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The management of acne in South-East Asia is unique, as Asian skin and local variables require a clinical approach unlike that utilized in other parts of the world. There are different treatment guidelines per country in the region, and a group of leading dermatologists from these countries convened to review these guidelines, discuss current practices and recent advances, and formulate consensus guidelines to harmonize the management of acne vulgaris in the region. Emphasis has been placed on formulating recommendations to impede the development of antibiotic resistance in Propionibacterium acnes. The group adopted the Acne Consensus Conference system for grading acne severity. The group recommends that patients may be treated with topical medications including retinoids, benzoyl peroxide (BPO), salicylic acid, a combination of retinoid and BPO, or a combination of retinoids and BPO with or without antibiotics for mild acne; topical retinoid with topical BPO and a oral antibiotic for moderate acne; and oral isotretinoin if the patient fails first-line treatment (a 6- or 8-week trial of combined oral antibiotics and topical retinoids with BPO) for severe acne. Maintenance acne treatment using topical retinoids with or without BPO is recommended. To prevent the development of antibiotic resistance, topical antibiotics should not be used as monotherapy or used simultaneously with oral antibiotics. Skin care, comprised of cleansing, moisturizing and sun protection, is likewise recommended. Patient education and good communication is recommended to improve adherence, and advice should be given about the characteristics of the skin care products patients should use.
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We prospectively evaluated 152 smokers with bronchoscopy and obtained biopsies from six sites. Subjects with dysplasia and/or a metaplasia index of greater than 15% were randomly assigned to receive either 1 mg/kg isotretinoin or placebo daily for 6 months. Of 86 subjects randomized (41 isotretinoin, 45 placebo), 69 were reevaluated at the completion of treatment.
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The small number of patients with acne treated with 13-cis RA was a major limitation.
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Rosacea is a multifactorial skin disorder that usually affects middle-aged persons. Little is known about the etiology of rosacea, although the disease most likely represents a vascular anomaly occurring in patients with fair skin. The mainstay of treatment for inflammatory lesions has been oral antibiotics, but topical metronidazole also may be effective. Because recurrences are common after discontinuation of therapy, doses should be tapered as tolerated. Antibiotics are more effective for inflammatory lesions than for erythema and telangiectasia. Isotretinoin may be effective for inflammatory lesions, edema and rhinophyma in some resistant cases, but its use is limited by its side effects and teratogenicity. Ablation of telangiectasia with the tunable dye laser and various surgical approaches to rhinophyma are effective newer treatments but are more expensive and less available than conventional therapy.
C57BL/6J mice were used to study the ocular teratogenic effects of cyclophosphamide administered to pregnant females on d 9 of pregnancy at a dose of 5 mg/kg body weight. Nile blue staining demonstrated increased cell death at the base of the optic stalk, in the optic vesicle, and in the perivesicular mesenchyme in treated embryos. Malformations studied at gestational d 11 and 16 by light and scanning electron microscopy included microphthalmos, microphakia, and aphakia and were predictable based upon patterns of increased cell death. These anomalies are similar to those reported with exposure to ethanol or isotretinoin on gestational d 7.
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Between 1958 and 1961 approximately 10,000 children with severe limb defects were born, whose mothers had taken the somnifacient thalidomid. Since then, pharmaceutical agents in pregnancy are applied with legitimate caution by the pharmaceutical industry, physicians and patients, although often accompanied by irrational panic. According to statistical inquests, 15 to 50 percent of expectant mothers take pharmaceutical agents in the first trimester of pregnancy, often being not aware of their pregnancy. Considering the sensitive phase of organogenesis, the consequences may be particularly fatal in the first three months of pregnancy. After thalidomid more teratogenic pharmaceutical agents were discovered, i.e. coumarin derivates (e.g. warfarin), vitamin A and its derivates (e.g. isotretinoin), antifolates or anticonvulsants such as hydantoin or valproic acid. A number of other drugs are supposed to be potentially embryotoxic/fetotoxic, the effect of those pharmaceutical agents above all depending on dose and time of exposure. Case reports on malformations are available for numerous drugs, but studies with statistical validity are often missing. The pharmaceutical industry takes a legally safe position noting "contraindication" or at least "strict indication" in the consumer information. Concerning expectant mothers with chronic diseases like epilepsy, hypertension or bronchial asthma a therapeutic nihilism may lead to a dramatic deterioration of the disease, thereby causing high risks in fetal development. On the other hand numerous abortions without profound indications are carried out due to insufficient information of patients and medical staff on the real risks of a medication during early pregnancy. On principle reliable drugs should be preferred to new agents during fertile age of women. Special information centres for reproductive toxicology with corresponding data banks should be established and consulted, if an exposure with an insufficiently tested substance has taken place in ignorance of pregnancy.
