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Works: 235 works in 248 publications in 1 language and 250 library holdings
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Medical Management of Chemical Casualties, Handbook. Second Edition( Book )

1 edition published in 1995 in English and held by 3 WorldCat member libraries worldwide

Chemical warfare is not a popular topic, and most military health care providers do not willingly become familiar with it. This was painfully obvious during Operation Desert Shield/Desert Storm when it soon became apparent that many health care providers knew little about the effects of chemical agents or about the medical defense against them. This ignorance was particularly striking in view of the seven-decade-long history of modern chemical warfare and the well-publicized use of mustard and nerve agent during the Iran-Iraq war in the 1980s. The prevailing attitude of military health care providers was that chemical agents would be used only on Hmong, Mghans, Kurds, or similarly unprepared and unprotected groups of people. Further, many health care providers believed if chemical weapons were used the outcome would be disastrous, defense would be impossible, and the casualty rate and loss of life would be high. Through education, however, medical professionals involved in Operation Desert Shield/Desert Storm learned that medical defenses were possible and effective, that chemical casualties could be saved and returned to duty, and that mortality could be minimized. Further, they realized that they might be the target of chemical agents. More importantly, they rapidly learned that General Pershing's warning (written shortly after World War I) about chemical agents was still true: ' ... the effect is so deadly to the unprepared that we can never afford to neglect the question.' The purpose of this handbook is to provide a small and concise handbook for attendees at the Medical Management of chemical Casualties Course. The handbook is small so that it can be easily carried, and the format is such that it can be easily updated. It is not intended to be a definitive text on the management of chemical casualties
Ultrastructural Correlates of Sulfur Mustard Toxicity( Book )

2 editions published between 1989 and 1990 in English and held by 2 WorldCat member libraries worldwide

Standardized ultrastructural technology was used to study subcellular effects of sulfur mustard (HD) on (1) human lymphocytes in vitro, (2) human keratinocytes in culture, and (3) the skin of the hairless guinea pig. While doses of mustard differed according to the dictates of individual protocols, all specimens were gathered 24 hours following exposure, aldehyde fixed, and processed for transmission and scanning electron microscopy. In the hairless guinea pig model the subcellular effects on basal cells of the stratum germinativum and the generation of microblisters at the dermal-epidermal junction were unequivocal to that reported for human-skin grafted to cogenitally athymic nude mice. Keywords: Sulfur mustard (HD), Toxicity, Lymphocytes in vitro, Keratinocytes in culture, Skin, Ultrastructure, Pathology. (JES)
Reversal of Saxitoxin (STX) and Tetrodotoxin (TTX) Induced Cardio-Respiratory Failure with 4-Aminopyridine (4-AP)( Book )

2 editions published in 1993 in English and held by 2 WorldCat member libraries worldwide

The effect of 3,4 diaminopyridine (3,4 DAP) on saxitoxin (STX) - and tetrodotoxin (TTX)-induced cardiorespiratory depression was examined in anesthetized guinea pigs which were instrumented to record medullary respiratory neuronal activity, arterial pressure, ECG, ECoG, diaphragm EMG (DEMG), end-tidal CO(2) and arterial pH, Co(2) and O(2). Infusion of STX or TTX (0.3 ug/kg/min, IV) elicited progressive vascular hypotension, bradycardia and bradypnea leading to complete inhibition of DEMG activity. Artificial ventilation was introduced when DEMG activity was reduced by 50% due to STX or TTX. Toxin infusion was stopped upon the inhibition of DEMG activity and 3,4 DAP (8 Mg/kg, IV) was given subsequently. Arterial pressure and heart rate returned to pretoxin levels and DEMG activity reappeared rapidly following 3,4 DAP infusion. In most cases, animals resumed spontaneous breathing within minutes after 3,4 DAP. Spontaneous breathing was often sustained for several hours after a single infusion of 3,4 DAP. Uncompensated arterial acidosis was typically observed during spontaneous breathing after 3,4 DAP treatment; however, this could be corrected with sodium bicarbonate (7.5%, IV). Despite the therapeutic actions of 3,4 DAP, some side effects were identified. Adverse side effects of 3,4 DAP administration included aberrant patterns of medullary discharge. Current investigations address strategies to minimize these medullary neuronal side effects of 3,4 DAP and to potentiate its therapeutic actions
Gas Chromatographic-Mass Spectrometric Analysis of Sulfur Mustard-Plasma Protein Adducts: Validation and Use in a Rat Inhalation Model( Book )

