Initial Wound Area Research Articles

Determinants and estimation of healing times in diabetic foot ulcers

Aims: To assess the wound size reduction and time course for healing and to establish equations to predict the time course of wound healing in neuropathic, neuroischemic, and ischemic diabetic foot ulcers. Methods: This prospective study evaluates wound healing over at least a 10-week period in 31 Type 1 or Type 2 diabetic patients with plantar foot ulcers. Thirteen consecutive diabetic patients with neuropathic foot ulceration, 10 consecutive diabetic patients with neuroischemic ulceration, and 8 diabetic patients with peripheral occlusive vascular disease were selected for the study. All patients received identical ulcer wound care including use of proper footwear, non-weight-bearing limb support, use of appropriate antibiotics, debridement, tight control of serum glucose levels, and careful monitoring of the ulcer. Ulcer healing was assessed by planimetric measurement of the wound area every second week until wound healing. The time course of wound healing was calculated by the daily wound radius reduction. Results: The wound area (mean±S.E.) in the patients with neuropathic foot ulceration was 61.2±17.1 at the beginning and 3.2±1.5 mm 2 after 70 days ( P=.005). The wound radius decreased by 0.045 mm (95% confidence interval [CI] 0.039–0.055) per day, with most of the wound healing being achieved between the first and seventh week of ulcer care. The average healing time was 77.7 (95% CI 62–93) days. In the neuroischemic group, the initial average wound area was 26.6±7.0 mm 2, and 6.25±1.7 mm 2 after 10 weeks ( P=.007). The wound radius reduction was 0.019 mm/day (95% CI 0.017–0.023) with an average healing time of 123.4 (95% CI 101–145) days. The diabetic patients with peripheral occlusive vascular disease had an average wound size of 32.6±13.1 at the beginning and 23.9±10.7 mm 2 after 70 days of ulcer care ( P=.06). The daily wound radius reduction was 0.0065 mm (95% CI 0.0039–0.0091). Average ulcer duration was 133 (95% CI 116–149) days, but three of eight patients achieved no wound healing. Conclusions: Providing standard care, the time course of wound healing in diabetic foot ulcers is predominantly determined by etiologic factors, and less by wound size. Taking wound etiology and wound radius into account, the expected healing time can reliably be estimated in neuropathic and neuroischemic ulcers.

Enhancement of wound repair with a topically applied nitric oxide‐releasing polymer

Nitric oxide is an important cytotoxic agent for host defense which also regulates gene expression, signal transduction, and vasodilation. In normal wounds, nitric oxide synthesis and metabolism are significantly increased during inflammation and tissue remodeling. However, nitric oxide production is suppressed in wounds where healing is impaired by diabetes or steroid-treatment. Topical delivery of nitric oxide in therapeutic amounts may alleviate this deficiency and thereby enhance wound repair. Consequently, we developed polyethyleneimine cellulose NONOate polymer, a nonsoluble, nontoxic, polymer-based NONOate--one of a new class of compounds that spontaneously release nitric oxide in a controlled fashion in aqueous media. Polyethyleneimine cellulose NONOate polymer was synthesized from polyethyleneimine cellulose to provide extended nitric oxide release with a half-life of 16 hours. Polyethyleneimine cellulose NONOate polymer or a control polymer was applied topically on full-thickness dermal wounds of rats at the time of wounding and days 3, 7, 10, 14, 17, and 21. Nitric oxide delivery was determined indirectly by measuring urinary nitrate. The first two polyethyleneimine cellulose NONOate polymer applications increased urinary nitrate output twofold to fourfold, whereas urinary nitrate output of control rats did not significantly increase. Nitrate output in polyethyleneimine cellulose NONOate polymer-treated rats was elevated compared with controls after each application, although this was attenuated in later applications. Rate of wound closure was measured with computer-based video imaging. Polyethyleneimine cellulose NONOate polymer-treated wounds were significantly smaller (p < 0.05) on days 7, 10, and 17 relative to controls, based on percentage of wound open relative to initial wound area. In a second experiment, telemetry-implanted rats were wounded to detect potential hypotensive effects as a result of polyethyleneimine cellulose NONOate polymer application. Topical polyethyleneimine cellulose NONOate polymer application to wounds showed no prolonged hypotensive effects, in contrast to a soluble NONOate which suppressed systolic blood pressure for over 6 hours. These results show that a nonsoluble, polymeric NONOate can provide topical nitric oxide delivery to wounds in a controlled manner, which may enhance wound healing. Further studies are in progress with other promising NONOate candidates to establish dose-response effects and therapeutic limits of exogenous nitric oxide release in impaired wound models.

