Stanley W. Hulet

United States Army, Washington, West Virginia, United States

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Publications (25)27.31 Total impact

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    ABSTRACT: Abstract Sexually mature male and female Gottingen minipigs were exposed to various concentrations of GB and GF vapor via whole-body inhalation exposures or to liquid GB or GF via intravenous or subcutaneous injections. Vapor inhalation exposures were for 10, 60 or 180 min. Maximum likelihood estimation was used to calculate the median effect levels for severe effects (ECT50 and ED50) and lethality (LCT50 and LD50). Ordinal regression was used to model the concentration × time profile of the agent toxicity. Contrary to that predicted by Haber's rule, LCT50 values increased as the duration of the exposures increased for both nerve agents. The toxic load exponents (n) were calculated to be 1.38 and 1.28 for GB and GF vapor exposures, respectively. LCT50 values for 10-, 60- and 180-min exposures to vapor GB in male minipigs were 73, 106 and 182 mg min/m(3), respectively. LCT50 values for 10-, 60 - and 180-min exposures to vapor GB in female minipigs were 87, 127 and 174 mg min/m(3), respectively. LCT50 values for 10-, 60- and 180-min exposures to vapor GF in male minipigs were 218, 287 and 403 mg min/m(3), respectively. LCT50 values for 10-, 60- and 180-min exposures in female minipigs were 183, 282 and 365 mg min/m(3), respectively. For GB vapor exposures, there was a tenuous gender difference which did not exist for vapor GF exposures. Surprisingly, GF was 2-3 times less potent than GB via the inhalation route of exposure regardless of exposure duration. Additionally GF was found to be less potent than GB by intravenous and subcutaneous routes.
    Inhalation Toxicology 02/2014; 26(3):175-84. · 1.89 Impact Factor
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    ABSTRACT: Human serum butyrylcholinesterase (Hu BChE) is a stoichiometric bioscavenger that is being developed as a prophylactic countermeasure against organophosphorus nerve agents. This study was designed to evaluate the efficacy of Hu BChE against whole-body inhalation exposure to a lethal dose of sarin (GB) vapor. Male Göttingen minipigs were subjected to: air exposure, GB vapor exposure, or pretreatment with Hu BChE followed by GB vapor exposure. Hu BChE was administered by i.m. injection 24 h prior to exposure to 4.1 mg/m(3) of GB vapor for 60 min. Electrocardiograms (ECG), electroencephalograms (EEG), and pupil size were recorded throughout exposure. Blood drawn before and throughout exposure was analyzed for blood gases, electrolytes, metabolites, acetylcholinesterase and BChE activities, and amount of GB present. Untreated animals exposed to GB vapor exhibited cardiac abnormalities and generalized seizures, ultimately succumbing to respiratory failure. Pretreatment with 3.0 or 6.5 mg/kg of Hu BChE delayed blood gas and acid-base disturbances and the onset of cardiac and neural toxic signs, but failed to increase survivability. Pretreatment with 7.5 mg/kg of Hu BChE, however, completely prevented toxic signs, with blood chemistry and ECG and EEG parameters indistinguishable from control during and after GB exposure. GB bound in plasma was 200-fold higher than plasma from pigs that did not receive Hu BChE, suggesting that Hu BChE scavenged GB in blood and prevented it from reaching other tissues. Thus, prophylaxis with Hu BChE alone not only increased survivability, but also prevented cardiac abnormalities and neural toxicity in minipigs exposed to a lethal dose of GB vapor.
