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  • 1
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previous analyses of fluids collected from chronic, nonhealing wounds found elevated levels of inflammatory cytokines, elevated levels of proteinases, and low levels of growth factor activity compared with fluids collected from acute, healing wounds. This led to the general hypothesis that chronic inflammation in acute wounds produces elevated levels of proteinases that destroy essential growth factors, receptors, and extracellular matrix proteins, which ultimately prevent wounds from healing. To test this hypothesis further, pro- and activated matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), and the ratios of MMPs/TIMPs were assayed in fluids and biopsies collected from 56 patients with chronic pressure ulcers. Specimens included ulcers treated for 0, 10, and 36 days with conventional therapy or with exogenous cytokine therapies. Quantitative assay data were correlated with the amount of healing. The average MMP-9/TIMP-1 ratio in fluids from 56 ulcers decreased significantly as the chronic pressure ulcers healed. Furthermore, the average MMP-9/TIMP-1 ratio was significantly lower for fluids collected on day 0 from wounds that ultimately healed well (≥85% reduction in initial wound volume) compared with wounds that healed poorly (〈50% wound volume reduction). These data show that the ratio of MMP-9/TIMP-1 levels is a predictor of healing in pressure ulcers and they provide additional support for the hypothesis that high levels of MMP activity and low levels of MMP inhibitor impair wound healing in chronic pressure ulcers.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Inc
    Wound repair and regeneration 8 (2000), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Accurate and clinically practical methods for measuring the progress of acute wound healing is necessary before interventions designed to optimize and even accelerate acute wound healing can be applied. Complete wound closure rates and operative wound closure severity are irrelevant to most acute wounds since most are closed at the time of primary tissue repair and remain closed throughout healing. Analogous to chronic wound closure, the rate of increase of incision tensile strength progressively decreases as time passes and 100% unwounded tissue strength is never achieved making the endpoint definition of “healed” vague. Conceptualizing acute wound healing in terms of its design elements with reintegration into a final outcome lends itself to the description of acute wound healing as a mathematical trajectory. Frequently such an equation is a rate expressing the change in an acute healing parameter, most often tensile strength, over time. Such an approach also normalizes misinterpretations in analysis or errors in theory developed by measuring healing parameters at fixed points in time. Distributions of fractional strength gain times (e.g., 85% normal strength) can be determined using statistical methodology similar that used for failure time of survival analysis. Preclinical studies show that acute wound healing trajectories can be shifted to the left from a “normal” or “impaired” curve to an accelerated or more “ideal” curve. A useful method for measuring acute wound healing outcomes is therefore required before the basic science of acute wound healing is inevitably applied to the problem of acute surgical wounds.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In chronic wounds, the healing process is prolonged and incomplete, proceeding in an uncoordinated manner, and resulting in poor anatomical and functional outcome. There have been numerous attempts to discover models that mimic human wound healing processes. The fibroblast populated collagen lattice is one such model that has been proposed. This study evaluated whether the fibroblast populated collagen lattice can be a model of chronic wound healing using the pressure ulcer as a paradigm. Fibroblast cultures of wound biopsies and wound volume measurements were obtained serially during a four arm blinded, placebo-controlled sequential cytokine clinical trial of pressure ulcers. Fibroblasts obtained from study patients were added to collagen lattices and contraction was determined daily for 10 days. Collagen gel-area measurements were converted to reflect percentage of gel contraction. These data of both edge and base wound biopsies on days 0, 10, and 36 were categorized into treatment groups and one-way analysis of variance showed no significant differences in contraction among these groups. When considering all fibroblast populated collagen lattices, there was significantly greater contraction at days 10 and 36 for cells from both edge and base biopsies compared to day 0 (p 〈 0.05). The Spearman Rank Correlation test comparing all patients with fibroblast populated collagen lattice results from fibroblasts obtained at the edge or base of the wound at days 0, 10, and 36 and clinical pressure ulcer healing on day 36 showed no correlation. This lack of correlation not only persisted for each of the four treatment arms but also for responder status based on decrease in wound volume over the 35 day trial period. In conclusion, chronic wound healing is a complex process that is not modeled by in vitro fibroblast populated collagen lattices.
    Type of Medium: Electronic Resource
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