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Biomedical subjects

E G Thorne

Publications and source records attributed to E G Thorne.

At least 19 recordsLinked to original sources

Tretinoin emollient cream: a new therapy for photodamaged skin.

BACKGROUND: Tretinoin administered topically in 0.1% concentration has been shown to improve the wrinkling and irregular pigmentation of photoaged skin. OBJECTIVE: The purpose of this study was to assess the safety and efficacy of various concentrations of tretinoin in a new emollient cream base in the treatment of photoaged skin. METHODS: Three concentrations of tretinoin (0.05%, 0.01%, and 0.001%) in a new emollient cream formulation were compared with vehicle in a 24-week, double-blind, randomized, multicenter study of 296 subjects with photodamaged facial skin. RESULTS: Tretinoin emollient cream 0.05% gave a significantly better global response to therapy than vehicle (p less than 0.001), with 68% of subjects exhibiting improvement at the end of therapy, compared with 43% of subjects in the vehicle group. An excellent or good response was found in 26% of subjects treated with tretinoin emollient cream 0.05% versus 11% of vehicle-treated subjects. Fine wrinkling, mottled hyperpigmentation, and roughness were more improved in subjects who received tretinoin emollient cream 0.05% than in vehicle-treated subjects (p less than 0.05). No significant difference was found between vehicle and tretinoin emollient cream 0.01% or 0.001%. Histologic examination showed increases in epidermal and granular layer thickness, decreased melanin content and compaction of the stratum corneum after therapy with tretinoin emollient cream 0.05% or 0.01%. Mild to moderate skin reactions, such as erythema, peeling, and burning, were the most common side effects and, although most prevalent in the group using the 0.05% concentration, generally did not limit tretinoin use. CONCLUSION: Tretinoin emollient cream 0.05% appears to be safe and effective in the treatment of photodamaged skin.

Administration, Topical

Long-term clinical experience with a topical retinoid.

Topical tretinoin is a well-established treatment for acne, with a low incidence of reported adverse effects, most of which are local skin reactions. The retinoid has limited absorption through the skin, so that even with repeated applications plasma concentrations do not exceed normal endogenous levels. In mice, lifetime treatment with topical tretinoin improved skin texture and did not have any tumorigenic effects. Data from multicentre clinical trials have shown that 0.05% tretinoin emollient cream reduced fine wrinkling, surface roughness and mottled hyperpigmentation caused by photodamage. Improvement of these clinical signs was maintained after 12 months of daily tretinoin therapy, and regressed slowly after cessation of therapy. However, maintenance of the visible effects of topical tretinoin was reported after continued therapy with once or three times weekly applications of tretinoin emollient cream. Data from multicentre studies suggested that 0.1% tretinoin cream has a potential role in the treatment of solar keratoses. It is concluded that the application of tretinoin to photodamaged skin used in conjunction with sunscreens and judicious sun exposure is an effective regimen to treat the damaging cutaneous effects of chronic sun exposure.

Administration, Topical

Lifetime topical application of tretinoin to hairless mice.

The discovery that topical tretinoin can reverse some of the effects of photodamage may lead to its chronic application. Examination of long-term effects was of interest. Three groups of hairless mice (age 6-8 weeks) were treated dorsally with 1) tretinoin (0.025%), 2) cream vehicle, 3) sham treatment. Applications were 3 times weekly and continued for up to 2 years until all mice were sacrificed or had died. Biweekly examinations showed no sign of retinoid toxicity, with growth and longevity similar in all groups. Tretinoin-treated skin was smooth and pink, resembling that of younger mice. Controls had yellowed, irregularly thickened skin. Histologically, tretinoin-treated skin had a hyperplastic epidermis consisting of plump, cytologically normal cells. Control skin had 3-4 compressed cell layers. Foci of new normally staining collagen were present in the subepidermal dermis of tretinoin-treated skin; fibroblasts were large and abundant in these areas. These foci were absent in controls. Mice treated with tretinoin also appeared to have increased amounts of elastic fibers and glycosaminoglycans.

Administration, Cutaneous

Skin replica analysis of photodamaged skin after therapy with tretinoin emollient cream.

