Longitudinal evaluation of markers of inflammation in HIV-positive and HIV-negative Rwandan women.

OBJECTIVES: African women are disproportionately affected by HIV infection and may experience non-AIDS-related complications associated with inflammation. High-sensitivity C-reactive protein (hsCRP), d-dimer and transthyretin have been examined as inflammatory markers elsewhere, but it is unclear how they change over time in HIV-negative or HIV-positive African women with or without antiretroviral therapy (ART) initiation. METHODS: We examined hsCRP, d-dimer and transthyretin levels at baseline and at follow-up of ≥2 years in 185 HIV-negative and 510 HIV-positive Rwandan women who were ART naïve at study entry. Generalized estimating equations for each marker were used to investigate the association with HIV infection/CD4 count, ART and follow-up time. RESULTS: Compared with HIV-negative women, HIV-positive women had higher hsCRP and d-dimer and lower transthyretin concentrations, with greater differences at lower CD4 counts. After adjusting for CD4 count and other factors, ART was not significantly associated with log hsCRP (P = 0.36) at follow-up, but was independently associated with lower log d-dimer (P = 0.03) and higher transthyretin (P = 0.0008) concentrations. At ≥ 2 years of follow-up, hsCRP had not significantly changed in any group but log d-dimer had decreased significantly in all groups. Transthyretin declined significantly over time in HIV-negative women and HIV-positive non-ART initiators, but increased significantly in HIV-positive ART initiators. CONCLUSIONS: HIV infection and advanced immune suppression were associated with higher hsCRP and d-dimer and lower transthyretin concentrations. ART (independently of CD4 changes) was significantly associated with decreases in d-dimer and increases in transthyretin, but, in contrast to other studies, was not associated with decreases in hsCRP. We found no change in hsCRP over time in any group.

Photosynthetic responses of a dominant C4 grass to an experimental heat wave are mediated by soil moisture.

Extreme heat waves and drought are predicted to increase in frequency and magnitude with climate change. These extreme events often co-occur, making it difficult to separate their direct and indirect effects on important ecophysiological and carbon cycling processes such as photosynthesis. Here, we assessed the independent and interactive effects of experimental heat waves and drought on photosynthesis in Andropogon gerardii, a dominant C4 grass in a native mesic grassland. We experimentally imposed a two-week heat wave at four intensity levels under two contrasting soil moisture regimes: a well-watered control and an extreme drought. There were three main findings from this study. First, the soil moisture regimes had large effects on canopy temperature, leading to extremely high temperatures under drought and low temperatures under well-watered conditions. Second, soil moisture mediated the photosynthetic response to heat; heat reduced photosynthesis under the well-watered control, but not under the extreme drought treatment. Third, the effects of heat on photosynthesis appeared to be driven by a direct thermal effect, not indirectly through other environmental or ecophysiological variables. These results suggest that while photosynthesis in this dominant C4 grass is sensitive to heat stress, this sensitivity can be overwhelmed by extreme drought stress.

Bone quality assessed using quantitative ultrasound at the distal radius does not differ in antiretroviral therapy-naïve HIV-positive and HIV-negative Rwandan women.

OBJECTIVES: The incidence of fractures appears to be increased in HIV-infected individuals. METHODS: We assessed bone quality using quantitative ultrasound (QUS) in HIV-infected and uninfected Rwandan women. A Sunlight Omnisense 7000 QUS was used to measure the speed of ultrasound (SOS) at the distal radius in 646 antiretroviral therapy (ART)-naïve HIV-infected women and 211 HIV-uninfected women. The Z-scores for SOS were based on data for women of the same age from the manufacturer's reference material. RESULTS: The mean CD4 cell count was 285 (± 166) cells/µL in the HIV-positive women. SOS Z-scores adjusted and unadjusted for body mass index did not differ between the groups. SOS did not differ by CD4 count (< 200 vs. ≥ 200 cells/µL: 4016 (± 117) vs. 4028 (± 107) m/s, respectively; p=0.19. CONCLUSIONS: In HIV-positive ART-naïve Rwandan women with advanced HIV disease, bone quality at the distal radius was similar to that in HIV-negative controls.

