Keratinocytes derived from embryonic stem cells induce wound healing in mice

The skin plays an important role in defending the body against the environment. Treatments for burns and skin injuries that use autologous or allogenic skin grafts derived from adult or embryonic stem cells are promising. Embryonic stem cells are candidates for regenerative and reparative medicine. We investigated the utility of keratinocyte-like cells, which are differentiated from mouse embryonic stem cells, for wound healing using a mouse surgical wound model. Mice were allocated to the following groups: experimental, in which dressing and differentiated cells were applied after the surgical wound was created; control, in which only the surgical wound was created; sham, in which only the dressing was applied after the surgical wound was created; and untreated animal controls with healthy skin. Biopsies were taken from each group on days 3, 5 and 7 after cell transfer. Samples were fixed in formalin, then stained with Masson’s trichrome and primary antibodies to interleukin-8 (IL-8), fibroblast growth factor-2 (FGF-2), monocyte chemoattractant protein-1 (MCP-1), collagen-1 and epidermal growth factor (EGF) using the indirect immunoperoxidase technique for light microscopy. Wound healing was faster in the experimental group compared to the sham and control groups. The experimental group exhibited increased expression of IL-8, FGF-2 and MCP-1 during early stages of wound healing (inflammation) and collagen-1 and EGF expression during late stages of wound healing (proliferation and remodeling). Keratinocytes derived from embryonic stem cells improved wound healing and influenced the wound healing stages.     

Application of wound dressing Molndal technique in clean and potentially contamined postoperative wounds--initial comparative study

Because of a possible delayed wound healing, critical colonization and infection of wounds present a problem for surgeons, particularly in patients with compromised immune system or in case where the wound is heavy contaminated or poorly perfused. Molndal technique of wound dressing has proven to be effective in prevention of infection. In our study we wanted to describe the benefits of the application of Molndal technique wound dressing compared to traditional wound dressing technique at potentially contaminated and clean postoperative wounds. We examined postoperative wound after radical excision of pilonidal sinus and after implantation of partial endoprosthesis in hip fracture. Molndal technique consisted of wound dressing with Aquacel Ag - Hydrofiber. Traditional technique was performed using gauze compresses and hypoallergic adhesives. We analyzed the results of 50 patients after radical excision of pilonidal sinus. 25 patients were treated by Molndal technique and 25 patients by the traditional technique of wound dressing. In the group treated by Molndal technique only 1 (4%) patient has revealed a wound infection, proven by positive microbiological examination and suppuration. In the traditional technique group 4 (16%) patients developed wound infection as inflammation and secretion as a sign of superficial infection. In the other group we analyzed the results of 50 patients after implantation of partial endoprosthesis after hip fracture. 20 patients were treated by Molndal technique and 30 patients by the traditional technique of wound dressing. In the group treated by Molndal technique no patient has revealed a wound infection (0%). In the traditional technique group 4 (13%) patients developed wound infection. All complication in both group were superficial incisional surgical infection (according to HPSC). There was no deep incisional surgical site infection or organ/space surgical site infection. Our results are clearly showing that Molndal technique is effective in preventing the postoperative wound infection.     

Effect of lidocaine and epinephrine on Staphylococcus aureus in a guinea pig model of surgical wound infection

Postoperative wound infection, most often with, is of ubiquitous concern in surgical practice, occurring in an average of 1.5 to 5 percent of all procedures. The antimicrobial properties of local anesthetics have been documented over the past 25 years by in vitro studies. This study evaluates the effects of lidocaine preparations on in an in vivo setting. In a wound infection model using live albino guinea pigs, inoculum was introduced for the reproducible bacterial colonization of clean surgical wounds. One of two sites on the dorsum of each animal was infiltrated with a commercial lidocaine preparation (with and without epinephrine) prior to inoculation with (10 cfu/ml). The other site, inoculated with without preinfiltration with lidocaine, served as the control. Cultures from the sites treated with lidocaine were then compared with cultures from the control sites. All control sites had a consistent presence >or=10 cfu/ml, the threshold for bacterial inhibition of wound healing. Infiltration of the wound with 2 ml of 2% lidocaine prior to inoculation was associated with an average decrease in bacterial count of >70 percent ( n= 19). On the other hand, the addition of epinephrine (1:100,000) to lidocaine was associated with a 20-fold in bacterial counts compared with control values ( n= 10). This is the first study to demonstrate inhibition of by a local anesthetic agent in an in vivo model of a surgical wound. This information suggests a possible role for local anesthetics in prophylaxis against surgical wound infection.     

