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Biomedical subjects

William E Brown

Publications and source records attributed to William E Brown.

9 recordsLinked to original sources
PubMed2006

Analysis of biomarkers in rats and dogs exposed to polymeric methylenediphenyl diisocyanate (pMDI) and its glutathione adduct.

Hemoglobin adducts (Hb-MDX) of monomeric methylenediphenyl diisocyanate (MDI) are often interpreted as indirect evidence of hydrolysis of the diisocyanate moiety to the respective amine (diphenylmethane-4,4'-diamine, 4,4'-MDA) which constitutes the rationale of using this biomarker as an internal dosimeter of exposure to putatively formed MDA. In contrast, more recently published data suggest that following inhalation the high concentration of glutathione (GSH) present in lungs favor an adduct formation with GSH and/or peptides/proteins rather than hydrolysis. The focus of this study was to test this alternate hypothesis, viz. whether Hb-MDX can also be formed by the GSH bis-adduct of monomeric MDI. The synthesized mMDI-GSH bis-adduct was administered to rats by single intratracheal instillation. Additional groups were dosed by gavage and intraperitoneal injection. Biomarkers of exposure were determined in blood (plasma protein and hemoglobin adducts) and urine after harsh alkaline and acid hydrolysis, respectively. Data from previous single inhalation exposure studies with aerosols of MDI and 4,4'-MDA in rats served as reference. As to whether N-acetylation plays any modifying role to yield these mMDI-specific biomarkers was addressed in similarly head-only exposed dogs, a species with no appreciable N-acetylation capacity whereas rats are strong N-acetylators. The results obtained suggest that biomarkers in blood from controlled exposures above current workplace standards of mMDI appear not to be suitable for reliable assessments of past exposures. The biomarkers typically used to assess past exposures to MDI were also identified following exposure to the MDI-GSH bis-adduct. Their yield was low but quite similar for MDI aerosol and the MDI-GSH bis-adduct, whilst that of MDA was distinctively higher. The findings of this study are supportive of a conceptual pathway that the MDI-derived biomarkers of exposure are formed through MDI-GSH adducts rather than MDA. Data from dogs support the findings from rats and show that N-acetylation does not appear to be an essential modifying factor. It is concluded that the yield of MDI-related markers of exposure is relatively low and dependent on the exposure dose (and route). MDA originating from hydrolyzed serum protein or hemoglobin appear to be confounded by false-positive background levels which are surmised to be associated with the method of hydrolysis. The determination of urinary biomarkers might be a useful tool to identify recent exposures (by any route). Due methodological uncertainties associated with the harsh hydrolysis of biological specimens may be reduced substantially when using incremental pre- to post-shift changes rather than relying solely on absolute data.

Acetanilides↗
PubMed2002

Synthesis, characterization, and solvolysis of mono- and bis-S-(glutathionyl) adducts of methylene-bis-(phenylisocyanate) (MDI).

Bifunctional isocyanates are highly reactive compounds that undergo nucleophilic attack by a variety of functional groups available in the biological system. While the etiology of the respiratory disease caused by diisocyanates is not fully understood, a great deal of research has been performed to elucidate the chemical mechanisms involved in the direct and indirect effects of these compounds. Since adducts of isocyanates are found not only to proteins along the entire respiratory tree but also to proteins in the circulatory system, it is likely that a transport mechanism for the isocyanate from the respiratory to the circulatory system exists. The initial reaction of isocyanates with cellular thiols to form thiocarbamates, which are known to release the isocyanate under physiological conditions, is believed to provide a possible carrier mechanism for the isocyanate functional group. Previous work with aliphatic mono-isocyanates and the aromatic diisocyanate toluene diisocyanate has demonstrated the feasibility of this mechanism. Adding to this database, the products of the reaction of the highly water-insoluble, low vapor pressure, methylene-bis-(phenylisocyanate) (MDI) with glutathione were synthesized, and their chemical stability under various pH and buffer conditions was tested. Novel synthetic routes were developed for both the mono- and bis-S-(glutathionyl) adducts with MDI that yielded each compound in analytically pure form. Both compounds were found to be unstable under mild basic conditions (phosphate-buffered saline, pH 7.4, and NaHCO(3), pH 8.2), however to a different degree. Furthermore, a significant influence of the pH value (the rate of degradation increases with pH) and the concentration of free glutathione (increasing thiol stabilizes the adduct) on the stability was observed, indicating a base-catalyzed mechanism of the degradation/formation of the thiocarbamate bond. Unlike the monoadduct, which forms almost exclusively the polyurea upon degradation, a variety of products were formed upon degradation of the bis adduct. Though the disappearance of the bis adduct was complete as measured by HPLC, (1)H NMR spectra showed the existence of residual thiocarbamate bonds in the final mixture. In both cases, no evidence of the free methylene-bis-phenylamine (MDA) could be detected under the applicable conditions.

