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Increasing cell size, lipid accumulation, and altered antigen expression are features of sebaceous differentiation in vivo. Enhanced lipid synthesis with progressive differentiation is also present in cultured human sebocytes. This study was conducted to investigate the evolution of cell size and antigen expression of human sebocytes with progressive differentiation in vitro. Subconfluent human sebocyte cultures were examined for sebocyte differentiation evaluated on cytocentrifuge preparations by light microscopy and classified in stages according to morphological criteria described for sebocytes in vivo. Rates of 5.1 +/- 2.2% undifferentiated sebocytes, 29.2 +/- 4.9% early differentiated, 20.7 +/- 4.1% advanced differentiated, 37.6 +/- 6.4% fully differentiated, and 5.9 +/- 1.9% mature sebocytes were calculated in secondary cultures. The size of cultured sebocytes measured by computer-assisted planimetry significantly increased with progressive differentiation up to 4-5.5 times. The low rates of mature sebocytes and the only moderate increase of their size with progressive differentiation indicate an incomplete terminal differentiation in vitro. Sebocytes were subsequently stained with a series of monoclonal antibodies (mAb) to determine antigen expression using the alkaline phosphatase anti-alkaline phosphatase technique. The number of sebocytes labeled with the anti-keratin mAb CK8.12 and KL1, and the mAb 34D11 (82 kD protein) increased with progressive differentiation; significant differences were found after comparing early and advanced differentiated sebocytes. Sebocytes were positively stained with the anti-keratin mAb 6B10 (K 4), RPN1162 (K 7), CK13 (K 13), RPN1165 (K 19), CK8.60, and the mAb 115F5 (MAM-6c), OM-1 (sebaceous gland antigen), and 24F10 (basic polypeptides) only at late-stage differentiation. The expression of keratins 4, 7, 13, and 19 was confirmed by gel electrophoresis and immunoblotting. The data obtained were used to study the effects of the duration of cultivation and of the retinoids isotretinoin and tretinoin on sebocyte differentiation in vitro. Subcultivation of sebocytes upregulated, and treatment with isotretinoin but not with tretinoin downregulated labeling with mAb which recognize indicating progressive and late-stage differentiation.
Extensive animal data have suggested that, in some systems, the induction of ornithine decarboxylase (ODC) is an essential, although not sufficient, aspect of tumor promotion and that compounds that inhibit ODC can inhibit tumor formation. Using fasting human volunteers, we report that human epidermal and dermal ODC are consistently induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in a manner similar to that seen in mouse skin. There is a marked intersubject variation in TPA-induced epidermal ODC activity levels. Orally administered compounds significantly inhibited TPA-caused human epidermal ODC induction. These data may be useful in the further development of drugs, doses, and dose schedules for use in human cancer chemoprevention studies.
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The aim of the authors was to give precise indications regarding the use of the systemic retinoid in the chemoprevention of non-melanoma skin cancer (NMSC).
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The aim of this study was to compare azithromycin and levamisole with azithromycin alone in the treatment of acne vulgaris.
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Tazarotene (AGN 190168) is a new acetylenic retinoid which is effective for the topical treatment of patients with stable plaque psoriasis and mild to moderate acne vulgaris. Topical gel application provides direct delivery of tazarotene into the skin. At 10 hours after a topical application of 0.1% tazarotene gel to the skin of healthy individuals and patients with psoriasis, approximately 4 to 6% of the dose resided in the stratum corneum and 2% of the dose distributed to the viable epidermis and dermis. Tazarotene is rapidly hydrolysed by esterases to its active metabolite, tazarotenic acid. Tazarotenic acid does not accumulate in adipose tissue, but undergoes further metabolism to its sulfoxide and to other polar metabolites and is rapidly eliminated via both urinary and faecal pathways with a terminal half-life of about 18 hours. Percutaneous absorption is similar between healthy individuals and patients with facial acne, leading to plasma concentrations below 1 microg/L. The systemic bioavailability of tazarotene (measured as tazarotenic acid) is low, approximately 1% after single and multiple topical applications to healthy skin. In patients with psoriasis under typical conditions of use, systemic bioavailability increased during the initial 2 weeks of treatment from 1% (single dose) to 5% or less (steady state). The increased bioavailability is probably related to decreases in plaque elevation and scaling due to successful treatment, resulting in a less effective skin penetration barrier to tazarotene. Steady-state concentrations of tazarotenic acid are achieved within 2 weeks of topical treatment in both healthy and psoriatic skin types. The large variability in plasma concentrations observed in patients with psoriasis is probably because of the large differences in lesional skin condition, the amount of drug applied and the surface area of application. There was no significant drug accumulation in the body with long term treatment of patients with psoriasis. Topical administration of tazarotene requires dosages much smaller than those usually required for oral retinoids, such as isotretinoin, acitretin and etretinate, and it delivers the drug directly into the target skin tissues. The low systemic absorption and rapid systemic elimination of tazarotene and tazarotenic acid results in limited systemic exposure. Thus, topical tazarotene has a low potential for systemic adverse effects and is effective in the treatment of patients with acne and psoriasis.
