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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Science Ltd/Inc.
    Wound repair and regeneration 12 (2004), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: The study of wound biology and effects of advanced modalities would benefit from a reliable human model for normal healing. Eaglstein et al. previously suggested that the forearm biopsy may be useful in acute wound healing studies (J Am Acad Dermatol 45:857, 2001). The Wound Healing Cooperative Group (WHCG) here validates this model in healthy individuals treated with topical growth factor therapy. Methods: In our randomized, double-blinded study design, 20 normal healthy volunteers underwent four 6 mm biopsies of the flexor surface of both forearms. Biopsy sites were randomly assigned to a control arm (daily bacitracin) or to one of three treatment arms: i) rhPDGF-BB 0.01% gel (Q.D.), ii) rhPDGF-BB (Q.O.D.), iii) rhPDGF-BB (Q.D. × 7 days followed by bacitracin alone daily). The wounds were examined, measured and photographed daily until complete healing was achieved. Adverse events were monitored. Rates of healing and time-to-complete closure were measured. Repeat biopsies of a subset of healing wounds were performed for gene microarray analysis. Results: The forearm biopsy model allowed direct quantitative and qualitative comparisons of acute wound healing outcomes achieved by rhPDGF-BB regimens versus standard care alone. There were no infectious complications. Subject compliance was excellent with 〈 3% of visits missed. Conclusion: The forearm biopsy model has several advantages in the study of acute wounds: it allows for comparison of topical agents in a controlled fashion; studies can be conducted easily with good patient compliance; and the forearm allows for repeat imaging and tissue harvesting for gene profiling during healing. Acknowledgements: Funding from The Angiogenesis Foundation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Science Ltd/Inc.
    Wound repair and regeneration 12 (2004), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Physiological differences between dominant and non-dominant arms may play an important role in wound healing of the upper extremities. The Wound Healing Cooperative Group (WHCG) studied this phenomenon in a human forearm model of acute wound healing. Methods: With informed consent, sixteen normal healthy volunteers underwent four 6 mm biopsies on the flexor surface of both forearms: 2 biopsies on the dominant arm, and 2 on the non-dominant arm. The acute wound sites were then treated with i) rhPDGF-BB 0.01% gel topically at various dosing intervals (Q.D. versus Q.O.D.), ii) rhPDGF-BB alone Q.D. × 7 days followed by bacitracin alone, or iii) bacitracin alone. Time-to-complete healing was measured as the primary endpoint. Results: The average time-to-complete healing for the dominant arm was shorter than the time required to heal the biopsies on the non-dominant arm, irregardless of the treatment applied. Conclusion: In the forearm biopsy model of acute wound healing, arm dominance is an independent variable and must considered in study designs. We postulate that this effect may be due to variation in microvascular perfusion. These results provoke further investigation into the physiological mechanisms underlying increased rate of healing in the dominant extremity. Acknowledgements: Funding from The Angiogenesis Foundation.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc.
    Wound repair and regeneration 13 (2005), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  According to The American Pain Society, pain should be considered a fifth vital sign. Pain is a prominent feature of venous leg ulcerations (VLUs). Sixty-five percent of VLU patients complain of severe pain. In several multicenter clinical trials, Apligraf, a bioengineered living skin construct, has been shown to accelerate healing in venous leg ulcerations. Anecdotal clinical observations suggest that Apligraf treatment is associated with pain relief. A treatment modality which promotes healing and reduces pain would significantly improve the quality of life in patients with VLU.Methods:  VLU patients with pain scores greater than 5/10 on a numerical scale or requiring narcotic analgesia were randomized to receive either Apligraf and compression or compression alone. There was a 3-week “wash-out” period to ensure that pain was not due to other factors such as inadequate compression or infection. Patients were enrolled only after a negative quantitative biopsy. The intensity of pain was self-scored and a quality-of-life questionnaire was completed at each visit. Weekly wound area measurements were obtained with digital planimetry.Results:  Thus far in the enrollment period we have already seen a trend toward a significant reduction in pain in the Apligraf group. This pain relief occurs shortly after application indicating that a mechanism distinct from clinical healing. The Apligraf group also demonstrated acceleration in wound healing as well as a decreased time-to-complete closure.Conclusion:  Interval analysis of this multicenter trial suggests that Apligraf accelerates wound healing and reduces the pain associated with venous leg ulcerations.Acknowledgment:  Unrestricted Educational grant, Organogenesis Inc.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Science Ltd/Inc.
