Hat-wearing patterns in persons attending baseball games.
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Baseball↗
Biomedical subjects
Mark G Lebwohl
Publications and source records attributed to Mark G Lebwohl.
Advances in psoriasis.
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Biological Therapy↗
The benefit/risk profile of TNF-blocking agents: findings of a consensus panel.
OBJECTIVE: To review the benefits and risks associated with the use of the tumor necrosis factor (TNF)-blockers in various indications (eg, rheumatoid arthritis [RA], Crohn's disease [CD], psoriasis). METHODS: The members of the consensus panel were selected based on their expertise. Centocor, Inc provided an educational grant to the Center for Health Care Education to facilitate the consensus panel. Peer-reviewed articles discussing clinical studies and clinical experiences with TNF-blockers form the basis of this review. Emerging data that have not been peer-reviewed are also included. RESULTS: The TNF-blockers infliximab, etanercept, and adalimumab are all approved for treatment of RA. All 3 are effective, and there are currently no published data from head-to-head clinical trials to support using 1 agent over another. Preliminary data from small, retrospective studies indicate that switching among agents to overcome inadequate efficacy or poor tolerability is beneficial in some patients. The only TNF-blocker currently approved for the induction and maintenance of remission in CD is infliximab. Preliminary data indicate that etanercept and infliximab are effective in treating psoriasis. Some risks associated with TNF-blockers have become apparent, including congestive heart failure, demyelinating diseases, and systemic lupus erythematosus, but in most cases can be identified and managed. Several of these risks (eg, lymphoma and serious infections) are associated with either the condition per se or the concomitant medication use. Simple screening procedures help manage the risk of tuberculosis infection; however, it is recommended that physicians and patients be alert to the development of any new infection so that appropriate treatment may be initiated promptly. Rare infusion reactions, particularly with infliximab, may also be effectively managed. CONCLUSION: TNF-blockers are effective and may be safely used for short- and long-term management of RA or CD. TNF-blockers also show efficacy in other emerging indications.
Adalimumab↗
Acanthosis nigricans in a plaque of scleredema on the back of a diabetic patient: a case report.
Acanthosis nigricans (AN) and scleredema are two skin conditions that have been reported in association with diabetes mellitus. Few cases associating scleredema and AN have been reported. A literature search did not reveal any reports of diabetic patients developing AN on top of a scleredema plaque. Here we report a patient with diabetes mellitus who developed AN within the same indurated scleredema plaque.
Acanthosis Nigricans↗
Treatment of psoriatic arthritis with etanercept, a tumour necrosis factor antagonist.
Psoriatic arthritis (PsA) is a chronic spondylarthritis that occurs in approximately 23% of plaque psoriasis sufferers. Traditional treatments for rheumatoid arthritis have been used as the first therapeutic approach to treat this inflammatory disease, which has both joint and skin manifestations. However, due to the inefficiency of current disease-modifying antirheumatic drugs and non-steroidal anti-inflammatory drugs in stopping the progression of the joint disease, biologics have emerged as a hopeful alternative to PsA therapy. Etanercept was the first approved tumour necrosis factor-alpha (TNF-alpha) inhibitor for reducing the signs and symptoms of PsA, as well as preventing the progression of the disease. Etanercept is a fully human, soluble, dimeric fusion protein that has the ability to bind to two molecules of TNF, thereby rendering them biologically inactive. Two clinical trials have demonstrated that etanercept is generally a safe, efficacious and well-tolerated biologic therapy for the treatment of PsA.
Animals↗
Use of etanercept in the dermatology setting. A review.
As psoriasis and psoriatic arthritis are chronic in nature, ideal treatment should have sustained efficacy, with minimal short- and long-term toxicities to allow lifelong treatment. Traditional therapies used for psoriatic arthritis or psoriasis, including phototherapies and systemic agents, do not satisfy these criteria. Ninety percent of patients surveyed in 1998 by The National Psoriasis Foundation were not satisfied with their treatment options. Several observations have supported the introduction of the tumor necrosis factor (TNF) antagonist etanercept as a treatment for psoriatic disease, including the failure of traditional therapies to meet patient needs, evidence that TNF plays a fundamental role in the inflammatory processes underlying psoriatic arthritis and psoriasis, and the safety and efficacy of this agent in other inflammatory, immune-mediated diseases, such as rheumatoid arthritis (RA). Etanercept prevents initiation of the proinflammatory cascade by competitively binding TNF. First indicated for RA, etanercept is also approved for the treatment of psoriatic arthritis, juvenile RA, ankylosing spondylitis, and most recently psoriasis. Etanercept provides dermatologists with a safe, effective, and convenient treatment option for patients with psoriatic arthritis and psoriasis, which can be used continuously with or without traditional therapies. The self-administered injections provide a distinct advantage over traditional therapies that often require frequent office visits and laboratory monitoring, and other biologic agents that require administration in the doctor's office. Dermatologists should be aware of the ongoing research with etanercept in psoriasis and other dermatologic conditions.
