Objective: Cement burns account for relatively few admissions to a burn unit; however, these burns deserve separate consideration because of special features of diagnosis and management. Cement burns, even though potentially disabling, have rarely been reported in literature. Methods: A retrospective review was performed of all patients admitted with cement burns injuries to the national burns unit at the St James's Hospital in Dublin, Ireland, over a 10-year period for the years 1996–2005. Results: A total of 46 patients with cement burns were admitted. The majority of patients were aged 16–74 years (mean age = 32 years). Eighty-seven percent of injuries occurred in an industrial and 13% in a domestic setting. The upper and lower extremities were involved in all the patients, and the mean total body surface area affected was 6.5%. The mean length of hospital stay was 21 days with a range of 1–40 days. Thirty-eight (82%) were surgically managed involving debridement and split-thickness skin graft (SSG) and four (9%) were conservatively managed. A further four did not have data available. Conclusion: Widespread inexperience in dealing with this group of cement burns patients and delays in referral to burns unit highlights the potential for greater levels of general awareness and knowledge in both prevention and treatment of these burns. As well, early debridement and split-thickness skin grafting at diagnosis constitutes the best means of reducing the high socioeconomic costs and allows for early return to work.
Objective: We evaluated the long-term outcome of the “pocket flap-graft” technique, used to cover acute deep burns of the dorsum of the hand, and analyzed surgical alternatives. Methods: This was a 6-year, retrospective study of 8 patients with extensive burns and 1 patient with a single burn (11 hands in all) treated by defatted abdominal wall pockets. We studied the medical records of the patients, and conducted a follow-up examination. Results: All hands had fourth-degree thermal burns caused by flames, with exposure of tendons, bones, and joints, and poor functional prognosis. One third of patients had multiple injuries. Burns affected an average of 36% of the hand surface, and mean coverage was 92.8 cm2. One patient died. The 8 others were seen at 30-month follow-up: the skin quality of the flap was found to be good in 55% of the cases, the score on the Vancouver Scar Scale was 2.4, the Kapandji score was 4.5, and total active motion was 37% of that of a normal hand. Hand function was limited in only 2 cases, 8 patients were able to drive, and 3 patients had gone back to work. Conclusion: The pocket flap-graft allows preservation of hand function following severe burns, when local or free flaps are impossible to perform. Debulking of the flap at the time of elevation limits the need for secondary procedures.
Background: A topical antimicrobial that can decrease the bacterial bioburden of chronic wounds without impairing the wound's ability to heal is a therapeutic imperative. A stabilized form of hypochlorous acid (NVC-101) has been demonstrated in vitro and in standard toxicity testing to possess properties that could fulfill these criteria. Materials and Methods: Using a standard rodent model of a chronically infected granulating wound, various preparations of NVC-101 and multiple treatment regimens were investigated to evaluate the role of NVC-101 in decreasing tissue bacterial bioburden and overcoming the inhibition of infection on wound healing. Quantitative bacteriology of tissue biopsies and wound healing trajectories were used to compare the various NVC-101 preparations and regimens to saline-treated negative controls and silver sulfadiazine–treated positive controls. Results: NVC-101 at 0.01% hypochlorous acid with a pH of 3.5 to 4.0 proved to be an effective topical antimicrobial. It was most effective when used for a brief period (15–30 minutes), and followed with another application. Possibly this was due to its rapid neutralization in the wound bed environment. Although not as effective at decreasing the tissue bacterial bioburden as silver sulfadiazine, NVC-101 was associated with improved wound closure. Conclusions: This stabilized form of hypochlorous acid (NVC-101) could have potential application as an antimicrobial wound irrigation and treatment solution if its effective pH range can be maintained in the clinical situation. NVC-101 solution was equally effective at pH 3.5 or 4.0 and more efficient soon after its application. As opposed to other antimicrobials investigated in this animal model, NVC-101 controls the tissue bacterial bioburden without inhibiting the wound healing process.
