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Biomedical subjects

Thomas J Smith

Publications and source records attributed to Thomas J Smith.

At least 37 records · Page 2Linked to original sources

Smoking behavior in trucking industry workers.

BACKGROUND: In retrospective occupational studies, the degree of confounding by smoking depends on variation in smoking among job-related exposure groups. We assessed the relationship between job title and smoking behavior as part of a study on occupational exposures and lung cancer. METHODS: A questionnaire on smoking was mailed to a sample of 11,986 trucking industry workers. Company records were used to gather other relevant information. RESULTS: The response rate was 40.5%. Among white males, the age-adjusted prevalence of ever smoking was highest among longhaul truck drivers (67%) and lowest among clerks (44%). Smoking rates among workers with other job titles were similar. CONCLUSIONS: Our results will be used to adjust for the differences in smoking among job-related exposure groups when assessing the association between particulate matter exposure and lung cancer mortality. Our study also suggests that an assessment of methods to control for smoking should be considered in the design of retrospective occupational health studies.

Aged↗

Historical estimation of diesel exhaust exposure in a cohort study of U.S. railroad workers and lung cancer.

We have previously shown an elevated risk of lung cancer mortality in diesel exhaust exposed railroad workers. To reduce exposure misclassification, we obtained extensive historical information on diesel locomotives used by each railroad. Starting in 1945, we calculated the rate each railroad converted from steam to diesel, creating annual railroad-specific weighting factors for the probability of diesel exposure. We also estimated the average annual exposure intensity based on emission factors. The U.S. Railroad Retirement Board provided railroad assignment and work histories for 52,812 workers hired between 1939-1949, for whom we ascertained mortality from 1959-1996. Among workers hired after 1945, as diesel locomotives were introduced, the relative risk of lung cancer for any exposure was 1.77 (95% CI = 1.50-2.09), and there was evidence of an exposure-response relationship with exposure duration. Exposed workers hired before 1945 had a relative risk of 1.30 (95% CI = 1.19-1.43) for any exposure and there was no evidence of a dose response with duration. There was no evidence of increasing risk using estimated measures of intensity although the overall lung cancer risk remained elevated. In conclusion, although precise historical estimates of exposure are not available, weighting factors helped better define the exposure-response relationship of diesel exhaust with lung cancer mortality.

Adult↗

Cotton dust and endotoxin levels in three Shanghai textile factories: a comparison of samplers.

The results of a field survey at three Shanghai textile factories were used to compare the performance of the Chinese dust sampler (CDS) with the standard American sampler, vertical elutriator (VE). Side-by-side samples using a CDS and a VE were collected in seven specific manufacturing processes, with additional area and personal samples collected with a modified Institute of Occupational Medicine (IOM) personal inhalable sampler. Filters were analyzed for mass and endotoxin concentration. The geometric mean (GM) of the samples collected by the CDS was 0.79 mg/m3 (geometric standard deviation [GSD] 1.9) compared with a GM of 0.31 mg/m3 (GSD 1.7) for the VE measurements. The correlation coefficient for the CDS and VE samples was 0.35. The CDS, a high-volume total dust area sampler, collects 2 to 10 times more dust than the VE, a size-selective method, depending on the manufacturing process. In spinning at Factory A, the VE and CDS measured concentrations of 0.15 mg/m3 and 1.62 mg/m3, respectively. Cotton dust concentration measurements collected by the IOM sampler demonstrated that personal exposure concentrations were significantly higher (GM 1.84 mg/m3, GSD 1.6) than fixed-position area samples (GM 0.68 mg/m3, GSD 1.9). The endotoxin concentration based on the VE samples was 366 EU/m3, with the highest levels found in the specific manufacturing process drawing (1871 EU/m3) and the lowest in spinning (43.5 EU/m3). The results of the field comparison were used to convert historic CDS data into comparable exposures and to assign retrospective exposures to subjects included in a case-cohort study of lung cancer among female textile workers in Shanghai.

Air Pollutants, Occupational↗

A randomized phase III study of radiotherapy alone or with 5-fluorouracil and mitomycin-C in patients with locally advanced adenocarcinoma of the pancreas: Eastern Cooperative Oncology Group study E8282.