Anti-Inflammatory Agents↗
Cutaneous T-cell lymphoma treatment using bexarotene and PUVA: a case series.
BACKGROUND: Mycosis fungoides, the most common form of cutaneous T-cell lymphoma, often presents as chronic eczematous or psoriasiform patches and plaques that can be resistant to a variety of single-agent treatment modalities, necessitating combination therapy. OBJECTIVE: To evaluate the efficacy of combination therapy with bexarotene and psoralen plus ultraviolet A (PUVA) in treating patients with cutaneous T-cell lymphoma (CTCL) that recurred following monotherapy with multiple agents, including electron-beam irradiation, interferon, PUVA, and topical steroids. This was done by retrospective chart review. METHODS: Retrospective chart review analysis of eight patients with CTCL ranging from stage Ia to IIb who failed multiple single-agent treatment regimens treated with low-dose oral bexarotene and PUVA combination therapy. RESULTS: We noted an initial response in all eight patients and complete remission in five of the patients treated, with pruritus being the most common adverse event. CONCLUSION: In view of its good safety profile, combination therapy with bexarotene and PUVA may be considered for patients with treatment resistant CTCL refractory to monotherapy.
Adult↗
Use of Ber-EP4 protein in recurrent metastatic basal cell carcinoma: a case report and review of the literature.
The occurrence of metastatic basal cell carcinoma (MBCC) is extremely low, ranging from 0.0028 to 0.5%. We present a rare case report of MBCC in a 57-year-old Caucasian male with a known history of numerous nonmelanoma cutaneous neoplasms. The patient presented with a large ulcerated right axillary mass that recurred 2 months after an initial BCC was resected from the same site. An excisional biopsy of the recurrent mass and regional lymph nodes showed atypical basaloid cells with hyperchromatic nuclei, stromal retraction and rare squamous features in the soft tissue and lymph node. The tumor cells were bcl-2 negative and positive for Ber-EP4. The negative expression of bcl-2 correlates with the aggressive nature of this tumor and Ber-EP4 confirmed the diagnosis of BCC.
Antibodies, Monoclonal↗
Biologics in combination with nonbiologics: efficacy and safety.
The mechanisms of action of biologic therapies differ from the currently used systemic therapies by attacking specific steps in the pathogenesis pathway of psoriasis. Preliminary data show that combination therapy using biologics may allow for improved therapeutic efficacy with fewer side effects, including decreased risk of hepatotoxicity and nephrotoxicity commonly associated with the most widely used systemic agents, methotrexate, and cyclosporine. However, some concerns have been raised regarding the increased immunosuppression, increased risk of infection, potential for development of certain types of malignancy, as well as the significant increased cost of therapy. Both potential benefits and toxicities of combination therapy will be reviewed here. Long-term clinical studies are warranted to more accurately quantify the risks and benefits associated with combination therapy. The role of combination therapy will continue to be refined over the next few years to maximize its potential in the treatment of resistant psoriasis.
Antibodies, Monoclonal↗
Shikonin modulates cell proliferation by inhibiting epidermal growth factor receptor signaling in human epidermoid carcinoma cells.
Shikonin isolated from the roots of the Chinese herb Lithospermum erythrorhizon has been associated with anti-inflammatory properties. We evaluated shikonin's chemotherapeutic potential and investigated its possible mechanism of action in a human cutaneous neoplasm in tissue culture. Shikonin preferentially inhibits the growth of human epidermoid carcinoma cells concentration- and time-dependently compared to SV-40 transfected keratinocytes, demonstrating its anti-proliferative effects against this cancer cell line. Additionally, shikonin decreased phosphorylated levels of EGFR, ERK1/2 and protein tyrosine kinases, while increasing phosphorylated JNK1/2 levels. Overall, shikonin treatment was associated with increased intracellular levels of phosphorylated apoptosis-related proteins, and decreased levels of proteins associated with proliferation in human epidermoid carcinoma cells.
Carcinoma, Squamous Cell↗
Ultraviolet radiation in alpine skiing: magnitude of exposure and importance of regular protection.
