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Biomedical subjects

A M Kligman

Publications and source records attributed to A M Kligman.

At least 37 records · Page 2Linked to original sources

The sodium hydroxide erosion assay: a revision of the alkali resistance test.

Burckhardt proposed the alkali resistance method as a means of assessing the integrity of the stratum corneum barrier in 1947. Researchers after Burckhardt largely found the test unreliable and nonreproducible; it therefore fell into disuse worldwide. We have upgraded the procedure by exposing the skin to 1.0 M sodium hydroxide under strictly specified conditions for successive 1-min periods until the emergence of the first erosions, revealed by staining with nitrazine yellow. Histology showed that the erosions were follicular and limited to the epidermis. The test was highly reproducible and repeatable. We demonstrated the usefulness of the test in the following ways: (1) the erosion time increased with aging, correlating with a thickened horny layer; (2) as few as five Scotch tape strippings greatly decreased the erosion time, although transepidermal water loss was only slightly increased; (3) slight damage to the horny layer by a 24-h exposure to 0.01% sodium lauryl sulfate sharply reduced the erosion time; (4) the erosion time decreased after daily open applications for 3 weeks of clobetasol propionate, corresponding to the thinned horny layer; (5) daily applications of petrolatum increased the erosion time. This new version of the alkali resistance test, renamed the sodium hydroxide erosion assay, promises to be a useful tool for studying the horny layer barrier in healthy and diseased skin.

Administration, Topical↗

Lack of correlation of skin thickness with bone density in patients receiving chronic glucocorticoid.

The objective was to test the hypothesis that there is a correlation between thinning of the skin and bone in patients on chronic oral glucocorticoids (GCs). This was a one-time cross-sectional analysis performed in an academic referral center. The study group consisted of 14 patients on GCs for a variety of disorders, including dermatomyositis, pemphigus vulgaris, pyoderma gangrenosum, and urticarial vasculitis. Skin thickness was compared with that of 24 sex- and age-matched controls. The main outcome measures were the bone density of the lumbar spine (L2-L4) and the skin thickness. The skin thickness (mm, mean +/- SEM) in GC-treated (n = 7) vs unmedicated age-matched Caucasian women (n = 20) was 0.84 +/- 0.04 vs 1.02 +/- 0.04 (t = 3.07, P < 0.01) in the upper arm, 1.13 +/- 0.09 vs 1.49 +/- 0.05 (t = 3.65, P < 0.002) in the dorsal forearm, and 0.96 +/- 0.07 vs 1.17 +/- 0.02 (t = 2.92, P < 0.01) in the ventral forearm. L2-L4 bone densities averaged 106 +/- 2% in the GC-treated female patients relative to the age and sex-matched controls. There was no correlation between skin thickness and bone density. In GC-treated (n = 4) vs unmedicated Caucasian men matched for age (n = 4), skin thickness was 1.09 +/- 0.4 vs 1.33 +/- 0.05 (t = 3.51, P < 0.02) in the upper arm, but was not significantly different at the two forearm sites. No correlation between skin thickness and bone density was observed. The level of type I procollagen mRNA in skin from three GC-treated patients was 45% of the value in three age-matched controls. In conclusion, GCs cause statistically significant thinning of skin independently of the effects on bone.

Absorptiometry, Photon↗

A twenty-four-hour occlusive exposure to 1% sodium lauryl sulfate induces a unique histopathologic inflammatory response in the xerotic skin of atopic dermatitis patients.

Twenty-four-hour occlusive exposures of 1% aqueous sodium lauryl sulfate (SLS) produced unique functional and histological responses in patients with atopic dermatitis. Disruption of the stratum corneum barrier, measured by transepidermal water loss, was much greater and longer lasting than in normal controls. In contrast to controls the histologic pattern induced reproduced the typical features of the disease with spongiosis, exocytosis of mononuclear cells and a perivenular infiltrate containing eosinophils. The perivascular infiltrate consisted of CD1a+, CD4+ and HLA-DR+ cells, which was much greater and more persistent in atopics. Eosinophilic major basic protein was abundant in atopics but absent in controls. SLS provocation of atopic dermatitis is a striking experimental example of Koebnerization, in which disruption of the stratum corneum barrier as well as cytokine activation of keratinocytes reproduces the clinical diseases.

Adolescent↗

Salicylic acid peels for the treatment of photoaging.

Several chemical agents are currently used to perform superficial chemical peels of the face. These include trichloracetic acid (15-30%), alpha-hydroxy acids (e.g., glycolic acid, 40-70%), and Jessner's solution (14% lactic acid, 14% resorcinol, and 14% salicylic acid). We have developed salicylic acid, a beta-hydroxy acid, at a higher strength (30% in a hydro-ethanolic vehicle) as an alternative peel. This peel has distinct advantages for resurfacing moderately photodamaged facial skin. We have peeled patients singly and multiply at 4-week intervals. The benefits are fading of pigment spots, decreased surface roughness, and reduction of fine lines.