PURPOSE: The median survival time of patients with locally advanced adenocarcinoma of the pancreas is 8-10 months. Radiation therapy has been used to improve local control and palliate symptoms. This randomized study was undertaken to determine whether the addition of 5-fluorouracil (5-FU) and mitomycin-C (MMC) to radiation therapy improves outcome in this patient population. PATIENTS AND METHODS: One hundred fourteen patients were randomized to receive 59.4 Gy external beam radiotherapy in 1.8 Gy fractions alone or in combination with 5-FU (1,000 mg/m2/day for 4 days by continuous infusion Days 2-5 and 28-31) and MMC (10 mg/m2 on Day 2). RESULTS: One hundred four patients were evaluable for efficacy. Hematologic and nonhematologic toxicities were more common in the combination arm. The response rates were 6% in the radiation therapy arm and 9% in the combination arm. There were no differences in median disease-free survival time (DFS) or overall survival time (OS) between the combination and radiation therapy alone arms: 5.1 vs. 5.0 months, respectively, for DFS (p = 0.19) and 8.4 vs. 7.1 months, respectively, for OS (p = 0.16). CONCLUSION: The addition of 5-FU and MMC to radiotherapy increased toxicity without improving DFS or OS in patients with locally advanced pancreatic cancer. Alternative drugs for radiosensitization may improve outcome.

Adenocarcinoma↗

Use of an implantable drug delivery system for refractory chronic sickle cell pain.

An increasing number of chronic sickle cell patients are being treated with sustained-release opioids in the same manner as cancer patients. In a randomized clinical trial of patients with refractory cancer pain, implantable intrathecal drug delivery systems (IDDS) improved clinical success compared to comprehensive medical management alone. We implanted IDDS pumps in two sickle cell patients with refractory bone pain. Both patients achieved rapid and sustained relief of pain, with dramatic reduction in the use of as-needed opioids, crises, and admissions. IDDS may offer relief for sickle cell patients with refractory pain. A prospective trial with more participants is planned.

Adult↗

Pain management, including intrathecal pumps.

Even when managed according to guidelines, approximately 14% of cancer patients have unrelieved pain or unacceptable side effects, and there is good evidence that patients still are not receiving optimal therapy. Implantable drug delivery systems (IDDS) administer small amounts of drugs directly to the spinal cord and reduce systemic narcotic exposure by a factor of 300 to one. In a large randomized trial of 202 patients with pain scores of 7.5 or higher, despite 200 mg or more of morphine or equivalent narcotics, IDDS gave better clinical success than comprehensive medical management (84.5% vs 70.8%, P=0.05). Pain scores were reduced by 52% versus 39%, drug toxicity scores were reduced by 50% versus 17%, and IDDS patients lived longer. Even the most refractory pain patients--those failed by a month of comprehensive medical management by experts--when subsequently provided with IDDS, had a 27% reduction in pain scores and a 50% reduction in drug side effects. Given multiple positive small cohort studies and a positive high-power randomized trial, IDDS should be considered as the best treatment for this population.

Drug Delivery Systems↗

Exposure of trucking company workers to particulate matter during the winter.

This study analyzed the workplace area concentrations and the personal exposure concentrations to fine particulate (PM2.5), elemental carbon (EC), and organic carbon (OC) measured during the winter period in trucking companies. The averaged personal exposure concentrations at breathing zones of workers are much greater than those of the microenvironment concentrations. The highest difference between the area (microenvironment) and personal exposure concentrations was in the PM2.5 concentrations followed by the OC concentrations. The area concentrations of PM2.5, EC, and OC at a large terminal were higher than those at a small one. The highest area concentrations of PM2.5, EC, and OC were observed in the shop areas followed by pick-up and delivery (P&D) areas. The area concentrations and personal exposure to PM2.5, EC, and OC in the shop and P&D areas which are highly affected by diesel engine exhaust emissions were much higher than those in the docks which are significantly affected by liquefied petroleum gas (LPG) engine exhaust emissions. The highest EC fraction to the total carbon (EC + OC) concentrations was observed in the shops, while the lowest one was identified in the offices. The personal exposure of the smoking workers to PM2.5 and OC was much higher than that of the non-smoking workers. However, the smoking might not significantly contribute to the personal exposure to EC. There were significant correlations between the PM2.5 and OC concentrations in both the area and personal exposure concentrations. However, significant correlations between the PM2.5 and EC concentrations and between the OC and EC concentrations were not identified.