2 editions published in 2008 in English and held by 2 WorldCat member libraries worldwide

An analytical method for determining exposure to 2,2'-dichlorodiethyl sulfide (sulfur mustard, HD) has been enhanced. The method is based on the cleavage of adducted HD (protein-hydroxyethylthioethyl esters) to produce thiodiglycol. Following cleavage, a deuterated internal standard is added, and the analytes are extracted, derivatized, and analyzed by gas chromatography-negative ion chemical ionization-mass spectrometry. Inclusion of a concentration step, addition of solid sodium bicarbonate to neutralize excess derivatization reagent, and optimization of method and instrument conditions provided dramatic increases in signal-to-noise ratio. A five-day precision and accuracy study was conducted, including interday and intraday unknown analysis. Linearity was verified by a R2> 0.9995 for all five curves evaluated. The precision and accuracy of the assay were demonstrated to be excellent by evaluation of the interday and intraday unknown samples (<10% relative standard deviation and relative error in most cases). Statistical treatment of the method blanks and calibration results demonstrated a reduction in the limit of quantitation from 25nM (HD, human plasma, in vitro) to 1.56nM. Sample and calibration stability through the analytical sequence was established by the inclusion of continuing calibration verification standards (<5% error). Short-term sample stability was verified by reinjection of a calibration set after 18 days (R2 =0.9997)
Non-invasive Serial Blood Collection in Guinea Pigs (Cavia porcellus)( Book )

1 edition published in 2007 in English and held by 1 WorldCat member library worldwide

Blood draws from guinea pigs (Cavia porcellus) became a requirement for animals trained in several behavioral tasks pre- and postexposure to chemical warfare agents (CWAs). Due to the number of animals, the sensitivity of the behavioral assessments and the need for serial blood draws, current methods for blood collection could not be used because they required anesthesia or analgesics, extensive training, a high level of competence, and multiple technicians. The toenail clip method provided an easily trained, easily performed method of blood collection that yielded up to one milliliter of blood, required only topical anesthesia and appeared to cause little pain or stress to the animal
Clinical Considerations in the Use of Pyridostigmine Bromide as Pretreatment for Nerve-Agent Exposure by Jim Madsen( Book )

2 editions published between 1998 and 2003 in English and held by 1 WorldCat member library worldwide

The currently fielded pretreatment for nerve-agent exposure is pyridostigmine bromide (PB). Military physicians and other health-care providers need to be familiar with this medication, with the rationale for its use, and with its effects on the body. They also need to be able to respond intelligently to questions from healthy soldiers taking PB, from patients, and from field commanders. This publication is intended to address the major issues that military health-care providers need to understand concerning nerve-agent pretreatment with PB. It is organized around a series of questions about PB in general and its pharmacokinetics (absorption, distribution, biotransformation, and elimination), pharmacodynamics (mechanism of action), field use, and reported and expected effects. The information is doctrinally consistent with and assumes a working knowledge of the tri-service field manual "Treatment of Chemical Agent Casualties and Conventional Military Chemical Injuries," Army FM8-285, Navy NAVMED P-5041, Air Force AFM 16011, dated 22 December 1995
Brain Damage from Soman-Induced Seizures Is Greatly Exacerbated by Dimethyl sulfoxide (DMSO): Modest Neuroprotection by 2-Aminoethyl diphenylborinate (2- APB), a Transient Receptor Potential Channel Inhibitor and Inositol 1,4,5-triphosphate Receptor Antagonist( Book )

1 edition published in 2008 in English and held by 1 WorldCat member library worldwide

