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Biomedical subjects

D C Christiani

Publications and source records attributed to D C Christiani.

At least 109 records · Page 6Linked to original sources

Cytochrome P450 1A1 MspI polymorphism and urinary 1-hydroxypyrene concentrations in coke-oven workers.

Coke-oven workers are regularly exposed to a high concentration of the benzene-soluble fraction (BSF) of total particulates, which are comprised mainly of polycyclic aromatic hydrocarbons (PAHs). A metabolite of pyrene, 1-hydroxpyrene (1-OHP), is readily measured in the urine of exposed individuals. Epidemiological studies have shown that P4501A1 (CYP1A1) genotypes are associated with PAH-related lung cancer risk. The purpose of this study was to investigate whether CYP1A1 MspI genotypes modulate the relationship of individual occupational exposure to air BSF to urinary 1-OHP concentrations among coke-oven workers. We monitored individual breathing zone air BSF over 3 consecutive days in 80 coke-oven workers in Taiwan from August 1995 to February 1996. Exposure was also dichotomized by work area (topside oven workers and sideoven workers). Preshift urine on the morning of day 1 and postshift urine on the afternoon of day 3 were measured by fluorescent spectrophotometry, and blood samples were analyzed to determine the relative distributions of CYP1A1 MspI polymorphisms. The frequency of the MspI homozygous variant genotypes of CYP1A1 was 15%. Multiple linear regression showed significant effects of individual occupational exposure to air BSF and preshift 1-OHP on postshift urinary 1-OHP concentrations (P = 0.002 and P < 0.001, respectively). After adjusting for preshift 1-OHP concentrations and air BSF, subjects with the homozygous variant genotype have a 2-fold higher postshift 1-OHP levels than the combined wild-type and heterozygous (P = 0.04). In addition, a positive trend was found in postshift 1-OHP and across-shift change of 1-OHP (postshift 1-OHP - preshift 1-OHP) in decreasing order, as follows: topside oven workers with the homozygous variant trait, topside oven workers with the heterozygous variant trait, sideoven workers with the homozygous variant trait, and sideoven workers with the heterozygous trait (P < 0.001). We conclude that CYP1A1 MspI variant genotype can modify the metabolism of PAHs in coke-oven workers.

Adult↗

A field investigation of the acute respiratory effects of metal working fluids. I. Effects of aerosol exposures.

A study of cross-shift change in pulmonary function was conducted among workers exposed to metal working fluids (MWF) in an automobile parts manufacturing company. Three hundred eighty-six workers (216 machinists exposed to straight or soluble MWFs, and 170 nonmachinists) were studied for 1 day, performing spirometry at the beginning and end of their shift. Airborne concentrations of inhalable particulate, culturable bacteria, and endotoxin were measured. We observed an approximately threefold increase in the incidence of 5% or greater cross-shift decrement in forced expiratory volume during the first second among those with exposures above about 0.15 mg/m3, compared to those with exposures below about 0.08 mg/m3. There was some evidence that chronic respiratory symptoms were more prevalent among machinists than among nonmachinists, notably for chronic cough. Baseline FEV1 was about 3% lower on average among those with soluble MWF exposure compared to nonmachinists. These findings are consistent with earlier studies showing respiratory effects of MWFs.

Adult↗

Loss of lung function among sheet metal workers: ten-year study.

One hundred and twenty-two sheet metal workers in New England were examined over a 10-year interval for loss of pulmonary function and the development of asbestosis or asbestos-related pleural fibrosis. Regression models using the generalized estimating equation (GEE) approach were created to investigate the relationship between exposure and pulmonary function after adjusting for smoking status, age, height, and asbestos-related x-ray changes. A history of shipyard work was a significant contributor to the loss of forced vital capacity (FVC). Among smokers, loss in forced expiratory volume at 1 sec (FEV1) also had a significant relationship to prior shipyard work. There was a borderline significant relationship between percentage predicted FEV1 and cumulative years of asbestos exposure in smokers, as well as years-since-initial-exposure in never-smokers. This study supports previous findings of obstructive airway changes in asbestos-exposed workers and identifies shipboard work as an important predictor of loss in pulmonary function even years after shipyard exposure to asbestos has ceased.

