Randomized prospective double-blind trial in healing chronic diabetic foot ulcers. CT-102 activated platelet supernatant, topical versus placebo.

OBJECTIVE: To assess the efficacy of topically applied CT-102 APST for treating diabetic neurotrophic foot ulcers. RESEARCH DESIGN AND METHODS: Thirteen patients entered a randomized, double-blind trial of topically applied CT-102 APST vs. placebo (normal saline) gauze dressings for the treatment of nonhealing diabetic neurotrophic foot ulcers. CT-102 APST (Curative Technologies, Setauket, NY) was prepared from homologous platelets and contained multiple growth factors including PDGF, PDAF, EGF, PF-4, TGF-beta, aFGF, and bFGF. Inclusion criteria for subjects included diabetes, ulcer of > 8 wk duration, peri-wound transcutaneous oxygen tension > 30 mmHg, platelet count > 100,000/mm3, and no wound infection. Wounds were excised before entry and were > 700 mm3 but < 50,000 mm3 in volume, < 100 cm2 in area, and involved subcutaneous tissue. RESULTS: In the CT-102 group, 5 of 7 ulcers were healed (100% epithelialized) by 15 wk, but only 1 of 6 ulcers was healed by 20 wk with placebo (P < 0.05). Average percent reduction in ulcer area at 20 wk was 94% for CT-102 vs. 73% for placebo. Daily reduction in ulcer volume was 73.8 +/- 42.4 mm3/day (mean +/- SE) for CT-102 vs. 21.8 +/- 8.1 mm3/day for placebo (P < 0.05). Daily reduction in ulcer area was 6.2 +/- 1.8 mm2/day for CT-102 vs. 1.8 +/- 0.4 mm2/day for placebo (P < 0.05). CONCLUSIONS: CT-102 significantly accelerated wound closure in diabetic leg ulcers when administered as part of a comprehensive program for the healing of chronic ulcers.

Stimulation of skin fibroblast collagenase production by a cytokine derived from basal cell carcinomas.

Our previous studies of human basal cell carcinomas (BCC) revealed increased skin collagenase in vivo. Immunocytochemically the collagenase was localized to adjacent stroma, not to the tumor cells. When grown in culture, skin fibroblasts derived from tumor stroma showed a 3- to 4-fold increase in collagenase for the first 10-14 mean population doublings, after which collagenase expression reverted to control levels. These studies suggested that tumors stimulated adjacent fibroblasts to produce more collagenase. In the present study we sought direct evidence for epithelial-stromal interaction in this neoplasm. Under dissecting microscopy tumor islands were freed of stroma, homogenized, sonicated, and centrifuged to remove insoluble tissue. Tumor extracts were incubated with monolayer cultures of normal human skin fibroblasts to assess their effect on collagenase synthesis in these target cells. Culturing the fibroblasts for 24 h in the presence of individual BCC extracts resulted in a 1.6- to 3-fold increase in trypsin-activatable collagenase in the culture medium. This was paralleled by an equal increase in immunoreactive protein, suggesting enhanced enzyme synthesis. There was no change in the activity per immunoreactive protein, indicating a catalytically unaltered enzyme. Gel filtration of pooled BCC extracts showed that the stimulatory activity was contained in eluent fractions of Mr approximately 19Kd. These data suggest that BCCs elaborate a macromolecular cytokine that induces collagenase synthesis in skin fibroblasts and emphasize the importance of epithelial-stromal interactions in cutaneous tumor invasion.

Establishment of a human cutaneous T-cell lymphoma in C.B-17 SCID mice.

Investigation into the immunobiology of cutaneous T-cell lymphomas (CTCL) would be facilitated by the development of a suitable experimental system. The recent use of mice with severe combined immune deficiency (SCID) as a vehicle to study the human immune system prompted us to try to establish CTCL in SCID mice. We found that a CD4+ lymphocytic infiltrate characteristic of CTCL was maintained within patient skin grafts in place on natural killer cell depleted SCID mice for the month of observation. CTCL cells were not found outside the human skin graft. This chimeric model using SCID mice and patient lesional skin should provide a useful tool to characterize CTCL/skin microenvironmental interactions and to test new therapeutic approaches.

