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Biomedical subjects

S M Kennedy

Publications and source records attributed to S M Kennedy.

At least 73 records · Page 4Linked to original sources

Assessment of respiratory limitation in activities of daily life among retired workers.

Epidemiologic studies of occupational lung diseases generally compare symptoms and pulmonary function between groups with differing exposure risks. However, the functional consequences (e.g., on activities of daily life) of statistically significant group differences in either symptoms or pulmonary function are rarely addressed. An understanding of this is important for both the scientific investigators and users of these public health investigations. To address this issue, we developed a 15-item questionnaire to assess breathing-related limitations in activities of daily life, and applied this in a study of 112 retired workers. For each subject, we calculated a limitation score as the number of items associated with breathing difficulty divided by the total number of applicable items. Results from this questionnaire were compared to respiratory symptoms, the Sickness Impact Profile (SIP), lung function test results, 6-min walking distance, and participants' assessment of breathing effort after the walk. The limitation score was significantly higher in subjects reporting dyspnea (22% versus 4%, p < 0.01) or occasional wheeze (27% versus 6%, p < 0.01), and correlated negatively with FEV1, MMEF, and FEV1/FVC (R2 = -0.47, -0.36, and -0.45, respectively, p < 0.0001) and breathing effort after the 6-min walk (R2 = 0.31, p < 0.01). Breathing related limitation in daily activities was also associated with a general health related limitation in household maintenance and ambulation in the SIP (p < 0.01). For each questionnaire item, we compared the responses among subjects with a normal FEV1 to those of subjects with an abnormal FEV1 (below the lower 95% confidence limit).(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

Persistent asthma after repeated exposure to high concentrations of gases in pulpmills.

This is a clinicopathologic study of three subjects with irritant-induced asthma. They were pulpmill workers who had a history of multiple "gassing" episodes that occurred over a period of years. Persistent symptoms of asthma and nonspecific bronchial hyperresponsiveness and/or variable airflow obstruction occurred after at least one episode of "gassing," resulting in symptoms severe enough to require emergency room treatment. One of the three subjects had normal spirometry values before he entered the pulpmill. Bronchial biopsy done on these subjects showed changes compatible with asthma, including thickened basement membrane in two and cellular infiltration with activated eosinophils and mononuclear cells in all three. The results of immunohistology of bronchial mucosal biopsy of these subjects were compared with those of patients with allergic asthma and patients with Western red cedar-induced asthma. Subjects with irritant-induced asthma had a greater density of activated eosinophils and fewer T-lymphocytes, suggesting that cell-mediated immune mechanisms are not involved in the pathogenesis of this condition.

Adult↗

Respiratory health among retired grain elevator workers.

Previous studies of grain elevator workers have shown exposure-related increased rates for respiratory symptoms and reduced levels of lung function compared with those of other employed populations. However, some reports have suggested that this effect may be reversible after cessation of exposure. To investigate this, we conducted a respiratory health survey among 75 retired grain elevator workers and 37 retired civic workers. Methods included a standard respiratory questionnaire, routine spirometry, chest radiography, a 6-min walk test, and a specialized questionnaire to assess the impact of breathing trouble on the activities of daily life. Grain retirees were slightly older than civic retirees (69 versus 67 yr, p < 0.05) and less likely to be atopic (7 versus 35%, p < 0.01). Grain elevator retirees reported more dyspnea (44 versus 11%, p < 0.01) and had significantly lower levels for both FEV1 (78.6 versus 88.2% pred) and FVC (90.0 versus 97.7% pred) (both p < 0.05). Compared with civic retirees, grain retirees reported the same average level of breathlessness after the 6-min walk test, but they walked a significantly shorter distance (p < 0.01); they also scored higher on the impairment of activities scale and had a greater proportion of persons reporting impairment of daily activities caused by breathing trouble (p < 0.05). Comparison of the changes in lung function from 1975 to the present study (i.e., from active employment to retirement) showed that grain workers had consistently lower levels of lung function than did civic workers while still employed, with no reversibility after retirement.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

Clinical and socioeconomic features of subjects with red cedar asthma. A follow-up study.

