Impact of interleukin 13 (IL13) genetic polymorphism Arg130Gln on total serum immunoglobulin (IgE) levels and interferon (IFN)-γ gene expression.

This cross-sectional study was designed to investigate the extent of genetic susceptibility by targeting variants in interleukin (IL)-4/IL-13 signalling pathways leading to atopic disease in early childhood. We evaluated involvement of five single nucleotide polymorphisms IL4 C-590T, IL13 C-1055T, IL13 Arg130Gln, IL4RA Ile50Val and IL4RA Gln576Arg, in the control of serum total and antigen-specific immunoglobulin (Ig)E levels. Furthermore, we analysed their association with changes in gene expression of five cytokines having key roles in inflammatory and anti-inflammatory immune response [IL-4, IL-13, interferon (IFN)-γ, IL-8 and IL-10]. Total and antigen-specific IgE levels in serum and gene expression of selected cytokines in peripheral blood were measured in 386 children aged 1-8 years. TaqMan allelic discrimination, amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and restriction fragment length polymorphisms (RFLP) methods validated by sequencing were used for genotyping. All genotypes for children with total and antigen-specific IgE levels in the normal range were in Hardy-Weinberg equilibrium. Gene expression analyses were carried out using TaqMan gene expression assays. We found elevated total IgE levels in carriers of IL13 Arg130Gln variant allele [odds ratio (OR) = 1·84; 95% confidence interval (CI) = 1·16-2·93]. This effect was more apparent for boys (OR = 2·31; 95% CI = 1·25-4·28). However, no significant association was observed for the other four variants examined. We found up-regulation of IFN-γ in children with elevated serum total IgE levels carrying the Arg130 allele (P = 0·005). No differences were found for IL4, IL8 or IL10, while IL13 gene expression was under the detection limit. IL13 Arg130Gln genotypes can play a role in genetic susceptibility to allergy via regulation of serum total IgE levels and affecting IFN-γ gene expression.

DNA repair and cyclin D1 polymorphisms and styrene-induced genotoxicity and immunotoxicity.

1-SO-adenine DNA adducts, DNA single-strand breaks (SBs), chromosomal aberrations (CAs), mutant frequency (MF) at the HPRT gene, and immune parameters (hematological and of humoral immunity) were studied in styrene-exposed human subjects and controls. Results were correlated with genetic polymorphisms in DNA repair genes (XPD, exon 23, XPG, exon 15, XPC, exon 15, XRCC1, exon 10, XRCC3, exon 7) and cell cycle gene cyclin D1. Results for biomarkers of genotoxicity after stratification for the different DNA repair genetic polymorphisms showed that the polymorphism in exon 23 of the XPD gene modulates levels of chromosomal and DNA damage, HPRT MF, and moderately affects DNA adduct levels. The highest levels of biomarkers were associated with the wild-type homozygous AA genotype. The exposed individuals with the wild-type GG genotype for XRCC1 gene exhibited the lowest CA frequencies, compared to those with an A allele (P < 0.05). Cyclin D1 polymorphism seems to modulate the number of leukocytes and lymphocytes in the analyzed subjects. The number of eosinophiles was positively associated with XPD variant C allele and negatively with XRCC1 variant A allele (P < 0.05) and XPC variant C allele (P < 0.05). Immunoglobulin IgA was positively associated with an XRCC3 variant T allele (P < 0.01) and negatively with XPC variant C allele (P < 0.05). Both C3- and C4-complement components were lower in individuals with XRCC3 CT (P < 0.05) and TT genotypes (P < 0.01). Adhesion molecules sL-selectin and sICAM-1 were associated with XPC genotype (P < 0.05). Individual susceptibility may be reflected in genotoxic and immunotoxic responses to environmental and occupational exposures to xenobiotics.

Effects of occupational exposure to styrene on expression of adhesion molecule on leukocytes.

Styrene is an indispensable chemical extensively used in plastic and synthetic rubber industries. Styrene is known to produce various types of hepatotoxic, neurotoxic, and genotoxic effects. Styrene may be immunotoxic by both direct and indirect mechanisms. Measurement of adhesion molecules is a new tool for the investigation of immune system modulation. The aim of this study was to evaluate the association of the expression of the adhesion molecules CD11a, CD11b, CD18, CD54, CD49d, and CD62-L in white blood cells and levels of soluble adhesion molecules ICAM-1 and L-selectin in serum with occupational exposure to styrene. Analyses by flow cytometry revealed elevated levels of most of the assessed adhesion molecules on surfaces of lymphocytes, monocytes, and granulocytes. Expression of the adhesion receptor antigens CD11a on lymphocytes, CD11b on monocytes, and CD18 on granulocytes were unaffected. Workers exposed to styrene had decreased concentrations of sICAM-1 and no changes in concentrations of sL-selectin. Styrene exposure appears to increase activation of the immune system and alter leukocyte adherence. This interaction is a critical first step in immune stimulation and leukocyte-endothelial interaction.

