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T J Smith

Publications and source records attributed to T J Smith.

At least 55 records · Page 3Linked to original sources
PubMed2001

Viral capsid mobility: a dynamic conduit for inactivation.

Mass spectrometry and fluorescent probes have provided direct evidence that alkylating agents permeate the protein capsid of naked viruses and chemically inactivate the nucleic acid. N-acetyl-aziridine and a fluorescent alkylating agent, dansyl sulfonate aziridine, inactivated three different viruses, flock house virus, human rhinovirus-14, and foot and mouth disease virus. Mass spectral studies as well as fluorescent probes showed that alkylation of the genome was the mechanism of inactivation. Because particle integrity was not affected by selective alkylation (as shown by electron microscopy and sucrose gradient experiments), it was reasoned that the dynamic nature of the viral capsid acts as a conduit to the interior of the particle. Potential applications include fluorescent labeling for imaging viral genomes in living cells, the sterilization of blood products, vaccine development, and viral inactivation in vivo.

Animals↗
PubMed2001

Why academic divisions of hematology/oncology are in trouble and some suggestions for resolution.

PURPOSE: Academic divisions of hematology/oncology seem to have difficulty recruiting and retaining excellent productive clinicians. A major reason for this is that salaries do not compete with the private sector for similar work. METHODS: We reviewed divisional finances productivity, and experiences from faculty members leaving. RESULTS: The academic salaries are approximately one third of practice because the chemotherapy concession has been given to the academic hospital. In addition, there may be substantial problems in under-billing, lack of attention to detail in billing, and poor collection practices. CONCLUSION: Academic practice still has much to offer, including opportunities for research and multidisciplinary team management, although the differences may narrow over the coming years. Attention to detail in the billing, collection for work performed, and increasing academic salaries to levels nearer to private practice are necessary components of the solution to recruit and retain quality productive clinicians.

Faculty↗
PubMed2001

Respiratory health of automobile workers and exposures to metal-working fluid aerosols: lung spirometry.

BACKGROUND: Despite substantial evidence that workers exposed to metal-working fluids (MWF) have increased respiratory morbidity, the few studies of chronic effects on lung function have not been conclusive. METHODS: Lung spirometry was measured and both current and past exposures to metal-working fluid (MWF) aerosols were estimated in this cross-sectional cohort of 1,811 male automobile workers. Satisfactory exposure data were available for 1,745 (96%): 239 assemblers (never-exposed to MWF), 487 assemblers (previously exposed), 352 machinists currently exposed to straight oils, 441 to soluble oils, and 226 to synthetic fluids. Operations were classified as either grinding or non-grinding machining. RESULTS: Current exposure was not found to be associated with either forced expiratory volume in 1 second (FEV(1)) or forced ventilatory capacity (FVC). Nor was past exposure to water-based fluids (soluble or synthetic MWF) related to pulmonary function. Past exposure to straight oils, however, was significantly associated with FVC. This association was more obvious among older workers and among workers who had never transferred from MWF exposed jobs to assembly. CONCLUSIONS: The magnitude of the association between FVC and lifetime exposure to straight MWF was slightly larger than the estimated cigarette effect, suggesting that the impact of an additional year of exposure to 1 mg/m(3) of mineral oil particulate in the thoracic particle size range, has the same impact on FVC as smoking one pack per day for one more year.

Adult↗
PubMed2001

Gamma probe-directed lymphatic mapping and sentinel lymphadenectomy in primary melanoma: Reliability of the procedure and analysis of failures after long-term follow-up.

BACKGROUND AND OBJECTIVES: Some patients presenting with cutaneous malignant melanoma without palpable adenopathy have regional metastatic disease. The results of a prospective clinical study of gamma probe-directed sentinel lymph node (SLN) biopsy are presented. METHODS: Over a 3-year period, 103 patients with a diagnosis of invasive primary cutaneous malignant melanoma (Breslow > 0.12 mm or > Clark level II) underwent preoperative lymphoscintigraphy with technetium sulfur colloid followed by gamma-probe-guided sentinel lymphadenectomy. There were 46 women and 57 men with a mean age of 55.7 years (range, 19-91). RESULTS: Mean Breslow thickness was 2.3 mm (range, 0.12-10 mm). Primary locations were head and neck in 12, trunk 46, upper extremity 19, and lower extremity in 26. One hundred sixteen lymph node basins were mapped in 103 patients. Axillary, inguinal, and cervical nodal basins comprised 55, 34, and 11% of the total basins evaluated, respectively. Sixty-eight patients (66%) underwent lymphatic mapping of one regional nodal basin, 27 patients (26%) underwent synchronous lymphatic mapping of 2 regional nodal basins, 6 patients (6%) underwent synchronous lymphatic mapping of 3 regional nodal basins, and 2 patients (2%) underwent synchronous lymphatic mapping of 4 regional nodal basins. Seroma or infection did not occur in any patients. Micrometastatic disease was identified in 15 sentinel lymph node biopsy sites in 13 (10%) patients. Of 10 patients undergoing lymph node dissection, 9(90%) had no additional pathological lymph node involvement. We achieved 99% success rate, 1% rate of failed sentinel node procedure, and 8% false-negative rate after median follow-up for 2 years. CONCLUSIONS: We concluded that gamma probe-directed sentinel lymph node biopsy is a straightforward procedure which can be done in the outpatient setting and facilitates management of patients with cutaneous malignant melanoma. It allows the surgeon to identify all basins at risk for metastatic disease and the location of the sentinel node(s) in relation to the basin.