UNLABELLED:Methicillin-resistant Staphylococcus aureus (MRSA) has become a leading cause of colonization and infection in both acute and chronic soft-tissue wounds.OBJECTIVE:Our objective is to define this current epidemic problem caused by both community-acquired MRSA (CA-MRSA) and hospital-acquired MRSA (HA-MRSA), focusing on the similarities and differences between these 2 isolates as well as the impact on wound management decisions.METHODS:Methods used include a literature review on the growth of the current MRSA problem and its International scope. In addition, a current up-to-date assessment had been made of the problem and the current approach to management of MRSA in acute soft-tissue and chronic wounds. Burns are not discussed because this injury usually does not fit either categories and is managed quite uniquely.RESULTS:Results included the following: (1) There are very distinct properties of CA-MRSA and HA-MRSA, which must be considered for acute and chronic wound care. Management of both requires rigorous barrier precaution techniques to avoid cross-contamination. The presence of MRSA as a carrier state increases the risk of both a systemic and local wound infection in the carrier. There are large and increasing reservoirs of CA-MRSA and HA-MRSA worldwide leading to more bacteremias and wound problems. Topical antimicrobial therapy has not been addressed in managing MRSA in acute and chronic wounds.CONCLUSION:Conclusions include the fact that both HA-MRSA and CA-MRSA wound infections are rapidly increasing, especially with CA-MRSA. This high incidence requires appropriate wound prediction and management decisions as well as attempts to avoid further cross-contamination and reservoir growth. Topical antimicrobial therapy would seem to be an important component in controlling this tremendous problem. Yet this topic has yet to be adequately addressed.
Surgery in patients with hepatic cirrhosis and ascites is associated with significant morbidity, including poor wound healing. Postoperative management of abdominal and perineal wounds in these patients poses a unique challenge owing to increased intra-abdominal pressure, risk for peritonitis, and ascitic fluid leakage. Vacuum-assisted closure (VAC) therapy reportedly improves angiogenesis and epithelialization, controls bacterial contamination, and removes excess tissue fluid. We present 4 cases of successful management of intractable postoperative ascitic fluid leaks utilizing VAC-based techniques. In one case, closure of a profusely draining perineal wound following an abdominoperineal resection was accomplished within 5 days of specialized VAC dressing application. In the other 3 cases, refractory drainage from midline laparotomy incision was successfully managed with the use of VAC therapy. In all 4 cases, the VAC-based system was effective in controlling drainage of ascites and subsequently sealing the wounds. Postoperative use of VAC in conjunction with optimization of medical therapy and judicious tapping of ascites provides a safe and effective method to control ascitic fluid leaks and promote definitive tissue sealing in patients with hepatic cirrhosis.
Objective: We plan to review the current problem of lean mass erosion in catabolic states, caused by injury and critical illness. This protein loss is driven by the hormonal imbalance and excess inflammation referred to as the “stress response to injury.” We then plan to provide the current concepts on the use of available anabolic agents to attenuate the excess catabolism. Data Source: The available published literature on the pathogenesis of acute catabolic states and the use of anabolic and anticatabolic agents, their indications, mechanism of action, and potential complications was reviewed. Data Extraction: The current understanding and experience of the available anabolic and anticatabolic agents as well as the rationale for the use of each anabolic agent are described. Conclusion: We conclude that the preservation of lean body mass (body protein) is extremely important in the management of critical care populations, as lean mass loss leads to severe morbidity and increased mortality. Essentially, all of the available anabolic agents stimulate protein synthesis and decrease protein breakdown, but all have different mechanisms of action. Adequate nutrition, especially protein intake, is essential for any anabolism to occur. Combined anabolic therapy also appears to be advantageous. Although controlling the inflammatory response would also be of major benefit in further controlling protein loss, effective and safe anti-inflammatory agents have not yet become clinically available for this purpose.
