Larry W. Mitcheltree
United States Department of the Army
SurgeryPathologyChemistryBiopsyHuman skinAnimal modelWeanlingGuinea pigErythemaHairlessWound healingSulfur mustardEdemaNiacinamideMicrovesicleSkin InjuryToxicityHistopathologyBiochemistryMedicineNAD+ kinasePharmacology
13Publications
12H-index
384Citations
Publications 13
Newest
#1John S. GrahamH-Index: 18
#2Robert S StevensonH-Index: 4
Last. Ann M. SchiavettaH-Index: 1
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Abstract Background Sulfur mustard (2,2′-dichlorodiethyl sulfide; HD) is a potent vesicating chemical warfare agent that poses a continuing threat to both military and civilian populations. Significant cutaneous HD injuries can take several months to heal, necessitate lengthy hospitalizations, and result in long-term complications. There are currently no standardized or optimized methods of casualty management. New strategies are needed to provide for optimal and rapid wound healing. Objective T...
35 CitationsSource
#1Ernest H. BraueH-Index: 5
#1Ernest H. Braue (DA: United States Department of the Army)H-Index: 12
Last. Larry W. MitcheltreeH-Index: 12
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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 t...
12 CitationsSource
#1John S. GrahamH-Index: 18
#2Robert S StevensonH-Index: 4
Last. Robyn B. LeeH-Index: 14
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Objective: The objective was to examine the efficacy of several treatment regimens in improving wound healing of cutaneous sulfur mustard (HD) injuries. Methods: Wound healing studies were conducted in weanling pigs. Superficial dermal HD injuries were debrided at 48 hours postexposure using an erbium-doped yttrium aluminum garnet (Er:YAG) laser, followed by application of a treatment adjunct. A variety of noninvasive bioengineering methods were conducted during the postsurgical observation peri...
19 Citations
#1Michael C. Babin (Battelle Memorial Institute)H-Index: 12
#2Karen M. RickettsH-Index: 6
Last. Robert P. Casillas (Battelle Memorial Institute)H-Index: 20
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The mouse ear vesicant model (MEVM) is a screening tool used to identify protective compounds against acute sulfur mustard (SM)‐induced skin injury. It provides endpoints of edema and histopathology 24 h following a topical SM exposure to assess protection against inflammation and tissue damage. To further evaluate successful compounds, the MEVM was modified for use as a 7‐day model. Dose response studies were conducted with SM to select an optimal challenge dose for the new model. Due to severi...
5 CitationsSource
#1John S. GrahamH-Index: 18
#2Jamie L. Martin (DA: United States Department of the Army)H-Index: 5
Last. Ernest H. BraueH-Index: 5
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Background/aims: The euthymic hairless guinea pig was the animal model of choice at this laboratory for vesicant injury research. The supply of these animals, however, was interrupted in 1993 by an outbreak of Lisferia monocyfogenes at the commercial supplier's breeding facility, thereby forcing a search for alternative animal models. This report describes the development of a weanling pig model for use in evaluating the severity of skin lesions induced by sulfur mustard [bis(2-chloroethyl)sulfi...
16 CitationsSource
#1Jeffrey J. Yourick (FDA: Food and Drug Administration)H-Index: 9
#2Jeffrey S. DawsonH-Index: 3
Last. Larry W. MitcheltreeH-Index: 12
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Erythema is the initial symptom that occurs after sulfur mustard (HD) cutaneous exposure. The time course of HD-induced erythema is similar to that observed after UV irradiation, which can be reduced by indomethacin. Sulfur mustard lethality is decreased by using promethazine, which is an antihistamine. Niacinamide can reduce microvesication after HD vapor exposure in hairless guinea pig (HGP) skin. The present study examines the effect of the combined administration of niacinamide, indomethacin...
38 CitationsSource
#1Jeffrey J. YourickH-Index: 5
#1Jeffrey J. YourickH-Index: 9
Last. Larry W. MitcheltreeH-Index: 12
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Abstract Developing skin lesions on hairless guinea pigs due to 2,2′-dichlorodiethyl sulfide (sulfur mustard, HD) exposure were examined to determine the time course for the appearance of histopathologic markers in relationship to skin NAD + and NADP + content after HD exposure. Hairless guinea pig skin was exposed to HD for 8 min by means of a vapor cup. Skin punches were taken at 1, 2, 4, 8, 12, 16, 20 and 24 h after HD exposure. Intracellular edema (IE) appeared at 2 h and increased steadily ...
23 CitationsSource
Abstract It has been postulated that sulfur mustard (HD) damage may activate poly(ADP-ribose) polymerase (PADPRP), resulting in depletion of cellular NAD + . This biochemical alteration is postulated to result in blister (vesicle) formation. It has been previously demonstrated that niacinamide (NAM), an inhibitor of PADPRP and a precursor for NAD + synthesis, may be useful as a pretreatment compound to reduce HD-induced microvesication. The present study was undertaken to determine whether niaci...
23 CitationsSource
#1Ernest H. Braue (DA: United States Department of the Army)H-Index: 12
#1Ernest H. BraueH-Index: 5
Last. Catherine R. BangledorfH-Index: 2
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The identification of antivesicant compounds has been hindered by the lack of a suitable in vivo model. Our laboratory has been evaluating the hairless guinea pig as a useful animal model to mimic the human cutaneous response to sulfur mustard (HD) exposure. The characterization of two cutaneous responses to HD, quantification of erythema using a reflectance color meter, and pathology by light microscopy, is described in this manuscript. Fifty-two hairless guinea pigs were exposed to saturated H...
25 CitationsSource
#1Millard M. MershonH-Index: 6
Last. John V. WadeH-Index: 4
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Abstract Sulfur mustard (HD; 1,1′-thiobis[2-chloroethane]) induces fluid-filled blisters in man but not in conventional laboratory animals. An animal model is needed to emulate both cytotoxic (vesicant) and vascular (irritant) responses of human skin to HD exposures. An acceptable model must permit reproducible comparisons of uniformly graded and dose-related HD control responses with reduced responses that may follow antivesicant treatments. Hairless guinea pigs were evaluated by exposing six o...
86 CitationsSource