The U.S. Department of Veterans' Affairs depleted uranium exposed cohort at 25 Years: Longitudinal surveillance results.

BACKGROUND: A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly-fire incidents have been monitored for health changes in a clinical surveillance program at the Veterans Affairs Medical Center, Baltimore since 1994. METHODS: During the spring of 2015, an in-patient clinical surveillance protocol was performed on 36 members of the cohort, including exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes. RESULTS: On-going mobilization of U from embedded fragments is evidenced by elevated urine U concentrations. The DU isotopic signature is observed principally in participants possessing embedded fragments. Those with only an inhalation exposure have lower urine U concentration and a natural isotopic signature. CONCLUSIONS: At 25 years since first exposure to DU, an aging cohort of military veterans continues to show no U-related health effects in known target organs of U toxicity. As U body burden continues to accrue from in-situ mobilization from metal fragment depots, and increases with exposure duration, critical tissue-specific U concentration thresholds may be reached, thus recommending on-going surveillance of this veteran cohort.

Biologic monitoring and surveillance results for the department of veterans affairs' depleted uranium cohort: Lessons learned from sustained exposure over two decades.

BACKGROUND: A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly fire incidents have been monitored in a clinical surveillance program at the Veterans Affairs Medical Center, Baltimore since 1994. METHODS: An in-patient clinical surveillance protocol was performed on 35 members of the cohort, including exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes. RESULTS: Although urine U concentrations continue to be elevated in this group, illustrating on-going in situ mobilization of U from embedded fragments, no consistent U-related health effects have been observed. CONCLUSIONS: Now more than 20 years since first exposure to DU, an aging cohort of military veterans continues to show no U-related health effects in known target organs of U toxicity. As tissue concentrations continue to accrue with exposure duration, critical tissue-specific U concentration thresholds may be reached, thus recommending on-going surveillance of this veteran cohort.

Chapter 4 embedded metal fragments.

The continued evolution of military munitions and armor on the battlefield, as well as the insurgent use of improvised explosive devices, has led to embedded fragment wounds containing metal and metal mixtures whose long-term toxicologic and carcinogenic properties are not as yet known. Advances in medical care have greatly increased the survival from these types of injuries. Standard surgical guidelines suggest leaving embedded fragments in place, thus individuals may carry these retained metal fragments for the rest of their lives. Nursing professionals will be at the forefront in caring for these wounded individuals, both immediately after the trauma and during the healing and rehabilitation process. Therefore, an understanding of the potential health effects of embedded metal fragment wounds is essential. This review will explore the history of embedded fragment wounds, current research in the field, and Department of Defense and Department of Veterans Affairs guidelines for the identification and long-term monitoring of individuals with embedded fragments.

Long-term exposure to depleted uranium in Gulf-War veterans does not induce chromosome aberrations in peripheral blood lymphocytes.

Depleted uranium (DU) is a high-density heavy metal that has been used in munitions since the 1991 Gulf War. DU is weakly radioactive and chemically toxic, and long-term exposure may cause adverse health effects. This study evaluates genotoxic effects of exposure to DU by measuring chromosome damage in peripheral blood lymphocytes with fluorescence in situ hybridization whole-chromosome painting. Study participants are Gulf War-I Veterans with embedded DU fragments and/or inhalation exposure due to involvement in friendly-fire incidents; they are enrolled in a long-term health surveillance program at the Baltimore Veterans Administration Medical Center. Blood was drawn from 35 exposed male veterans aged 39 to 62 years. Chromosomes 1, 2, and 4 were painted red and chromosomes 3, 5, and 6 were simultaneously labeled green. At least 1800 metaphase cells per subject were scored. Univariate regression analyses were performed to evaluate the effects of log(urine uranium), age at time of blood draw, log(lifetime X-rays), pack-years smoked and alcohol use, against frequencies of cells with translocated chromosomes, dicentrics, acentric fragments, color junctions and abnormal cells. No significant relationships were observed between any cytogenetic endpoint and log(urine uranium) levels, smoking, or log(lifetime X-rays). Age at the time of blood draw showed significant relationships with all endpoints except for cells with acentric fragments. Translocation frequencies in these Veterans were all well within the normal range of published values for healthy control subjects from around the world. These results indicate that chronic exposure to DU does not induce significant levels of chromosome damage in these Veterans.

