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Wound healing. Comparison of healing rates of burn wounds and of excisional wounds.

The process of healing of skin excisions and skin burns of equal sizes has been compared in rabbits. Excisions heal definitely quicker than burns, despite the fact that the part of the skin exposed to the burning agent does not undergo necrosis. Small excisional wounds heal more rapidly than larger ones but the healing rate of burn wounds in our series was independent of their size. Secondary excision of the burned tissue accelerates the healing process. Thus the healing time of burn wounds seems to depend more on clearing the wounds of the necrotic tissue than on the mere repair of the skin loss.

Animals↗

A histological study of cutaneous thermal wounds using a Clostridium perfringens-derived wound healing substance with wound healing stimulation activity.

We studied the effects of a Clostridium perfringens-derived wound-healing substance (WHS) on the healing of thermal burn wounds. Third-degree burn injuries were inflicted on the back skin of rats. We histologically evaluated the effects of WHS ointments and compared them with those of lysozyme chloride ointment. We observed the formation of dermal collagen fibers and the increase of capillaries in the WHS ointment treated groups. From the results of hematoxylin and eosin staining and silver staining, an increase in capillaries was observed one week after the application of WHS ointment. Three weeks after the application, when the epithelization was in the final stage, capillary formation ceased. In the WHS ointment-applied groups, electron microscopic observation showed that new collagen fibers were regularly formed in the dermis. On the other hand, in the lysozyme chloride ointment-applied groups, new collagen fibers were present, but were irregularly formed. The main wound healing stimulative action of the WHS ointment could be due to its acceleration of new capillary formation.

Animals↗

General and plastic surgery devices; classification of the nonresorbable gauze/sponge for external use, the hydrophilic wound dressing, the occlusive wound dressing, and the hydrogel wound dressing. Food and Drug Administration, HHS. Final rule.

The Food and Drug Administration (FDA) is classifying the nonresorbable gauze/sponge for external use, the hydrophilic wound dressing, the occlusive wound dressing, and the hydrogel wound dressing into class I (general controls). FDA is also exempting these devices from premarket notification procedures. This action is being taken under the Federal Food, Drug, and Cosmetic Act (the act), as amended by the Medical Device Amendments of 1976 (the 1976 amendments), the Safe Medical Devices Act of 1990 (SMDA), and the Food and Drug Administration Modernization Act of 1997 (FDAMA).

Bandages↗

The JCR:LA-cp rat: a novel model for impaired wound healing.

JCR:LA-cp/cp obese rats and their lean controls were evaluated as a type 2 diabetic wound healing model and the healing quality was characterized. This model of insulin resistance has been used extensively to study atherosclerosis but has not previously been used to study wound healing. Six circular excisional wounds were made on the dorsum of each rat and followed to day 21. Tracings of the wounds were made and used to assess the rate of wound closure. Planimetry showed a significantly diminished contraction of wounds in obese rats, but no significant difference in reepithelialization was observed. Collagen content was determined from the hydroxyproline content in wounded and unwounded skin. There were significantly lower levels of hydroxyproline in the wounds of obese compared to lean animals at day 21. Histology showed adipose tissue in place of dermal tissue in the JCR:LA-cp/cp rat in both unwounded tissue and in the wound at day 21. Active transforming growth factor-beta 1 (TGF-beta 1) was measured in the serum using the plasminogen activator inhibitor-1/luciferase assay and serum total TGF-beta was measured using an enzyme-linked immunosorbent assay. Active TGF-beta was significantly higher in the serum of obese animals compared with lean animals, while total TGF-beta 1 was not significantly different between the groups. Both active and total TGF-beta was measured in tissue sections using the plasminogen activator inhibitor-1/luciferase assay. There was no significant difference in active TGF-beta between genotypes, while obese rats had significantly higher levels of total TGF-beta at day 21. These results indicate a deficiency in wound healing in obese animals characterized by decreased wound contraction, decreased collagen production, and changes in histology. The JCR:LA-cp rat develops insulin resistance, atherosclerosis and early type 2 diabetes and may be a good model for impairment of wound healing in humans with metabolic syndrome.

Animals↗

Effect of wound location and the use of topical collagen gel on exuberant granulation tissue formation and wound healing in the horse and pony.