Immunocorrection with pentaglobin in wound infection and burn disease

Patients with wound infections and extended burns were treated with pentaglobin (Biotest-Pharma), a serum preparation containing high concentrations of immunoglobulin M. The use of the preparation at early stages after surgical operations in the patients with wound infections or at the beginning of active surgical treatment of the patients with burns decreased the terms of the body temperature normalization as well as normalization of the immunological, hematological and biochemical indices. The most pronounced efficacy of pentaglobin was observed in the patients with severe microbial toxemia. A scheme for pathogenetic immunocorrection of wound infections and burns was developed. It is based on simultaneous recording of intensity of immunological responses in peripheral blood and intensity of protective reactions in wound tissues.     

Immediate hair transplantation into a newly closed wound to conceal the final scar on the hair-bearing skin

A surgical incision after suturing usually leaves a visible scar on the hair-bearing skin, even after optimal wound conditions. The conspicuousness of such a scar results from its linear continuity and hairlessness. To prevent this effect, a row of micrografts or minigrafts was inserted between the wound edges immediately after wound closure. The hair grafts that were transplanted were dissected from the discharged skin in the same surgical procedure, if feasible. Otherwise, a mini donor strip was harvested from the mastoid scalp to dissect the hair grafts. The final linear scar was interrupted and concealed sufficiently with the growth of the transplanted hairs. Tension-free closure is required to obtain a satisfactory result with this technique.     

Expression of basic fibroblast growth factor and transforming growth factor-Beta 1 in patients with fasciocutaneous and muscle flaps

Angiogenesis involves multiple sequential mechanisms stimulating the growth of host endothelium. It occurs in surgical flaps at the interface with the reconstructed wound bed. In this study, concentrations of basic fibroblast growth factor (bFGF) and transforming growth factor-beta 1 (TGF-beta ) were analyzed in sera and wound fluids of 30 patients who underwent surgical treatment with muscle (n = 15) and fasciocutaneous flaps (n = 15). At 12 hours after operation, bFGF levels in wound fluids of patients with muscle flaps were significantly (p < 0.05) higher than in patients with fasciocutaneous flaps. At 24 and 36 hours after surgical treatment, there was no significant difference between them. Each group showed a significant decrease in bFGF levels after 24 and 36 hours. In sera, bFGF was not detectable. The two different groups presented no remarkable difference in TGF-beta concentrations in wound fluids. A correlation between angiogenic factors in sera and wound fluids could not be observed. The results show that angiogenesis is initially more activated in the wound bed of muscle flaps. This might be of great consequence to the healing process and might explain the curative effect of muscle flaps on bradytrophic tissue.     

Effect of a Synthetic Dressing Formed on a Burn Wound in Rats: a Comparison of Allografts, Collagen Sheets, and Polyhydroxyethylmethacrylate in the Control of Wound Infection

Allograft dressings to control Pseudomonas wound infections in rats were studied on surgical wounds and escharectomized burn wounds. The effects of allografts were compared with a collagen sheet (Aviderm) and a synthetic dressing, polyhydroxyethylmethacrylate (Hydron), formed on the wound by mixing the polymer and the solvent. The results indicated that infections in surgical wounds were more easily controlled by dressings than similar contaminations in burn wounds. A procedure was described for the formation of a synthetic dressing directly on the wound from a mixture of polymer and solvent. This type of preparation completely filled the wound area and sealed the edges, preventing further contamination, and gave excellent coverage of the wound. With 24 h of coverage of escharectomized burn wounds, allografts provided the best dressing for reduction of wound organisms. At 96 h of coverage, Hydron and Aviderm produce significant reductions in the Pseudomonas resident in the burn wound. The results support the thesis that suitable dressings promote local host defense processes which kill the contaminating bacteria.     