A follow-up study of 128 subjects with red cedar asthma was conducted to evaluate the clinical and socioeconomic impact of the disease in determining the working status of the subjects after the diagnosis was made. The results suggest that the severity of asthma is not the main determinant of working status. Comparing the data at diagnosis and at follow-up examination, we found that the persistence of exposure resulted in a deterioration in the asthma despite the use of more medications. Subjects who were working were younger and had a larger number of dependents than the subjects who were not working at the time of the follow-up examination. We conclude that the socioeconomic factors are important in determining the working status of subjects with red cedar asthma. To prevent severe impairment and disability, there should be more economic incentives for these subjects to choose other jobs.

Adult↗

Five cross-sectional studies of grain elevator workers.

Five cross-sectional studies were conducted on grain workers in all the terminal elevators in British Columbia, Canada, at 3-year intervals from 1976 to 1988. Civic workers were studied in the same manner as a referent group. The studies consisted of questionnaires, spirometry using the same spirometers, allergy skin tests, and measurement of dust concentration by personal sampling. Although the dust concentration in the elevators was reduced progressively over the years, grain workers had more respiratory symptoms and lower lung function compared with the civic workers in each of the five cross-sectional studies. Exposure to grain dust was associated with significant reduction in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) but not in maximal midexpiratory flow rate or FEV1/FVC, suggesting reduction in volume which may be due to lesions in the lung parenchyma or in the small airways. Cigarette smoking was associated with significant reduction in FEV1, maximal midexpiratory flow rate, and FEV1/FVC due to airflow obstruction, but had no influence on FVC. Workers who took part in all five surveys tended to be a "healthier" selected group, but the grain workers still had lower lung function compared with the civic workers. This study confirmed previous findings that grain dust has adverse effects on the lungs. Cross-sectional study of the grain elevator workers proved to be a consistent and useful method to evaluate occupational health hazards.

Adult↗

Bilateral Kimura's disease of the eyelids.

A case of Kimura's disease affecting the eyelids bilaterally is reported in a 5-year-old boy of Afro-Caribbean extraction who has been followed for 12 years with repeat biopsies. He initially presented at 5 years of age with swelling of the left upper eyelid, left cervical lymphadenopathy, and eosinophilia. One year later he developed swelling of the right upper eyelid. There has been no change in the clinical appearance over the next 12 years. Repeated biopsies of the eyelids showed a diffuse inflammatory infiltrate with many eosinophils and lymphocytes. A lymph node biopsy showed reactive lymphoid hyperplasia. Immunohistochemistry using lymphoid markers showed a polyclonal pattern. Kimura's disease is a rare cause of eyelid swelling, particularly at such a young age and with bilateral involvement. This case demonstrates that bilateral orbital lymphoid lesions with cervical node involvement do not always imply lymphoma, but may have a benign pathogenesis. The unusually long follow up in this case confirms an excellent prognosis for Kimura's disease with conservative management. Accurate diagnosis in small orbital biopsies may spare the patient unnecessary radical surgery.

Angiolymphoid Hyperplasia with Eosinophilia↗

Methacholine responsiveness, smoking, and atopy as risk factors for accelerated FEV1 decline in male working populations.

Longitudinal lung function data from four occupational health surveys was used to explore the relationship between nonspecific bronchial responsiveness (NSBR) and the rate of decline of FEV1 (RDFEV) and to address other factors that may predict or influence RDFEV. Of the 1,203 subjects with baseline methacholine and lung function data, follow-up data were available for 733 individuals (61%). The data-available and data-unavailable groups were well matched with respect to baseline lung function, atopy, and smoking status. Compared with the unavailable group, those available for follow-up were younger (42.5 versus 37.7 yr; p less than 0.0001) and slightly less responsive to methacholine (p less than 0.01). Somewhat unexpectedly, RDFEV was lower in the 30 asthmatic subjects than in the nonasthmatics. Among the nonasthmatic subgroup (96% of those available for follow-up), age, occupational group, and baseline FEV1 (% predicted) were independent predictive factors for RDFEV. When these factors were included in the model, RDFEV was found to be increased among current smokers compared with never-smokers or ex-smokers. In the final regression model, a relationship was found between methacholine sensitivity (calculated as a dose-response slope) and RDFEV in nonasthmatics (p less than 0.05). Stratification by smoking status revealed that the relationship between RDFEV and bronchial responsiveness was confined to current smokers and that atopy was an additional risk factor in this subgroup only. This relationship was valid among current smokers in each of the three occupational groups studies. However, reinclusion of the 30 asthmatic subjects in the study population obscured the relationship between NSBR and RDFEV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Detection of dysplasia and carcinoma in situ by ratio fluorometry.

