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Biomedical subjects

T J Smith

Publications and source records attributed to T J Smith.

At least 163 records · Page 9Linked to original sources
PubMed1998

Antibody-mediated neutralization of human rhinovirus 14 explored by means of cryoelectron microscopy and X-ray crystallography of virus-Fab complexes.

The structures of three different human rhinovirus 14 (HRV14)-Fab complexes have been explored with X-ray crystallography and cryoelectron microscopy procedures. All three antibodies bind to the NIm-IA site of HRV14, which is the beta-B-beta-C loop of the viral capsid protein VP1. Two antibodies, Fab17-IA (Fab17) and Fab12-IA (Fab12), bind bivalently to the virion surface and strongly neutralize viral infectivity whereas Fab1-IA (Fab1) strongly aggregates and weakly neutralizes virions. The structures of the two classes of virion-Fab complexes clearly differ and correlate with observed binding neutralization differences. Fab17 and Fab12 bind in essentially identical, tangential orientations to the viral surface, which favors bidentate binding over icosahedral twofold axes. Fab1 binds in a more radial orientation that makes bidentate binding unlikely. Although the binding orientations of these two antibody groups differ, nearly identical charge interactions occur at all paratope-epitope interfaces. Nucleotide sequence comparisons suggest that Fab17 and Fab12 are from the same progenitor cell and that some of the differing residues contact the south wall of the receptor binding canyon that encircles each of the icosahedral fivefold vertices. All of the antibodies contact a significant proportion of the canyon region and directly overlap much of the receptor (intercellular adhesion molecule 1 [ICAM-1]) binding site. Fab1, however, does not contact the same residues on the upper south wall (the side facing away from fivefold axes) at the receptor binding region as do Fab12 and Fab17. All three antibodies cause some stabilization of HRV14 against pH-induced inactivation; thus, stabilization may be mediated by invariant contacts with the canyon.

Amino Acid Sequence↗
PubMed1998

Urinary 1-hydroxypyrene concentrations in coke oven workers.

OBJECTIVES: To investigate the relation of individual occupational exposure to total particulates benzene soluble fraction (BSF) of ambient air with urinary 1-hydroxypyrene (1-OHP) concentrations among coke oven workers in Taiwan. METHODS: 80 coke oven workers and 50 referents were monitored individually for the BSF of breathing zone air over three consecutive days. Exposures were categorised as high, medium, or low among coke oven workers based on exposure situations. The high exposure group (n = 18) worked over the oven. The medium and low exposure groups (n = 41 and n = 21) worked at the side of the oven for > 4 hours and < 4 hours a day, respectively. Urine was collected before the shift on the morning of day 1 and after the shift on the afternoon of day 3 to find the change of 1-OHP concentrations across the shift. RESULTS: The median (range) changes of urinary 1-OHP concentrations across the shift for various exposure situations (microgram/g creatinine) were as follows: high 182 (7 to 3168); medium 9 (-8 to 511); low 7 (-6 to 28); and referents 0.2 (-2 to 72). This change of urinary 1-OHP was highly associated with individual occupational exposure to the BSF in air (r = 0.74 and 0.64, p < 0.001). The regression model showed significant effects of individual exposures to the BSF and alcohol consumption on urinary postshift 1-OHP after adjusting for preshift 1-OHP in the total population (n = 130). More exposure to the BSF led to higher postshift 1-OHP (p < 0.001); current drinkers of > 120 g/week had lower urinary postshift 1-OHP than never and former drinkers (p = 0.01). A 10-fold increase in the average BSF in air resulted in about a 2.5-fold increase in postshift 1-OHP among the 80 coke oven workers. CONCLUSION: Urinary 1-OHP concentrations can be used as a good biomarker to assess individual exposure to the BSF in air. Alcohol drinking may modify the toxicokinetic pathway of the BSF; the effects of alcohol should be investigated further in occupational studies.

Adult↗
PubMed1998

Human orbital fibroblasts are activated through CD40 to induce proinflammatory cytokine production.