Adult↗
PubMed2001

Resorbable bioceramics based on stabilized calcium phosphates. Part II: evaluation of biological response.

Synthetic materials capable of being remodelled in vivo by the same processes responsible for natural bone turnover have long been sought for use as an artificial bone substitute. These materials must ideally combine osteoinductive capacity with the ability to withstand random dissolution at normal physiological pH, while being resorbed by natural cell-mediated processes. Resorbable calcium phosphate based coatings and bulk ceramics have been developed which promote the uniform deposition of new mineralized bone matrix thus enabling rapid integration with the surrounding host bone tissue in vivo. Furthermore, a critical result of this study is the determination that the silicon-stabilized calcium phosphate ceramics are essentially insoluble in biological media but are resorbed when acted upon by osteoclasts. In vitro biological testing and preliminary in vivo testing show that the important features of this new biomaterial are a characteristic calcium phosphate phase composition and a unique microporous morphology.

Absorbable Implants↗
PubMed2001

Ethics of rural health care.

One quarter of the US population live in areas designated as rural. Delivery of rural health care can be difficult with unique challenges including limited access to specialists such as oncologists. The Rural Cancer Outreach Program is an alliance between an academic medical center and five rural hospitals. Due to the presence of this program, the appropriate use of narcotics for chronic pain has increased, the number of breast conserving surgeries has more than doubled and accrual to clinical trials has gone from zero to nine over the survey period. An increase in adjuvant chemotherapy has been noted. The rural hospitals and the academic center have seen a positive financial impact. The most prominent ethical issues focus on justice, especially access to health care, privacy, confidentiality, medical competency, and the blurring of personal and profession boundaries in small communities. As medical care has become more complex with an increasing number of ethical issues intertwined, the rural hospitals have begun to develop mechanisms to provide help in difficult situations. The academic center has provided expertise and continued education for staff, both individually and within groups, regarding ethical dilemmas.

Academic Medical Centers↗
PubMed2001

Activation of diacetyldapsone and a preliminary evaluation of a cyclodextrin-diacetyldapsone complex in cultured lung cells.

A diacetyldapsone-2-hydroxypropyl-beta-cyclodextrin complex (DADDS-CD) was evaluated with regard to the ability of cultured lung cells to activate DADDS to the active metabolite dapsone. The same system was used to assess the effect of the complex on cell growth. The complex was incubated with cells for periods of 24 to 72 h, followed by extraction of metabolites from the incubation medium and analysis by HPLC. In addition, the Trypan Blue exclusion technique was used to assess cell viability during this time period. Results indicated that lung cells could activate DADDS to dapsone and that, while the complex appeared to delay cell growth in the first 24 h period, no significant difference was seen between cells incubated in the presence and absence of the complex at 72 h. These results indicate that DADDS-CD has significant potential as a drug-delivery system for DADDS in the lung based upon the ability of the cells to activate DADDS. The mixed effects of the complex on cell growth may have important implications when considering the frequency of administration of the complex to the lung.

Acedapsone↗
PubMed2001

KP4 fungal toxin inhibits growth in Ustilago maydis by blocking calcium uptake.

KP4 is a virally encoded fungal toxin secreted by the P4 killer strain of Ustilago maydis. From our previous structural studies, it seemed unlikely that KP4 acts by forming channels in the target cell membrane. Instead, KP4 was proposed to act by blocking fungal calcium channels, as KP4 was shown to inhibit voltage-gated calcium channels in rat neuronal cells, and its effects on fungal cells were abrogated by exogenously added calcium. Here, we extend these studies and demonstrate that KP4 acts in a reversible manner on the cell membrane and does not kill the cells, but rather inhibits cell division. This action is mimicked by EGTA and is abrogated specifically by low concentrations of calcium or non-specifically by high ionic strength buffers. We also demonstrate that KP4 affects (45)Ca uptake in U. maydis. Finally, we show that cAMP and a cAMP analogue, N 6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate, both abrogate KP4 effects. These results suggest that KP4 may inhibit cell growth and division by blocking calcium-regulated signal transduction pathways.

