Younger rats are more susceptible to the lethal effects of sarin than adult rats: 24 h LC50 for whole-body (10 and 60 min) exposures.

Chemical warfare nerve agents (CWNA) inhibit acetylcholinesterase and are among the most lethal chemicals known to man. Children are predicted to be vulnerable to CWNA exposure because of their smaller body masses, higher ventilation rates and immature central nervous systems. While a handful of studies on the effects of CWNA in younger animals have been published, exposure routes relevant to battlefield or terrorist situations (i.e. inhalation for sarin) were not used. Thus, we estimated the 24 h LC50 for whole-body (10 and 60 min) exposure to sarin using a stagewise, adaptive dose design. Specifically, male and female Sprague-Dawley rats were exposed to a range of sarin concentrations (6.2-44.0 or 1.6-12.5 mg/m³) for either 10 or 60 min, respectively, at six different times during their development (postnatal day [PND] 7, 14, 21, 28, 42 and 70). For male and female rats, the lowest LC50 values were observed for PND 14 and the highest LC50 values for PND 28. Sex differences were observed only for PND 42 for the 10 min exposures and PND 21 and 70 for the 60 min exposures. Thus, younger rats (PND 14) were more susceptible than older rats (PND 70) to the lethal effects of whole-body exposure to sarin, while adolescent (PND 28) rats were the least susceptible and sex differences were minimal. These results underscore the importance of controlling for the age of the animal in research on the toxic effects associated with CWNA exposure.

Hormone-dependence of sarin lethality in rats: Sex differences and stage of the estrous cycle.

Chemical warfare nerve agents (CWNAs) are highly toxic compounds that cause a cascade of symptoms and death, if exposed casualties are left untreated. Numerous rodent models have investigated the toxicity and mechanisms of toxicity of CWNAs, but most are limited to male subjects. Given the profound physiological effects of circulating gonadal hormones in female rodents, it is possible that the daily cyclical fluctuations of these hormones affect females' sensitivity to the lethal effects of CWNAs, and previous reports that included female subjects did not control for the stage of the hormonal cycle. The aim of the current study was to determine the 24-hour median lethal dose (LD50) of the CWNA sarin in male, ovariectomized (OVEX) female, and female rats during different stages of the estrous cycle (diestrus, proestrus, and estrus). Additionally, baseline activity levels of plasma acetylcholinesterase, butyrylcholinesterase, and carboxylesterase were measured to determine differences among the groups. Results indicated that females in proestrus had a significantly higher LD50 of sarin compared to OVEX and estrous females. Although some sex differences were observed in the activity levels of plasma esterases, they were not consistent and likely not large enough to significantly affect the LD50s. These results suggest that hormonal cyclicity can influence the outcome of CWNA-related studies using female rodents, and that this variability can be minimized by controlling for the stage of the cycle. Additional research is necessary to determine the precise mechanism of the observed differences because it is unlikely to be solely explained by plasma esterase activity.

Correlational sperm motility analysis: wild rodent progressive sperm motility as a potentially improved reproduction-assessment parameter in mammals.

Progressive sperm motility, describing the directed or linear movement of sperm, is infrequently reported in reproductive studies conducted with rodents. This is a curious circumstance given that progressive motility can be easily reported with current computer-assisted sperm-analysis equipment, and because progressively motile sperm seemingly display a greater likelihood of fertilizing ova than do sperm that move in a random or undefined pattern. This study presents a comparison of the routinely reported total motility (i.e., the percentage of moving sperm cells in a sample) and the progressive motility of sperm from rodents captured at soil-contaminated sites and at habitat-matched noncontaminated reference locations. Progressive motility's trending with total motility at all areas, in terms of direction of shift, magnitude of change, and degree of correlation, was extremely high. Based on these results and in the interest of assisting ecological health assessments at contaminated sites, it would seem prudent to conduct the empirical research to determine progressive sperm motility's threshold-for-effect, which may be lower than that for total motility.

The effects of visual acuity on target discrimination and shooting performance.