First high-convergence cryogenic implosion in a near-vacuum hohlraum.

Recent experiments on the National Ignition Facility [M. J. Edwards et al., Phys. Plasmas 20, 070501 (2013)] demonstrate that utilizing a near-vacuum hohlraum (low pressure gas-filled) is a viable option for high convergence cryogenic deuterium-tritium (DT) layered capsule implosions. This is made possible by using a dense ablator (high-density carbon), which shortens the drive duration needed to achieve high convergence: a measured 40% higher hohlraum efficiency than typical gas-filled hohlraums, which requires less laser energy going into the hohlraum, and an observed better symmetry control than anticipated by standard hydrodynamics simulations. The first series of near-vacuum hohlraum experiments culminated in a 6.8 ns, 1.2 MJ laser pulse driving a 2-shock, high adiabat (α∼3.5) cryogenic DT layered high density carbon capsule. This resulted in one of the best performances so far on the NIF relative to laser energy, with a measured primary neutron yield of 1.8×10(15) neutrons, with 20% calculated alpha heating at convergence ∼27×.

Improved Performance of High Areal Density Indirect Drive Implosions at the National Ignition Facility using a Four-Shock Adiabat Shaped Drive.

Hydrodynamic instabilities can cause capsule defects and other perturbations to grow and degrade implosion performance in ignition experiments at the National Ignition Facility (NIF). Here, we show the first experimental demonstration that a strong unsupported first shock in indirect drive implosions at the NIF reduces ablation front instability growth leading to a 3 to 10 times higher yield with fuel ρR>1 g/cm(2). This work shows the importance of ablation front instability growth during the National Ignition Campaign and may provide a path to improved performance at the high compression necessary for ignition.

First measurements of hydrodynamic instability growth in indirectly driven implosions at ignition-relevant conditions on the National Ignition Facility.

Ignition experiments have shown an anomalous susceptibility to hydrodynamic instability growth. To help understand these results, the first hydrodynamic instability growth measurements in indirectly driven implosions on the National Ignition Facility were performed at ignition conditions with peak radiation temperatures up to ∼300 eV. Plastic capsules with two-dimensional preimposed, sinusoidal outer surface modulations of initial wavelengths of 240 (corresponding to a Legendre mode number of 30), 120 (mode 60), and 80 µm (mode 90) were imploded by using actual low-adiabat ignition laser pulses. The measured growth was in excellent agreement, validating 2D hydra simulations for the most dangerous modes in the acceleration phase. These results reinforce confidence in the predictive capability of calculations that are paramount to illuminating the path toward ignition.

Frailty-Related Factors among Women Living with and without HIV Aged 40 Years and Older. The Women's Interagency HIV Study.

BACKGROUND: Frailty is a clinical, geriatric syndrome linked to disability and mortality; and may be associated with a variety of factors among underrepresented and underserved women living with HIV (WLWH) and without HIV (WLWOH) transitioning through the adult life course. OBJECTIVES: Determine whether a published set of factors associated cross-sectionally with frailty in WLWH and similar WLWOH at average age 39 years in 2005/2006 were associated with frailty in 2018/2019 among women who initiated frailty assessments at age ≥40 years, or whether a new set of factors were associated with frailty. DESIGN: Cross-sectional analyses within a longitudinal cohort study. SETTING: The multi-center Women's Interagency HIV Study (WIHS). PARTICIPANTS: 1285 participants (951 WLWH, 334 WLWOH), median age 53 years (interquartile range 47-58 years). MEASUREMENTS: The Fried Frailty Phenotype (FFP) in association with 23 factors representing HIV serostatus, other infections, sociodemographic factors, health behaviors, and chronic diseases. RESULTS: Frailty prevalence was 11.1% in 2018/2019 (12.6% among WLWOH, 9.6% among WLWH, p=0.121). The published 2005/2006 final multivariable stepwise regression model contained 9 predictors of frailty. When refit to women in 2018/2019, only age ≥50 years and annual income ≤$12,000 were independently positively associated with frailty; other significant 2005/2006 factors, HIV serostatus, CD4+ count <500 cells/mL among WLWH, smoking, drinking, FIB-4 and eGFR, were not. A newly-derived stepwise model considering all 23 predictors measured in 2018/2019, showed independent positive associations between frailty and age ≥50 years, annual income ≤$12,000, obesity (body mass index (BMI) ≥30kg/m2), and history of tuberculosis and cancer. CONCLUSION: Different chronic and infectious disease factors were associated with frailty among WLWH and WLWOH over the adult life course. Understanding factors associated with frailty by adult life stage, allows identification and implementation of novel, temporal interventions to alleviate frailty-associated outcomes and enhance quality of life among WLWH and WLWOH.

