Biomedical subjects

D C Christiani

Publications and source records attributed to D C Christiani.

At least 19 recordsLinked to original sources

PubMed1999

Implications and prognostic value of K-ras mutation for early-stage lung cancer in women.

BACKGROUND: Because there is no clear consensus as to the predictive value of K-ras gene mutation for survival in patients with lung cancer, we examined the occurrence of K-ras mutations in a large, prospective case series of non-small-cell lung cancer (NSCLC). Our goals were to define the patient characteristics associated with K-ras mutation and to determine whether mutation of this gene might be a biomarker of patient prognosis. METHODS: Consecutive, newly diagnosed patients with lung cancer treated with potentially curative resection over a 4-year period were recruited for study. The mutation status of K-ras codon 12 in each patient's tumor DNA was determined by means of polymerase chain reaction-restriction fragment length polymorphism analysis of archived pathology specimens. Analyses were restricted to adenocarcinoma. RESULTS: There was a statistically significant association between female sex and K-ras mutation after adjustment for carcinogen exposures (odds ratio = 3.3; 95% confidence interval [CI] = 1.3-7.9); mutations were found only in smokers. Comparison of Kaplan-Meier curves indicated a strong association between K-ras mutation and decreased patient survival (two-sided P =.009); analysis stratified by pathologic staging groups revealed that this association was statistically significant only for stage I tumors (two-sided P =.002). Cox proportional hazards modeling indicated that K-ras codon 12 mutation was a statistically significant predictor of patient survival, after adjustment for the effects of age, sex, and stage (risk ratio = 1.8; 95% CI = 1.1-3.1). CONCLUSIONS: After adjustment for environmental exposures, non-small-cell lung tumors in women appear to be more likely than those in men to harbor K-ras mutations, suggesting a possible role of estrogen exposure in either the initiation or the selection of K-ras mutant clones in adenocarcinoma. In addition, our data suggest that K-ras codon 12 mutation is a marker of aggressive NSCLC, as evidenced by its association with decreased patient survival, particularly for early-stage disease.

Adenocarcinoma↗

PubMed1999

k-ras mutation and occupational asbestos exposure in lung adenocarcinoma: asbestos-related cancer without asbestosis.

Environmental carcinogen exposure is requisite for the development of nearly all lung cancer, and it is well known that asbestos exposure interacts synergistically with tobacco smoke to induce lung cancer. However, the precise molecular lesions induced by asbestos are unknown. Furthermore, it is also unknown whether asbestos carcinogenesis proceeds in a fashion independent of or dependent upon the induction of fibrosis in workers with high asbestos exposures. Previous studies have suggested that asbestos is associated with the presence of a k-ras mutation in adenocarcinoma of the lung. We aimed to test whether occupational asbestos exposure was associated with k-ras codon 12 mutations in lung adenocarcinoma tumors and to determine whether this was conditional on the presence of asbestosis. All newly diagnosed, resectable lung cancer patients receiving treatment at the Massachusetts General Hospital between November 1992 and December 1996 were eligible to participate. Because k-ras mutation is very strongly associated with adenocarcinoma, and men were more likely to be occupationally exposed to asbestos, the study was restricted to males with this histological diagnosis. There were 84 male patients with available questionnaire-derived work history data and paraffin-embedded tumor tissue for determination of k-ras mutation status. Chest radiographic evaluation was done for all of the patients who reported occupational exposure to asbestos. The prevalence of k-ras mutation was higher among those with a history of occupational asbestos exposure (crude odds ratio, 4.8; 95% confidence interval, 1.5-15.4) compared to those without asbestos exposure, and this association remained after adjustment for age and pack-years smoked (adjusted odds ratio, 6.9; 95% confidence interval, 1.7-28.6). An index score that weights both the dates of exposure and the estimated intensity of exposure indicated that those with k-ras mutations had significantly greater asbestos exposures than those without mutations (P < 0.01). Analysis of the descriptive components of exposure indicated that the duration of exposure was not associated with k-ras mutation, but that the time since initial exposure was significantly associated with mutation status. The association of k-ras mutation and reported asbestos exposure was not dependent on the presence of radiographic evidence of asbestos-related disease. These data suggest that asbestos exposure increases the likelihood of mutation at k-ras codon 12 and that this process occurs independently of the induction of interstitial fibrosis.