Preformed collagen gel was topically applied to cutaneous wounds of the equine dorsal fetlock (thoracic limb) and metatarsal regions to evaluate the effect on exuberant granulation tissue production and wound healing. In 6 horses and 3 ponies (less than 140 cm high at the withers and less than 365 kg), 36 standardized cutaneous limb wounds were surgically induced (4 wounds/animal); 18 wounds were treated topically with collagen gel, and 18 wounds were not treated (controls). Collagen gel was initially applied to the wound at 0, 2, or 7 days after wound formation (groups 1, 2, and 3, respectively). Four measurements were regularly made: amount of wound contraction and the size of the granulation bed, epithelial covering, and total wound. Sequential skin and wound biopsies were evaluated histologically to assess wound healing. Using a computer, data were analyzed for differences in the 4 measurements between treated and control wounds, between fetlock wounds and metatarsal wounds, and among groups 1, 2, and 3. Analyses were performed on days 15 and 45 of wound healing and on the final day of healing. A significant difference (P greater than 0.05) in the production of exuberant granulation tissue, rate of epithelialization, or degree of wound contraction was not detected between the collagen-treated and control wounds. Total healing time and final scar size were similar. Wound healing patterns were significantly different (P less than 0.05) in the fetlock wounds and metatarsal wounds. All wounds enlarged up to day 15 with fetlock wounds enlarging significantly more than did the metatarsal wounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Wound bed preparation: a systematic approach to wound management.

The healing process in acute wounds has been extensively studied and the knowledge derived from these studies has often been extrapolated to the care of chronic wounds, on the assumption that nonhealing chronic wounds were simply aberrations of the normal tissue repair process. However, this approach is less than satisfactory, as the chronic wound healing process differs in many important respects from that seen in acute wounds. In chronic wounds, the orderly sequence of events seen in acute wounds becomes disrupted or "stuck" at one or more of the different stages of wound healing. For the normal repair process to resume, the barrier to healing must be identified and removed through application of the correct techniques. It is important, therefore, to understand the molecular events that are involved in the wound healing process in order to select the most appropriate intervention. Wound bed preparation is the management of a wound in order to accelerate endogenous healing or to facilitate the effectiveness of other therapeutic measures. Experts in wound management consider that wound bed preparation is an important concept with significant potential as an educational tool in wound management. This article was developed after a meeting of wound healing experts in June 2002 and is intended to provide an overview of the current status, role, and key elements of wound bed preparation. Readers will be able to examine the following issues; the current status of wound bed preparation; an analysis of the acute and chronic wound environments; how wound healing can take place in these environments; the role of wound bed preparation in the clinic; the clinical and cellular components of the wound bed preparation concept; a detailed analysis of the components of wound bed preparation.

Cell Proliferation↗

Home care nurses' ratings of appropriateness of wound treatments and wound healing.

PURPOSE: The purpose of this study was to examine nurses' ratings of appropriateness of wound treatments and wound healing for patients in home care in relation to patient demographic and visit variables. DESIGN: A cross-sectional design was used. SETTING AND SUBJECTS: Data were collected about patients with wounds by 281 nurses from 13 home care agencies located throughout lower Michigan. Patients with wounds (n = 881) ranged in age from 21 to 100 years. They included 492 women and 383 men who were white (72.4%) or African-American (26%). INSTRUMENTS: The Community Wound Assessment Tool was developed for the study and was used to obtain demographic and wound data. The demographic section contained information about the patient's age, sex, reason for the visit, length of visit, and time the case was opened. The wound section included the wound type, treatments, presence of incontinence, nutritional supplementation, and adverse home environmental factors. Nurses rated wounds as healing or not healing. Wound treatments were rated as all appropriate, some appropriate/inappropriate, and all inappropriate. METHODS: Nurses were systematically selected from each agency and collected data about each patient visited on one occasion. MAIN OUTCOME MEASUREMENTS The main outcome measurements were the relationship of patient demographic variables and visit variables to the appropriateness of wound treatments and wound healing. RESULTS: The nurses' rating of wound treatments as appropriate was significantly related to younger patient age and a shorter time for the case to be open. Wound healing was initially associated with younger patient age, continence of urine or stool, shorter home visits, shorter time for the case to be open, and fewer reasons for the visit. When wound healing was controlled for the type of wound in path analysis, the patient's age was no longer significant and incontinence appeared to impair healing of nonsurgical wounds. The appropriateness of the wound treatments was significantly related to wound healing. CONCLUSIONS: Nurses' ratings of appropriateness of wound treatments and healing are significantly related to factors that affect length of service and complexity of care for the home care patient with a wound. Decisions nurses make about wound treatments and healing are important for the patient as well as for the agency.