Adult↗

Serum liver function profiles in coking workers.

Coking workers are regularly exposed to coke oven emissions (COE), which consist mainly of polycyclic aromatic hydrocarbons and volatile organic compounds. In a previous cross-sectional study, we found that coking and by-product workers with heavy exposure to COE in the older of two coke operation areas in Taiwan had higher serum activities of hepatic aminotransferase than the controls. In this study, we further examine the relationship of exposure to COE with liver function profiles in coking workers. Liver function profiles included serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin (BIL). The exposed group included 88 workers working 3 months or more in the older coke oven plant. Fifty-nine referents, not visiting the coke operation areas in the last 3 months, came from the administrative area in the same company. Each participant wore a personal monitor that was used to measure benzene soluble fraction (BSF) of total particulates, as a surrogate of COE, for 3 consecutive days between August 1995 and February 1996. Serum liver function profiles, hepatitis B surface antigens, and anti-hepatitis C antibodies were examined in the morning following the exposure measurements. Exposure levels were categorized by exposure situations (high, medium, low) among coking workers. The high exposure group (n = 23) worked topside of the oven. The medium exposure group (n = 44) worked at the sideoven for more than 4 hr/day, whereas the low exposure group (n = 21) worked at the sideoven for less than 4 hr/day and mostly remained in the control rooms. The low exposure group was used as an internal comparison group. The median BSF concentrations for various exposure situations were as follows, high exposure group: 372 micrograms/m3, medium exposure group: 61 micrograms/m3, low exposure group: 49 micrograms/m3, and referents: 10 micrograms/m3. The coking workers (n = 88) did not significantly differ from the referents (n = 59) in any of the liver function profiles. Excluding the referents, workers in the high exposure group had a mean AST level that was 31% higher (95% confidence interval (CI) = 9-57%) and a mean ALT level that was 46% higher (95% CI = 7-98%) than those in the low exposure group after adjusting for appropriate confounders in multivariate models. The prevalence of an abnormal hepatocellular pattern (AST > 37 IU/L or ALT > 39 IU/L) was more common in the high exposure group than in the low exposure group (adjusted odds ratio = 4.4; 95% CI = 0.9-22.6). However, these associations were not found in GGT, ALP, or BIL. After controlling for the possible effects of nonoccupational factors on serum activity of AST and ALT, we conclude that increased AST and ALT levels among topside coking workers may be caused by heavy inhalation exposure to COE. Additionally, the adverse hepatic effect seems to be caused by a mixture of hazards, rather than a unique identifiable chemical.

Adult↗

Injuries caused by hazardous materials accidents.

STUDY OBJECTIVE: To describe exposures that prehospital and ED personnel may encounter as a result of hazardous material incidents. METHODS: Retrospective analysis of hazardous material incident reports from six district hazardous material teams in Massachusetts from their inception through May 1996. RESULTS: The chemicals most frequently involved were various hydrocarbons and corrosive materials. Chlorine derivatives were involved in 18% of all incidents and 23% of all incidents resulting in victims. Victims were produced by 47 of 162 (29%) incidents. Respiratory exposures were the most frequent type of exposure and resulted in the largest number of victims transported to a hospital. Overall 24 of 26 (92%) incidents with chemical exposures resulted in symptomatic victims and 33 of 35 (94%) incidents produced victims requiring hospital transport. Respiratory symptoms were the most frequent, both in the number of incidents where they were observed and the total number of victims with symptoms. CONCLUSION: Multiple victim transport to EDs from a single hazardous material incident is most likely to result from an inhalation exposure to a respiratory irritant. Information from descriptive studies should allow improved preparation for potential hazardous material victims.

Accidents↗

Environmental and occupational determinants of blood pressure in rural communities in China.