    Biochemical pharmacology 09/2011; 82(12):1984-93. · 4.25 Impact Factor
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    ABSTRACT: Human serum butyrylcholinesterase (Hu BChE) is currently under advanced development as a pretreatment drug for organophosphate (OP) poisoning in humans. It was shown to protect mice, rats, guinea pigs, and monkeys against multiple LD(50) challenges of OP nerve agents by i.v. or s.c. bolus injections. Since inhalation is the most likely route of exposure to OP nerve agents on the battlefield or in public places, the aim of this study was to evaluate the efficacy of Hu BChE against whole-body inhalation exposure to sarin (GB) vapor. Male Göttingen minipigs were subjected to one of the following treatments: (1) air exposure; (2) GB vapor exposure; (3) pretreatment with 3 mg/kg of Hu BChE followed by GB vapor exposure; (4) pretreatment with 6.5 mg/kg of Hu BChE followed by GB vapor exposure; (5) pretreatment with 7.5 mg/kg of Hu BChE followed by GB vapor exposure. Hu BChE was administered by i.m. injection, 24h prior to whole-body exposure to GB vapor at a concentration of 4.1 mg/m(3) for 60 min, a dose lethal to 99% of untreated exposed pigs (LCt99). EEG, ECG, and pupil size were monitored throughout exposure, and blood drawn from a surgically implanted jugular catheter before and throughout the exposure period, was analyzed for acetylcholinesterase (AChE) and BChE activities, and the amount of GB present in plasma. All animals exposed to GB vapor alone or pretreated with 3 or 6.5 mg/kg of Hu BChE, died following exposure to GB vapor. All five animals pretreated with 7.5 mg/kg of Hu BChE survived the GB exposure. The amount of GB bound in plasma was 200-fold higher compared to that from plasma of pigs that did not receive Hu BChE, suggesting that Hu BChE was effective in scavenging GB in blood. Additionally, pretreatment with 7.5 mg/kg of Hu BChE prevented cardiac abnormalities and seizure activity observed in untreated animals and those treated with lower doses of Hu BChE.
    Chemico-Biological Interactions 06/2008; 175(1-3):267-72. · 2.97 Impact Factor
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    ABSTRACT: A rapid and sensitive method for the determination of the chemical warfare agent VX in plasma taken from Göttingen minipigs has been developed using isotope-dilution gas chromatography-tandem mass spectrometry (GC-MS-MS). Chromatographic separation was achieved on a 5% diphenyl/95% dimethyl polysiloxane capillary column with a total run time of about 11 min. The analyte was detected using ammonia chemical ionization in the multiple reaction monitoring mode, following a simple extraction with 10% 2-propanol in hexane. A good linear relationship was obtained in the quantitative concentration range of 10 ng/mL to 1000 ng/mL (r(2) = 0.9998) with an average slope of 1.275 +/- 0.037 (n = 7), and an absolute detection limit of 0.4 pg on column. The average recovery for VX was 95% in saline in the concentration range of 50-100 ng/mL. The method was successfully applied to the analysis of VX in minipig plasma in a preliminary toxicokinetic study.
    Journal of analytical toxicology 01/2008; 32(1):63-7. · 2.11 Impact Factor
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    ABSTRACT: The present study utilized infrared pupillometry to digitally capture images of pupils in real-time during whole-body vapor GF exposures of Gottingen minipigs. Binary normal regression was used to fit various response models to the data. Values for EC50 and ECT50 were calculated for miosis in male and female minipigs exposed to GF vapor for 10, 60, and 180 min. There is a 32% overall difference (area basis) in the model fits for the miotic ECT50 values between the genders, with the males being more sensitive. The difference between the genders became more pronounced at the longer exposure-durations. The ECT50 associated with miosis was not constant over time as predicted by Haber's rule. Rather, the data were best described by a toxic load model. The value of the best model fit for the toxic load exponent was 1.60 with 95% confidence interval of 1.38 to 1.82. The best estimate of the probit slope (concentration) was 12.4 with 95% confidence interval of 4.8 to 20.0. Potential curvature in the data with respect to fitting by the toxic load model was evaluated by inserting the term, (LogT)2, and this term was found to be statistically insignificant (p > 0.3).