Antifungal Agents↗
PubMed2001

Advanced breast biopsy instrumentation (ABBI) and management of nonpalpable breast abnormalities: a community hospital experience.

A range of diagnostic techniques have been in use for determining the nature of non-palpable mammographic abnormalities over the last decade, these include stereotactic and ultrasound guided cytology, core biopsy and vacuum assisted core biopsy techniques as well as open surgical breast biopsy. Recently, a less invasive alternative has been investigated; the Advanced Breast Biopsy Instrumentation (ABBI) technique (U.S. Surgical Corporation, Norwalk, CT). ABBI employs computer-guided stereotactic localization to target and excise mammographic lesions under local anesthesia, without the need for an operating theatre. We conducted a prospective review of all cases involving the use of the ABBI system during the first 17 months' of its use in a community hospital. One hundred and twenty six patients were referred for an ABBI procedure. One hundred fourteen ABBI procedures were performed on 113 patients (average age, 53 years; range, 33-82). The lesion was removed successfully in 113 of the 114 cases. Of the 114 lesions removed with the ABBI system, 88 were microcalcifications and 26 were masses. Cancer was diagnosed in 21 patients (18%). Of the patients who had carcinoma, 11 (52%) had ductal carcinoma in situ, 9 (43%) had infiltrating ductal carcinoma, and 1 (5%) had infiltrating lobular carcinoma. Postprocedural complications occurred in 7 patients (6%); 4 had small haematomas, 2 had superficial wound infections, and 1 had an abscess. We conclude that the ABBI system, is an excellent alternative (to open biopsy after needle localization or large-core biopsy) for nonpalpable breast abnormalities. It has a relatively low complication rate and should be considered as part of the surgical armamentarium for the diagnosis of indeterminate nonpalpable mammographic lesions.

Journal Article↗
PubMed2001

Mechanisms of inhibition of chemical toxicity and carcinogenesis by diallyl sulfide (DAS) and related compounds from garlic.

Diallyl sulfide (DAS) is a flavor compound derived from garlic and is sequentially converted to diallyl sulfoxide (DASO) and diallyl sulfone (DASO(2)) by cytochrome P(450) 2E1 (CYP2E1). These compounds have been shown to reduce the incidence of a multitude of chemically induced tumors in animal models. The impediment of phase I activation of these carcinogens is hypothesized to be accountable for the reduction in tumor incidence. Indeed, DAS, DASO and DASO(2) are competitive inhibitors of CYP2E1. DASO(2), in addition, is a suicide inhibitor of CYP2E1. These compounds have been shown to reduce carbon tetrachloride-, N-nitrosodimethylamine- and acetaminophen-induced toxicity in rodents. All three chemicals are substrates for CYP2E1. The protective effect was observed when the organosulfur compounds were given before, during or soon after chemical treatment. DAS and DASO(2) inhibited the bioactivation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and related lung tumorigenesis in A/J mice. Because CYP2E1 does not play a key role in NNK activation, the inhibition of other CYP enzymes active in NNK metabolism is likely. DAS also has been shown to induce other CYP and phase II enzymes as well as decrease hepatic catalase activity. All of these effects are observed at concentrations much higher than what is normally ingested by humans. The biological activities of garlic and its related compounds at lower concentrations that mimic human consumption remain to be studied further.

Allyl Compounds↗
PubMed2001

Impact on internal doses of photon SAFs derived with the GSF adult male voxel phantom.

This paper describes the effect on over 3,000 sets of internal dose estimates of using photon Specific Absorbed Fractions (SAFs) calculated using two different types of phantoms, specifically the MIRD-type anthropomorphic phantom originally developed by Snyder and the new adult male voxel phantom, GOLEM, developed at GSF. The SAFs based on the MIRD-type phantom are currently used by the International Commission on Radiological Protection (ICRP) in internal dose calculations, but there are suggestions of moving towards SAFs generated from voxel phantoms, thus there is an interest in the potential differences in internal doses. Overall, it is found that some tissue doses calculated using the voxel phantoms can differ significantly from those of the MIRD-type phantom; however, the effective dose appears to be quite robust to changes in photon SAFs.

Administration, Inhalation↗
PubMed2001

Effects of exposure to organic solvents on menstrual cycle length.