Fluorescence bronchoscopy was performed in 82 volunteers recruited from occupational groups at risk of exposure to asbestos and/or diesel fumes to determine whether differences in tissue autofluorescence between normal and malignant bronchial tissues can be used to improve the sensitivity of standard fiberoptic bronchoscopy in detecting dysplasic and carcinoma in situ (CIS). This study consisted of 25 nonsmokers, 40 exsmokers, and 17 current smokers with mean ages of 52, 55, and 49 yr, respectively. Tissue autofluorescence was induced by a blue light from an He-Cd laser coupled to the illumination channel of the bronchoscope and analyzed by a ratiofluorometer. One or more sites of moderate or severe dysplasia were found in 12% of the exsmokers and current smokers but in none of the nonsmoker volunteers. CIS was found in two of the exsmokers. The sensitivity of fluorescence bronchoscopy (86%) was found to be 50% better than that of conventional white-light bronchoscopy (52%) in detecting dysplasia and CIS. Pre- and post-bronchoscopy sputum cytology failed to detect these precancerous lesions. Our results suggest that fluorescence bronchoscopy may be an important new method that can improve the ability to detect and localize precancerous and/or CIS lesions.

Asbestos↗

First-aid reports of acute chlorine gassing among pulpmill workers as predictors of lung health consequences.

Workers in pulpmills can be exposed to a multitude of gases hazardous to respiratory function, the most common of which is chlorine gas. First-aid reports of acute gas overexposure incidents ("gassings") over an 8 year period were used to generate exposure data on a group of pulpmill workers whose respiratory function had been studied cross-sectionally in 1981 and 1988. Three hundred forty-eight incidents representing 174 workers were identified, 78% of these being treated solely by the first-aid attendant with the administration of O2 and cough suppression medication. Among 316 workers tested during a 1988 respiratory health survey, 78 had at least one chlorine or chlorine dioxide "gassing" incident. There was a significant decrease in the FEV1/FVC ratio (p less than .05) as well as increased risk for workplace associated chest symptoms in this group with at least one "gassing" incident. In an age- and smoking-matched analysis, among workers tested both in 1981 and 1988, there was a greater decline in FEV2/FVC ratio and MMF (p less than .05) in the "gassed" group than in the nonexposed group over the 7 year period of observation. These results emphasize the need for worker protection against accidental chlorine gas exposures.

Analysis of Variance↗

Lung function and chest radiograph abnormalities among construction insulators.

We carried out a prevalence survey of pulmonary health parameters among current and retired construction insulators (50 years old and older) from all areas of British Columbia, Canada. The study population included 59 active workers (81 percent participation in this group) and 29 workers who were retired or inactive due to illness (69% participation). Radiograph results were compared to those from actively working bus mechanics from the same age group, and retired grain and civic workers, who were all tested in the same manner. Chest radiographs were read independently by two readers and were graded according to the ILO classification system. Pleural abnormalities alone were found in 34% (20) of active workers (5% in comparison group) and 45% (13) of non-active workers (14% in comparison group). Rates for parenchymal abnormalities for these same groups (ILO grade 1/0 or higher) were 17% (5%) and 20% (5%), respectively. Airflow obstruction was present in 35% (31) of the insulators and was associated with age and the presence of diffuse pleural thickening, and 5 or more years of employment in pulp mills. Restrictive lung function was present in 22% (19) of the insulator population and was associated with age and radiographic evidence of parenchymal fibrosis. The results indicate that construction insulators, a group at high risk for asbestos-related lung disease, also have a high prevalence of airflow obstruction. This was associated not only with smoking, but also with diffuse pleural thickening and a history of pulp-mill employment, suggesting that airflow obstruction in this population is also partly work related.

Aged↗

Immunomagnetic separation, primary culture, and characterization of cortical thick ascending limb plus distal convoluted tubule cells from mouse kidney.