Potential health effects related to pesticide use on athletic fields.

OBJECTIVES: Children come in contact with athletic fields on a daily basis. How these fields are maintained may have an impact on children's potential exposure to pesticides and associated health effects. DESIGN AND SAMPLE: This is a cross-sectional, descriptive study that utilized a survey to assess playing field maintenance practices regarding the use of pesticides. Athletic fields (N = 101) in Maryland were stratified by population density and randomly selected. MEASURES: A survey was administered to field managers (n = 33) to assess maintenance practices, including the use of pesticides. Analysis included descriptive statistics and generalized estimating equations. RESULTS: Managers of 66 fields (65.3%) reported applying pesticides, mainly herbicides (57.4%). Managers of urban and suburban fields were less likely to apply pesticides than managers of rural fields. Combined cultivation practice was also a significant predictor of increased pesticide use. CONCLUSIONS: The use of pesticides on athletic fields presents many possible health hazards. Results indicate that there is a significant risk of exposure to pesticide for children engaged in sports activities. Given that children are also often concurrently exposed to pesticides as food residues and from home pest management, we need to examine opportunities to reduce their exposures. Both policy and practice questions are raised.

Methodology for collecting, storing, and analyzing human milk for volatile organic compounds.

Biomonitoring, or the measurement of environmental chemicals in human tissues and fluids, is used to supplement-and in some cases replace-more traditional exposure assessments which measure chemicals in environmental media. Volatile organic compounds (VOCs) in physiological fluids are biomarkers of exposure that present numerous challenges for sample collection and analysis. To date, a thorough evaluation of methods for collection and analysis of breast milk samples for volatiles has not been conducted. In this paper, we describe the development and validation of methods for collecting, storing, and analyzing 36 volatile organic compounds (VOCs) in breast milk to assess VOC exposure of lactating women and nursing infants. Volatile analyte loss was minimized by collecting and storing samples in containers with small headspace volume resulting in recovery >or=70% for all 10 VOCs detected in most breast milk samples. Potential contamination by chloroform, benzene, toluene, ethylbenzene, xylenes, and methyl-tert-butyl ether was minimized by using specially treated sample collection materials. Method detection limits in the low parts per trillion range were achieved by using solid-phase microextraction headspace sampling, gas chromatography, and selective ion monitoring mass spectrometry. We used this method to analyze 3 mL aliquots of breast milk collected from 12 women and found that 10 of the 36 VOCs were detectable in most samples (median values follow): m/p-xylene, 0.539 ng mL(-1); toluene, 0.464 ng mL(-1); 1,4-dichlorobenzene, 0.170 ng mL(-1); tetrachloroethylene, 0.165 ng mL(-1); o-xylene, 0.159 ng mL(-1); ethylbenzene, 0.0149 ng mL(-1); styrene, 0.129 ng mL(-1); benzene, 0.080 ng mL(-1); chloroform, 0.030 ng mL(-1); and methyl-tert-butyl ether, 0.016 ng mL(-1).

Semen Uranium Concentrations in Depleted Uranium Exposed Gulf War Veterans: Correlations with Other Body Fluid Matrices.

Environmental metal exposure, as well as dietary metals, may adversely affect semen quality even as others play an essential role in normal spermatogenesis and fertility. Measures of seminal fluid metals have therefore been of high interest in the last several decades but have shown inconsistent results in correlations with some semen quality parameters. As well, environmental metal measures across various body fluid matrices have not been consistently correlated contrary to what one might hypothesize based on a systemic body burden of metal. This may be due to the body fluid matrices assessed and to other differences in laboratory methods and sample preparation. Measures of uranium, a potentially toxic metal in humans, have not previously been reported in the semen of environmentally metal-exposed populations. We report here uranium seminal fluid results and the high correlation of uranium concentrations across several body fluid matrices in a cohort of military veterans exposed to depleted uranium in combat events during the Iraqi Gulf War. These results inform the risk communication conversation for exposed populations and broaden the public health assessments from various exposure scenarios.