PURPOSE: To explore the effects of visual acuity on target discrimination and marksmanship. METHODS: A randomized, single-blind, repeated measures study was conducted to evaluate the effect of visual acuity on target discrimination and marksmanship. Subjects were examined for inclusion criteria and equivalent plus lens over-refractions necessary to obtain the five test visual acuity ranges. Qualified subjects fired at randomized target presentations from 50 to 300 m while wearing customized spectacles to yield the visual acuity levels being evaluated. Subjects then rotated foxholes for target discrimination sequences. Randomized targets marked as friend or enemy were presented in like manner for each of the five visual acuity levels. RESULTS: Subjects at acuities better than 0.2 LogMAR were significantly more likely to hit the target than those with acuities equal to or worse than 0.7 LogMAR. Target discrimination results show subjects with acuities between -0.2 and 0.6 LogMAR were significantly more likely to correctly identify the target than those with acuities equal to or worse than 0.7 LogMAR. In addition, those at acuities of 0.0 LogMAR or better performed significantly better than those with acuities between 0.3 and 0.6 LogMAR. CONCLUSIONS: Visual acuity significantly affects target discrimination and marksmanship performance. Results of this study closely mirror expected findings based on visual angles with acuities in the range 0.3 to 0.4 LogMAR (20/40-20/50) being the transition zone where performance begins to deteriorate. This performance-based evidence fully supports a vision classification system that mandates eyewear to maximize visual performance for deployable military members. Based on the results of this study, the current U.S. Army, U.S. Navy, and U.S. Marine Corps vision readiness standards of 20/40 or better uncorrected or corrected vision seems to be a valid choice because it is the transition point for performance in both target discrimination and marksmanship ability.

Age-Related Susceptibility to Epileptogenesis and Neuronal Loss in Male Fischer Rats Exposed to Soman and Treated With Medical Countermeasures.

Elderly individuals compose a large percentage of the world population; however, few studies have addressed the efficacy of current medical countermeasures (MCMs) against the effects of chemical warfare nerve agent exposure in aged populations. We evaluated the efficacy of the anticonvulsant diazepam in an old adult rat model of soman (GD) poisoning and compared the toxic effects to those observed in young adult rats when anticonvulsant treatment is delayed. After determining their respective median lethal dose (LD50) of GD, we exposed young adult and old adult rats to an equitoxic 1.2 LD50 dose of GD followed by treatment with atropine sulfate and the oxime HI-6 at 1 min after exposure, and diazepam at 30 min after seizure onset. Old adult rats that presented with status epilepticus were more susceptible to developing spontaneous recurrent seizures (SRSs). Neuropathological analysis revealed that in rats of both age groups that developed SRS, there was a significant reduction in the density of mature neurons in the piriform cortex, thalamus, and amygdala, with more pronounced neuronal loss in the thalamus of old adult rats compared with young adult rats. Furthermore, old adult rats displayed a reduced density of cells expressing glutamic acid decarboxylase 67, a marker of GABAergic interneurons, in the basolateral amygdala and piriform cortex, and a reduction of astrocyte activation in the piriform cortex. Our observations demonstrate the reduced effectiveness of current MCM in an old adult animal model of GD exposure and strongly suggest the need for countermeasures that are more tailored to the vulnerabilities of an aging population.

Mouthguards in sport activities : history, physical properties and injury prevention effectiveness.

Three systematic reviews were conducted on: (i) the history of mouthguard use in sports; (ii) mouthguard material and construction; and (iii) the effectiveness of mouthguards in preventing orofacial injuries and concussions. Retrieval databases and bibliographies were explored to find studies using specific key words for each topic. The first recorded use of mouthguards was by boxers, and in the 1920s professional boxing became the first sport to require mouthguards. Advocacy by the American Dental Association led to the mandating of mouthguards for US high school football in the 1962 season. Currently, the US National Collegiate Athletic Association requires mouthguards for four sports (ice hockey, lacrosse, field hockey and football). However, the American Dental Association recommends the use of mouthguards in 29 sports/exercise activities. Mouthguard properties measured in various studies included shock-absorbing capability, hardness, stiffness (indicative of protective capability), tensile strength, tear strength (indicative of durability) and water absorption. Materials used for mouthguards included: (i) polyvinylacetate-polyethylene or ethylene vinyl acetate (EVA) copolymer; (ii) polyvinylchloride; (iii) latex rubber; (iv) acrylic resin; and (v) polyurethane. Latex rubber was a popular material used in early mouthguards but it has lower shock absorbency, lower hardness and less tear and tensile strength than EVA or polyurethane. Among the more modern materials, none seems to stand out as superior to another since the characteristics of all the modern materials can be manipulated to provide a range of favourable characteristics. Impact studies have shown that compared with no mouthguard, mouthguards composed of many types of materials reduce the number of fractured teeth and head acceleration. In mouthguard design, consideration must be given to the nature of the collision (hard or soft objects) and characteristics of the mouth (e.g. brittle incisors, more rugged occusal surfaces of molars, soft gingiva). Laminates with different shock absorbing and stress distributing (stiffness) capability may be one way to accommodate these factors.Studies comparing mouthguard users with nonusers have examined different sports, employed a variety of study designs and used widely-varying injury case definitions. Prior to the 1980s, most studies exhibited relatively low methodological quality. Despite these issues, meta-analyses indicated that the risk of an orofacial sports injury was 1.6-1.9 times higher when a mouthguard was not worn. However, the evidence that mouthguards protect against concussion was inconsistent, and no conclusion regarding the effectiveness of mouthguards in preventing concussion can be drawn at present. Mouthguards should continue to be used in sport activities where there is significant risk of orofacial injury.

