As part of an historical cohort study to investigate the mortality experience of industrial workers exposed to chloroprene (CD) and other substances, including vinyl chloride monomer (VC), we ...analyzed mortality from all cancers combined, respiratory system (RSC) and liver cancer in relation to CD and VC exposures. Subjects were 12,430 workers ever employed at one of two U.S. sites (Louisville, KY (
n
=
5507) and Pontchartrain, LA (
n
=
1357)) or two European sites (Maydown, Northern Ireland (
n
=
4849) and Grenoble, France (
n
=
717)).
Historical exposures for individual workers were estimated quantitatively for CD and VC. For sites L, M, P and G, respectively, average intensity of CD exposures (median value of exposed workers in ppm) were 5.23, 0.16, 0.028 and 0.149 and median cumulative exposures (ppm
years) were 18.35, 0.084, 0.133 and 1.01. For sites L and M, respectively, average intensity of VC exposures (median value of exposed workers in ppm) was 1.54 and 0.03 and median cumulative exposures (ppm
years) were 1.54 and 0.094.
We performed relative risk (RR) regression modeling to investigate the dependence of the internal cohort rates for all cancers combined, RSC and liver cancer on combinations of the categorical CD or VC exposure measures with adjustment for potential confounding factors. We categorized exposure measures into approximate quartiles based on the distribution of deaths from all cancers combined. We also considered 5- and 15-year lagged exposure measures and adjusted some RR models for worker pay type (white/blue collar) as a rough surrogate for lifetime smoking history. All modeling was site-specific to account for exposure heterogeneity. We also computed exposure category-specific standardized mortality ratios (SMRs) to assess absolute mortality rates.
With the exception of a one statistically significant association with duration of exposure to CD and all cancers combined in plant M, we observed no evidence of a positive association with all cancers, RSC or liver cancer and exposure to CD and/or VC using both the unlagged and lagged exposure measures: duration, average intensity or cumulative exposure to CD or VC; time since first CD or VC exposure; and duration of CD exposure or time since first CD exposure in presence or absence of VC exposure. We observed elevated and statistically significantly elevated RRs for some analysis subgroups, but these were due to inordinately low death rates in the baseline categories. With the possible exception of all cancer mortality in plant G, our additional adjustment of RRs for pay type revealed no evidence of positive confounding by smoking.
We conclude that exposures to CD or VC at the levels encountered in the four study sites do not elevate mortality risks from all cancers, RSC or liver cancer. This conclusion is corroborated by our analysis of general mortality patterns among the CD cohort reported in our companion paper G. Marsh, A. Youk, J. Buchanich, M. Cunningham, N. Esmen, T. Hall, M. Phillips, Mortality patterns among industrial workers exposed to chloroprene and other substances. I. General mortality patterns, Chem.-Biol. Interact., submitted for publication.
In a four-facility occupational epidemiology study of chloroprene monomer and polymer production workers, the chloroprene (CD) and vinyl chloride monomer (VCM) exposures were modeled for plant ...specific job title classes. In two facilities an acetylene-based process was used and in the other two plants only a butadiene-based process was used in the monomer synthesis. In the Acetylene process VCM was an undesirable by-product to be removed. In the newer butadiene-based process, VCM was not involved and the exposures to CD were considerably lower than they were in the earlier years. One of the limiting factors was the operator rotation within a number of job titles. This rotation and inability to differentiate between job titles subsumed in job classifications recorded in the work histories required an exposure classification scheme based on an order of magnitude separation of exposure classes.
In the four facilities with considerable variation in the mix of the production methods, the CD exposures were remarkably similar in both calculated and measured values. The reductions in exposures were much more dependent upon the improvement of the production methods, rather than deliberate exposure control for occupational hygiene considerations. This is reasonable since the exposures were generally lower than the coeval exposure limits and/or guidelines. The estimated exposures were less than 100
ppm in the pre-1960 era and less than 10
ppm in the 1960–1980 era, less than 1
ppm 1980–1990 era and less than 0.5
ppm thereafter. The exposures were categorized in four classes for VCM and six classes for CD. The characteristic class exposure values were used to cumulate individual exposures over time with a quantification of the potential range for exposures that are reasonably certain to ascribe correct ranking to job classes.
We conducted an historical cohort study to investigate the mortality experience of industrial workers potentially exposed to chloroprene (CD) and other substances, including vinyl chloride (VC), with ...emphasis on cancer mortality, including respiratory system (RSC) and liver. In 1999, the International Agency for Research on Cancer (IARC) classified CD as a possible carcinogen (Group 2B); VC was classified in 1987 as a known human carcinogen (Group 1).
Subjects were 12,430 workers ever employed at one of two U.S. industrial sites (Louisville, KY (
n
=
5507) and Pontchartrain, LA (
n
=
1357)) or two European sites (Maydown, Northern Ireland (
n
=
4849) and Grenoble, France (
n
=
717)), with earliest CD production dates ranging from 1942 (L) to 1969 (P). Two sites (L and M) synthesized CD with the acetylene process that produced VC exposures. We determined vital status through 2000 for 95% of subjects and cause of death for 95% of the deaths. Historical exposures for individual workers were estimated quantitatively for CD and VC. Workers ever exposed to CD ranged from 92.3% (M) to 100% (G); to VC from 5.5% (M) to 22.7% (L). We computed standardized mortality ratios (SMRs) (using national and regional standard populations) in relation to selected demographic, work history and exposure factors. We used worker pay type (white or blue collar) as a rough surrogate for lifetime smoking history.
