Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility.

BACKGROUND: Topical ophthalmic atropine sulfate is an important part of the treatment protocol in equine uveitis. Frequent administration of topical atropine may cause decreased intestinal motility and colic in horses due to systemic exposure. Atropine pharmacokinetics are unknown in horses and this knowledge gap could impede the use of atropine because of the presumed risk of unwanted effects. Additional information could therefore increase safety in atropine treatment. RESULTS: Atropine sulfate (1 mg) was administered in two experiments: In part I, atropine sulfate was administered intravenously and topically (manually as eye drops and through a subpalpebral lavage system) to six horses to document atropine disposition. Blood-samples were collected regularly and plasma was analyzed for atropine using UHPLC-MS/MS. Atropine plasma concentration was below lower limit of quantification (0.05 µg/L) within five hours, after both topical and IV administration. Atropine data were analyzed by means of population compartmental modeling and pharmacokinetic parameters estimated. The typical value was 1.7 L/kg for the steady-state volume of distribution. Total plasma clearance was 1.9 L/h‧kg. The bioavailability after administration of an ophthalmic preparation as an eye drop or topical infusion were 69 and 68%, respectively. The terminal half-life was short (0.8 h). In part II, topical ophthalmic atropine sulfate and control treatment was administered to four horses in two dosing regimens to assess the effect on gastro-intestinal motility. Borborygmi-frequency monitored by auscultation was used for estimation of gut motility. A statistically significant decrease in intestinal motility was observed after administration of 1 mg topical ophthalmic atropine sulfate every three hours compared to control, but not after administration every six hours. Clinical signs of colic were not observed under any of the treatment protocols. CONCLUSIONS: Taking the plasma exposure after topical administration into consideration, data and simulations indicate that eye drops administrated at a one and three hour interval will lead to atropine accumulation in plasma over 24 h but that a six hour interval allows total washout of atropine between two topical administrations. If constant corneal and conjunctival atropine exposure is required, a topical constant rate infusion at 5 µg/kg/24 h offers a safe alternative.

Arc and resistance welding and tumours of the endocrine glands: a Swedish case-control study with focus on extremely low frequency magnetic fields.

BACKGROUND: Mechanisms for potential effects of extremely low frequency (ELF) magnetic fields on carcinogenesis have not been identified. A potential pathway could be an interaction with the endocrine system. AIMS: To analyse occupational exposure to ELF magnetic fields from welding, and tumours of the endocrine glands. METHODS: This case-control study was based on a cohort with an increased prevalence of high exposed individuals. A total of 174 incident cases of tumours of the endocrine glands, 1985-94, were identified and data were obtained from 140 (80%) of these cases; 1692 controls frequency matched on sex and age were selected, and information on 1306 (77%) individuals was obtained. A short questionnaire was sent to a work administrator at the workplaces of the cases and controls. The exposure assessment was based on questions about job tasks, exposure to different types of welding, and exposure to solvents. RESULTS: There was an overall increased risk for all tumours of the endocrine glands for individuals who had been welding sometime during the follow up. The increased risk was attributable to arc welding; for resistance welding there was no clear evidence of an association. We found an increased risk for the adrenal glands in relation to arc welding, and for the parathyroid glands in relation to both arc welding and resistance welding. An imprecise increase in risk was also noted for tumours of the pituitary gland for arc welding. No confounding effect was found for solvent exposure, and there was no sign of biological interaction. CONCLUSION: The increased risks of endocrine gland tumours related to welding might be explained by exposure to high levels of ELF magnetic fields.

Passive smoking in cystic fibrosis.

The families of 32 children with cystic fibrosis (CF) were interviewed about both their tobacco consumption and their childrens physical activities. Hospital records informed about treatment frequency, lung function and clinical score. Cystic fibrosis families smoked far more than the Swedish average and the passive smokers among our patients seemed to fare less well in all parameters. The children of smoking mothers required significantly longer periods of intravenous antibiotic treatment (P greater than 0.05). Frequent physical exercise seemed to compensate for the potential harmful effects of passive smoking and children with high physical activity living in families who smoked needed significantly less frequent antibiotic treatment than the inactive children (P greater than 0.02). Although this series is small, the results indicate that a smoke-free environment may be important for CF patients. General information is insufficient and extensive psychological support to the families is probably necessary.

Occupational exposure to magnetic fields in relation to male breast cancer and testicular cancer: a Swedish case-control study.