Plasma Concentration of Meloxicam in Pediatric Rats.

In this study, we compared the plasma concentrations of meloxicam in pediatric rat pups (ages: 7, 14, 21, and 28 d) with those of young adult rats. Adult rats received 1.34 mg/kg SC meloxicam to determine the target peak plasma concentration (Cmax) for comparison with the pediatric animals. Pediatric rats received 1.34 mg/kg SC meloxicam, and in all age groups, Cmax met or exceeded that in adults (11.5 ±2.7 µg/mL). Plasma concentrations were similar between male and female pups within age groups, and peak plasma concentration was achieved more rapidly in rat pups than adults. The analgesic efficacy of this dose was not evaluated in this study.

Sulfur mustard-induced neutropenia: treatment with granulocyte colony-stimulating factor.

Although best known as a blistering agent, sulfur mustard (HD) can also induce neutropenia in exposed individuals, increasing their susceptibility to infection. Granulocyte colony-stimulating factor (G-CSF) and pegylated G-CSF (peg-G-CSF) have been approved by the U.S. Food and Drug Administration as hematopoietic growth factors to treat chemotherapy-induced neutropenia. The goal of this study was to determine the effectiveness of G-CSF and peg-G-CSF in ameliorating HD-induced neutropenia. African green monkeys (Chlorocebus aethiops) were challenged with HD and, at 1, 3, 5, or 7 days after exposure, G-CSF therapy (10 microg/kg per day for 21 days) was initiated. Peg-G-CSF (300 microg/kg, single treatment) was similarly tested, with treatment given at 3 days after exposure. Untreated HD-exposed animals recovered from neutropenia 28 days after exposure, whereas G-CSF- or peg-G-CSF-treated animals recovered 8 to 19 days after exposure (p < 0.05). These results indicate that G-CSF or peg-G-CSF may provide Food and Drug Administration-approved treatments that will reduce the duration of HD-induced neutropenia.

Comparison of the lethal effects of chemical warfare nerve agents across multiple ages.

Children may be inherently more vulnerable than adults to the lethal effects associated with chemical warfare nerve agent (CWNA) exposure because of their closer proximity to the ground, smaller body mass, higher respiratory rate, increased skin permeability and immature metabolic systems. Unfortunately, there have only been a handful of studies on the effects of CWNA in pediatric animal models, and more research is needed to confirm this hypothesis. Using a stagewise, adaptive dose design, we estimated the 24h median lethal dose for subcutaneous exposure to seven CWNA in both male and female Sprague-Dawley rats at six different developmental times. Perinatal (postnatal day [PND] 7, 14 and 21) and adult (PND 70) rats were more susceptible than pubertal (PND 28 and 42) rats to the lethal effects associated with exposure to tabun, sarin, soman and cyclosarin. Age-related differences in susceptibility were not observed in rats exposed to VM, Russian VX or VX.

Female rats are less susceptible during puberty to the lethal effects of percutaneous exposure to VX.

Nerve agents with low volatility such as VX are primarily absorbed through the skin when released during combat or a terrorist attack. The barrier function of the stratum corneum may be compromised during certain stages of development, allowing VX to more easily penetrate through the skin. However, age-related differences in the lethal potency of VX have yet to be evaluated using the percutaneous (pc) route of exposure. Thus, we estimated the 24 and 48 h median lethal dose for pc exposure to VX in male and female rats during puberty and early adulthood. Pubescent, female rats were less susceptible than both their male and adult counterparts to the lethal effects associated with pc exposure to VX possibly because of hormonal changes during that stage of development. This study emphasizes the need to control for both age and sex when evaluating the toxicological effects associated with nerve agent exposure in the rat model.