Computerized image analysis of silicone replicas, a reproducible, objective technique for measuring skin topography, was used in addition to clinical measures in two multicenter, double-blind, randomized, controlled studies of tretinoin emollient cream, a new formulation for treating photodamaged skin. Previously, the skin replica technique had been successfully used in a pilot study of tretinoin 0.05% cream by one investigator. In the present studies, subjects treated for 24 weeks with tretinoin emollient 0.05% cream consistently showed more improvement in skin topography than did vehicle-treated patients. A 0.01% concentration of tretinoin emollient cream also improved skin topography to a greater extent than the vehicle, while the lowest concentration tested (0.001%) showed little difference from vehicle. These results, reflecting a smoothening of the skin surface in tretinoin emollient cream-treated subjects, were consistent with clinical data showing greater improvement in fine wrinkling and roughness after tretinoin emollient cream therapy than after vehicle therapy. Findings from these multicenter studies confirm the value of the skin replica technique and help establish the efficacy of tretinoin emollient 0.05% cream for photodamaged skin.

Adult

Topical tretinoin for treatment of photodamaged skin. A multicenter study.

The clinical and histologic effects of a new emollient cream formulation of topical tretinoin at concentrations of 0.05% and 0.01% were examined in 251 subjects with mild to moderate photodamaged facial skin in a randomized, double-blind, vehicle-controlled, multicenter study. Seventy-nine percent of the subjects who received 0.05% tretinoin for 24 weeks showed overall improvement in photodamaged skin compared with improvement in 48% of the vehicle-treated control subjects. Significant reductions were found in fine wrinkling, mottled hyperpigmentation, roughness, and laxity after 0.05% tretinoin therapy when compared with controls. In addition, histologic changes of increased epidermal thickness, decreased melanin content, and stratum corneum compaction provide independent evidence supporting clinical improvement. Side effects of erythema, peeling, and stinging were usually mild and well tolerated.

Administration, Cutaneous

Effects of tretinoin on photodamaged skin. A histologic study.

The histologic effects of topical tretinoin therapy on photodamaged facial skin were investigated in two 24-week, double-blind, randomized, vehicle-controlled studies involving 533 subjects at eight US centers. Three concentrations of tretinoin (0.05%, 0.01%, and 0.001%) in a new emollient cream were studied. Pretherapy and posttherapy biopsy specimens from the periorbital (crow's foot) area were examined by conventional light microscopy and computerized image analysis. Four significant dose-dependent differences from vehicle were found in the tretinoin groups: increased epidermal thickness, increased granular layer thickness, decreased melanin content, and stratum corneum compaction. There was no significant difference between 0.001% tretinoin and the vehicle, and no obvious dermal changes were detected in any group. The four epidermal changes in tretinoin-treated skin establish the biologic activity of the new emollient cream formulation and may partially account for the clinical improvements in photodamage observed in the same group of subjects.

Administration, Cutaneous

Topical tretinoin research: an historical perspective.

The topical tretinoin epoch began almost 30 years ago in the laboratories of Stüttgen where he first recognized that a vitamin A derivative, tretinoin, had the potential to be a truly significant form of dermatological therapy. His early clinical trials in a variety of skin disorders provided the first indication of topical activity for the retinoids. Kligman evaluated further the utility of topical tretinoin; focusing his attention on acne. Through these initial studies, topical tretinoin became a fundamental treatment modality for acne. Soon after topical tretinoin was made available, elderly patients using it to treat acne noted a general improvement in the quality of their skin. Kligman began open clinical trials to investigate the effects of topical tretinoin on treatment of photodamaged skin. Positive findings from these trials led to double-blind, vehicle-controlled pilot studies which supported the concept that topical tretinoin could improve the fine wrinkling, mottled hyperpigmentation and tactile roughness which are characteristic of photodamaged skin. These results were verified in two large double-blind, multicentre studies of approximately 700 patients that used not only clinical and patient evaluations but also biopsies and skin surface replicas.

Administration, Topical

Treatment of photodamaged facial skin with topical tretinoin.

A 6-month, randomized, double-blind, vehicle-controlled study was conducted with 0.05% tretinoin cream once daily in the treatment of photodamaged facial skin. Significant amelioration of many of the signs of photodamage were achieved with minimal side effects. Clinical grading showed significant improvement both in the assessments based on changes in clinical scores and in pre- and posttreatment comparisons of standardized photographs. Fine wrinkling, coarse wrinkling, sallowness, looseness, and hyperpigmentation were significantly improved with tretinoin therapy. Furthermore, a self-appraisal questionnaire indicated that tretinoin-treated patients, but not vehicle-treated patients, were able to perceive improvement in their facial appearance. An objective method based on digital image processing of silicone rubber casts obtained from the crow's-feet area also indicated that the skin surface topography was smoother and less wrinkled in the tretinoin-treated group compared with the vehicle-control group.