Arrachement du scrotum par morsure humaine: présentation d’un cas et revue de la littérature

Human bites of male external genitalia are rare. We report a case of scrotal wound caused by human bite during a sexual dispute. Lesion was recent wound caused by tearing off the summit of scrotal skin without any testicular injury. The wound was successfully treated by antibiotics, surgical debridement and suture. The patient was immunized against tetanus.     

Experimental and clinical study of immunomodulators Immunomax and Gepon in complex treatment of acute purulent surgical infection]

The efficacy of the immunomodulators immunomax and gepon in the treatment of acute purulent surgical infection of soft tissues was studied under experimental and clinical conditions. Gepon was used in the form of 0.04% ointment in the phase of the wound infection regeneration vs. the routine use of 10% methyluracil ointment. Immunomax was administered in a dose of 40 units under the experimental conditions and 200 units in the clinical trial 3 times every 2nd day intramuscularly. The experimental investigation was performed on 20 male guinea pigs in a model of a suppurating wound. The animals were divided into 2 groups (main and control) of 10 animals each. Flat wounds were prepared according to the A. V. Nikolaev's method. The clinical trial enrolled 126 patients with acute surgical infection of the soft tissues. The patients were treated in the Hospital of General Surgery of the Faculty of Pediatrics of the Russian State Medical University during the period from 2003 to 2004. The patients were divided into 2 groups (main and control). The structure of the main and control groups was comparable by the sex and age of the patients, nosological forms and severity of the disease. The patients of the main group (65 subjects) were given the immunomodulators in complex with the routine surgical treatment and drug therapy. The patients of the control group (61 subjects) were given the same surgical treatment and drug therapy but without the use of the immunomodulators. General and local manifestations of the purulent infection were considered as the criteria of the treatment efficacy. The qualitative and quantitative composition of the wound bacterial infection was determined and histological examination of the wound bioptates was performed. Planimetry of the wound surface was carried out and the acceleration index of the wound clearing and healing was evaluated. In the total, high therapeutic efficacy of immunomax and gepon, practically no contraindications and adverse reactions to their use, the ease and simplicity of their handling can be stated.     

Ward Design in Relation to Postoperative Wound Infection: Part I

The incidence of postoperative wound infection in a general surgical unit is reported both before and after transfer from a “Nightingale” type multibed ward to a new “race-track” type of surgical ward with controlled ventilation and with 40% of its beds in single rooms. Following transfer postoperative wound infection was reduced by about 55%.With the use of certain types of staphylococcal infection as an index of cross-infection it was shown that transfer was followed by a 72% reduction in cross-infection of wounds.A case is made for control of hospital cross-infection in surgical wards. The principal change in ward architecture resulting from the transfer was the extensive division of ward space into separate compartments (40% of single-bed rooms), which make controlled ventilation easier.     

早期伤口切开对血循毒蛇咬伤患者预后的影响

目的探讨血循毒类毒蛇咬伤患者早期伤口切开对预后的影响。方法回顾性分析我院2011年3月~2014年3月诊治的血循毒类毒蛇咬伤患者223例的临床资料,总结并比较其临床特点及预后。结果本组患者轻度肿胀97例中,伤后12h内切开21例,未溃疡12例,Ⅰ°溃疡7例,Ⅱ°溃疡2例;晚期切开或未切开76例,未溃疡15例,Ⅰ°溃疡41例,Ⅱ°溃疡16例,Ⅲ°溃疡4例。中度肿胀患者85例中,伤后12h内切开32例,未溃疡8例,Ⅰ°溃疡21例,Ⅱ°溃疡2例,Ⅲ°溃疡1例;晚期切开或未切开53例,未溃疡6例,Ⅰ°溃疡16例,Ⅱ°溃疡24例,Ⅲ°溃疡7例。重度肿胀患者41例中,伤后12h内切开17例,Ⅰ°溃疡11例,Ⅱ°溃疡4例,Ⅲ°溃疡2例;晚期切开或未切开24例,Ⅰ°溃疡2例,Ⅱ°溃疡6例,Ⅲ°溃疡16例。在蛇伤后12h内切开的患者坏死溃疡的形成、肿胀程度的改善均明显优于晚期切开或未切开的患者,差异有显著统计学意义(P0.05)。结论随着患者凝血功能的改善,早期伤口切开对血循毒类毒蛇伤患者局部伤口状况有较好的改善作用。     