    Wound repair and regeneration 12 (2004), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: More than three quarters of patients with a connective tissue disorder will develop secondary Raynauld’s disease. This more severe form of the Raynauld’s can lead to digital ischemia, tissue loss and may even result in the need for amputation of one or more digits. Cilostazol is a phosphodiesterase inhibitor currently approved for use in vascular disease of the lower extremities. Case History: In August of 2002 a 62 year old female pianist with scleroderma presented to the wound clinic with a two year history of intractable digital pain secondary to ischemic ulcerations of the index, long and ring fingers of the right hand. She suffered from secondary Raynauld’s disease. Prior unsuccessful treatments included warming the hands, calcium channel blockade, anticoagulation, topical xylocaine and narcotic analgesics. In August of 2002 cilostazol was started at 100mg BID. Wound care consisted of serial debridement, moist wound healing and topical rhPDGF. Results: Four weeks into treatment the patient’s narcotic requirement decreased substantially and the fingers had a pink appearance. The ring finger healed after eight weeks. At three months the patient discontinued narcotic pain medication. Nine months into treatment the index finger had healed and she resumed playing the piano. The long finger finally healed one year after she initially presented to the wound clinic. Conclusion: Cilostazol may be an important adjunct in the treatment of secondary Raynauld’s disease particularly when digital ischemia has developed. Acknowledgements: Funding from Otsuka Pharmaceuticals.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc.
    Wound repair and regeneration 13 (2005), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Apligraf, a bioengineered living skin construct, has been shown to accelerate the healing of venous leg and diabetic foot ulcerations. It appears to function as cell-based therapy (e.g., delivering growth factors), rather than as a true graft. Given this mechanism of action, its use could be expanded to areas in which traditional skin grafting is not routinely employed.Methods:  A 64-year-old wheel-chairbound Caucasian male presented to the wound clinic with a grade III left trochanteric pressure ulcer which had been present since 1976. He had been seen by numerous physicians and treated with debridement, topical antimicrobials, negative pressure therapy, growth factors, and a variety of dressings. We spent several months preparing the wound bed: maintaining adequate moisture balance, performing serial debridement, utilizing offloading surfaces and reducing the bacterial burden. His nutritional status was optimized. The wound bed developed a healthy granulating base but failed to close.Results:  A single unit of Apligraf was meshed at a 1:1.5 ratio and applied to the wound. It was fixed in place using a nonstick silicone dressing, foam, and a self-adhesive covering. The dressing was changed weekly in the wound clinic. The initial response was a decrease in wound depth followed by steady epithelialization. Complete closure occurred 17 weeks after grafting. The wound has not recurred.Conclusion:  This single case study suggests that bilayered cell therapy may have application in difficult wounds, such as pressure ulcerations. Further study into the efficacy of Apligraf in pressure ulcerations is ongoing.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Science Ltd/Inc.
