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Biomedical subjects

S M Kennedy

Publications and source records attributed to S M Kennedy.

At least 55 records · Page 3Linked to original sources
PubMed1996

Recommendations for reducing the effect of grain dust on the lungs. Canadian Thoracic Society Standards Committee.

OBJECTIVE: To assess the appropriateness of the current Canadian standards for exposure to grain dust in the workplace. OPTIONS: The current permissible exposure limit of 10 mg of total grain dust per cubic metre of air (expressed as mg/m3) as an 8-hour time-weighted average exposure, or a lower permissible exposure limit. OUTCOMES: Acute symptoms of grain-dust exposure, such as cough, phlegm production, wheezing and dyspnea, similar chronic symptoms, and spirometric deficits revealing obstructive or restrictive disease. EVIDENCE: Articles published from 1924 to December 1993 were identified from Index Medicus and the bibliographies of pertinent articles. Subsequent articles published from 1994 (when the recommendations were approved by the Canadian Thoracic Society Standards Committee) to June 1996 were retrieved through a search of MEDLINE, and modification of the recommendations was not found to be necessary. Studies of interest were those that linked measurements of total grain dust levels to the development of acute and chronic respiratory symptoms and changes in lung function in exposed workers. Papers on the effects of grain dust on workers in feed mills were not included because other nutrients such as animal products may have been added to the grain. Unpublished reports (e.g., to Labour Canada) were included as sources of information. VALUES: A high value was placed on minimizing the biological harm that grain dust has on the lungs of grain workers. BENEFITS, HARMS AND COSTS: A permissible exposure limit of 5 mg/m3 would control the short-term effects of exposure to grain dust on workers. Evidence is insufficient to determine what level is needed to prevent long-term effects. The economic implications of implementing a lower permissible exposure limit have not been evaluated. RECOMMENDATIONS: The current Canadian standards for grain-dust exposure should be reviewed by Labour Canada and the grain industry. A permissible exposure level of 5 mg/m3 is recommended to control short-term effects. Further measurements that link the levels of exposure to respiratory health effects in workers across Canada should be collected to establish an exposure-response relation and possible regional differences in the effects of grain dust. VALIDATION: There has been no external review of these recommendations. However, the American Conference of Governmental Industrial Hygienists has recommended an 8-hour average exposure limit of 4 mg/m3 for wheat, oats and barley.

Air Pollutants, Occupational↗
PubMed1996

Multidrug resistance in ocular melanoma.

AIMS/BACKGROUND: Metastatic disease in patients with ocular melanoma is resistant to chemotherapy. One of the main mechanisms of modulating multidrug resistance is the expression of the multidrug resistance gene 1 (MDR1) product (p-glycoprotein) by tumour cells. The purpose of this study was to evaluate the frequency of expression of the MDR1 gene in ocular melanoma whose primary treatment was surgical excision or enucleation. METHODS: Twelve recent ocular melanomas were received fresh, snap frozen and cryostat sections of tumour were analysed for expression of MDR1 by immunohistochemistry using a well characterised monoclonal antibody to MDR1. Tumour explants were established in short term tissue culture from four tumours and cell blocks were examined by immunohistochemistry. RESULTS: MDR1 expression was present in five of 12 ocular melanomas. Upregulation of protein expression was found in four cell lines established in short term culture from tumour explants. A recurrent tumour, initially treated by local excision and radioactive plaque, showed overexpression of MDR1 mRNA. CONCLUSIONS: These results suggest that significant level of MDR1 may be intrinsically present in ocular melanomas before exposure to drugs involved in multidrug resistance, and indicate the possible importance of MDR1 in modulating chemoresistance in ocular melanoma. Chemosensitisation may be of potential value in planning adjuvant chemotherapy for patients with metastatic disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Comparison of dust related respiratory effects in Dutch and Canadian grain handling industries: a pooled analysis.

