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Notes: About 600,000 people in the United States are estimated to be affected by venous ulcers. The cornerstone of care of chronic venous ulcers involves the application of compression bandages. Other therapies include treatment of associated infection, treatment for edema and inflammation, and debridement when necessary. Repifermin, a recombinant human KGF-2 (fibroblast growth factor-10), exerts a proliferative effect on epithelial cells, in vitro and in vivo, and has been shown to accelerate wound healing in several experimental animal models. A randomized, double-blind, parallel-group, placebo-controlled, multicenter study was conducted to evaluate the safety and efficacy of topical repifermin treatment, for 12 weeks, in the healing of chronic venous ulcers in 94 patients. Repifermin was shown to accelerate wound healing, with significantly more patients achieving 75% wound closure with repifermin than with placebo. The treatment effect appeared more marked for a subgroup of patients with initial wound areas ≤ 15 cm2 and wound ages of ≤ 18 months. A longer duration of treatment (e.g., 26 weeks) may allow better differentiation of the benefit of repifermin compared with placebo, particularly with respect to complete wound closure. The safety assessment showed that repifermin was well tolerated.

Notes: A previously healthy 71-year-old Caucasian woman presented with an ulcer on her left leg. She had a 5-month history of bilateral, indurated erythematous, and had purplish nodules and plaques on both lower extremities. One of the plaques on the right leg had ulcerated and healed spontaneously. The present ulceration began as a small opening at an incisional biopsy site. Later, she developed two adjacent ulcers that coalesced into a larger ulcer. She was not taking any medication, and there was no history of exposure to tuberculosis. Examination of the right leg demonstrated two hyperpigmented, indurated plaques, one on the calf and one over the medial malleolus. On the left posterior calf there was another hyperpigmented, indurated plaque with a central area of ulceration measuring 9 × 2 cm. The ulcer bed had a mixture of fibrinous adherent tissue and granulation tissue. (〈link href="#f15801"〉Fig. 1) There was no peripheral edema, varicose veins, nor signs of peripheral neuropathy. Peripheral pulses and capillary refilling were within normal limits. The ankle brachial index was greater than 1.0 bilaterally. Biopsy of a subcutaneous nodule revealed a superficial and deep perivascular lymphocytic infiltrate with an admixture of neutrophils and numerous extravasated red blood cells. Mixed septal and lobular panniculitis consisting of an inflammatory infiltrate of histiocytes, giant cells, and neutrophils was observed. Focal neutrophilic microabscesses in the deep dermis and fibrinoid necrosis of small blood vessels were present in the deep dermis and subcutaneous tissue (〈link href="#f15802 #f15803"〉Figs 2 and 3). A smear was negative for acid fast bacilli.〈figure xml:id="f15801"〉1〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD1580:IJD_1580_f1"/〉A hyperpigmented, indurated plaque with a central area of ulceration measuring 9 × 2 cm on the left posterior calf. The ulcer bed has a mixture of fibrinous adherent tissue and granulation tissue〈figure xml:id="f15802"〉2〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD1580:IJD_1580_f2"/〉A scanning magnification〈figure xml:id="f15803"〉3〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD1580:IJD_1580_f3"/〉Mixed septal and lobular panniculitis consisting of an inflammatory infiltrate of histiocytes, giant cells, and neutrophils. Focal neutrophilic microabscesses in the deep dermis and fibrinoid necrosis of small blood vessels in the deep dermis and subcutaneous tissueA diagnosis of nodular vasculitis was made. A complete blood count with differential and platelets was within normal limits, tuberculin testing was negative twice, and antineutrophil cytoplasmic antibodies (p-ANCA, c-ANCA) were also negative. Fungal, mycobacterial and bacterial cultures were negative. Chest X-rays were normal.The patient received supersaturated potassium iodide (SSKI) 15 drops per day with good response. With rapid tapering of SSKI, the ulcerations on the lower legs reappeared. Therapy was reinstituted with a more gradual taper. Two years after the initial diagnosis of nodular vasculitis the patient presented with new complaints of increased urinary frequency, increased abdominal girth, and weight gain. The patient was found to be borderline anemic, and a computer tomography scan revealed ascites, a normal liver, a normal uterus, and a soft tissue density in the region of the cecum. After an exploratory laparotomy she was found to have a moderately differentiated mucinous adenocarcinoma of the colon with metastases to periaortic lymph nodes, abdominal wall, and both ovaries. She is currently receiving adjuvant chemotherapy for stage IV colon carcinoma. Only one lesion of nodular vasculitis has remained active, and the patient is continuing treatment with SSKI at a low dose.

Notes: Background:  Ultraviolet (UV) irradiation to the skin causes apoptosis of keratinocytes. Melanocytes are more resistant to UV-induced apoptosis, due, in part, to high levels of antiapoptotic proteins such as Bcl-2. In vitro studies have shown that nerve growth factor (NGF), a neurotrophic polypeptide, is produced by keratinocytes and exerts a protective role for melanocytes by upregulating Bcl-2. The purpose of this study was to determine NGF and Bcl-2 modulations in UV-irradiated human skin.Methods:  Nine volunteers were irradiated with two minimal erythema doses using solar-simulated UV irradiation. Seventy-two hours post irradiation, skin biopsies were obtained from irradiated and sun-protected skin. The skin specimens were stained with anti-tyrosinase-related protein-1 monoclonal antibody IgG2a (Mel-5), anti-Bcl-2 (monoclonal antibody IgG-kappa), and with anti-NGF (polyclonal antibody IgG).Results:  NGF staining was identified within the cytoplasm of epidermal melanocytes, similar to the staining observed for TRP-1 and Bcl-2. While no significant difference in the number of TRP-1- and Bcl-2-positive melanocytes was observed between irradiated and non-irradiated skin within 72 h, the number of NGF-positive melanocytes decreased significantly, 72 h after UV irradiation (p 〈 0.024). NGF was also identified within keratinocytes, and while non-irradiated skin exhibited cytoplasmic NGF staining throughout the epidermis, NGF staining was reduced in the lower epidermal layers after UV irradiation.Conclusions:  This is the first in vivo study showing NGF to be present in melanocytes, as well as showing modulations of NGF and Bcl-2 in melanocytes, following solar-simulated UV irradiation.