CD40 is an important signaling and activation antigen found on certain bone marrow-derived cells. Recently, CD40 has also been shown to be expressed by nonhematopoietic cells, including certain human fibroblasts, but not others. Little is known about the function of CD40 on fibroblasts. The current study investigates the hypothesis that CD40 is expressed on orbital fibroblasts and represents a pathway for interaction between these fibroblasts and CD40 ligand-expressing cells, such as T lymphocytes and mast cells. We report here that orbital connective tissue fibroblasts, obtained from normal donors and from patients with severe thyroid-associated ophthalmopathy (TAO), express functional CD40. CD40 is upregulated approximately 10-fold by interferon-gamma (500 U/ml) treatment for 72 h. These fibroblasts become activated through triggering of CD40 with CD40 ligand (CD40L). This is evidenced by nuclear translocation of nuclear factor-kappa B and induction of the proinflammatory and chemoattractant cytokines interleukin-6 and interleukin-8, respectively. These data support the concept that cognate interactions between orbital fibroblasts and infiltrating T lymphocytes, via the CD40-CD40L pathway, may promote the tissue remodeling observed in TAO and other inflammatory diseases of the orbit. Disruption of the CD40-CD40L interaction may represent a therapeutic intervention to reduce the inflammatory components of TAO, which remains a vexing clinical problem.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1998

Cytokine-mediated PGE2 expression in human colonic fibroblasts.

We investigated prostanoid biogenesis in human colonic fibroblasts (CCD-18Co and 5 primary fibroblast cultures) and epithelial cell lines (NCM460, T84, HT-29, and LS 174T) and the effect of PGE2 on fibroblast morphology. Cytokine-stimulated PGE2 production was measured. PGH synthase-1 and -2 (PGHS-1 and -2) protein and mRNA expression were evaluated. Basal PGE2 levels were low in all cell types (0.15-6.47 ng/mg protein). Treatment for 24 h with interleukin-1beta (IL-1beta; 10 ng/ml) or tumor necrosis factor-alpha (50 ng/ml), respectively, elicited maximal 25- and 6-fold inductions of PGE2 synthesis in CCD-18Co cultures and similar results in primary fibroblast cultures; maximal inductions with IL-1beta in colonic epithelial cell lines were from zero to fivefold. Treatment of CCD-18Co fibroblasts with IL-1beta caused maximal 21- and 53-fold increases, respectively, in PGHS-2 protein and mRNA levels without altering PGHS-1 expression. PGE2 (0.1 micromol/l) elicited a dramatic shape change in selected fibroblasts. Colonic fibroblasts are potentially important as cytokine targets and a source of and target for colonic prostanoids in vivo.

Cell Line↗
PubMed1998

Molecular markers of acute upper airway inflammation in workers exposed to fuel-oil ash.

Biomarkers in nasal lavage (NL) fluid may be useful in determining the presence and severity of upper airway inflammation. We studied 18 boilermakers overhauling a large, oil-fired boiler and 11 utility workers who served as controls for 6 wk. NL was performed before (NL1), during (NL2), and after (NL3) the overhaul. We measured nasal fluid levels of interleukins 6 (IL-6) and 8 (IL-8), eosinophilic cationic protein (ECP), and myeloperoxidase (MPO) as markers of response to fuel-oil ash exposure. In boilermakers, MPO was elevated during boiler work versus preboiler work (mean = 33.8 versus 22.7 ng/ml, p < 0.05), and at the 2-wk postexposure lavage (NL3) it had declined to 24.2 ng/ml (p = 0.08). Mean IL-8 levels increased in boilermakers between NL1 and NL2 (mean = 83.8 versus 134.8 pg/ml, p < 0.05), then decreased at NL3 (mean = 134.8 versus 89.0 pg/ml, p < 0.05). Nasal fluid vanadium increased in boilermakers between NL1 and NL2 (median < 1.0 versus 4.7 ppb, respectively, p < 0.05), then decreased at NL3 (median, 4.7 versus < 1.0 ppb, respectively, p < 0. 05). Levels of IL-6 and ECP did not change significantly during the study. Utility workers showed no significant change in any marker during the study period. Particulate matter < 10 micro(m) (PM10) levels were higher for boilermakers than for utility workers before boiler work (geometric mean (GM) = 0.40 versus 0.10 mg/m3, p < 0.05). This difference was more significant during boiler work (GM = 0.47 versus 0.13 mg/m3, p < 0.001). Ozone levels were low during the study. These data suggest that exposure to fuel-oil ash results in acute upper airway inflammation, potentially mediated by increased IL-8 levels and the recruitment and activation of polymorphonuclear leukocytes. These changes were associated with significantly increased PM10 levels and concentrations of upper airway vanadium.