BACKGROUND: Participation in outdoor alpine sports has been increasing over the last decade. Ultraviolet exposure levels for these activities can be extreme owing to the venue altitudes. The purpose of this study was to measure the levels of UV-A and UV-B radiation exposure incurred by performance skiers in a typical alpine venue and to determine the need for protection in that environment. OBSERVATIONS: Total UV-B exposure ranged from 12 to 185 mJ/cm(2) (0.5-7.6 times the minimum erythemal dose [MED] for individuals with type II skin). Ten percent of subjects received more than 1 MED/h at peak exposure times. Daily UV-A exposure ranged from 10.6 to 28 J/cm( 2) (daily average, 0.55 minimum melanogenic dose). CONCLUSIONS: Alpine skiers with skin types I and II are exposed to measurable erythemal and suberythemal levels of UV radiation repeatedly over the long term at levels that can cause photodamage to their skin and potentially increase their later risk for skin cancer. Programs should be developed to educate skiers regarding the need for UV protection. Given the high levels of exposure noted, skiers should use UV protective measures, including sun-protection factor 30 broad-spectrum sunscreen.
Altitude↗
Tazarotene cream in the treatment of psoriasis: Two multicenter, double-blind, randomized, vehicle-controlled studies of the safety and efficacy of tazarotene creams 0.05% and 0.1% applied once daily for 12 weeks.
BACKGROUND: Tazarotene in a gel formulation is widely used in the treatment of psoriasis. OBJECTIVE: To determine the efficacy and safety of tazarotene 0.1% and 0.05% creams in the treatment of psoriasis. METHODS: A total of 1303 patients participated in 2 clinical trials. Patients applied tazarotene creams 0.1% and 0.05% or vehicle once daily to all psoriatic lesions for 12 weeks followed by a 12-week posttreatment period. RESULTS: Both creams were significantly more effective than vehicle on the basis of an overall assessment of psoriasis, a global response to treatment, and reduction in plaque elevation and scaling. Therapeutic effect was maintained during the posttreatment period. Common adverse events included signs and symptoms of skin irritation. CONCLUSION: Tazarotene creams were associated with significant reductions in the severity of the clinical signs of psoriasis and were found to be safe with acceptable tolerability. Tazarotene cream 0.1% was generally more effective, although slightly less well tolerated, than the 0.05% cream.
Administration, Topical↗
Cutaneous ulceration caused by methotrexate.
Methotrexate has been associated with the development of skin ulceration in small numbers of patients with psoriasis. We describe a 58-year-old man with a 15-year history of plaque-type psoriasis. He had been treated with methotrexate therapy (15 mg orally per week for 32 weeks) and had ulcers develop within psoriatic plaques on both elbows, on the mucosal aspect of the lower lip, and in an appendectomy scar on the right lower quadrant of the abdomen. Ulcers healed upon discontinuation of methotrexate, but the scar eroded again upon reintroduction of methotrexate.
Administration, Oral↗
Isoflavone genistein: photoprotection and clinical implications in dermatology.
Genistein is a soybean isoflavone with diverse biological activities. It is a potent antioxidant, a specific inhibitor of protein tyrosine kinase, and a phytoestrogen. In recent years, increasing evidence has accumulated that this natural ingredient shows preventative and therapeutic effects for breast and prostate cancers, postmenopausal syndrome, osteoporosis, and cardiovascular diseases in animals and humans. In the past decade we have conducted a series of studies and demonstrated that genistein has significant antiphotocarcinogenic and antiphotoaging effects. Genistein substantially inhibits skin carcinogenesis and cutaneous aging induced by ultraviolet (UV) light in mice, and photodamage in humans. The mechanisms of action involve protection of oxidative and photodynamically damaged DNA, downregulation of UVB-activated signal transduction cascades, and antioxidant activities. In this article, we review the biological activities of genistein, as well as published and unpublished research from our laboratory. In addition, we discuss the potential application of genistein to clinical dermatology.
Animals↗
6-thioguanine in the treatment of psoriasis: a case report and literature review.
BACKGROUND: 6-Thioguanine is a purine analog primarily indicated for acute myelogenous leukemia. Its use in psoriasis was first investigated in the 1950s and current interest in serious treatments for psoriasis, such as cyclosporine, has renewed interest in this medication. Newer therapies, such as PUVA and retinoids, have side effects as do some older treatments, such as methotrexate, which fell into favor at the same time 6-thioguanine was being investigated. Reexamining older treatments can open up new therapeutic options in difficult cases. OBJECTIVE: The goal of this article is to provide a comprehensive review of the literature regarding the use of 6-thioguanine in the treatment of psoriasis as well as an illustrative case report demonstrating the use and side effects of 6-thioguanine in a patient with pustular psoriasis. Topics reviewed include efficacy, side effects, laboratory monitoring, different dosing regimens, and proposed mechanisms of action. CONCLUSIONS: 6-Thioguanine has been highly effective in treating and maintaining improvement in patients with psoriasis. A study comparing efficacies with methotrexate would be extremely useful. Because of the possibility of severe bone marrow depression, 6-thioguanine is not a first-line treatment. However, with new dosing regimens, proper laboratory monitoring, and further studies, use of 6-Thioguanine could expand in the future.