A Comparison of Strategies to Increase Household Survey Response Rates in a Predominantly Indigenous Community Population.

The present study describes 4 strategies for increasing response rates to a community-based survey on youth violence in an ethnically diverse population in Hawai'i. A total of 350 households were mailed a Safe Community Survey using 4 different randomly assigned incentive strategies. The strategies varied by length of survey and timing of incentive for completion (given before completion, after completion, or both). In univariate analyses, there were no significant differences across survey strategies on participant demographics, community perceptions of violence-related behaviors, or percent of missing items. However, in multivariate regressions, respondents' sex and percent of missing items on the surveys were consistently significant predictors across multiple outcomes. Although the use of strategies to increase response rates in community-based surveys might be desirable, resulting data need to be examined for the potential that strategies might recruit different populations, which may have an impact on the data obtained. This study offers lessons and recommendations for surveying Native and Indigenous communities.

Use of zero-valent iron biosand filters to reduce Escherichia coli O157:H12 in irrigation water applied to spinach plants in a field setting.

AIMS: Zero-valent iron (ZVI) filters may provide an efficient method to mitigate the contamination of produce crops through irrigation water. METHODS: A field-scale system was utilized to evaluate the effectiveness of a biosand filter (S), a biosand filter with ZVI incorporated (ZVI) and a control (C, no treatment) in decontaminating irrigation water. An inoculum of c.8·5log CFU100ml(-1) of Escherichia coli O157:H12 was introduced to all three column treatments in 20-l doses. Filtered waters were subsequently overhead irrigated to 'Tyee' spinach plants. Water, spinach plant and soil samples were obtained on days 0, 1, 4, 6, 8, 10, 13 and 15 and analysed for E. coli O157:H12 populations. RESULTS: ZVI filters inactivated c.6logCFU100ml(-1) E. coli O157:H12 during filtration on day 0, significantly (P<0·05) more than S filter (0·49CFU100ml(-1)) when compared to control on day 0 (8·3log CFU100ml(-1)). On day 0, spinach plants irrigated with ZVI-filtered water had significantly lower E. coli O157 counts (0·13logCFUg(-1)) than spinach irrigated with either S-filtered (4·37logCFUg(-1)) or control (5·23logCFUg(-1)) water. Soils irrigated with ZVI-filtered water contained E. coli O157:H12 populations below the detection limit (2logCFUg(-1)), while those irrigated with S-filtered water (3·56logCFUg(-1)) were significantly lower than those irrigated with control (4·64logCFUg(-1)). CONCLUSIONS: ZVI biosand filters were more effective in reducing E. coli O157:H12 populations in irrigation water than sand filters. SIGNIFICANCE AND IMPACT OF THE STUDY: Zero-valent ion treatment may be a cost-effective mitigation step to help small farmers reduce risk of foodborne E. coli infections associated with contamination of leafy greens.

Longitudinal health surveillance in a cohort of Gulf War veterans 18 years after first exposure to depleted uranium.