    04/2007;
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    ABSTRACT: Constriction of the pupils (miosis) is often identified as the first noticeable sign of exposure to vapor nerve agents. We have previously identified that in minipigs there is a 30-40 fold difference in vapor dosages of sarin (GB) that elicit miosis vs. those vapor dosages that are potentially lethal. The ratio for miotic vs. lethal vapor dosages ranges from 100-135 fold when cyclo-sarin (GF) is the nerve agent. Due to the extremely low volatility of VX the nerve agent's primary hazard comes from percutaneous absorption. In laboratory settings a combination of high temperatures and airflow can be used to generate vapor VX at stable and measurable concentrations. In a field setting, the generation of VX vapor is less likely, although it is theoretically possible in extreme environments such as the inside of an armored HUMVEE in a desert. In the current studies sexually mature male Gottingen minipigs were exposed to various concentrations of VX vapor in order to determine the lethal (LCT50s) and effective concentrations (ECT50s) for miosis over exposure durations of 10, 60 and 180 minutes. In minipigs VX vapor is less potent than either GB or GF at causing pupil constriction. Additionally, the onset of pupil constriction is delayed in comparison to onset upon exposure to GB or GF. VX vapor was more potent than either GB or GF when lethality was the endpoint. However, unlike with GB or GF vapor exposures, constriction of the pupils was not the definitive first noticeable effect upon a potentially lethal VX vapor exposure. The ratio of ECT50 for miosis vs. LCT50 values for vapor VX exposures ranges from 3-6 fold. Therefore, the dosages of VX vapor that elicit pupil constriction are much closer to the dosages that result in severe toxic signs or lethality than are seen for either GB or GF vapor exposures. Male Gottingen minipigs were also exposed to liquid VX via intravenous (IV) or subcutaneous (SC) injections. Signs of nerve agent exposure were classified as lethal, severe, or moderate. Maximum likelihood estimation using a probit model was used to calculate the median effective (severe effects) and lethal doses (LD50) for IV and SC exposures. For intravenously injected VX, the LD50 was 11.8 µg/kg (9.7 - 14.5 µg/kg) and the ED50 (severe) was 6.6µg/kg (4.8 - 9.0 µg/kg). For subcutaneously injected VX, the LD50 was 16.1µg/kg (12.9 - 19.9 µg/kg) and the ED50 (severe) was 12.8µg/kg (10.1 - 16.2 µg/kg). VX was more potent than either sarin (GB) or cyclo-sarin (GF) by both routes of exposure.
    01/2007;
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    ABSTRACT: Recent developments to improve nerve agent biomarker techniques include methods for measuring fluoride regenerated Sarin (GB) in blood and tissue. Our efforts extend the fluoride ion regeneration method to be able to determine cyclosarin (GF) in red blood cells, plasma, and tissue of minipig blood samples after whole body exposure to GF at miosis levels. Blood samples were taken serially before, during, and after whole body GF exposure from the minipig via venous catheter allowing agent exposure profiles to be generated. After processing the samples with fluoride ion and extracting with C-18 solid phase extraction cartridges the ethyl acetate extract was analyzed by GC/MS. The GC/MS method utilized an autoinjector, a large volume injector port (LVI), positive ion ammonia chemical ionization detection in the SIM mode, and a 2H11-GF stable isotope internal standard. Results indicated that the method range was 10-1000 pg on column. The detection limit was 3 pg of GF on column despite the complexity of the red blood cell/tissue matrix. Conditions that needed to be optimized for the LVI included injection volume, initial temperature, pressure, and flow rate. The regenerated GF (R-GF) profiles differ greatly from the regenerated GB (R-GB) profiles in the minipig at similar exposure levels. The onset of the appearance of R-GF in the blood seems to be delayed and maximum levels are reached at much later times as compared to GB exposures. The rate of R-GB production was 5- 10 times greater than that of R-GF at equimolar exposures.