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The arotinoid Ro 15-0778 is a potent inhibitor of sebum secretion in rodents but not in humans, while isotretinoin (13-cis-retinoic acid, Accutane) inhibits sebum secretion in rodents and humans. The concentrations of Ro 15-0778 and isotretinoin were determined in plasma and target tissues of castrated, testosterone-stimulated hamsters after oral and topical dosing and in castrated, testosterone-stimulated rats after oral dosing. Comparison of this concentration data to that obtained in the plasma and sebum of humans after dosing with Ro 15-0778 and with isotretinoin did not explain why Ro 15-0778 was a potent inhibitor of sebum production in rodents but not in humans.
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Epidemiology literally means "the study of what is upon the people." It puts the individual's condition in a population context and is the path to disease prevention. In the first part of this review, important aspects of epidemiology are discussed. Fundamentals of epidemiologic research include the measurement of occurrence of an event (prevalence and incidence) and the identification of factors that are associated with this event. The main study designs in observational studies are cohort, case-control, and cross-sectional studies, all of which have intrinsic strengths and limitations. These limitations include a variety of biases, which can be regrouped into selection bias, information bias, and confounding. The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist is an important tool to further improve the reporting and quality of epidemiologic studies, and it is introduced. In the second part of this review, practical examples are presented, illustrating how dermatoepidemiology has contributed to an improved understanding of skin diseases and patient care, specifically in the case of melanoma therapy, serious cutaneous adverse reactions, Lyme disease, long-term safety of psoralin plus UVA (PUVA), teratogenicity of isotretinoin, and comorbidities in psoriasis.
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Corneal damage can have a variety of causes, including infections, chemical splashes, environmental factors (radiation, trauma, contact lenses, etc.), and systemic diseases (genetic, autoimmune, inflammatory, metabolic, etc.). A wide range of drugs can also damage the cornea. The severity of drug-induced corneal changes can range from simple asymptomatic deposits to irreversible, sight-threatening damage. Several factors can influence the onset of corneal lesions. Some factors, such as the dose, are treatment-related, while others such as contact lenses, are patient-related. A variety of mechanisms may be involved, including corneal dryness, changes in the corneal epithelium, impaired wound healing and deposits. Many drugs can damage the cornea through direct contact, after intraocular injection or instillation, including VEGF inhibitors, anti-inflammatory drugs, local anaesthetics, glaucoma drugs, fluoroquinolones, and preservatives. Some systemically administered drugs can also damage the cornea, notably cancer drugs, amiodarone and isotretinoin. Vulnerable patients should be informed of this risk if they are prescribed a drug with the potential to damage the cornea so that they can identify problems in a timely manner. It may be necessary to discontinue the suspect drug when signs and symptoms of corneal damage occur.
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There was no correlation between isotretinoin use and the development of depression, based on either the Centre for Epidemiologic Studies Depression scale (Fisherâs exact test, P=0.497) or Zung Depression Status Inventory (ANOVA; F=1.4, P=0.2).
Since spontaneous resolution is rare and progressive disability the rule, early definitive surgical treatment of HS is advisable.
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We describe the evolution of the tumor and the combined therapy carried out and review the treatments employed in previously reported cases, comparing them with ours.
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Skeletal effects of retinoids on the spine were studied in two clinical trials. In the first study, spinal radiographs of 96 patients who had been treated with isotretinoin for 4 to 9 months were reviewed. The average age of these patients was 25 years, and during treatment or within 2 1/2 years after the end of treatment, 26% of the patients showed progressive formation of small bony spurs consisting of tiny horizontal excrescences that arose at the anterior margin of one or more vertebral bodies adjacent to the intervertebral disk. In a second study, the radiographs of 241 patients with psoriasis who were treated continually for 1 to 2 years with acitretin were examined. Many of these patients had abnormal radiographs at the start of therapy. These preexisting conditions included psoriatic arthritis, degenerative arthritis, and diffuse idiopathic skeletal hyperostosis. Five percent of the patients showed progression of their abnormalities during the study. The difference in the rate of spur formation in the two groups may be due to multiple factors and not simply to retinoid therapy. Because of the extensive amount of preexisting disease in the psoriasis group compared with the relatively normal appearance of the spine in the isotretinoin group, the underlying disease process may be more important than the retinoid therapy. The development of the spinal spurs was not associated with specific clinical symptoms. Since there was no control group, it is unknown whether the spurs would have developed or progressed in the absence of retinoid therapy.
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Isotretinoin is a remarkably effective drug for severe, recalcitrant acne vulgaris. Soon after the drug's release in the early 1980s, a number of important adverse effects were reported subsequently leading to a variety of medical and medicolegal controversies. Three of these controversies will be highlighted concerning the putative role of isotretinoin in (1) depression and suicide, (2) inflammatory bowel disease, and (3) iPledge and pregnancy prevention programs. It appears that a very small subset of patients receiving isotretinoin for acne are at risk for depression, which is very manageable provided there is adequate patient awareness of the possibility, maximum communication between the patient and physician, and cessation of therapy if clinically important depression occurs (after which the depression rapidly resolves in a week or less). Multiple controlled studies actually suggest a very favorable effect of isotretinoin on depression and anxiety common in the population requiring isotretinoin. With regard to inflammatory bowel disease, in just one study, only ulcerative colitis association with isotretinoin reached statistical significance. The actual incidence of this association is strikingly low. Finally, it is clear that even the most recent pregnancy prevention program (iPledge) is no more successful than prior programs; there will likely always be a small number of female patients becoming pregnant while receiving isotretinoin for acne vulgaris.
