Occupational health in British agriculture.
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Agricultural Workers' Diseases↗
Biomedical subjects
C Solomon
Publications and source records attributed to C Solomon.
Accidental injuries in agriculture in the UK.
The rate of occupational accidents in British agriculture is higher than in most other industries. The most common fatal accidents are those involving vehicles and machinery, falls from a height and electrocution. A substantial proportion of reported non-fatal injuries in agricultural employees is attributable to manual handling, but among self-employed farmers the contribution is much smaller. Few data are available on longer-term determinants of risk, but accidental deaths are most frequent in July, August and September. The main approaches to preventing agricultural accidents are through engineering improvements, and education and training of the workforce. The introduction of roll-over protection structures for tractors has been an important development in recent decades. Other engineering controls include guards for power take off shafts, guard rails to prevent falls, better handling facilities for animals and closed transfer systems for pesticides. Training on safety is available from several sources, but its effectiveness in reducing accidents is uncertain.
Accidents, Occupational↗
Chlorine exposure and the upper respiratory tract.
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Air Pollutants↗
Physical activity and risk for cardiovascular events in diabetic women.
BACKGROUND: Increased physical activity has been associated with reduced risk for cardiovascular disease in the general population, but data are limited on its role among persons with type 2 diabetes mellitus. OBJECTIVE: To determine whether physical activity decreases risk for cardiovascular disease among diabetic women. DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study. PATIENTS: 5125 female nurses with diabetes. MEASUREMENTS: Physical activity was first assessed in 1980 and was updated in 1982, 1986, 1988, and 1992 through validated questionnaires. Average hours of moderate or vigorous exercise and a metabolic equivalent of task (MET) score were computed. RESULTS: During 14 years of follow-up (31 432 person-years), 323 new cases of cardiovascular disease were documented (225 cases of coronary heart disease and 98 cases of stroke). The age-adjusted relative risks according to average hours of moderate or vigorous activity per week (<1, 1 to 1.9, 2 to 3.9, 4 to 6.9, >/=7) were 1.0, 0.93 (95% CI, 0.69 to 1.26), 0.82 (CI, 0.61 to 1.10), 0.54 (CI, 0.39 to 0.76), and 0.52 (CI, 0.25 to 1.09) (P < 0.001 for trend). These figures did not change materially after adjustment for smoking, body mass index, and other cardiovascular risk factors (1.0, 1.02, 0.87, 0.61, and 0.55, respectively; P = 0.001 for trend). In separate analyses, levels of physical activity were inversely associated with coronary heart disease and ischemic stroke. Among women who did not exercise vigorously, the multivariate relative risks for cardiovascular disease across quartiles of MET score for walking were 1.0, 0.85, 0.63, and 0.56 (P = 0.03 for trend). Faster usual walking pace was independently associated with lower risk. CONCLUSION: Among diabetic women, increased physical activity, including regular walking, is associated with substantially reduced risk for cardiovascular events.
Adult↗
Melanoma risk in relation to height, weight, and exercise (United States).
Height and weight and derivations thereof are positively associated with a number of cancers. While several authors have reported an increased risk of melanoma among people at the higher extremes of these measures, the association has not been fully explored. New cases of primary cutaneous melanoma in 1997 in western Washington State (n = 386) were compared to controls selected by random-digit dialing (n = 727). Each study participant completed a telephone survey, and data were collected on height, weight, sun-related melanoma risk factors, demographic characteristics, as well as habits such as diet and exercise. Risk of melanoma was analyzed by logistic regression with adjustment for age, hair color, lifetime sun exposure, and fruit and vegetable intake. An excess risk of melanoma was identified in men in the upper quartiles of height (OR = 2.4, 95% confidence interval (CI) = 1.3-4.5), weight (OR = 2.8, CI = 1.5-5.2), and body surface area (OR = 2.8, CI = 1.5-5.1) vs. the lowest quartiles. In women, no association was present for any anthropometric measure. In addition, we found that men and women exercising five to seven days per week were at a decreased risk of melanoma (OR = 0.7, CI = 0.5-1.0). The anthropometric findings are largely consistent with previous studies, while this is the first report of an association of exercise with melanoma risk. The mechanisms for the effect of exercise and for the difference between men and women in the effect of anthropometric factors are unknown. Future research in basic and epidemiologic science should focus on biochemical or behavioral explanations for these observations.
