Proteolytic enzymes as adjuncts to antibiotic prophylaxis of surgical wounds

The success of antibiotic treatment of contaminated open wounds is related to the time at which the antibiotic is administered. In standardized guinea pig wounds contaminated with 10⁶S aureus, immediate treatment with topical benzyl penicillin prevents the development of infection. When this same treatment is delayed three hours, all wounds become infected. It is our belief that the fibrinous exudate present in open wounds prevents the antibiotic from gaining access to the sites of bacterial contamination and limits the therapeutic benefits of delayed antibiotic therapy.Enzymatic hydrolysis of the wound coagulum with the proteolytic enzyme trypsin significantly enhances the therapeutic value of antibiotics in the delayed treatment of contaminated wounds. On the basis of these experimental studies, a regimen has been established for the use of proteolytic enzymes as an adjunct to delayed antibiotic treatment of contaminated wounds. When treatment is delayed three hours, the optimal dose of trypsin is 25,000 NF units per wound. The effectiveness of trypsin is enhanced by prolonging its application time; contact of the enzyme with the wound for thirty minutes prevents the development of infection and limits bacterial growth. The effectiveness of the enzyme is increased by repeating the applications. The route by which the antibiotic is administered does not affect the value of proteolytic enzymes; proteolytic enzymes enhance the therapeutic value of both topical and systemic antibiotics.     

Survival after a second episode of toxic epidermal necrolysis

Toxic epidermal necrolysis resulting from severe hypersensitivity to medication has a reported mortality of up to 66%. A patient surviving two episodes with more than a 50% skin loss is unprecedented in the medical literature. Mortality has been associated with many factors, including delayed reepithelialization, persistent skin slough, coagulopathy, severe hypoproteinemia, and sepsis. It may be possible to decrease morbidity and mortality by preventing the shearing of epidermis, thereby limiting the denuded areas. This case report describes the successful management of our patient's second episode of toxic epidermal necrolysis. The treatment of this patient in our specialized burn center consisted of careful fluid and electrolyte management, nutritional support, standard topical antimicrobials, and new modalities of local wound management.     

Oxidized regenerated cellulose in cardiac computer tomography imaging

Oxidized regenerated cellulose is widely used as a bioabsorbable topical hemostatic agent. Postoperative visualization of this material through routine chest imaging, such as conventional radiography, computer tomography (CT), magnetic resonance imaging as well as sonography, may prove difficult and, to our knowledge, is not described in the literature. We describe a case where the mediastinal packing with Surgicel? Nu-Knit? after a mitral valve repair procedure led to a delayed obstruction of the superior vena cava, necessitating a re-thoracotomy and curettage of the hemostatic material. The hemostatic agent was not prospectively interpreted as the cause of a severe upper inflow restriction, despite repeated imaging. Retrospectively, the hemostatic material as a cause of the upper inflow obstruction could have been identified earlier if its presence would have been known to the radiologist. We strongly recommend that the surgeon inform the radiologist that such materials were used to improve the diagnostic yield of CT interpretation.     

Argon laser therapy of occult recurrent hyphema from anterior segment wound neovascularization

Recurrent hyphema is a complication of anterior segment surgery that may present with a variety of signs and symptoms. The appropriate diagnosis of this syndrome may be overlooked because its presentation is frequently delayed, and its symptoms and signs are varied and frequently evanescent. Major forms of surgical intervention have been recommended for this syndrome, but we believe that many such cases can be treated relatively simply and effectively with argon laser goniophotocoagulation using topical anesthesia. We present five cases of recurrent hyphema from neovascularization of a surgical incision.     

Proteolytic enzymes as adjuncts to antimicrobial prophylaxis of contaminated wounds.