Adenocarcinoma↗

PubMed1999

Carcinogen exposure, p53 alteration, and K-ras mutation in synchronous multiple primary lung carcinoma.

BACKGROUND: Synchronous multiple primary lung tumors (SMPLT) have been estimated to occur in 1% of lung carcinoma patients. Criteria for SMPLT diagnosis include different cancer histologies, location in different lobes of the lung, or genetic discordance. Patients with SMPLT have a poor clinical prognosis with decreased 5-year disease survival, despite diagnosis at an early stage. Field cancerization (the induction of somatic mutation in large clones of epithelial cells after carcinogen exposure) has been proposed to be an integral process involved in the development of SMPLT. Host factors also may contribute to the development of SMPLT. METHODS: The authors investigated the occurrence of p53 and K-ras alterations in tumors from SMPLT patients and also studied the association between carcinogen exposure and polymorphic metabolic traits in SMPLT patients, comparing these patients with individuals with one primarily lung tumor. RESULTS: In a case-control study of lung carcinoma susceptibility, 6 patients were identified whose 33 multiple tumors met the criteria of SMPLT. The incidence was 3.6% (16 of 451 patients), which was higher than many previously published series. Among the multiple tumors, 73% (24 of 33 tumors) were adenocarcinomas. Patients with SMPLT smoked more (73.0 pack-years vs. 56.2 pack-years; P = 0.07) and longer (45.8 years vs. 37.0 years; P < 0.03) than patients with only 1 tumor. For those patients who stopped smoking, patients with SMPLT had stopped smoking more recently than those with a single primary tumor (3.4 years vs. 7.3 years; P = 0.08). A total of 39% of SMPLT tumors (13 of 33 tumors) had detectable p53 alterations; 36% had genetic changes in p53 measured by polymerase chain reaction-single strand conformation polymorphism, and 33% showed positive immunostaining for p53 protein. This was comparable to the occurrence of p53 mutations and immunostaining in single tumor cases (30%). Age, gender, family history of cancer, and the prevalence of polymorphic metabolic traits previously associated with lung carcinoma susceptibility did not differ among SMPLT patients compared with patients with a single tumor. CONCLUSIONS: The patients with SMPLT had significantly more tobacco exposure, and their tumors apparently had independently arising p53 and K-ras mutations, suggesting that field cancerization may be important in lung carcinogenesis.

Adenocarcinoma↗

PubMed1999

Early age at smoking initiation and tobacco carcinogen DNA damage in the lung.

BACKGROUND: DNA adducts formed as a consequence of exposure to tobacco smoke may be involved in carcinogenesis, and their presence may indicate a high risk of lung cancer. To determine whether DNA adducts can be used as a "dosimeter" for cancer risk, we measured the adduct levels in nontumorous lung tissue and blood mononuclear cells from patients with lung cancer, and we collected data from the patients on their history of smoking. METHODS: We used the 32P-postlabeling assay to measure aromatic hydrophobic DNA adducts in nontumorous lung tissue from 143 patients and in blood mononuclear cells from 54 of these patients. From the smoking histories, we identified exposure variables associated with increased DNA adduct levels by use of multivariate analyses with negative binomial regression models. RESULTS/ CONCLUSIONS: We found statistically significant interactions for variables of current and former smoking and for other smoking variables (e.g., pack-years [number of packs smoked per day x years of smoking] or years smoked), indicating that the impact of smoking variables on DNA adduct levels may be different in current and former smokers. Consequently, our analyses indicate that models for current and former smokers should be considered separately. In current smokers, recent smoking intensity (cigarettes smoked per day) was the most important variable. In former smokers, age at smoking initiation was inversely associated with DNA adduct levels. A highly statistically significant correlation (r=.77 [Spearman's correlation]; two sided P<.001) was observed between DNA adduct levels in blood mononuclear cells and lung tissue. IMPLICATIONS: Our results in former smokers suggest that smoking during adolescence may produce physiologic changes that lead to increased DNA adduct persistence or that young smokers may be markedly susceptible to DNA adduct formation and have higher adduct burdens after they quit smoking than those who started smoking later in life.