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Acne inversa (synonyms: acne triad, acne tetrad or hidradenitis suppurativa, and others) is an inflammatory disease that develops mostly in the axillae, under the breasts and in the anogenital region. The new term, acne inversa, encompasses what was previously called the occlusion triad or tetrad. The disease is relatively common, but the diagnosis is frequently missed. Many different modalities of treatment are recommended in the literature. Radical surgical intervention should be performed at the earliest recognized stage. In the light of experience with our own patients, we propose surgical intervention with wide excision and subsequent healing by secondary intent.
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The causative role of Demodex folliculorum should be considered in immunocompetent children with rosacea or rosacea-like refractory eruptions. In such cases, treatment with ivermectin can be beneficial.
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Isotretinoin is an effective acne medication. The evidence for it causing depression and suicide, although widely publicised, remains uncertain.
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We have previously reported that human sebaceous glands can be maintained for up to 14 d as whole organs with full retention of the physiological rate and pattern of new cell formation, but we have also reported that the newly formed cells did not differentiate normally, causing a progressive loss of lipogenesis in vitro. We now show that this abnormal sebocyte differentiation was attributable to the presence of epidermal growth factor (EGF) and phenol red in our maintenance medium. In their absence, human sebaceous glands apparently retain in vivo rates of cell division and lipogenesis over 7 d of maintenance in addition to a retention of in situ morphology. This is reversible on the re-addition of 10 ng EGF/ml and 10 mg phenol red/ml. The addition of 600 pM 17 beta-estradiol results in a significant fall in the rate of lipogenesis over 7 d of maintenance, without affecting the rate of cell division. This effect is apparently due to abnormal differentiation of newly formed sebocytes. Neither 1 nM testosterone nor 1 nM dihydrotestosterone (DHT) has any effect on rates of cell division of lipogenesis over 7 d. In the presence of phenol red, however, 1 nM testosterone or 1 nM DHT cause a significant reduction in the rate of lipogenesis over 7 d of maintenance. One micromolar 13-cis retinoic acid caused a significant reduction in the rate of lipogenesis over 7 d in both the presence and absence of phenol red. These findings show that we can model the physiological effects of steroids, EGF, and 13-cis retinoic acid in vitro.
We report a case of actinic folliculitis in a 29-year-old woman who presented with a 10-year history of a recurrent pustular eruption affecting her face, typically appearing 4-6 h after exposure to sunlight. Actinic follicuitis is a rare photodermatosis, which falls into the same spectrum as acne aestivalis and actinic superficial folliculitis.
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Since the spinal cord tumour was inoperable, the patient was treated with x-radiation, continued on isotretinoin treatment and was followed closely for tumour response.
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Acne Vulgaris is one of the most common skin disorders which dermatologists have to treat. It mainly affect adolescent, though may present at any age. In recent years, due to better understanding of the pathogenesis of acne, new therapeutic modalities and various permutation and combinations have been designed. In topical agents; benzoyl peroxide, antibiotics, retinoids, etc are the mainstay of treatment; can be given in combinations. While systemic therapy includes oral antibiotics, hormonal therapy, and isotretinoin, depending upon the need of patients it has to be selected. Physical treatment in the form of lesion removal, photo-therapy is also helpful in few of them. Since various old and new topical and systemic agents are available to treat acne, it sometime confuse treating dermatologist. To overcome this, panel of physicians and researchers worked together as a global alliance and task force to improve outcomes in acne treatment. They have tried to give consensus recommendation for the treatment of acne. Successful management of acne needs careful selection of anti-acne agents according to clinical presentation and individual patient needs.
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We conclude that the long-term administration of isotretinoin has positive effects on the clinical results of chronic rhinosinusitis.
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This study clearly showed that patients treated with isotretinoin experienced oral side effects.
A suppurated and fistulized nodule on an anoperineal or axillary location must suggest this disease. Our series is characterized by the prevalence of men and the frequency of severe forms.
