Linda G. Phillips

Platelet-derived growth factor BB for the treatment of chronic pressure ulcers

A randomised, phase I/II, double-blind, placebo-controlled study was designed to assess the effect of topically applied recombinant human BB homodimeric platelet-derived growth factor (rPDGF-BB) on healing of chronic pressure ulcers. Twenty patients were randomly allocated daily treatment for 28 days with 1, 10, or 100 micrograms/ml rPDGF-BB (0.01, 0.1, or 1.0 micrograms per cm2 ulcer area) or placebo. Patients treated with 100 micrograms/ml rPDGF-BB showed a greater healing response than the placebo group, but the lower doses had little effect. After 28 days, ulcers treated with 100 micrograms/ml rPDGF-BB were smaller than those treated with placebo (mean [SE] volume 6.4 [4.0] vs 21.8 [5.6]% of day 0 volume). There were no toxic effects. These preliminary findings suggest that rPDGF-BB is a potent wound-healing agent in soft tissue.

Guidelines for the treatment of pressure ulcers

1. Co-chaired this panel 2. University of Washington, Seattle, WA 3. University of Texas Medical Branch Galveston, Galveston, TX 4. Sinai Hospital, Baltimore, MD 5. Johns Hopkins Medical Institutions, Baltimore, MD 6. University of Southern Denmark, Odense University Hospital, Odense, Denmark 7. University of South Florida, Tampa, FL 8. University of Virginia Health System, Charlottesville, VA 9. St. Louis Medical Center, St. Louis, MO, and 10. University of San Francisco, San Francisco, CA

Recombinant human platelet-derived growth factor-BB for the treatment of chronic pressure ulcers.

A randomized phase I/II double-blind, placebo-controlled study was designed to evaluate 1, 10, and 100 µg/ml (0.01, 0.1, and 1.0 µg/cm2) recombinant human BB homodimeric platelet-derived growth factor (rPDGF-BB) applied topically to chronic pressure ulcers for 28 days. Twenty patients were enrolled and completed the trial. No toxicities were associated with rPDGF-BB treatment. Patients treated with 100 µg/ml of rPDGF-BB had a pronounced healing response compared with placebo-treated patients. By day 29, ulcers treated with 100 µg/ml of rPDGF-BB were smaller in remaining size compared with those of placebo-treated patients when the following specific parameters were measured: percentage of initial depth (14.1 ± 7.4 vs. 34.9 ± 6.7) and percentage of initial volume (6.4 ± 4.0 vs. 21.8 ± 5.6). Histological analyses of biopsies revealed active wound healing processes in all groups with no disruption in the normal healing sequence in rPDGF-BB-treated wounds. The results of this small, descriptive study suggest rPDGF-BB is a potent vulnerary agent for accelerating soft-tissue repair, warranting further study.

Creep vs. stretch: a review of the viscoelastic properties of skin.

Possessing viscous and elastic rheological properties, skin is viscoelastic. Mechanical creep, defined as the elongation of skin with a constant load over time beyond intrinsic extensibility, has been described as the vehicle harnessed for wound closure with presuturing, intraoperative tissue expansion, skin-stretching devices, and skin retraction with undermining. Resulting from the generation of new tissue due to a chronic stretching force, biological creep plays a role in conventional tissue expansion.

Umbilical reconstruction after repair of omphalocele and gastroschisis.

This article presents our technique of umbilical reconstruction after the repair of omphalocele and gastroschisis. We have treated 8 patients with an average follow-up period of 13 months (range, 6 approximately 24 months). No major complications have occurred; minor complications have included delayed wound healing, decreased umbilical depth, and hematoma. Our procedure is especially useful for patients who have a midline abdominal scar and relatively intact bilateral rectus abdominis muscles. Most of the patients and their parents have been satisfied with the results of umbilical reconstruction.

Guidelines for the prevention of pressure ulcers

The Wound Healing Society is a professional organization of physicians, nurses, physical therapists, basic scientists, clinical researchers, and industrial researchers dedicated to assuring that every patient receives optimal wound care. Its mission is to advance the science and practice of wound healing. To that end, the following comprehensive, evidence- and consensus-based guidelines were developed to address the Prevention of Pressure Ulcers. The guidelines are presented in generic terms; the details of specific tests, therapies, and procedures are the discretion of an interdisciplinary team of health care professionals who establish, implement, and evaluate policies and procedures directed at the prevention of pressure ulcers.