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Topical retinoids appear as an alternative choice in OLP treatment. Whether keratotic OLP better responds to topical retinoids than erosive OLP is still an open question that deserves further comparative and controlled clinical trials. The benefits and harms of using topical retinoids in people with OLP require thorough evaluation in properly designed controlled studies.
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Osteoporosis has been observed with chronic hypervitaminosis A but has not been established as a toxic effect of synthetic retinoid therapy in humans. This cross-sectional study was designed to assess bone mineral density (BMD) during long-term therapy with the retinoids etretinate or isotretinoin. Twenty-four patients were evaluated for osteoporosis with the standard techniques: single- and dual-photon absorptiometry. They received 50 g or more of etretinate (15 patients) or isotretinoin (nine patients) for 2 years or longer for the treatment of skin disease (ichthyosis [nine patients], Darier's disease [six patients], xeroderma pigmentosum [four patients], skin cancer [three patients], or psoriasis [two patients]). In each of the two treatment groups, BMDs (measured in grams per square centimeter) were measured at five standard sites (ie, lumbar spine, femoral neck, trochanter, Ward's triangle, and radius) and evaluated against a standardized database to control for age, sex, and weight. In addition, for each measurement site, BMDs (controlled for age, sex, and weight) were compared between the two groups, as a direct control for each other.
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This substudy of pathologic results from a randomized clinical trial suggests that, although the risk of progression of low-grade squamous intraepithelial lesions is low, follow-up cytologic testing is unreliable. Colposcopic evaluation with directed biopsies should be continued.
The patients all wore protective clothing and sunscreens when outdoors. Estimated mean vitamin D intake was normal. The mean values of serum 25-OHD were low normal, but 1,25-(OH)2D, calcium, ionized calcium and parathyroid hormone levels were normal. Lack of seasonal variation in serum 25-OHD indicated rigorous photoprotection.
Previous studies showed that many chemotherapeutic agents can induce immuno-suppression at therapeutic drug concentrations whereas low drug doses induce immuno-augmentation.
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A 6-month, multicentre, randomized, double-blind, parallel-group, vehicle-controlled study of 346 subjects with photoaged skin, as defined by the presence of fine lines in the periorbital region. The main outcome measure was profilometry measurements of replicas of the periorbital region, taken at 0 and 6 months. Subsidiary outcome measures were clinical scoring of wrinkles/fine lines at 0, 1, 3, 6 and 9 months and histopathology at 0 and 6 months.
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Due to a dedifferentiation of tumor cells, some thyroid carcinomas lose their capability for radioiodine (RI) concentration. This phenomenon is associated with a worse prognosis and prevents effective treatment. Retinoic acid (RA) is known to induce redifferentiation in various kinds of tumors and has been used recently in thyroid cancer.
Fluorescein angiography did not demonstrate the leakage points throughout the subretinal fluid. Spectral-domain optical coherence tomography showed the excessive subretinal fluid and serous retinal detachment at macula. Two weeks after presentation, visual acuity was partially increased and subretinal fluid was disappeared at macula.
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While there are some limitations to this study, the results are consistent with recent international research suggesting previous pregnancy rates on isotretinoin have been underestimates. Widening funding of isotretinoin will likely increase the absolute numbers of pregnancies but also has the potential to increase relative numbers. As such, it will be vital that primary care is alert to the risks of isotretinoin use and gain experience in its day-to-day usage. Although access has been widened, all requests for funding will now be recorded on a national database (Special Authority database) to enable closer monitoring of isotretinoin usage.
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This Phase II study was designed to determine the median survival time of adults with supratentorial glioblastoma treated with a combination of temozolomide (TMZ) and 13-cis-retinoic acid (cRA) given daily with conventional radiation therapy (XRT).
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Fifty-four patients, 63% with Pa and 37% with Bt ADK, received 3 courses of cisplatin-gemcitabine induction chemotherapy. Progression-free (PF) patients were given consolidation radiotherapy with concurrent capecitabine. PF patients had, as maintenance immunotherapy (MI), interleukin 2 (1.8x10 IU) and 13-cis-retinoic acid (0.5 mg/kg) [DOSAGE ERROR CORRECTED].
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A retrospective study investigated a case series of patients who presented with nasal tip deformities subsequent to the use of isotretinoin after rhinoplasty. Patients who had taken isotretinoin after rhinoplasty were identified from a single surgeon's case log. Clinic charts and operative reports were reviewed. Predisposing factors and time intervals to complications were identified.
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Data are presented for 1181 patients enrolled in a placebo-controlled chemoprevention trial of 13-cis-retinoic acid. Nearly 17% of patients presented with a SPT. The log rank test and Cox proportional hazards model were used to examine risk factors for SPT development.