    10/2006;
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    T-M Shih, S W Hulet, J H McDonough
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    ABSTRACT: This project assessed the effects of repeated low-dose exposure of guinea pigs to the organophosphorus nerve agent sarin. Animals were injected once a day, 5 days per week (Monday-Friday), for 2 weeks with fractions (0.3x, 0.4x, 0.5x, or 0.6x) of the established LD(50) dose of sarin (42 microg/kg, s.c.). The animals were assessed for changes in body weight, red blood cell (RBC) acetylcholinesterase (AChE) levels, neurobehavioral reactions to a functional observational battery (FOB), cortical electroencephalographic (EEG) power spectrum, and intrinsic acetylcholine (ACh) neurotransmitter (NT) regulation over the 2 weeks of sarin exposure and for up to 12 days postinjection. No guinea pig receiving 0.3, 0.4 or 0.5 x LD(50) of sarin showed signs of cortical EEG seizures despite decreases in RBC AChE levels to as low as 10% of baseline, while seizures were evident in animals receiving 0.6 x LD(50) of sarin as early as the second day; subsequent injections led to incapacitation and death. Animals receiving 0.5 x LD(50) sarin showed obvious signs of cholinergic toxicity; overall, 2 of 13 animals receiving 0.5 x LD(50) sarin died before all 10 injections were given, and there was a significant increase in the angle of gait in the animals that lived. By the 10th day of injection, the animals receiving saline were significantly easier to remove from their cages and handle and significantly less responsive to an approaching pencil and touch on the rump in comparison with the first day of testing. In contrast, the animals receiving 0.4 x LD(50) sarin failed to show any significant reductions in their responses to an approaching pencil and a touch on the rump as compared with the first day. The 0.5 x LD(50) sarin animals also failed to show any significant changes to the approach and touch responses and did not adjust to handling or removal from the cage from the first day of injections to the last day of handling. Thus, the guinea pigs receiving the 0.4 and 0.5 x LD(50) doses of sarin failed to habituate to some aspects of neurobehavioral testing. Spectral analysis of EEG data suggested that repeated sarin exposure may disrupt normal sleeping patterns (i.e., lower frequency bandwidths). While these EEG changes returned to relative normalcy 6 days after the last injection in animals receiving 0.4 x LD(50) sarin, these changes were still observed in the animals that received 0.5 x LD(50) sarin. Ten to twelve days after the last sarin injection (in 0.4 x LD(50) group only), neurochemical data showed that striatal choline levels were reduced in comparison to the saline group. At this time, atropine sulfate (5 mg/kg, i.p.) challenge resulted in a transient elevation in striatal ACh levels in animals exposed to repeated 0.4 x LD(50) sarin as well as in control animals. No evidence of brain or heart pathology was found in any guinea pig that survived all 10 sarin injections.
    Toxicology and Applied Pharmacology 10/2006; 215(2):119-34. · 3.98 Impact Factor
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    ABSTRACT: One of the goals of this study was to determine the lowest sarin (GB) vapor concentration of physiological significance. During the whole body exposure to GB vapor of a living species, the first noticeable effect is constriction of the pupil (miosis). The Gottingen minipig was chosen as a model for studying the effects of GB vapor because of the anatomical and physiological similarities between humans and minipigs. The minipigs were secured in a sling during exposure and their pupil size was continuously monitored under dim-light conditions using an infrared light-sensitive video camera. High-resolution images of the eye were collected before, during, and after each exposure. The pupil area was then quantified using a custom-designed software package. Ordinal regression was used to fit various response models to the data. The effective concentrations resulting in miosis in 50% (EC (sub 50)) of the exposed subjects were determined for 3 exposure-durations (10, 60, and 180 minutes). The median effective dose (ECT (sub 50)) associated with miosis was not constant over time. The value of the toxic load exponent was essentially independent of the model used: 1.32 +/- 0.18 (95% confidence interval of 1.14 to 1.50). Since this interval did not overlap one, Haber's rule was found to be an inappropriate time dependence model for this data set.