Allergens↗
PubMed2002

Biomarkers of toluene diisocyanate exposure.

Biomarkers are very useful tools when the metabolic fate of the compound or the etiology of a resultant disease is completely understood. They may contribute to confusion if it is not possible to distinguish between markers of exposure and markers of disease. Such is the case for biomarkers used in the assessment of diisocyanate exposure. Biomarkers for diisocyanate exposure result from both direct and indirect effects. Molecules such as hemoglobin, albumin, tubulin, glutathione, and laminin have been implicated as having been directly modified as a result of exposure to toluene diisocyanate (TDI). In addition, indirect biomarkers have included profiles of molecules such as antibodies, cytokines, cell accumulation or proliferation, and markers of oxidative stress. While a brief presentation of each of these markers is provided here, the focus is primarily on immunological markers as an example of the difficulties with using biomarkers in assessing diisocyanate exposure in general, and TDI specifically. Compiled data will be used to demonstrate where gaps exist in our understanding of how the results of measured biomarkers are used with regard to isocyanate exposure, and whether it may be possible to develop these tools to define thresholds between exposure and disease. Issues addressed include whether the marker represents a measure of exposure or disease, whether the methods are sufficiently uniform between labs to be able to compare between studies, and whether the ambiguities are the result of the complexity of the isocyanate reactivity in the biological system, or our inability to accurately measure the end point of the reactions.

Air Pollutants, Occupational↗
PubMedDate not supplied

Peer evaluation of the professional behaviors of emergency medical technicians.

INTRODUCTION: Professional behavior is one of the cornerstones of effective emergency medical services (EMS) practice and is a required part of the National Standard Curricula for advanced levels of EMS education. However, peer rating of emergency medical technicians with respect to the 11 categories of professional behavior never has been quantified. This study uses a peer evaluation methodology to assess the affective competencies of practicing EMS providers. METHODS: A professional behavior evaluation form was included as part of a survey that was sent to 2,443 randomly selected, nationally registered emergency medical technicians (EMTs). Participants were asked to rate the EMT partner with whom they worked most closely in the past year using 11 different categories of professional behavior using a Likert scale. RESULTS: One thousand, five hundred, ten (61.8%) surveys were returned and analyzed. Both nationally registered EMTs at the Basic and Paramedic levels rated their partners with respect to 11 categories of professional behavior. The overall average score was 0.68 on a 0-1 scale, with one being the highest. The rating of each of the categories was: (1) integrity (0.77); (2) appearance/personal hygiene (0.74); (3) patient advocacy (0.73); (4) empathy (0.72); (5) self-confidence (0.70); (6) careful delivery of service (0.70); (7) respect (0.65); (8) communication skills (0.64); (9) time management skills (0.63); (10) teamwork/diplomacy skills (0.62); and (11) self-motivation (0.61). Overall, the NREMT-Paramedics rated their partners significantly lower than did the NREMT-Basics (p = 0.0156) and experienced EMT-Basics rated their partners significantly lower than did the newer EMT-Basics (p = 0.0002). Those EMTs who indicated high satisfaction with their current EMS assignment rated their partner more highly on professional behaviors than did those EMTs who were not as satisfied. CONCLUSION: Overall, EMTs peer evaluation of professional behavior was "good." The behaviors most highly rated were integrity and appearance/personal hygiene. The behaviors rated lowest were self-motivation and team work/diplomacy. It appears that paramedics are more critical of their colleagues than are EMT-Basics, that experienced EMT-Basics are harsher critics than are newer EMT-Basics, and that there is a relationship between job satisfaction and peer evaluation.

Emergency Medical Services↗
PubMedDate not supplied

Longitudinal Emergency Medical Technician Attribute and Demographic Study (LEADS): an interim report.