Age Factors↗

PubMed1999

Cotton dust and endotoxin exposure and long-term decline in lung function: results of a longitudinal study.

BACKGROUND: To evaluate the relationship between long-term exposure to cotton dust and Gram-negative bacterial endotoxin on lung function, we conducted an 11-year follow-up study of cotton textile workers in Shanghai, China. METHODS: Workers at a nearby silk-thread manufacturing mill were used as a referent population. Ninety percent of the original cohort of 445 cotton and 467 silk textile workers--both active and retired--were identified for testing in the 11th year. Questionnaires and spirometric testing were performed, as well as cotton dust and endotoxin sampling at three points over the 11-year follow-up period: at baseline, at Year 5, and at Year 11. After excluding deaths and subjects on sick-leave, 84% of the original cohort had complete health and environmental data. RESULTS: The data were reanalyzed using generalized estimating equations feedback model which allow for subject transfer over time between work areas, various exposure levels to dust and endotoxin, and FEV1. Cotton workers had a larger loss of FEV1 during the first 5 years of study (-40 mls/yr) as compared with the second 6 years of follow-up (-18 mls/yr). During the same periods, the average decline among silk workers was slightly higher in the first period, but was more consistent (-30 mls/yr vs. -27 mls/yr), and these differences could not be explained by worker selection or dropout. When cumulative exposure to dust and endotoxin were estimated and used in a multivariate model (GEE) for FEV1 loss, cumulative dust, but not endotoxin, was associated with 11-year loss in FEV1 after adjustments for confounders. There was evidence of feedback between dust-exposure levels and FEV1, indicating the existence of a healthy-worker survivor effect. After accounting for a healthy-worker survivor effect, we found a significant relationship between dust exposure and FEV1 decline. CONCLUSIONS: Our results suggest that cotton dust is more strongly associated with chronic airflow limitation than associated endotoxins. Further work is needed to clarify potential reversibility after cessation of exposure, and the relative contributions of dust, endotoxin, and tobacco to chronic respiratory impairment in cotton and other vegetable-exposed workers.

Case-Control Studies↗

PubMed1999

Sperm aneuploidy among Chinese pesticide factory workers: scoring by the FISH method.

BACKGROUND: A study of the prevalence of sperm aneuploidy among pesticide factory workers was conducted in Anhui, China. METHODS: We recruited 75 men: 32 subjects from a large pesticide-manufacturing plant and 43 subjects from a nearby textile factory free of pesticide exposure. Each subject met the following criteria: age of 20-40 years; continuous work in the plant for 3 months prior to the study, no congenital anomalies or acquired disease of the external genitalia and no history of recent febrile illness or mumps. Within one hour after collection from each subject, semen was evaluated in terms of several parameters and smear slides were prepared. RESULTS: Exposure assessment revealed that workers in the pesticide plant were exposed to ethyl parathion or methamidophos, each of which is a potent organophosphate pesticide, at a median level of 0.02 mg/m3 (8-hour time weighted average as measured by personal pump) while workers in the control plant had no such occupational exposure. Twenty-nine semen slides (13 from the exposed group and 16 from the unexposed group) were randomly chosen for aneuploidy scoring by the three-color fluorescence in situ hybridization (FISH) method with scorers being unaware of exposure status. Median semen parameters were as follows for exposed (and unexposed) men: abstinence period, 3 days (4 days); sperm concentration, 52.8x10(6)/ml (53.1x10(6)/ml); proportion of sperm with normal motility, 50.5% (61.3%); and proportion of sperm with normal morphology, 59% (61.5%). The specific chromosome abnormalities of interest were disomy for chromosome 18 and the three different types of sex chromosome disomy (i.e. XX, XY, YY disomy). The crude proportion of all aneuploidy combined was 0.30% and 0.19% for sperm from exposed and unexposed men, respectively. Poisson regression with overdispersion adjustment yielded significantly different crude risks of aneuploidy - 3.03 and 1.94 per 1,000 sperm from exposed and unexposed men, respectively - giving a rate ratio of 1.56 (95% CI, 1.06-2.31). The regression coefficients remained statistically significant after adjustment for inter-technician variability giving a rate ratio of 1.51 (95% CI, 1. 04-2.20). CONCLUSIONS: We conclude that occupational exposure to organophosphate pesticides moderately increases the prevalence of sperm aneuploidy.