Allergenicity testing of supermethrin, phenoxyacetic acid and DNCB using in vivo and in vitro modifications of the local lymph node assays, maximization and epicutaneous testing.

The purpose of this study was to compare two methods of testing for allergenicity: in vivo and in vitro modifications of local lymph node assays (LLNA) in mice and the maximization and epicutaneous skin tests in guinea pigs as per the Organization for Economic Cooperation and Development (1981). Two pesticides-the synthetic pyrethroid insecticide supermethrin (SM) and the herbicide phenoxyacetic acid (PAA)-were evaluated using this testing battery. 1-Chloro-2,4-dinitrobenzene (DNCB) was selected as a reference allergen for the local lymph node assay. In vitro modification of LLNA proliferative response per standard cell count in lymphocyte cultures derived from treated Balb/c mice did not differ from control mice. Results of the in vivo modification showed that treatment with 50% PAA and 50% SM resulted in a lower proliferation response of lymphocytes in lymph nodes compared with control animals. The vigour of the proliferative response varied more in in vivo modification of LLNA. Stimulation indices were <3, so PAA and SM did not indicate classification as allergens. Lymphocyte proliferation in 1% DNCB-activated lymph nodes was approximately fivefold higher than in those derived from control mice. Proliferation response in vitro calculated as stimulation index was higher in DNCB-treated mice than those observed in vivo, but differences were not dramatic. Auricular lymph node weight and cellularity in mice treated with PAA and SM were similar to controls. The DNCB stimulation index for lymph node cellularity was 5.5. Lymph node weight was three times higher in comparison with controls. In the maximization test in guinea pigs SM and PAA acid resulted in 40% and 50% of animals demonstrating sensitization, respectively. Epicutaneous administration resulted in weaker reaction. Both SM and PAA are mildly strong sensitizers by this battery.

Epidemiology of occupational injuries and illnesses in a university population: a focus on age and gender differences.

BACKGROUND: Occupational injuries and illnesses are a major preventable public health problem. METHODS: This study evaluated the incidence, nature, and cause of awarded workers' compensation claims for a large state university and teaching hospital. Rates and types of injury were compared across age and gender. RESULTS: Rates of injury varied over twofold with age, with those 16-25 having the lowest rates of injury and those 36-45 having the highest rates. Claims rates were 1.36-fold higher for women than men. Women had higher rates for injury resulting from lifting, falling, noxious exposures, repetitive motion, and carpal tunnel syndrome. Similarly women had significantly higher rates of claims for pain, sprains, bruises, burns, concussion, and inhalation injury; with lower rates of cuts, ligament injury, and jammed joints. CONCLUSIONS: These group differences suggest the need to examine age and gender job distributions and relevant ergonomic and environmental causative factors.

Early indicators of the effect of a breast cancer screening program for low-income women.

The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) was developed to increase screening among low-income women who are uninsured or underinsured. This study reports early indicators of the effectiveness of this breast screening program in Iowa. Using data from the Census Bureau and the Iowa Behavioral Risk Factor Surveillance System, we found that racial and ethnic minorities aged 50 to 64 more likely were screened by the NBCCEDP than were their counterparts. Data collected by the Iowa BCCEDP showed a breast cancer detection rate (7.1 per 1,000 women screened) that was at least three times higher than its historical comparison, an indication of the lead time of the screened over the nonscreened population. Predictive values positive (referral and biopsy) and stage distribution were typically higher than for the national program but lower than in other countries. In conclusion, a breast cancer screening program among low-income women can be implemented successfully, judged by early indicators of program effectiveness.

Indoor environmental quality in six commercial office buildings in the midwest United States.