As part of a longitudinal surveillance program, 35 members of a larger dynamic cohort of 79 Gulf War I veterans exposed to depleted uranium (DU) during combat underwent clinical evaluation at the Baltimore Veterans Administration Medical Center. Health outcomes and biomonitoring results were obtained to assess effects of DU exposure and determine the need for additional medical intervention. Clinical evaluation included medical and exposure histories, physical examination, and laboratory studies including biomarkers of uranium (U) exposure. Urine collections were obtained for U analysis and to measure renal function parameters. Other laboratory measures included basic hematology and chemistry parameters, blood and plasma U concentrations, and markers of bone metabolism. Urine U (uU) excretion remained above normal in participants with embedded DU fragments, with urine U concentrations ranging from 0.006 to 1.88 µg U/g creatinine. Biomarkers of renal effects showed no apparent evidence of renal functional changes or cellular toxicity related to U body burden. No marked differences in markers of bone formation or bone resorption were observed; however, a statistically significant decrease in levels of serum intact parathyroid hormone and significant increases in urinary calcium and sodium excretion were seen in the high versus the low uU groups. Eighteen years after first exposure, members of this cohort with DU fragments continue to excrete elevated concentrations of uU. No significant evidence of clinically important changes was observed in kidney or bone, the two principal target organs of U. Continued surveillance is prudent, however, due to the ongoing mobilization of uranium from fragment depots.

A Mixed Methods Study on Engagement and Satisfaction with a Digitally-Enhanced Pilot Intervention Among African American and Hispanic Women.

African American and Hispanic women report less physical activity (PA) than non-Hispanic White women. As such, a digitally-enhanced 16-week social support pilot intervention was conducted to promote PA among African American and Hispanic women dyads. This study quantitatively and qualitatively examined the engagement and satisfaction of participants (N = 30; 15 dyads) assigned to the intervention. Intervention participants received telephone counseling calls based on motivational interviewing and a Jawbone UP activity monitor. Intervention engagement and satisfaction data were collected from the Jawbone UP, call logs, self-report questionnaires conducted at the 16-week follow-up, and two post-intervention focus groups. Nonparametric tests assessed group differences across engagement and satisfaction measures, and a manually-driven coding scheme was used to evaluate emerging themes from qualitative text. Participants demonstrated high engagement in the telephone counseling sessions and moderate engagement with the Jawbone UP. Friend/co-worker dyads and participants who were 45 years and older were more likely to use the device. Qualitative results emphasized participants' appreciation for the counseling calls, the Jawbone UP, and the overall dyadic framework of the study to collectively nurture social support and accountability for PA. Overall, the intervention group reacted positively to study components. Additional research is needed to understand the role of technology in facilitating long-lasting PA change via social support in minority populations.

Fate of Escherichia coli O157:H7 in ground beef following high-pressure processing and freezing.

AIMS: The purposes of this study were to evaluate the efficacy of high pressure to inactivate Escherichia coli O157:H7 in ground beef at ambient and subzero treatment temperatures and to study the fate of surviving bacteria postprocess and during frozen storage. METHODS AND RESULTS: Fresh ground beef was inoculated with a five-strain cocktail of E. coli O157:H7 vacuum-packaged, pressure-treated at 400 MPa for 10 min at -5 or 20 degrees C and stored at -20 or 4 degrees C for 5-30 days. A 3-log CFU g(-1) reduction of E. coli O157:H7 in the initial inoculum of 1 x 10(6) CFU g(-1) was observed immediately after pressure treatment at 20 degrees C. During frozen storage, levels of E. coli O157:H7 declined to <1 x 10(2) CFU g(-1) after 5 days. The physiological status of the surviving E. coli was affected by high pressure, sensitizing the cells to pH levels 3 and 4, bile salts at 5% and 10% and mild cooking temperatures of 55-65 degrees C. CONCLUSIONS: High-pressure processing (HPP) reduced E. coli O157:H7 in ground beef by 3 log CFU g(-1) and caused substantial sublethal injury resulting in further log reductions of bacteria during frozen storage. SIGNIFICANCE AND IMPACT OF THE STUDY: HPP treatment of packaged ground beef has potential in the meat industry for postprocess control of pathogens such as E. coli O157:H7 with enhanced safety of the product.