Adult↗

Infected chronic wounds show different local and systemic arginine conversion compared with acute wounds.

BACKGROUND: Several experimental studies have shown the importance of arginine in wound healing. However, little is known about its role in human wound healing. In this study, we investigated arginine metabolism in impaired wound healing. MATERIALS AND METHODS: Twenty patients with chronic wounds and 10 patients with acute wounds were included in a prospective study. Amino acids, nitrate/nitrite, and arginase concentrations were determined in plasma and wound fluid using high-performance liquid chromatography and enzyme-linked immunosorbent assay. Chronic wounds were divided into two groups: noninfected chronic wounds (n = 11) and infected chronic wounds (n = 9), based on quantitative bacterial analysis of wound fluid samples. RESULTS: Plasma arginine levels, next to total plasma amino acid levels, were significantly decreased in patients with infected chronic wounds compared with patients having acute or noninfected wounds. Citrulline and ornithine levels were significantly increased in infected chronic wounds and related to decreased nitrate/nitrite levels, whereas wound fluid arginine levels were similar in all groups. In addition, wound fluid arginase levels of infected chronic wounds were significantly enhanced. CONCLUSIONS: This study demonstrates that patients with infected chronic wounds have decreased plasma arginine levels and suggests enhanced arginine conversion in the wound. In contrast to noninfected chronic wounds, arginine seems to be mainly metabolized by arginase in infected chronic wounds. In conclusion, our hypothesis is that impaired wound healing is related to an altered arginine usage.

Acute Disease↗

[Preliminary study on the improvement of wound microcirculation and retrospection on several methods of the management of deep partial thickness burn wound].

OBJECTIVE: To analyze several methods of wound repair for deep partial thickness burn wounds retrospectively, so as to evaluate the significance of improvement of wound microcirculation on wound healing. METHODS: (1) 2,976 burn patients admitted to our department were enrolled in the study, among them 614 undertook tangential excision, 32, eschar abrasion, 86 allo-skin coverage after debridement, 1836 tropical application of silver sulfadiazine and 408 with traditional Chinese medicine (Jing Wan Hong ointment) with gauze bandage. The results of the management with different methods were compared. (2) Rat model with deep partial thickness burn was reproduced and topical application of silver sulfadiazine was given. The rats were randomly divided into control (n = 10, with normal saline injected via caudal vein within 5 minutes postburn), and treatment (n = 10, with batroxobin injected via caudal vein within 5 minutes postburn) groups. The blood flow perfusion unit in the wound skin was measured before burn and at 0.5 to 72 postburn hours by Laser Doppler. The wound healing rate, contraction rate and wound healing time in each group were calculated on 14 and 18 postburn days (PBDs). The number of hair follicles after wound healing was observed by histological method. RESULTS: (1) The burn wound treated by tangential excision healed within 2 to 3 post operation weeks (POWs), with the healing rate of 94.8% in patients with burn covering 50% - 70% TBSA and 93.4% in those with burn of 80% approximately 98% TBSA. The healing time of patients with allo-grafts coverage after eschar abrasion was 13.8 +/- 2.1 days without scar formation. The wound healing time was 18.0 +/- 2.3 day in 82 patients with allo-graft coverage after debridement, and it was 26.0 +/- 3.2 days with subeschar healing in 1658 patients with topical application of silver sulfadiazine. Infection in burn wound was encountered in most patients undergoing traditional Chinese medicine bandage treatment with wound healing time of 26.0 +/- 2.8 days in the lower extremities. (2) The blood flow perfusion unit of the rats in the treatment group was significantly higher than that in the control group (P < 0.01). The wound healing rate in treatment group on 14 and 18 PBD was obviously higher than that in the control group (P < 0.01). But the wound contraction rate in the two groups was similar (P > 0.05). The wound healing time in treatment group was much shorter than that in control group (P < 0.01). A few hair follicles remained in the dermis of the rats in the control group on 30 PBD, and the number was evidently smaller than that in the treatment group (P < 0.01). CONCLUSION: Early tangential excision and eschar abrasion remained better methods in the management of deep partial thickness burn wounds, as they could ameliorate burn wound infection, shorten treatment period, raise wound healing rate and quality. Application of batroxobin could accelerate wound healing rate by improving wound microcirculation in deep partial thickness burn wound.

Adult↗

Outcomes of conventional wound treatment in a comprehensive wound center.