To investigate the association between organic solvent exposure and menstrual disturbance, we conducted a cross-sectional study among 1408 petrochemical workers in China. Based on an industrial hygiene evaluation, we classified the workshops according to the presence or absence of organic solvents (benzene, styrene, toluene, or xylene). We used logistic regression to estimate odds ratios and 95% confidence intervals for prolonged menstrual cycle length (oligomenorrhea: average cycle length > 35 days during the previous year) associated with the exposure. After adjustment for confounders, each additional year of work in an exposed workshop was associated with a 7% increase in oligomenorrhea (odds ratio, 1.07; 95% confidence interval, 1.00 to 1.14). Compared with no exposure, 3 or more years of exposure was associated with a 53% increase in oligomenorrhea (odds ratio, 1.53; 95% confidence interval, 1.00 to 2.34). We concluded that exposure to organic solvents is associated with a trend toward increased frequency of oligomenorrhea.

Adult↗
PubMed2001

Historical cohort study of US man-made vitreous fiber production workers: I. 1992 fiberglass cohort follow-up: initial findings.

This 1986 to 1992 update and expansion of an earlier historical cohort study examined the 1946 to 1992 mortality experience of 32,110 workers employed for 1 year or more during 1945 to 1978 at any of 10 US fiberglass (FG) manufacturing plants. Included are (1) a new historical exposure reconstruction for respirable glass fibers and several co-exposures (arsenic, asbestos, asphalt, epoxy, formaldehyde, polycyclic aromatic hydrocarbons, phenolics, silica, styrene, and urea); and (2) a nested, matched case-control study of 631 respiratory system cancer (RSC) deaths in male workers during 1970 to 1992 with interview data on tobacco smoking history. Our findings to date from external comparisons based on standardized mortality ratios (SMRs) in the cohort study provide no evidence of excess mortality risk from all causes combined, all cancers combined, and non-malignant respiratory disease. Also, excluding RSC, we observed no evidence of excess mortality risk from any of the other cause-of-death categories considered. For RSC among the total cohort, we observed a 6% excess (P = 0.05) based on 874 deaths. Among long-term workers (5 or more years of employment) we observed a not statistically significant 3% excess based on 496 deaths. Among the total cohort, we observed increases in RSC SMRs with calendar time and time since first employment, but these were less pronounced among long-term workers. RSC SMRs were not related to duration of employment among the total cohort or long-term workers. In an externally controlled analysis of male workers at risk between 1970 and 1992, we observed no association between RSC SMRs and increasing exposure to respirable FG. Our findings to date from internal comparisons based on rate ratios in the case-control study of RSC were limited to analyses of categorized study variables with and without adjustment for smoking. On the basis of these analyses, the duration of exposure and cumulative exposure to respirable FG at the levels encountered at the study plants did not appear to be associated with an increased risk of RSC. RSC risk also did not seem to increase with time since first employment. There is some evidence of elevated RSC risk associated with non-baseline levels of average intensity of exposure to respirable glass, but when adjusted for smoking this was not statistically significant, and there was no apparent trend with increasing exposure. This same pattern of findings was observed for duration of exposure, cumulative exposure, and average intensity of exposure to formaldehyde. None of the other individual co-exposures encountered in the study plants appeared to be associated with an increased risk of RSC. The primary focus of ongoing analyses is to determine the extent to which our present findings are robust to alternative characterizations of exposure.

Adult↗
PubMed2001

Historical cohort study of US man-made vitreous fiber production workers: III. Analysis of exposure-weighted measures of respirable fibers and formaldehyde in the nested case-control study of respiratory system cancer.

The most recent findings of our nested case-control study of respiratory system cancer (RSC) among male fiberglass workers showed some evidence of elevated RSC risk associated with non-baseline levels of average intensity of exposure (AIE) to respirable fibers (RFib). When adjusted for smoking, this was not statistically significant, and no trend was apparent with increasing levels of exposure. Similar findings for RSC were noted for both cumulative exposure (Cum) and AIE to formaldehyde (FOR). In this reanalysis of our nested case-control study, we explored a possible exposure-response relationship between RSC and exposure to RFib or FOR using exposure weighting as an alternative characterization of exposure. Because of the uncertainties in selecting an appropriate exposure-weighting scheme, a range of plausible time lags and unlagged/lagged time windows was considered. As in the initial analysis of the nested case-control study, RFib and FOR exposures were categorized at the deciles of the RSC case distribution. For none of the exposure weighting schemes considered did we observe an increasing RSC risk with increasing levels of RFib_Cum or RFib_AIE. The exposure-weighted estimated risk ratios (RR) for both RFib_Cum and RFib_AIE were generally lower than those obtained from an unweighted model. For FOR_Cum, RRs were generally lower for the time-lagged and unlagged time window models than for the unweighted models, although some decile-specific RRs were higher for the lagged time window models. The exposure-weighted RRs for FOR_AIE were generally lower than the unweighted RRs for all of the weighting schemes considered. This reanalysis in terms of categorized exposures reveals no exposure-response relationships that were undetected in the original analysis where unweighted exposure measures were used. In the schemes considered, exposure weighting generally reduced the estimated risk of RSC.