Depression in the first year of stay for elderly long-term nursing home residents in the USA.

BACKGROUND: Understanding the prevalence, incidence and cofactors of depression among long-term elderly nursing home (LTNH) residents domiciled for eight months or more may help optimize depression treatment in this vulnerable group. We quantified first year depression in American LTNH residents and the associations between depression and resident/facility characteristics. METHODS: Data were obtained from the Minimum Data Set and Online Survey Certification and Reporting for 634,060 LTNH residents admitted from 1999 to 2005 in 4,216 facilities. Depression first diagnosed at admission and at subsequent quarterly intervals through the first year of stay was examined. Logistic regressions modeled correlates of newly identified depression in each time-period. RESULTS: Recorded depression at admission and during the first year increased from 1999 to 2005. By 2005, 54.4% of LTNH residents had depression diagnosed over the first year; 32.8% at admission and a further 21.6% later during the first year. Antidepressant use was reported prior to depression diagnosis for 48% of those first identified depressed after admission. Men, non-Hispanic blacks, never married, and severely-cognitively impaired LTNH residents were less often identified with depression, particularly at admission. Pain and physical comorbidity were positively associated with depression identified throughout the first year. Prior institutionalization was associated with depression at admission, but not new depression after admission. Facility characteristics had weaker associations with depression. CONCLUSIONS: High depression rates at admission and during the first year indicate a need to monitor and treat large numbers of American LTNH residents for depression. Reduced associations between demographics and depression as stays progress suggest other factors have increased roles in depression etiology.

Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa.

Usher syndrome type IIa (OMIM 276901), an autosomal recessive disorder characterized by moderate to severe sensorineural hearing loss and progressive retinitis pigmentosa, maps to the long arm of human chromosome 1q41 between markers AFM268ZD1 and AFM144XF2. Three biologically important mutations in Usher syndrome type IIa patients were identified in a gene (USH2A) isolated from this critical region. The USH2A gene encodes a protein with a predicted size of 171.5 kilodaltons that has laminin epidermal growth factor and fibronectin type III motifs; these motifs are most commonly observed in proteins comprising components of the basal lamina and extracellular matrixes and in cell adhesion molecules.

Surveillance results of depleted uranium-exposed Gulf War I veterans: sixteen years of follow-up.

As part of a longitudinal surveillance program, 35 members of a larger cohort of 77 Gulf War I veterans who were victims of depleted uranium (DU) "friendly fire" during combat underwent a 3-day clinical assessment at the Baltimore Veterans Administration Medical Center (VAMC). The assessment included a detailed medical history, exposure history, physical examination, and laboratory studies. Spot and 24-h urine collections were obtained for renal function parameters and for urine uranium (U) measures. Blood U measures were also performed. Urine U excretion was significantly associated with DU retained shrapnel burden (8.821 mug U/g creatinine [creat.] vs. 0.005 mug U/g creat., p = .04). Blood as a U sampling matrix revealed satisfactory results for measures of total U with a high correlation with urine U results (r = .84) when urine U concentrations were >/=0.1 mug/g creatinine. However, isotopic results in blood detected DU in only half of the subcohort who had isotopic signatures for DU detectable in urine. After stratifying the cohort based on urine U concentration, the high-U group showed a trend toward higher concentrations of urine beta(2) microglobulin compared to the low-U group (81.7 v. 69.0 mug/g creat.; p = .11 respectively) and retinol binding protein (48.1 vs. 31.0 mug/g creat.; p = .07 respectively). Bone metabolism parameters showed only subtle differences between groups. Sixteen years after first exposure, this cohort continues to excrete elevated concentrations of urine U as a function of DU shrapnel burden. Although subtle trends emerge in renal proximal tubular function and bone formation, the cohort exhibits few clinically significant U-related health effects.