Adult↗
PubMed1998

The ethical challenge and the futile treatment in the older population admitted to the intensive care unit.

Projections for the future suggest that the United States population will grow by 10-15% by the year 2000, but the number of people over the age of 80 will increase by 66%. As a result, the increase that has already been observed in the number of elderly patients requiring major medical attention can only be expected to grow. This study reviews the admissions to the intensive care unit (ICU) over the last 5 years by age to analyze whether the ICU admissions are higher for the patients older than 60 years of age. We considered all the admissions to the surgical (SICU) and medical (MICU) intensive care units at Morristown Memorial Hospital from January 1, 1992, to December 31, 1996. Patients were divided into age brackets (0-9 years, 10-19 years, 20-29 years,... > 90 years) and by gender. Medical and surgical admissions were analyzed including the average length of stay in the ICU. Daily charge for bed occupancy was reviewed based on the hospital data reported in 1995. The death rate was also considered. Fisher-corrected chi 2 and a Student t test were used for statistical analysis. A total of 6243 patients (2926 female and 3317 male) were admitted to the ICU over the 5-year period. The ICU admissions rate was higher in patients above 60 years of age compared with those below 60 (60% versus 30%, respectively). The age group with the highest admissions rate was between 70 and 79 years, followed by the 60-69-year group. These two groups had significantly more admission than all other groups (P < 0.001). Medical patients' length of stay was shorter than the surgical group, and they had a lower rate of admission to the ICU. The death rate was higher in the group older than 60 years. They also spent a longer time in ICU compared with the younger group (22 +/- 7 days versus 12 +/- 8 days). The charge per day per bed was $2100 in the ICU, $1600 in a telemetry floor, and $950 in a regular floor. The charge per bed in the group above 60 years old was double compared with the one for the younger group. Older patients were admitted to the ICU with a significantly higher frequency than was the younger group. There were more surgical than medical patients admitted to the ICU. The mortality rate and the daily cost, based on daily bed charge, was significantly higher in the older group. Based on our experience, older people had a more difficult recovery in ICU than did the younger people. In our opinion we should treat acute critical illness but not terminal pathology. A problem exists in educating physicians about which patients will derive no benefit from the ICU. This will determine if we can decrease or avoid the use of the ICU and its accompanying expense, in situations where it does not significantly increase survival and the quality of life.

Adolescent↗
PubMed1998

Costs of care associated with non-small-cell lung cancer in a commercially insured cohort.

PURPOSE: To examine the cost of incident cases of non-small-cell lung cancer (NSCLC) in a commercially insured cohort. METHODS: Claims from Virginia Blue Cross and Blue Shield (BCBS) beneficiaries with lung cancer from 1989 to 1991 were merged with records from the Virginia Cancer Registry (VCR). Data from the VCR identified incident cases, stage, and type of cancer at diagnosis. Costs for all medical care included insurance payment, copayments, and deductibles for 2 years after diagnosis or until death. RESULTS: Three hundred forty-nine incident NSCLC patients were evaluated. The mean 2-year cost for each patient after diagnosis or until death was $47,941 (95% confidence interval, $43,758 to $52,124). Total average costs and hospital days were significantly lower for local disease ($37,514, 21.2 days), but were similar for regional ($52,797, 30.0 days) and distant ($49,382, 33.0 days) disease. Hospital days accounted for 48% and hospital-based claims for 70% of costs. Initial treatments, which included radiation, unadjusted for stage, had the lowest survival rates and the highest costs, and were associated with the most hospital days. Initial stage, race, gender, and age were not predictors of total 2-year costs. The independent predictors of total 2-year costs were type of treatment: any radiation therapy, any surgery, or any chemotherapy (all, P < .001). Inpatient hospital days was only a modest predictor of costs after adjusting for type of treatment. Patients who survived less than 1 year spent 30.5 days in hospital and had an average cost of $47,280. CONCLUSION: The direct health care costs of younger NSCLC patients care are substantial. These results should serve as a benchmark for future comparisons as the United States market shifts to managed care.

Blue Cross Blue Shield Insurance Plans↗
PubMed1998

Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points.

PURPOSE: To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. PATIENTS AND METHODS: The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. RESULTS: The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost difference ranged from a saving of $9,200 for M + P (with palliative benefit) to an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was consistently less expensive in whichever time period was used to compare costs. Cost-utility analysis showed M + P to be the preferred strategy with an upper 95% confidence interval for the incremental cost-utility ratio of CDN $19,700 per quality-adjusted life-year (QALY). CONCLUSION: A treatment that reduces symptoms and improves quality of life has the potential to reduce costs in other areas. Economic factors should not influence the clinical decision as to whether to use M + P in a symptomatic patient.

