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Biomedical subjects

M Lebwohl

Publications and source records attributed to M Lebwohl.

At least 19 recordsLinked to original sources
PubMed2001

Genital lentigines in a 6-year-old boy with a family history of Cowden's disease: clinical and genetic evidence of the linkage between Bannayan-Riley-Ruvacalba syndrome and Cowden's disease.

BACKGROUND: In 1997, it was reported that a PTEN gene deletion, a common genetic mutation in Cowden's disease (CD), was identified in a patient with Bannayan-Riley-Ruvacalba (BRR), suggesting that the two diseases were allelic. However, the clinical overlap between the two diseases has largely remained unclear. OBJECTIVE: To confirm the genetic and clinical association in a family segregating both CD and BRR. METHODS: Clinical evaluation and genetic analysis using a denaturing gradient gel electrophoresis (DGGE), temporal temperature gradient electrophoresis (TTGE), and DNA sequencing techniques. RESULTS: Our patient presents with typical BRR clinical manifestations, including multiple lentigines on his penis, while his mother presents with typical manifestations of CD, including multiple malignancies. Genetic analyses of leukocytes from the patient and his mother showed mutations in exon 8 that was identified as the presumably truncating mutation R335X. CONCLUSION: This report provides clinical evidence that both BRR and CD are closely related and confirms the PTEN gene mutation in BRR and CD patients segregating in the same family, thus confirming the genetic linkage between the two genodermatoses.

Abnormalities, Multiple↗
PubMed2001

Combination therapy with vitamin D analogues.

Monotherapy with vitamin D analogues has been shown to be effective in the treatment of psoriasis. Vitamin D analogues have also been used in combination with other topical therapies, systemic therapies and phototherapy. In many instances, the efficacy of these other treatments can be maximized and adverse effects minimized when combined with vitamin D analogues. The combination of a topical corticosteroid with a vitamin D analogue can work synergistically to improve efficacy and reduce the side-effects from both treatments. However, caution must be used when mixing the two agents, as some topical corticosteroids will result in the degradation of the vitamin D analogue. Benefit from phototherapy is also increased when using vitamin D analogues, so that greater improvement occurs with fewer treatments. Effects on minimal erythema dose must be considered and the potential for ultraviolet blocking by vitamin D analogues may affect treatment. Some vitamin D analogues may also be susceptible to degradation by certain wavelengths of ultraviolet light. Combining vitamin D analogues with systemic agents exerts a dose-sparing effect, thus reducing the possibility of side-effects, but such combinations require further study. As long as treatments are used correctly, the benefits of combination therapy with vitamin D analogues usually outweigh the few drawbacks.

Calcitriol↗
PubMed2001

Altered expression of angiopoietins and Tie2 endothelium receptor in psoriasis.

Psoriasis is a chronic inflammatory skin disease in which epidermal proliferation is closely associated with excessive microvascular expansion within the papillary dermis. Angiopoietins have recently been identified as the major ligands of the endothelial- specific receptor Tie2. Angiopoietin 1 induces Tie2 signaling as a receptor activator and maintains blood vessel formation, whereas angiopoietin 2 destabilizes vessels by blocking Tie2 signaling as an antagonist of angiopoietin 1 and acts with vascular endothelial growth factor to initiate angiogenesis. In this study we examined the potential role of angiopoietins and the Tie2 receptor in vascular changes of psoriasis. Angiopoietin 1, angiopoietin 2, and Tie2 were upregulated in involved psoriasis skin compared to uninvolved psoriasis skin, healthy skin, and chronic spongiotic dermatitis skin. Angiopoietin 1 was expressed by stromal cells in the highly vascularized papillary dermis of involved psoriasis skin. Angiopoietin 2 was expressed by endothelial cells in the vicinity of the proliferating epidermis that abundantly expressed vascular endothelial growth factor. Vascular endothelial growth factor and basic fibroblast growth factor, which were overexpressed in involved psoriasis skin, enhanced angiopoietin 2 and Tie2 expression in dermal microvascular endothelial cell cultures. Thus, our findings suggest that upregulation of angiopoietin 1, angiopoietin 2, and Tie2 is closely associated with the development of microvascular proliferation in psoriasis, and that the angiopoietin-Tie2 system may act coordinately with vascular endothelial growth factor and basic fibroblast growth factor to promote neovascularization in psoriasis. Moreover, successful antipsoriatic treatment was accompanied by noticeable reduction of angiopoietin 2 expression, suggesting that alteration of angiopoietin 2 expression may be particularly important in controlling vascular proliferation in the treatment of psoriasis.

Angiopoietin-1↗
PubMed2001

Acne therapy: clinical pearls.

Several classes of medications successfully treat acne. Systemic and topical retinoids, systemic and topical antimicrobials, and systemic hormonal therapy are the major categories. Failure of therapy may result from drug interactions, antibiotic resistance, or coexisting conditions; therefore, a detailed history including these points should be used to decide which therapy is appropriate for each patient. Furthermore, one must consider the potential side effects of each treatment and make sure that (1) the benefits outweigh the risks of the treatment, (2) the side effects can be avoided by adding another agent, or (3) the side effects can be safely treated.