Air Pollutants↗

Determinants of airborne fiber size in the glass fiber production industry.

Size distributions of airborne fiber exposures should be characterized for studies of respiratory disease because size determines the region of the lung where a fiber will deposit and its ability to produce toxic effects in cells. Yet fiber size is not measured precisely with standard air sampling methods. Specific fiber dimensions hypothesized to have biologic activity have been proposed, but these have not been evaluated in epidemiologic studies because there has not been a way to account for fiber size in historical air monitoring data. In this study, methods were developed to predict fibrous aerosol size fractions generated during glass wool fiber production using regression models and factors related to bulk fiber products and processing. A set of air samples representing a range of products and process applications was collected in eight fiber glass production facilities. The samples were analyzed more intensively than standard methods require. For each air sample, total fiber size distributions were measured using electron microscopy and two proportions were then calculated: (1) fibers meeting the size criteria of the standard NIOSH Method 7400 B rules method (pB), and (2) fibers meeting the size criteria for a biologically based exposure index, the hypothetically active fiber (HAF1) index (pH1). The fiber size proportions were used as dependent variables in regression models with production process factors. It was found that two factors, the nominal diameter of the bulk fiber product and whether oil was applied to it, determine more than 80% of the variability in the proportions (for the pB model, R2 = 0.86; for the pH1 model, R2 = 0.82). Using these two predicted proportions, it is possible to estimate the concentration of fibers in the biologically based HAF1 size fraction from a standard fiber concentration measurement. The models developed here can be used to size-adjust historical fiber concentration measurements for use in epidemiologic studies of respiratory disease.

Air Pollution, Indoor↗

Exposure to fuel-oil ash and welding emissions during the overhaul of an oil-fired boiler.

The health effects of exposure to vanadium in fuel-oil ash are not well described at levels ranging from 10 to 500 microg/m(3). As part of a larger occupational epidemiologic study that assessed these effects during the overhaul of a large oil-fired boiler, this study was designed to quantify boilermakers' exposures to fuel-oil ash particles, metals, and welding gases, and to identify determinants of these exposures. Personal exposure measurements were conducted on 18 boilermakers and 11 utility workers (referents) before and during a 3-week overhaul. Ash particles < 10 microm in diameter (PM(10), mg/m(3)) were sampled over full work shifts using a one-stage personal size selective sampler containing a polytetrafluoroethylene filter. Filters were digested using the Parr bomb method and analyzed for the metals vanadium (V), nickel (Ni), iron (Fe), chromium (Cr), cadmium (Cd), lead (Pb), manganese (Mn), and arsenic (As) by inductively coupled plasma mass spectrometry. Nitrogen dioxide (NO(2)) was measured with an Ogawa passive badge-type sampler and ozone (O(3)) with a personal active pump sampler.Time-weighted average (TWA) exposures were significantly higher (p < 0.05) for boilermakers than for utility workers for PM(10) (geometric mean: 0.47 vs. 0.13 mg/m(3)), V (8.9 vs. 1.4 microg/m(3)), Ni (7.4 vs. 1.8 microg/m(3)) and Fe (56.2 vs. 11.2 microg/m(3)). Exposures were affected by overhaul time periods, tasks, and work locations. No significant increases were found for O(3) or NO(2) for boilermakers or utility workers regardless of overhaul period or task group. Fuel-oil ash was a major contributor to boilermakers' exposure to PM(10) and metals. Vanadium concentrations sometimes exceeded the 2003 American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value.

Adult↗

Implantable drug delivery systems (IDDS) after failure of comprehensive medical management (CMM) can palliate symptoms in the most refractory cancer pain patients.