Adult↗
PubMed2001

Historical cohort study of US man-made vitreous fiber production workers: IV. Quantitative exposure-response analysis of the nested case-control study of respiratory system cancer.

As part of the 1992 update of an historical cohort study of 32,110 workers employed for at least 1 year in any of 10 US fiberglass manufacturing plants, a nested case-control study was done in which data on tobacco smoking were obtained for 631 male case subjects with respiratory system cancer (RSC) and 570 control subjects matched on age and year of birth. In this more extensive analysis of the nested case-control data, we provide a detailed assessment of the most prominent findings from the initial report. We expand the scope of the analysis to consider quantitative measures of exposure to respirable fibers (RFib), formaldehyde (FOR), and silica (Sil) and consider these and other exposures together in the same model. We investigate the functional form of possible exposure-response relationships between RSC risk, RFib, and FOR. In addition, we address the statistical issues of collinearity, effect modification, and potential confounding by coexposures. All analyses are adjusted for smoking. Neither measure of exposure to RFib (average intensity of exposure or cumulative exposure) was statistically significantly associated with RSC risk in any of the hundreds of fractional polynomial models considered. This more extensive analysis has substantiated our initial finding of no apparent exposure-response relationship between RSC risk and either cumulative or average intensity of exposure to RFib at the levels experienced by these workers. This study provides some evidence of increased RSC risk among workers at the higher observed levels of average intensity of exposure to FOR and/or Sil. No positive associations were identified between RSC risk and any of the other exposures considered in this case-control study.

Adult↗
PubMed2001

Historical cohort study of US man-made vitreous fiber production workers: VII. Overview of the exposure assessment.

Data and procedures used to reconstruct the history of exposures at each of the 15 plants (19 distinct sites) are presented. The assessment consisted of five steps: (1) develop a Technical History of operations, stable periods, and time points of changes relevant for exposures, and identify the presence of potentially confounding co-exposures; (2) develop a set of unique department-job names with descriptions and a Job Dictionary for all verbatim names in work histories; (3) collect all company and other exposure data (> 1600 observed), and develop quantitative fiber, formaldehyde, and silica exposure estimates; (4) integrate estimates with the Technical History to make Exposure Extrapolation Tables; and (5) use the the Tables with job data to develop an Exposure Matrix for each plant. Nineteen Exposure Matrices were made, with 82 to 621 lines, covering up to 54 years of operations.

Air Pollutants, Occupational↗
PubMed2001

Historical cohort study of US man-made vitreous fiber production workers: VIII. Exposure-specific job analysis.

UNLABELLED: All jobs held by a cohort of US man-made vitreous fiber production workers were analyzed for airborne fiber exposure. This exposure-specific job analysis was part of an exposure assessment for an epidemiologic study of mortality patterns, with particular focus on respiratory cancer, among 35,145 workers employed in 10 fiberglass and five rock or slag wool plants. The exposure assessment was conducted from the start-up date of each plant (1917 to 1946) to 1990. For the job analysis, 15,465 crude department names and 47,693 crude job titles were grouped into 1668 unique department and job pairs (UDJobs), which represented a job title linked to a specific department within each plant. Every UDJob was evaluated according to a set of job elements related to airborne fiber exposure. The distribution of the cohort person-years by UDJob and the job-exposure elements was then evaluated. The results show the main departments and jobs that employed the workers for each plant. The distribution of person-years varies across the job-exposure elements. The same job title was used in different departments within and across plants. When job titles not linked to departments were evaluated, the values of the job-exposure elements varied considerably across all plants and within plant. IN CONCLUSION: (1) exposure misclassification could occur if job title alone were used for the exposure assessment; (2) the job-exposure elements analysis provides an efficient way to identify major job determinants of exposure without relying on the more detailed, resource-intensive task-based approach; and (3) the evaluation of the cohort person-years by UDJobs and job-exposure elements is an effective way to identify which plants, departments, and jobs have sufficient information for making precise risk estimates in the broader epidemiologic study.

Air Pollutants, Occupational↗