Adult↗
Interleukin-13 induces dramatically different transcriptional programs in three human airway cell types.
Interleukin (IL)-13, a cytokine released by T lymphocytes during immediate hypersensitivity responses, is a central mediator of asthma. Because IL-13 induces phenotypic features of asthma in mice deficient in T and B lymphocytes, it is likely that this cytokine contributes to the development of asthma by acting directly on resident airway cells. To analyze the global effects of IL-13 on gene expression in airway cells that could contribute to the phenotypic features of asthma, we used Genechip HuGene FL arrays (Affymetrix, Santa Clara, CA) that contain probes for approximately 6,500 human genes. Despite activating a common signaling pathway, IL-13 induced dramatically different patterns of gene expression in primary cultures of airway epithelial cells, airway smooth muscle cells, and lung fibroblasts, with little overlap among cell types. The most prominent effects of IL-13 were on airway smooth muscle, but several genes induced in airway epithelial cells and fibroblasts are also candidates that may contribute to phenotypic features of asthma. These results suggest that the in vivo response to IL-13 in the airways likely results from a combination of distinct effects on each of several resident airway cell types.
Cells, Cultured↗
The unique tryptophan residue of the vitamin D receptor is critical for ligand binding and transcriptional activation.
The human vitamin D receptor (hVDR) is a member of the nuclear receptor superfamily of transcriptional regulators. Here we show that tryptophan 286 of the hVDR is critical for ligand binding and transactivation of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] target genes. Two mutants of the hVDR were produced, W286A and W286F, in which the tryptophan was replaced with an alanine or a phenylalanine, respectively. The W286A mutant did not bind 1,25(OH)2D3, interact with steroid receptor coactivator 1 (SRC-1) in vitro, or activate transcription. Moreover, the W286A receptor did not heterodimerize in a ligand-dependent manner with the human retinoid X receptor alpha (hRXRalpha). Although the W286F receptor heterodimerized with hRXRalpha, interacted with SRC-1, and bound 1,25(OH)2D3, its capacity to transactivate was attenuated severely. Thus, tryptophan 286 of hVDR plays an important role in specific 1,25(OH)2D3 ligand interaction and subsequently in hVDR/RXR interaction, SRC-1 binding, and ligand-dependent transactivation of 1,25(OH)2D3 target genes. These results identify the first amino acid that is absolutely required for ligand binding in the VDR and further define the structure-function relationship of 1,25(OH)2D3 interaction with its receptor.
Amino Acid Substitution↗
Vitamin D resistance in RAS-transformed keratinocytes: mechanism and reversal strategies.
Human retinoid X receptor alpha (hRXRalpha) plays a critical role in DNA binding and transcriptional activity through its heterodimeric association with several members of the nuclear receptor superfamily, including the vitamin D receptor (VDR). Several cancer cell lines derived from different tissues have been shown to be resistant to the growth-inhibitory action of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], the biologically active metabolite of vitamin D(3). Here we show that in RAS-transformed keratinocytes, Ser260 of hRXRalpha is phosphorylated through the RAS-RAF-MAP kinase cascade. This phosphorylation event results in the inhibition of vitamin D signaling via VDR/hRXRalpha heterodimers. Strategies to reverse this resistance include the use of the MAP kinase inhibitor, PD098059, and a non-phosphorylatable hRXRalpha mutant, Ala260, which completely abolishes RXR phosphorylation and restores the function of both 1,25(OH)(2)D(3) and a specific RXR ligand, LG1069 (4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphtalenyl)ethenyl]-benzoic acid). In addition, we show that a vitamin D analog with low calcemic activity (EB1089) is more potent than 1,25(OH)(2)D(3) in inhibiting cancer cell growth in this system. Targeted therapy with selective analogs such as EB1089, in combination with the inhibition of phosphorylation of the RXR, could play a critical role in the development of strategies for cancer treatment.