OBJECTIVES: This ten-year longitudinal study examines various attributes and demographic characteristics of emergency medical technicians (EMTs) and paramedics to identify factors that influence their careers, to identify trends in emergency medical services (EMS), and to provide data on why individuals report leaving the EMS career field. METHODS: A 46-item core survey and a 16-item cross-sectional survey were administered to EMT-basics and EMT-paramedics who were randomly selected and placed in cohort groups stratified by duration of continuous registration at each level and by race. The core survey focused on five broad areas of attributes and demographics, including general, professional, educational, personal, and financial. Case weights were calculated for respondents in each stratum, reflecting the individual's probability of selection. These case weights were adjusted, within strata, for nonresponse. The survey will be administered annually. The cross-sectional survey focused on EMS education. RESULTS: This interim report is descriptive of the overall responses of EMT-basics and EMT-paramedics to core survey items. The demographic characteristics of EMT-basics and EMT-paramedics are described as well as a description of their work activities, working conditions, and job satisfaction CONCLUSIONS: The initial EMT and paramedic attribute and demographic data have been collected, analyzed, and reported. The longitudinal nature of this study requires further data collection and analysis to accurately present trends in EMS, as well as correlations and associations between identified attributes and other factors that influence the careers of EMTs and paramedics. Further reports of the findings will be necessary.

Adult↗
PubMedDate not supplied

Compensation, benefits, and satisfaction: the Longitudinal Emergency Medical Technician Demographic Study (LEADS) Project.

OBJECTIVE: To determine the compensation, benefit package, and level of satisfaction with the benefits of nationally registered emergency medical technicians (NREMTs) in 2001. METHODS: The Longitudinal EMT Attribute Demographic Study (LEADS) Project included an 18-question snapshot survey on compensation with the 2001 core survey. This survey was sent to 4,835 randomly selected NREMTs. A total of 1,718 NREMT-Basics and NREMT-Paramedics, from 1,317 different postal zip codes, responded to the survey. RESULTS: Most NREMTs in the survey (86% of the compensated NREMT-Basics and 85% of the compensated NREMT-Paramedics) were employed primarily as patient care providers. For their emergency medical services (EMS) work in the previous 12 months, compensated NREMT-Basics had mean earnings of 18,324 US dollars (standard error, 978 US dollars) and compensated NREMT-Paramedics had mean earnings of 34,654 US dollars (standard error, 646 US dollars). At least 26% of compensated NREMT-Basics and 9% of compensated NREMT-Paramedics had no health insurance. The majority of compensated NREMTs (62% of the Basics and 57% of the Paramedics) reported their retirement plans were not adequate to meet their financial needs. EMTs are not satisfied with the appreciation and recognition they receive from EMS employers. About one-third (35% of the compensated NREMT-Basics and 30% of the compensated NREMT-Paramedics) were not satisfied with all of the benefits they receive from their EMS employer. Nearly all (94% of both compensated NREMT-Basics and NREMT-Paramedics) believed that EMTs should be paid more for the job that they do. CONCLUSIONS: The adequacy of EMT compensation and benefit packages is an area of concern. It is not unreasonable to believe that these factors are associated with EMT retention and attrition. Additional longitudinal EMT information on compensation and benefits are anticipated to determine the extent to which compensation and benefits are factors in EMT retention.

Adult↗
PubMedDate not supplied

Assessment of nationally registered emergency medical technician certification training in the United States: the LEADS Project. Longitudinal Emergency Medical Technician Attributes Demo-graphic Study.

OBJECTIVES: To describe the adequacy and characteristics of emergency medical services education as assessed by a population-based sample of emergency medical technician (EMT)-basics and EMT-paramedics from the National Registry of Emergency Medical Technicians. METHODS: Stratified random samples of EMT-basics and EMT-paramedics from the National Registry of Emergency Medical Technicians were mailed a 46-item demographic survey and a 16-question education survey in 1999. RESULTS: Overall, EMT-basics and EMT-paramedics reported that course cost and distance to the course were not barriers. The majority of EMT-basic and EMT-paramedic respondents rated their course instructors and course materials as excellent or very good. EMT-basic and EMT-paramedic respondents felt that they were very well prepared from their training in the areas of trauma assessment (63% and 72%), medical assessment (59% and 65%), cardiac arrest management (64% and 76%), and airway management (69% and 77%), respectively. However, EMT-basic and EMT-paramedic respondents were less likely to feel very well prepared regarding childbirth (29% and 44%) and pediatric patient management (36% and 38%). Overall, EMT-paramedics were more likely to report being very well prepared for clinical activities and tasks from their training compared with EMT-basics. CONCLUSIONS: These findings suggest that EMT-basics and EMT-paramedics were satisfied and felt well prepared by their certification courses. Opportunities to improve certification training exist, particularly related to childbirth and pediatric patient management.

Adolescent↗