Cost analysis of military eye injuries in fiscal years 1988-1998.

Army, Navy, and Air Force safety center ground eye injuries were evaluated from fiscal year 1988 through fiscal year 1998. The U.S. Army Safety Center data revealed that the average Army military eye injury mishap caused a loss of 6.1 days from work, at a cost averaging 9724 dollars. The U.S. Navy Safety Center data showed that the average Navy military eye injury mishap caused a loss of 5.9 days from work, at a cost averaging 4222 dollars. The Air Force Safety Center data revealed that the average Air Force eye injury mishap caused a loss of 4.7 days from work, at a cost averaging 3196 dollars. Comparing safety center data with Defense Medical Surveillance System data exposed an underreporting of safety center data by at least 250%. To improve accurate meaningful data collection, an automated eye injury collection system should be initiated.

Postdeployment hearing loss in U.S. Army soldiers seen at audiology clinics from April 1, 2003, through March 31, 2004.

PURPOSE: U.S. Army soldiers face unique noise exposures in the current deployed setting. The effects of these deployment-related exposures have not previously been documented. METHOD: In an attempt to initiate this process, medical evaluations performed at military audiology clinics from April 2003 through March 2004 were reviewed to compare noise-induced hearing loss injury (NIHLI) outcomes among soldiers whose diagnoses were classified as postdeployment-related versus non-postdeployment-related. Sentinel NIHLI outcomes of interest included acoustic trauma, permanent threshold shift, eardrum perforation, tinnitus, and military-specific H-3 and H-4 hearing loss profiles. RESULTS: Significantly higher rates of NIHLI and associated outcomes were observed among soldiers whose diagnoses were postdeployment-related. CONCLUSIONS: Based on the findings from this evaluation, recommendations are provided for enhancing the force health protection posture for prevention of hearing loss in future deployments.

Dietary oral exposure to l,3,5-trinitro-1,3,5-triazine in the northern bobwhite (Colinus virginianus).

The potential risk to wildlife from exposure to explosives, including 1,3,5-trinitro-1,3,5-triazine (RDX), has been an issue at numerous U.S. military installations where these substances are found in soil and water. Presently, no data describing the effects of RDX exposure in avian species exist. Therefore, an acute lethal dose (ALD) and 14- and 90-d subchronic dietary exposures to RDX were evaluated in a species potentially present at many contaminated sites, i.e., the northern bobwhite (Colinus virginianus). The ALDs for females and males were 187 and 280 mg/kg, respectively. Data from the 14-d dietary trial suggested that RDX exposure inhibited food consumption, weight gain, and egg production. Dietary RDX exposure for 90-d produced a dose-dependant decreasing trend in total feed consumption, total egg production, and hen-housed production parameters. These collective data suggest that quail may respond differently to oral RDX exposure compared with mammals.

Follow-up study on vision health readiness in the military.

A retrospective study reviewed medical records of military personnel who had participated in a vision readiness study the previous year. The review evaluated (1) the number of personnel who returned for an eye examination (as recommended), (2) the number of dilated eye examinations, (3) the number of optical devices ordered, (4) the number of patients requiring continuing treatment, (5) the types of eye disease in personnel who were classified as nondeployable in the original study, and (6) the relationship between patient vision complaints and the need for spectacles. Analyses revealed 44% of military personnel have never had a comprehensive eye examination. Of these personnel who never had an eye examination, 15% to 26% could improve their vision with spectacles. Finally, even though having an eye examination is important, whether or not the individual has had a comprehensive eye examination should not be a significant criterion for deployment.

Vision readiness in Operation Restore Hope.

Ensuring that our forces are vision ready for their mission is essential on today's battlefield. Vision readiness considers optical readiness (appropriate correcting eyewear) and visual readiness (adequate job-required visual acuity). A study of vision readiness among deploying personnel for Operation Restore Hope in Bosnia from December 1995 to September 1997 was conducted at Fort Benning, Georgia. Of the 10,063 personnel screened, 3,554 (35.3%) were not optically ready for deployment and 406 (4.0%) were not visually ready for deployment. Analyses indicated a statistically significant difference between the active duty and reserve components in optical and visual readiness. A more effective vision readiness process should be implemented before deployment to ensure that all personnel are deployment ready. Optometry personnel, commanders, and deploying soldiers, sailors, airmen, and marines must take a more active role in ensuring that our forces have the appropriate visual acuity and optical devices to deploy.