BACKGROUND: A randomized clinical trial of implantable drug delivery system (IDDS) plus comprehensive medical management (CMM) versus CMM alone in 200 patients with refractory cancer pain showed better clinical success with IDDS. The objective of this study was to evaluate whether IDDS could help the most refractory patients failed by expert CMM. PATIENTS AND METHODS: This was a planned longitudinal prospective analysis of 30 of 99 (30%) patients for whom CMM failed who crossed over to IDDS by 6 months, as part of the randomized clinical trial. Patients had a pain visual analogue scale (VAS) score of 5 or more despite CMM with 320 mg or morphine-equivalent opioids and adjunct drugs for 1 month. The intervention was an implantable intrathecal programmable pump with opioids and local anesthetics. Clinical success was measured as a 20% change in pain VAS score and NCI CTEP drug toxicity scales. RESULTS: Clinical success was achieved with pain scores and drug toxicity scores significantly reduced by 27% (p = 0.011) and 51% (p < 0.0001). Median survival was 103 days after IDDS implant, similar to IDDS patients who received implantation as part of the initial randomization. CONCLUSIONS: CMM patients who crossed over to IDDS for the most refractory pain had significant reductions in pain and drug toxicity. The survival time of 3 months may be long enough for the IDDS implant to be cost effective. In this prospective longitudinal study, patients with refractory cancer pain despite comprehensive medical management derived benefit from IDDS.

Aged↗

Estimation of personal exposures to particulate matter and metals in boiler overhaul work.

OBJECTIVE: We sought to develop an algorithm and estimate unmeasured exposures to particulate matter (PM) and metals in an epidemiologic study of boilermakers. METHODS: The algorithm was based on limited measurements and workers' task and time activity patterns. Half of the measurements were used to develop exposure estimates for unmeasured person days. The other half was used for method validation. RESULTS: The validation demonstrated good approximations of actual exposures with differences less than 5% for PM and vanadium (V). Average estimated exposures to PM (mg/m3) and V (microg/m3) were significantly higher for workers doing boiler repair than utility work (0.36 vs. 0.09 for PM and 5.99 vs. 0.38 for V). CONCLUSIONS: This algorithm provided reasonably accurate exposure indices for our epidemiologic study in this population. It also is likely applicable to similar exposure scenarios in other studies.

Air Pollutants, Occupational↗

Adaptation and acclimatization to formaldehyde in methylotrophs capable of high-concentration formaldehyde detoxification.

Formaldehyde is a highly toxic chemical common in industrial effluents, and it is also an intermediate in bacterial metabolism of one-carbon growth substrates, although its role as a bacterial growth substrate per se has not been extensively reported. This study investigated two highly formaldehyde-resistant formaldehyde utilizers, strains BIP and ROS1; the former strain has been used for industrial remediation of formaldehyde-containing effluents. The two strains were shown by means of 16S rRNA characterization to be closely related members of the genus Methylobacterium. Both strains were able to use formaldehyde, methanol and a range of multicarbon compounds as their principal growth substrate. Growth on formaldehyde was possible up to a concentration of at least 58 mM, and survival at up to 100 mM was possible after stepwise acclimatization by growth at increasing concentrations of formaldehyde. At such high concentrations of formaldehyde, the cultures underwent a period of formaldehyde removal without growth before the formaldehyde concentration fell below 60 mM, and growth could resume. Two-dimensional electrophoresis and MS characterization of formaldehyde-induced proteins in strain BIP revealed that the pathways of formaldehyde metabolism, and adaptations to methylotrophic growth, were very similar to those seen in the well-characterized methanol-utilizing methylotroph Methylobacterium extorquens AM1. Thus, it appears that many of the changes in protein expression that allow strain BIP to grow using high formaldehyde concentrations are associated with expression of the same enzymes used by M. extorquens AM1 to process formaldehyde as a metabolic intermediate during growth on methanol.

Acclimatization↗

Adventitious reactions of alkene monooxygenase reveal common reaction pathways and component interactions among bacterial hydrocarbon oxygenases.