Renal cortical thick ascending limbs of Henle's loop (CAL) and distal convoluted tubules (DCT) represent sites at which much of the final regulation of urinary ionic composition, particularly that of calcium, is accomplished in both humans and in rodents. We sought in the present work to develop an efficient means for isolating parathyroid hormone (PTH)-sensitive cells from these nephron segments and to grow them in primary culture. [CAL+DCT] cells were isolated from mouse kidney using an antiserum against the Tamm-Horsfall glycoprotein which, in the renal cortex, is produced exclusively by these cells. A second antibody conjugated to coated ferrous particles permitted magnetic separation of [CAL+DCT] cells from Tamm-Horsfall negative renal cortical cells. Approximately 3 X 10(6) cells per kidney with a trypan blue exclusion greater than 94% were isolated by these procedures. Experiments were performed to characterize the cells after 7 to 10 days in primary culture. PTH and isoproterenol, but neither calcitonin nor vasopressin, stimulated cyclic AMP (cAMP) formation in [CAL+DCT] cells, consistent with the pattern of hormone-activated cAMP synthesis found in freshly isolated CAL and DCT segments. Alkaline phosphatase, an enzyme present dominantly in proximal tubule brush border membranes, was virtually absent from [CAL+DCT] cells but was present in Tamm-Horsfall negative cells. Similarly, Na-glucose cotransport was absent in [CAL+DCT] cells but present in Tamm-Horsfall negative renal cortical cells. Finally, transport-related oxygen consumption in [CAL+DCT] cells was blocked by bumetanide and by chlorothiazide, diuretics that inhibit sodium transport in CAL and DCT nephron segments. These results demonstrate that PTH-sensitive [CAL+DCT] cells can be isolated in relatively high yield and viability and grown in cell culture. Primary cultures of these cells exhibit a phenotype appropriate to their site of origin in the nephron.

Animals↗

Lung health consequences of reported accidental chlorine gas exposures among pulpmill workers.

The long-term consequences of accidental chlorine gas exposure have been investigated, mainly in the community setting, among persons exposed as a result of a nearby chlorine spill. This circumstance is not analogous to the more frequent chlorine or chlorine dioxide gas overexposures that occur commonly in pulpmills over a background of a low level of gas exposure. To investigate the respiratory health consequences of these accidental exposures ("chlorine gassing") in the industrial setting, we carried out a cross-sectional respiratory health survey among workers at a British Columbia coastal pulpmill and a nearby rail maintenance yard. A greater proportion of pulpmill workers were unavailable for study because of illness (10.5% versus 2.4% in the railyard, p less than 0.01). Procedures involved simple spirometry, respiratory symptom assessment, and measurement of average levels of air contaminants. Average chlorine levels in the pulpmill were below 1 ppm; however, 60% of the pulpmill workers reported one or more accidental "chlorine gassing" incidents. Pulpmill workers who reported being "gassed" were significantly more likely to report wheezing on occasion than were other pulpmill workers and railyard workers (rate for these three groups: nonsmokers: 8, 2, 1%; ex-smokers: 17, 11, 7%; current smokers: 42, 21, 19%; p less than 0.05). No significant lung function differences were found between the overall pulpmill group and the railyard workers; however, nonsmoking and formerly smoking pulpmill workers who reported being "gassed" had significantly lower average midmaximal flow rate and FEV1/FVC ratio than did their counterparts in the remainder of the pulpmill population (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Occupational↗

Grain dust and lung function. Dose-response relationships.

Grain dust exposure has been associated with both acute and chronic respiratory abnormalities. We sought to answer two questions with regard to this exposure: (1) is there a dose-response relationship between grain dust and respiratory abnormalities, and (2) is there evidence to suggest that the allowable exposure (currently 10 mg/m3 in Canada) be lowered? We compared respiratory symptoms and lung function among 454 grain elevator workers and 55 civic workers to estimates of lifetime average grain dust exposure. A total of 781 personal air samples representing 20 different job titles over a 15-yr period were used to construct a job title-time period matrix for average dust exposure levels. The matrix was applied to each worker's detailed job history to obtain a value for estimated cumulative and average dust exposure. Significant dose-response relationships were seen for chronic phlegm production, breathlessness on exertion, FEV1, and FVC; and dose-response trends were evident for the longitudinal change in both FEV1 and FVC. Workers with estimated average exposure between 4 and 9 mg/m3 were found to have significantly lower values for FEV1 and FVC compared to both grain workers exposed to less than 4 mg/m3 on average and civic workers, despite no difference in duration of employment among these groups. The results indicate a strong dose-response relationship between grain dust exposure and both respiratory symptoms and lung function and also suggest that the current Canadian allowable exposure level of 10 mg/m3 is too high.

