The effects of acitretin (free acid of etretinate) on the serum lipoprotein pattern and on the fat elimination in serum of 8 patients with psoriasis and 4 with palmo-plantar pustulosis were studied. The drug was given for 12 weeks; the average daily dose was 40 mg. Lipoprotein analyses and an intravenous fat tolerance test (IVFTT) were performed on three occasions (before, after 8 weeks' treatment, as well as 8 weeks after the end of the treatment). Acitretin increased the triglyceride concentration of the very low density lipoproteins by about 50% (p less than 0.02) and reduced the cholesterol of the high density lipoproteins significantly (p less than 0.001), leading to an increased low density/high density lipoprotein cholesterol ratio (p less than 0.02). The IVFTT indicated a lowering of the fat elimination capacity. All changes reverted to the original values after an 8-week wash-out period. The data suggest that the effects of acitretin on the lipoprotein metabolism resemble those of etretinate and isotretinoin.
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Retinoic acid (RA) has been demonstrated to drive both phenotypic and functional in vitro differentiation of B cell hybridomas from patients with common variable immunodeficiency (CVI) who manifest an "intrinsic" defect in terminal B cell differentiation (J Exp Med 1988;168: 55-71). Therefore, we conducted an open trial to determine the effects of oral 13-cis RA (0.5 mg/kg/day; 12 weeks receiving and 12 weeks without drug) on in vivo B cell differentiation in subjects with CVI. At various times before, during, and after drug administration, patients' B cells were tested for changes in cell-surface phenotype and in vitro immunoglobulin production in response to recombinant cytokines. Before 13-cis RA, all patients had decreased Leu-8 coexpression on CD20+ cells. Seven of eight subjects demonstrated "normalization" of this phenotype after 8 to 16 weeks of 13-cis RA administration. Patients whose B cells demonstrated more than normal CD20 display also had a fall toward normal in this parameter. These effects persisted for 6 to 12 weeks after drug was stopped. It appears that 13-cis RA drives B cells of patients with CVI to express a more differentiated cell-surface phenotype and may promote functional differentiation in some patients.
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Treatment of lung cancer remains frustrating. Most patients with lung cancer are not candidates for curative therapy, and new therapies have not made a substantial impact on survival. Consequently, some clinical investigators have focused their efforts on developing prevention strategies. Chemoprevention, the administration of agents to block or reverse carcinogenesis, is being investigated in ongoing trials. Studies of chemoprevention in lung cancer have included trials to reverse premalignant lesions such as sputum atypia or squamous metaplasia of the bronchial epithelium. Clinical trials of lung cancer prevention have often studied groups of participants with tobacco or asbestos exposure. Other clinical trials are being conducted among patients who have been treated for an early-stage lung cancer. As the result of diffuse epithelial injury, these patients are at very high risk for developing second primary tumors, predominantly in the lungs and upper aerodigestive tract. It is our hope that these studies may establish a new strategy for preventing lung cancer.
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This study was performed to detect possible toxic effects of oral isotretinoin treatment on the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL).
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Patients who had iodine-uptake-negative metastatic papillary or follicular thyroid cancers were selected from the thyroid database at The Royal Marsden Hospital and enrolled to an open-label, non-randomised phase II trial. Sites of metastatic disease were assessed using computed tomography or magnetic resonance imaging, and absence of iodine uptake was confirmed using a diagnostic radio-iodine scan before study entry. In eligible patients, isotretinoin was prescribed at 1.5 mg/kg/day orally for 8 weeks. Response was assessed within 2 weeks of completing treatment with repeat radio-iodine scan. All patients were reviewed every 2 weeks during treatment for assessment of toxicity.
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Psychiatric adverse drug reactions (ADRs) are distressing for patients and have important public health implications. We identified the drugs with the most frequent spontaneous reports of depression, and fatal and non-fatal suicidal behaviour to the UK's Yellow Card Scheme from 1998 to 2011.
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A patient with steatocystoma multiplex (SM) with severe inflammation was treated with oral isotretinoin. Inflamed cysts markedly improved with treatment. However, after eight weeks of therapy, many pre-existing cysts rapidly enlarged and new cysts occurred. Therapy was then discontinued. Isotretinoin may have exacerbated or worsened this condition.
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We performed an analysis of PAs registered in the French pharmacovigilance database between 01/01/1985 and 05/11/2014.
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Dissecting cellulitis of the scalp is a chronic, relapsing, inflammatory disease of the scalp that results in scarring alopecia. We present a case of a 32-year-old man with recalcitrant disease who is now responding to treatment with isotretinoin. The pathogenesis, clinical presentation, disease associations, and histopathological findings are reviewed. Treatment can be challenging. The literature on medical and surgical therapeutic options is reviewed.
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Issues related to lung cancer chemoprevention are reviewed, including risk factors and identification of high-risk cohorts, endpoint biomarkers, and current and new chemopreventive agents. Also, important findings from chemoprevention randomized, controlled trials are summarized.