Transcutaneous oxygen measurements predict healing of leg wounds with hyperbaric therapy

Twenty-six patients with chronic leg wounds had transcutaneous oxygen measurements taken from the peri-wound area and a chest reference site before undergoing hyperbaric oxygen therapy in order to evaluate the utility of transcutaneous oxygen measurements in predicting the response of wounds to hyperbaric therapy. Wound scores and wound areas were determined before treatment and after 10 hyperbaric exposures. Patients whose wounds averaged a 5% or greater reduction in wound score per treatment were designated "responders." Nine patients' wounds exhibited at least a 5% reduction in wound score per treatment. There were no differences observed between responders and the 17 nonresponders in age, duration of the wound, initial wound area, initial wound score, or in wound or reference transcutaneous oxygen measurements. Responders required significantly fewer treatments to achieve wound closure than did nonresponders. Peri-wound transcutaneous oxygen pressure when the patient was exposed to 2.4 atmospheres absolute correlated directly with the improvement in wound score per treatment (r = 0.64, p = 0.03). An inverse correlation was noted between surface peri-wound transcutaneous oxygen pressure and improvement in wound score per treatment (r = -0.74, p = 0.006). Elevated peri-wound transcutaneous oxygen measurements at 2.4 atmospheres absolute and reduced peri-wound oxygen measurements at 1 atmosphere absolute were associated with a more rapid response to hyperbaric oxygen treatments in patients with chronic leg wounds. The use of these measurements should allow this expensive and time-consuming therapy to be limited to those patients most likely to benefit.

A prospective randomized trial of autologous platelet-derived wound healing factors for treatment of chronic nonhealing wounds: A preliminary report

Previous studies have suggested that topically applied platelet-derived wound healing factors (PDWHF) accelerate wound healing by stimulating angiogenesis, fibroblast proliferation, and collagen synthesis. To assess the ability of platelet factors to facilitate healing of chronic cutaneous ulcers we performed a randomized, prospective, double-blind, placebo-controlled study of topical PDWHF in 18 patients with 26 lower extremity wounds refractory to conventional therapy. Wounds were present for at least 8 weeks (mean, 5.5 ± 4.3 months). They were extensively debrided initially and were measured and photographed at weekly intervals for 12 weeks. Eight patients with nine wounds were treated with placebo solution (controls), and 10 patients with 17 wounds were treated with PDWHF (treatment group). Seventy-eight percent of patients had diabetes mellitus, 72% had occlusive peripheral vascular disease, and 28% had venous disease; distribution of these disorders was equivalent in both groups. Ankle-brachial indexes, which were often spuriously elevated, averaged 0.93 ± 0.54 in controls and 1.04 ± 0.56 in patients treated with PDWHF (p > 0.5). Mean transcutaneous oxygen tension was 37.8 ± 11.9 mm Hg in controls and 37.1 ± 9.1 mm Hg in patients treated with PDWHF. Initial wound area was larger in controls than in the patients treated with PDWHF (28.9 ± 45.2 cm2 vs 13.0 ± 14.4 cm2), but this difference was not statistically significant (p = 0.19). Three (33%) wounds (in two patients) healed in controls, and four (24%) wounds (in three patients) healed in the PDWHF group (p > 0.5). The rate of healing in controls was 1.9 ± 2.7 cm2/week. Wounds in patients treated with PDWHF increased in size during treatment, averaging −4.3 ± 12.2 cm2/week. This preliminary study suggests that treatment of chronic wounds with autologous PDWHF provides no additional benefit over traditional therapy.

Le benzoyl peroxyde dans le traitement des ulcères de jambe

40 leg ulcers were treated for 6 weeks by application twice a day of a 20% benzoyl peroxide lotion. Each ulcer was regularly measured and its bacterial flora was determined. Therapeutic results were very satisfactory: the average healing rate of the ulcers was 62.8% of the initial wound area after 4 weeks of treatment and 76.5% after 6 weeks of treatment. The bacterial flora of the ulcers changed during treatments, streptococci and staphylococci disappeared. Pseudomonas aeruginosa became abundant.