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Several treatments have been described in the literature, such as corticosteroids, psoralen plus ultraviolet A (PUVA) light therapy, topical nitrogen mustard, and radiation therapy. Isolated cases have documented the beneficial responses of pimecrolimus, dapsone, indomethacin, minocycline, isotretinoin, hydroxychloroquine and interferons. No single treatment has been shown to be consistently effective.
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SMART may have lead to a decrease in isotretinoin prescriptions. Further research is needed to determine whether the reduced number of isotretinoin prescriptions reflects appropriate use or inhibited use resulting in loss of access to the product's benefits.
Sebum production has been measured in twenty patients in whom 13-cis-retinoic acid therapy had been discontinued for at least 20 weeks. While sebum production had returned to pretreatment levels by 30 weeks in seven subjects, 30% to 80% reduction in sebaceous gland activity was still present for as long as 80 weeks in eight subjects. Four of these eight patients, who were followed for more than a year, still had marked sebaceous inhibition when last tested. The prolonged remission seen in patients with nodulocystic acne may be related in part to continued sebaceous gland inhibition in some patients, but it obviously is not the only actor responsible for the long-term improvement that is seen.
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Adult T-cell leukemia (ATL) is a peripheral T-cell neoplasm caused by human T-cell leukemia virus type I (HTLV-I). Despite the administration of combined intensive chemotherapy, the reported survival time of patients with acute and lymphoma types of ATL is less than 10 months. We therefore examine the effects of all-trans-retinoic acid (ATRA), 9-cis-RA and 13-cis-RA and tried to elucidate the mechanisms of inducing growth inhibition and apoptosis by these RAs using four ATL cell lines established in our laboratory. All the investigated RAs inhibited cell growth and the cells were arrested at the G1 phase. Apoptosis was induced in three out of four cell lines. Among the growth regulatory proteins examined, the level of p21Waf1/Cip1 protein was found to increase after RA treatment, thus resulting in pRb hypophosphorylation which also induced the arrest of the cells at the G1 phase. In addition, the p53 level decreased at the same time. Fas-FasL system and the downregulation of CD25 (IL-2R/alpha) expression did not seem to be involved. Based on these findings, the ability of RAs to induce a remission of ATL is thus strongly suggested.
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Ocular contraindications to LRS include unstable refractive error, corneal ectatic disorders, a history of herpetic keratitis, Avellino corneal dystrophy, significant cataract, and uncontrolled glaucoma. LRS should also be avoided in uncontrolled diabetes, collagen vascular disease (CVD), pregnancy, and in patients taking amiodarone and isotretinoin.
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The psychological consequences of acne have been the subject of many studies. As a particularly visible skin disorder, acne complicates the daily lives of adolescents who are undergoing multiple transformations: physical, intellectual and emotional. While it is well established that acne can be responsible for depression and low self-esteem, it is likely that this impact is aggravated by the sociological evolution of adolescents in the 21st century. Understanding the codes of adolescents today (who can be characterized as being more concerned by their appearance than previous generations at the same age) allows us to optimize our medical approach to acne and facilitates treatment compliance and adherence.
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Thirty-six patients with advanced premalignant lesions of the upper aerodigestive tract, without cancer during the 2 years before the intervention, with evaluable lesions, and without retinoid therapy for 3 months before the trial.
The combinations of cyproterone acetate (2 mg)/ethinyl estradiol (35 microg), drospirenone (3 mg)/ethinyl estradiol (30 microg), and desogestrel (25 microg)/ ethinyl estradiol (40 microg) for 1 week followed by desogestrel (125 microg)/ethinyl estradiol (30 microg) for 2 weeks showed the strongest anti-acne activity. Gestagens or estrogens as monotherapy, spironolactone, flutamide, gonadotropin-releasing hormone agonists, and inhibitors of peripheral androgen metabolism cannot be endorsed based on current knowledge. Low dose prednisolone is only effective in late-onset congenital adrenal hyperplasia and dopamine agonists only in hyperprolactinemia. Treatment with antiandrogens should only be considered if none of the contraindications exist.