Adult

Immune complex vasculitis, polymyositis, and hyperglobulinemic purpura.

This is the first description of a patient with both polymyositis and Waldenström hyperglobulinemic purpura. There was evidence of circulating immune complexes, and immune deposits were found in dermal and muscular vessels. Similar electron-dense deposits were seen ultrastructurally in the basement membrane of both normal and abnormal microvasculature. The findings suggest that the muscle and skin lesions may be associated with deposition of circulating immune complexes in and around blood vessels, followed by complement activation and subsequent inflammation.

Adult

Keratoacanthoma of the glans penis.

A patient with a solitary keratoacanthoma of the glans penis is presented. Since this area is devoid of hair, this keratoacanthoma could not have arisen from a hair follicle as has been suggested as the cause of keratoacanthoma. Keratoacanthoma should be included in the differential diagnosis of rapidly growing keratotic tumors of the glans penis. Correct diagnosis of this tumor may save patients from needless mutilating surgery of the penis.

Humans

Leukocytoclastic vasculitis: sequential appearance of immunoreactants and cellular changes in serial biopsies.

To study the mechanisms responsible for leukocytoclastic vasculitis, we evaluated the kinetics of immunologic and cellular changes in induced vasculitis lesions. In four of five consecutive patients with active vasculitis, lesions were induced by increasing vascular permeability via injecting histamine into the skin. Biopsies were obtained for light and electron microscopy and immunofluorescence at 1, 4, 8, and 24 hr after injection. The results show that immunoglobulin, C3, and electron-dense material are deposited in vessel walls early and are followed by cellular infiltration. The characteristics of the cellular infiltrates were quite diverse at different times after histamine provocation and no distinctive patterns were seen. Nevertheless, the kinetics of the appearance of immunoreactants and cells implies that immunoglobulin and probably circulating immune complexes are present prior to the development of inflammation and supports the contention that deposition of immune complexes within vessel walls is responsible for leukocytoclastic vasculitis.

Adult

Leukocytoclastic vasculitis.

Patients with leukocytoclastic vasculitis have purpuric, palpable lesions, most commonly on the lower part of the legs. Systemic involvement, particularly of the kidneys, is found frequently. Characteristic pathological features include necrosis of small vessels within the dermis, infiltration by polymorphonuclear leukocytes within and around the vessel walls, hemorrhage, and occasionally thrombosis. Immunofluorescence study frequently shows granular deposits of immunoglobulins and complement in vessel walls. Etiologic agents that have been implicated include infection, foreign proteins, chemicals, drugs, and a variety of diseases. The mechanism causing tissue damage is thought to be mediated by immune complexes, although specific antigens have only occasionally been unequivocally identified. Treatment includes bedrest, corticosteroids, and sometimes, cytotoxic agents.

Animals

Netherton's syndrome: an electronmicroscopic study.

An ultrastructural study of 2 patients with Netherton's syndrome (bamboo hair, scaling dermatosis, and an atopic diathesis) showed features of psoriasis and a dermatitis. Although the biopsies from the patients showed histological and ultrastructural similarities, the clinical presentations were different. One patient had ichthyosis linearis circumflexa, while the other had a generalized ichthyosiform eruption. The ultrastructural findings in the 2 patients, while not specific, may help distinguish the eruption of Netherton's syndrome from other scaling dermatoses.

Adult

Production of Sézary-like cells from normal human lymphocytes.

The present study was designed to determine if lymphocytes from healthy humans could be stimulated to assume the morphologic appearance of Sézary-like cells. Lymphocyte-rich populations of cells were incubated for 72 hours with pokeweed mitogen and phytohemagglutinin, both potent cellular mitogens. With light microscopy, differential cell counts performed on 0.5mu epoxy resin-embedded sections showed that 5% to 11% of the lymphocytes had cerebriform nuclei, and were designated as Sézary-like cells. The morphological results were confirmed by electron microscopy. Production of Sézary-like cells from stimulated, normal, human lymphocytes suggests that cells with cerebriform nuclei may represent reactive lymphocytes, and may explain their presence in benign inflammatory dermatoses.

Cell Nucleus