Elevated ambient air zinc increases pediatric asthma morbidity.

BACKGROUND: Recent studies indicate that the composition of fine particulate matter [PM

Measuring extent of surface contamination produced by the handling of antineoplastic drugs in low- to middle-income country oncology health care settings.

Antineoplastic drugs are known to cause detrimental effects to health care workers who are exposed through work tasks. Environmental monitoring studies are an excellent approach to measure the extent of surface contamination produced by the handling of antineoplastic drugs in the workplace and to assess the potential for occupational exposures in oncology health care settings. The main aim of the study was to establish the extent of surface contamination produced by the handling of antineoplastic drugs in a limited-resource oncology health care facility in Colombia by conducting an environmental monitoring study using affordable analytical instrumentation. Contamination with antineoplastic drugs was widespread in the health care facility under evaluation, which could result in health care worker exposure to antineoplastic drugs. A comprehensive review of current safety guidelines and protocols including assessment of adherence in the health care facility should be done.

Metal Exposure in Veterans With Embedded Fragments From War-Related Injuries: Early Findings From Surveillance Efforts.

OBJECTIVE: To characterize systemic metal exposures from retained fragments in a cohort of war-injured US Veterans enrolled in the Department of Veterans Affairs' Embedded Fragment Registry. METHODS: Five hundred seventy nine registry-enrolled Veterans submitted an exposure questionnaire and urine sample for analyses of 14 metals often found in fragments. Urine metal results were compared with reference values of unexposed populations to identify elevations. RESULTS: 55% of Veterans had normal urine metal values. When observed, tungsten and zinc were the metals most frequently elevated, followed by cobalt; however, cobalt levels were not associated with a fragment source, but with surgical implants present. CONCLUSIONS: Though most metal elevations observed are not significantly outside the normal range, on-going accrual of metal burdens in these Veterans over time recommends continued surveillance which may inform future medical management.

Mobilization of Metal From Retained Embedded Fragments in a Blast-Injured Iraq War Veteran.

A frequent comorbidity of traumatic injury due to a blast or explosion, commonly reported in Iraq and Afghanistan veterans, is that of retained embedded fragments typically of unknown content. Because of concerns over both local and systemic health effects related to both the physical presence of and mobilization of materials from embedded fragments, the Department of Veterans Affairs established a surveillance program for this group of veterans. We present here the case of a surveillance-enrolled veteran who submitted: (1) three surgically removed fragments for content analyses, (2) tissue adhered to the fragments for histology and metal concentration evaluation, and (3) pre- and postfragment removal urine samples to assess concentrations of various metals often found in fragments. Results indicate that removed fragments were aluminum-copper alloys. Surrounding tissue analyses revealed elevated concentrations of these metals and evidence of chronic inflammation, but no neoplastic changes. Urine aluminum concentrations, initially elevated compared to normal population values, decreased significantly after fragment removal, illustrating the utility of urine biomonitoring to provide insight into fragment composition. A medical surveillance program integrating fragment composition data, tissue analyses, and repeat urine biomonitoring can help inform the patient-specific medical management of both the local and systemic effects of retained metal fragments.

Prediction of renal concentrations of depleted uranium and radiation dose in Gulf War veterans with embedded shrapnel.