Alkene monooxygenase (AMO) from Rhodococcus rhodochrous (formerly Nocardia corallina) B-276 belongs to a family of multicomponent nonheme binuclear iron-centre oxygenases that includes the soluble methane monooxygenases (sMMOs) found in some methane-oxidizing bacteria. The enzymes catalyse the insertion of oxygen into organic substrates (mostly hydrocarbons) at the expense of O2 and NAD(P)H. AMO is remarkable in its ability to oxidize low molecular-mass alkenes to their corresponding epoxides with high enantiomeric excess. sMMO and other well-characterized homologues of AMO exhibit two adventitious activities: (1) turnover-dependent inhibition by alkynes and (2) activation by hydrogen peroxide in lieu of oxygen and NAD(P)H (the peroxide shunt reaction). Previous studies of the AMO had failed to detect these activities and opened the possibility that the mechanism of AMO might be fundamentally different from that of its homologues. Thanks to improvements in the protocols for cultivation of R. rhodochrous B-276 and purification and assay of AMO, it has been possible to detect and characterize turnover-dependent inhibition of AMO by propyne and ethyne and activation of the enzyme by hydrogen peroxide. These results indicate a similar mechanism to that found in sMMO and also, unexpectedly, that the enantiomeric excess of the chiral epoxypropane product is significantly reduced during the peroxide shunt reaction. Inhibition of the oxygen/NADH-activated reaction, but not the peroxide shunt, by covalent modification of positively charged groups revealed an additional similarity to sMMO and may indicate very similar patterns of intersubunit interactions and/or electron transfer in both enzyme complexes.

Alkynes↗

Toenail arsenic concentrations, GSTT1 gene polymorphisms, and arsenic exposure from drinking water.

Toenail arsenic (As) concentrations were evaluated as a biomarker of inorganic As (As(in)) exposure in a population residing in an As-endemic region of Bangladesh. Drinking water and toenail samples were collected from 48 families (n = 223) every 3 months for 2 years and analyzed for As using inductively coupled plasma-mass spectrometry. Drinking water collected 3, 6, and 9 months before each toenail sample collection was combined into a weighted lagged exposure variable. The contribution of each water sample to the measured toenail As concentration was estimated using maximum likelihood that accounted for fluctuations in drinking water exposure and toenail growth. The best model attributed 69%, 14%, and 17% of the toenail As content to drinking water exposures that occurred 3, 6, and 9 months before toenail collection [95% confidence intervals (95% CI), 0.46-0.97, 0.00-0.31, and 0.03-0.35, respectively]. Generalized additive mixed models using penalized regression splines were employed to model the data. Below a drinking water concentration of 2 mug As/L, no relationship between drinking water As and toenail As concentrations was observed. Above this concentration, toenail As content increased in a dose-dependent fashion as drinking water As increased. Age was a significant effect modifier of drinking water As exposure on toenail As (beta = 0.01; 95% CI, 0.002-0.02). Individuals possessing GSTT1-null genotypes had significantly more As in their toenails in contrast to GSTT1 wild-type individuals (beta = 0.11; 95% CI, 0.06-0.2). Therefore, it seems that GSTT1 modifies the relationship between As(in) exposure and toenail As(in) content.

Adolescent↗

Improving palliative and supportive care in cancer patients.

Twenty years of research in controlling symptoms such as pain and nausea have shown persistent suboptimal performance by the US oncology system. The data suggest that some of the tools of palliative care programs can improve physical symptoms of seriously ill patients at a cost society can afford. To fix these problems will require recognition of the symptoms or concerns, a system such as an algorithm or care plan for addressing each, measurement of the change, and accountability for the change. Symptom assessment scales such as the Edmonton Symptom Assessment Scale or Rotterdam Symptom Check List work to make symptoms manifest. Listing symptoms on a problem list is a necessary step in addressing them. Physical symptoms such as pain can be improved by use of computer prompts, algorithms, dedicated staff time, team management, or combinations of these strategies. Less concrete problems such as medically appropriate goal-setting, integrating palliative care into anticancer care sooner, and informing patients about the benefits and risks of chemotherapy near the end of life require more complex solutions. We review what is known about symptom control in oncology, how and why some programs do better, and make suggestions for practice. Finally, we suggest a practical plan for using symptom assessment scales, listing the problems, and managing them according to algorithms or other predetermined plans.

Attitude of Health Personnel↗