Evidence of carcinogenicity in humans of water-soluble nickel salts

Background  

Increased risks of nasal cancer and lung cancer in nickel refiners have been investigated scientifically and discussed since they were detected in the 1930s. Nickel compounds are considered to be the main cause of the cancer excess. Parts of the nickel producing industry and their consultants oppose the classification of water-soluble nickel salts as human carcinogens, and argue that the risk in exposed workers should be ascribed to other occupational exposures and smoking.     

Cancer in the Norwegian printing industry

OBJECTIVES: The aim of this study was to investigate cancer risk among Norwegian workers in the printing industry, particularly lung and bladder cancer. METHODS: Cancer incidence was investigated from 1953 through 1998 in a cohort of 10 549 male members of a trade union in the printing industry in Oslo and nearby areas. Rates from the region, were used to calculate standardized incidence ratios (SIR) separately for the skilled and unskilled workers. Smoking data from a sample of the cohort were utilized for evaluating the risk estimates of smoking-related cancers. Specific exposure data were not available. RESULTS: Among the skilled workers, significantly elevated risks of cancer of the urinary bladder [standardized incidence ratio (SIR) 1.47, 95% confidence interval (95% CI) 1.19-1.79], liver (SIR 1.92, 95% CI 1.15-2.99), pancreas (SIR 1.46, 95% CI 1.07-1.94) and colon (SIR 1.27, 95% CI 1.05-1.55) were observed, whereas an increased risk of lung cancer in this group was confined to those born before 1910. Among the unskilled workers, there were significantly increased risks of cancer of the mouth, esophagus, stomach, larynx, lung, and all sites. CONCLUSIONS: The study showed that workers in the printing industry were at increased risk of several types of cancer. In particular the increased risk of bladder cancer among the skilled workers is suggestive of an occupational cause. However, no specific agent could be identified as an occupational carcinogen. The results did not support the hypothesis of a generally increased risk of lung cancer. The risk pattern for unskilled workers may reflect confounding by nonoccupational factors.     

Height and body mass index in relation to total mortality

BACKGROUND: The relation between body mass index (BMI) and mortality is not clear in the literature. An inverse relation between height and mortality has been suggested. We explore these relations in a very large cohort in Norway. METHODS: We studied two million men and women, age 20-74 years, who were measured during 1963-2000. These persons were followed for an average of 22.1 years. We used Cox proportional hazard models in the analyses. Also, the optimal BMI (the BMI at the time of measurement that was subsequently related to the lowest mortality) was estimated. RESULTS: Over the study period, 723,000 deaths were registered. The relative risk of death by BMI showed a J- or U-shaped curve, with the lowest rates of death at BMI between 22.5 and 25.0. In men, the optimal BMI increased from 21.6 when measured at age 20-29 to 24.0 when measured at age 70-74. In women, the optimal BMI was consistently higher, increasing from 22.2 to 25.7. Mortality decreased with increased height in men; in women, mortality decreased with height only up to heights of about 160-164 cm and then increased among the tallest women. CONCLUSIONS: The relation between BMI and mortality was J- or U-shaped, with the "optimal" BMI varying by age and sex. Height was inversely related to mortality in men and in women up to a height of 165 cm.     

Night work and breast cancer risk among Norwegian nurses: assessment by different exposure metrics

Associations between night work and breast cancer risk were investigated in a nested case-control study within a cohort of 49,402 Norwegian nurses. A total of 699 (74%) of the live cases diagnosed in 1990-2007 and 895 (65%) controls, cancer free at the time of sampling, were interviewed about work history and potential risk factors. The odds ratios for risk of breast cancer in relation to different exposure metrics were estimated by multivariate unconditional logistic regression models. No increase of risk was found after long duration of work by nurses working ≥3 night shifts per month. Small, nonsignificantly increased risks were observed for exposure to ≥30 years in hospitals or other institutions (odds ratio (OR) = 1.1), ≥12 years in schedules including night work (OR = 1.3), ≥1,007 night shifts during the lifetime (OR = 1.2), and lifetime average number of ≥4 night shifts per month (OR = 1.2). Nonsignificantly increased risks of breast cancer were observed in nurses who worked ≥5 years with ≥4 (OR = 1.4) and ≥5 (OR = 1.6) consecutive night shifts. Significantly increased risks were seen in nurses who worked ≥5 years with ≥6 consecutive night shifts (OR = 1.8, 95% confidence interval: 1.1, 2.8). The results suggest that risk may be related to number of consecutive night shifts.     

Perinatal exposure to low doses of PCB 153 and PCB 126 affects maternal and neonatal immunity in goat kids