The aims of this study were to characterize physical, mechanical, and environmental factors influencing indoor environmental quality (IEQ) in commercial office buildings; document occupant perceptions and psychosocial attributes; and evaluate relationships among these parameters. Six large office buildings in metropolitan areas were selected in Iowa, Minnesota, and Nebraska. Comprehensive sampling was conducted over one week in each building, during all four seasons. This paper presents the study methods and selected results from the first round of sampling (November 1996 to April 1997). Air flow and recirculation rates were quite variable, with the proportion of outdoor air provided to occupants ranging from 10 to 79 CFM/person. Carbon dioxide, carbon monoxide, and temperature were within ranges anticipated for nonproblem buildings. Relative humidity was low, ranging from 11.7 to 24.0 percent. Indoor geometric mean concentrations of total volatile organic compounds (TVOCs) ranged from 73 to 235 microg/m3. The most prevalent compounds included xylene, toluene, 2-propanol, limonene, and heptane. Geometric mean formaldehyde concentrations ranged from 1.7 to 13.3 microg/m3, and mean acetaldehyde levels ranged from <3.0 to 7.5 microg/m3. Airborne concentrations of culturable bacteria and fungi were low, with no samples exceeding 150 CFU/m3. Total (direct count) bioaerosols were more variable, ranging from 5010 to 10,700 organisms/m3. Geometric mean endotoxin concentrations ranged from 0.5 to 3.0 EU/m3. Respirable particulates (PM10) were low (14 to 36 microg/m3). Noise levels ranged from 48 to 56 dBA, with mean light values ranging from 200 to 420 lux. Environmental parameters were significantly correlated with each other. The prevalence of upper respiratory symptoms (dry eyes, runny nose), central nervous system symptoms (headache, irritability), and musculoskeletal symptoms (pain/stiffness in shoulders/neck) were elevated compared to other studies using similar questionnaires. Importantly, psychosocial factors were significantly related to increased symptoms in females, while environmental factors were more closely correlated with symptoms in males. Endotoxin concentrations were associated with symptoms in both males and females. These data will help to identify and quantify the relative role of factors that contribute to sick building syndrome. The data collected in this study may also be used to evaluate the effectiveness of current building operation practices, and can be used to prioritize allocations of resources for reduction of risk associated with IEQ complaints.

Changes in cellular immunity among workers occupationally exposed to styrene in a plastics lamination plant.

BACKGROUND: Styrene is a widely used industrial chemical. Immune and hematological parameters were examined in 29 hand laminators and sprayers exposed to styrene for an average of 14 years and in 19 in-factory unexposed controls. The workers performed hand lamination procedures in a production area with an average area airborne styrene level of 139.5 mg/m(3). Mean concentration of styrene in the blood of exposed workers was 945.7 microg/L and the mean styrene in exhaled air was 38.8 microg/L. METHODS: Parameters of internal and external exposure, immune function assays, immunoglobulins, acute phase reactants and hematology were evaluated in exposed and non-exposed populations. RESULTS: Using multifactorial analysis of variance we found a significant decrease in proliferation of lymphocytes stimulated by Concanavalin A but not by pokeweed mitogen (PWM) in workers occupationally exposed to styrene. Proliferative response to PWM was significantly correlated with the levels of styrene in blood. Phagocytic activity of monocytes, levels of IgG, IgA, IgM, IgE and alpha-2-macroglobulin in serum were indistinguishable in the two groups. The population exposed to styrene had increased levels of C4-component of complement. Levels of C3-component of complement were positively correlated with duration of exposure. A significant elevation in the percentage and number of monocytes and a significantly decreased number of lymphocytes were seen in exposed workers. Styrene concentrations in both blood and exhaled air were associated with decreased percentage of large granular lymphocytes. CONCLUSIONS: These results suggest immune alterations of cell-mediated immune response of T-lymphocytes and imbalance in leucocyte subsets in peripheral blood of workers exposed to styrene.

Marked elevation of urinary zinc levels and pleural-friction rub in metal fume fever.

Zinc fume is a well-recognized cause of metal fume fever, characterized by acute or subacute symptoms of respiratory tract inflammation, myalgias and fever (similar to influenza) associated with a variety of metal oxide fumes. A welder of galvanized steel developed metal fume fever, a pleural friction rub and markedly elevated urinary zinc excretion despite work-site surveillance data indicating exposures close to the Occupational Safety and Health Administration, Permissible Exposure Limit. This patient suggests that exposure data may be misleading. This case had the highest urine zinc levels reported in the literature and a previously unreported coexistent pleural friction rub. The symptoms resolved with administrative and engineering controls to decrease exposure.

Ambulatory care for traumatic brain injuries in the US, 1995-1997.

The burden of mild traumatic brain injury (TBI) is not well understood at the national level, but hospitalization rates show a decline over time. This paper describes ambulatory care for TBI patients at physician offices, hospital outpatient departments, and emergency departments (EDs) in comparison with non-TBI visits for the US during 1995-1997. An estimated 1.4 million visits for TBI were made each year for an average annual rate of 5.4/1,000 population. A decline in annual visit rate was noted during 1995-1997. Visit rates were higher for those aged 0 -14 and 75 and older. Falls (44%) and motor vehicles (28%) were the primary injury causes. Rural-urban differences were found, also in comparison with non-TBI. In 23% of visits to EDs, a CT scan was ordered or performed and in 33%, a mental status exam was conducted. Further investigations are warranted to describe ambulatory care for TBI in more detail, particularly in light of a decline in hospitalization rates.