Adult↗

PubMed1999

Paraoxonase polymorphism and its effect on male reproductive outcomes among Chinese pesticide factory workers.

BACKGROUND: Serum paraoxonase has been associated with the metabolism of organophosphate pesticides in humans. Molecular analysis of the human paraoxonase gene (PON1) has revealed that Arg192 homozygotes have a greater detoxifying capability than Gln192 homozygotes. We examined the effects of PON1 genotypes on male reproductive outcomes and its interaction with exposure to organophosphate pesticides. METHODS: We studied 60 Chinese pesticide-factory workers and 89 textile-factory workers who were unexposed to pesticides. The respective allele frequencies of Arg192 and Gln192 were 0.62 and 0.38. Pesticide exposure among 36 exposed subjects and 12 unexposed subjects, regardless of gender, was assessed by personal measurement of pesticide residues over an entire 8-hr shift and measurement of urinary p-nitrophenol level over a 24-hr period. We analyzed semen and hormone data collected from male subjects. RESULTS: When the three PON1 genotypes were analyzed separately, a gene dose effect was not detected. We used the unexposed Arg192 homo/heterozygotes as the reference group, and re-analyzed the data. Exposed Arg192 homo/heterozygotes had significantly lower sperm count (chi 2 = 9.01, P < 0.01) and lower percentage of sperm with normal morphology (chi 2 = 4.18, P < 0.05) than the reference group. Both unexposed Gln192 homozygotes (chi 2 = 4.90, P < 0.05) and exposed Arg192 homo/heterozygotes (chi 2 = 10.00, P < 0.01) showed significantly lower sperm concentrations than the reference group. In addition, exposed Arg192 homo/heterozygotes had significantly higher serum LH levels (chi 2 = 7.94, P < 0.01) than the reference group. CONCLUSIONS: Because of a small sample size, our findings are highly preliminary. Nevertheless, it calls for further investigation of the interaction between the PON1 genotype and organophosphate pesticide exposure on male reproductive outcomes.

Adult↗

PubMed1999

Correlates of fitness for duty in hazardous materials firefighters.

BACKGROUND AND METHODS: From a statewide medical examination program, we identified firefighters who were deemed unfit for duty by attending physicians (ATTENDING FAIL, n=9) and those who would have been disqualified by the application of selected numerical criteria from the 1997 National Fire Protection Association (NFPA) guidelines (NFPA FAIL, n=27) and criteria from a Medical Workshop (WORK FAIL, n=16). The subjects who were unfit for duty or failed numerical criteria were compared with those who were fit for duty and passed all objective criteria (FIT group, n=302). All subjects were given an overall morbidity rating by a board certified internist. Comparisons on two surrogate measures of fitness, VO(2) max predicted and predicted coronary heart disease (CHD) risk, were also performed. RESULTS: We found a significant tendency towards worse results (e.g. higher blood pressure or lower spirometric function) among the three FAIL groups compared with the FIT group. The FAIL groups shared only a small overlap, however, with the firefighters with the highest morbidity ratings, lowest predicted VO(2) max, and highest CHD risks. Increasing morbidity was associated with higher age, lower spirometric function, lower predicted VO(2) max, increasing cholesterol, greater BMI, and higher predicted 10 year CHD risk. CONCLUSIONS: Although the presence of a single serious or poorly controlled condition may render an individual unfit for safe performance as a firefighter, examination of our cohort suggests that multiple risk factor models or overall clinical assessments are superior means of identifying firefighters with poor health status and increased CHD risk.

Adult↗

PubMed1999

Determination of total arsenic concentrations in nails by inductively coupled plasma mass spectrometry.