Soman is a nerve-agent that produces seizures and seizure-related brain damage (SRBD). It is well known that termination of soman-induced seizures, using anticonvulsant drug therapy, would be the ideal means of preventing SRBD. However, these seizures quickly develop into status epilepticus and become refractory to anticonvulsant therapy shortly after their onset. Medical care for some battlefield casualties will likely be delayed beyond the therapeutic window of opportunity to terminate soman-induced seizures. Moreover, SRBD that has already been triggered will continue, along the pathological cascade, unabated by the currently fielded therapeutic regimen. Thus, there is a need for adjunct drug therapy that is capable of interrupting ensuing pathology and augmenting neuroprotection when administered, in conjunction anticonvulsants, during the refractory phase of soman-induced seizures. Considerable evidence supports a pivotal role of sustained elevations in intracellular calcium (i.e., delayed calcium overload) in SRBD resulting from soman-induced seizures and status epilepticus. In addition, there are several reports that a neuroprotective approach, aimed at attenuating delayed calcium overload, combined with standard anticonvulsant therapy, provides greater protection against soman-induced SRBD than anticonvulsant therapy alone. Transient receptor potential (TRP) channels, a new class of membrane ion channels, are responsible for capacitative calcium entry and have been linked to delayed calcium overload. The TRP channel antagonist, 2-aminoethyl diphenylborinate (2-APB), blocks calcium capacitative entry and is reported to be neuroprotective in various excitotoxic models. 2-APB is also a potent inositol 1,4,5, triphosphate (IP3) receptor antagonist and blocks release of calcium from internal stores. In the present study, we assessed the neuroprotective efficacy of 2-APB against somaninduced SRBD
Production of Normal Human Epidermal Keratinocytes for Use in Biochemical Research( Book )

2 editions published in 1999 in English and held by 1 WorldCat member library worldwide

This technical report outlines procedures that have been developed to provide a cost effective and high efficiency quality control quantity of normal human epidermal keratinocyte (NHEK) cells to conduct research into the mechanism of action of chemical warfare (CW) agents and to reduce the dependence on live animal testing with toxic CW agents. Adult NHEK cell lines were grown at different cell densities in a variety of diverse tissue culture vessels. The purpose of this technical report is to provide an overall review of important tissue culture parameters for the optimal production and use of NHEK in toxicological research. These cells have provided valuable information for the design of therapeutic intervention against 2,2'- dichlorodiethyl sulfide (sulfur mustard, HD) induced lesions
Issues Related to the Decontamination of Chemically Contaminated Human Remains( Book )

2 editions published in 1993 in English and held by 1 WorldCat member library worldwide

This report, based on a search of the available literature, addressed issues specific to problems of decontamination of chemically contaminated human remains. Specific areas of concern included: (1) identification of a worst case situation; (2) determining if hypochlorite is the best decontaminant available; (3) determining the optimum pH for hypochlorate use as a decontaminant; (4) determining an optimum concentration of hypochlorite; (5) determining whether there is benefit in using the sodium salt over the calcium salt of hypochlorite; (6) determination/identification of the agent(s) most difficult to decontaminate; (7) estimation of amount of agent to which remains would be exposed; (8) estimation of how much, if any, agent could be found in decontaminated remains that might be hazardous to handlers of the remains subsequent to decontamination; and (9) determining if there are cosmetic effects produced by the decontamination process. Because the Army was proceeding to write doctrine for a specific decontamination procedure, the questions addressed in this report were focused to those issues that were of prime importance to near-term development of a field system for decontamination of chemically contaminated human remains so that the remains could be released to the family of the deceased
Measure of O(6)-Alkylguanine-DNA Alkyltransferase Activity in Normal Human Epidermal Keratinocytes in Culture and Effects of Bis-(2-chloroethyl)sulfide in the Activity( Book )

2 editions published in 1999 in English and held by 1 WorldCat member library worldwide

O(sup 6)-Alkylguanine-DNA alkyltransferase (AGT) is a DNA repair protein that removes alkyl adducts from O(sup 6)-alkylguanine in DNA. AGT may be important in DNA repair following injury induced by bis-(2-chloroethyl)sulfide (sulfur mustard, HD), since O(sup 6)-alkylguanine is one of the HD alkylation products. One model for HD-induced injury uses normal human epidermal keratinocytes (NHEK) in culture. In this study we measured the levels of AGT in NHEK grown to either 60 - 80% or to 100% confluency and then studied the effects of a one-hour exposure to 50, 100, and 300 micro-M HD on AGT activity. Mean AGT activity in NHEK grown to 60.89% and 100% confluency was 470 +/- 404 and 518 +/- 737 fmol/mg protein, respectively. In general, AGT activity appeared to increase after exposure to 100 micro-M HD and decrease with increased confluency and after exposure to 50 and 300 micro-M HD. However, a two-way analysis of variance for cell confluency and HD concentration showed no significant differences between cell confluencies or the different HD concentrations
Detection and Measurement of Sulfur Mustard (HD) Offgassing from the Weanling Pig Following Exposure to Saturated HD Vapor( Book )