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Oral retinoids are effective in the treatment of patients with a variety of malignant and nonmalignant skin disorders, including mycosis fungoides. We treated six patients with cutaneous T-cell lymphomas with isotretinoin 1 to 2 mg/kg/d. All patients experienced symptomatic relief (fading of skin lesions and disappearance of pruritus) within two to eight weeks of starting the drug therapy; pretreatment and posttreatment biopsy specimens were unchanged. Adverse effects were minor and primarily consisted of drying of the mucous membranes. We conclude that isotretinoin is a well-tolerated, easily administered drug that provides good palliation of symptoms and signs associated with cutaneous T-cell lymphoma in patients who are unable or unwilling to comply with standard therapy.
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Isotretinoin was administered orally for 16 weeks, in a dosage of 1 mg/kg/day, to seven men with severe acne. A 36.2% reduction of nodulocystic lesions was observed at the conclusion of treatment and a 47.2% reduction was noted at the end of a 16-week follow-up period. However, there was an 88.4% decrease in sebum production and a marked reduction histologically in sebaceous gland size after 16 weeks of treatment, with a partial recovery of glandular activity at 32 weeks. The failure to observe a more striking overall response clinically resulted primarily from two of the seven patients showing worsening or no improvement of their disease, despite profound sebaceous gland inhibition. These findings suggest that the marked sebostatic effect of isotretinoin may not be the sole explanation for its mechanism of action in reducing the severity of acne.
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A total of 139 patients completed the study. Overall, patients received a mean of 80.92 mg/kg cumulative dose of isotretinoin. In the 2-year follow-up, relapse only appeared in 13 patients (9.35%).
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Isotretinoin is frequently prescribed for the treatment of acne vulgaris. Among the numerous documented adverse effects, most common are xerostomia and cheilitis. Lip abscesses as a consequence of cheilitis present dramatically and may pose a diagnostic challenge.
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A total of 261 adverse ocular reactions occurred in 237 patients who received isotretinoin, a commonly used drug in the treatment of severe cystic acne. Blepharoconjunctivitis, subjective complaints of dry eyes, blurred vision, contact lens intolerance, and photodermatitis are reversible side effects. More serious ocular adverse reactions include papilledema, pseudotumor cerebri, and white or gray subepithelial corneal opacities; all of these are reversible if the drug is discontinued. Reported cases of decreased dark adaptation are under investigation. Isotretinoin is contraindicated in pregnancy because of the many reported congenital abnormalities after maternal use (including microphthalmos, orbital hypertelorism, and optic nerve hypoplasia).
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Patient case report.
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The effect of 13-cis-retinoic acid (cRA) and all-trans-retinoic acid (tRA) used alone or in combination with interferon alpha-2a (alpha-IFN 2a) was tested on three established human cell lines: KB (epidermoid carcinoma of the oral cavity), SCC-25 (tongue squamous cell carcinoma) and MCF-7 (mammary carcinoma). Both retinoids significantly decreased cell proliferation (growth curves) and colony forming efficiency (CFE) in all cell lines, in a dose-dependent way (at a concentration ranging from 10(-5) to 10(-9) M) and differing from line to line, following the pattern: MCF-7 > SCC-25 > KB. Retinoids at any concentration (already at 10(-7) M) combined with alpha-IFN 2a (ranging from 100 to 500 IU/ml) were more effective in inhibiting cell proliferation than each of the two compounds alone. This was particularly evident with SCC-25 cells. Concerning MCF-7 cells, on the contrary, the effects produced by the association suggested a possible additive more than synergistic amplification of growth inhibition.
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A 19-year-old female patient is presented who was taking isotretinoin for severe, nodulocystic acne. She subsequently developed abdominal pain during the course of treatment, thought to be related to an adverse reaction to the medication. A concerning side effect of isotretinoin is hypertriglyceridemia, which may be a cause of pancreatitis. A lipase level was determined to be elevated in this case. The patient was diagnosed with acute pancreatitis and the offending agent was discontinued. Clinicians need to be aware of the side effects when prescribing isotretinoin for recalcitrant acne.