    Wound repair and regeneration 12 (2004), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Physiological healing in acute wounds generally occurs by granulation from the wound base and by migration of epithelium from the wound edges toward the center of the wound in a uniform, concentric fashion. The Wound Healing Cooperative Group (WHCG) compared this phenomenon in acute wounds treated with standard care versus acute wounds pharmacologically stimulated with growth factor therapy. Methods: With informed consent, 20 normal healthy volunteers underwent four 6 mm biopsies of the flexor surface of both forearms. The biopsy sites were randomly assigned to a control arm (daily bacitracin) or to one of three treatment arms: i) rhPDGF-BB 0.01% gel Q.D., ii) rhPDGF-BB Q.O.D., iii) daily rhPDGF-BB (Q.D. × 7 days followed by bacitracin alone daily). Wound morphology was carefully examined and photographed daily until complete healing was achieved. Results: There were distinct differences in the morphological pattern of healing seen between control wounds and growth factor-stimulated wounds. Acute wounds treated with bacitracin tended to heal in circumferential fashion, as predicted. Growth factor-stimulated wounds, by contrast, exhibited accentuated angiogenesis (granulation), with non-uniform epithelial islands streaming into the wound. Conclusion: This pilot study suggests that rhPDGF-BB influences acute wound healing by promoting accelerated granulation and epithelialization. Accelerated healing is manifest by different healing morphologies. The biological basis for these differences requires further histological and molecular analyses. Acknowledgements: Funding from The Angiogenesis Foundation.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc.
    Wound repair and regeneration 13 (2005), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Preclinical animal studies with a fetal bovine dermal collagen matrix suggest that fibroblasts quickly populate the material. At the same time there is a rapid ingrowth of new blood vessels. In short, the matrix quickly becomes living tissue. Experience with bioengineered skin constructs and porcine small intestinal submucosal products suggest that the application of a scaffold or matrix may play a role in the healing of venous leg ulcerations in humans.Methods:  A fetal bovine dermal collagen matrix (Primatrix) was applied to patients with long-standing venous leg ulcerations. Histologic examination pre and post application with trichrome staining was employed to differentiate matrix from native collagen. Comparisons between animal and human ulcers were made grossly and histologically.Results:  In all patients there was rapid formation of granulation tissue with a decrease in the depth of the wound. This was followed by epithelialization and wound closure. The stimulatory effect persisted for approximately 1 month after which time a second matrix was applied. In contrast to the animal study the grafts exhibited “take” in only one of our patients. Histologic examination in both animals and humans suggests a stimulation of native collagen production as well as an initial incorporation of the Primatrix into the wound bed.Conclusion:  Primatrix has demonstrated efficacy in preclinical studies and in a series of patients with venous leg ulcerations. The product may function as a scaffold for the ingrowth of cells essential to wound healing. Further investigation in a randomized controlled study setting is recommended.Acknowledgment:  TEI Biosciences
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc.
    Wound repair and regeneration 13 (2005), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  The human forearm biopsy model is employed by the Wound Healing Cooperative Group to evaluate the effect of novel agents on acute wounds. Bismuth Subgallate/Borneal (Suile) is a new product with FDA permission for the treatment of partial thickness wounds. However, there is a growing body of evidence suggesting that Suile may be effective in the treatment of full thickness wounds because of its antimicrobial, hemostatic and antiinflammatory properties.Methods:  In our randomized, investigator-blinded study, 20 normal healthy volunteers underwent two 6 mm full-thickness skin biopsies on the flexor surface of each forearm (two wounds per subject). Biopsy sites were randomly assigned to control (daily bacitracin) or to the treatment arm (daily Suile). The wounds were examined, measured by digital planimetry, and photographed daily until complete healing was achieved. Adverse events and pain levels were monitored. Healing velocity and time-to-complete closure were determined.Results:  The forearm biopsy model allowed direct quantitative and qualitative comparisons of wound healing outcomes achieved by the Suile regimen versus bacitracin alone. Subject compliance was excellent. The conduct of the study was further facilitated by the use of handheld electronic documentation.Conclusion:  The forearm biopsy model has several advantages: It allows for a direct comparison of topical agents in a controlled fashion, studies can be conducted rapidly with good patient compliance and it allows investigators to gain firsthand experience with products prior to embarking on large clinical trials in chronic wounds.Acknowledgments:  Grant from Hedonist Biochemical Technologies Co.
    Type of Medium: Electronic Resource
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