2 editions published in 1997 in English and held by 1 WorldCat member library worldwide

Sulfur mustard (HD) is a chemical warfare agent for which there is neither antidote nor adequate therapeutic protection. Animal models are employed to investigate mechanisms of injury and to evaluate protective measures against HD exposure. Researchers whose experiments involve cutaneous application of HD vapor to animals benefit from the detection and quantitation of HD at the exposed site. The ability to detect and quantify HD enables the researcher to follow safe procedures in handling skin samples. We have designed an experimental procedure to measure HD offgassing from animal models. A Minicams(R), which is a portable gas chromatograph (GC) equipped with a flame photometric detector (FPD) and with online sorbent collection and desorption, was used to monitor the HD concentration. Confirming measurements were made using a two-step process that trapped HD on a Tenax sorbent offline and then transferred the sample by means of an ACEM 900 to a OC equipped with either FPD or a mass spectrometer (MS). We collected data from six experiments in which weanling pigs were exposed to saturated HD vapor via vapor caps containing 10 micro of HD. HD concentration was measured in time-weighted-average (TWA) units at a specific HD application site. The currently recommended exposure value for HD is 3 ng/l, 1 TWA unit. In five of the six experiments, Minicams HD concentration values were less than 0.5 TWA, 2 hours postexposure, and in one of the experiments, TWA Minicams concentration was less than 0.5 TWA, 5 hours post-exposure. OCIMS detection was used in three of the experiments to confirm Minicams data and to provide greater sensitivity and selectivity at 0.1 TWA. GC/MS data confirmed that HD concentrations fell below 0.1 TWA in less than S hours for a specific site
A Method for the Analysis of Tabun in Multisol Using Gas Chromatographic Flame Photometric Detection( )

2 editions published in 2006 in English and held by 0 WorldCat member libraries worldwide

In the past we have found tabun (GA) in saline at 2 microgram/ml to be stable for only a month or less at -70 degrees C. Previous studies have shown that Multisol provides stable solutions of GA. We confirmed the stability of GA in Multisol with phosphorus nuclear magnetic resonance and developed a method for the analysis of GA in Multisol using gas chromatographic flame photometric detection (GCFPD) in the phosphorus mode. The GC method used acetonitrile (CH3CN) for a dilution solvent because of its miscibility with GA in chloroform (CHC13) standards and GA in Multisol samples at 1% (v/v). Furthermore, the dilutions with CH3CN made the phosphorus mode interference peak present in CHC13 analytically manageable, reduced the interferences of Multisol in the GC separation, and contributed to a safe and reliable analysis of GA at 20 microgram/ml. We demonstrated the stability of GA in Multisol stored for more than a year at -70 degrees C. This method contributes a suitable technique for the preparation and analysis of reliable solutions of GA in nerve agent medical research and demonstrates the extended stability of GA in Multisol
Human Dermal Fibroblasts (Adult): Instructions for Initiation of Cultures from Cryopreserved Cells and Subculture( )

2 editions published between 2002 and 2004 in English and held by 0 WorldCat member libraries worldwide

This technical report outlines procedures that have been developed to provide a cost effective way to produce large quantities of normal human skin fibroblast cells (NHSFs) for studying the mechanism(s) of action of chemical warfare agents (CWAs) and medical counter-measurements against CWAs. Various growth factors were added to media recommended by the supplier, American Type Culture Collection (ATCC), Manassas, Virginia, USA. Cell viability, cell differentiation and cell proliferation were evaluated using different tissue culture assays in particular the CyQUANT(Registered) Cell Proliferation Assay kit obtained from Molecular Probes, Inc., Eugene, Oregon, USA. This particular assay measures cell proliferation and was used as indicated in the experimental protocol provided by the product brochure. We found cultured human skin cells to be a useful model for skin irritation testing
A Comparison of the Treatment of Cyanide Poisoning in the Cynomolgus Monkey with Sodium Nitrite of 4-Dimethylaminophenol (4-DMAP), with and without Sodium Thiosulfate( )

1 edition published in 1994 in English and held by 0 WorldCat member libraries worldwide