Canada↗
PubMed1998

Sixteen-week multidrug regimen versus cyclophosphamide, doxorubicin, and fluorouracil as adjuvant therapy for node-positive, receptor-negative breast cancer: an Intergroup study.

PURPOSE: The Intergroup conducted this breast cancer adjuvant trial to compare an investigational 16-week regimen with cyclophosphamide, doxorubicin, and fluorouracil (5-FU; CAF). The 16-week regimen features greater doxorubicin and 5-FU dose-intensity than CAF and improved scheduling of antimetabolites with sequential methotrexate and 5-FU, as well as infusion 5-FU. PATIENTS AND METHODS: A total of 646 node-positive, receptor-negative patients were randomly assigned to receive either the 1 6-week regimen or six cycles of CAF. Breast cancer outcomes included recurrence as well as disease-free and overall survival. Toxicity was evaluated by the Common Toxicity Criteria (CTC). Treatment-related quality of life was assessed by the Breast Chemotherapy Questionnaire (BCQ) before, during, and 4 months after treatment in 163 patients. The trial was designed to use one-sided tests of significance for power calculations, but is now reported with both one-sided and the traditional two-sided tests of significance. RESULTS: At a median follow-up of 3.9 years, the estimated 4-year recurrence-free survival rate was 67.5% with the 16-week regimen versus 62.7% with CAF (P = .19, two-sided; P = .095, one-sided). The estimated 4-year survival rate was 78.1% with the 16-week regimen versus 71.4% with CAF (P = .10, two-sided; P = .05, one-sided). CAF produced significantly higher grades of leukopenia, granulocytopenia, and thrombocytopenia, as well as liver and cardiac toxicity, whereas the 16-week regimen produced significantly higher grades of anemia, nausea, stomatitis, and weight loss, as well as skin and neurotoxicity. There were three treatment-related deaths with CAF but none with the 16-week regimen. During treatment, quality of life declined significantly more with the 16-week regimen than CAF, but by 4 months posttreatment, there was no difference. CONCLUSION: The 16-week regimen produced marginally better breast cancer outcomes than CAF with similar toxicity but a greater reduction in during-treatment quality of life. The 16-week regimen should not be used instead of a standard-dose regimen without careful consideration of the 16-week regimen's pros and cons, which include its complicated schedule. It should probably not be tested further, but its antimetabolite schedules and frequent drug administration (ie, dose density) should be considered in the development of new regimens.

Adult↗
PubMed1998

Overview of economic analysis of Le Chevalier Vinorelbine Study.

The costs and relative cost-effectiveness of different treatments for common illnesses are an increasing concern. New treatments for advanced non-small-cell lung cancer are having an impact. However, these treatments vary markedly in their direct financial costs, toxicity, and quality-of-life profiles. Direct comparisons between most combination regimens are not yet completed. Vinorelbine (Navelbine) is the first new agent approved in the United States for the treatment of metastatic non-small-cell lung cancer in more than a decade. We previously reported results of a post-hoc economic analysis that compared the anticipated cost-effectiveness of three regimens used to treat non-small-cell lung cancer (vinorelbine alone versus vinorelbine plus cisplatin [Platinol] versus vindesine plus cisplatin, the assumed standard treatment in Europe). Results showed that vinorelbine plus cisplatin was the most effective regimen. Using vinorelbine alone as a baseline, vinorelbine plus cisplatin added 56 days of life at an additional cost of $2,700, resulting in a cost-effectiveness ratio of $17,700 per year of life gained. Similarly, vindesine plus cisplatin added 19 days of life at a cost of $1,150, or $22,100 per year of life gained. Compared to vindesine plus cisplatin, vinorelbine plus cisplatin added 37 days of life at a cost of $1,570, or $15,500 per year of life gained. We conclude that the incremental cost-effectiveness of the vinorelbine plus cisplatin regimen was less than most commonly accepted medical interventions. If vinorelbine is preferred because of its favorable toxicity profile, the additional effectiveness of cisplatin added substantial efficacy at an acceptable cost.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Chitosan-membrane interactions and their probable role in chitosan-mediated transfection.

