Glutathione S-transferases M1-1 and T1-1 as risk modifiers for renal cell cancer associated with occupational exposure to chemicals

Aims: To investigate the possible interaction between occupational risk factors and genotype for glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) in renal cell cancer (RCC).

Methods: One hundred patients with RCC and 200 outpatient controls were enrolled at Parma University Hospital. The polymorphisms of glutathione S-transferase M1-1 (GSTM1) and T1-1 (GSTT1) were investigated by PCR; occupational history was collected by a structured questionnaire.

Results: Subjects with GSTM1 present genotype showed higher risks for RCC, compared to GSTM1 null subjects, if exposed to metals (OR 2.73; 95% CI 0.91 to 8.22 v 1.14; 95% CI 0.46 to 2.82) or pesticides (OR 3.46; 95% CI 1.12 to 10.74 v 1.59; 95% CI 0.48 to 5.34). The GSTT1 present genotype also enhanced the risk (about twofold) of RCC among subjects exposed to solvents and pesticides, compared with those GSTT1 null.

Conclusions: Results support the hypothesis that GSTM1 and GSTT1 polymorphisms can interact with several occupational exposures to significantly modify the risk of RCC among exposed subjects.

     

Accommodation and vergence latencies in human infants

PURPOSE: Achieving simultaneous single and clear visual experience during postnatal development depends on the temporal relationship between accommodation and vergence, in addition to their accuracies. This study was designed to examine one component of the dynamic relationship, the latencies of the responses. METHODS: Infants and adults were tested in three conditions (i) binocular viewing of a target moving in depth at 5 cm/s (closed loop) (ii) monocular viewing of the same target (vergence open loop) (iii) binocular viewing of a low spatial frequency Difference of Gaussian target during a prism induced step change in retinal disparity (accommodation open loop). RESULTS: There was a significant correlation between accommodation and vergence latencies in binocular conditions for infants from 7 to 23 weeks of age. Some of the infants, as young as 7 or 8 weeks, generated adult-like latencies of less than 0.5 s. Latencies in the vergence open loop and accommodation open loop conditions tended to be shorter for the stimulated system than the open loop system in both cases, and all latencies were typically less than 2 s across the infant age range. CONCLUSIONS: Many infants between 7 and 23 weeks of age were able to generate accommodation and vergence responses with latencies of less than a second in full binocular closed loop conditions. The correlation between the latencies in the two systems suggests that they are limited by related factors from the earliest ages tested.     

Factors affecting the clinical testing of accommodative facility

A number of variables in the accommodation flipper test are thought to contaminate the results: the time for naming symbols; the manual facility to actually operate the flippers; the minification or magnification of symbol target size by the lenses; saccadic eye movements; and the relationship between the accommodation stimulus and its response. With the exception of the last variable, all undesirable factors have been eliminated in a newly developed modified method of accommodation facility measurement. In this method, double measurement through plano and +/- 2.00 D lenses, is executed. The average time in seconds per one cycle, taking only the accommodation into account for a group of 43 children (age from 7 years 11 months to 9 years 11 months), is 3.7 monocularly and 8.5 binocularly and the average number of cycles per minute in this group is 32.1 and 33.8 monocularly (for the dominant and nondominant eye, respectively) and 22.6 binocularly. These results in sec/cycle do not differ considerably from results received by other authors, if one considers the time necessary for naming the digits, mechanically changing the lenses, saccadic eye movements etc., and even those results given in cycles/minute do not differ either taking the wide ranges of standard deviations into account. However, the method reported here reflects accommodation facility more precisely. Measurements were performed also with the hand held flipper. Comparison of results summarised above and those obtained with a hand held flipper demonstrates that the hand held flipper is not a good device to measure accommodative facility.     

Urinary 8-Hydroxydeoxyguanosine in Belarussian Children Relates to Urban Living Rather Than Radiation Dose After the Chernobyl Accident: A Pilot Study

As a result of the Chernobyl accident in 1986, exposure to radioactive cesium is still a concern in the contaminated regions of Belarus. We tested the hypothesis that long-term radiation exposure from the Chernobyl accident might increase the urinary excretion of the oxidative stress marker, 8-hydroxydeoxyguanosine (8-OHdG), in Belarussian children. Urinary 8-OHdG was determined in two groups of children (—n = 31 and n = 46) —living in contaminated and uncontaminated areas of Belarus, respectively (the majority of the unexposed children lived in the capital Minsk). The children from the contaminated areas had a significantly higher annual summary effective dose but significantly lower urinary 8-OHdG levels than the children from the uncontaminated areas. Unexpectedly, children living in uncontaminated urban areas had significantly higher urinary 8-OHdG levels than children living in uncontaminated rural areas. There was no statistically significant effect of sex or body mass index on urinary 8-OHdG, but there was a weak significant inverse correlation to age as well as to the annual summary effective dose. These findings suggest that radiation from the Chernobyl accident is now a less important contributor to oxidative stress in Belarussian children than urban living.     