OBJECTIVES: Four previously conducted epidemiological studies in more than 1200 grain workers were used to compare exposure-response relations between exposure to grain dust and respiratory health. METHODS: The studies included Dutch workers from an animal feed mill and a transfer grain elevator and Canadian workers from a terminal grain elevator and the docks. Relations between forced expiratory volume in one second (FEV1) and exposure were analysed with multiple regression analysis corrected for smoking, age, and height. Exposure variables examined included cumulative and current dust exposure and the numbers of years a subject was employed in the industry. Sampling efficiencies of the Dutch and Canadian measurement techniques were compared in a pilot study. Results of this study were used to correct slopes of exposure-response relations for differences in dust fractions sampled by Dutch and Canadian personal dust samplers. RESULTS: Negative exposure-response relations were shown for regressions of FEV1 on cumulative and current exposure and years employed. Slopes of the exposure-response relations differed by a factor of three to five between industries, apart from results for cumulative exposure. Here the variation in slopes differed by a factor of 100, from -1 to -0.009 ml/mg.y/m3. The variation in slopes between industries reduced to between twofold to fivefold when the Dutch transfer elevator workers were not considered. There was evidence that the small exposure-response slope found for this group is caused by misclassification of exposure and a strong healthy worker effect. Alternative, but less likely explanations for the variation in slopes were differences in exposure concentrations, composition of grain dust, exposure characteristics, and measurement techniques. CONCLUSION: In conclusion, this study showed moderately similar negative exposure-response relations for four different populations from different countries, despite differences in methods of exposure assessment and exposure estimation.

Adult↗
PubMed1996

Western red cedar dust exposure and lung function: a dose-response relationship.

The relationship between levels of cumulative red cedar dust exposure and decline in lung function was explored in an 11-yr follow-up study of 243 sawmill workers who participated in at least two occasions. We also studied 140 office workers in a similar manner as control subjects. Workers with asthma were excluded from the analysis. During the period of the study, 916 personal and 216 area samples of dust were collected from the sawmill. Cumulative wood dust exposure was calculated for each sawmill worker according to the duration and exposure in each job, based on the geometric mean of all dust measurements for that job. Average daily dust exposure was calculated by dividing the total cumulative exposure by the number of days of work. Workers were divided into low-, medium-, and high-exposure groups with mean daily level of exposure of < 0.2, 0.2 to 0.4, and > 0.4 mg/m3, respectively. Sawmill workers had significantly greater declines in FEV1 and FVC compared with office workers adjusted for age, smoking, and initial lung function. A dose-response relationship was observed between the level of exposure and the annual decline in FVC. We conclude that exposure to Western red cedar dust is associated with a greater decline in lung function which may lead to development of chronic airflow limitation.

Adult↗
PubMed1996

Parathyroid hormone stimulation of calcium transport is mediated by dual signaling mechanisms involving protein kinase A and protein kinase C.

PTH stimulates calcium absorption by renal distal convoluted tubules. The PTH receptor is capable of coupling to adenylyl cyclase and phospholipase C. However, it is not known whether the actions of PTH require activation of both pathways. Three approaches were taken to identify the signaling pathways responsible for stimulating calcium entry in distal convoluted tubule cells: second messengers formed in response to PTH were identified, the effects on calcium uptake of inhibiting protein kinase A (PKA) or protein kinase C (PKC) with chemical or peptide blockers were determined, and calcium transport was reconstituted by the addition of exogenous second messengers. PTH increased cAMP formation in primary cultures of mouse distal and proximal tubule cells. However, PTH stimulated inositol trisphosphate formation only in proximal tubule cells. Blocking PKA with Rp-cAMPS or the cAMP-dependent protein kinase inhibitor inhibited PTH-stimulated Ca uptake. Likewise, the PKC inhibitors, calphostin C and PKC pseudosubstrate, inhibited PTH-induced calcium uptake. Addition of forskolin (30 nM) or phorbol 12-myristate 13-acetate (10 nM) alone had no effect on Ca uptake. However, when added in combination, Ca uptake was stimulated to nearly the same extent as with concentrations of PTH that maximally stimulate calcium transport. We conclude that stimulation of calcium uptake by distal convoluted tubule cells requires activation of both PKA and PKC.

Animals↗
PubMed1995

Prevalence and predictors of asthma in working groups in British Columbia.

We evaluated the prevalence of asthma and its predictors in studies of several male working groups: 619 cedar sawmill, 724 grain elevator, 399 pulpmill, 798 aluminum smelter, and 1,127 unexposed workers. These workers had taken part in health studies for assessment of chronic respiratory effects of various workplace exposures between 1979 and 1982. The American Thoracic Society Adult Questionnaire (ATS-DLD-78) was used for these studies. Allergy skin tests were also performed. The participation rates were > 80%. The overall prevalance of physician-diagnosed asthma was 4.6%, and current asthma 3%. The prevalence of asthma after employment in the current industry, as a surrogate for work-related asthma, was 3.9 times higher in cedar sawmill workers, 2.2 times higher in pulpmill and aluminum smelter workers, and 1.7 times higher in grain elevator workers compared with unexposed workers. Atopy and a positive parental history of asthma, but not smoking, were important risk factors for asthma before the onset of first employment. Also, for asthma after employment in the current industry, atopy and a positive parental history of asthma were important risk factors. Smoking was associated with a significant reduction in the risk for asthma after employment in the current industry. Within specific work groups, the prevalence of atopy was significantly higher among pulpmill workers with asthma after employment in current industry than those without asthma. Conversely, cedar sawmill workers who had asthma after employment in the current industry were nonatopic and nonsmokers.