The analysis of trace elements in biological samples will extend our understanding of the impact that environmental exposure to these elements has on human health. Measuring arsenic content in nails has proven useful in studies evaluating the chronic body burden of arsenic. In this study, we developed methodology with inductively coupled plasma-mass spectrometry (ICP-MS) for the determination of total arsenic in nails. We assessed the utility of the washing procedures for removing surface contamination. Four types of preanalysis treatments (water bath, sonication, water bath plus sonication, and control) after sample decomposition by nitric acid were compared to evaluate the digestion efficiencies. In addition, we studied the stability of the solution over 1 wk and the effect of acidity on the arsenic signal. Arsenic content in the digested solution was analyzed by using Ar-N2 plasma with Te as the internal standard. The results suggest that washing once with 1% Triton X-100 for 20 min for cleaning nail samples prior to ICP-MS analysis is satisfactory. Repeated measurement analysis of variance revealed that there was no significant difference among the various sample preparation techniques. Moreover, the measurements were reproducible within 1 wk, and acidity seemed to have no substantial influence on the arsenic signal. A limit of detection (on the basis of three times the standard deviation of the blank measurement) of 7 ng As/g toenail was achieved with this system, and arsenic recoveries from reference materials (human hair and nails) were in good agreement (95-106% recovery) with the certified/reference values of the standard reference materials. ICP-MS offers high accuracy and precision, as well as high-throughput capacity in the analysis of total arsenic in nail samples.

Arsenic↗

PubMed1999

Lung cancer and occupational risk factors in Greece.

This study estimated the proportion of lung cancer in Greece that was attributable to occupational exposure. Two hundred eighty-two patients with lung cancer and 494 controls were interviewed about their socioeconomic characteristics, sex, age, and occupational, smoking, and residential histories. Each subject was classified as exposed or unexposed to known occupational lung carcinogens. Because of the small number of females exposed, only males were included in the multivariate analyses. When the occupationally exposed subjects were compared with the unexposed subjects and an adjustment for smoking was made, the relative risk for lung cancer was 2.9 (95% confidence interval, 1.95-4.31). If 5% to 10% of the Greek population were occupationally exposed, the attributable risk would be 9.9% to 16.6%, respectively. Occupational exposures conferred an additional risk that was approximately threefold that of smoking alone. Risks increased in a dose-response fashion with increasing cigarette consumption.

Adult↗

PubMed1999

Clinical practices in the management of new-onset, uncomplicated, low back workers' compensation disability claims.

Recent consensus guidelines delineate what appears to be the most successful and cost-effective management of low back pain (LBP), and some recent studies have suggested that better outcomes occur with the least aggressive forms of medical intervention. The purpose of this study was to describe how practitioners manage new-onset, uncomplicated low back workers' compensation (WC) disability cases. A sample of cases was randomly selected from a large insurance carrier's national data source. An effort was made to select only uncomplicated cases, which would be expected to have relatively minimal need for medical intervention. There was an apparent overuse of diagnostic and treatment modalities. Diagnostic imaging was overutilized, not only in terms of the number of studies done (65% had plain films, 22% had magnetic resonance imaging scans) but also in the time frame in which they were performed (38% had plain films on the first clinic visit). Ninety percent received at least one medication, and 38% received more than one prescription for opioid analgesics. Expensive non-steroidal anti-inflammatory drugs were prescribed more often than acetaminophen (61% versus 6%, respectively). Sixty-two percent received physical therapy that often included modalities with as yet unproven efficacy. Overutilization of either diagnostic or treatment procedures increases the likelihood of iatrogenic complications, is not cost-effective, and may adversely impact clinical and occupational outcomes.

Adolescent↗

PubMed1999

Correlates of body mass index in hazardous materials firefighters.

We analyzed results from the medical examinations of 340 hazardous materials (HAZMAT) firefighters and observed the relationships between selected parameters and body mass index (BMI). Heights and weights were available for 98% of the subjects (333 of 340). The mean BMI was 28.9 +/- 4.1 kg/m2. Eighty-seven percent (290 of 333) of subjects were overweight (BMI > or = 25) and 34% (113 of 333) were obese (BMI > or = 30). Two percent (7 of 333) were morbidly obese (BMI > or = 39). For comparison purposes, we divided subjects into low (BMI < 27), medium (BMI 27 to < 30), and high (BMI > or = 30) BMI groups. The results demonstrated adverse associations between increasing BMI and resting blood pressures, forced vital capacity, alanine aminotransferase, aspartate aminotransferase, serum cholesterol, and overall morbidity scores. The high prevalence of overweight and obesity and the associated adverse health effects support the development and implementation of fitness-promotion programs for firefighters.