Conventional wound care is the elementary treatment modality for treating chronic wounds. However, early treatment with topical growth factors may be needed for a subset of chronic wounds that fail to heal with good wound care alone. A prospective nonrandomized case series from a single-community outpatient wound care clinic is presented here in an effort to identify the subset of chronic wounds that may require early adjuvant intervention. There were 378 consecutive patients with 774 chronic wounds of varying etiology. All patients received 4 weeks of conventional wound care, including weekly debridement and twice-daily dressing changes. Wounds not reduced by 50 per cent volume at 4 weeks were nonrandomly treated with human skin equivalent (Apligraf), platelet-derived wound healing factor, or platelet-derived growth factor isoform BB (becaplermin gel, Regranex). A total of 601 of 774 (78%) wounds healed regardless of treatment type. The median time to heal for all wounds was 49 days (interquartile range = 26-93). More women than men healed (85% vs 71%, respectively, P < 0.0001). Diabetic wounds were as likely to heal as nondiabetic wounds (78% vs 80%, P = 0.5675). Wounds that did not heal had larger volumes and higher grade compared with wounds that healed (P < 0.0001 for both variables). The data presented here show that the majority of chronic wounds will heal with conventional wound care, regardless of etiology. Large wounds with higher grades are less responsive to conventional wound care and will benefit from topical growth factor treatment early in the treatment course.

Aged↗

[Arnebia root oil promotes wound healing and expression of basic fibroblast growth factor on the wound surface in rabbits].

OBJECTIVE: To observe the promoting effect of arnebia root oils on expression of basic fibroblast growth factor (bFGF) in skin wound of rabbits and the histomorphological changes in the wound surface, and to discuss its mechanism. METHODS: Bilateral round skin wounds were made on the back of 15 rabbits. The three wounds on one side of the back of each rabbit were treated with arnebia root oils, while the three wounds on the other side were treated with vaseline in order to promote the wound healing. The histomorphology and ultrastructure under electron microscopy of the wounds, and the rate of wound healing were examined at different time. Western blotting assay was used to detect the expression of bFGF in the wound surface. RESULTS: The healing rate of the arnebia root oils-treated wounds was evidently higher than that of the vaseline-treated wounds (P<0.05). The quantities of fibroblast, collagen and capillary in the arnebia root oils-treated wounds were much more than those in the vaseline-treated wounds, and the expression of endogenous bFGF in the arnebia root oils-treated wounds was enhanced obviously as compared with that in the vaseline-treated wounds in different period of wound healing. There existed a parallel correlation between the expression level of bFGF and the rate of wound healing. CONCLUSION: The promoting effect of arnebia root oils on wound healing may be related to increasing the expression level of basic fibroblast growth factor in the skin wound.

Animals↗

The influence of wound geometry on the measurement of wound healing rates in clinical trials.

PURPOSE: The comparison of wound healing rates in clinical trials presents a challenging problem. Wound healing typically has been expressed as a change in area over time or a percent change in area over time. These methods are inaccurate, however, when applied to wounds of varying size and shape. A relatively small amount of healing in a large wound will produce a greater change in area than in a smaller wound. Conversely, measurement of the percent change in area of a wound will tend to exaggerate the healing rates of smaller wounds. A method of calculating average linear healing of the wound edge toward the center of the wound has been proposed that should not be influenced by wound size: D = delatA divided by P, where D = linear healing, deltaA = change in area, and P = mean perimeter. The purpose of this study was to examine linear healing of the wound edge as a method of measuring wound healing in clinical trials. METHODS: We observed 39 patients with venous stasis ulcers. The area, perimeter, length, and width of each wound were calculated with computerized planimetry. Change in area per day and linear healing rate of the wound edge per day were calculated. Multiple linear regression analysis was used to explore factors that influence wound healing as measured by these methods. RESULTS: The change in area per day was significantly and independently influenced by initial area (p < .0001), perimeter (p < .0001), length (p < .00055), and width (p < .0175). Linear healing per day was not influenced by any geometric variable, including area, perimeter, length, width, and ratio of width to length. CONCLUSION: Linear healing per day is a valid means of comparing wound healing rates in wounds of different dimensions. Linear healing per unit of time should be preferred to measurements of change in wound area to quantify wound healing rates in clinical trials.

Chronic Disease↗

[Differentiated local therapy of chronic wounds with modern wound dressings].