British Columbia↗

Polycystic kidneys, pancreatic cysts, and cystadenomatous bile ducts in the oral-facial-digital syndrome type I.

Oral-facial-digital syndrome type I is a group of X-linked dominant conditions, lethal in utero in male individuals. Internal anomalies are less well documented than are external findings. We report a case of typical phenotype and absent family history of kidney disease in a 15-year-old white girl (46,XX) who died of renal failure and massive cerebral hemorrhage. At necropsy, the kidneys were greatly enlarged but of fairly normal shape. The cortex was replaced by thin-walled spherical cysts, 0.5 to 2.0 cm in diameter; the majority of the smaller cysts were located deep in the cortex, and the medulla contained lesser numbers of larger cysts. No distal urinary tract obstruction was present. Microdissection revealed cysts and diverticula located in all segments of the nephrons and collecting ducts. Uninvolved nephrons showed diffuse hypertrophy. These findings were correlated with immunoperoxidase stains using peanut lectin, Lotus tetragonolobus agglutinin, antibodies to cytokeratins, stage-specific embryonic antigen-1, Tamm-Horsfall protein, and epithelial membrane antigen. Other visceral anomalies included biliary cystadenomatous proliferation in the liver and pancreatic cysts. The renal changes are similar to those of autosomal dominant (adult-type) polycystic disease.

Adolescent↗

Collecting duct carcinoma of the kidney.

Collecting duct carcinoma is an unusual variant of renal cell carcinoma, whose appearance and behavior are not well established. We identified six cases of collecting duct carcinoma in our files. The clinical, pathologic, and immunohistochemical characteristics of these tumors are reported. The most common symptom was gross hematuria (four cases). Two patients had cervical adenopathy due to metastatic tumor. Four rapidly developed systemic metastases and died within 4 to 24 months. The primary renal tumors were located predominantly in the renal medulla and pelvis and had a partially cystic white-gray appearance. Histologic examination showed prominent tubulopapillary structures, nests of clear cells, and infiltrating tubules in a dense desmoplastic stroma. Atypical hyperplastic changes were found in some of the adjacent collecting ducts. Mucicarminophilic material was present in glandular elements in all six cases. Immunohistochemical studies revealed positivity with antibodies to epithelial membrane antigen, keratins, peanut agglutinin, vimentin, Leu M1 and lysozyme. The location of this tumor in the medulla, its distinctive histologic appearance, mucin positivity, expression of high molecular weight cytokeratins, and peanut agglutinin suggest that this is a distinct clinicopathologic entity which has an aggressive clinical course.

Adult↗

Methacholine responsiveness among working populations. Relationship to smoking and airway caliber.

It has been suggested that the development of bronchial hyperresponsiveness (BHR) in some smokers may be an intermediate event in the progression to chronic obstructive pulmonary disease in this group. If this is true, prevalence data on BHR in a general population should show an independent association between BHR and smoking status. To test this, we analyzed BHR to inhaled methacholine in 654 white men without known asthma, in relation to smoking, skin-test reactivity, type of work (office versus industrial), and indicators of baseline airway caliber (FEV1 % predicted and FEV1/FVC). BHR was measured in the traditional way (PC20) and as the slope of FEV1 versus the methacholine concentration (linear scale). A PC20 of less than 16 mg/ml was considered "responsive" for analyses of this outcome. We found that although a positive skin test, smoking, and being an industrial worker all appeared to be significant predictors of increased BHR (p less than 0.05), once FEV1 (% predicted) and FEV1/FVC% were taken into account, none of these variables alone remained significantly associated with BHR. The strongest predictors of BHR were prechallenge FEV1 and FEV1/FVC (both p less than 0.01). The combination of smoking, atopy, and work groups, which identified a small subgroup of atopic smokers who were office workers, also remained significantly associated with increased BHR. We also used a regression model that allowed for comparison of predictors for BHR between the most responsive subset of the population (n = 84) and the remainder of the study population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