When a tissue is injured, its vessels exhibit a marked increase in vascular permeability. Blood proteins, including fibrinogen, traverse the vessel walls and lead to the development of a surface coagulum. This inflammatory response continues until primary closure of the wound edges is accomplished. The thickness of the surface coagulum is roughly proportional to the time interval between wounding and closure. This coagulum encompasses the surface contaminants, preventing contact with either topical or systemic antibiotics. The presence of this surface coagulum limits the time in which antibiotic prophylaxis is effective. At three hours after injury, antimicrobial prophylaxis of contaminated wounds has no therapeutic value. Hydrolysis of the protein coagulum by proteolytic enzymes enhances the activity of the antibiotic in experimental wounds. The success of proteolytic enzymes as adjuncts to delayed antibiotic treatment can be correlated with the clot lysis activity of the enzymes in vitro. Travase, the most potent fibrinolytic enzyme, is the most effective adjunct to delayed antibiotic therapy of contaminated wounds. In contrast, the active enzymes found in Elase, which exhibit no significant clot lysis activity in vitro, do not potentiate the activity of antibiotics in wounds subjected to a delay in treatment. Travase prolongs the period of effective topical antibiotic action for at least eight hours in experimental contaminated wounds. The therapeutic merit of Travase is also apparent when the antibiotic is administered systemically. Travase shows promise as an adjunct to a variety of antibiotics that are effective against both gram-positive and gram-negative organisms. The results of these experimental studies support our belief that clinical studies support our belief that clinical studies should now be initiated to test the therapeutic value of Travase as an adjunct to antibiotics in heavily contaminated wounds subjected to an unavoidable delay in treatment.     

Lip Silicone Granulomatous Foreign Body Reaction Treated With Aldara (Imiquimod 5%)

We report a case of a lip granulomatous reaction after injection of silicone being treated successfully with topical Aldara (Imiquimod 5%). Silicone granulomas and the inflammatory foreign body reaction that can occur are some of the complications that arise from using silicone for cosmetic enhancement. The inflammatory reaction of this patient first appeared shortly after silicone injection of both the upper and lower lips. Histopathologic examination revealed a foreign body inflammatory reaction that is consistent with silicone granuloma. Although this reaction has been described extensively in the dermatologic literature as one of the disfiguring side effects of silicone injection, its treatment has plagued cosmetic dermatologists. We report the use of an immunomodulatory cream Aldara (Imiquimod 5%) to treat this type of reaction.     

Late-Onset Granulomatous Reaction to Artecoll

BACKGROUND: Artecoll is permanent filler that is used for the correction of facial wrinkles. It has been used mainly in Europe in the last 9 years. It is a suspension of 25% polymethylmethacrylate microspheres of 30 to 40 microns in diameter and 75% athecollagen. OBJECTIVE: To report a side effect of a late-onset granulomatous reaction to Artecoll. METHODS: We report the case of a 54-year-old woman who presented with longitudinal hard nodules with slight overlying erythema in the glabella and nasolabial folds 14 months after she was treated with Artecoll injections to her glabellar and nasolabial wrinkles. An excisional biopsy of a glabellar nodule was performed. RESULTS: Microscopic examination of hematoxylin and eosin-stained specimen revealed histiocytic granulomas with giant cells and vacuoles, a picture of Artecoll granulomas. Treatment with topical steroids showed no improvement. Intralesional injections of Kenalog caused temporary disappearance of the granulomas. A few months later the nodules reappeared. No further treatment was done. CONCLUSION: Artecoll injection to wrinkles of the face can cause delayed granulomatous reaction. This side effect is not reversible and should be addressed in the informed consent.     

Postoperative acute disseminated encephalomyelitis after exposure to microfibrillar collagen hemostat

Microfibrillar collagen hemostat, known by its trade name Avitene, has been used in neurosurgery for decades. Complications with this product have been documented in other surgical specialties and described as mostly immune-mediated foreign-body reactions that can lead to a granulomatous reaction. There has never been a case of disseminated encephalomyelitis associated with this topical hemostatic agent. In this report the authors present a case of postoperative acute disseminated encephalomyelitis after exposure to Avitene. Possible pathophysiological mechanisms are discussed and the pertinent literature is reviewed.     