Adult↗

The myth of lanolin allergy.

Lanolin has the reputation of being an important contact sensitizer. The market place abounds with products that are labeled "lanolin free". In fact, lanolin is at most a weak contact allergen. The supposed hazards of sensitization to lanolin products are a resultant of faulty science and failure to appreciate the limitations of patch testing. Lanolin allergy is a myth created mainly by overzealous professional patch testers. No one has succeeded in sensitizing animals or humans to lanolin or wool wax alcohols. Most of the case reports are false positives, in association with the angry back syndrome.

Dermatitis, Allergic Contact↗

Topical tretinoin replenishes CD1a-positive epidermal Langerhans cells in chronically photodamaged human skin.

Excessive exposure to sunlight results in drastic degradative changes in the constitutive cells of the epidermis. Among these is a profound abrogation of Langerhans cell number and function, leading to compromised immunologic competency. Retinoids have recently been shown to restore immunologic function in the setting of iatrogenic immunosuppresion. We asked whether topical tretinoin would reverse Langerhans cell depletion in chronically photodamaged skin. We examined the skin of 8 volunteers immunohistochemically before and after 6 months of daily applications of tretinoin. At baseline, there was a profound depletion of CD1a-positive Langerhans cells in the interfollicular epidermis, but not in the adjoining follicular epithelium. After tretinoin, all patients demonstrated replenishment of interfollicular epidermis by CD1a-positive Langerhans cells. This was associated with induction of HLA-DR expression on infundibular keratinocytes, as well as the appearance of CD1a dendritic cells in the papillary dermis. Thus, the enhancement of epidermal immunity in photodamaged skin may reflect restoration of antigen-presenting Langerhans cells. The source of this renewed dendritic cell population is likely to be follicular infundibulum and the papillary dermis.

Administration, Topical↗

The treatment of acne with topical retinoids: one man's opinions.

Acne is a family of disorders that vary greatly in pathogenesis and clinical manifestation. Accordingly, no simple recipe for treatment can be given, and treatment options vary with the stage and intensity of the disease. Topical retinoids are the mainstay for treating common varieties of acne vulgaris. They also prevent development of comedones, halting progression to inflammatory lesions. Tretinoin was the first retinoid used in the topical treatment of acne more than 25 years ago. Isotretinoin, which has recently become available, is less irritating, but is probably somewhat less effective. Adapalene is a recently introduced topical retinoid used to treat acne. It enjoys therapeutic equivalence to tretinoin but is less irritating. Except for very mild acne cases, topical retinoids should be used concommitantly with other drugs. The operating principle is to choose drugs whose modes of action are different from topical retinoids, that is, antibiotics or benzoyl peroxide. Topical retinoids, however, constitute the core of nearly all therapeutic programs for acne.

Acne Vulgaris↗

Chemotherapy for disseminated actinic keratoses with 5-fluorouracil and isotretinoin.

BACKGROUND: Disseminated actinic keratoses are a therapeutic problem. OBJECTIVE: Our purpose was to evaluate the efficacy of a combination of topical 5-fluorouracil twice a day and 20 mg of oral isotretinoin daily for disseminated actinic keratoses. METHODS: Twenty-seven patients who had disseminated actinic keratoses (3 women, 24 men) were treated with 5-fluorouracil (5%) twice a day applied to the photodamaged area bearing actinic keratoses along with oral isotretinoin, 20 mg daily. The median treatment time was 21 days. RESULTS: Actinic keratoses disappeared and signs of photodamaged skin improved in all patients. Side effects were burning and itching as well as painful erosions during the final stage of treatment. CONCLUSION: The combination of topical 5-fluorouracil and isotretinoin is highly effective in the treatment of disseminated actinic keratoses on photodamaged skin.

Administration, Oral↗

Demographics and psychological implications for the aging population.

The aging of skin is more than a decline in physiologic functions. Aging skin is associated with regressive anatomical changes such as looseness, roughness, wrinkles, and dyspigmentations (age spots) which adversely affect appearance. Unattractive aged persons tend to have less confidence, have low self-esteem, and are in fact less healthy than those who have aged well. Physicians must educate the public to follow life-styles that prevent a prematurely aged appearance. Additionally, resources which make it possible to remarkably correct the various deteriorations of the photo damaged face are now available. Patients should be told that these interventions are not simply an expression of vanity, but add to self-esteem and improved social relations.

Aged↗

Histologic effects of the high-energy pulsed CO2 laser on photoaged facial skin.