    08/2006;
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    ABSTRACT: The current studies estimated effective (miosis) concentrations of the nerve agents' sarin (GB) and cyclosarin (GF) as a function of exposure duration in the Gottingen minipig and determined dependency of the median effective dosage (ECT50) over time. Male and female Gottingen minipigs were exposed to various concentrations of vapor GB or GF for 10, 60, or 180 min. Infrared images of the pig's pupil before, during, and after nerve agent exposure were captured digitally and pupil area was quantified. An animal was classified "positive" for miosis if there was a 50% reduction in pupil area (as compared to baseline) at any time during or after the GB or GF exposure. Maximum likelihood estimation was used on the resulting quantal data to calculate ECT50 (miosis) values, with approximate 95% confidence intervals, for each of the six gender-exposure duration groups. As a group, male minipigs were significantly more sensitive to the pupil constricting effects of GF than were female minipigs. In male minipigs, GF is approximately equipotent to GB for 60-min exposures and more potent for 10- and 180-min exposures. In the female minipig GF is slightly more potent than GB for 10-min exposures but then progressively becomes less potent over the 60- and 180-min durations of exposure. The values of the toxic load exponents were essentially independent of the model fits used: 1.32 +/- 0.18 for GB exposures and 1.60 +/- 0.22 for GF exposures. Since neither of these intervals overlaps 1, Haber's rule is not an appropriate time-dependence model for these data sets.
    Inhalation Toxicology 03/2006; 18(2):143-53. · 1.89 Impact Factor
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    ABSTRACT: Sexually mature male and female Gottingen minipigs were exposed to various concentrations of GB vapor via whole-body inhalation for 10, 60, or 180 min. Signs of nerve agent exposure were classified as lethal, severe, or moderate. Maximum likelihood estimation was used to calculate the median effect levels: lethal (LCT50) and severe (ECT50) for each gender-duration combination. Ordinal regression was used to model the product of concentration and time profile of the agent toxicity. Contrary to the values predicted by Haber's rule, LCT50 and ECT50 values increased as the duration of the exposures increased. The values for LCT50 (with 95% confidence limits) for 10-, 60-, and 180-min exposures in male minipigs were 72.5 (57.3-91.6), 105.7 (85.6-130.6), and 182.3 (145.2-228.9) mg.min/m3, respectively. The LCT50 values (with 95% confidence limits) for 10-, 60-, and 180-min exposures in female minipigs were 86.9 (69.2-109.2), 127.1 (100.7-160.4), and 174.3 (134.7-225.5) mg.min/m3, respectively. The data were best fit using a probit slope of 15.7 and toxic load exponent of 1.38 (95% confidence limits of 1.25-1.51). Although males were significantly (p = 0.01) more sensitive than females to the lethal effects of GB vapor, the ratios of lethal to severe concentrations were higher in female minipigs (99% ANOVA confidence), indicating that there is less difference between severely toxic and lethal dosages in the female as compared to male pigs.
    02/2006;
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    ABSTRACT: Chemometric approaches have the potential to enhance defense operations against chemical warfare agents (CWAs), for which complex data must be analyzed. Therefore, we have begun an exploration of the use of chemometrics for the correlation of metabolic change with low-level CWA exposure in animal models. In this exploratory study, pigs were exposed to GB (sarin) over a range of concentrations (0.028-0.310 mg/cubic meters) and exposure times (0-180 minutes). Blood (4-8 mL) was collected periodically during miosis-level exposure and the plasma analyzed by proton nuclear magnetic resonance spectroscopy (NMR) at 500 MHz. Principle component (PC) analysis of a small preliminary data set resulted in a PC2 PC1 scores plot showing clustering of the spectra from exposed pigs. Variance highlighted by the first and second principal components corresponded to specific spectral regions which were tentatively assigned to EDTA /choline (NMR peaks overlap) and lactate. Lactate concentration was found to vary in a parallel clinical analysis. The results of this initial study indicate that a combination of chemometrics and NMR will yield metabonomics data useful for establishing biochemical markers for agent exposure. Ideally, such markers would identify metabolic changes that occur prior to visible external symptoms (e.g. miosis, convulsions).