Adult↗
PubMed1995

Association of Epstein-Barr virus with sinonasal angiocentric T cell lymphoma.

AIM: To investigate whether non-Hodgkin's lymphomas arising in the sinonasal region or Waldeyer's ring contain the Epstein-Barr virus (EBV) genome in lesional tissue. METHOD: Sections from paraffin wax blocks of 22 lymphoid proliferations arising in the sinonasal region or Waldeyer's ring were studied with EBV encoded RNAs (EBER-1 and -2) using in situ hybridisation. RESULTS: EBV was detected in nuclei of tumour cells of five of seven T cell lymphomas and in nuclei of two of seven diffuse, large cell immunoblastic lymphomas of B phenotype in the sinonasal region. Of tumours arising in Waldeyer's ring, two of 10 non-Hodgkin's lymphomas (both large cell) were positive, as was a single case of Hodgkin's disease. Lymphoma of other types, including Western type Burkitt's lymphoma, and nodular and diffuse small cleaved cell lymphoma, were negative. CONCLUSION: EBV is highly associated with large cell lymphomas especially T cell lymphomas of sinonasal origin in the indigenous Irish population, underlining the importance of this virus in nasopharyngeal lymphomas in Northern European as well as Asian populations.

Adolescent↗
PubMed1995

Maintenance of stellite and tungsten carbide saw tips: respiratory health and exposure-response evaluations.

OBJECTIVE: To study exposure to cobalt and chromium in saw maintenance rooms and test respiratory health among saw filers at lumber mills. Hard-metal lung disease is associated with cobalt in the manufacture of tungsten carbide tools; recently it has also been reported among tool maintenance workers. Lumber mills often use saws tipped with tungsten carbide or with a newer alloy, stellite (containing more cobalt, as well as chromium). METHODS: A cross sectional study of 118 saw filers at eight lumber mills was carried out that included a standardised questionnaire, spirometry, personal air sampling, and examination of tasks every 10 minutes (by observation). Comparison data were from a study of bus mechanics tested with similar methods. RESULTS AND CONCLUSION: Cobalt exposure was associated with tungsten carbide grinding but not with stellite grinding. Chromium exposure was associated mainly with stellite welding. Saw filers had a twofold increase in phlegm and wheeze (P < 0.01) and a threefold increase in cough, phlegm, and wheeze related to work (P < 0.001), but no increase in breathlessness. Stellite welding was associated with a significant increase in nasal symptoms and cough related to work and a small decrease in airflow (forced expiratory volume in one second/forced vital capacity (FEV1/FVC%), P < 0.05). Saw filers wet grinding with tungsten carbide had significant reductions in forced expiratory lung volumes (FEV1 and FVC, P < 0.05) and were significantly more likely to have FEV1 and FVC values in the abnormal range. Cobalt exposure (in wet grinding) and duration of work that involved tungsten carbide grinding were both associated with significant reductions in FEV1 and FVC. Average cobalt exposures in this study were about 5 micrograms/m3, well below the currently accepted permissible concentration, which suggests that the current workplace limit for cobalt may be too high.

Adult↗
PubMed1995

Evaluation of the respiratory health of dock workers who load grain cargoes in British Columbia.

OBJECTIVES: To investigate the respiratory health of dock workers who load grain cargoes. METHODS: The respiratory health of 118 dock workers who load grain cargoes in the ports of Vancouver and Prince Rupert was compared with that of 555 grain elevator workers from the same regions. 128 civic workers were used as an unexposed control group. RESULTS: The prevalences of chronic cough and phlegm were at least as high in dock workers as those found in the elevator workers, and when adjusted for differences in duration of employment and smoking, dock workers had an eightfold higher risk of developing chronic phlegm than did civic workers. Symptoms of eye and skin irritation that were experienced at least monthly were highest for dock workers. Average percentage of the predicted FEV1 and FVC for dock workers (mean 100.6% and 105.3% respectively) were similar to the civic workers but significantly higher than those found for elevator workers. Higher subjective estimates of duration of exposure to grain dust (hours/day) were associated with lower values of FEV1. CONCLUSIONS: The more intermittent grain dust exposure patterns of dock workers may have allowed for some recovery of lung function, but chronic respiratory symptoms were less labile.

Adult↗
PubMed1994

Effect of different questionnaire formats on reporting of occupational exposures.