For the combined cohort, SMRs (95% CIs) for all causes combined, all cancers combined, RSC and liver cancer were, respectively, 0.72 (0.69–0.74), 0.73 (0.68–0.78), 0.75 (0.67–0.84) and 0.72 (0.43–1.13). Site-specific (L, M, P and G, respectively) SMRs were: for all cancers combined: 0.75 (0.69–0.80), 0.68 (0.56–0.80), 0.68 (0.47–0.95) and 0.59 (0.36–0.91); for RSC: 0.75 (0.66–0.85), 0.79 (0.58–1.05), 0.62 (0.32–1.09) and 0.85 (0.41–1.56); for liver cancer: 0.90 (0.53–1.44) (17 deaths), 0.24 (0.01–1.34) (1 death), 0.0 (0–2.39) (no deaths) and 0.56 (0.01–3.12) (1 death). Among all workers ever exposed to CD, SMRs were: for all cancers combined: 0.71 (0.66–0.76); for RSC: 0.75 (0.67–0.84); for liver cancer: 0.71 (0.42–1.14). We also observed no increased mortality risks among cohort subgroups defined by race, gender, worker pay type, worker service type (short/long term), time period, year of hire, age at hire, duration of employment, the time since first employment, and CD or VC exposure status (never/ever exposed).
In summary, our study has many strengths and is the most definitive study of the human carcinogenic potential of exposure to CD conducted to date. We conclude that persons exposed to chloroprene or vinyl chloride at the levels encountered in the four study sites did not have elevated risks of mortality from any of the causes of death examined, including all cancers combined and lung and liver cancer, the cancer sites of
a priori interest. This conclusion is corroborated by our detailed analyses of mortality in relation to qualitative and quantitative exposures to CD and VC at each of the four study sites, reported in our companion paper (Marsh et al., submitted for publication).
Surfactant-associated proteins (SP) A and D are both innate immunity mediators and produced in normal and diseased sinus mucosa. Cystic fibrosis (CF) is associated with Th1 adaptive inflammation ...whereas allergic fungal rhinosinusitis (AFRS) is associated with Th2 adaptive inflammation. The purpose of this study is to show and quantify the presence of SP A, SP D, tumor necrosis factor (TNF) alpha, (a Th1 marker), and eotaxin (a Th2 marker) in normal and diseased sinus mucosa.
Intraoperative sinus mucosal biopsy specimens from human volunteers were obtained during endoscopic sinus surgery for CF (n = 4), AFRS (n = 10), and normal controls (CTLs; n = 4). Specimens were evaluated for presence and quantity of SP A, SP D, and TNF-alpha using Western blot with semiquantitative immunoblot analysis. Eotaxin was quantified using ELISA immunoassay. Results were standardized and reported as picograms of mediator per microgram of total protein.
SP A, SP D, and TNF-alpha levels in CF tissue extracts were 2-10 times higher than levels in AFRS tissue (with SP D and TNF-alpha reaching statistical significance) but CF tissue was not significantly higher than CTL tissue. SP A, SP D, and TNF-alpha were not significantly elevated in AFRS. Eotaxin showed elevated levels in CF and AFRS when compared with CTLs (p = 0.03 and 0.003, respectively).
SP D and TNF-alpha are significantly increased in CF compared with AFRS, suggesting activation of both innate immunity and Th1-mediated inflammation and potential correlation between SPs and downstream adaptive immune responses.
Ethical issues in the biotechnology industry Whellams, Melissa; Berg, Cheryl; Fryer-Edwards, Kelly ...
Journal of business ethics,
01/2008, Letnik:
77, Številka:
1
Journal Article
The β-phaseolin ( phas ) gene, which encodes one of the major seed storage proteins of P. vulgaris , is tightly regulated at the transcription level resulting in strict tissue-specific and spatial ...expression during embryonic
development. The phas proximal promoter contains a complex arrangement of core promoter elements including three TATA boxes as well as several
putative initiator elements. To delineate the respective contributions of the core promoter elements to transcription initiation
we have performed site-directed mutagenesis of the phas promoter. In vivo expression studies were performed on transgenic Arabidopsis harboring phas promoter mutants driving expression of the β-glucuronidase ( gus ) reporter gene. Quantitative assessment of GUS activity in seeds bearing the promoter mutants indicated that both sequence
and spacing of the TATA elements influenced the efficiency of transcription. Substitution, insertion or deletion mutations
had no effect on histochemical staining patterns indicating that strict spacing requirements are not essential for correct
spatial expression of phas during embryogenesis. Further evaluation of the phas promoter by in vitro transcription analysis revealed the presence of multiple TATA-dependent transcription initiation start sites. The distance
between TATA elements and transcription start sites was maintained in insertion and deletion mutants through the creation
of novel initiation sites, indicating that positioning of the TATA elements rather than DNA sequence was the primary determinant
of start site location. We conclude that, while dispensable for proper spatial distribution, the complex architecture of the
phas promoter is required to ensure high levels of accurate phas transcription initiation in the developing embryo.
