To assess the risk of vitamin D deficiency in a sunlight-deprived population, we studied eight ambulatory patients with xeroderma pigmentosum (XP) who practiced intensive sun protection during a chemoprevention study of oral isotretinoin.
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The 9-cis-retinoic acid (9cRA)-inducible enhancer of the rat cellular retinol-binding protein type II gene (CRBP II) was shown to be differentially regulated by the murine retinoid X receptor alpha (RXR alpha) as compared with RXR beta. Transient transfection assays performed in NIH 3T3 fibroblast cells demonstrated that RXR alpha yielded a high level of 9cRA-dependent transcription of a reporter gene linked to the CRBP II enhancer, when compared with RXR beta. This effect was cell type-dependent, since both receptors elicited comparable transcriptional activation of the same reporter in P19 embryonal carcinoma cells. To further explore the structural determinants responsible for the differences between these two receptors, a series of chimeric receptor constructs were made. Co-transfection assays utilizing these chimeras demonstrated that both the N terminus and the hinge region connecting the DNA binding domain with the ligand binding domain of RXR alpha were responsible for the high level of 9cRA-dependent transcription observed in NIH 3T3 cells, Furthermore, the hinge region of RXR alpha was shown to be necessary to repress, in the absence of hormone, the transcriptional activation function located in the N-terminal domain of RXR alpha. These results stress the importance of functional links between different RXR domains and suggest an RXR subtype and cell type-dependent specificity in the control of the 9cRA response.
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No significant differences were found in lumbar spine and femoral BMD between the patient and control groups at the beginning of the study (P > 0.05), and no statistically significant difference was observed between the BMD values in patients at the beginning vs. the end of treatment (P > 0.05). No statistically significant difference in bone turnover markers was found between patients and controls at the beginning of the study (P > 0.05), and no statistically significant changes in bone turnover markers were observed in patients at the beginning vs. the end of treatment (P > 0.05).
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Ataxia-Telangiectasia is a rare multisystem autosomal recessive disorder [OMIM 208900], caused by mutations in Ataxia-Telangiectasia Mutated gene. It is characterized by neurological, immunological and cutaneous involvement. Granulomas have been previously reported in Ataxia-Telangiectasia patients, even if acne rosacea has not been described.We report a case of a young Ataxia-Telangiectasia patient with a severe immunological and neurological involvement, who developed granulomatous skin lesions diagnosed by skin biopsy as acne rosacea. Considering the severe clinical picture and the lack of improvement to multiple topic and systemic therapies, treatment with Isotretinoin was started and the skin lesions disappeared after five months. However the therapy was stopped due to drug-hepatotoxicity.Systemic treatment with Isotretinoin should be carefully considered in patient with Ataxia-Telangiectasia for the treatment of multi-drug resistant acne rosacea, however its toxicity may limit long-term use and the risk/benefit ratio of the treatment should be evaluated.
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This paper examines the existing literature and MedWatch reports concerning a proposed relationship between isotretinoin and depression and suicide. The authors provide a brief overview of the biology of isotretinoin and depressive disorder and find no basis for a putative molecular mechanism linking the two. They also address the complexities of Substance-Induced Mood Disorder (SIMD) as a psychiatric diagnosis and its relevance to isotretinoin. Based on this review, the authors conclude that there is no evidence to support a causal connection between isotretinoin and major depression or suicide, because reported cases do not meet the established criteria for causality. The authors also conclude, however, that it is important for dermatologists to be aware of the risk factors for suicide and to monitor patients who exhibit depressive symptoms.
Sixteen patients with minimal facial acne but with symptoms of dysmorphophobia related to their acne were treated with isotretinoin, 0.5 mg/kg/day, (n = 5); 1 mg/kg/day (n = 11) for 16 weeks. All 16 had previously received long-term antibiotic therapy with no 'perceived' improvement in their acne. Formal psychiatric assessment was not possible through lack of cooperation. Fourteen of 16 patients derived benefit from isotretinoin therapy in that all 14 were subsequently satisfied with the cosmetic results achieved. However, the incidence of relapse was greater than that for a control group, 14 requiring additional therapy in the form of antibiotics or further isotretinoin (seven patients) within 20 months of completing the original course. Patients with acne and dysmorphophobia represent an important group of patients who benefit from treatment with isotretinoin; if possible this should be in conjunction with psychotherapy.
