Showing papers by "Carrie A. Redlich published in 2005"

Predictors of Lung Cancer among Asbestos-exposed Men in the β-Carotene and Retinol Efficacy Trial

Abstract: Despite numerous published studies, debate continues regarding the risk of developing lung cancer among men exposed occupationally to asbestos, particularly those without radiographic or functional evidence of asbestosis. The beta-Carotene and Retinol Efficacy Trial (CARET), a study of vitamin supplementation for chemoprevention of lung cancer, has followed 4,060 heavily exposed US men for 9-17 years. Lung cancer incidence for 1989-2002 was analyzed using a stratified proportional hazards model. The study confirmed excessive rates of lung cancer among men with radiographic asbestosis. Comparison of study arms revealed a strong, unanticipated synergy between radiographic profusion category and the active intervention. In the large subgroup of men with normal lung parenchyma on chest radiograph at baseline, there was evidence of exposure-related lung cancer risk: Men with more than 40 years' exposure in high-risk trades had a risk approximately fivefold higher than men with 5-10 years, after adjustment for covariates. The effect in these men was independent of study intervention arm, but pleural plaques on the baseline radiograph and abnormal baseline flow rate were strong independent predictors of subsequent lung cancer. Residual confounding by subclinical asbestosis, exposure to unmeasured lung carcinogens, or differences in smoking are unlikely to explain these observations better than a carcinogenic effect of asbestos per se.

Glutathione protects human airway proteins and epithelial cells from isocyanates

Abstract: BACKGROUND Glutathione (GSH), one of the major anti-oxidants of the lung, has been linked to the human response to isocyanate exposure. However, the ability of GSH to modulate key chemical reactions, thought to be central to the development of human isocyanate allergy, has not been directly analyzed under biologic exposure conditions. OBJECTIVE To better understand the potential role of GSH in the response to occupational isocyanate exposure, we evaluated its effects on two processes thought to be involved in the development of isocyanate allergy, isocyanate-protein conjugation and epithelial cell toxicity. METHODS The effects of GSH on (1) isocyanate conjugation with albumin, its major target in the airway fluid and (2) isocyanate-induced toxicity to human airway epithelial cell lines, A549 and NCI-H292, were tested using two different in vitro models. For protein conjugation studies, a newly described vapour exposure system was used to model the air/liquid interface at the surface of the epithelial fluid in the airways. Epithelial cell exposures were performed in fluid phase to mimic the in vivo exposure of airway cells covered by epithelial lining fluid. RESULTS Reduced GSH prevented hexamethylene diisocyanate (HDI) conjugation to albumin in a dose-dependent manner, while oxidized GSH (GSSG) conversely increased conjugation rates. GSH levels equivalent to those found in normal human airway fluid (100 microm) provided >90% protection against HDI-protein conjugation when albumin was exposed to HDI vapour levels 10-fold above permissible occupational limits. Physiologic levels of GSH, but not GSSG, also reduced HDI toxicity to human airway epithelial cells in a dose-dependent manner, when present extracellularly, however, drugs that modulate intra-cellular GSH levels did not significantly alter isocyanate toxicity. CONCLUSIONS Together with previously reported genetic and toxicity studies, the data suggest that airway GSH plays an important role in protection against HDI exposure and may help prevent the development of allergic sensitization and asthma.

Short-term outcomes in older intensive care unit patients with dementia.