OBJECTIVE:Sulfur mustard (bis-2-(chloroethyl) sulfide) is a chemical warfare agent (military code: HD) causing extensive skin injury. The mechanisms underlying HD-induced skin damage are not fully elucidated. This review will critically evaluate the evidence showing that oxidative stress is an important factor in HD skin toxicity. Oxidative stress results when the production of reactive oxygen (ROS) and/or reactive nitrogen oxide species (RNOS) exceeds the capacity of antioxidant defense mechanisms. METHODS:This review will discuss the role of oxidative stress in the pathophysiology of HD skin toxicity in both in vivo and in vitro model systems with emphasis on the limitations of the various model systems. Evidence supporting the therapeutic potential of antioxidants and antioxidant liposomes will be evaluated. Antioxidant liposomes are effective vehicles for delivering both lipophilic (incorporated into the lipid bilayers) and water-soluble (encapsulated in the aqueous inner-spaces) antioxidants to skin. The molecular mechanisms interconnecting oxidative stress to HD skin toxicity are also detailed. RESULTS:DNA repair and inflammation, in association with oxidative stress, induce intracellular events leading to apoptosis or to a programmable form of necrosis. The free radical, nitric oxide (NO), is of considerable interest with respect to the mechanisms of HD toxicity. NO signaling pathways are important in modulating inflammation, cell death, and wound healing in skin cells. CONCLUSIONS:Potential future directions are summarized with emphasis on a systems biology approach to studying sulfur mustard toxicity to skin as well as the newly emerging area of redox proteomics.
OBJECTIVE:Sulfur mustard is a well-known blistering chemical warfare agent that has been investigated for its toxicological mechanisms and an efficacious antidote. Since sulfur mustard injury involves dermal:epidermal separation, proteolytic enzymes were suspected to be involved for this separation and eventual blister development. Therefore, protease inhibitors could be of therapeutic utility against sulfur mustard injury. In this study, the effects of Kunitz-domain 1 of human tissue factor pathway inhibitor-2 were evaluated against the toxic effects of 2-chloroethyl ethyl sulfide, a surrogate agent of sulfur mustard. Tissue factor pathway inhibitor-2 is a 32-kDa serine protease inhibitor produced by a variety of cell types including human epidermal keratinocytes, fibroblasts, and endothelial cells. It consists of 3 Kunitz-domains and the first Kunitz-domain contains the putative P(1) residue (arginine at position 24) responsible for protease inhibitory activity.METHODS:Recombinant wild-type and R24Q mutant Kunitz-domain 1s were expressed in Escherichia coli and purified. The purified proteins were refolded, and their effects were tested in an in vitro human epidermal keratinocyte cell wounding assay.RESULTS:Wild-type but not R24Q Kunitz-domain 1 inhibited the amidolytic activity of trypsin and plasmin. Wild-type Kunitz-domain1 was stable for 4 weeks at 42 degrees C and for more than 8 weeks at room temperature. Wild-type Kunitz-domain 1 significantly improved wound healing of unexposed and 2-chloroethyl ethyl sulfide-exposed cells without influencing cell proliferation. Although R24Q Kunitz-domain 1 lacked trypsin and plasmin inhibitory activity, it promoted wound closure of untreated and 2-chloroethyl ethyl sulfide-treated cells but to a much lesser degree.CONCLUSION:These data suggest that wild-type Kunitz-domain 1 of human tissue factor pathway inhibitor-2 can be developed as a medical countermeasure against sulfur mustard cutaneous injury.
OBJECTIVE:Human beta-defensin (HBD) and the complement system are two important innate immune mechanisms active against a broad range of burn and wound pathogens. However, excessive or uncontrolled complement activation, following thermal injury, contributes to tissue damage. Previous studies from our laboratory suggested a decreased expression of HBD-2 in burn wounds and its absence in burn blister fluid. Prior studies have demonstrated that human neutrophil peptide can bind to the C1q component of the complement system and prevent complement activation. The objective of this study was to determine whether HBD-1 and HBD-2 can also bind to the C1q component and modulate complement activity.METHODS:The binding efficiency of HBD-1 and HBD-2 to the C1q component was determined by utilizing dot blot hybridization. The effect of HBD-2 on the activation of the complement system by the classical and alternative pathways was determined by CH50 and AP50 assays. In addition, the ability of HBD-1 and HBD-2 to inhibit C1q activity was predicted by a comparison with known C1q inhibitor peptide 2J in a DNAStar computer modeling study.RESULTS:C1q binding to HBD-2 was strong, whereas C1q binding to HBD-1 was weak. HBD-2 inhibits the classical pathway significantly without affecting the alternative pathway. In addition, a computer modeling study also revealed structural homology of HBD-2 with known C1q inhibitory sequences of HBD-2.CONCLUSION:HBD-2 inhibits the classical pathway. The replacement of missing defensin, a natural inhibitor of the complement system, may have a dual protective role not only as an antimicrobial agent but also in providing protection against uncontrolled activation of the complement system.
