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Dan K. Chalker

Bio: Dan K. Chalker is an academic researcher from Rhode Island Hospital. The author has contributed to research in topics: Isotretinoin & Acne. The author has an hindex of 9, co-authored 12 publications receiving 3050 citations.

Papers
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Journal ArticleDOI
25 Dec 1996-JAMA
TL;DR: Results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites and require confirmation in an independent trial of appropriate design before new public health recommendations regarding seenium supplementation can be made.
Abstract: Objective. —To determine whether a nutritional supplement of selenium will decrease the incidence of cancer. Design. —A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial. Setting. —Seven dermatology clinics in the eastern United States. Patients. —A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years. Interventions. —Oral administration of 200 μg of selenium per day or placebo. Main Outcome Measures. —The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers. Results. —After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls (RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR, 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality (29 deaths in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred. Conclusions. —Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made.

2,780 citations

Journal ArticleDOI
TL;DR: The isotretinoin 0.05% gel proved to be statistically more effective than vehicle in reducing inflammatory lesions after 5 weeks and in reducing noninflammatory lesions and acne severity grade after 8 weeks.
Abstract: Two hundred sixty-eight patients with mild to moderate acne vulgaris completed a multicenter, double-blind, controlled study comparing isotretinoin 0.05% gel with its vehicle. Patients were treated twice daily for up to 14 weeks. Efficacy was measured by counting facial inflammatory and noninflammatory lesions and by grading acne severity initially and at 2- to 3-week intervals throughout the study. The isotretinoin 0.05% gel proved to be statistically more effective than vehicle in reducing inflammatory lesions after 5 weeks and in reducing noninflammatory lesions and acne severity grade after 8 weeks. Except for two patients who dropped out because of irritation, isotretinoin 0.05% gel was well tolerated.

76 citations

Journal ArticleDOI
TL;DR: This animal model demonstrates corticosteroid-induced skin atrophy and telangiectasia and the correlation of the degree of atrophy of the skin as determined by double skin-fold thickness micrometer measurement, and the link to body-weight change.
Abstract: • A bioassay for the evaluation of certain adverse effects of various corticosteroids was performed. Twenty-eight daily topical applications of corticosteroids to young rats produced reduction in body-weight gain, atrophy of the skin as determined by double skin-fold thickness micrometer measurement, and mild to severe telangiectasia. This animal model demonstrates corticosteroid-induced skin atrophy and telangiectasia and the correlation of the degree of atrophy and telangiectasia to body-weight change. Nine corticosteroids were evaluated by this method and are listed in terms of increasing severity of side-effects as follows: 1.0% hydrocortisone cream, 0.1% betamethasone valerate cream, 0.025% betamethasone benzoate cream, 0.05% flurandrenolide cream, 0.05% fluocinonide cream, 0.1% dexamethasone cream, and 0.03% flumethasone pivalate cream. Triamcinolone acetonide cream, 0.5%, and 0.2% fluocinolone acetonide cream resulted in death of the animals prior to completion of 28 days of topical application. ( Arch Dermatol 112:1115-1117, 1976)

58 citations

Journal ArticleDOI
TL;DR: Once-daily use of the micronized and more bioavailable formulation of isotretinoin under fasted conditions is clinically equivalent to the standard twice-daily formulation under fed conditions in the treatment of severe recalcitrant nodular acne.
Abstract: Background: Isotretinoin is very frequently the drug of choice for the management of severe recalcitrant nodular acne. Recently, a new micronized and more bioavailable formulation of isotretinoin has been developed that permits once-daily administration in lower doses than usually used with standard isotretinoin (Accutane), regardless of whether it is taken with or without food. Objective: Our purpose was to determine whether micronized isotretinoin and standard isotretinoin are clinically equivalent. Methods: In this multicenter, double-blind, double-dummy study, 600 patients with severe recalcitrant nodular acne were treated with either 0.4 mg/kg of micronized isotretinoin once daily without food (n = 300) or 1.0 mg/kg per day of standard isotretinoin in two divided doses with food (n = 300). Lesion counts were monitored over 20 weeks. Results: Both treatment groups in this well-controlled clinical trial experienced an equivalent reduction in the number of total nodules (facial plus truncal). In addition, an equivalent proportion of patients achieved 90% clearance of the total number of nodules. Both formulations had similar results for other efficacy variables. Conclusion: Once-daily use of the micronized and more bioavailable formulation of isotretinoin under fasted conditions is clinically equivalent to the standard twice-daily formulation under fed conditions in the treatment of severe recalcitrant nodular acne. (J Am Acad Dermatol 2001;45:187-95.)

55 citations

Journal ArticleDOI
TL;DR: In this article, the authors report the incidence and intensity of adverse events found in a comparative, double-blind efficacy study that showed clinical equivalence of the new micronized formulation of isotretinoin and the standard isotretin formulation (Accutane).
Abstract: Background: 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. Objective: The objective of this article is to report the incidence and intensity of adverse events found in a comparative, double-blind efficacy study that showed clinical equivalence of the new micronized formulation of isotretinoin and the standard isotretinoin formulation (Accutane). Methods: Six hundred patients with severe recalcitrant nodular acne were treated with micronized isotretinoin (n = 300) under fasted conditions or standard isotretinoin (n = 300) under fed conditions. One cohort received single daily doses of 0.4 mg/kg of micronized isotretinoin without food and the other cohort received 1.0 mg/kg per day of standard isotretinoin in two divided doses with food. Adverse events were monitored during 20 weeks of drug therapy. Results: The proportion of adverse events in most body systems was generally lower in patients receiving micronized isotretinoin than in those receiving standard isotretinoin. Conclusion: Micronized isotretinoin appears to have a safety profile similar to that of standard isotretinoin and to carry a lower risk of mucocutaneous events and hypertriglyceridemia. (J Am Acad Dermatol 2001;45:196-207.)

52 citations


Cited by
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Journal ArticleDOI
TL;DR: This review examines the evidence for involvement of the oxidative stress in the carcinogenesis process and the role of enzymatic and non-enzymatic antioxidants in the process of carcinogenesis as well as the antioxidant interactions with various regulatory factors.

5,937 citations

Journal ArticleDOI
TL;DR: Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS.

3,359 citations

01 Jan 2001
TL;DR: The essential trace mineral, selenium, is of fundamental importance to human health as mentioned in this paper, and it is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS.
Abstract: The essential trace mineral, selenium, is of fundamental importance to human health. As a constituent of selenoproteins, selenium has structural and enzymic roles, in the latter context being best-known as an antioxidant and catalyst for the production of active thyroid hormone. Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS. It is required for sperm motility and may reduce the risk of miscarriage. Deficiency has been linked to adverse mood states. Findings have been equivocal in linking selenium to cardiovascular disease risk although other conditions involving oxidative stress and inflammation have shown benefits of a higher selenium status. An elevated selenium intake may be associated with reduced cancer risk. Large clinical trials are now planned to confirm or refute this hypothesis. In the context of these health effects, low or diminishing selenium status in some parts of the world, notably in some European countries, is giving cause for concern.

3,068 citations

Journal ArticleDOI
TL;DR: The TrxR-catalyzed regeneration of several antioxidant compounds, including ascorbic acid (vitamin C), selenium-containing substances, lipoic acid, and ubiquinone are summarized.

2,632 citations

Journal ArticleDOI
TL;DR: The crucial factor that needs to be emphasised with regard to the health effects of selenium is the inextricable U-shaped link with status; whereas additional seenium intake may benefit people with low status, those with adequate-to-high status might be affected adversely and should not take selenum supplements.

2,297 citations