Antiseptic therapy with a polylacticacid–acetic acid matrix in burns

Bacterial colonization and infection are still the major causes of delayed healing and graft rejection following burns and they are furthermore the basis for second and third hit sepsis. Topical treatment is necessary to reduce the incidence of burn wound infection. Silver sulphadiazine (SD‐Ag) is a frequently used microbicidal agent. However, this treatment causes adverse reactions and side‐effects. Additionally, in recent years multiresistant bacteria, which have not been treated sufficiently, are on the rise. On the basis of experimental data and clinical application of a polylacticacid–acetic acid matrix, we performed this study to establish the effectiveness of the antiseptic therapy with the topical application of a polylacticacid–acetic acid matrix to provide an alternative method for burn treatment, using SD‐Ag as a reference. Twenty patients with IIb° or III° burns from the Plastic Surgery and Burns Unit were treated within a matched pair comparative setting. One burned area was treated with SD‐Ag, the other corresponding area with the polylacticacid–acetic acid matrix. All patients underwent a necrectomy 4–5 days after the trauma. The excised burned skin was sent to our microbiological laboratory to determine the different bacteria per gram in this tissue. Despite the number of 20 patients, statistical significance was not achieved, there were tendencies to a better antiseptic effectiveness of the polylacticacid–acetic acid matrix. These results suggest that the polylacticacid–acetic acid matrix should be studied in greater depth and could be used as a valid alternative for the topical treatment of burns, as it is equivalent or even more effective than SD‐Ag.     

Effect of Topical Mitomycin C on the Healing of Surgical and Laser Wounds: A Hint on Clinical Application

OBJECTIVES: Mitomycin C (MMC) is used in otolaryngological surgery to reduce complications from postoperative scarring. However, the effects of MMC on wound healing at different doses and on different wound types have not been fully described. The aim of this study was to evaluate the effects of topical MMC at 2 different doses on the healing of surgical and laser wounds. STUDY DESIGN AND SETTING: This was a randomized study using 20 rabbits. Six full-thickness wounds were made by excision or laser vaporization on the flank skin. The wounds were randomly treated by topical MMC of 0.4 or 1.0 mg/mL or saline for 5 minutes. RESULTS: Re-epithelialization and contraction of the original wounds were significantly delayed by the use of MMC (P < 0.01). The delayed healing effect of MMC was more prominent in the laser wounds than in the excision wounds. MMC inhibited collagen deposition and fibroblast proliferation of wounds on histological analysis. The 2 different concentrations of MMC showed no difference in gross or histological wound healing characteristics. CONCLUSION: Our results showed that MMC delays the healing of wounds as a result of the inhibition of fibrosis, especially for laser wounds.     

Incidence of methemoglobinemia in patients receiving cerium nitrate and silver sulfadiazine for the treatment of burn wounds: A burn center's experience

In 1976, the combination of cerium nitrate and silver sulfadiazine was introduced as a topical therapy for burn wounds. Experience with a locally prepared combination agent has shown physical change of the eschar and delayed subeschar bacterial colonization. A potential systemic complication of this treatment is the development of methemoglobinemia (Met‐Hba) due to the oxidizing nature of Ce(NO₃)₃. Met‐Hba has a spectrum of clinical consequences, ranging from headache and cyanosis to cardiac ischemia, hypotension, and even death. Given the frequent use of this combination agent at our burn center, a retrospective review was conducted to evaluate the incidence of Met‐Hba. A query of pharmacy records revealed 170 patients from January 2005 to October 2009 that had received this treatment. Eighteen patients (～10%) developed Met‐Hba as noted on arterial blood gas (methemoglobin>3%) and only three patients (～2%) had methemoglobin levels >10%. In the majority of cases, there were no clinical symptoms of Met‐Hba. Most patients' relative hypoxia resolved with cessation of treatment; however, five patients required treatment with methylene blue. The presence of Met‐Hba associated with this topical therapy can be diagnosed early by vigilant monitoring, thereby reducing morbidity and mortality. In our experience, cerium combined with silver sulfadiazine is a valuable and safe treatment for deep partial and full‐thickness burn wounds.     

The prevention of wound infections with the use of local antibiotics.

The local use of kanamycin, a broad spectrum antibiotic, has been successful in preventing primary wound infections. There have been no instances of drug reaction or sensitivity when kanamycin is used as a dilute topical irrigating solution. Secondary wound infections, which occurred in two cases, responded to local and systemic antibiotic therapy. Kanamycin can be recommended as an effective and safe topical antibiotic to prevent wound infections in foot surgery.     

The thermally injured ear: a systematic approach to reconstruction.