Two methemoglobin generating compounds, sodium nitrite (iv) or 4- dimethylaminophenol (4-DMAP (im), with and without sodium thiosulfate (iv), were compared as post-treatment therapy in anesthetized monkeys poisoning with cyanide. Arterial blood samples were taken before and after an injection of sodium cyanide (8.4 mg/kg) and treatment for analyses of blood cyanide, plasma cyanide, thiocyanate and methemoglobin content. Physiologic parameters were monitored in these treated cyanide-poisoned animals. The time course of methemoglobin formation and physiologic parameters were also monitored in animals receiving only 4-DMAP or sodium nitrite. A maximal methemoglobin level was observed at 30 minutes following injection of 4-DMAP, and 60 minutes post injection with sodium nitrite. Volumes of distribution (Vd) of cyanide were calculated from the concentrations of cyanide in blood samples and doses of cyanide injected. Although 4-DMAP forms methemoglobin more rapidly than sodium nitrite, both compounds form methemoglobin quickly enough to provide protection against cyanide poisoning. The protection offered by either compound against the lethal effects of cyanide was potentiated when used in combination with sodium thiosulfate. Cyanide, Sodium nitrite, 4-Dimethylaminophenol, Sodium thiosulfate, Thiocyanate, Methemoglobin
Effects of Prednisolone Acetate on Ocular Sulfur Mustard Injury in a Rabbit Model( )

1 edition published in 2003 in English and held by 0 WorldCat member libraries worldwide

Eye injury from HD (sulfur mustard) exposure continues to remain a threat to soldiers in the battlefield. This study was designed to explore the effects of Pred-Forte (prednisolone) in treating ocular HD injury. Sixteen female New Zealand White rabbits were exposed to 0.51 mg of undiluted HD as a liquid droplet. One group (n=8) received 2 drops of Pred-Forte into the eye every 10 minutes for the first 30 minutes postexposure, then every 30 minutes for 2 hours, after which treatments were given three times daily (tid). The control group of animals (n=7) received 2 drops of Artificial Tears. Eyes of rabbits were evaluated and scored weekly for 56 weeks, then at 12, 13 and 16 weeks. Measurements included slit lamp evaluation, corneal thickness (Pachymetry), and modified ocular severity score (MOSS). Lesions or ulcers resulting in corneal perforations developed within the first 34 weeks in 9 out of 15 rabbits. Treatments were discontinued at 3 weeks; however, observations continued to 16 weeks. Adverse reactions were attributed to treatment effect, inexperienced operators (HD) and/or both. The use of different applications of HD to the eye should also be considered to eliminate variability seen with the droplet method
Telechemistry Projecting Laboratory Expertise to a Deployed TAML( )

2 editions published in 2003 in English and held by 0 WorldCat member libraries worldwide

The 520th Theater Army Medical Laboratory (TAML) is a unique Army asset with worldwide responsibility to deploy on short notice and conduct health surveillance as part of a comprehensive Force Health Protection Program. The TAML is staffed by permanent party enlisted and officers and augmented with Professional Filler System (PROFIS) officers upon deployment. The staff is required to set up, operate, maintain, and troubleshoot sophisticated, delicate, analytical equipment in a hostile environment. Training of TAML soldiers on analytical chemistry techniques is the joint responsibility of the U.S. Army Medical Research Institute of Chemical Defense (USAMRICD) and the U.S. Array Center for Health Promotion and Preventive Medicine (USACHPPM) who, collectively, possess the expertise needed by the TAML soldiers for analysis, data interpretation, troubleshooting, and consultation.- However, implementing a comprehensive training plan has been undermined by routine deployments and the constant turnover of TAML personnel. We have addressed these issues using telemedicine technology to link the TAML to the experts in instrument operations and data analysis residing in these partnership units. The proposal was conducted in three phases; Equipment Procurement and Training, Proof of Concept, and Concept Validation. All tested scenarios met or exceeded established operating standards. By all measures the proposal was determined to be successful and to tremendously enhance the TAML's operational capability
Noninvasive Methods for Determining Lesion Depth from Vesicant Exposure( )

2 editions published between 2004 and 2007 in English and held by 0 WorldCat member libraries worldwide

