one of the eight operations and observed the other seven. Streptococcus strains from the hands of this surgeon were identical to the patient strains. After the surgeon was suspended from duty and underwent eradication treatment, the outbreak was controlled.
Conclusions
This outbreak of GAS infection is believed to have occurred by airborne transmission. Suspending patient care by healthcare workers who carry the causative GAS in a site(s) other than the respiratory tract for only the first 24 h they are receiving chemoprophylaxis may not be long enough. Sampling of the hands of healthcare workers during an investigation of nosocomial GAS infection is valuable.
doi:10.1089/sur.2012.050
PMCID: PMC3752502  PMID: 23859674
20.  Extrinsic allergic alveolitis caused by a cold water humidifier. 
Thorax  1987;42(1):32-37.
Three workers developed classical extrinsic allergic alveolitis while working in a printing works that had a contaminated cold water humidifier. All had nodular shadows on their chest radiographs, reduced gas transfer measurements, and lung biopsy specimens that showed an alveolitis with giant cells and cholesterol clefts. In two subjects bronchoalveolar lavage was performed and the lavage fluid contained more than 70% lymphocytes in each case. Bronchial provocation tests with the humidifier antigen in these two workers reproduced their symptoms. Unlike previously reported cases, where exposure was to humidifiers working at generally higher temperatures, challenge with thermophilic actinomycetes in our two patients produced no reaction. Tests for precipitins to the humidifier antigen gave strongly positive reactions in the three workers but no single organism isolated from the humidifier produced a significantly positive reaction.
Images
PMCID: PMC460600  PMID: 3616972
21.  Application of Infrequent-Restriction-Site PCR to Clinical Isolates of Acinetobacter baumannii and Serratia marcescens 
Journal of Clinical Microbiology  1999;37(10):3108-3112.
We applied infrequent-restriction-site PCR (IRS-PCR) to the investigation of an outbreak caused by 23 isolates of Acinetobacter baumannii in an intensive care unit from November 1996 to May 1997 and a pseudoepidemic caused by 16 isolates of Serratia marcescens in a delivery room from May to September 1996. In the epidemiologic investigation of the outbreak caused by A. baumannii, environmental sampling and screening of all health care workers revealed the same species from the Y piece of a mechanical ventilator and the hands of two health care personnel. IRS-PCR showed that all outbreak-related strains were genotypically identical and that three strains from surveillance cultures were also identical to the outbreak-related strains. In a pseudoepidemic caused by S. marcescens, IRS-PCR identified two different genotypes, and among them one genotype was predominant (15 of 16 [93.8%] isolates). Extensive surveillance failed to find any source of S. marcescens. Validation of the result of IRS-PCR by comparison with that of field inversion gel electrophoresis (FIGE) showed that they were completely concordant. These results suggest that IRS-PCR is comparable to FIGE for molecular epidemiologic studies. In addition, IRS-PCR was less laborious and less time-consuming than FIGE. To our knowledge, this is the first report of the application of IRS-PCR to A. baumannii and S. marcescens.
PMCID: PMC85504  PMID: 10488162
22.  Semen quality in workers exposed to 2-ethoxyethanol. 
To evaluate whether long term exposure to 2-ethoxyethanol (2EE) may affect semen quality, a cross sectional study was conducted among men exposed to 2EE used as a binder slurry in a metal castings process. Full shift breathing zone exposures to 2EE ranged from non-detectable to 24 ppm (geometric mean 6.6 ppm). Because of the potential for substantial absorption of 2EE through skin exposure, urine measurements of the metabolite of 2EE, 2-ethoxyacetic acid (2EAA) were conducted, showing levels of 2EAA ranging from non-detectable to 163 mg 2EAA/g creatinine. Only 37 exposed men (50% participation) and 39 non-exposed comparison (26% participation) from elsewhere in the plant provided a sperm sample. A questionnaire to determine personal habits, and medical and work histories, and a physical examination of the urogenital tract were also administered. The average sperm count per ejaculate among the workers exposed to 2EE was significantly lower than that of the unexposed group (113 v 154 million sperm per ejaculate respectively; p = 0.05) after consideration of abstinence, sample age, subjects' age, tobacco, alcohol and caffeine use, urogenital disorders, fever, and other illnesses. The mean sperm concentrations of the exposed and unexposed groups did not significantly differ from each other (44 and 53 million/ml respectively). No effect of exposure to 2EE on semen volume, sperm viability, motility, velocity, and normal morphology or testicular volume was detected, although some differences in the proportion of abnormal sperm shapes were observed. These data suggest that there may be an effect of 2EE on sperm count among these workers, although the possibility that other factors may be affecting the semen quality in both exposed and unexposed men in this population or that the results reflect bias introduced by the low participation rates cannot be excluded.