Mobilization of uranium (U) from embedded depleted uranium (DU) metal fragments in Gulf War veterans presents a unique exposure scenario for this radioactive and nephrotoxic metal. In a cohort of exposed veterans, urine U concentrations measured every two years since 1993 persistently range from 10 to over 500 times normal levels, indicating that embedded DU fragments give rise to chronic, systemic exposure to U. Health effects of this exposure are not fully known, but clinical surveillance of these soldiers continues in light of animal studies showing that U released from implanted DU pellets results in tissue accumulation of U. The biokinetic model for uranium recommended by the International Commission on Radiological Protection was used to predict kidney U concentrations and tissue radiation doses in veterans with DU shrapnel based on their urine U excretion. Results suggest that kidney U concentrations in some individuals reached their peak within six years after the war, while in others, concentrations continue to increase and are approaching 1 ppm after 10 y. These results are consistent with urine biomarker tests of renal proximal tubular cell function and cytotoxicity which have shown elevated mean urinary protein excretion indicative of functional effects in veterans with high urine U concentrations (> or =0.10 microg g(-1) creatinine). Predicted lifetime effective radiation dose from DU released to the blood for the highest exposed individual in this cohort was substantially less than the National Council on Radiation Protection (NCRP) limit for occupational exposure. These results provide further support for current health protection guidelines for DU, which are based on the metal's chemical rather than its radiological toxicity. In light of the potential for continued accumulation of U in the kidney to concentrations approaching the traditional guidance level of 3 ppm U, these results indicate the need for continued surveillance of this population for evidence of developing renal dysfunction.

Detection of a wide variety of human and veterinary fluoroquinolone antibiotics in municipal wastewater and wastewater-impacted surface water.

As annual sales of antibiotics continue to rise, the mass of these specially-designed compounds entering municipal wastewater treatment systems has also increased. Of primary concern here is that antibiotics can inhibit growth of specific microorganisms in biological processes of wastewater treatment plants (WWTPs) or in downstream ecosystems. Growth inhibition studies with Escherichia coli demonstrated that solutions containing 1-10 µg/L of fluoroquinolones can inhibit microbial growth. Wastewater samples were collected on a monthly basis from various treatment stages of a 30 million gallon per day WWTP in Maryland, USA. Samples were analyzed for the presence of 11 fluoroquinolone antibiotics. At least one fluoroquinolone was detected in every sample. Ofloxacin and ciprofloxacin exhibited detection frequencies of 100% and 98%, respectively, across all sampling sites. Concentrations of fluoroquinolones in raw wastewater were as high as 1900 ng/L for ciprofloxacin and 600 ng/L for ofloxacin. Difloxacin, enrofloxacin, fleroxacin, moxifloxacin, norfloxacin, and orbifloxacin were also detected at appreciable concentrations of 9-170 ng/L. The total mass concentration of fluoroquinolones in raw wastewater was in the range that inhibited E. coli growth, suggesting that concerns over antibiotic presence in wastewater and wastewater-impacted surface water are valid. The average removal efficiency of fluoroquinolones during wastewater treatment was approximately 65%; furthermore, the removal efficiency for fluoroquinolones was found to be negatively correlated to biochemical oxygen demand removal and positively correlated to phosphorus removal.

Significance of dermatologic findings in a cohort of depleted uranium-exposed veterans of Iraqi conflicts.

BACKGROUND: Depleted uranium (DU)-containing weapons have been used in military operations since 1991. There is interest in following veterans who were occupationally exposed to DU by either inhalation or retention of fragments. A cohort of DU-exposed Gulf War I veterans has been followed longitudinally at the Baltimore Veterans Administration Medical Center since 1993. OBJECTIVE: The aim was to monitor chronic dermatological findings associated with occupational DU exposure in the 2013 cohort. METHODS: Thirty-five veterans were evaluated. This study was reviewed and approved by the institutional review board and the Baltimore Veterans Administration Medical Center research service. Depleted uranium exposure was measured using creatinine-adjusted urine uranium concentrations (micrograms of uranium per gram of creatinine [µgU/gCrea]). Detailed medical histories, physical examinations, and exposure histories were performed. RESULTS: Using a cutoff level of 0.1 µgU/gCrea, 11 veterans were placed in the high-uranium exposure group, whereas 23 veterans were placed in the low-uranium exposure group. Retained fragments were documented in 91% of the high-exposure group versus that in 13% of the low-exposure group (P < 0.001), and fragment-related scarring was significantly increased in the high-exposure group (P = 0.002). Other dermatological findings such as dermatitis were also assessed. CONCLUSIONS: Fragment retainment and related scarring was significantly increased in veterans exposed to high levels of DU. Continuous monitoring of this cohort will yield interesting dermatological findings related to DU exposure.