Aged↗
An open-label study of the safety and efficacy of limited application of fluticasone propionate ointment, 0.005%, in patients with atopic dermatitis of the face and intertriginous areas.
BACKGROUND: The treatment options for facial and intertriginous skin are limited because these sites are more susceptible to corticosteroid-induced atrophy. The long-term management of these corticosteroid-sensitive sites requires the use of dosing regimens that are effective, but also safe. METHODS: The affected areas in 21 patients with atopic dermatitis were treated twice daily for 2 weeks, and then once daily for two consecutive days each week for eight more weeks. RESULTS: After 2 weeks, treatment success occurred in 95% of facial and intertriginous lesions and also in 95% of nonfacial, nonintertriginous lesions. During long-term therapy, treatment success was maintained in > 76% of facial and intertriginous lesions, and > 76% of other lesions. Recurrence rates were low, and skin atrophy and telangiectasia did not occur. CONCLUSIONS: Patients with atopic dermatitis of facial and intertriginous areas were successfully treated with a limited application of fluticasone propionate ointment, 0.005%. The treatment resulted in rapid healing and provided efficacy with a low rate of recurrence and no evidence of skin atrophy or telangiectasia over 8 weeks.
Administration, Topical↗
Clinical effect of imiquimod 5% cream in the treatment of actinic keratosis.
BACKGROUND: Actinic keratosis (AK) is the earliest clinical manifestation of squamous cell carcinoma. Metastatic SCC causes the majority of the 1300 to 2300 deaths attributed to nonmelanoma skin cancer in the United States each year. Recent studies have shown that intralesional administration of interferon can be used successfully in the treatment of AK. OBJECTIVE: Imiquimod is an immune response modifier, currently approved for the treatment of genital warts. The topically applied immune response modifier acts by up-regulating interferon and other cytokines involved in the cell-mediated immune response at the site of application. The aim of this was to determine the efficacy and safety of imiquimod 5% cream for the treatment of AK. METHODS: Twenty-two patients with AK lesions were treated with imiquimod 5% cream, initially at 3 times per week for 8 weeks, or until total clearance of lesions. Patients applied imiquimod to lesions on one side of the body and vehicle cream to the other side. A total of 17 patients who completed treatment were evaluated for number of lesions and adverse reactions before treatment and at weeks 2, 4, 6, and 8 after initiation of treatment. AK lesions were also assessed 4 and 8 weeks after treatment. RESULTS: A significant reduction in the average number of lesions per patient was observed for patients treated with imiquimod. The most frequent reactions to treatment were erythema, itching, and scabbing; however, all adverse events were mild to moderate. CONCLUSION: Imiquimod 5% cream may be a promising treatment for AK.
Adjuvants, Immunologic↗
Effects of ultraviolet B exposure on the expression of proliferating cell nuclear antigen in murine skin.
Proliferating cell nuclear antigen (PCNA) is an active nuclear protein involved in DNA replication, recombination and repair. PCNA is found throughout the basal layer in normal skin and in all layers of the epidermis in malignancy. This study evaluates PCNA's expression after acute and chronic UV-B irradiation. Skh-1 hairless mice exposed to 1.5 and 4.5 kJ/m2 of UV-B were sacrificed at 6, 12, 24, 48, 72 and 168 h. Immunohistochemical analysis revealed PCNA expression throughout the basal layer of untreated skin, with diminished expression at 6 h, indicative of immediate UV damage, and evidenced by the observable upregulation in pyrimidine dimer formation early on. Subsequently, PCNA immunoreactivity progressively increased, demonstrating an aberrant upward epidermal migratory pattern in association with chronic exposure. The 4.5 kJ/m2 group exhibited prolonged recovery in staining and also demonstrated this altered migratory pattern with chronic exposure. Progressive reactivation of PCNA expression occurs with repair. PCNA migration to upper layers of the epidermis indicates proliferation and possibly a subsequent increased malignant potential. We conclude that PCNA can serve as a marker of DNA repair and indirectly as an indicator of UV-B-induced damage, expression being time dependent and dose related. Specific immunoreactivity patterns and the observable atypia in keratinocytes are relevant in elucidating malignant potentiation.
Animals↗