Nonsurgical repair of perinasal skin defects

Immediate reconstruction of full-thickness skin defects after cancer surgery is a commonly accepted surgical principle used to preserve function and minimize cosmetic deformity. Healing by secondary intention, however, offers the advantages of optimal cancer surveillance, simplified wound management, and avoidance of reconstructive procedures with their associated costs and potential complications. Accurate prediction of the course of wound healing, and thereby the final functional and cosmetic result, would allow a rational approach to selection of patients for surgical or nonsurgical repair. We observed 282 patients with full-thickness perinasal (glabella, medial canthus, dorsum, sidewall, tip, ala, philtrum, alar base, and nasolabial fold) skin defects after Mohs' surgery and documented a variety of parameters affecting wound healing, including location, depth, and size of the wound. Patients were examined at intervals, and a final determination regarding cosmesis and function was made at 6 months or later. We conclude that the most important considerations in predicting the final functional and cosmetic result include location by subunit, followed by size and depth of the wound.     

The effect of systemic isotretinoin on wound contraction in guinea pigs

An experimental study was designed using Hartley guinea pigs to evaluate wound contraction on animals receiving systemic isotretinoin at a dose of 10 mg/kg. Half the animals received isotretinoin for 4 weeks before the surgery and for 2 weeks after the surgical procedure. A square of skin and panniculus carnosus measuring 200 mm2 was excised from the back of each animal, and the amount of wound contraction was determined by a computer program from the drawings on celluloid overlays done weekly. The animals on systemic isotretinoin had a significant delay in wound contraction when compared to control animals (p less than 0.001). When the medication was discontinued, all the animals had complete wound healing within a week.     

Assay of radiation effects in mouse skin as expressed in wound healing

The effect of 150 kVp X irradiation on the healing of full depth surgical wounds in the lower dorsal skin of the mouse was assayed by measuring the wound strength of seven 2-mm-wide segments along each wound. The strength of unirradiated wounds increased with time in two phases: during the first 2 weeks it reached nearly half of the values recorded from unwounded skin, after which the rate of increase slowed for at least 2 weeks before beginning a second increase. By 150 days, the breaking strength of the wound was about 80% of that of unwounded skin. A single dose of 18 Gy prior to wounding reduced the strength of the wounds to about one-third to one-half that of an unirradiated wounds within the 3 months of follow-up. The effect of irradiation on wound strength did not change as the interval between exposure and wounding was increased to 2 months but decreased slightly when this interval was extended to 3 months. When the healing wound was irradiated within 5 days of surgery, the effect on healing was about the same as with preirradiation; if irradiation was delayed for 12 days after wounding the second phase of healing was only postponed and the wound strength ultimately approached the values recorded from unirradiated wounds. The wound strength of skin preirradiated by X rays and assayed 14 days after wounding showed a clear sigmoid dose response with a threshold between 8 and 10 Gy and a plateau at the maximum effect above 20 Gy. The persistence for at least 3 months of the effect of radiation on wound healing suggests that the tissues involved in the healing process are normally proliferating slowly. The accelerated expression of radiation injury through surgical wounding permits the early quantification of the radiation response of tissues that would normally be delayed in their expression of radiation damage.     

A comparison of the effects of temperature on wound healing in a tropical and a temperate teleost

The rate of healing of a surgical wound was studied in two teleost fish, one with a tropical, and the other with a temperate temperature range. Comparisons were made of both the rate and qualitative nature of wound healing within and between species at temperatures of 30,23,10 and 5° C. The rate of wound healing was found to be proportional to temperature and temperature stress had little effect on healing rates. The findings were related to reported rates of wound healing in man. In general the wounds studied healed at a rate comparable to those reported for the healing of superficial skin wounds in man and other mammals despite the fact that the fish wounds were not merely superficial but involved integument and muscle.     