The ears are special and unique structures that ordinarily are ignored during our daily routines. A thermal injury of relatively moderate proportions can irreparably alter their shape and appearance. Many reconstructive techniques have been garnered to restore these delicate structures. Herculean efforts will consistently fall short of these goals if tissue preservation is not in the forefront of our treatment protocol. Iontophoresis coupled with topical antimicrobial agents have been shown to ameliorate cartilage loss, allowing for delayed operative intervention, when more consistent results may be obtained. Early radical resection of ear soft tissue or structural cartilage should be an endeavor of last resort in all but a few instances, such as unresponsive suppurative chondritis. Segmental restoration of the injured ear allows for dismantling of the various parts to recreate the whole. A facsimile of the original is possible if the major visible distinguishing landmarks are salvaged. Flap resurfacing of exposed cartilage yields closer tissue match, color, and texture, and it affords a greater proclivity for survival than does graft closure. Sacrifice of the helical lip relegates the ear to that of a flat, less-than-optimal appearance. Tissue expansion coupled with cutaneous flap closure will usually preclude this situation. Skin grafting is a valuable tool in our armamentarium but should be used judiciously in situations where graft coverage is either necessary or desired to produce enhanced results. In such instances, the thickness of the graft must be considered, ranging from an almost translucent quality for the antihelix to that of a much thicker graft for the helix. Application and direction of the graft will be determined by the underlying surface contours. Until the reconstruction has been completed, burn patients and their families usually do not view the injured ear that has been snatched from the fires of adversity. The unveiling frequently effects a felicitous atmosphere, because they perceive a relatively normal-looking ear. The final result is all that matters.     

Clinical application of sapphire pins as an internal fixation device for the upper extremity

Since June 1980, sapphire pins (monocrystalline alumina ceramic pins) have been used in 22 patients as an internal fixation device for hand and elbow problems. In our follow-up studies, good bone healing was observed in all cases except for one delayed union in a fracture of the diaphysis of the proximal phalanx. Radiographs showed no pin migration or osteolytic reaction around the pins. We therefore conclude that our device and its insertion technique can be successfully applied to intraarticular fractures and fractures in the vicinity of the joint.     

Topical administration of pterostilbene accelerates burn wound healing in diabetes through activation of the HIF1α signaling pathway

Impaired wound healing is one of a variety of severe diabetic complications and involves many factors, including consistent oxidative stress, prolonged inflammation, impaired angiogenesis, and delayed re-epithelialization. Despite the severe negative impacts that impaired wound healing has on patients’ lives, detailed mechanisms and effective therapies are still not fully developed. In this study, we aim to investigate the potential effects and mechanisms of topical administration of pterostilbene and resveratrol on burn wound healing in diabetes. Our in vitro experiments in human umbilical vein endothelial cells showed that long term exposure of hyperglycemia induces oxidative stress and suppression of hypoxia inducible factor1α (HIF1α) signaling pathway, and pterostilbene treatment completely, while resveratrol treatment partly, reversed this effect. Further in vivo experiments in diabetic rats showed that topical administration of pterostilbene exhibited stronger efficacy than resveratrol in normalizing oxidative stress, HIF1α activity, and accelerating burn wound healing in diabetes. We conclude that topical administration of pterostilbene accelerates burn wound healing in diabetes through activation of the HIF1α signaling pathway; thus, pterostilbene may be a potential candidate for clinical treatment of burn wound healing in diabetes.     

Metastatic Crohn’s disease of the penis: two cases

Metastatic Crohn’s disease is a rare inflammatory process that is non-contiguous from the bowel. It can affect the penis and is variable in presentation and onset in relation to bowel symptoms. It has been treated with oral, topical, systemic, and surgical therapies. We describe our experience with two cases of penile metastatic Crohn’s disease and their management in comparison with other cases described in the literature. Both our patients were of the lymphoedematous type and had sexual and voiding dysfunction. They were treated with topical and intra-lesional steroids and circumcision after unsuccessful systemic treatments.     

Complete urinary obstruction following periurethral polytetrafluoroethylene injection for urinary incontinence

We report a unique case of foreign body granulomatous reaction after periurethral polytetrafluoroethylene injection causing complete urinary obstruction. Urinary obstruction in the immediate postoperative period and granuloma formation following polytetrafluoroethylene injection are not unusual. To our knowledge delayed complete urinary obstruction after polytetrafluoroethylene injection has not been described previously in the urological literature.     