PURPOSE: To identify and characterize major environmental and occupational determinants of blood pressure in rural communities in China. METHODS: In 1993 we conducted a large cross-sectional, community-based study of 20,216 residents aged 15 years or older, from the Yijing area of Anhui Province (8022 men, 12,194 women), one of whom were receiving treatment for hypertension. The mean systolic blood pressure was 116.7 +/- 19.5 mmHg for men and 113.2 +/- 19.4 mmHg for women. RESULTS: The mean diastolic blood pressure was 72.4 +/- 12.1 mmHg for men and 70.4 +/- 11.6 mmHg for women. Age and body mass index were the two most important determinants of blood pressure in this population. With controls for age and body mass index, height and weight remained significant predictors of blood pressure. Multiple linear regression analysis indicated that alcohol consumption, self-reported exposure to noise, drinking of tap water and pond water, occupational exposure to dust/fumes/gases, rice consumption, inferior housing, household crowdedness, and being unmarried were related to increased blood pressure levels. Vegetable intake, frequent consumption of meat at meals, high level of physical activity, exposure to straw-combustion smoke, and pesticide use were negatively associated with blood pressure. CONCLUSIONS: Our study demonstrated that a broad array of demographic, ergonomic, nutritional, and environmental factors are critical determinants of blood pressure in this rural Chinese population.

Adolescent↗

A case-control study of cytochrome P450 1A1, glutathione S-transferase M1, cigarette smoking and lung cancer susceptibility (Massachusetts, United States)

Cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genetic polymorphisms are involved in the activation and detoxification of chemical carcinogens found in tobacco smoke; thus they may influence host susceptibility to lung cancer. In this study at Massachusetts General Hospital (Boston, MA, USA) of 416 cases and 446 controls (mostly White) we evaluated the association between the CYP1A1 MspI and GSTM1 polymorphisms and lung cancer risk, and their interaction with cigarette smoke. The CYP1A1 MspI heterozygous genotype was present in 18 percent of cases and 16 percent of controls, and one percent of cases and controls were CYP1A1 MspI homozygous variant. The GSTM1 null genotype was detected in 54 percent of cases and 52 percent of controls. After adjusting for age, gender, pack-years of smoking, and years since quitting smoking, while neither the CYP1A1 MspI heterozygous genotype alone nor the GSTM1 null genotype alone were associated with a significant increase in lung cancer risk, having both genetic traits was associated with a twofold increase in risk (95 percent confidence interval [CI] = 1.0-3.4). Our data did not provide enough evidence for a substantial modification of the effect of pack-years on lung cancer risk by the CYP1A1 MspI and GSTM1 genotypes. However, limitations of our study preclude a conclusion about this potential interaction.

Adult↗

Ethnic variation in the prevalence of a common NAD(P)H quinone oxidoreductase polymorphism and its implications for anti-cancer chemotherapy.

The NAD(P)H quinone oxidoreductase (NQO1:EC 1.6.99.2) is an important biotransformation enzyme system that is also known to metabolize important novel chemotherapeutic compounds. The gene that codes for this enzyme has recently been found to be polymorphic in humans. Here, we describe the ethnic distribution of the polymorphism and note that this may have implications for anti-tumour drug development and use.

Antineoplastic Agents↗

Medical surveillance of hazardous materials response fire fighters: a two-year prospective study.

Hazardous materials releases can cause substantial morbidity and mortality, and an increasing number of communities have developed hazardous materials (HAZMAT) teams to deal with such incidents. Little is known, however, about the health effects of chemical accidents on HAZMAT team participants. Baseline and periodic medical surveillance of all 40 fire fighters from the Metrofire Haz-mat team was conducted in 1992/1993 and 1995, respectively. A database on incidents responded to by the team during the study period was also developed. From June 1990 through April 1995, the team responded to a total of 34 hazardous materials incidents. No injuries to HAZMAT team members were reported. Few biochemical abnormalities were observed, and those that were could not be linked to specific exposures or incidents. Four individuals had abnormal audiometry on both occasions. There was a trend toward a lower percent predicted FEV1 for the entire group on follow-up: 106 +/- 13% vs 105 +/- 12%, P = 0.07. For fire fighters older than age 35 (n = 21), the percent predicted FEV1 was significantly lower at follow-up: 108 +/- 12% vs 106 +/- 14%, P = 0.01. The results suggest significant noise exposure and exposure to pulmonary irritants, which support the use of baseline and periodic audiometry and spirometry. The potential utility of other laboratory testing is also discussed.

Adult↗

Elevated serum liver enzymes in coke oven and by-product workers.