Collecting And Measuring Wound Exudate Biochemical Mediators In Surgical Wounds

We describe a methodology by which we are able to collect and measure biochemical inflammatory and nociceptive mediators at the surgical wound site. Collecting site-specific biochemical markers is important to understand the relationship between levels in serum and surgical wound, determine any associations between mediator release, pain, analgesic use and other outcomes of interest, and evaluate the effect of systemic and peripheral drug administration on surgical wound biochemistry. This methodology has been applied to healthy women undergoing elective cesarean delivery with spinal anesthesia. We have measured wound exudate and serum mediators at the same time intervals as patient''s pain scores and analgesics consumption for up to 48 hours post-cesarean delivery. Using this methodology we have been able to detect various biochemical mediators including nerve growth factor (NGF), prostaglandin E2 (PG-E2) substance P, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, TNFα, INFγ, G-CSF, GM-CSF, MCP-1 and MIP-1β. Studies applying this human surgical wound bioassay have found no correlations between wound and serum cytokine concentrations or their time-release profile (J Pain. 2008; 9(7):650-7).¹ We also documented the utility of the technique to identify drug-mediated changes in wound cytokine content (Anesth Analg 2010; 111:1452-9).²     

Inhibition of placental growth factor improves surgical outcome of glaucoma surgery

Excessive post‐operative wound healing with subsequent scarring frequently leads to surgical failure of glaucoma filtration surgery (trabeculectomy). We investigated the hypothesis that placental growth factor (PlGF) plays a role in post‐operative scar formation, and that it therefore may be a target for improvement of filtration surgery outcome. ELISA experiments showed that PlGF levels were significantly increased in aqueous humour of glaucoma patients and after VEGF treatment, which may indicate an important contribution of this growth factor to wound healing after trabeculectomy. Using a mouse model of glaucoma filtration surgery, we were able to show that intracameral injection of a previously characterized anti‐PlGF antibody (ThromboGenics NV) significantly improved surgical outcome by increasing bleb survival and bleb area. This was associated with a significant reduction in post‐operative proliferation, inflammation and angiogenesis during the first post‐operative days after surgery, and with a decrease in collagen deposition at later stages. Furthermore, inhibition of PlGF seemed to be more effective than anti‐VEGF‐R2 treatment in improving surgical outcome, possibly via its additional effect on inflammation. These results render PlGF an appealing target for ocular wound healing and point to potential therapeutic benefits of PlGF inhibition for the prevention of surgical failure.     

Ward Design in Relation to Postoperative Wound Infection: Part III

The wound infection rates, nasal carriage rates, and nasal colonization rates were studied in a recently built surgical unit for two years when it was first opened. Five years later a further two-year period of study was undertaken.Judging by the incidence of postoperative wound infection, as far as both Staphylococcus pyogenes and Gram-negative organisms are concerned, there is no evidence that the environment has become less safe with use over the seven-year period since opening.     

Morphofunctional characteristics of wound inflicted by an ultrasonic destroyer]

A surgical model of EstoRex ultrasound destroyer operating at a frequency of 60 KHz, power of 6 W, and vibration amplitude at the tip of the tool of 15 microns was used to make incisions on rat liver. 5 to 7 s or 24 hr after surgery the specimens of the wound wall were fixed and further processed for electron microscopy and histochemical visualization of glucose-6-phosphatase at the ultrastructural level. In a separate series 2 mm-thick strips of the tissue were excised from the liver, processed by the destroyer for 45 s, and then exposed to a digestion treatment with mixture of trypsin and chymotrypsin for 24 hr at 37 degrees C or in solution of cathepsin L for 60 hr at 25 degrees C. The results showed that ultrasound caused not only thermal but also nonthermal ultrastructural and histochemical alterations, due probably to cavitation and viscous stresses. The ultrasound wound did not contain any proteolytically resistant material. Since ultrasound-processed tissue turned out to be highly susceptible to proteolytic digestion we suggest that the ultrasound destroyer, unlike Nd:YAG laser surgical instrument, would be a promising surgical tool with respect to wound cleaning and healing.