Factors associated with adequacy of diagnostic workup after abnormal breast cancer screening results.

BACKGROUND: Women with certain characteristics, such as those residing in rural areas, are less likely screened for breast cancer. To enhance detection of early breast cancer, it is imperative that all women who have abnormal screening results receive appropriate diagnostic procedures. This study reports differences in receipt of diagnostic services following abnormal screening results. METHODS: Screening and diagnostic data were collected as part of a breast and cervical cancer early detection program aimed at reaching women of lower socioeconomic status. Women with completed diagnostic information after having abnormal screening results were included. We based adequacy of diagnostic services on guidelines from the Society for Surgical Oncology, The Commission on Cancer of the American College of Surgeons, and the Centers for Disease Control and Prevention. Several factors were assessed for their association with adequacy of diagnostic follow-up: income, age, race, education, health insurance status, rural-urban residence, reported breast lump, family history of breast cancer, and clinical beast examination or mammogram results. RESULTS: Overall, 14.1% of the 351 abnormal findings were considered inadequately followed up based on the algorithm used. Eighty percent involved an abnormal finding on a clinical breast examination regardless of the mammogram results. Rural women, those with abnormal clinical breast examination findings but normal or equivocal findings on mammograms, and those who self-discovered a mass were less likely to receive adequate follow-up than were their counterparts in multivariate analysis. Rural women were less likely to receive a biopsy or fine-needle aspiration, although it was indicated. One facility accounted for most of the inadequate follow-up screenings among urban women. CONCLUSIONS: Women who have specific demographic and clinical characteristics were less likely to have received adequate diagnostic services. Breast cancers could have been missed initially as a result of inappropriate follow-up. Further investigation of the clinical scenarios using chart reviews is warranted.

Lead contamination of imported candy wrappers.

Lead toxicity in a young Hispanic woman from sucking on a terra cotta candy container led to investigating lead contamination in candy packaging materials imported from Mexico. Printed cellophane candy wrappers may present a significant risk for lead exposure.

Use of the capture-recapture method to estimate severe traumatic brain injury rates.

OBJECTIVE: This study assessed the applicability of using three different data sources (hospital discharge data, Traumatic Brain Injury Registry data, and death certificates) to identify high-risk groups for traumatic brain injuries (TBI). Reporting biases were also addressed. METHODS: Linkage of the data sources and log-linear modelling in conjunction with the capture-recapture method was used to estimate the number of missing TBI. Biased reporting to each data source was assessed by using the total number of estimated TBI by age and sex. RESULTS: An estimated 2% of TBI that occurred in Iowa were not reported to any of the data sources. Overall, women 85 years old and older were more likely to be missed by the combined data sources. Males and those of advanced age were less likely to be reported to the Registry. By using the capture-recapture method, falls among the elderly were found to be a significant public health problem in Iowa. CONCLUSION: Despite biased reporting to the three data sources, the capture-recapture method can be used to identify high-risk groups for TBI in Iowa.

Lead exposure among workers renovating a previously deleaded bridge: comparison of trades, work tasks.

Airborne and surface lead exposures were evaluated for construction trade groups at a previously deleaded bridge renovation site in the midwestern United States. Although all lead-based paint should have been removed, old layers of leaded paint were still present on some sections of the bridge. Ironworkers performing metal torch cutting had the highest exposures (188 microg/m3), followed by workers engaged in clean-up operations and paint removal (p < 0.001). Respirators were most frequently worn by workers with the greatest lead exposures; however, laborers performing clean-up operations had exposures to lead dust of 43 microg/m3 and often wore no respiratory protection. Wipe samples revealed that almost all contractor vehicles were contaminated with lead. Heavy equipment operators with low airborne lead exposure had the highest levels of surface contamination in personal vehicles (3,600 microg/m2). Laborers cleaning structural steel with compressed air and ironworkers exposed to lead fumes from cutting had the highest concentrations of lead dust on clothing (mean 4,766 microg/m2). Handwashing facilities were provided, but were infrequently used. No separate clothes changing facility was available at the site. The potential for "take-home" contamination was high, even though this site was thought to be relatively free of lead. Construction contractors and their workers need to be aware that previous deleading of a site may not preclude exposure to significant amounts of lead.