Occupational exposure to extremely low-frequency magnetic fields (MF) was studied in 56 male subjects with breast cancer (adenocarcinoma) diagnosed in 1985-91, and 144 subjects with testicular cancer (seminoma and non-seminoma), diagnosed in 1985-87. The cases were compared with 1,121 control subjects from a previous case-control study on MF and cancer. Exposure assessment was based on the job held longest during the decade before diagnosis linked to a job exposure matrix based on MF measurements. The results refer to an estimated average mean of > 0.28 microT (Q4) and > 0.40 microT (P90, part of Q4) with < or = 0.15 microT (Q1) as reference. For breast cancer, the odds ratios (OR) and the 95 percent confidence intervals (CI) were 0.7 (CI = 0.3-1.9) and 0.7 (CI = 0.2-2.3), respectively. For men 60 years or younger, the corresponding estimates were OR = 0.9 (CI = 0.2-4.5) and 1.5 (CI = 0.3-8.3). For testicular cancer, the ORs were 1.3 (CI = 0.7-2.5) and 2.1 (CI = 1.0-4.3), and for men 40 years or younger the ORs were 1.9 (CI = 0.8-4.4) and 3.9 (CI = 1.4-11.2). The results were mainly attributable to non-seminoma, the more malignant type of testicular cancer. Our conclusion is that the results for male breast cancer, based on limited numbers, fail to support the suggested association with MF exposure. The results for testicular cancer gave some support to the hypothesis of a hormonal link between MFs and cancer, and should be further explored.

Incidence of selected cancers in Swedish railway workers, 1961-79.

Among all Swedish men, 20 to 64 years of age and employed in 1960, railway workers were selected and compared with the population at large, concerning the incidence of leukemia, lymphoma, tumors of the brain, breast, and the pituitary gland. The study was a re-analysis of the 1961-79 incidence data previously showing no increase in risk for leukemia and brain tumors for railway workers. In the present study, follow-up was divided into two 10-year periods, and elevated relative risks (RR) were found for the first decade. For the first decade, engine drivers and conductors combined had an RR of chronic lymphocytic leukemia, acute myeloid leukemia, and lymphoma of 1.9 (95 percent confidence interval [CI] = 0.9-4.0), 1.4 (CI = 0.4-4.3), and 1.0 (CI = 0.5-1.9), respectively. For all brain tumors, the RR was 1.2 (CI = 0.8-1.9), with a higher risk estimate for those below age 30 (RR = 12.2, CI = 2.8-52.5). Three cases of breast cancer and nine cases of tumors of the pituitary gland occurred among engine drivers and conductors, corresponding to RRs of 4.9 (CI = 1.6-11.8) and 3.2 (CI = 1.6-6.2), respectively. Work on trains entails extremely high exposure to low frequency magnetic fields (EMF). The results give some support to the hypothesis of an association between EMF and certain types of cancers. The outcome for the pituitary gland, being a focal point of hormonal regulation, suggests a hormonal link.

Occupational magnetic field exposure and site-specific cancer incidence: a Swedish cohort study.

OBJECTIVE: Based on 1,596,959 men and 806,278 women, site-specific cancer incidence during 1971 through 1984 was analyzed in relation to occupational magnetic field exposure. The objective was to explore potential associations for cancer diseases beyond those extensively studied before (leukemia and brain tumors). METHODS: Exposure was assessed from Census information on occupations that were linked to a job exposure matrix based on measurements. In a basic analysis, three levels of exposure were used. In addition, subjects with a more definite low exposure were compared with an aggregate of occupations with more definite exposures. RESULTS: Observed associations were weak and there were no evident exposure-response relationships. For all cancer, an approximate 10% increase in risk was seen in the medium and high exposure groups. Several types of cancer were associated with exposure among men, including cancer of the colon, biliary passages and liver, larynx and lung, testis, kidney, urinary organs, malignant melanoma, non-melanoma skin cancer, astrocytoma III-IV. For women, associations were seen for cancer of the lung, breast, corpus uteri, malignant melanoma and chronic lymphocytic leukemia. CONCLUSIONS: In the analysis of occupations with a more definite exposure, the most notable finding for men was an increased risk of testicular cancer in young workers, and for women a clear association emerged for cancer of the corpus uteri. The outcome suggests an interaction with the endocrine/immune system.

Magnetic-field Exposures in the Workplace: Reference Distribution and Exposures in Occupational Groups.