    09/2005;
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    ABSTRACT: Inhibition of acetylcholinesterase (AChE) by the organophosphorous compound sarin (GB) results in the accumulation of acetylcholine and excessive cholinergic stimulation. There are few data in the literature regarding the effects of multiple low-level exposures to GB and other organophosphorous compounds via relevant routes of exposure. Therefore, the present study was undertaken, and is the first, to investigate the effect of low-level repeated whole-body inhalation exposures to GB vapor on pupil size and cholinesterase activity in the eyes and blood. Male Sprague-Dawley rats were exposed to 4.0 mg/m3 of GB vapor for 1 h on each of 3 consecutive days. Pupil size and cholinesterase activities were determined at various points throughout the exposure sequence. The results demonstrate that multiple inhalation exposures to GB vapor produce a decrease in the miotic potency of GB in rats. This tolerance developed at a dose of GB that produced no overt signs of intoxication other than miosis. AChE and butyrylcholinesterase activity did not increase throughout the exposure sequence, suggesting that the tolerance cannot be attributed to a reduced inhibitory effect of GB. A decrease in the amount of GB present in the eye occurred after the third exposure. However, this change is insufficient to explain the tolerance, as there was no corresponding increase in AChE activity. Thus, the mechanism mediating the miotic tolerance observed after multiple inhalation exposures to the nerve agent GB remains uncertain, although several possibilities can be excluded based on the results of the present study.
    Journal of Ocular Pharmacology and Therapeutics 07/2005; 21(3):182-95. · 1.29 Impact Factor
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    ABSTRACT: The median effective concentrations (EC sub 50's) for miosis in male and female rats exposed to VX vapor for 10, 60 and 240 min were estimated using whole body vapor exposures conducted in a 750 liter dynamic airflow inhalation chamber. Miosis was defined as at least a 50% reduction in pupil diameter relative to baseline measurements. Results show that the median effective dosages (ECt sub 50) for miosis are approximately an order of magnitude lower than the calculated ECt sub 50 values for both GB and GF at each of the 3 exposure durations. There were significant gender differences in the ECt sub 50 values for male and female rats with female rats being more sensitive to the effects of VX than males. There was significant whole blood AChE depression at the highest concentrations at each of the exposure times. The results of this study have identified several effects of VX vapor that could impact operational readiness and serve as a basis for predictions useful for military Operational Risk Management (ORM) decisions.
    11/2004;
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    ABSTRACT: Exposure to nerve agent vapors may result in a diverse array of clinical responses including threshold effects to lethality over a relatively small range of dosages. In order to assess the toxic hazards of such exposures and define chemical defense materiel requirements, it is essential to fill gaps in toxicological databases that define the physiological progression; from the first noticeable effect (miosis) to potentially fatal effects of inhalation exposure. Although there are numerous published works investigating the progression of toxic signs elicited by sarin (GB) exposures, both by accidental exposures and in research applications, never has there been a systematic whole-body inhalation study investigating the effects on multiple systems in real-time. While information gleamed from accidental inhalation exposures provides valuable insights on the short and long term sequalae of the exposure, by their nature they do not provide this information until after the subject has been removed from imminent danger, detoxified, and stabilized. In the past, the logistical problems encountered when performing whole-body inhalation experiments with nerve agents have severely limited the ability to collect data in real-time during the exposure. Therefore, the majority of work encompassing nerve agent studies and real-time data collection involves subcutaneous or intravenous injections as the delivery route. While the data collected from these studies is invaluable for assessing medical treatments and short and long-term effects from the agents, the time course of effects (from first evidence of agent in the systemic circulation, to onset of signs, to progression from mild to moderate to severe signs, to death) and compartmental distribution is vastly different. Additionally, and most importantly, they do not address the most likely route of exposure on the battlefield, i.e., inhalation.