During an exposure monitoring study, 78 saw maintenance tradesmen were randomly assigned to be interviewed about their exposures using one of two questionnaire formats: open-ended and partly prompted questions about five categories of materials; and detailed prompting about 75 agents. The more open-ended questionnaire elicited fewer exposure responses overall, but more responses about agents not included on the detailed questionnaire. Composite materials and trade name products were more frequently cited as exposures than individual metals or compounds. Validity of responses was ascertained using air measurements (individual metals) or observations of the employees (composite materials). Sums of sensitivities and specificities were very low (near 1.0) for most of the metals for both types of questionnaire. For composite materials, validity improved substantially. Sensitivities with the partly promoted format (0.44-0.85) were always lower than with detailed prompting (0.80-1.00). Specificities were usually, but not always, higher with partial prompting (0.66-0.92) than with detailed prompting (0.18-0.86). Selection of questionnaire format for an epidemiologic study would depend on the likely prevalence of exposure in controls and the effects of trade-offs in sensitivity and specificity.

Data Collection↗
PubMed1994

Overexpression of the oncoprotein p53 in primary hepatic tumors of childhood does not correlate with gene mutations.

High levels of expression of the p53 protein and gene mutations have been described in adult hepatocellular carcinomas. It has been postulated that specific mutations in exon 7 may be caused by aflatoxin exposure. To determine whether p53 mutations occur in childhood liver cancer unassociated with aflatoxin exposure or hepatitis B virus (HBV) infection, we have analyzed three histologically distinct tumor types. Two techniques were used to access p53 in the tumors: (1) expression studies of the p53 protein were performed using the polyclonal antibody CM1 and immunohistochemistry, and (2) DNA sequencing was performed. p53 Protein was detectable by immunohistochemistry in 10 of 15 hepatoblastomas, six of nine hepatocellular carcinomas, and one of one embryonal sarcomas. Solid phase single-stranded DNA sequencing across exons 5 through 9 showed normal sequence in all cases. These results indicate that p53 is overexpressed in a majority of childhood liver cancers, but this abnormal p53 expression does not seem to be caused by mutations in the p53 gene.

Base Sequence↗
PubMed1994

Pathology of hereditary retinal degeneration associated with hypobetalipoproteinemia.

BACKGROUND: The clinical features and previously unreported ocular pathology in a case of heterozygous hypobetalipoproteinemia (HBL) associated with a pigment epitheliopathy are documented. Night blindness developed in a white woman with familial heterozygous HBL (cholesterol and low-density lipoprotein levels < 5% of normal) at 51 years of age. Ophthalmoscopy showed bilateral symmetric depigmentation at the posterior pole with pigment clumping and pavingstone configuration in the periphery. By the time the patient died, at 75 years of age, vision had deteriorated to hand motions. METHODS: One eye was removed 2 hours postmortem for light and electron microscopic study. RESULTS: The photoreceptors were absent, and the outer nuclear layer was replaced by glial cells throughout most of the retina, but there was some focal photoreceptor preservation in isolated regions. The outstanding feature was a massive deposition of basal linear deposit which was calcified in segments and which contained macrophages and the processes of glial cells: trilaminar bodies and melanin granules were identified in the macrophages. The remaining retinal pigment epithelial cells contained melanin but very little lipofuscin: intraretinal migration was minimal. CONCLUSIONS: The authors postulate that the pigment epitheliopathy associated with HBL is an abiotrophy in which photoreceptor discs are unable to regenerate due to locally disordered metabolism resulting from or acting in concert with the pigment epitheliopathy.

Aged↗
PubMed1994

Effect of grain exposure and smoking on the longitudinal changes in immediate skin reactivity.

The study was carried out to investigate the effect of occupational exposure and smoking on the longitudinal changes of immediate skin reactivity over 3 years in working populations. A total of 480 grain elevator workers and 707 transit and ferry (control) workers were included because they had allergy skin tests on both surveys. Skin-prick texts using three common allergens and a negative and histamine controls were administered during both surveys. The reaction was considered positive if the mean weal size was 3 mm or greater than that of the negative control. Conversion was defined as a change from the non-atopic state in the initial survey to the atopic state in the follow-up survey. Reversion was defined as a change from the atopic state in the initial survey to the non-atopic state in the follow-up survey. The findings showed that grain workers had two times risk of conversion than control workers. Recent smokers, who changed their habit from non-smoker/ex-smoker to smoker in the follow-up survey, were at a three times risk of conversion than non-smokers. The reversion of skin-test reactivity was not associated with age, smoking habits, or working exposure. When investigating studies of longitudinal changes in immediate skin reactivity, the effects of age, changes in smoking habit and occupational exposure should be considered.

Adult↗