Cell Division↗
Team spirit. Four steps to cleaning success.
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Efficiency, Organizational↗
Effects of azithromycin on ozone-induced airway neutrophilia and cytokine release.
Exposure of humans to ozone causes increased neutrophils and inflammatory cytokines in airway lining fluid. Recent research shows that macrolide antibiotics may reduce interleukin (IL)-8 production by bronchial epithelial cells and inhibit neutrophil chemotaxis. A double-blind, cross-over study was performed in which 12 healthy subjects underwent two separate 4-h exposures to 0.2 parts per million ozone while exercising intermittently. In the 73.5 h before exposure, subjects were pretreated with either 1,250 mg azithromycin or placebo. Sputum induction conducted 74 h pre- and 18 h post-exposure was used to measure total cells, per cent neutrophils, IL-6, and IL-8. There were significant (p<0.05) pre- to post-exposure increases in total cells, neutrophils, IL-6 and IL-8 in both the azithromycin and placebo arms. However, no significant differences were found between azithromycin and placebo conditions in the post- minus pre-exposure value for these variables. The results suggest that in healthy subjects, in the design used, azithromycin, in usual clinical doses, does not have anti-inflammatory effects on human airways as indicated in the measured variables.
Adult↗
Effect of serial-day exposure to nitrogen dioxide on airway and blood leukocytes and lymphocyte subsets.
Nitrogen dioxide (NO2) is a free radical-producing oxidant gas. Inhalation of NO2 could cause airway inflammation, and decrease immune function. This experiment tested the hypothesis that exposure to NO2 would: 1) increase leukocytes in bronchoalveolar lavage (BAL); and 2) change the distribution of lymphocyte subsets and activation in BAL and peripheral blood (PB). Using a counter-balanced, repeated-measures design, 15 healthy volunteers were exposed to filtered air (FA) or 2.0 parts per million NO2 for 4 h x day(-1) (4 x 30 min of exercise), for three consecutive days. Bronchoscopy was performed 18 h following each exposure set, and PB was drawn pre-exposure and pre-bronchoscopy. Flow cytometry was used to enumerate lymphocyte subsets and activation makers in BAL and PB. In the bronchial fraction, there was an increase in the percentage of neutrophils following NO2 exposure compared to FA (median (interquartile range): 10.6 (4.8-17.2)% versus 5.3 (2.5-8.3)%; p=0.005). In the BAL, there was a decrease in the percentage of T-helper cells following NO2 exposure compared to FA (55.9 (40.8-62.7)% versus 61.6 (52.6-65.2)%; p=0.022). For PB, there were no between-condition differences in any leukocyte or lymphocyte subsets, or activation. In conclusion exposure to nitrogen dioxide results in bronchial inflammation and a minimal change in bronchoalveolar lavage T-helper cells, and no changes in peripheral blood cells.
Adult↗
Variation in the quality of lumbar spine MR images in Washington State.
PURPOSE: To investigate the variation in quality of lumbar spine magnetic resonance (MR) images as a function of type of ownership of the imaging center, number of studies performed per month, specialty training of the image interpreter, and field strength of the MR unit. MATERIALS AND METHODS: Data were collected from all imaging facilities in western Washington state that received reimbursement from the Washington State Health Care Authority. Three readers with expertise in spine imaging, who were blinded to center and patient identification information, rated the technical image quality of each study. All MR images of the lumbar spine (maximum of six) paid for by the health care authority were evaluated. If a center had performed more than six studies, then six were randomly selected for evaluation. RESULTS: Variation in quality scores among sites was significant (P =.001). Field strength was the strongest predictor of better quality. Poorer quality was associated with for-profit ownership, a larger number of radiologists at the site reading MR images, and a larger percentage of studies checked by a radiologist prior to the end of the examination. CONCLUSION: There was significant variation in the quality of MR images of the lumbar spine, and at least a portion of this variation was attributable to characteristics of the imaging center.
Ambulatory Care Facilities↗
Recurrent varicose veins: patterns of reflux and clinical severity.
