John C. Murray

A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation

BACKGROUND Skin cancer and photoaging changes result from ultraviolet (UV)-induced oxidative stress. Topical antioxidants may protect skin from these effects. OBJECTIVE We sought to determine whether a stable topical formulation of 15% L-ascorbic acid, 1% alpha-tocopherol, and 0.5% ferulic acid (CEFer) could protect human skin in vivo from substantial amounts of solar-simulated UV radiation. METHODS CEFer and its vehicle were applied to separate patches of normal-appearing human skin for 4 days. Each patch was irradiated with solar-simulated UV, 2 to 10 minimal erythema doses, at 2-minimal erythema dose intervals. One day later, skin was evaluated for erythema and sunburn cells, and immunohistochemically for thymine dimers and p53. UV-induced cytokine formation, including interleukin (IL)-1alpha, IL-6, IL-8, and IL-10, and tumor necrosis factor-alpha, were evaluated by real-time polymerase chain reaction. RESULTS CEFer provided significant and meaningful photoprotection for skin by all methods of evaluation. LIMITATIONS The number of patients evaluated was relatively small. CONCLUSION CEFer provided substantial UV photoprotection for skin. It is particularly effective for reducing thymine dimer mutations known to be associated with skin cancer. Its mechanism of action is different from sunscreens and would be expected to supplement the sun protection provided by sunscreens.

Keloids and hypertrophic scars.

Abstract Keloids and hypertrophic scars are fibrous growths that result from an abnormal connective tissue response. Since both share certain similarities and the distinction between the two may be blurred in some cases, both will be discussed in this chapter. These fibrous tumors follow trauma, inflammation, or burns and appear as firm, variably pruritic, or tender growths near the injury site. They usually occur in patients 10 to 30 years of age and are located commonly on upper trunk, shoulders, earlobes, and face. Although the etiology is unknown, these fibrous growths demonstrate increased cellularity and metabolic activity. Many treatments have been variably successful, including intralesional corticosteroid injection, surgery, pressure devices, radiation, cryotherapy, and systemic chemotherapy, used alone and in combination.

Keloids treated with excision followed by radiation therapy

BACKGROUND In the treatment of keloids surgical excision followed by radiation therapy provides the highest reported control rates of 72% to 92%. OBJECTIVE We evaluated the effectiveness of excision followed by radiation therapy in the treatment of keloids and compared the efficacy of orthovoltage and electron beam radiation. METHODS One hundred twenty-six keloids were treated with radiation therapy after surgical excision. Median follow-up period was 12 years. Recurrence rate, side effects, and effectiveness of therapy were assessed. Data were analyzed with multivariate analysis for significant objective and subjective factors. RESULTS Higher posttreatment recurrence rates were noted with keloids forming at infected sites and in patients with a family history. No increased likelihood of recurrence was noted with respect to patient age, sex, or ethnicity; keloid size or location; individual keloid history; or prior therapy or radiation type used. CONCLUSION Excision followed by radiation therapy is a useful and effective method of keloid eradication, particularly in cases in which lesions are disfiguring or refractory. Electron beam radiation offers no advantage over orthovoltage as a treatment.

Modern approaches to photoprotection.

UV light reacts with skin to produce undesirable changes, including photoaging and skin cancer. Sunscreen strategies are useful for protection against UV-B and short-wave UV-A, but complete protection against long-wave UV-A has not been achieved. Because UV-A is especially efficient at generating reactive oxygen species, it is being recognized increasingly as an important cause of photoaging and skin cancer.

Acquired cutaneous smooth muscle hamartoma

A 35-year-old white man had an indurated, indistinct plaque on the anterior aspect of the neck for 10 years. Results of biopsy specimens showed an excess of smooth muscle bundles scattered throughout the dermis. Unlike previously reported cases of acquired smooth muscle hamartomas, it did not occur in association with a Becker nevus.

Bullous pemphigoid. Occurrence in a patient with mycosis fungoides receiving PUVA and topical nitrogen mustard therapy.