PMCID: PMC1009793  PMID: 2818974
23.  Relationship between plasma cell levels and profile of bronchoalveolar lavage fluid in patients with subacute extrinsic allergic alveolitis. 
Thorax  1993;48(8):835-839.
BACKGROUND--Plasma cells are usually absent in bronchoalveolar lavage (BAL) fluid. Extrinsic allergic alveolitis is associated with increased numbers of T and B lymphocytes in BAL fluid, as well as the presence of a few plasma cells. The aim of this study was to investigate whether there is a relationship between the presence of plasma cells and other cells, and immunoglobulin levels in BAL fluid of patients with extrinsic allergic alveolitis. METHODS--Thirty non-smoking patients with extrinsic allergic alveolitis who had a bronchoalveolar lavage 2-7 days after their last exposure to the causative antigen were selected, retrospectively. RESULTS--Patients suffering from extrinsic allergic alveolitis with plasma cells in the BAL fluid (n = 18) had increased absolute numbers of lymphocytes, eosinophils and mast cells, a decreased percentage of alveolar macrophages and lower CD4/CD8 ratio, as well as higher immunoglobulin levels, when compared with patients with extrinsic allergic alveolitis having no plasma cells in the BAL fluid (n = 12). CONCLUSIONS--The results suggest a relationship between the presence of plasma cells and the other constituents in BAL fluid and a more intense alveolitis. In addition there was a positive relationship between the number of plasma cells in BAL fluid and immunoglobulin levels. These data support the concept of local production of immunoglobulins by plasma cells in the lung following antigen exposure in susceptible individuals.
PMCID: PMC464717  PMID: 8105558
24.  Historical cohort study of a New Zealand foundry and heavy engineering plant 
OBJECTIVES: To investigate the mortality of workers who had been exposed to asbestos, machining fluids and foundry work in a foundry and heavy engineering plant in the railway rolling stock manufacturing industry in New Zealand. METHODS: Historical cohort study design. RESULTS: For the total workforce of 3522 men employed between 1945 and 1991, follow up was 90% of person-years to 31 December 1991. Significantly increased standardised mortality ratios (SMRs) were found for all causes of death combined (SMR 1.07; 95% confidence interval (95% CI) 1.01 to 1.14), all malignancies (SMR 1.15; 95% CI 1.01 to 1.31), circulatory (SMR 1.16; 95% CI 1.07 to 1.27) and musculoskeletal diseases (SMR 3.06; 95% CI 1.39 to 5.84), all digestive cancers (SMR 1.29; 95% CI 1.04 to 1.59), all respiratory cancers (SMR 1.34; 95% CI 1.08 to 1.65), cancer of the oesophagus (SMR 1.97; 95% CI 1.01 to 3.45), and mesothelioma of the pleura (SMR 6.58; 95% CI 1.24 to 19.49). Three deaths from pleural mesothelioma were recorded, with latency times of 51, 53, and 57 years. There were no dose-response relations between exposure to asbestos, machining fluids or foundry work, or by duration of employment in the plant, and any cause of death. CONCLUSIONS: This study found small increases in risk for several causes of death among foundry and heavy engineering workers; however, these increases were small and the possible effects of smoking and other lifestyle factors could not be excluded. There was evidence of asbestos related disease in those involved in engineering work in the past.
 
PMCID: PMC1757697  PMID: 10448319
25.  The effect of inter-compartmental water exchange on the apparent myelin water fraction in multi-exponential T2 measurements of rat spinal cord 
Magnetic Resonance in Medicine  2011;67(3):793-800.
The myelin water fraction (MWF) has been used as a quantitative measure of the amount of myelin present in tissue. However, recent work has suggested that inter-compartmental exchange of water between myelin and non-myelin compartments may cause the MWF to underestimate the true myelin content of tissue. In this work, multi-exponential T2 experiments were performed in-vivo within the rat spinal cord, and a wide variation of the MWF (10–35%) was measured within four rat spinal cord tracts with similar myelin content. A numerical simulation based upon segmented histology images was used to quantitatively account for T2 variations between tracts. The model predicts that a difference in exchange between the four spinal cord tracts, mediated by a difference in the average axon radius and myelin thickness, is sufficient to account for the variation in MWF measured in-vivo.
doi:10.1002/mrm.23053
PMCID: PMC3188335  PMID: 21713984
MRI; exchange; multi-exponential T2; myelin water fraction

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