OBJECTIVE:Hypochlorous acid (HOCl), a major inorganic bactericidal compound of innate immunity, is effective against a broad range of microorganisms. Owing to its chemical nature, HOCl has never been used as a pharmaceutical drug for treating infection. In this article, we describe the chemical production, stabilization, and biological activity of a pharmaceutically useful formulation of HOCl.METHODS:Stabilized HOCl is in the form of a physiologically balanced solution in 0.9% saline at a pH range of 3.5 to 4.0. Chlorine species distribution in solution is a function of pH. In aqueous solution, HOCl is the predominant species at the pH range of 3 to 6. At pH values less than 3.5, the solution exists as a mixture of chlorine in aqueous phase, chlorine gas, trichloride (Cl(3) (-)), and HOCl. At pH greater than 5.5, sodium hypochlorite (NaOCl) starts to form and becomes the predominant species in the alkaline pH. To maintain HOCl solution in a stable form, maximize its antimicrobial activities, and minimize undesirable side products, the pH must be maintained at 3.5 to 5.RESULTS:Using this stabilized form of HOCl, the potent antimicrobial activities of HOCl are demonstrated against a wide range of microorganisms. The in vitro cytotoxicity profile in L929 cells and the in vivo safety profile of HOCl in various animal models are described.CONCLUSION:On the basis of the antimicrobial activity and the lack of animal toxicity, it is predicted that stabilized HOCl has potential pharmaceutical applications in the control of soft tissue infection.
Objective: Acute wound failure is a common complication following surgical procedures and trauma. Laparotomy wound failure leads to abdominal dehiscence and incisional hernia formation. Delayed recovery of wound-breaking strength is one mechanism for laparotomy wound failure. Early fascial wounds are relatively acellular, and there is a delay in the appearance of acute wound growth factors and cytokines. The objective of this study was to accelerate and improve laparotomy wound healing using amnion-derived multipotent cells (AMPs). AMPs' nonimmunogenic phenotype and relative abundance support its role as a cell therapy. Methods: AMPs were injected into the load-bearing layer of rat abdominal walls prior to laparotomy, and cell viability was confirmed. Wound mechanical properties were measured over 28 days. The incidence and severity of laparotomy wound failure was measured in an incisional hernia model. Results: AMP cells were viable in laparotomy wounds for at least 28 days and did not migrate to other tissues. Laparotomy wound-breaking strength was increased by postoperative day 7 following AMP therapy. AMP therapy reduced the incidence of hernia formation and the size of hernia defects. Histology suggested stimulated wound fibroplasia and angiogenesis. Conclusions: AMP cell therapy reduces the incidence of laparotomy wound failure by accelerating the recovery of wound-breaking strength. This results in fewer incisional hernias and smaller hernia defects.
