Limited application of mometasone furoate on the face and intertriginous areas: analysis of safety and efficacy.
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Biomedical subjects
Publications and source records attributed to M Lebwohl.
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The major histological characteristic of sun-damaged skin is the accumulation of an elastotic material that appears to replace collagen. This elastotic material consists primarily of elastin and histological studies suggest a large loss of collagen in the dermis of chronically sun-damaged skin. In this study, we examine the content and distribution of collagen and procollagen in sun-damaged human skin. The total collagen content of sun-damaged skin was 20% less than nonsolar-exposed skin (524 micrograms collagen per mg total protein in sun-damaged skin and 667 micrograms collagen per mg total protein in nonsolar-exposed skin). In addition, there was a 40% decrease in the content of intact amino propeptide moiety of type III procollagen in sun-damaged skin (0.68 U per 50 mg wet weight) as compared to nonsolar-exposed skin (1.12 U per 50 mg wet weight). The data suggest that this change in collagen content is due to increased degradation. The distribution of collagen in sun-damaged skin was examined by indirect immunofluorescence. Mild digestion of sun-damaged skin with elastase removed the elastin and revealed the presence of collagen in the elastotic material. Therefore, the elastin appears to mask the presence of collagen fibers in the dermis of sun-damaged skin.
Topical recombinant alpha-2 interferon treatment of recurrent genital herpes was studied in a randomized, double-blind, placebo controlled clinical trial. Three hundred and eighty-seven patients were treated at eight study centers with either interferon gel or placebo four times daily for four days. Interferon therapy caused a 26% decrease in the duration of viral shedding. For male patients, there were also significant decreases in the time to crusting (17%) and duration of pain (34%) and itching (21%). For patients with recurrent genital herpes, treatment with topical interferon was found to be effective in decreasing the duration of viral shedding and, for males, pain, itching and time to crusting.
A patient with Crohn's disease and peristomal pyoderma gangrenosum is described. This patient is unique because she had a rapid response to intralesionally injected steroids. This treatment is ideal for peristomal pyoderma gangrenosum because it is administered intermittently when the ostomy appliance is changed and it does not interfere with adhesion of the device. All 11 cases of peristomal pyoderma gangrenosum described in the literature are reviewed.
BACKGROUND: Injectable collagen has been used for more than 15 years to correct soft tissue cosmetic defects. After injection, the collagen remaining in the syringe is often refrigerated for later use in the same patient, despite manufacturer and Food and Drug Administration recommendations to discard the unused collagen. OBJECTIVE: This study examined the incidence of bacterial contamination of stored collagen. METHODS: Syringe needle tips and collagen from 50 previously used syringes containing either Zyderm I, Zyderm II, or Zyplast were cultured separately under aerobic and anaerobic conditions. Bacterial isolates were identified. RESULTS: Propionibacterium acnes was cultured from 7 of 50 needle tips. One positive needle tip culture grew both P. acnes and Staphylococcus aureus. Bacteria were isolated from only one collagen sample that grew a nonhemolytic streptococcus that may have represented a laboratory contaminant. CONCLUSION: Syringes of collagen stored for repeated use rarely become contaminated with bacteria despite frequent contamination of their needle tips. Skin abscesses after collagen injection should be cultured under anaerobic, as well as aerobic, conditions so that infections caused by P. acnes will not be missed.
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Pseudoxanthoma elasticum (PXE) is a heritable disorder of connective tissue that is characterized by redundant folds of skin in flexural areas. There is considerable evidence that suggests that the elastic fiber is the main site of the abnormality although the primary molecular defect has not been identified. The aim of this study was to identify differences between PXE and normal skin elastins. Elastins from normal, nonsolar-exposed skin, and pseudoxanthoma elasticum lesional skin were purified and their solubilization by pancreatic elastase was compared. Results demonstrated that elastin derived from normal skin was more susceptible to proteolytic cleavage than elastin purified from either pseudoxanthoma elasticum lesional skin or ligamentum nuchae. Pretreatment of the lesional elastin with testicular hyaluronidase increased its solubilization two-fold and generated a unique 15,000 Da molecular weight fragment. Elastin prepared from PXE skin may contain bound glycosaminoglycans which interfere with elastase activity. The susceptibility of normal skin elastin to proteolytic degradation may have implications in the study of aging skin.