Recent studies in our laboratory have shown that chitosan, a polycationic polymer of glucosamine, can facilitate the transfection of HeLa cells with a plasmid that codes for beta-galactosidase. Although chitosan can bind to DNA and other polyanions, the kinetics of complexation might differ depending on the polyanion tested. This evidence suggests that, in addition to ionic interactions, the carbohydrate backbone of chitosan might have an important role in the process of transfection. Beads prepared by the complexation of chitosan with polyphosphate were used to investigate the nature of cellular interactions with chitosan. HeLa cells bound to chitosan-polyphosphate beads could be readily displaced from the beads with methyl alpha-D-mannopyranoside but not with NaCl. Membrane proteins solubilized by CHAPS bound readily to chitosan-polyphosphate beads. A major fraction of the membrane proteins could be eluted from the beads with methyl alpha-D-mannopyranoside. These results suggest that non-ionic interactions between the carbohydrate backbone of chitosan and cell surface proteins might have an important role in the chitosan-mediated transfection of HeLa cells.

Biopolymers↗
PubMed1998

Isolation and functional analysis of the histone H3 promoter from atlantic salmon (Salmo salar L.).

The histone H3 (sH3) promoter of Atlantic salmon (Salmo salar) was cloned via polymerase chain reaction using primers designed from the rainbow trout (Oncorhynchus mykiss) promoter sequence. A comparison of the nucleotide sequence with the equivalent sequences from rainbow trout and sockeye salmon (Oncorhynchus nerka) revealed a high degree of conservation. In vivo expression analysis of the sH3 promoter was carried out in both rainbow trout and zebrafish (Danio rerio) embryos. A direct comparison of the sH3 promoter with the viral RSV promoter in rainbow trout resulted in stronger expression of the sH3 promoter. Furthermore, lacZ expression directed by the sH3 promoter was ubiquitous in several different cell types in developing zebrafish embryos. These results suggest that the sH3 promoter will be useful in transgenic studies in Atlantic salmon.

Animals↗
PubMed1998

Action of the pyrethroid insecticide cypermethrin on rat brain IIa sodium channels expressed in xenopus oocytes.

Pyrethroid insecticides bind to a unique site on voltage-dependent sodium channels and prolong sodium currents, leading to repetitive bursts of action potentials or use-dependent nerve block. To further characterize the site and mode of action of pyrethroids on sodium channels, we injected synthetic mRNA encoding the rat brain IIa sodium channel alpha subunit, either alone or in combination with synthetic mRNA encoding the rat sodium channel beta1 subunit, into oocytes of the frog Xenopus laevis and assessed the actions of the pyrethroid insecticide [1R,cis,alphaS]-cypermethrin on expressed sodium currents by two-electrode voltage clamp. In oocytes expressing only the rat brain IIa alpha subunit, cypermethrin produced a slowly-decaying sodium tail current following a depolarizing pulse. In parallel experiments using oocytes expressing the rat brain IIa alpha subunit in combination with the rat beta1 subunit, cypermethrin produced qualitatively similar tail currents following a depolarizing pulse and also induced a sustained component of the sodium current measured during a step depolarization of the oocyte membrane. The voltage dependence of activation and steady-state inactivation of the cypermethrin-dependent sustained current were identical to those of the peak transient sodium current measured in the absence of cypermethrin. Concentration-response curves obtained using normalized tail current amplitude as an index of the extent of sodium channel modification by cypermethrin revealed that coexpression of the rat brain IIa alpha subunit with the rat beta1 subunit increased the apparent affinity of the sodium channel binding site for cypermethrin by more than 20-fold. These results confirm that the pyrethroid binding site is intrinsic to the sodium channel alpha subunit and demonstrate that coexpression of the rat brain IIa alpha subunit with the rat beta1 subunit alters the apparent affinity of this site for pyrethroids.

Action Potentials↗
PubMed1997

Characterization of early pulmonary hyperproliferation and tumor progression and their inhibition by black tea in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis model with A/J mice.