Differentiated local therapy of chronic wounds with modern wound dressings. The therapy of chronic wounds comprises besides treating the underlying disease, for instance compression therapy and phlebosurgery with venous ulcus cruris modern differentiated local therapy. Conventional wound therapy comprises primarily of colour solutions, various ointments, local antimicrobial agents, and sterile pressure bandages. Although it has been proven that conventional methods impede wound healing compared with modern wound dressings they are still widely used. In comparison the principle of moist wound healing is the basis of modern differentiated wound therapy. Therefore a vast number of modern wound dressings has been established in the last years. As not every wound dressing is suitable for every type of wound the knowledge of available modern wound dressings is essential in order to choose the wound dressing which is most suitable for the individual case. In the exudation/cleaning phase polyurethane foams, alginates and dressings containing activated charcoal are indicated. They can also be used in the granulation phase. The granulation phase is main indication for hydrokolloids and hydrogels. They are also used beside non-adhesive dressings and alginates in the epithelialisation phase. Besides the above synthetic wound dressings cytokines and biological skin equivalents are increasingly used in modern wound therapy. Biological skin equivalents comprise of epidermis equivalents, dermis substitutes and combined epidermis-dermis equivalents which are being developed at present. These will possibly be more effective on wound closure. Phase adapted use of modern wound dressings enables acute and chronic wounds to heal quickly and without complications. Present clinical studies are evaluating the importance of cytokines and new vital skin substitutes, which might offer interesting possibilities for further improvement in wound treatment.

Bandages↗

Paradoxical effects of elastase inhibitor guamerin on the tissue repair of two different wound models: sealed cutaneous and exposed tongue wounds.

Innate elastase inhibitors are known to be putatively involved in the regulation of tissue inflammation by inhibiting polymorphonuclear leukocyte (PMN) derived proteinases. The aim of this study was to evaluate affects of leukocyte elastase suppression and PMN infiltration on wound healing in mouse by administering the recombinant elastase inhibitor guamerin (rEIG) in two different wound models; 1) impaired pin-punctured dorsal mucosa of anterior tongue wound, 60 mice, treated with saline containing rEIG that were fed ad libitum and 2) stable linear excisional cutaneous wound, 40 mice, covered with fibrin sealant containing rEIG. The progress of healing was analyzed by histological methods. The tongue wounds treated with rEIG became edematous around the pin-punctured tongue wound, and influx of inflammatory cells and PMN into the underlying stromal tissue were seen rapidly after wounding and peaked between 2-4 days. Whereas the control mice showed almost no wheal formation in the pin-punctured wound, a far lesser levels of PMN infiltration, and almost complete wound closure in 4 days. In the other model, the liner excisional cutaneous wound treated with fibrin sealant containing rEIG showed early wound constriction, lesser degree of inflammatory cells influx, and complete reepithelialization in 4-5 days, whereas the wound of control mice with the fibrin sealant alone showed contrary delayed reepithelialization, greater degree of inflammatory cell infiltration, and consequencial formation of greater granulation tissue at wound site. Taken together, these data suggest paradoxical effects of rEIG on the wound healing where in the wound exposed to infiltrating milieu of microorganisms in the oral cavity, the rEIG aggravates the wound healing by interfering with other innate defensive factors and extended greater flux of PMNs to inflamed wound site, while in the wound enclosed by fibrin, the rEIG accelerated wound healing by inhibiting the inflammation-generated proteases and the acute inflammatory reaction.

Animals↗

Topical platelet-derived growth factor in patients enhances wound closure in the absence of wound contraction.

Recombinant human platelet-derived growth factor (PDGF) is reported to promote wound closure in problem wounds. The mechanism of PDGF enhancement of wound closure is not clear. Does PDGF enhance wound contraction, or re-epithelialization, or both? In four patients undergoing elective surgery, a full excision 5 cm(2) punch wound was made behind each ear. The left post-articular wound received daily PDGF in a gel and each right post-articular wound received placebo-gel daily. The placebo-treated wounds closed in 19.8 days, while the PDGF-treated wounds closed significantly faster, in 15.6 days, p=0.002. At Day 20, all healed wounds were processed for histology. PDGF-treated wounds showed granulation tissue beneath an uninterrupted epidermis. A fine birefringence pattern, consistent with granulation tissue, was found by polarized light microscopy. The control closed-wounds had a smaller area of granulation tissue under an intact epidermis and polarized light microscopy showed mostly normal dermis. The presence of intact dermis within the closed-wound site is the hallmark of wound contraction. Topical PDGF limits the role of wound contraction in wound closure. Control wounds healed by wound contraction, while PDGF-treated wounds close by re-epithelialization and filling in with scar.

Administration, Topical↗