Duplex scanning was used to determine patterns of recurrent varicose veins in 264 limbs and to relate these to clinical factors. All limbs had previously undergone sapheno-femoral ligation in the groin. A recurrent sapheno-femoral junction was present in 172 (65.2%). Incompetence was found in long or short saphenous veins in 232 limbs (87.9%), perforators in 176 (66.7%), and deep veins in 156 (59.1%). Residual long saphenous veins were present in 43.4% and 73.6% of limbs that were with and without stripped long saphenous veins, respectively. An incompetent thigh perforator was present in 14.0% and 15.3% of these two groups, respectively. Multiple sites of incompetence were observed in the majority (75.4%). In general, no particular reflux pattern in the groin was related to an increased incidence of ulceration. However, ulceration was more frequent in limbs with deep reflux to knee or below-knee levels. None of those with isolated reflux in the groin that was unrelated to the common femoral vein had ulceration. The pattern of reflux was unrelated to striping or non-striping of the long saphenous veins and the time since initial surgery. A history of deep vein thrombosis was invariably associated with some degree of deep reflux. A system of recurrent patterns in the groin is described for the purpose of surgical audit. In 15.1%, recurrence was attributed with some confidence to inadequate surgery. These results indicate that the pattern of recurrence is highly variable and often with multiple sites of incompetence. In a few instances, the pattern of recurrence was associated with specific clinical factors. A full work-up including duplex scanning is recommended.
Aged↗
Tamoxifen and risk of large bowel cancer in women with breast cancer.
BACKGROUND: The increasingly consistent association between estrogen replacement therapy and colorectal cancer suggests that the anti-estrogen tamoxifen may also be associated with large bowel cancer incidence. METHODS: Women with new diagnoses of breast cancer were identified from the Surveillance Epidemiology and End Results (SEER) Program, a set of geographically defined, population based cancer registries representing approximately ten percent of the U.S. population. Of 85,411 women with local or regional breast cancer diagnosed from 1983-90, 14,984 women were reported to have received hormonal therapy and 70,427 were not known to have received hormonal therapy. Subsequent cancer diagnoses were identified in this cohort beginning 6 months after initial breast cancer diagnosis until death, or December 31, 1994. Multivariate Cox proportional hazards models were used to estimate the risk of developing colorectal cancer and other second cancers according to hormonal therapy use. RESULTS: Over the follow-up period 793 colorectal, 2,648 contralateral breast, 506 endometrial, 250 ovarian, 98 gastric, and 1,765 other cancers were identified in the study cohort. While overall there was no association between hormonal therapy use and colorectal cancer (relative risk (RR) 1.09, 95% confidence interval (CI) 0.88-1.35), in the period five or more years after diagnosis, risk was increased significantly by about 50% (95% CI 1.00-2.15). As expected, based upon clinical trials data, cancers of the contralateral breast were significantly decreased, and cancers of the uterine endometrium were significantly increased. No other meaningful associations were observed. When women were excluded for whom hormonal therapy might represent therapy other than tamoxifen (premenopausal women and those who received chemotherapy), this did not meaningfully alter these estimates. CONCLUSIONS: The results of this large population based cohort study suggest that tamoxifen therapy may modestly increase risk of large bowel cancer in women, but only after 5 years following initiation of breast cancer therapy.
Age Factors↗
Venous morphology predicts class of chronic venous insufficiency.
OBJECTIVES: this study aimed to determine specific morphological differences in long saphenous veins from patients with various grades of chronic venous insufficiency. DESIGN: comparable veins from a control group were compared with patients with either primary varicose veins or those with associated skin changes including venous ulcers. MATERIALS: below-knee segments of saphenous vein were examined from a total of 64 patients. METHODS: veins were examined for elastic-tissue disruption and endothelial-cell changes and comparisons made between clinical groups. RESULTS: elastic-tissue disruption, as measured by fragmentation of the elastic lamina and the percentage of the intimal-medial boundary containing elastin, increased with increasing severity of venous disease. Moreover, endothelial cells became more densely packed, as measured by endothelial cell and endothelial-cell nuclei density, with increasing severity of disease. Other measures such as the density of multinucleated "giant" endothelial cells and the number of nuclei per "giant" cell did not correlate with venous disease, however. CONCLUSIONS: this study demonstrates that several morphological characteristics of superficial saphenous veins correlate with severity of venous disease. In particular, the alterations to the structure of elastic tissue within these veins appears indicative of the progressive nature of chronic venous insufficiency.