As part of an historical cohort study to investigate the mortality experience of industrial workers exposed to chloroprene (β-CD) and other substances, all available industrial hygiene exposure ...monitoring data were collected and summarized. From discussions with on-site industrial hygiene personnel, it was apparent that these data were not collected for epidemiological purposes and, therefore, their use in characterization of exposures was problematic as the data mostly pertained to samples collected to investigate the performance of specific tasks. These data were, however, informative for validating the exposure modeling process used to estimate historical exposures. The data summarized below clearly indicate that exposures to β-CD were lowered across the time period of this study. Typically, the exposures recorded were less than the occupational exposure limits of the periods in which the exposures were recorded. Additionally, exposure measurements recorded in the recent past do not represent the exposure actually experienced by the worker as a strict personal protective equipment use program has been in place for the facilities studied since the mid-1980s.
OBJECTIVE--To examine the impact of amenorrhoea on bone mineral density in women of reproductive age. DESIGN--Cross sectional study of 200 amenorrhoeic women compared with normally menstruating ...controls. SETTING--Teaching hospital outpatient clinic specialising in reproductive medicine. SUBJECTS--200 Women aged 16-40 with a past or current history of amenorrhoea from various causes and of a median duration of three years, and a control group of 57 age matched normal volunteers with no history of menstrual disorder. MAIN OUTCOME MEASURE--Bone mineral density in the lumbar spine (L1-L4) as measured by dual energy x ray absorptiometry. RESULTS--The amenorrhoeic group showed a mean reduction in bone mineral density of 15% (95% confidence interval 12% to 18%) as compared with controls (mean bone mineral density 0.89 (SD 0.12) g/cm2 v 1.05 (0.09) g/cm2 in controls). Bone loss was related to the duration of amenorrhoea and the severity of oestrogen deficiency rather than to the underlying diagnosis. Patients with a history of fracture had significantly lower bone density than those without a history of fracture. Ten patients had suffered an apparently atraumatic fracture. CONCLUSIONS--Amenorrhoea in young women should be investigated and treated to prevent bone mineral loss. Menopausal women with a past history of amenorrhoea should be considered to be at high risk of osteoporosis.
Psychological distress is considered to be common as patients with cancer move beyond their diagnosis and into intensive treatment. However, the absolute prevalence of elevated psychological distress ...among patients is reported to be about 30% at the diagnosis and when the disease recurs. In all probability, patients enter their initial experience with cancer with preexisting levels of distress. Without intervention, their level of distress remains elevated, whereas patients with a lower level of distress gradually adapt to the diagnosis and treatment. To target interventions, understanding the relationship between a cancer diagnosis and the level of psychological distress at any point in time is essential. This article describes a study undertaken to determine the prevalence of psychological distress across the disease continuum in a sample of 386 adult cancer patients selected at random from 12 oncology outpatient departments across the United States. Psychological distress was measured with the Brief Symptom Inventory, and quality of life was measured with the Functional Living Index-Cancer. The results indicated that the prevalence of psychological distress did not vary significantly across the disease continuum, with the exception of the terminal phase.
Objective. To assess bone mineral density (BMD) in postmenopausal women with rheumatoid arthritis (RA) and the relative effects of disease activity, disability, and past and current use of ...corticosteroids.
Methods. One hundred ninety‐five postmenopausal patients with RA were compared with 597 postmenopausal control subjects. Bone density was measured at the lumbar spine and the proximal femur using dual x‐ray absorptiometry. Patients were divided into 3 groups according to corticosteroid use, i.e., never users (61%), current users (21%), and ex‐users (18%).
Results. Compared with controls, the never users had no difference in BMD at the lumbar spine, but a 6.9% reduction at the femur (95% confidence interval 95% CI 3.4–10.3%). In current users (mean daily prednisolone dosage 6.9 mg), BMD was reduced by 6.5% at the spine (95% CI 0–13.0%) and by 7.4% at the hip (95% CI 1.2–13.6%) compared with never users, after adjustment for age, weight, duration of menopause, and functional disability. Mean BMD was similar in the ex‐user and never user groups. Results were confirmed in 54 patients who had whole‐body BMD measurements. There were inverse correlations between BMD and Health Assessment Questionnaire scores (femoral BMD r = –0.23, P < 0.01; whole‐body BMD r = –0.40, P < 0.01) and between BMD and cumulative steroid dose (femoral BMD r = –0.32, P < 0.01; whole‐body BMD r = –0.72, P < 0.01).
Conclusion. Osteoporosis in postmenopausal women with RA is more evident at the hip than the spine, and the most important determinants of bone loss are disability and cumulative corticosteroid dose. Low‐dose steroids cannot be used with complacency, but recovery after discontinuation of use may be possible.
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