Effects of moderately high pressure plus heat on the germination and inactivation of Bacillus cereus spores lacking proteins involved in germination.

AIMS: To determine the germination and inactivation of Bacillus cereus spores lacking various germination proteins using moderately high pressure (MHP) and heat. METHODS: The inactivation and germination of wild-type B. cereus spores in buffer by MHP (150 MPa) at various temperatures, as well as the MHP inactivation and germination of B. cereus spores lacking individual germinant receptors and monovalent cation antiporters, was determined. RESULTS: Loss of individual germinant receptors had no large effects on spore inactivation or germination, although germination of receptor-deficient spores was generally slightly decreased. Loss of the GerN in particular the GerN and GerT antiporters also decreased spore germination by MHP, especially at 40 and 50 degrees C. CONCLUSIONS: Both inactivation and germination of B. cereus spores by MHP increased with rise of temperature; however, mutant strains lacking individual germinant receptor had similar levels of germination as compared to wild-type spores. To evaluate the role of germinant receptors in MHP, a strain lacking a large number of germinant receptors is needed. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this work may lead to a better understanding of how MHP causes germination of spores of B. cereus.

Cholinergic neurons of mouse intrinsic cardiac ganglia contain noradrenergic enzymes, norepinephrine transporters, and the neurotrophin receptors tropomyosin-related kinase A and p75.

Half of the cholinergic neurons of human and primate intrinsic cardiac ganglia (ICG) have a dual cholinergic/noradrenergic phenotype. Likewise, a large subpopulation of cholinergic neurons of the mouse heart expresses enzymes needed for synthesis of norepinephrine (NE), but they lack the vesicular monoamine transporter type 2 (VMAT2) required for catecholamine storage. In the present study, we determined the full scope of noradrenergic properties (i.e. synthetic enzymes and transporters) expressed by cholinergic neurons of mouse ICG, estimated the relative abundance of neurons expressing different elements of the noradrenergic phenotype, and evaluated the colocalization of cholinergic and noradrenergic markers in atrial nerve fibers. Stellate ganglia were used as a positive control for noradrenergic markers. Using fluorescence immunohistochemistry and confocal microscopy, we found that about 30% of cholinergic cell bodies contained tyrosine hydroxylase (TH), including the activated form that is phosphorylated at Ser-40 (pSer40 TH). Dopamine beta-hydroxylase (DBH) and norepinephrine transporter (NET) were present in all cholinergic somata, indicating a wider capability for dopamine metabolism and catecholamine uptake. Yet, cholinergic somata lacked VMAT2, precluding the potential for NE storage and vesicular release. In contrast to cholinergic somata, cardiac nerve fibers rarely showed colocalization of cholinergic and noradrenergic markers. Instead, these labels were closely apposed but clearly distinct from each other. Since cholinergic somata expressed several noradrenergic proteins, we questioned whether these neurons might also contain trophic factor receptors typical of noradrenergic neurons. Indeed, we found that all cholinergic cell bodies of mouse ICG, like noradrenergic cell bodies of the stellate ganglia, contained both tropomyosin-related kinase A (TrkA) and p75 neurotrophin receptors. Collectively, these findings demonstrate that mouse intrinsic cardiac neurons (ICNs), like those of humans, have a complex neurochemical phenotype that goes beyond the classical view of cardiac parasympathetic neurons. They also suggest that neurotrophins and local NE synthesis might have important effects on neurons of the mouse ICG.

Simple Power and Sample Size Estimation for Non-Randomized Longitudinal Difference in Differences Studies.