Tamoxifen Downregulates Tgf-β Production in Keloid Fibroblasts

Keloids occur only in humans and are characterized by fibroblast overproduction of collagen types I and III. Keloid fibroblasts have been shown to make elevated levels of transforming growth factor beta (TGF-β), a growth factor known to promote extracellular matrix production and fibrosis. Thus, the pathophysiology underlying keloid formation may be driven by the biological activity of TGF-β. Tamoxifen, a synthetic, nonsteroidal antiestrogen has been shown to inhibit keloid fibroblast proliferation and decrease collagen production. The purpose of this study was to determine if a mechanism by which tamoxifen decreases keloid collagen production is through a downregulation of TGF-β. Through a luciferase TGF-β bioassay we found that 4 μM of tamoxifen generated a 49% reduction in total TGF-β activity and 8 μM generated an 85% reduction compared with controls. Thus we propose that one of the mechanisms by which tamoxifen decreases keloid fibroblast collagen synthesis is by decreasing TGF-β production.

Impairments to wound healing

Impaired wound healing is a complication faced by all physicians, regardless of their field of practice. Plastic surgeons are frequently called on to help treat patients who fail to heal properly. Therefore, plastic surgeons must be well versed in the intrinsic and extrinsic factors that can impair wound healing, such as nutrition, drugs, radiation, smoking, and hypoxia. Only by limiting detrimental factors can wound healing progress in a beneficial fashion.

A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers

Chronic wounds such as venous stasis ulcers have become a socioeconomic problem. Even with successful initial management, the recurrence rate approaches 70%. With the advent of new wound healing agents, nonoperative attempts to heal these wounds appear indicated. This study reports a prospective randomized evaluator-blinded trial comparing two potential wound healing agents to an inert vehicle placebo. Eighty-six evaluable patients completed the trial. Silver sulfadiazine 1% in a cream proved to statistically reduce the ulcer size compared with a biologically active tripeptide copper complex 0.4% cream formulation or the placebo. There was no difference between the latter two treatments. Silver sulfadiazine has been shown to allow keratinocyte replication and to have antiinflammatory properties. In this trial its antibacterial action was not used since all ulcers had comparable bacterial levels (less than or equal to 10(5)/gm of tissue) before treatment. These results suggest that the silver sulfadiazine cream used in this study may facilitate healing in wounds healing largely by the process of epithelialization.

MOC-PSSM CME article: Pressure sores.

Learning Objectives: After studying this article, the participant should be able to: 1. Understand and describe the physiology of pressure sore development. 2. Understand and describe population risk factors. 3. Understand and describe examination and classification. 4. Understand and describe common surgical treatment algorithms. 5. Understand and describe strategies for prevention and postoperative recurrence. Summary: Pressure sores are ischemic damage to soft tissues resulting from unrelieved pressure, usually over a bony prominence. In both acute and chronic circumstances, a careful, structured multidisciplinary strategy is required from initial diagnosis to resolution. Mechanical issues, such as the relief of pressure, adequate surgical debridement, and flap coverage, are of little value if educational, nutritional, social, and resource-based issues are not in place. The authors discuss a range of topics, including etiology, physiology, classification, operative options, and strategies to prevent recurrence. The Maintenance of Certification module series is designed to help the clinician structure his or her study in specific areas appropriate to his or her clinical practice. This article is prepared to accompany practice-based assessment of preoperative assessment, anesthesia, surgical treatment plan, perioperative management, and outcomes. In this format, the clinician is invited to compare his or her methods of patient assessment and treatment, outcomes, and complications with authoritative, information-based references. This information base is then used for self-assessment and benchmarking in parts II and IV of the Maintenance of Certification process of the American Board of Plastic Surgery. This article is not intended to be an exhaustive treatise on the subject. Rather, it is designed to serve as a reference point for further in-depth study by review of the reference articles presented.