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To compare the clinical benefit of isotretinoin (0.05%) and erythromycin (2%) gels alone and in combination (Isotrexintrade mark) in acne patients.
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We previously reported a favorable histologic response of dysplastic nevi to topical tretinoin in three patients. To investigate the anticancer and cancer preventive effects of retinoids we have examined the effect of systemic isotretinoin on dysplastic nevi. After confirmatory baseline biopsies, eleven patients with the dysplastic nevus syndrome were treated with oral isotretinoin, 40 mg twice a day for 4 months. At completion of therapy, at least three previously identified and photographed clinically typical dysplastic nevi were rephotographed and removed for histologic evaluation. Eight patients completed the full course of medication. There were no clinical changes in the dysplastic nevi in these patients. Posttherapy biopsy specimens in six volunteers revealed most of the remaining lesions to be dysplastic nevi. The majority of lesions biopsied in two subjects showed normal, benign nevi only. This proportion of clinically typical dysplastic nevi that prove to be normal nevi histologically (28%) is not significantly different from that reported by others. Oral isotretinoin does not appear to have a significant biologic effect on the clinical or histologic appearance of dysplastic nevi in the treatment schedule employed.
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We sought to determine whether isotretinoin can be safely administered to patients with RDEB as a possible chemopreventive agent.
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Phase I cohort design. Cisplatin was administered every 3 weeks. 5-FU and LV were administered together as a weekly 24-h infusion. Cis-RA was given orally twice daily. IFN was initially given subcutaneously at a dose of 3 million units (MU) daily.
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For intermediate risk, conventional chemotherapy appears to be acceptable treatment. However, for high-risk patients, every effort should be made to control residual disease including the use of myeloablative chemotherapy, differentiating agents and immune-modulating agents.
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Dermatologists frequently are consulted by a pregnant patient or a woman of childbearing age who desires acne therapy. Because there are no published studies in which women took acne medications throughout pregnancy, information about safety must be obtained indirectly from studies in which the agents were taken for another indication during some portion of pregnancy. Oral tetracycline is associated with maternal liver toxicity and deciduous tooth staining in the infant, and tetracycline occasionally has been associated with other congenital anomalies. Maternal isotretinoin ingestion is associated with major craniofacial and cardiac deformities, as well as other congenital anomalies. Erythromycin, however, appears to be safe. Topical acne medications never have been implicated as a cause of fetal deformities in human beings. Dermatologists should be aware of potential toxic and teratogenic effects of acne medicines before prescribing them to women of childbearing age. Prompt reporting of adverse effects is encouraged.
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The recent interest in treating acne with one of the retinoid drugs has been accompanied by a wide variety of ocular side effects involving the eyelids, cornea, lens, optic nerve and retina. In one group of patients being evaluated for possible efficacy of a retinoic acid analogue in treating psoriasis, several patients complained of difficulty driving at night due to decreased dark adaptation which we were able to document. Fortunately, most of the above side effects tend to disappear within months after the drug is discontinued. However, we have recently seen two cases of dry eye syndrome associated with Accutane therapy that have persisted for more than two years. In addition, scattered reports have appeared regarding cataracts in young patients (teens to early 40's) which developed during, and/or after Accutane treatment. We have examined lens matter derived from two such patients who had extracapsular cataract extractions. Their lens proteins showed an elevation in UV absorptivity (between 330-390 nm) compared with matched control material (derived from Eye Bank specimens) and HPLC analyses demonstrated an abnormal peak in their profiles which was similar to one present in control samples incubated with retinoic acid and was not present in lens protein samples derived from cataracts not associated with Accutance therapy. These observations demonstrate that some of the Accutane induced ocular side affects are not reversible when the drug is stopped, and patients on such therapy should be carefully monitored.