Adult↗

PubMed1999

Pulmonary function in workers exposed to low levels of fuel-oil ash.

Previously, we reported significant lung function changes after exposure to fuel-oil ash during a boiler overhaul in which median PM10 and vanadium concentrations were 2.9 mg/m3 and 11.9 micrograms/m3, respectively. In this study, we examined prospectively 18 boilermakers involved in the short-term, partial overhaul of a large, oil-fired boiler where occupational exposures to PM10 and metals were relatively low. Vanadium and PM10 exposure levels were measured before and during boiler work. For PM10, median exposure before and during boiler work was 0.5 and 0.6 mg/m3, respectively. For vanadium, median exposure before and during boiler work was 1.0 and 12.7 micrograms/m3, respectively, comparable with the results of our previous study. Spirometric (PFT) testing was done three times: first day on the job (PFT1), end of overhaul (PFT2), and 2 weeks post-overhaul (PFT3). Spirometry results were analyzed using repeated measures analysis of variance. No significant differences were found. Boilermakers working on a short-term overhaul of an oil-fired boiler exhibited no significant change in any lung function parameter comparing pre-, during, and 2 weeks post-exposure. The comparatively low levels of exposure to PM10 and vanadium observed during boiler work, the short duration of the overhaul, and the healthy worker effect are possible explanations for these results.

Adult↗

PubMed1999

Modulating influence of cytochrome P-450 MspI polymorphism on serum liver function profiles in coke oven workers.

OBJECTIVES: It was reported previously that topside oven workers with heavy exposure to coke oven emissions had increased serum activities of hepatic aminotransferase in one coke oven plant. This study was conducted to investigate the modifying effect of CYP1A1 MspI polymorphism on liver function profiles in coke oven workers. METHODS: 88 coke oven workers from a large steel company in Taiwan were studied in 1995-6. Exposure was categorised by work area: topside oven workers and sideoven workers. Liver function profiles including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), r-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin (BIL) were examined in the morning after personal exposure measurements. The MspI polymorphism was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: Five of 23 (22%) topside oven workers and seven of 65 (11%) sideoven workers had the CYP1A1 MspI homozygous variant genotype. With sideoven workers with the combined wild type and heterozygous variant as the reference group in multiple regression models, it was found that topside oven workers with the combined traits had mean AST and ALT activities that were 21% and 46% higher (95% confidence interval (95% CI) 4% to 42% and 12% to 91%, respectively) than the reference group after adjusting for appropriate confounders. Also, topside oven workers with the homozygous variant trait had mean AST, ALT, and GGT activities that were 59%, 68%, and 157% higher (95% CI 21% to 109%, 6% to 168%, and 39% to 374%, respectively) than the reference group. The prevalence of an abnormal hepatocellular pattern (AST > 37 IU/l or ALT > 39 IU/l) was more common in the topside oven workers with the homozygous variant than in the sideoven workers with the other combined genotypes (adjusted odds ratio 9.9, 95% CI 1.2 to 82.3) after adjusting for appropriate confounders. CONCLUSIONS: The CYP1A1 MspI polymorphism may modify the biotransformation of coke oven emissions, which results in hepatocellular damage in coke oven workers.

Adult↗

PubMed1999

Long-term respiratory health effects of the herbicide, paraquat, among workers in the Western Cape.

OBJECTIVE: To evaluate the possible effects of paraquat spraying among workers on deciduous fruit farms in the Western Cape, South Africa. Paraquat is a commonly used herbicide world wide and is a well documented cause of pulmonary fibrosis in studies of laboratory animals and in humans after exposure to a high dose (usually accidental or as parasuicide). The respiratory effects of long term, low dose exposure to paraquat have not been fully evaluated. METHODS: A cross sectional study of 126 workers. Administered questionnaires generated information on exposure, respiratory symptoms, and potential confounding variables. Spirometry and gas transfer were measured and chest radiographs performed. Oxygen desaturation on exercise testing was by oximetry during a modified stage one exercise test. RESULTS: No association was found between long term exposure to paraquat and reported symptoms, spirometry (forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC) and gas transfer (TLCO and KCO) or chest radiography. Multivariate analysis showed a significant relation between measures of long term exposure to paraquat and arterial oxygen desaturation during exercise independent of short term exposure. CONCLUSION: Previous studies have not shown a significant relation between measures of exposure to paraquat and standard tests of lung function. Arterial oxygen desaturation during exercise represents a more sensitive test. The findings indicate that working with paraquat under usual field conditions is associated with abnormal exercise physiology in a dose dependent fashion independent of recent exposure and acute poisoning events.