Cutaneous polyarteritis nodosa. Report of a case associated with Crohn's disease.

A patient had cutaneous polyarteritis nodosa associated with Crohn's disease. Immunopathologic studies disclosed evidence of circulating immune complexes as measured by C1q binding. Immunofluorescent microscopy of lesional skin showed C3 and fibrin deposition. Histamine injection of normal skin and subsequent biopsy specimens and immunofluorescent microscopy showed immune deposits. The patient was treated with cyclophosphamide and prednisone with a good clinical response, but within two years, histiocytic lymphoma developed. There is an association of cutaneous polyarteritis and Crohn's disease, and also, immunosuppressive therapy plays a role in the development of histiocytic lymphoma.

Cancer of the perioral region.

The management of difficult perioral malignancies is often facilitated by an organized, multidisciplinary approach that utilizes the skills of a Mohs micrographic surgeon as well as a head and neck surgeon. This article summarizes such an approach with attention to anatomic considerations, tumor classification, prognosis, and a practical approach to such malignancies. Finally, an approach to reconstruction is presented that emphasizes the usefulness of a Karapandzic flap in large reconstructions of this region.

Wound healing for the dermatologic surgeon.

An understanding of the basic science of cutaneous wound repair is essential to the dermatologic surgeon for the management of the postoperative wound. This review discusses the stages of wound healing and then applies these principles to the preoperative, intraoperative, and postoperative management of the surgical patient.

Basal cell carcinoma and collagenase.

The interaction of connective tissue stroma and epithelial cutaneous cancer is an active area of investigation in dermatology. Studies summarized here explore the role of collagenase in basal cell carcinoma (BCC) invasiveness. Evidence is presented to support the role of a cytokine or cytokines secreted by BCCs that stimulate collagenase production by surrounding stromal fibroblasts. Prospects for further research in this area are proposed.

Small-cell neuroepithelial tumor of skin: a Merkel-cell neoplasm?

Two patients with small-cell undifferentiated neuroepithelial tumors of skin are reported. The histologic and ultrastructural features of this neoplasm are presented. Characteristic membrane-bound, dense-core neurosecretory granules were seen in the cytoplasm of the tumor cells in both cases. The literature is reviewed in regard to the clinical behavior of these lesions and their possible cell of origin. Dermatologists should be aware of these tumors because they may require electron microscopy for accurate diagnosis. The tumors should be treated aggressively to minimize the chance of local recurrence and nodal or visceral metastases.

The treatment of benign sebaceous hyperplasia with the topical application of bichloracetic acid.

Sebaceous hyperplasia is a benign lesion that occurs commonly on the face of older individuals. A variety of treatment options have been described, including oral isotretinoin, electrodesiccation, CO2 laser surgery, cryosurgery, and shave excision with curettage. Problems have been noted with these approaches. These techniques are more complex, less effective, require more time, or are more likely to scar than the procedure we describe. The treatment of sebaceous hyperplasia with bichloracetic acid is described with results presented after treatment of our first 20 patients.

Rhabdomyolysis with cardiac and respiratory involvement.

A case of acute nontraumatic rhabdomyolysis in a heroin addict is described. In addition to respiratory failure, the patient's course was complicated by life-threatening arrhythmias and electrocardiographic changes compatible with primary cardiac involvement. This case suggests that rhabdomyolysis may involve cardiac muscle on rare occasions.

Linear and dermatomal trichoepitheliomas.

A 10-year-old black girl presented with multiple trichoepitheliomas. They appeared at an early age and were grouped on her neck. Later they also involved her face, trunk, and lower extremity in a dermatomal distribution. The lower extremity showed a narrow linear band extending from the ankle to the upper portion of the thigh. To the best of our knowledge, this is the first case of linear and dermatomal trichoepitheliomas. We therefore present this case and review the literature.

The biology of basal cell carcinoma: a review.

Features of basal cell carcinoma are reviewed within the broad categories of growth characteristics, histogenesis, ultrastructural features, biochemical properties, site of origin, metastatic potential, and immunobiology. Biologic features that pertain to host-tumor interactions are emphasized. Perhaps a better understanding of these host-tumor relationships will offer more effective methods of treating and preventing these neoplasms in the future.