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Isotretinoin is a very effective drug for treating severe recalcitrant nodular acne. A new micronized formulation of isotretinoin has been shown to be clinically equivalent to standard isotretinoin with improved bioavailability and minimal food effect. The safety profile of the micronized formulation has not been described previously.
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Isotretinoin is the most efficacious long-lasting treatment for acne; however, some factors, including polycystic ovary syndrome (PCOS), patient age, family history, and type and number of acne lesions, may lead to treatment resistance or relapse following treatment. The aim of this study was to compare the efficacy and permanence of systemic isotretinoin (SI) in nodulocystic acne patients with and without PCOS and to evaluate the factors associated with relapse during the first and second post-treatment years.
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A poor oxygenation defined as a median pO2 of 10 mm Hg or less was present in 15/38 tumors (39%) in which measurements prior to any treatment were done. Low pO2 readings below 5 mm Hg were present in 70% of all tumors prior to treatment. In 13 of 15 hypoxic tumors, pO2 measurements at 19.8 Gy were performed. In these tumors, a significant increase of the median pO2 from 6.0+/-3.1 mm Hg to 20.7+/-21.2 mm Hg was found, p<0.01. The increase in the median pO2 was more pronounced in patients with radiotherapy plus additional cRA/IFN treatment as compared to patients treated with irradiation alone (median pO2 raised from 7.0+/-3.5 mm Hg to 40.9+/-21.3 mm Hg versus 5.7+/-3.1 mm Hg to 14.7+/-17.9 mm Hg). In a multivariate analysis, both the effect of radiation dose (pretreatment versus 19.8 Gy) and the type of treatment (XRT alone versus XRT plus cRA/IFN) had significant impact on the pO2 (P = 0.003 and p = 0.04). In patients with well-oxygenated tumors (pretreatment median pO2>10 mm Hg), 20/23 (87%) achieved a clinically complete response. In patients with primarily hypoxic tumors, 6/6 patients whose primarily hypoxic tumors showed an increase of the median pO2 above 10 mm Hg at 19.8 Gy achieved a complete remission (CR). In contrast, only 4/7 patients with a low pretreatment and persisting low median pO2 achieved a CR.
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BACKGROUD/AIMS: Widely prescribed in routine practice, isotretinoin has an unknown impact on ovarian reserve. With a long history in acne treatment and numerous potential side effects, it is surprising that very few prospective studies have investigated its effect on ovarian reserve. Therefore, we aimed to evaluate the impact of oral isotretinoin on ovarian reserve based on hormonal parameters, anti-Müllerian hormone (AMH), ovarian volume (OV), and antral follicle count (AFC) in women of reproductive age with acne.
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Isotretinoin treatment for acne can lead to inflammatory flare-ups or an aggravation, occasionally leading to acne fulminans. The purpose of this work was to examine our cases and to propose a classification system for management.
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13-cis-retinoic acid is an established component of treatment for children with high-risk neuroblastoma. However, significant hypercalcemia is increasingly recognized as a potentially life-threatening dosage-related side effect. We present 2 patients with significant hypercalcemia secondary to 13-cis-retinoic acid and their management, and identified the predictive factors for susceptibility to hypercalcemia. Assessing glomerular filtration rate and concomitant medication help predict individual susceptibility to hypercalcemia. Calcium levels should be monitored at days 1, 7, and 14 of each course of retinoic acid. An algorithm for the management of hypercalcemia during the affected and subsequent cycles of retinoid therapy is proposed.
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Isotretinoin is an effective drug utilized in the management of acne vulgaris and is known to cause dry mouth. In this study, we aimed to evaluate this effect of isotretinoin on the salivary gland function in patients with acne vulgaris using technetium-99m (Tc-99m) pertechnetate imaging of the salivary glands.