Descriptive analysis of military eye injuries from fiscal year 1988 to 1998.

An 11-year retrospective study of ground eye injuries collected by the Army Safety Center, Navy Safety Center, and Air Force Safety Center from fiscal year 1988 through 1998 was performed. The statistics for eye injuries indicate that the average Army, Navy, and Air Force individual sustaining an eye injury is a 20- to 24-year-old man with a rank of E2 through E5. The average military individual sustaining an eye injury is not wearing eye protection when injured. In addition, Army personnel lost 1.9 more workdays, Navy personnel lost 1.5 more workdays, and Air Force personnel lost 3.4 more workdays than those individuals who were wearing eye protection at the time of the eye injury. Proactive vision conservation education at local levels needs to focus on the military personnel that are at the highest risk for an eye injury.

Visual acuity, optical, and eye health readiness in the military.

Optimum vision readiness is essential on today's technologically advanced battlefield. A vision readiness screening of 4,825 active duty personnel at 13 Department of Defense sites from September through December 1997 revealed 4,021 (83.3%) not vision ready: 500 (10.4%) had substandard visual acuity, 1,249 (25.9%) had deficient optical devices, and 3,562 (73.8%) had eye health-related deficiencies. This suggests a more effective ongoing vision readiness process should be implemented to ensure all personnel are vision ready prior to deployment.

The incidence of eye injuries at three U.S. Army installations.

Studies addressing the impact of eye injuries on U.S. Army readiness and the effectiveness of countermeasures are lacking. In 1989, the U.S. Army Environmental Hygiene Agency undertook a prospective, multicenter study of military units in the peacetime Army at selected installations to define the incidence of eye injuries, assess associated variables, and identify targets for intervention. During the first 5 months of 1989 at Fort Bragg, North Carolina, Fort Campbell, Kentucky, and Fort Lewis, Washington, health care providers saw 103 new eye injuries with an overall rate of 14.18 injuries per 1,000 personnel annually. Almost one-half of the injuries (48 cases, 46.60%) occurred during on-duty work and training. Most (93 cases, 90.29%) of the soldiers were not wearing eye protection when injured. This study identifies possible targets for intervention and provides a baseline against which the interventions of the last decade may be assessed for effectiveness.

Field verification of Test-mate ChE.

The objective was to evaluate the ability of the Test-mate ChE to determine acetylcholinesterase (AChE) activity under field conditions. To mimic nerve agent exposure, the U.S. Army Medical Research Institute of Chemical Defense spiked blood samples with variable amounts of soman. Blinded to the identity of the samples, the 520th Theater Army Medical Laboratory tested the samples during a field training exercise inside their environmentally controlled mobile facility. The technicians repeated measurements for 6 consecutive days, and on 1 of the days repeated the measurements six times. The technicians accurately identified all of the samples and quantified the AChE activity. The major trend was that the Test-mate ChE is more precise and reproducible for smaller doses of soman. The results were reliable over all temperatures during the field exercise. In conclusion, the Test-mate ChE is a reliable field instrument to determine blood AChE activity.

Wanted: a national standard for early hearing detection and intervention outcomes data.

The Joint Committee on Infant Hearing (JCIH, 2000) has presented principles and guidelines for universal newborn hearing screening and early hearing detection and intervention (EHDI). The guidelines describe the need for a national data set for early hearing detection and intervention. The guidelines fail to provide the specific constructs for such a data set. To the authors' knowledge, no nationally proposed uniform data structure exists to capture EHDI services' outcome metrics. This article presents a proposed newborn hearing screening and EHDI data model. This model was developed to record EHDI outcomes data from Military Health System birthing centers. The data are to be collected for tracking implementation of Healthy People 2010 goals related to newborn hearing screening and EHDI programs within the Military Health System. In this article, the authors use the T. Helfer, A. Shields, and K. Gates (2000) methods to model a uniform structure for collection of newborn hearing screening and EHDI data. They also discuss expansion of the data model for application to public health reporting of EHDI outcomes in the civilian sector to include integration of Census Bureau demographic data and geographic information system data to further enhance the research value of these EHDI outcomes data. They offer the data model with the intention of supporting national research efforts for studying the efficacy of EHDI programs and to help establish a national evidence-based practice database for such programs.