Abstract: A 57‐year‐old woman with mycosis fungoides developed blisters within cutaneous plaques while receiving PUVA therapy and topical nitrogen mustard. Direct and indirect immunofluorescence studies showed the findings of bullous pemphigoid. Her bullous disease was controlled after cessation of these therapies and institution of prednisone and methotrexate. During the 5 months following completion of a course of electron‐beam therapy, she has been free of the cutaneous manifestations of both diseases. Previous instances of PUVA‐related pemphigoid have occurred in psoriatics. The role of ultraviolet light in the induction of pemphigoid is discussed, particularly with regard to its possible interaction with the altered skin of psoriasis or mycosis fungoides. Some of the rare cases of bullous mycosis fungoides might actually have represented ultraviolet‐unmasked bullous pemphigoid.

In vitro inhibition of chick embryo lysyl hydroxylase by homogentisic acid. A proposed connective tissue defect in alkaptonuria.

Homogentisic acid inhibits the in vitro activity of chick embryo lysyl hydroxylase, a microsomal enzyme which catalyzes the transformation of certain lysyl residues in collagen to hydroxylysine. Chick embryo lysyl hydroxylase activity was measured as specific tritium release as tritium water from a [4,5-(3)H]lysine-labeled unhydroxylated collagen substrate prepared from chick calvaria. Kinetic studies revealed a linear, noncompetitive type of inhibition with respect to collagen substrate with a Ki of 120-180 muM. The inhibition by homogentisic acid was reversible in that enzyme activity could be restored after dialysis of preincubated mixtures of homogentisic acid with enzyme or substrate. The inhibition by homogentisic acid was competitive with respect to ascorbic acid, and the addition of reducing agents, such as ascorbic acid or 1,4-dithiothreitol, protected lysyl hydroxylase activity from homogentisic acid inhibition.In organ cultures of embryonic chick calvaria, biosynthesis of hydroxylysine-derived intermolecular collagen cross-links was inhibited in a dose-dependent manner by 0.5-5 mM homogentisic acid. Because homogentisic acid inhibits the formation of hydroxylysine in a cell-free assay and in organ cultures, this compound must pass into the cells of calvaria to inhibit intracellular hydroxylysine formation and subsequently to diminish the reducible intermolecular cross-links of the newly synthesized collagen. We propose that the inhibition of lysyl hydroxylase and the resulting hydroxylsine-deficient, structurally modified collagen may be clinically significant in the defective connective tissue found in alkaptonuric patients.

Cutaneous infection caused by Curvularia pallescens: A case report and review of the spectrum of disease

A 75-year-old woman being treated with prednisone and methotrexate had a 5.5 x 2.2 cm ulcer on the leg. A biopsy specimen revealed suppurative, granulomatous dermal inflammation with necrotic areas of septate, branching hyphae containing brown pigment. Cultures grew Curvularia pallescens. Oral ketoconazole therapy was started and the lesion was excised. The site healed after multiple excisions and grafts, and ketoconazole therapy was stopped after 7 months. This is the first reported case of invasive cutaneous infection by C. pallescens.

Treatment of Mycobacterium haemophilum infection with an antibiotic regimen including clarithromycin

A patient with rheumatoid arthritis developed ulcerated nodules predominantly on his legs. Skin biopsy and culture demonstrated rheumatoid vasculitis and infection with Mycobacterium haemophilum. Improvement was not seen until clarithromycin was added to his treatment regimen.

Generalized papular xanthomatosis in mycosis fungoides

Xanthomas can occur in association with underlying lymphoproliferative disease, or they can result from lipid deposition in damaged or altered skin. We report a case of generalized papular xanthomas that developed in a patient with Sézary syndrome. The xanthomas were composed of foamy histiocytes that were shown by immunoperoxidase staining to be of the monocyte/macrophage lineage. Electron microscopic studies revealed lipid vacuoles, lysosomes, and myelin figures but no Birbeck granules, features that are consistent with a non-X histiocytosis. Generalized papular xanthomatosis has not been previously described in a patient with cutaneous T-cell lymphoma.