Aged↗
Mitogen-activated protein kinase inhibits 1,25-dihydroxyvitamin D3-dependent signal transduction by phosphorylating human retinoid X receptor alpha.
Human retinoid X receptor alpha (hRXR alpha) is a member of the nuclear receptor family of transcriptional regulators. It regulates transcription through its association with several heterodimeric partners, including the vitamin D3 receptor (VDR). Signaling through the VDR is essential for normal calcium homeostasis and has been shown to inhibit the proliferation of cancer cells derived from a number of tissues. Here we show that phosphorylation of hRXR alpha in ras-transformed human keratinocytes through the activated Ras-Raf-mitogen-activated protein kinase (Ras-Raf-MAP kinase) pathway results in attenuated transactivation by the VDR and resistance to the growth inhibitory action of 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] and RXR-specific agonist LG1069 (4-[1-(5,6,7, 8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl) ethenyl]-benzoic acid). Phosphorylation of hRXR alpha occurs at serine 260, a consensus MAP kinase site. Inhibition of MAP kinase activity or point mutagenesis of serine 260 of hRXR alpha reverses the observed resistance to 1,25(OH)2D3 and LG1069. Thus, hRXR alpha is a downstream target of MAP kinase, and its phosphorylation may play an important role in malignant transformation.
Animals↗
Opportunities for pregnant and parenting teenagers: a school-based and school-linked intervention program.
Three hundred and ninety (390) pregnant and parenting teens participated in a school-based and school-linked federally funded program at 10 high-risk schools. The program was designed to (1) increase the use of referred services and attendance at these services without students' missing school, (2) increase academic skills, and (3) increase health and well-being of the students and their infants. The program provided 18 services coordinated at the school or provided on site. The end-of-year evaluations indicated 88% to 95% of teens attended services that were recommended, and 69% did not miss school to receive these services. The teens' rate of passing their grade level increased at the end of the program year. Additionally, 78% used birth control, and over 90% of the infants received timely health care. The qualitative data provided by students indicated pregnant and parenting teens wanted to remain in school despite the struggles they encountered. The process evaluation provided by the coordinators at each school indicated that communication and cooperation between program staff and school nurses were the key elements in enabling teens to receive the targeted services.
Adolescent↗
Disruption of vitamin D receptor-retinoid X receptor heterodimer formation following ras transformation of human keratinocytes.
A partial resistance to the growth inhibitory influence of 1, 25-dihydroxyvitamin D3 is apparent when immortalized keratinocytes are transformed by the ras oncogene. The vitamin D receptor (VDR) was isolated, analyzed, and found to be identical in normal, immortalized, and ras-transformed keratinocytes. Subsequently, nuclear extracts from immortalized and ras-transformed keratinocytes were analyzed in gel mobility shift assays utilizing labeled vitamin D response elements or thyroid hormone response elements. A specific protein.DNA complex that was shown to contain VDR using an anti-VDR antibody was identified in both types of extracts; however, the addition of an anti-retinoid X receptor (RXR) antibody identified RXR in the complex of both normal and immortalized keratinocyte cell extracts, but not in ras-transformed keratinocytes. Furthermore, transfection of ras-transformed keratinocytes with wild-type human RXRalpha rescued VDR.RXR and thyroid hormone receptor.RXR complexes as demonstrated by a supershift in the presence of the anti-RXR antibody. Both cell lines were found to express RXRalpha message in equal amounts. Western blot analysis revealed that RXRalpha protein from ras-transformed keratinocytes was indistinguishable from that from immortalized keratinocytes and from control cells. These results suggest a causal relationship between resistance to the growth inhibitory influences of 1,25-dihydroxyvitamin D3 and disruption of the VDR.RXR complex in malignant keratinocytes.
Base Sequence↗