The efficacy and safety of clobetasol propionate 0.05% scalp application was evaluated in 378 patients with moderate to severe scalp psoriasis in a double-blind vehicle-controlled parallel group study. After 2 weeks of twice-daily applications, 81% receiving active drug versus 22% receiving vehicle had clearing of 50% or greater. Complete clearing was seen in 26% with active drug and 1% with vehicle. Local side effects were primarily burning or stinging in 11% and 10% of patients treated on an active or a vehicle regimen, respectively. The morning cortisol levels of 168 patients were checked at baseline and again after 2 weeks of drug therapy. Subnormal morning plasma cortisol values were seen in 5% of the patients receiving active drug and in 5% receiving vehicle; 13% of those taking active drug versus 5% taking vehicle had a 50% or greater decrease in morning cortisol at the 2-week visit compared with baseline values. Clobetasol propionate 0.05% scalp application appears to be a safe and an effective treatment for scalp psoriasis.
Acanthosis nigricans (AN) is a frequent clinical finding in hyperandrogenic women. Its presence has been used to subgroup such women. We performed this study in order to determine the actual histological prevalence of AN and its relationship to sex hormone levels and insulin action. Insulin-mediated glucose disposal was determined by the euglycemic clamp technique, and neck or axillary skin biopsies were graded blind for the presence and severity of AN in lean and obese women with the polycystic ovary syndrome (PCO) and in age- and weight-matched normal ovulatory controls. AN was present on clinical examination in 11 of 13 obese PCO, 3 of 6 lean PCO, 4 of 14 obese normal, and 0 of 4 lean normal women. AN was present on histological examination in 13 of 13 obese PCO, 5 of 6 lean PCO, 13 of 14 obese normal, and 1 of 4 lean normal women. The severity of histological AN was most highly correlated with insulin-mediated glucose disposal (r = -0.61; P less than 0.001) rather than fasting (r = 0.46; P less than 0.05) or glucose-stimulated insulin levels (r = 0.48; P less than 0.01). The only sex steroid correlated with histological AN was dehydroepiandrosterone sulfate (r = 0.46; P less than 0.01). We conclude that 1) clinical skin examination was very insensitive for detecting AN; 2) the best biochemical correlate of histological AN was decreased insulin action, rather than insulin or androgen levels per se; and 3) AN is a very common epiphenomenon of insulin resistance, and its clinical presence should not be used as a criterion for stratifying hyperandrogenic women.
In situ hybridization and peroxidase anti-peroxidase immunodetection were used in the same tissue sections to elucidate the spatial distribution of collagen gene expression in cutaneous neurofibromas, particularly in relation to blood vessels; the latter structures were identified by the presence of factor VIII-related antigen. The data indicate a clear relationship between the vascular structures and sites of locally elevated expression of type I and VI collagen genes. Specifically, some, but not all, blood vessels were surrounded by stromal cells highly active in expressing pro alpha 1(I) and alpha 2(VI) collagen genes. Furthermore, these genes were expressed by a subpopulation of endothelial cells within the walls of blood vessels traversing the lesion. To quantitate the overall expression of five genetically distinct collagen genes in cutaneous neurofibromas, we performed Northern analyses and slot blot hybridizations with pro alpha 1 (I), pro alpha 2 (I), pro alpha 1 (III), pro alpha 1 (IV) and alpha 2(VI) collagen cDNAs. Although the mRNA levels for all five genes were slightly increased in neurofibroma tissue, only the abundance of alpha 2(VI) collagen mRNAs was significantly elevated, as compared with normal skin. We conclude that endothelial cell populations with different levels of collagen gene expression exist within cutaneous neurofibromas: some are actively expressing type I and VI collagen genes, whereas in other the expression of these genes is effectively down-regulated. The markedly elevated steady-state levels of type VI collagen mRNAs suggest that synthesis of type VI collagen may contribute to the growth and architecture of cutaneous neurofibromas.
Abnormalities in the amount of skin elastin occur in several cutaneous disorders. The number of elastic fibers is increased in elastotic disorders such as pseudoxanthoma elasticum (PXE) and cutis rhomboidalis nuchae (actinic elastosis, AE) and is decreased in elastolytic disorders such as cutis laxa (CL). We describe a procedure to quantify desmosines and elastin in small amounts of skin using high-performance liquid chromatography (HPLC). Biopsies were obtained from normal, nonsolar exposed skin and from the lesional skin of patients with PXE, cutis rhomboidalis nuchae, and CL. Specimens were subjected to hot alkali treatment and the desmosines were released by acid hydrolysis and quantified by HPLC. The mean value for normal skin was 252 +/- 28 ng desmosines per milligram wet weight (SD, n = 5). The disorders of elastosis (PXE and AE) demonstrated a two- to fivefold increased content of desmosines. In contrast, the elastolytic disorder (CL) had only 20% of the normal content of desmosines. Furthermore, PXE and normal skin elastins had the same amount of desmosines per milligram purified elastin. This method could be used to evaluate the extent of elastosis or elastolysis in a particular lesion.