Before sulfur mustard (HD) injuries can be effectively treated, assessment of lesion depth must occur. Accurate depth assessment is important because it dictates how aggressive treatment needs to be to minimize or prevent cosmetic and functional deficits. Depth of injury typically is assessed by physical examination. Diagnosing very superficial and very deep lesions is relatively easy for the experienced burn surgeon. Lesions of intermediate depth, however, are often problematic in determining the need for grafting. This study was a preliminary evaluation of two noninvasive bioengineering methodologies, laser Doppler perfusion imaging (LDPI) and indocyanine green fluorescence imaging (ICGH), to determine their ability to accurately diagnose depth of sulfur mustard lesions in a weanling swine model. Histological evaluation was used to assess the accuracy of the imaging techniques in determining burn depth. Six female weaning swine (8-12 kg) were exposed to 400 microliters of neat sulfur mustard on six ventral sites for 2, 8, 30, or 60 minutes. This exposure regimen produced lesions of varying depths from superficial to deep dermal. Evaluations of lesion depth using the bioengineering techniques were conducted at 24, 48, and 72 hours after exposure. After euthanasia at 72 hours alter exposure, skin biopsies were taken from each site and processed for routine hematoxylin and eosin histological evaluation to determine the true depth of the lesion. Results demonstrated that LDPI and ICGH were useful tools to characterize skin perfusion and provided a good estimate of HD lesion depth. Traditional LDPI and the novel prototype ICGFI instrumentation used in this study produced images of blood flow through skin lesions, which provided a useful assessment of burn depth. LDPI and ICGH accurately predicted the need for aggressive treatment (30- and 60-minute HD lesions) and nonaggressive treatment (2- and 8-minute HD lesions) for the lesions generated in this study
Acute versus Subchronic Pyridostigmine Administration: Effects on the Anticholinergic Properties of Atropine( )

1 edition published in 1993 in English and held by 0 WorldCat member libraries worldwide

Acute, subchronic and chronic exposures to cholinergic compounds may result in differing effects. The efficacy of pyridostigmine bromide (PY) prophylaxis against organophosphorus poisoning depends on post exposure atropine (AT) administration. AT induces a dose-dependent increase in rate of rise of core temperature in heat exposed humans and rats. To determine whether AT's anticholinergic potency is altered following PY administration, we examined AT's effects following acute or subchronic (2 weeks) PY administration in the sedentary heat-stressed rat. Unrestrained rats were used in the following 8 groups of 12: acute (a,2 injections via tail vein) aSAL+SAL, aSAL+AT, aPY+SAL, aPY+AT; subchronic (c, osmotic pump + tail vein) cSAL+SAL, cSAL+AT, cPY+SAL, CPY+AT (SAL- saline, AT- 200 ug/kg, aPY- 100 ug/kg, cPY- 20 ug/hr.) Fifteen minutes following the final injection, rats were subjected to an ambient temperature of 41.5 deg C until a core temperature of 42.6 deg C was attained
A Convenient Fluorometric Method to Study Sulfur Mustard-Induced Apoptosis in Human Epidermal Keratinocytes Monolayer Microplate Culture( )

2 editions published between 2004 and 2005 in English and held by 0 WorldCat member libraries worldwide

Sulfur mustard [SM; bis-(2-chloroethyl) sulfide], which causes skin blistering or vesication [(1991). Histo- and cytopathology of acute epithelial lesions. In: Papirmeister, 13., Feister, A.J., Robinson, S.I., Ford, R.D., eds. Medical Defense Against Mustard Gas: Toxic Mechanisms and Pharmacological Implications. Boca Raton: CRC Press, pp. 43-78.], is a chemical warfare agent as well as a potential terrorism agent. SM-induced skin blistering is believed to be due to epidermal-dermal detachment as a result of epidermal basal cell death via apoptosis an & or necrosis. Regarding the role of apoptosis in SM pathology in animal skin, the results obtained in several laboratories, including ours, suggest the following: 1) cell death due to SM begins via apoptosis that proceeds to necrosis via an apoptotic-necrotic continuum and 2) inhibiting apoptosis decreases SM-induced microvesication in vivo. To study the mechanisms of SM-induced apoptosis and its prevention in vitro, we have established a convenient fluorometric apoptosis assay using monolayer human epidermal keratinocytes (HEK) adaptable for multiwell plates (24-, 96-, or 384-well) and high-throughput applications
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