Mutagenicity monitoring following battlefield exposures: Longitudinal study of HPRT mutations in Gulf War I veterans exposed to depleted uranium.

A total of 70 military Veterans have been monitored for HPRT T-cell mutations in five separate studies at 2-year intervals over an 8-year period. Systemic depleted uranium (DU) levels were measured at the time of each study by determining urinary uranium (uU) excretion. Each HPRT study included 30-40 Veterans, several with retained DU-containing shrapnel. Forty-nine Veterans were evaluated in multiple studies, including 14 who were in all five studies. This permitted a characterization of the HPRT mutation assay over time to assess the effects of age, smoking and non-selected cloning efficiencies, as well as the inter- and intra-individual variability across time points. Molecular analyses identified the HPRT mutation and T-cell receptor (TCR) gene rearrangement in 1,377 mutant isolates. An unexpected finding was that in vivo clones of HPRT mutant T-cells were present in some Veterans, and could persist over several years of the study. The calculated HPRT mutant frequencies (MFs) were repeatedly elevated in replicate studies in three outlier Veterans with elevated urinary uranium excretion levels. However, these three outlier Veterans also harbored large and persistent in vivo HPRT mutant T-cell clones, each of which was represented by a single founder mutation. Correction for in vivo clonality allowed calculation of HPRT T-cell mutation frequencies (MutFs). Despite earlier reports of DU associated increases in HPRT MFs in some Veterans, the results presented here demonstrate that HPRT mutations are not increased by systemic DU exposure. Additional battlefield exposures were also evaluated for associations with HPRT mutations and none were found.

Mutagenicity monitoring following battlefield exposures: Molecular analysis of HPRT mutations in Gulf War I veterans exposed to depleted uranium.

Molecular studies that involved cDNA and genomic DNA sequencing as well as multiplex PCR of the HPRT gene were performed to determine the molecular mutational spectrum for 1,377 HPRT mutant isolates obtained from 61 Veterans of the 1991 Gulf War, most of whom were exposed to depleted uranium (DU). Mutant colonies were isolated from one to four times from each Veteran (in 2003, 2005, 2007, and/or 2009). The relative frequencies of the various types of mutations (point mutations, deletions, insertions, etc.) were compared between high versus low DU exposed groups, (based on their urine U concentration levels), with HPRT mutant frequency (as determined in the companion paper) and with a database of historic controls. The mutational spectrum includes all classes of gene mutations with no significant differences observed in Veterans related to their DU exposures.

Pesticides, gene polymorphisms, and bladder cancer among Egyptian agricultural workers.

This study examined the associations between pesticide exposure, genetic polymorphisms for NAD(P)H: quinone oxidoreductase I (NQO1) and superoxide dismutase 2 (SOD2), and urinary bladder cancer risk among male agricultural workers in Egypt. Logistic regression was used to analyze data from a multicenter case-control study and estimate adjusted odds ratio (OR) and 95% confidence interval (CI). Exposure to pesticides was associated with increased bladder cancer risk (odds ratio (95% confidence interval): 1.68 (1.23-2.29)) in a dose-dependent manner. The association was slightly stronger for urothelial (1.79 (1.25-2.56)) than for squamous cell (1.55 (1.03-2.31)), and among participants with combined genotypes for low NQO1 and high SOD2 (2.14 (1.19-3.85)) activities as compared with those with high NQO1 and low SOD2 genotypes (1.53 (0.73-3.25)). In conclusion, among male agricultural workers in Egypt, pesticide exposure is associated with bladder cancer risk and possibly modulated by genetic polymorphism.