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The possible causative role of the yeastlike fungus Pityrosporum (Malassezia) orbiculare in the pathogenesis of seborrheic dermatitis in patients with and without acquired immunodeficiency syndrome (AIDS) has been discussed but not resolved. Ten patients with AIDS-related seborrheic dermatitis were studied for the presence of Pityrosporum organisms. On the basis of a quantitative correlation between numbers of yeast cells adherent to and extruded from keratinocytes and the clinical severity of seborrheic dermatitis, an association, if not a causative role, for Pityrosporum is strongly suggested in seborrheic dermatitis in patients with AIDS. This association was further strengthened by the marked clinical response to ketoconazole in two patients with a concomitant decrease in the number of Pityrosporum cells per keratinocyte.
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A congenital arrector pili hamartoma is a neoplasm that presents as multiple or solitary dermal nodules in a dermatomal distribution. To elucidate and clarify its histogenesis, a lesion derived from a 3-year-old boy was studied by light microscopy, indirect immunofluorescence, using antibodies against basal lamina constituents and against interstitial matrix components, and electron microscopy. In addition, a rabbit antibody specific for bovine smooth-muscle myosin was used. The antibodies against the basal lamina components and fibronectin all showed an intense perimysial fluorescence that ensheathed and surrounded individual leiomyocytes. Anti-smooth-muscle myosin exhibited intense cytoplasmic fluorescence. Furthermore, electron microscopy showed fusiform cells with abundant myofilaments, dense bodies, and pericellular basal lamina as seen in smooth muscle. These studies suggest the probable origin of this hamartoma from pili arrector muscle and could be used as an adjunct in histopathological diagnosis.
The cellular heterogeneity of cutaneous tumors from nine patients with type 1 (von Recklinghausen's) neurofibromatosis was studied using several antigenic markers with special reference to focal heterotopic differentiation and interindividual variation. Furthermore, cells which actively express the genes for type I and III collagens and fibronectin, the major components of the abundant extracellular matrix of neurofibromas, were localized using in situ hybridizations. In eight of nine cases, the S-100 protein positive cells, i.e. Schwann-like cells, composed 60 to 80% of the total cell population. However, in one case, only about 40% of the cells were S-100 protein positive. The latter tumor was studied with respect to perineurial cell differentiation and stained with a mixture of two antibodies, directed against the S-100 protein and type IV collagen. In Schwann cells, the staining reaction for S-100 protein was observed in the nuclear region, whereas the staining reaction for type IV collagen was located peripherally, corresponding to the basement membrane zone covering the cells. The stromal cells which showed only the peripheral staining profile were considered to be neoplastic perineurial cells. Distinct structures with epithelial, endothelial, or smooth muscle cell differentiation were present within the benign tumors, as detected by immunostaining for cytokeratin, epithelial membrane antigen, factor VIII-related antigen and desmin, respectively. In situ hybridizations revealed a clearly detectable expression of type I procollagen genes in less than 10% and type III procollagen gene in less than 5% of the total cell population. Active synthesis of fibronectin was limited to the vascular walls, when examined by in situ hybridization, and antibodies to cellular fibronectin localized to the same areas. However, antibodies to plasma fibronectin produced a uniform staining reaction throughout the tumors suggesting that most of the fibronectin in neurofibromas is plasma-derived. The latter observation suggests that neurofibroma cells are freely accessible to various plasma proteins, including growth factors, which may influence the growth characteristics of these lesions.
Pseudoxanthoma elasticum is a disorder of connective tissue that is associated with numerous systemic complications, including accelerated atherosclerosis, gastrointestinal bleeding, angioid streaks in the ocular fundus, and blindness. Diagnosis of the disease is important because many of its complications can be prevented and genetic counseling can be offered to family members of affected patients. The purpose of this study was to examine the usefulness of scar biopsy in establishing a diagnosis of pseudoxanthoma elasticum in patients with angioid streaks but without characteristic skin lesions. Ten patients with angioid streaks but without cutaneous findings indicative of pseudoxanthoma elasticum were evaluated by biopsy of scars and flexural skin. The biopsy specimens were compared with those from unaffected controls. In 6 of the 10 patients, scar biopsies showed fragmentation and clumping of elastic tissue in the deep dermis. Three patients also had these histologic features of pseudoxanthoma elasticum in biopsy specimens of flexural skin that appeared to be normal. We conclude that biopsies of scars in randomly chosen sites may be useful when pseudoxanthoma elasticum is suspected despite the absence of typical skin lesions.