In Thailand and in many parts of the world, the annoyances and potential health hazards of mosquitoes1 have led to the development of many devices designed to kill them.2 The electric fly-swatter (Yongtong,Yongtong Electronics Co, Ltd, China) is thought by many to be a safe antimosquito device that is used widely for killing mosquitoes in tropical countries (Figure (Figure1).1). It is free of toxic chemicals or other poisonous materials, and it combines the common household fly-swatter with an electrical screen designed to incinerate the insect.3 Unfortunately, the tennis racket shape, the sparkling sound of electrical shock, and a flash of light with incineration of the fly can be enticing to children. Figure 1 The electrical fly-swatter. A 2-year-old boy was admitted to the Siriraj Burn Unit, Siriraj Hospital, Bangkok, Thailand, following a 25% body surface area burn. The boy entered a workroom in the home where his father was painting flammable adhesive shoe glue on the floor (Elephant Adhesive Glue, TN Chemical Supply, Bangkok, Thailand). He sat down near his father and soon began waving the electric fly-swatter device toward a mosquito. After the insect made contact with the metallic mesh screen, an electrical arc was generated and the insect was incinerated. The boy then placed the hot device onto the floor, which ignited the glue and, in turn, the boy's clothing. The boy's physical examination on his arrival revealed superficial partial-thickness burns to his face, neck, left upper extremity, posterior trunk, and bilateral lower extremities (Figure (Figure2).2). The burn wound was immediately cleansed and debrided and dressed with 1% silver zinc sulfadiazine cream daily until the wounds had healed. The patient was discharged from the hospital after 24 days. No infection or other complications were observed during the hospital stay. Figure 2 The appearance of the patient revealed second degree 25% total body surface area burn. Although the electric fly-swatter is a useful personal insect eliminator, care must be taken to prevent application of the metallic mesh to flammable surfaces and to allow sufficient time for cooling of the mesh following its use.3 Adhesive shoe glue is a known flammable substance with the disastrous ability to ignite spontaneously upon contact with heat. It should never be used in close proximity to electrical equipment, sources of static electricity, or machinery with moving parts, and it should be stored in closed airtight safety containers after use. We also recommend a heightened awareness of the risks associated with the use of the electric mosquito swatter, which should be kept out of children' reach. Guidelines for safe handling of the device are in place.
OBJECTIVE:To assess mortality risk and extent of increased length of hospital stay in patients with burn injury with preexisting liver disease.METHODS:Records of 31,338 adults who were admitted with burns to 70 burn centers were reviewed from the American Burn Association National Burn Repository. Demographics, percentage burn, and medical characteristics of 180 patients with liver disease were compared with all patients without liver disease and to a propensity score-matched sample of 180 patients without liver disease. Risk of mortality as well as lengths of both intensive care and total stay were compared after matching for demographics, burn injury, and preexisting medical conditions.RESULTS:Patients with liver disease were significantly more likely to have a history of a number of medical comorbidities, including alcohol abuse, drug abuse, a psychiatric diagnosis, chronic pulmonary disease, hypertension, and diabetes. Patients with liver disease were significantly more likely to die in the hospital (27.2% vs 6.9%, odds ratio = 5.0, 95% confidence interval = 3.6-7.0, P < .01), and this held even when compared with a propensity score-matched group of patients without liver disease, but with similar demographics, burn injury, and medical profiles. Lengths of both intensive care and total hospital stay were 122.5% (P < .01) and 86.7% (P < .01) longer, respectively, among patients with liver disease than among all other patients. In a matched sample, lengths of both intensive care and total stays were longer, albeit not significantly so (41.6%, P = .12; 35.5%, P = .07).CONCLUSIONS:Liver impairment worsens the prognosis in patients with thermal injury.
OBJECTIVE:Cement burns account for relatively few admissions to a burn unit; however, these burns deserve separate consideration because of special features of diagnosis and management. Cement burns, even though potentially disabling, have rarely been reported in literature.METHODS:A retrospective review was performed of all patients admitted with cement burns injuries to the national burns unit at the St James's Hospital in Dublin, Ireland, over a 10-year period for the years 1996-2005.RESULTS:A total of 46 patients with cement burns were admitted. The majority of patients were aged 16-74 years (mean age = 32 years). Eighty-seven percent of injuries occurred in an industrial and 13% in a domestic setting. The upper and lower extremities were involved in all the patients, and the mean total body surface area affected was 6.5%. The mean length of hospital stay was 21 days with a range of 1-40 days. Thirty-eight (82%) were surgically managed involving debridement and split-thickness skin graft (SSG) and four (9%) were conservatively managed. A further four did not have data available.CONCLUSION:Widespread inexperience in dealing with this group of cement burns patients and delays in referral to burns unit highlights the potential for greater levels of general awareness and knowledge in both prevention and treatment of these burns. As well, early debridement and split-thickness skin grafting at diagnosis constitutes the best means of reducing the high socioeconomic costs and allows for early return to work.