To delineate the histologic effects of laser resurfacing at photoaged skin, a protocol was designed to biopsy laser test sites in conjunction with adjacent actinically damaged skin at the time of rhytidectomy. Five patients with photodamaged skin underwent resurfacing of the preauricular region to examine the effect of increasing pulse energy and increasing number of passes on depth of dermal penetration. Histologic examination of these specimens showed that the depth of laser injury was dose-dependent. Increasing pulse energy created a deeper wound, and increasing the number of passes similarly produced a larger band of necrosis. Ten patients with photodamaged skin underwent resurfacing of the preauricular region 15 days to 6 months prior to undergoing a rhytidectomy. A comparison of the laser-resurfaced test spot with the adjacent untreated photodamaged skin demonstrated consistent histologic changes to both epidermis and dermis in all specimens examined. Following laser resurfacing, epidermal atrophy and atypia were eliminated, and all specimens exhibited a regeneration of epithelium that was normal in its morphology. Melanocytic hypertrophy and hyperplasia were corrected following treatment, although density and function of epidermal melanocytes appeared normal. All specimens exhibited a substantial amount of neocollagen formation involving both the superficial and middermis following resurfacing. In association with new collagen development within the dermis, there was noted to be a similar degree of proliferation of elastic fibers, as well as a diminution of glycosaminoglycans, which are typically present in actinically damaged elastotic dermis. To determine the effect of laser resurfacing on-black skin, laser test spots were placed in the postauricular region of three black patients. Biopsy of these test sites showed that the histologic effects of laser resurfacing were similar to those observed in Caucasian patients, with complete repopulation of epidermal melanocytes in specimens biopsied 3 months following resurfacing. The histologic effects of laser resurfacing are microscopically similar to those of phenol peeling in terms of the amelioration of photodamage. The distinction between these two treatment methods lies in their apparent effect on epidermal melanocytes, which appear to function normally following laser resurfacing.

Atrophy↗

Disaggregation of corneocytes from surfactant-treated sheets of stratum corneum in hyperkeratosis on psoriasis, ichthyosis vulgaris and atopic dermatitis.

To elucidate the pathogenesis of impaired barrier function and the influence of surfactant on the stratum corneum in hyperkeratosis, we investigated morphological alterations of the corneocytes with soap solution. Groups of five patients each with psoriasis vulgaris (PV), ichthyosis vulgaris (IV), atopic dermatitis (AD), and normal controls were examined. Four samples of the horny layer were obtained from the same site by cyanoacrylate adhesive biopsy. The first sample was used for the superficial layer, and the fourth, for the basal horny layers. Each sample was agitated in 1% stirred soap solution at 60 degrees C. The number and size of isolated corneocytes and the morphologic changes were investigated. The release of corneocytes was greater and the swelling and morphological changes of corneocytes exposed to soap solutions were less in PV and AD than in IV or in healthy subjects. In IV, the release was markedly less than in controls. The release and swelling were greater in the superficial than in the basal horny layers. It was concluded that the cohesiveness of corneocytes was probably less in PV and AD and greater in IV than in normals. It was also suggested that the cohesion of corneocytes from the superficial horny layer was less than that from the deep layer. The permeability of the cornified envelope in PV and AD patients was less than in IV or healthy subjects. It was confirmed that highly potent soaps induce loss of many corneocytes and reduce the barrier function of the stratum corneum.

Adolescent↗

A new model for assessing the damaging effects of soaps and surfactants on human stratum corneum.

To elucidate the damage to the horny layers of human skin produced by surfactants and soaps, we evaluated the cytological alterations of corneocytes using an in vitro assay. Suction blisters, 8 mm in diameter, were raised on the forearms of young adult Caucasoids. The roofs were cut off and the viable epidermis was removed. The discs of stratum corneum were then agitated for up to 6 h at 60 degrees C in 1% solution of five soap bars of differing irritancy. Additionally, individual examples of anionic, cationic and nonionic surfactants were similarly evaluated. Measurements of corneocytes included: (1) the number released with time (disaggregation), (2) size (swelling) and (3) morphologic degradation. The effects of the cationic and non-ionic surfactants did not differ significantly from those of distilled water. The anionic surfactant caused more release and less swelling and morphological change. The test soaps had vastly different effects on the structural integrity of the stratum corneum. The harsher ones caused greater disaggregation, more swelling and greater morphologic deterioration of corneocytes, whereas the milder ones had less marked effects on these parameters. This model would be a useful screening technique for formulating milder soaps and might also provide insights into the complex modes of action of surfactants on the stratum corneum.

Adult↗

Topical treatments for photoaged skin. Separating the reality from the hype.

Most patients have committed the usual folly of recreational sunbathing in childhood, and in adulthood they notice the manifestations in the mirror. Increasingly, they are seeking professional advice regarding the growing stream of products that promise to improve their photoaged skin. Physicians need to be informed about the great range and complexity of products available, if for no other reason than to steer patients clear of traveling-medicine-show products. A better reason is to be able to provide guidance on proper use of formulations that have proven benefit.

Administration, Topical↗