    11/2004;
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    ABSTRACT: During the aftermath of the 1995 subway terrorist attack in Tokyo, the thousands of individuals who sought treatment completely overwhelmed resources at local emergency rooms. Of these patients, those who thought they had been exposed to nerve agent outnumbered those who were truly exposed by a ratio of five to one. The most common test for OP compound exposure is measurement of blood acetylcholinesterase. Unfortunately, this blood test is neither rapid, nor can it provide a uniformly reliable assessment of low-level exposure to organophosphate compound in this scenario. Thus, a rapid, reliable, and non-invasive test would be invaluable for the effective management of medical resources in the event of a similar civilian terrorist incident in the U.S. In order to address this need, we have begun a series of experiments designed to identify protein biomarkers in follicles (hair and whisker) of animals exposed to low levels of OP nerve agents.
    11/2004;
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    ABSTRACT: The need to develop a rapid, low-level chemical nerve agent exposure detection system necessitates the development of a blood test that does not require individual initial baseline measurements. Toward this goal, we have begun a series of experiments to screen serum from animals exposed to low levels of OP nerve agents for biomarkers associated with exposure. This manuscript describes the use of strong anion exchange chromatography and Surface Enhanced Laser Desorbtion Ionization (SELDI)-Mass Spectrometry (MS) to efficiently screen serum for protein biomarkers of exposure to GB and VX in the minipig and rat models, respectively. Our most recent data indicates that several protein species are uniquely altered in the serum of low-level agent-exposed animals up to one week after exposure.
    11/2004;
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    ABSTRACT: A method was developed employing an infrared (IR) light source, IR capable video camera, digital processor and image acquisition/analysis software for quantifying pupil constriction resulting from nerve agent vapor exposure. Image acquisition and analysis routines were developed to capture images and automate pupil area measurements or manually analyze images based upon operator-selected parameters. The latter option is useful in cases where the pupil image is partially obstructed or pupil shape is other than circular. The method described here allows for remote/non-invasive assessment of the level as well as the time course of onset and duration of pupil constriction.
    06/2003;
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    ABSTRACT: The goal of these experiments was to determine the lowest sarin (GB) vapor concentration of physiological significance. Gottingen-minipigs were individually exposed to concentrations of GB vapor ranging from 0.03-2.0 mg/cu m for 60 minutes. Pupil constriction was assessed, under dim-light conditions, using an infrared light sensitive video camera and capturing high-resolution images of the eye before, during and after exposure. Pupil area was then quantified automatically off-line using a custom-designed software package. Pupil area was graphed as a function of time. The relationship between the dose-response curve (percent pupil constriction as a function of time) and vapor concentration was investigated.
    06/2003;
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    ABSTRACT: An analysis method was developed in order to quantify the pupil sizes of rats and swine inside a vapor chamber. It employs an infrared (IR) light source, IR capable video camera and computer equipped with image acquisition hardware and novel analysis software for quantifying pupil constriction resulting from nerve agent vapor exposure. An image acquisition and analysis routine was developed to capture images and automate pupil area measurements. The method described here allows for remote/non-invasive assessment of the level as well as the time course of onset and duration of pupil constriction in real-time.
    Bioengineering Conference, 2003 IEEE 29th Annual, Proceedings of; 04/2003

Publication Stats

92 Citations
27.31 Total Impact Points

Institutions

  • 2006–2008
    • United States Army
      Washington, West Virginia, United States
  • 2005
    • National Academy of Sciences
      Washington, Washington, D.C., United States
  • 2002
    • US Army Medical Research Institute of Chemical Defense
      • Research Division
      Aberdeen Proving Ground, Maryland, United States