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To ascertain whether retinoids can cause regression or prevent progression of CIN.
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AML2 is a member of the acute myelogenous leukemia, AML family of transcription factors. The biologic functions of AML1 and AML3 have been well characterized; however, the functional role of AML2 remains unknown. In this study, we found that AML2 protein expressed predominantly in cells of hematopoietic origin is a nuclear serine phosphoprotein associated with the nuclear matrix, and its expression is not cell cycle-related. In HL-60 cells AML2 expression can be induced by all three natural retinoids, all-trans-retinoic acid (RA), 13-cis-RA, and 9-cis-RA in a dose-dependent manner. A synthetic retinoic acid derivative, 4HPR, which neither activates RA receptor (RAR) alpha nor retinoic X receptor alpha was unable to induce the expression of AML2. A RAR-selective activator, TTNPB, induced AML2 expression similar to RA. Our study further showed that AGN193109, a potent RARalpha antagonist, suppressed AML2 expression induced by RA and that a retinoic X receptor pan agonist AGN194204 had no effect on its expression. Taken together, these studies conclusively demonstrated that the expression of AML2 in HL-60 cells is regulated through the RARalpha-specific signaling pathway. Our study further showed that after all-trans-retinoic acid priming, AML2 expression could be augmented by vitamin D(3). Based on these studies we hypothesize that AML2 expression is normally regulated by retinoid/vitamin D nuclear receptors mainly through the RARalpha-dependent signaling pathway and that it may play a role in hematopoietic cell differentiation.
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Myeloablative chemoradiotherapy and immunomagnetically purged autologous bone marrow transplantation has been shown to improve outcome for patients with high-risk neuroblastoma. Currently, peripheral blood stem cells (PBSC) are infused after myeloablative therapy, but the effect of purging is unknown. We did a randomised study of tumour-selective PBSC purging in stem-cell transplantation for patients with high-risk neuroblastoma.
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The effect of 2 retinoids, 13-cis-retinoic acid and 4-methoxy-2,3,6-trimethylphenyl analog of retinoic acid ethyl amide (designated Roll-1430), on tracheal tumor development in hamsters exposed to N-nitroso-N-methylurea was tested. Hamsters were intratracheally exposed either 18, 20, or 23 times to 1% N-nitroso-N-methylurea before the retinoids were administered in the diet. Evidence was presented which indicates that the great majority of the animals are free of invasive neoplasia at the start of retinoid feeding. In none of the 6 retinoid-treated groups could a statistically significant inhibition of tumor development be demonstrated. Hamsters treated with 13-cis-retinoic acid (128 or 172 mg/kg of diet) tended to have an elevated cancer risk; this effect was at a statistically significant level in the group treated with 172 mg/kg of diet. The distribution of histologic tumor types seemed to be shifted in favor of adeno and mixed adeno-epidermoid tumors in the group receiving a low carcinogen dose and Roll-1430. Similar to earlier studies with retinyl acetate tested in hamsters and rats, 13-cis retinoic acid and the retinoic acid ethyl amide analog Roll-1430, failed to inhibit development of respiratory tract neoplasms. We suspect that the reason for this is the absence of significant promoting influences in the current lung cancer models and that retinoids act mostly as anti-promoters.
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Oral isotretinoin (ISO) is the only drug which promotes prolonged remission or cure of severe acne. It also has other properties, supporting its use for non-acne indications. Retinoic acid (RA) is gold standard treatment for photoaging. ISO for photoaging treatment was reported in non-controlled trials as alternative to RA, which causes skin irritation.
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This study was funded by research grant CA176726 from the National Institute of Health. M.K. is supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (#PIOF-GA-2011-302078). The funding agencies had no role in the design of the study, in the analysis and interpretation of the data, in the writing of the report or in the decision to submit the paper for publication.
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These findings suggest that gram-negative folliculitis is not only a complication of long-lasting antibiotic treatment of acne and rosacea, but might be an entity of its own. Immunologic factors may play a critical role in the pathogenesis of gram-negative folliculitis.
The prognosis for neuroblastoma in advanced stage is still poor, even under conventional chemotherapy. This study aimed to investigate if very high dose chemotherapy in conjunction with autologous peripheral blood stem cell transplantation and 13-cis-retinoic acid could get excellent results in children with high risk neuroblastoma.
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Eosinophilic pustular folliculitis is a secondary symptom associated with HIV infection appears as levels of CD4 lymphocyte cells and T4 lymphocyte cell. Isotretinoin, an analog of vitamin A (retinoid) alters the DNA transcription mechanism and interferes in the process of DNA formation. It also inhibits the eosinophilic chemotactic factors present in sebaceous lipids and in the stratum corneum of patients suffering from this ailment.
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Rosacea is a chronic inflammatory disease affecting roughly 16 million Americans. Topical and oral antibiotic/anti-inflammatory agents are currently the mainstay of therapy and are often used in combination. In this article, the authors discuss the use of oral isotretinoin in the management of rosacea, exploring dosage, comparable efficacy, safety, and cost.