BACKGROUND:In experimental models in vivo, it is difficult to characterize the effect of thermal burns on epidermal keratinocytes. Since the response to thermal injury involves several systemic mechanisms, especially because of the stimulus to coagulation and inflammatory cascades, it becomes hard to evaluate the specific effect of thermal burns on keratinocytes. The aim of this study is to propose the use of human keratinocytes cultured on collagen matrix as an in vitro experimental burn model. METHODS:Human keratinocytes derived from neonatal foreskins were isolated and cultured following standard methods. All experiments used the same keratinocyte lineage and were carried out in triplicate. Initially, gels of collagen and Matrigel were prepared. For each gel, 2 x 10(6) keratinocytes were seeded and cultured to form stratified epithelia. Following, burn wounds were induced at 170 degrees C. RESULTS:Keratinocytes were cultured on collagen-coated Millicell membranes. Stratified epithelia were formed and burned on the seventh day after the cultures were raised to the air-liquid interface. The burn procedure is reproducible and can be easily executed. CONCLUSION:The proposed model can be used to study the effects of induced burn wounds on keratinocytes in a specific way.
OBJECTIVE:Human defensins and cathelicidins are a family of cationic antimicrobial peptides (AMPs), which play multiple roles in both innate and adaptive immune systems. They have direct antimicrobial activity against several microorganisms including burn pathogens. The majority of components of innate and adaptive immunity either express naturally occurring defensins or are otherwise chemoattracted or functionally affected by them. They also enhance adaptive immunity and wound healing and alter antibody production. All mechanisms to explain multiple functions of AMPs are not clearly understood. Prior studies to localize defensins in normal and burned skin using deconvolution fluorescence scanning microscopy indicate localization of defensins in the nucleus, perinuclear regions, and cytoplasm. The objective of this study is to further confirm the identification of HBD-1 in the nucleus by deconvolution microscopic studies involving image reconstruction and wire frame modeling.RESULTS:Our study demonstrated the presence of intranuclear HBD-1 in keratinocytes throughout the stratum spinosum by costaining with the nuclear probe DAPI. In addition, HBD-1 sequence does show some homology with known cationic nuclear localization signal sequences.CONCLUSION:To our knowledge, this is the first report to localize HBD-1 in the nuclear region, suggesting a role for this peptide in gene expression and providing new data that may help determine mechanisms of defensin functions.
BACKGROUNDThe reconstruction of major burn and other deformities resulting from significant soft tissue deficits of the face and neck is a continuing challenge for surgeons who wish to reliably restore facial function and aesthetic appearance. A primary problem is deficiency of well-matched donor skin. Other problems include the unique characteristics of facial skin, the fine anatomic nuances, and the unique functional demands placed on the face. This article describes an expanded shoulder transposition flap that can provide a large amount of both flap and full-thickness skin graft for total and subtotal reconstruction of the face.METHODSAn expanded shoulder transposition flap has been used since 1986 for head and neck resurfacing 58 times in 41 patients ranging in age from 2 to 62 years. The details of the technique and the results of the flap including complications are described.RESULTSThe flap proved remarkably reliable and reproducible in resurfacing the peripheral facial aesthetic units. The pedicle skin is often used for grafting of the central face with its finer features. The donor site of the flap is closed primarily.CONCLUSIONSTwenty years' experience with expanded transposition flaps has shown it to be reliable and versatile in the reconstruction of major soft tissue deficits of the face and neck. It is a technique that provides economy of tissue, versatility, and is well within the skill, patience, and courage of most reconstructive surgeons.