Adult↗

PubMed1999

Suspected nasopharyngeal carcinoma in three workers with long-term exposure to sulphuric acid vapour.

Sulphuric acid vapour has been suspected of being an industrial carcinogen. In this study, a cluster is presented of three patients with nasopharyngeal carcinoma (NPC) who worked in the same building of a telecommunications conveyance station in southern Taiwan with long term exposure to sulphuric acid vapour concentrations as high as 0.18 mg/m3. All three workers were diagnosed with NPC within a 5 month period between September 1992, and March 1993. Compared with 19 other healthy workers from the same building, these three workers with NPC had worked significantly longer in this building than had the others (mean (SD) (years): 12.7 (0.6) v 7.4 (4.4); p = 0.01). With an in situ nucleic acid hybridisation and immunostaining method for colocalised Epstein-Barr virus (EBV) and secretory component (SC) protein among biopsy specimens of these three patients with NPCs, it was found that some tumour cells did not contain EBV and SC protein staining signals. These results indicate that EBV infection is not the only risk factor for NPC and long term exposure to relatively low concentrations of sulphuric acid vapour may be associated with the development of NPC.

Adult↗

PubMed1999

CD23 and allergic pulmonary inflammation: potential role as an inhibitor.

CD23, a receptor for immunoglobulin E, is expressed at increased levels in asthmatic and atopic individuals and has been associated with disorders characterized by chronic inflammation. Using an established murine model, we employed several complementary strategies to investigate the role of CD23 in allergic pulmonary inflammation and airway hyperresponsiveness (AHR). Specifically, these approaches included the modulation of CD23 function in vivo by administration of anti-CD23 monoclonal antibody (mAb) or Fab fragments to wild-type mice and the analysis of CD23-deficient mice. Administration of anti-CD23 mAb, but not anti-CD23 Fab fragments, produced attenuation of pulmonary inflammation, AHR, and CD8(+) T-cell activation. On the basis of a model that the anti-CD23 mAb transduces, whereas the Fab fragment inhibits, CD23 signaling, these results suggest that CD23 negatively regulates pulmonary inflammation and AHR. This hypothesis is supported by our observation that CD23-deficient mice developed increased inflammation and AHR after sensitization and challenge with allergen. Together, these results indicate that CD23 negatively regulates pulmonary inflammation and airway hyperreactivity.

Animals↗

PubMed1999

A retired shipyard worker with rapidly progressive pulmonary interstitial fibrosis.

We present a case of progressive interstitial fibrosis in a retired shipyard worker who was exposed to asbestos during the postwar era of the late 1940s and 1950s, when asbestos exposures in the workplace were not regulated. Forty years later, at 63 years of age, the patient presented with restrictive lung disease. The patient was diagnosed with asbestos-related pleural disease and parenchymal asbestosis. He remained stable for the next 7 years, but then he began to manifest rapid clinical progression, which raised the possibility of an unusual variant of asbestosis, a concomitant interstitial process, or an unrelated disease. Lung biopsy was not undertaken because of the patient's low pulmonary reserve and limited treatment options. An empiric trial of oral steroids was initiated, but his pulmonary status continued to deteriorate and he died of pulmonary failure at 72 years of age. Many diseases result in pulmonary interstitial fibrosis. Ideally, open lung biopsy should be performed, but this procedure inevitably causes complications in many patients with end-stage restrictive lung disease. Furthermore, while the presence of asbestos bodies in tissue sections is a sensitive and specific marker of asbestos exposure, neither this finding nor any other charge is a marker indicative of asbestosis or the severity of asbestosis. With the enactment of the Asbestos Standard in the United States, asbestos exposures have been decreasing in this country. However, industries that produce asbestos products and wastes continue to expand in developing countries. Prevention of asbestos-related lung disease should be a global endeavor, and asbestos exposures should be regulated in both developed and developing countries.

Asbestos↗