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The effective treatment for juvenile myelomonocytic leukemia (JMML) patients lacking access to stem cell transplantation remains unavailable. Here, we describe a promising result obtained with novel regimen comprised of a combination of chemotherapy and differentiation therapy. Five patients diagnosed as JMML were treated with a standard regimen (cytosine arabinoside (Ara-C) 100mg/m(2) per day continuous infusion (days 0-6), etoposide 100mg/m(2) per day (days 0-4), vincristine 1.5mg/m(2) per d (day 9) and isotretinoin 75-100mg/m(2) per day (days 10-20)). All patients responded to the standard regimen. Three of the five were later treated with salvage a regimen (Ara-C 100mg/m(2) per day continuous infusion (days 0-4), etoposide 100mg/m(2) per day (days 0-4) and Ara-C 15mg/m(2) per day SC (days 6-15)) when immature myeloid cells reappeared in the peripheral blood, the spleen increased or blast crisis occurred. Immature myeloid cells disappeared again after one cycle of salvage regimen in all patients. All patients are alive now with a median follow up duration of 27 months (8-69 months). Although the number of patients enrolled was limited, the standard and salvage regimens were found to be safe and effective alternatives for JMML patients without a matched donor. These regimens also could be used safely before stem cell transplantation.
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ABSTRACT.: In the reaction of kidneys to injury, cytokine-driven proliferation plays an important role and precedes the development of glomerulosclerosis. There is great interest in agents that may interfere with such proliferation. Therefore, a rat model of mesangioproliferative glomerulonephritis (induced by anti-Thy1.1) was studied, and the effects of all-trans-retinoic acid (all-trans-RA) and isotretinoin, powerful antiproliferative and anti-inflammatory substances, on glomerular damage and cell proliferation were examined. Vehicle-injected control rats were compared with rats treated with daily subcutaneous injections of 10 mg/kg body wt all-trans-RA or 40 mg/kg body wt isotretinoin (n = 9 to 11 per group), using either a pretreatment (days -2 through 8) or posttreatment (days +3 through +8) protocol, i.e., starting before or after the induction of anti-Thy1.1 nephritis, respectively. All-trans-RA prevented the BP increase evoked by anti-Thy1.1 (anti-Thy1.1/vehicle, 112.2 +/- 4.8 mmHg; anti-Thy1.1/RA, 87.5 +/- 2. 5 mmHg; P < 0.001). Treatment with all-trans-RA or isotretinoin produced a 70% decrease in the urinary albumin excretion rate (P < 0. 02). Periodic acid-Schiff staining of saline-perfused kidneys (day 8) revealed significantly fewer glomerular cells in RA-treated nephritic rats (anti-Thy1.1/vehicle, 97 +/- 3.1 cells/glomerulus; anti-Thy1.1/RA, 80 +/- 4.4; P < 0.02; control/vehicle, 69 +/- 1.2). No difference was observed between all-trans-RA and isotretinoin treatment. The capillary occlusion scores were significantly lower for the anti-Thy1.1/RA-treated group (1.9 +/- 0.1) than for the anti-Thy1.1/vehicle-treated group (2.9 +/- 0.5, P < 0.001). In the anti-Thy1.1/vehicle-treated group, 11.9 +/- 1.1 glomerular cells were proliferating cell nuclear antigen-positive; however, in the anti-Thy1.1/RA-treated group, only 5.3 +/- 0.8 cells were proliferating cell nuclear antigen-positive (P < 0.002; control, 2.2 +/- 0.2). Glomerular mitoses were reduced by 67% in the anti-Thy1. 1/RA-treated group, compared with the anti-Thy1.1/control group (P < 0.002). Glomerular staining for platelet-derived growth factor B-chain was significantly reduced in anti-Thy1.1-treated nephritic rats in the presence of isotretinoin or all-trans-RA, compared with the vehicle-treated group (P < 0.001). It is concluded that all-trans-RA limits glomerular proliferation, glomerular lesions, and albuminuria in an established model of renal damage. The findings point to retinoids as potential novel modulators of glomerular injury.
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Since the proposal of the tumor stem cell hypothesis, considerable interest has been devoted to the isolation and purification of tumor stem cells. Tumor stem cell enrichment from primary tumor derived cell spheres has been demonstrated in specific, serum-free media. This goal of this study is to establish a method of cultivating floating tumor spheres from neuroblastoma cells and to confirm that neuroblastoma spheres are rich in tumor stem cells.
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The goal of the current report was to demonstrate the long-term efficacy of outpatient subcutaneous (sc) interferon alpha (IFN-alpha) and sc interleukin 2 (IL-2)-based combination regimens in patients with metastatic renal cell carcinoma.
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Oral isotretinoin is highly effective in all forms and grades of acne, even in lower dosages (<0.5 mg/kg/day). There is a paucity of comparative data on the various low-dose regimens of oral isotretinoin in the Indian literature.