Exposures to extremely-low-frequency magnetic fields were assessed by taking personal measurements with a dosimeter calibrated at 50 Hz with a bandwidth of 40-400 Hz. The study group was a population-based random sample of 1,098 Swedish men. Exposures were determined as workday mean, median, maximum, and standard deviation, and the time fraction of the day when exposures exceeded 0.20 µT. For workday means, the 50th percentile was 0.17 µT, and the 75th percentile was 0.27 µT. For median values, the 50th percentile was 0.11 µT and the 75th percentile was 0.16 µT. The strongest correlation (Spearman rank correlation = r&infs;) found was between the workday mean and the fraction of time above 0.20 µT (r&infs; = 0.89). The authors used the same data to estimate exposures for the 100 most common occupations according to the 1990 Swedish census. A minimum of four independent measurements for each occupation was required. Among occupations with low workday mean values were earth-moving machine operator, health care worker, and concrete worker. Among occupations with high workday mean exposures were welder and electrical or electronics engineer or technician. High exposure levels were also found in occupations outside the study base, such as train engine driver and glass, ceramic, or brick worker. Exposures to magnetic fields vary widely, since levels of exposure are strongly affected by factors such as duration of exposure and distance from the source. Large variations often found between individuals within occupations could reflect variations in tasks across different workdays for the particular occupations and/or local conditions such as tools and installations, and/or how the work is organized and performed.

Occupational exposure to electromagnetic fields in relation to leukemia and brain tumors: a case-control study in Sweden.

Occupational exposure to low-frequency electromagnetic fields (EMF) was studied in 250 leukemia patients and 261 brain-tumor cases, diagnosed in 1983-87 and compared with a control group of 1,121 randomly selected men, from the mid-region of Sweden, 1983-87. We based the exposure assessment on measurements from 1,015 different workplaces. On the basis of the job held longest during the 10-year period before diagnosis, we found an association between the average, daily, mean level of EMF and chronic lymphocytic leukemia (CLL). The risk increased with increasing level of exposure. The odds ratios (OR) and the 95 percent confidence interval (CI) for three consecutive levels of exposure were: 1.1 (CI = 0.5-2.3); 2.2 (CI = 1.1-4.3); 3.0 (CI = 1.6-5.8), respectively. No association was observed for acute myeloid leukemia (OR = 1.0, CI = 0.5-1.8; OR = 0.8, CI = 0.4-1.6; OR = 1.0, CI = 0.6-1.9). For brain tumors, the corresponding risk estimates were 1.0 (CI = 0.7-1.6); 1.5 (CI = 1.0-2.2); 1.4 (CI = 0.9-2.1). Different EMF indices were tested. Tasks with frequent or large variations between high and low field-densities (high standard deviation) were more common among CLL subjects. For brain tumors, a prolonged high level (high median values) showed the strongest association. Confounding by place of residence, smoking, benzene, ionizing radiation, pesticides, and solvents was evaluated, and these factors did not seem to have a decisive influence on the associations. We also analyzed other potential sources of bias. For CLL, there were indications of an excess number of low-exposure subjects among non-responders, which, to some extent, may have enhanced but not caused the risk estimates obtained. Our conclusion is that the study supports the hypothesis that occupational EMF exposure is a hazard in the development of certain cancers.

Occupational exposure to magnetic fields and brain tumours in central Sweden.

Occupations with exposure to magnetic fields were studied in a population-based case-control study of male glioma and meningioma in Central Sweden. The study included 84 cases of glioma, 20 cases of meningioma and 155 controls. Information about job titles was obtained by means of a questionnaire. Three different methods were used to classify exposure 1) 'electrical occupations', 2) assessment of magnetic fields by an electrical engineer, 3) job values based on magnetic field measurements at work sites for occupational groups. When analyses were based on 'electrical occupations' a relative risk (RR) of 1.0 (95% CI: 0.4-2.4) was seen for glioma and 1.8 (95% CI: 0.3-3.6) for meningioma. When analyses were based on measurements a relative risk of 1.9 (95% CI: 0.8-5.0) was seen for glioma and 1.6 (95% CI: 0.3-10.2) for those ever in an exposed job of an average mean value of > 0.4 microT. A larger number of individuals was classified as exposed, when exposure was based on measurements. Information was available regarding several potential confounders, but none of them seemed to be of any importance. Our conclusion is that the results based on magnetic field measurements give some support to the hypothesis that magnetic fields exposure may play a role in the development of brain tumours.