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Vitamin A (retinol) and its analogues (retinoids) are clinically effective in cystic acne and psoriasis, diseases in which neutrophils may constitute major components of inflammatory cell infiltrates. We found that the earliest histopathologic alteration in psoriasis is the disappearance of neutrophils at 2 to 4 weeks after the initiation of therapy with etretinate. Since retinoids may exert anti-inflammatory effects by virtue of an action upon neutrophils, we studied the effects of the following retinoids on discrete neutrophil functions in vitro: retinol, retinyl acetate, retinal, tretinoin, isotretinoin, etretinate, and Ro 10-1670. Although they had no significant effects upon aggregation, chemokinesis, or chemotaxis, all of the retinoids, with the exception of etretinate and Ro 10-1670, profoundly inhibited superoxide anion production and lysosomal enzyme release. Tretinoin and isotretinoin were the most effective inhibitors. We propose that these drugs exert their pharmacologic effects (resolution of inflammatory lesions) by inhibiting the release of mediators of inflammation and by preventing the accumulation of neutrophils in acne lesions when applied topically or systemically, respectively.
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Different immunologic mechanisms contribute to development of inflammation in acne vulgaris and immunologic effect of levamisole has been demonstrated.
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Thirty-nine patients were enrolled. All were assessable for survival, 35 for response and toxicity (median follow-up was 38 months). The overall and complete response rates were 34% and 17%, respectively, with median durations of 9 and 35.4 months, respectively. The response rate was higher in locally advanced (67%) than metastatic (17%) disease (P =.007). Median survival was 14.6 months. One-, 2-, and 5-year survival rate estimates were 58%, 32%, and 21%, respectively. Toxicity included generally mild to moderate fatigue and mucocutaneous dryness, moderate to severe neutropenia (38%), and neutropenic fever (6%). There were no treatment-related deaths. In vitro growth inhibition and apoptosis effects of cisplatin were differential and inversely associated with those of retinoic acid and especially IFNalpha in two skin SCC lines.
9-cis-retinoic-acid, a common acne cream, is being examined as a treatment for Kaposi's sarcoma (KS). Participants will apply the cream directly on the lesions twice daily for the first two weeks, and four times daily for two more weeks. Participants must not have systemic KS or be using any other KS treatments.
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Patients treated with dietary supplement had lower side effects, with a less degree of erythema and dryness, and greater degree of hydration; a greater adherence to therapy was also reported.
Oral isotretinoin (13-cis retinoic acid) is the most effective drug in the treatment of acne and restores all major pathogenetic factors of acne vulgaris. isotretinoin is regarded as a prodrug which after isomerizisation to all-trans-retinoic acid (ATRA) induces apoptosis in cells cultured from human sebaceous glands, meibomian glands, neuroblastoma cells, hypothalamic cells, hippocampus cells, Dalton's lymphoma ascites cells, B16F-10 melanoma cells, and neuronal crest cells and others. By means of translational research this paper provides substantial indirect evidence for isotretinoin's mode of action by upregulation of forkhead box class O (FoxO) transcription factors. FoxOs play a pivotal role in the regulation of androgen receptor transactivation, insulin/insulin like growth factor-1 (IGF-1)-signaling, peroxisome proliferator-activated receptor-γ (PPArγ)- and liver X receptor-α (LXrα)-mediated lipogenesis, β-catenin signaling, cell proliferation, apoptosis, reactive oxygene homeostasis, innate and acquired immunity, stem cell homeostasis, as well as anti-cancer effects. An accumulating body of evidence suggests that the therapeutic, adverse, teratogenic and chemopreventive effecs of isotretinoin are all mediated by upregulation of FoxO-mediated gene transcription. These FoxO-driven transcriptional changes of the second response of retinoic acid receptor (RAR)-mediated signaling counterbalance gene expression of acne due to increased growth factor signaling with downregulated nuclear FoxO proteins. The proposed isotretinoin→ATRA→RAR→FoxO interaction offers intriguing new insights into the mode of isotretinoin action and explains most therapeutic, adverse and teratogenic effects of isotretinoin in the treatment of acne by a common mode of FoxO-mediated transcriptional regulation.
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The search yielded 2778 citations, of which 20 studies met inclusion criteria. Tretinoin was used in 14 of the studies. Other retinoids assessed included isotretinoin, adapalene, alitretinoin, and tazarotene. Within patients receiving topical tretinoin, 27.9% reported the occurrence of at least one noncutaneous AE. The majority of noncutaneous AE were transient and judged not to be related to tretinoin treatment.