Intervention effects on continuous longitudinal normal outcomes are often estimated in two-arm pre-post interventional studies with b≥1 pre- and k≥1 post-intervention measures using "Difference-in-Differences" (DD) analysis. Although randomization is preferred, non-randomized designs are often necessary due to practical constraints. Power/sample size estimation methods for non-randomized DD designs that incorporate the correlation structure of repeated measures are needed. We derive Generalized Least Squares (GLS) variance estimate of the intervention effect. For the commonly assumed compound symmetry (CS) correlation structure (where the correlation between all repeated measures is a constantρ) this leads to simple power and sample size estimation formulas that can be implemented using pencil and paper. Given a constrained number of total timepoints (T), having as close to possible equal number of pre-and post-intervention timepoints (b=k) achieves greatest power. When planning a study with 7 or less timepoints, given large ρ(ρ≥0.6) in multiple baseline measures (b≥2) or ρ≥0.8 in a single baseline setting, the improvement in power from a randomized versus non-randomized DD design may be minor. Extensions to cluster study designs and incorporation of time invariant covariates are given. Applications to study planning are illustrated using three real examples with T=4 timepoints and ρ ranging from 0.55 to 0.75.

Health surveillance of Gulf War I veterans exposed to depleted uranium: updating the cohort.

A cohort of seventy-four 1991 Gulf War soldiers with known exposure to depleted uranium (DU) resulting from their involvement in friendly-fire incidents with DU munitions is being followed by the Baltimore Veterans Affairs Medical Center. Biennial medical surveillance visits designed to identify uranium-related changes in health have been conducted since 1993. On-going systemic exposure to DU in veterans with embedded metal fragments is indicated by elevated urine uranium (U) excretion at concentrations up to 1,000-fold higher than that seen in the normal population. Health outcome results from the subcohort of this group of veterans attending the 2005 surveillance visit were examined based on two measures of U exposure. As in previous years, current U exposure is measured by determining urine U concentration at the time of their surveillance visit. A cumulative measure of U exposure was also calculated based on each veteran's past urine U concentrations since first exposure in 1991. Using either exposure metric, results continued to show no evidence of clinically significant DU-related health effects. Urine concentrations of retinol binding protein (RBP), a biomarker of renal proximal tubule function, were not significantly different between the low vs. high U groups based on either the current or cumulative exposure metric. Continued evidence of a weak genotoxic effect from the on-going DU exposure as measured at the HPRT (hypoxanthine-guanine phosphoribosyl transferase) locus and suggested by the fluorescent in-situ hybridization (FISH) results in peripheral blood recommends the need for continued surveillance of this population.

Experimental induction of neoplasia in the accessory sex organs of male Lobund-Wistar rats.

Experimental induction of neoplasia in the urogenital tract was studied in male Lobund-Wistar rats. Animals were given single 30.0-mg/kg i.v. injections of N-nitroso-N-methylurea (NMU) followed 7 days later by s.c. implantation of a 2.0-cm Silastic capsule containing testosterone propionate (TP). Additional rats were given the NMU or TP treatments individually. Control animals were given a single i.v. injection of saline followed by implantation of an empty Silastic capsule. The Silastic implants for each group were replaced every 2 months. This hormone treatment regimen produced significantly (P less than 0.05) elevated serum testosterone concentrations relative to control for 42 days following implantation. Animals were killed at 92, 177, 259, 361, or 427 days post-NMU injection. A high treatment-related incidence of adenocarcinoma occurred in the dorsal and lateral prostatic lobes of animals given the combined NMU-TP treatment. In addition, a few animals had adenocarcinomas of the coagulating gland or the seminal vesicle. The estimated probability of neoplasia in the accessory sex organs by 427 days after initiation of the NMU-TP treatment was 68%, with no occurrence before 9 months. The NMU-TP treatment was also associated with an incidence of focal dysplasia in the accessory sex organs, particularly in the coagulating gland. These findings indicate that NMU-TP treatment of Lobund-Wistar rats can provide a useful experimental system to study the biochemical and molecular events involved in the induction of accessory sex organ neoplasia.