Local administration of anti-cancer drugs

Anti-cancer drugs in the forms of an emulsion, a microsphere, and of conjugates with high molecular dextran have been developed in our laboratories, namely a fat emulsion of anticancer drug, MMC-microsphere, or MMC-dextran conjugates. The main advantages of these forms of pharmaceutical preparation are that they give prolongation of pharmacological actions by slow release and that they are applicable for topical use because of their reduced toxicities to local tissue yet maintaining local therapeutic potency. In this study we found that the rate of sustained release of drugs and antitumor effects were enhanced when used in such modified forms of drugs for topical injections. Results of clinical trials of those drugs have been promising. However, the number of trials has been limited so far. Further studies would be required for evaluating on of their clinical utilities.     

The impact of topical mupirocin on peritoneal dialysis infection in Singapore General Hospital.

BACKGROUND: Peritonitis and exit-site infections (ESI) are major causes of morbidity in peritoneal dialysis (PD) patients. The application of topical mupirocin to exit sites reduces such complications, and prolongs life in PD. Since the year 2000, this topical treatment has been used in our hospital on new PD patients. We analysed the results of this protocol, and studied the effects of comorbidities on the incidence of peritonitis. METHODS: We studied 740 incident PD patients, who were divided into two groups based on year of entry into PD (Group 1 from January 1998 to December 1999 inclusive, topical mupirocin not used, and Group 2 from January 2000 to March 2004 inclusive, topical mupirocin used). The variables we studied included gender, age, diabetic status, ischaemic heart disease, peripheral vascular disease, cerebrovascular disease and serum albumin. RESULTS: The application of topical mupirocin at the exit site led to a significant reduction in the rate of peritonitis (0.443 vs 0.339 episodes per patient-year; P<0.0005) and in ESI (0.168 vs 0.156 episodes per patient-year; P<0.005), results attributed primarily by the significant (P<0.005) reduction in Staphylococcus aureus infection. There was also an unexpected lowering of Pseudomonas aeruginosa peritonitis in the mupirocin group (P<0.005). Stepwise multiple logistic regression analysis revealed that only the application of mupirocin and serum albumin levels were significant predictors of peritonitis. CONCLUSIONS: Our study, although retrospective, has demonstrated that the topical use of mupirocin was associated with a significant reduction in ESI and peritonitis and, unexpectedly, with findings of fewer incidences of Pseudomonas peritonitis. Serum albumin level before the initiation of PD was a strong predictor of subsequent peritonitis. Mupirocin, with its low toxicity, ease of application and demonstrable beneficial effect in reducing ESI and peritonitis is now used on all of our incident PD patients.     

Total nasopharyngeal stenosis: treatment with laser excision, nasopharyngeal obturators, and topical mitomycin-c.

OBJECTIVE: Severe nasopharyngeal stenosis after uvulopalatopharyngoplasty (UPPP) is a dreaded complication. Very little has been written about successful treatment because attempts at correction frequently fail. Severe stenosis of the nasopharynx drastically worsens speech, swallowing, and obstructive sleep apnea (OSA). We present our successful experience with severe stenosis focusing on a simple functional repair using topical mitomycin-c as well as differing daytime and nighttime palatal obturators. METHODS: Three adults with total or near-total nasopharyngeal stenosis secondary to UPPP were referred to our institution after multiple failed attempts at repair. Each presented with significant OSA on polysomnogram (PSG), with excessive daytime somnolence and voice and swallowing complaints. Under general anesthesia, a CO2 laser is used to create an opening in the nasopharynx. Removable and adjustable palatal obturators are fashioned to keep the nasopharynx open with a daytime insert piece with a small obturator hole for diminished velopharyngeal insufficiency and a nighttime piece without an insert to maximize recumbent airflow. Obturators are removed 6 months later with topical application of mitomycin-c as a fibroblast inhibitor. All patients were followed clinically for at least 1 year and received posttreatment PSG. RESULTS: All patients experienced resolution of their stenoses. Swallowing and voice complaints resolved. Either OSA was eliminated or any residual OSA was successfully treated with nasal continuous positive airway pressure. Serial videoendoscopic images throughout the treatment phase demonstrate the effectiveness of this new technique. CONCLUSIONS: Severe nasopharyngeal stenosis is a rare but devastating complication of UPPP. We introduce a simple technique that uses functional palatal obturators and topical mitomycin-c and describe our success with this treatment algorithm.