Pregnant does (10 goats/group) were dosed orally either with polychlorinated biphenyl (PCB) 153 (98 microg/kg body weight/d) or PCB 126 (ng/kg body weight/d) dissolved in corn oil or with corn oil only (control group) from gestation day (GD) 60 until delivery. An additional group (n = 5) of pregnant does received the synthetic estrogen diethylstilbestrol (DES; 0.4 microg/kg body weight/d) by intramuscular injection using the same treatment schedule as for the PCB groups. Blood samples for immune analysis were collected at wk 0, 1, 2, 4, 6, and 8 of age. The effects of perinatal PCB exposure on postnatal humoral immune responses were examined by assessing the levels of total immunoglobulin G (IgG) and immunoglobulins to specific microbes at wk 0, 1, 2, 4, 6, and 8 of age, and immune responses following immunization of kids at 2 wk of age. PCB 153 exposure suppressed maternal and neonatal immunity, as demonstrated by reduced transfer of maternal IgG and specific antibodies to the environmental microbes Arcanobacterium pyogenes, Mannheimia haemolytica, and reovirus (REO-1). Furthermore, PCB 153 reduced the level of maternal antibodies to Mycobacterium avium paratuberculosis and equine influenza virus (EIV-1) in the newborn kids. The antibody response against EIV-1 was significantly higher in PCB 153-exposed kids 2 wk following immunization. PCB 126 exposure reduced the levels of maternal antibodies to REO-1. In contrast, gestational exposure to PCB 126 increased the concentrations of maternal antibodies to tetanus toxoid. No differences from controls in plasma total IgG levels at birth or colostrum IgG concentrations were observed in the PCB 126-treated does. However, a significant reduction in IgG levels from GD 60 until delivery was found in this group. Gestational exposure to DES reduced the concentrations of maternal antibodies against A. pyogenes, M. haemolytica, M. avium Paratuberculosis, and REO-1. These results suggest that perinatal exposure to low doses of PCB 126 and PCB 153 affects the maternal immunity in kids. The difference in responses between PCB 126 and PCB 153 treatment groups may strengthen the hypothesis that PCBs mediate immunotoxic effects through both AhR-dependent and -independent mechanisms. The observation that the effects produced by PCB 153 resembled those produced by DES raises the question of whether this congener may modulate immunity by estrogenic mechanisms.     

Cancer risk among 43000 Norwegian nurses

OBJECTIVES: This study evaluated the influence of occupational exposure on cancer risk among female Norwegian nurses. METHODS: A historical prospective cohort study was performed. The cohort was established from the Norwegian Board of Health's registry of nurses and included women who graduated from a nursing school before 1985. The cohort (N=43 316) was linked to the Cancer Registry of Norway. The observed number of cases was compared with the expected number on the basis of national rates. Time since first employment, period of first employment, and duration of employment were used as indicators of exposure. Poisson regression analyses were used for internal comparisons, adjusting for age, period, and fertility. RESULTS: The nurses were followed over 1473931 person-years. During the follow-up (1953-2002), 6193 cancer cases were observed. The standardized incidence ratio (SIR) for all cancers combined was close to unity. Significantly lower risks were found for cancers with a known association with alcohol and tobacco consumption and sexual activity. A significantly increased risk was found for breast cancer (SIR 1.14, 95% confidence interval (95% CI) 1.09-1.19), ovarian cancer (SIR 1.14, 95% CI 1.04-1.25), malignant melanoma (SIR 1.15, 95% CI 1.04-1.28), and borderline significant risk appeared for other skin cancer (SIR 1.12, 95% CI 0.98-1.29). A positive trend for increasing time since first exposure was found for breast cancer and malignant melanoma. CONCLUSIONS: The results indicate an association between working as a nurse and an increased risk of breast cancer and malignant melanoma. Decreased risks, found for several cancers, indicate favorable lifestyle habits among nurses.     

A closer look at RapidArc® radiosurgery plans using very small fields

RapidArc? has become the treatment of choice for an increasing number of treatment sites in many clinics. The extensive use of multiple subfields in RapidArc? treatments presents unique challenges, especially for small targets treated in few fractions. In this work, very small static fields and subsequently RapidArc? and conventional plans for two targets (0.4 and 9.9 cm(3)) were investigated. Doses from static fields 1-4 MLC leaves (0.25-1.00 cm) wide, and larger fields with 1-4 MLC leaves closed in their centres, were measured using the portal dosimeter-based QA system EPIQA (v?1.3) and gafchromic film. RapidArc and conventional plans for two tumours were then measured using EPIQA, gafchromic EBT2 film and the phantom-based QA system Delta4. Eclipse 8.6 and 8.9, grid spacings of 1.25 and 2.50 mm and a Varian HD linac were used. For static fields one MLC leaf wide, the dose was underestimated by Eclipse by as much as 53% (v?8.6, 2.5 mm grid). Eclipse underestimated the dose downstream from a few MLC leaves closed in the centre of a large MLC field by as much as 30%. Eclipse consistently overestimated the width of the penumbra by about 100%. For the conventional plans, there was good agreement between the calculated and measured dose for the 9.9 cm(3) PTV, but a 10% underdose was observed for the 0.4 cm(3) PTV. For the RapidArc? plans, the measured dose for the 9.9 cm(3) PTV was in good agreement with the calculated one. However, for the 0.4 cm(3) PTV about 10% overdosing was detected (Eclipse v 8.6, 2.5 mm grid spacing). EPIQA data indicated that the measured dose profiles were overmodulated compared to the calculated one. The use of small subfields, typically a few MLC leaves wide, or larger fields with one or a few MLC leaves closed in its centre can result in significant errors in the dose calculation. The detector systems used vary in their ability to detect the discrepancies. Using a smaller grid size and newer version of Eclipse reduces the discrepancies observed in this work but does not eliminate them.     

Chronic vascular irritation of the facial nerve causes facial spasm in rats

Abstract

The abnormal muscle response, elicited by electrical stimulation of one branch of the facial nerve and recorded from muscles innervated by another branch, has been used previously as an objective sign of hemifacial spasm in the development of animal models of this disorder. In the present study we recorded spontaneous electromyographic activity from the orbicularis oculi muscle from both sides in rats in which a demyelination of the peripheral portion of the facial nerve and vascular contact had been made previously. The root mean square value of the electromyographic activity on the affected side was significantly larger than that on the unaffected side in all rats in which the vascular irritation had caused the abnormal muscle response to appear. The results support our earlier finding that vascular contact together with demyelination of the peripheral facial nerve can cause the development of signs of hemifacial spasm, including involuntary muscle contractions. [Neurol Res 1994; 16: 284-288]