Surgery in patients with hepatic cirrhosis and ascites is associated with significant morbidity, including poor wound healing. Postoperative management of abdominal and perineal wounds in these patients poses a unique challenge owing to increased intra-abdominal pressure, risk for peritonitis, and ascitic fluid leakage. Vacuum-assisted closure (VAC) therapy reportedly improves angiogenesis and epithelialization, controls bacterial contamination, and removes excess tissue fluid. We present 4 cases of successful management of intractable postoperative ascitic fluid leaks utilizing VAC-based techniques. In one case, closure of a profusely draining perineal wound following an abdominoperineal resection was accomplished within 5 days of specialized VAC dressing application. In the other 3 cases, refractory drainage from midline laparotomy incision was successfully managed with the use of VAC therapy. In all 4 cases, the VAC-based system was effective in controlling drainage of ascites and subsequently sealing the wounds. Postoperative use of VAC in conjunction with optimization of medical therapy and judicious tapping of ascites provides a safe and effective method to control ascitic fluid leaks and promote definitive tissue sealing in patients with hepatic cirrhosis.
Background: A topical antimicrobial that can decrease the bacterial bioburden of chronic wounds without impairing the wound's ability to heal is a therapeutic imperative. A stabilized form of hypochlorous acid (NVC-101) has been demonstrated in vitro and in standard toxicity testing to possess properties that could fulfill these criteria. Materials and Methods: Using a standard rodent model of a chronically infected granulating wound, various preparations of NVC-101 and multiple treatment regimens were investigated to evaluate the role of NVC-101 in decreasing tissue bacterial bioburden and overcoming the inhibition of infection on wound healing. Quantitative bacteriology of tissue biopsies and wound healing trajectories were used to compare the various NVC-101 preparations and regimens to saline-treated negative controls and silver sulfadiazine-treated positive controls. Results: NVC-101 at 0.01% hypochlorous acid with a pH of 3.5 to 4.0 proved to be an effective topical antimicrobial. It was most effective when used for a brief period (15-30 minutes), and followed with another application. Possibly this was due to its rapid neutralization in the wound bed environment. Although not as effective at decreasing the tissue bacterial bioburden as silver sulfadiazine, NVC-101 was associated with improved wound closure. Conclusions: This stabilized form of hypochlorous acid (NVC-101) could have potential application as an antimicrobial wound irrigation and treatment solution if its effective pH range can be maintained in the clinical situation. NVC-101 solution was equally effective at pH 3.5 or 4.0 and more efficient soon after its application. As opposed to other antimicrobials investigated in this animal model, NVC-101 controls the tissue bacterial bioburden without inhibiting the wound healing process.
OBJECTIVE:Oxandrolone, administered to severely burned children over the first year postburn, produces increased lean body mass by 6 months; however, an increase in total body bone mineral requires 12 months. Consequently, this bone mineral response may be due to increased muscle mass. Alternatively, oxandrolone may act directly on bone. The current study seeks to determine whether oxandrolone can transactivate the androgen receptor in osteoblasts.METHODS:Collagen, alkaline phosphatase, osteocalcin, osteoprotegerin, and androgen receptor abundance were determined by qRT-PCR, confocal laser scanning microscopy, or immunoquantitative assay. To determine the effect of oxandrolone on gene expression in differentiated cells, osteocytic cultures were grown to confluence in differentiation medium and then treated 24 hours or 5 days with 15 microg/mL oxandrolone.RESULTS:Increased nuclear fluorescence of the androgen receptor and increased cellular type I collagen were observed with oxandrolone at 15 and 30 microg/mL but not at lower doses. Alkaline phosphatase (7%-20%) and osteocalcin (13%-18%) increases were modest but significant. Short-term treatment produced no significant effects, but at 5 days androgen receptor levels were increased while collagen levels were significantly decreased, with little effect on alkaline phosphatase, osteocalcin, or osteoprotegerin.CONCLUSIONS:These data suggest oxandrolone can stimulate production of osteoblast differentiation markers in proliferating osteoblastic cells, most likely through the androgen receptor; however, with longer treatment in mature cells, oxandrolone decreases collagen expression. Thus it is possible that oxandrolone given to burned children acts directly on immature osteoblasts to stimulate collagen production, but also may have positive effects to increase bone mineral through other mechanisms.