Coke oven and by-product workers are potentially exposed to coke oven emissions (COE), which contain hundreds of chemicals and are primarily composed of polycyclic aromatic hydrocarbons (PAH) and volatile organic compounds. Some of these compounds are hepatotoxins. The objective of this study was to examine the relationship between work in coke oven and by-product plants and serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), the most commonly performed liver-function tests. The exposed group was composed of current workers who had been employed at least 3 months in the two coke-operation work areas, including one coke oven plant and one by-product plant (Area I: n = 117; Area II: n = 96) of a large steel company in Taiwan. Control subjects (Area III: n = 131), not visiting either coke-operation area in the last 3 months, were collected from the administrative and nonproduction areas in the same company. PAH exposure, as a surrogate of COE, was measured monthly by PM-10 size-selective high-volume-area air samplers in or around these three areas between June and December 1990, as well as between November 1992 and June 1993. The mean total respiratory particulate PAH exposure levels (< 10 microns) between November 1992 and June 1993 in Area I, II, and III were 6.8 x 10(3), 2.1 x 10(3), and 6.5 x 10(1) ng/m3, respectively. AST, ALT, and hepatitis B surface antigen tests were performed in 1994. Workers who showed either AST or ALT levels greater than reference levels (abnormal > 25 IU/L) were regarded as showing "elevated liver enzyme levels." Workers in Area I had AST levels that were 17% higher (95% confidence interval [CI], 3% to 32%]) and ALT levels that were 35% higher (95% CI, 10% to 65%)] than those in Area III after controlling for appropriate confounders. The adjusted odds ratio (Area I vs Area III) for elevated liver enzymes was 4.4 (95% CI, 1.5 to 13.4). In addition, coke oven (n = 91) and by-product workers (n = 26) from Area I had ALT levels 37% and 45% higher, respectively, compared with control subjects from Area III, after adjusting for appropriate confounders. Similar effects are also seen for AST. Workers in Area II had slightly, but not significantly, elevated AST and ALT levels. These results indicate that workers most heavily exposed to COE exhibit elevated aminotransferase levels.

Adult↗

The prevalence of pulmonary and upper respiratory tract symptoms and spirometric test findings among newspaper pressroom workers exposed to solvents.

To investigate the relationship between exposure to organic solvents and the presence of pulmonary and upper respiratory tract mucous membrane symptoms, we conducted a cross-sectional study of 215 newspaper pressroom workers who were occupationally exposed to organic solvent and lubricant mixtures. Thirty-four compositors, who were not occupationally exposed to the solvents or lubricants, served as controls. Pressroom workers and compositors underwent spirometric testing and were also asked about the presence of cough, phlegm, hemoptysis, dyspnea, wheezing, chest tightness, nose or throat irritation, eye irritation, and sinus trouble. The spirometric results did not significantly differ between the two groups. However, the pressroom workers were significantly more likely to report pulmonary or upper respiratory tract mucous membrane symptoms than were compositors (P < 0.005). An exposure-response relationship could be demonstrated when comparing the number of solvents exposed with the total number of symptoms (P < 0.001). Similarly, an exposure-response relationship could be demonstrated when comparing the frequency of use of each of the seven solvents with the total number of symptoms (P < 0.002). Each of these findings was supported in a multivariable linear regression model that adjusted for potential confounders such as age, smoking history, and number of years in the industry. A high prevalence of these symptoms was reported even though the degree of exposure to solvents and lubricants was within the current permissible exposure limits.

Adult↗

Mechanisms of and facility types involved in hazardous materials incidents.

The purpose of this study was to systematically investigate hazardous materials (hazmat) releases and determine the mechanisms of these accidents, and the industries/activities and chemicals involved. We analyzed responses by Massachusetts' six district hazmat teams from their inception through May 1996. Information from incident reports was extracted onto standard coding sheets. The majority of hazardous materials incidents were caused by spills, leaks, or escapes of hazardous materials (76%) and occurred at fixed facilities (80%). Transportation-related accidents accounted for 20% of incidents. Eleven percent of hazardous materials incidents were at schools or health care facilities. Petroleum-derived fuels were involved in over half of transportation-related accidents, and these accounted for the majority of petroleum fuel releases. Chlorine derivatives were involved in 18% of all accidents and were associated with a wide variety of facility types and activities. In conclusion, systematic study of hazardous materials incidents allows the identification of preventable causes of these incidents.