The pathogenesis of pulmonary tumors induced by a tobacco carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and its inhibition by black tea have been characterized. Female A/J mice (6 weeks old) were treated with a single dose of NNK (103 mg/kg of body weight, i.p.) on day 0, and the cell proliferation index was measured by the incorporation of bromodeoxyuridine (BrdUrd) immunohistochemically. The number of BrdUrd-labeled cells increased in the bronchiolar epithelium from day 2 to day 14, with the highest proliferation rate observed on day 5. By day 35, the BrdUrd-labeling index returned to the level of the control group. Further examination of the day 35 samples revealed the presence of foci of hyperproliferative cells in the bronchiolar epithelium, particularly in the bronchiolalveolar regions. These proliferating bronchiolar epithelial cells (Clara cells) may be the initiated sites for pulmonary tumorigenesis. In this short-term model, administration of black tea polyphenols (0.3%) through the drinking water starting 24 h after NNK treatment significantly inhibited NNK-induced early bronchiolar cell proliferation on day 5. In long-term studies, adenomas were observed in 100% (15 of 15) of the mice at week 16, with 7.8 +/- 0.8 tumors per mouse. At week 52, a malignant tumor incidence of 80% (41 of 51 mice) and a malignant tumor multiplicity of 2.39 +/- 0.19 were observed. The growth patterns of the malignant tumors, which included solid, papillary, and mixed types, may be associated with the cellular origin of the tumor. The cell proliferation indices, as measured by proliferating cell nuclear antigen immunohistochemistry, were significantly higher in dysplasia within adenoma than in adenoma, and significantly higher in adenoma at week 52 than in adenoma at week 16. Administration of black tea, starting 16 weeks after a single dose of NNK, inhibited the progression of adenoma to adenocarcinoma as determined by both malignant tumor incidence and multiplicity. The cell proliferation rate in adenomas was also suppressed by black tea treatment. The present work demonstrates the antiproliferative activities of black tea and its polyphenols. Such activities, at the early and late stages of lung tumorigenesis, may be important for the cancer-chemopreventive activities of black tea.

Animals↗
PubMed1997

Mortality studies of machining fluid exposure in the automobile industry. IV: A case-control study of lung cancer.

Machining fluids are diverse products that contain numerous additives and contaminants, including polycyclic aromatic hydrocarbons. Studies treating machining fluids as an aggregate exposure have found both positive and negative associations with lung cancer. In this nested case-control study of automotive workers (667 cases and 3,041 matched controls), individual estimates of exposure quantity and duration for specific classes of machining fluids were derived. An inverse dose-response relationship was found between synthetic machining fluids and lung cancer mortality, with an odds ratio of 0.6 (95% CI = 0.4, 0.8) for the highest level of lifetime exposure. The relationship was strongest for recent exposures. There was little evidence of an association with soluble or straight oil machining fluids. Risks were inconsistently elevated in workers exposed to aluminum. Results from this study provide strong evidence that exposure to machining fluids is not associated with an increased risk of lung cancer mortality in automotive workers.

Aluminum↗
PubMed1997

Conceptual and definitional issues in occupational injury epidemiology.

This paper presents several models that further define the concept of occupational injury. While traditional models have proved successful in isolating specific research questions and health phenomena, the conceptual model presented permits a broader view of all injury morbidity. This model is based on both the level and frequency of energy transfers. A process model of occupational injury is also presented to describe the basic pathophysiological relationships associated with tissue effects/damage and recovery/repair. Numerous tradeoffs exist in variable selection, and a third model explores some of these tradeoffs. Differences in terminology and fundamental principles can limit the progress of occupational injury research. Accordingly, an argument is made for consolidation and consensus of terms. Finally, considerations for research are suggested, with an emphasis on the severity of the injury, the risk ratio, and the population at risk.

Accidents, Occupational↗
PubMed1997

Mortality studies of machining fluid exposure in the automobile industry. V: A case-control study of pancreatic cancer.

Results are presented from a case-control study of 97 cases of pancreatic cancer nested in a cohort of workers from three automobile manufacturing plants. Risk was examined for lifetime exposure to straight, soluble, and synthetic metalworking fluids, as used in specific machining or grinding operations, as well as for constituents of the fluids. Pancreatic cancer was associated with exposure to synthetic fluids in grinding operations, with an odds ratio of 3.0 (95% CI: 1.2-7.5) among those with more than 1.4 mg/m3-years of exposure. We were unable to examine synthetic exposure in the absence of grinding because there was virtually no exposure to synthetics in machining operations in this study population. Although a disproportionately high percent of the cases were black, no black workers had any exposure to synthetic fluids, and no other measured exposure was found to be related to risk. Thus, the previously documented excess risk of pancreatic cancer among blacks in this cohort remains unexplained.

Adult↗