Health effects of depleted uranium on exposed Gulf War veterans: a 10-year follow-up.

Medical surveillance of a group of U.S. Gulf War veterans who were victims of depleted uranium (DU) "friendly fire" has been carried out since the early 1990s. Findings to date reveal a persistent elevation of urine uranium, more than 10 yr after exposure, in those veterans with retained shrapnel fragments. The excretion is presumably from ongoing mobilization of DU from fragments oxidizing in situ. Other clinical outcomes related to urine uranium measures have revealed few abnormalities. Renal function is normal despite the kidney's expected involvement as the "critical" target organ of uranium toxicity. Subtle perturbations in some proximal tubular parameters may suggest early although not clinically significant effects of uranium exposure. A mixed picture of genotoxic outcomes is also observed, including an association of hypoxanthine-guanine phosphoribosyl transferase (HPRT) mutation frequency with high urine uranium levels. Findings observed in this chronically exposed cohort offer guidance for predicting future health effects in other potentially exposed populations and provide helpful data for hazard communication for future deployed personnel.

Efficacy of laser debridement with autologous split-thickness skin grafting in promoting improved healing of deep cutaneous sulfur mustard burns.

The consequences of receiving a cutaneous sulfur mustard (SM) burn are prolonged wound healing and secondary infection. This study was undertaken to find a treatment that promotes quick healing with few complications and minimal disfigurement. Multiple deep SM burns (4 cm diameter) were generated on the ventrum of weanling pigs and treated at 48 h. Four treatments were compared: (1) full-thickness CO(2) laser debridement followed by skin grafting; (2) full-thickness sharp surgical tangential excision followed by skin grafting, the "Gold Standard" used in deep thermal burns management; (3) partial-thickness laser ablation with no grafting; and (4) partial-thickness sharp excision with no grafting. A computer controlled, raster scanned, high-powered continuous wave (cw) CO(2) laser was utilized. Ulceration, wound geometry, and wound contraction were evaluated during a 36-day healing period. Histopathological evaluations were conducted at the end of the healing period. Engraftment rates were similar between both methods of debridement. Laser debridement followed by skin grafting was as efficacious in improving the wound healing of deep SM burns as the "Gold Standard." Full-thickness laser debridement of these small total body surface area (TBSA) burns was time efficient and provided adequate beds for split-thickness skin grafting. Laser debridement offered additional benefits that included hemostatic control during surgery and minimal debridement of normal perilesional skin. Mid-dermal debridement by sharp excision or laser ablation without grafting produced less desirable results but was better than no treatment.

Biologic monitoring for urinary uranium in gulf war I veterans.

Biologic monitoring for total uranium in urine of Gulf War I veterans concerned about past exposure to depleted uranium (DU) has been offered by the Departments of Veterans Affairs and Defense since the late 1990's. DU, a component of U.S. munitions and tank armor, was first used during that conflict. Two hundred and twenty-seven veterans submitted samples for analysis from January 2000 through December 2002, which included a 24-h urine sample for determination of total urinary uranium concentration and completed questionnaires describing their wartime exposure experiences. Thirty questionnaire items characterizing DU exposure opportunities were collapsed into 19 exposure categories. Urine uranium (U) results were stratified into low and high uranium groups with 0.05 microg U g creatinine as the cut point. Exposure scenarios in the high and low uranium groups were similar in frequency and type with only the presence of retained shrapnel being predictive of a high urine uranium value, as found in the first phase of this surveillance of 169 veterans performed prior to 2000. Twenty-two veterans exhibited U levels in the high range. Isotopic analysis, available for 21 of these 22, revealed that all but three of these samples contained natural and not depleted uranium. These three participants had retained DU shrapnel as a result of their past injuries. Thus, even with an enlarged cohort, elevated urine uranium values in the absence of retained DU fragments are unlikely. The utility of isotopic analysis to more fully characterize uranium biomonitoring results is also demonstrated.