Data Collection↗

Reproducibility of nasal peak inspiratory flow among healthy adults: assessment of epidemiologic utility.

STUDY OBJECTIVE: To assess the reproducibility of nasal peak inspiratory flow (PIFn). PARTICIPANTS: Twelve healthy nonsmoking volunteers were studied. METHODS: Repeated measurements of PIFn and oral (PIFm) peak inspiratory flow were performed for 5 consecutive days. Two methods of inhalation were compared. In the residual volume (RV) method, the forced maximal inspiratory maneuver was initiated from the end of a maximal expiration, while in the functional residual capacity (FRC) method, the maneuver was from the end of a tidal breath. Reproducibility was assessed by the intraclass correlation coefficient. Time trend for the 5 days was assessed by random effect models adjusting for different baseline for each subject. RESULTS: The intraclass correlation coefficient (ICC) of PIFn was 0.89 (lower limit of one-sided 95% confidence interval is 0.80) by the RV method and 0.78 (95% lower limit is 0.63) by the FRC method, suggesting that both methods have good reproducibility. These were similar to the ICCs of PIFm by each method. The FRC method did not show a significant time trend for PIFn. The RV method had a small, but significant, decreasing time trend of a magnitude considered inconsequential for the purpose of epidemiologic study. CONCLUSION: PIFn, measured from either RV or from FRC, showed good reproducibility and can be employed in epidemiologic studies investigating the upper airways' response to air pollutant exposure. Further studies of the relationships between PIFn and signs and symptoms of rhinitis are needed to evaluate the utility of this test for clinical and epidemiologic use.

Adult↗

Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model.

Activation of naive T cells requires at least two signals. In addition to the well characterized interaction of the T cell antigen receptor with the antigen/MHC expressed on an antigen-presenting cell, T cell activation also requires costimulation by a second set of signals. The best characterized costimulatory receptor is CD28, which binds to a family of B7 ligands expressed on antigen-presenting cells. In asthma, although activated T cells play a role in the initiation and maintenance of airway inflammation, the importance of T cell costimulation in bronchial hyperresponsiveness had not been characterized. Therefore, we tested the hypothesis that inhibition of the CD28:B7 costimulatory pathway would abrogate airway hyperresponsiveness. Our results show that blockade of costimulation with CTLA4-Ig, a fusion protein known to prevent costimulation by blocking CD28:B7 interactions, inhibits airway hyperresponsiveness, inflammatory infiltration, expansion of thoracic lymphocytes, and allergen-specific responsiveness of thoracic T cells in this murine model of allergic asthma.

Airway Resistance↗

Increased micronucleus frequency in lymphocytes from smokers with lung cancer.

We investigated whether lung cancer was associated with an increased micronucleus (MN) frequency in lymphocytes in a case-control study. Epidemiological data were obtained by an interviewer-administered questionnaire and included information on smoking history, intake of dietary micronutrients, general medical history, environmental and occupational exposures to mutagens and carcinogens, and family history of cancer. A modified cytokinesis-block method was used to determine individual MN frequency. Polymorphisms in glutathione S-transferase class mu were determined by PCR analysis. Overall, 55 controls and 42 cases were studied. MN frequency in cases and controls was not associated with age, smoking, metabolic genetic polymorphisms, environmental and occupational exposures, or medical history. Female controls had a significantly higher MN frequency than male controls (p = 0.05). Overall, MN frequency was significantly higher in cases than in controls (p < 0.01). Twenty-four cases (57%) had an MN frequency higher than the upper 95% confidence interval of the mean value for controls (11.5 MNs/1000 binucleated cells). Further analysis showed that, cases who were current and former smokers had significantly higher MN frequencies than controls (p = 0.04); this difference was not seen in the group that had never smoked. The significantly higher MN frequency among cases with a history of smoking may be attributable to the presence of lung neoplasm per se or to the interaction of smoking with endogenous factors associated with the development of lung cancer.

Aged↗