Graham John S, Stevenson Robert S, Mitcheltree Larry W, Hamilton Tracey A, Deckert Robin R, Lee Robyn B, Schiavetta Ann M
Medical Toxicology Branch Analytical Toxicology Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA.
Toxicology. 2009 Sep 1;263(1):47-58. doi: 10.1016/j.tox.2008.07.067. Epub 2008 Aug 14.
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.
The primary aim of this research was to develop improved clinical strategies (treatment guidelines) for optimal treatment of superficial dermal (second degree) cutaneous HD injuries, with the goal of returning damaged skin to optimal appearance and normal function in the shortest period of time.
Superficial dermal HD injuries were created on the ventral abdominal surface of weanling pigs. At 48h post-exposure, lesions were laser debrided and a treatment adjunct applied. Cultured epithelial allografts and 11 commercial off-the-shelf (COTS) products were examined for their efficacy in improving wound healing of these injuries. Clinical evaluations and a variety of non-invasive bioengineering methods were used at 7 and 14 days post-surgery to follow the progress of wound healing and evaluate various cosmetic and functional properties of the wounds. Measurements included reflectance colorimetry to measure erythema; evaporimetry to examine transepidermal water loss as a method of evaluating barrier function; torsional ballistometry to evaluate the mechanical properties of skin firmness and elasticity; and two-dimensional high frequency ultrasonography (HFU) to monitor skin thickness (e.g., edema, scar tissue). Histopathology and immunohistochemistry were performed 14 days following surgery to examine structural integrity and quality of healing. Logical Decisions((R)) for Windows was used to rank the 12 treatment adjuncts that were studied.
The most efficacious treatment adjuncts included (1) Vacuum Assisted Closure, V.A.C., involving application of topical negative pressure, (2) Amino-Plex Spray (biO(2) Cosmeceuticals International, Inc., Beverly Hills, CA), a nutritive cosmeceutical product that is designed to increase oxygen in cells, stimulate ATP synthesis, improve glucose transportation, stimulate collagen formation, and promote angiogenesis, and (3) ReCell Autologous Cell Harvesting Device (Clinical Cell Culture Americas LLC, Coral Springs, Florida), an innovative medical device that was developed to allow rapid harvesting of autologous cells from a thin split-thickness biopsy followed by spray application of a population of skin cells onto wounds within 30 min of collecting the biopsy, without the need of culturing the keratinocytes in a clinical laboratory.
Complete re-epithelialization of debrided HD injuries in 7 days is possible. In general, shallow laser debridement through the basement membrane zone (100 microm) appears to provide better results than deeper debridement (400 microm) with respect to early re-epithelialization, cosmetic appearance, functional restoration, and structural integrity. Of the 12 treatment adjuncts examined, the most promising included Vacuum Assisted Closure, Amino-Plex Spray, and ReCell Autologous Cell Harvesting Device.
硫芥（2,2'-二氯二乙硫醚；HD）是一种强效的起疱性化学战剂，对军事人员和平民都构成持续威胁。严重的皮肤HD损伤可能需要数月才能愈合，需要长时间住院治疗，并会导致长期并发症。目前尚无标准化或优化的伤员管理方法。需要新的策略来实现最佳且快速的伤口愈合。
本研究的主要目的是制定改进的临床策略（治疗指南），以对浅表真皮（二度）皮肤HD损伤进行最佳治疗，目标是在最短时间内使受损皮肤恢复到最佳外观和正常功能。
在断奶仔猪的腹部腹侧制造浅表真皮HD损伤。暴露后48小时，对损伤部位进行激光清创并应用一种治疗辅助剂。研究了培养的同种异体上皮移植物和11种商用现成产品（COTS）在改善这些损伤伤口愈合方面的疗效。在手术后7天和14天，使用临床评估和多种非侵入性生物工程方法来跟踪伤口愈合进程，并评估伤口的各种外观和功能特性。测量包括用反射比色法测量红斑；用蒸发测定法检查经表皮水分流失，以此作为评估屏障功能的一种方法；用扭转冲击测量法评估皮肤紧致度和弹性的力学性能；以及用二维高频超声检查（HFU）监测皮肤厚度（如水肿、瘢痕组织）。术后14天进行组织病理学和免疫组织化学检查，以检查愈合的结构完整性和质量。使用适用于Windows的Logical Decisions((R))对所研究的12种治疗辅助剂进行排名。
最有效的治疗辅助剂包括：（1）真空辅助闭合（V.A.C.），即施加局部负压；（2）氨基复合喷雾（biO(2) 国际美容药妆公司，加利福尼亚州比佛利山庄），一种营养性美容药妆产品，旨在增加细胞中的氧气、刺激ATP合成、改善葡萄糖转运、刺激胶原蛋白形成并促进血管生成；（3）ReCell自体细胞采集装置（美国临床细胞培养公司，佛罗里达州珊瑚泉），一种创新的医疗设备，其开发目的是允许从薄的断层皮片中快速采集自体细胞，然后在采集活检后30分钟内将一群皮肤细胞喷洒到伤口上，而无需在临床实验室中培养角质形成细胞。
清创后的HD损伤在7天内实现完全重新上皮化是可能的。一般来说，相对于更深的清创（400微米），通过基底膜带（100微米）进行浅激光清创在早期重新上皮化、外观、功能恢复和结构完整性方面似乎能提供更好的效果。在所研究的12种治疗辅助剂中，最有前景的包括真空辅助闭合、氨基复合喷雾和ReCell自体细胞采集装置。
