Homocysteine– A Stealth Mediator of Impaired Wound Healing: A Preliminary Study
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Following dermal substitute therapy, all 12 patients receiving treatment were classified as either “responders” or “non-responders” to the 8-week treatment (Table 1). Demographic parameters for study patient comparisons for wound healing included the initial wound area prior to treatment (baseline ulcer area), the wound area following 2 weeks of dermal substitute therapy (ulcer area at 2 weeks), and the corresponding percentage reduction in wound area for that patient (% reduction ulcer area) (Table 1). Homocysteine determinations were recorded following the completion of treatment and were listed as either normal or elevated according to the cardiovascular parameters previously outlined (Table 2). The number of dermal substitute patients experiencing complete wound closure within 12 weeks of the completion of dermal substitute treatment was also recorded (Table 2). Patients responding to dermal substitute were observed with early wound contraction, robust granulation tissue formation, epidermal migration, and re-epithelization of the wound. Patients not responding to dermal substitute treatment were generally observed with a decreased rate of wound contraction, poor granulation tissue formation, and poor clinical evidence of epidermal migration or re-epithelization. For the entire group of 12 patients, 6 were classified as responders and the remaining 6 were classified as non-responders (Tables 1 and 2).
There were no significant differences between the baseline wound areas of responding and non-responding patients (Table 2). However, responding patients demonstrated a significantly greater rate of wound area reduction at 2 weeks as compared to the non-responding patients. All responding patients were observed with normal serum homocysteine levels, while 83% (5/6) of the non-responding patients were observed with elevated serum homocysteine levels. In the responder group, 67% of the patients displayed complete healing of their wounds within 12 weeks of the completion of dermal substitute treatments. None of the patients in the non-responder group were observed with wound closure during this same period. Mean wound fluid NOx determinations for the patients sampled from each group were obtained for the baseline measurement prior to dermal substitute therapy (Table 2). Prior to dermal substitute applications (baseline values), the mean wound fluid NOx value in micromoles (mmol/L ± SE) for the responders group was significantly elevated at 12.98 (± 1.73) as compared to the mean wound fluid NOx value of the non-responders group at 3.50 (± 1.13).
Mean wound fluid NOx value for the responder group was not significantly different from the mean wound fluid NOx (13.9 ± 2.3 mmol/L; n = 13) for lower-extremity ulcers with normal healing responses and normal serum Hcy at the authors’ wound center.19 However, the non-responder mean wound fluid NOx value is significantly lower than the mean wound fluid NOx value associated with normal wound healing and normal serum Hcy values.
Wound fluid NOx and wound area were correlated following dermal substitute treatment for lower-extremity ulcers for a responding and non-responding diabetic lower-extremity ulcer patient in Figures 1 and 2, respectively.
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