Abstract: Objective: To determine the impact of dementia on the outcomes of intensive care unit (ICU) care and use of ICU interventions among older patients. Design: Prospective observational cohort study. Setting: Urban university teaching hospital. Patients: Patients were 395 patients age >65 consecutively admitted to a medical ICU. Interventions: None. Measurements and Main Results: Dementia was determined by a previously validated proxy measure, the Modified Blessed Dementia Rating Scale. We chose cut points to focus on patients with moderate-severe dementia at baseline. Our primary outcomes included length of mechanical ventilation and ICU and hospital length of stay. Secondary outcomes included ICU readmission, changes in code status, discharge location, mortality, and use of ICU interventions. Medical record abstraction was performed to determine the rates of ICU outcomes, use of ICU interventions, and potential confounders. Our study documented a prevalence of moderate-severe dementia of 17% in patients age >65 admitted to the ICU. Patients with dementia were significantly older (80 vs. 76), more likely to be female (65% vs. 52%), and more likely to be admitted from a nursing home (46% vs. 11%). Patients with dementia had significantly higher Acute Physiology and Chronic Health Evaluation II scores on admission to the ICU (25 vs. 23). Patients with dementia were more likely to have their code status changed to less aggressive in the ICU (24% vs. 14%). There was no significant difference in readmission to the ICU, discharge location, ICU or hospital mortality rate, or use of ICU interventions between patients with and without dementia. Conclusions: Our study documents no difference in outcomes from ICU care in older patients with and without dementia. There was no increased short-term mortality rate in older patients with dementia compared with those without dementia after admission to the ICU. Presumptions that outcomes from critical care are less favorable in patients with dementia should not drive treatment decisions in the ICU. (Crit Care Med 2005; 33:1371‐1376)

Evidence for excess colorectal cancer incidence among asbestos-exposed men in the Beta-Carotene and Retinol Efficacy Trial

Abstract: The relation between asbestos exposure and colorectal cancer remains controversial. The authors of this 1984-2004 US study examined the association among 3,897 occupationally exposed participants in the Beta-Carotene and Retinol Efficacy Trial (CARET) for chemoprevention of lung cancer, followed prospectively for 10-18 years. When a Cox stratified proportional hazards model was used, risks of colorectal cancer were elevated among male heavy smokers exposed to asbestos. Their relative risk was 1.36 (95% confidence interval: 0.96, 1.93) when compared with that for CARET heavy smokers not exposed to asbestos, after adjusting for age, smoking history, and intervention arm. The presence of asbestos-induced pleural plaques at baseline was associated with a relative risk of 1.54 (95% confidence interval: 0.99, 2.40); colorectal cancer risk also increased with worsening pulmonary asbestosis (p = 0.03 for trend). A dose-response trend based on years of asbestos exposure was less evident. Nonetheless, these data suggest that colorectal cancer risk is elevated among men occupationally exposed to asbestos, especially those with evidence of nonmalignant asbestos-associated radiographic changes.

Changes in cholesterol and triglyceride concentrations in the Vanguard population of the Carotene and Retinol Efficacy Trial (CARET)

Abstract: Changes in cholesterol and triglyceride concentrations in the Vanguard population of the Carotene and Retinol Efficacy Trial (CARET)

A laboratory investigation of the effectiveness of various skin and surface decontaminants for aliphatic polyisocyanates.

Abstract: Isocyanates may cause contact dermatitis and respiratory sensitization leading to asthma. Dermal exposure to aliphatic isocyanates in auto body shops is very common. However, little is known about the effectiveness of available commercial products used for decontaminating aliphatic polyisocyanates. This experimental study evaluated the decontamination effectiveness of aliphatic polyisocyanates for several skin and surface decontaminants available for use in the auto body industry. The efficiency of two major decontamination mechanisms, namely (i) consumption of free isocyanate groups via chemical reactions with active hydrogen components of the decontaminant and (ii) physical removal processes such as dissolution were studied separately for each decontaminant. Considerable differences were observed among surface decontaminants in their rate of isocyanate consumption, of which those containing free amine groups performed the best. Overall, Pine-Sol® MEA containing monoethanolamine was the most efficient surface decontaminant, operating primarily via chemical reaction with the isocyanate group. Polypropylene glycol (PPG) had the highest physical removal efficiency and the lowest reaction rate with isocyanates. All tested skin decontaminants performed similarly, accomplishing decontamination primarily via physical processes and removing 70–80% of isocyanates in one wiping. Limitations of these skin decontaminants are discussed and alternatives presented. In vitro testing using animal skins and in vivo testing with field workers are being conducted to further assess the efficiency and identify related determinants.