Occupational determinants of cryptogenic polyneuropathy

OBJECTIVES: The aim was to investigate different occupational and leisure time exposures as determinants for cryptogenic polyneuropathy. METHODS: A case-referent study was conducted in Sweden including 232 cases of cryptogenic polyneuropathy 40-79 years of age at diagnosis who were enrolled from the out-patient neurology departments of 3 hospitals. From the population register 853 referents were randomly selected. Information on occupational and leisure time exposure was obtained from a postal questionnaire. The response rate was 71% for cases and for referents. Crude odds ratios (CORs) and logistic regression odds ratios (LORs) were calculated for exposures with 5 or more exposed cases and referents taken together. The reference category was defined as individuals unexposed to any of the occupational or leisure time risk factors in the questionnaire. RESULTS: As expected, male sex and increasing age were significant determinants for cryptogenic polyneuropathy. Occupational exposures in men to Stoddard solvent, petrol exhausts, herbicides or hand and foot vibrations generated significantly increased CORs. LORs >3.50 were found in men for occupational exposure to sulphur dioxide, xylene, methyl ethyl ketone, herbicides and in women for occupational exposure to lead, nitrous oxide and insecticides. Only solvent exposure in leisure time remained significant in the regression analysis indicating that not only occupational exposures were of importance. Interactions between occupational and leisure time exposure were seen for several agents. CONCLUSIONS: Several known determinants for polyneuropathy, from animal studies and case reports, were confirmed. New determinants were also indicated, i.e. sulphur dioxide, xylene and methyl ethyl ketone.     

The risk for multiple sclerosis in female nurse anaesthetists: a register based study

Background

Previous studies have suggested that exposure to organic solvents, including volatile anaesthetic agents, may be a risk factor for multiple sclerosis (MS), possibly in combination with genetic and other environmental factors.

Aims

To further investigate the role of volatile anaesthetic agents having similar acute toxic effects to other organic solvents.

Methods

Female nurse anaesthetists, other female nurses, and female teachers from middle and upper compulsory school levels were identified and retrieved from the 1985 census, Statistics Sweden. By means of the unique personal identity number in Sweden, these individuals were linked with the disability pension registers at The National Social Insurance Board and also with data on hospital care 1985–2000 at The National Board of Health and Welfare.

Results

The cumulative incidence rate ratio of MS was found to be increased in female nurse anaesthetists in relation to other nurses (statistically not significant) and teachers (statistically significant), respectively.

Conclusions

These findings give some support to previous findings of an increased risk for MS in nurse anaesthetists. This is interesting in the context of previous observations of organic solvents in general as a potential risk factor in MS.     

Increased incidence of malignancies in Sweden after the Chernobyl accident—a promoting effect?

BACKGROUND: After the Chernobyl accident in 1986, as much as 5% of the released caesium-137 was deposited in Sweden due to a heavy rainfall 2 days after the event. A study of increased incidence of malignancies was initiated after the accident. METHODS: The cohort included 1,137,106 inhabitants who were 0-60 years old in 1986 and lived in 8 counties of Sweden with the highest fallout of caesium-137. With the dwelling coordinate, GIS-technique and a digital map on caesium-137, each individual was matched for the exposure. Adjustments were made for several potential confounding factors. During the follow-up 33,851 malignancies was recorded 1988-1999. RESULTS: Exposure categories were: 0-8 (reference), 9-23, 24-43, 44-66, 67-84, and > or =85 nGy/hr. The corresponding adjusted Mantel-Haenszel incidence rate ratios for total malignancies during follow-up amounted to 1.000, 0.997, 1.072, 1.114, 1.068, 1.125, respectively. The excess relative risk per 100 nGy/hr with the same adjustments and time period was 0.042 95% confidence limit 0.001;0.084. An excess for thyroid cancer or leukemia could not be ruled out. CONCLUSION: Increased incidence of total malignancies possibly related to the fallout from the Chernobyl accident is seen.     

Increase of regional total cancer incidence in north Sweden due to the Chernobyl accident?

STUDY OBJECTIVE: Is there any epidemiologically visible influence on the cancer incidence after the Chernobyl fallout in Sweden? DESIGN: A cohort study was focused on the fallout of caesium-137 in relation to cancer incidence 1988-1996. SETTING: In northern Sweden, affected by the Chernobyl accident in 1986, 450 parishes were categorised by caesium-137 deposition: < 3 (reference), 3-29, 30-39, 40-59, 60-79, and 80-120 kiloBecquerel/m(2). PARTICIPANTS: All people 0-60 years living in these parishes in 1986 to 1987 were identified and enrolled in a cohort of 1 143 182 persons. In the follow up 22 409 incident cancer cases were retrieved in 1988-1996. A further analysis focused on the secular trend. MAIN RESULTS: Taking age and population density as confounding factors, and lung cancer incidence in 1988-1996 and total cancer incidence in 1986-1987 by municipality as proxy confounders for smoking and time trends, respectively, the adjusted relative risks for the deposition categories were 1.00 (reference < 3 kiloBecquerel/m(2)), 1.05, 1.03, 1.08, 1.10, and 1.21. The excess relative risk was 0.11 per 100 kiloBecquerel/m(2) (95% CI 0.03 to 0.20). Considering the secular trend, directly age standardised cancer incidence rate differences per 100 000 person years between 1988 to 1996 and the reference period 1986-1987, were 30.3 (indicating a time trend in the reference category), 36.8, 42.0, 45.8, 50.1, and 56.4. No clear excess occurred for leukaemia or thyroid cancer. CONCLUSIONS: Unless attributable to chance or remaining uncontrolled confounding, a slight exposure related increase in total cancer incidence has occurred in northern Sweden after the Chernobyl accident.