Homocysteine– A Stealth Mediator of Impaired Wound Healing: A Preliminary Study
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The dermal substitute responder was a 49-year-old woman with type II diabetes (HgbA1C 8.8%) and a history of rheumatoid arthritis, coronary artery disease, a plantar diabetic neuropathic ulcer, and diabetic retinopathy (Table 1, Patient #2). This patient was observed with a normal serum Hcy at the completion of the study. The baseline wound fluid NOx of the plantar neuropathic ulcer was 12.0 mmol/L, and the baseline wound area was 3.8 cm2. Following 2 weeks of dermal substitute treatment, wound fluid NOx had increased maximally to 18 mmol/L, which correlated with a 49% reduction in the area of the neuropathic ulcer. Following the second week of treatment, wound fluid NOx levels decreased along with wound area until the end of the eighth week of treatment when the wound had healed completely (Figure 1). All monitored responder patients displayed a similar pattern of maximal wound fluid NOx elevation at 2 weeks following dermal substitute application. These increases ranged from 130% to 150% above baseline values for wound fluid NOx.
The dermal substitute non-responder was a 79-year-old man with type II diabetes (HgbA1C 6.8%) and a history of hypertension, coronary artery disease, spinal stenosis, status/post left femoral-popliteal bypass, and bilateral medial ankle venous stasis ulcerations (Table 1, Patient #5). This patient had an untreated, elevated serum Hcy of 14.9 mmol/L measured at the end of the study. The baseline wound fluid NOx (right ankle sample only) was 1.47 mmol/L. The initial area of the right ankle ulcer was 4.4 cm2; the initial area of the left ankle ulcer was 1.1 cm2 (Figure 2). Wound fluid NOx increased gradually following dermal substitute application and was maximally elevated at 4 weeks (2.6 mmol/L). During this period, the right ankle ulcer area was reduced by more than 60%; however, the left ankle ulcer area during this same time increased by about 50% (2.2 cm2). By the end of the eighth week of dermal substitute treatment, the right ankle ulcer area was unchanged from the area at 4 weeks; however, the left ankle ulcer area during the last 4 weeks of treatment declined and had returned to near baseline value by the end of the eighth week of treatment. The wound fluid NOx levels during the last 4 weeks of dermal substitute treatment declined and had returned to near baseline values (1.5 mmol/L) by the end of the eighth week of treatment.
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