Dissolution of 226Radium from pipe-scale deposits in a public water supply.

This study was undertaken to determine if dissolution of 226Radium from pipe-scale deposits contributes to enhanced waterborne 226Radium concentrations at the point of use. Water samples were collected from residential water customers of a small rural Iowa town. Sites were evenly divided between new and old water main connections. Daily samples were collected from the point-of-entry water. Point-of-use 226Radium concentrations ranged from 0.4 to 12.9 pCi L-1 (0.01 to 0.5 Bq L-1). The mean 226 Radium concentration for homes connected to old water mains was significantly higher than the mean 226Radium concentration of homes connected to new water mains, mean(standard deviation) equal 8.3(1.1) and 5.3(0.8) pCi L-1 [0.3(1.1) and 0.2(0.8) Bq L-1], respectively. 226Radium concentrations of the point-of-entry water ranged from 5.0 pCi L-1 to 10.3 pCi L-1 (0.2 Bq L-1 to 0.4 Bq L-1). This study indicates considerable variability of 226Radium exposure from drinking water among residents of the same water supply and has implications for regulatory compliance and exposure assessment in epidemiologic studies.

Biomonitoring of occupational exposure to styrene in a plastics lamination plant.

A comprehensive approach to biological monitoring of 44 workers occupationally exposed to styrene in a hand lamination plant was performed by using several end-points: styrene in workplace air, styrene in exhaled air, styrene in blood, DNA strand breaks (SBs) and oxidised bases in mononuclear leukocytes, chromosomal aberrations in lymphocytes, immune parameters and genotyping of polymorphic genes of some xenobiotic-metabolizing enzymes (CYP 1A1, EPHX, GSTM1 and GSTP1). We found a significantly higher number of DNA SBs, measured by a modified comet assay, in mononuclear leukocytes of the styrene-exposed workers compared with results from 19 unexposed controls (P<0.001). A fairly strong correlation was observed between SBs and years of exposure (P<0.001, r=0.545). The styrene-exposed workers also showed a significantly increased frequency of chromosomal aberrations (P<0.0001 for highly exposed group, P<0.004 for medium-exposed group, and P=0.0001 for low-exposed group). The proliferative response of T-lymphocytes stimulated with concanavalin A was significantly suppressed in people exposed to styrene (P<0.05). We recorded a significant increase of the percentage of monocytes in differential white blood cell counts in the exposed group (P<0.05). Using flow cytometry, we found an increased expression of adhesion molecules CD62L, CD18, CD11a, CD11b, CD49d and CD54 in the exposed workers as compared with the control group (P<0.05).

Breast and cervical carcinoma: the correlation of activity limitations and rurality with screening, disease incidence, and mortality.

BACKGROUND: Although screening for breast and cervical carcinoma has been widely accepted as beneficial, specific segments of the population are not receiving these services as frequently as recommended. The objective of this study was to describe differences in breast and cervical screening prevalence among those with activity limitations and those residing in rural areas. Disparities in the incidence rates of in situ breast carcinoma and cervical carcinoma, as well as mortality among rural and urban women, are also described. METHODS: Data from the Iowa Behavioral Risk Factor Surveillance System (BRFSS) and Iowa's Surveillance, Epidemiology, and End Results (SEER) were used to determine the prevalence of screening and adverse outcomes among rural populations. To describe the rural nature of counties, the authors used the number of residents per square mile for each county and classified the results into five groups. Mulitple logistic regression was used to determine the prevalence of screening among those with activity limitations and rural residents. RESULTS: Using the BRFSS, those with activity limitations and those residing in rural Iowa were less likely screened for breast or cervical carcinoma. This translated into a lower in situ breast carcinoma incidence rate and a higher invasive cervical carcinoma incidence rate among rural women relative to their urban counterparts. No differences were found for mortality from these cancers. CONCLUSIONS: Lower screening prevalence among rural residents translated into adverse health outcomes. Interventions for increasing the frequency of screening are described.

An assessment of exposure to mercury and mercuric chloride from handling treated herbarium plants.

A curator at a university herbarium reported headache, nausea and mucosal irritation after initiating a project to remount plant specimens treated with mercuric chloride. Workplace exposure assessment indicated potential for mercury compound ingestion through hand-to-mouth contact. Blood, hair and urine assays were negative.

Urticaria due to airborne permethrin exposure.

Although naturally derived pyrethrins are well recognized sensitizers, there is currently some degree of controversy regarding the sensitizing potential of synthetic pyrethroids. The literature is briefly reviewed, and an outbreak of several cases of urticaria occurring in children from 1 household and associated with airborne exposure to permethrin is reported.