Acne Vulgaris↗
PubMed2001

Pseudoxanthoma elasticum: significance of limited phenotypic expression in parents of affected offspring.

The inheritance pattern of pseudoxanthoma elasticum (PXE) is controversial. Inheritance patterns are confounded by delayed diagnosis and mild or limited phenotypic expression among certain family members. Because testing for the genetic mutation(s) responsible for PXE is not routine, genetic counseling must be done with caution. We describe 4 families in which one or more children were diagnosed with PXE. Detailed examination of the parents was carried out, including skin biopsy and ophthalmologic examination. In 3 of the 4 families, one parent had limited phenotypic expression, such as ocular findings without skin lesions or very mild skin lesions with no ocular findings. In the other family, one parent had very mild skin and ocular disease. All 4 affected parents had diagnostic skin biopsy findings. In none of the 4 families was the inheritance pattern clear-cut. Although the inheritance pattern of PXE has been debated, clinically significant stigmata of PXE, which are not always readily apparent, can occur in successive generations. Therefore all first-degree relatives of affected patients should receive a full dermatologic examination as well as a funduscopic examination. If even mild typical skin or eye findings are present, then skin biopsy should be performed.

Adolescent↗
PubMed2001

The penetration of 0.005% fluticasone propionate ointment in eyelid skin.

BACKGROUND: The use of corticosteroids to treat periorbital dermatoses carries significant risk of serious side effects such as glaucoma, cataracts, and blindness. Studies to assess levels of corticosteroid penetration in the eyelid are lacking. OBJECTIVE: We assessed corticosteroid penetration in eyelid skin in vitro to obtain information leading to the establishment of safer dosing regimens. METHODS: Fluticasone propionate ointment, 0.005%, was applied (approximately 2-5 mg/cm(2)) to samples of human eyelid skin, and penetration was assessed by using modified Franz diffusion cells. Drug concentration was determined at 12, 24, 36, and 48 hours after application by liquid chromatography tandem mass spectrometry. RESULTS: Only very small amounts of fluticasone propionate penetrated the skin (range, 0.618% +/- 0.339% to 1.467% +/- 0.695%). CONCLUSION: Further studies are warranted to examine the safety and efficacy of 0.005% fluticasone propionate ointment for the treatment of eyelid dermatoses.

Administration, Topical↗
PubMed2001

Consensus conference: acitretin in combination with UVB or PUVA in the treatment of psoriasis.

Although adjunctive treatment with retinoids in concert with either psoralen-ultraviolet A (PUVA) or ultraviolet B (UVB) phototherapy has been a treatment option for chronic, moderate to severe plaque psoriasis for nearly two decades, acitretin-UV therapy is an underutilized therapeutic modality. According to a recent member survey by the National Psoriasis Foundation, many psoriasis patients are frustrated with available treatment options, which they perceive as ineffective, inconvenient, and/or excessively conservative. Treatment of psoriasis with acitretin in concert with UVB or PUVA is emerging as a viable clinical strategy. Compared with either acitretin or UV light monotherapy alone, the combination regimen enhances efficacy and limits treatment frequency, duration, and cumulative doses. These effects translate into care that is more effective, better tolerated, more convenient, less costly, and, perhaps, safer during long-term treatment than phototherapy alone. Drawing from an extensive literature search and the expertise of its participants, this consensus conference advances clinical recommendations as well as "clinical pearls" for health providers who treat patients with chronic, moderate to severe plaque psoriasis and suggests avenues for future research.

Acitretin↗
PubMed2001

Treatment of psoriasis. Part 1. Topical therapy and phototherapy.

UNLABELLED: New developments in the topical therapy and phototherapy of psoriasis have greatly improved our ability to safely and effectively treat this debilitating disease. Topical corticosteroids remain the most commonly prescribed agents for psoriasis, but they are frequently prescribed with other agents. Investigations of corticosteroids claiming an improved benefit/risk ratio have yielded promising results, but more work is needed. Use of anthralin and tar has declined with the availability of the noncorticosteroids calcipotriene and tazarotene. Other experimental topical therapies are in various stages of development. Broadband ultraviolet B (UVB) remains the most commonly used phototherapy light source, but many patients are being treated with a new form of ultraviolet light, narrowband UVB. Although PUVA remains one of the most effective psoriasis treatments, its use is declining because of its association with cutaneous malignancies. New radiation sources such as lasers have been added to our armamentarium of available therapies and even newer light source-based treatments are being examined. LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should be familiar with the varying topical treatments for psoriasis as well as the different modalities of phototherapy. Participants should also have a better understanding of side effects associated with each treatment, which should help in determining options for therapy.

Administration, Topical↗
PubMed2001

Treatment of psoriasis. Part 2. Systemic therapies.

The array of systemic medications used in the treatment of psoriasis is rapidly expanding. In the United States, methotrexate, retinoids, and cyclosporine are the only systemic drugs approved by the Food and Drug Administration for the treatment of psoriasis. Monitoring and dosage recommendations for these medications are reviewed. Other drugs that are currently available include tacrolimus, mycophenolate mofetil, hydroxyurea, 6-thioguanine, and sulfasalazine. Experience with these drugs is summarized, and dosage and monitoring recommendations in published literature are presented. Combinations of different treatments are addressed and investigational therapies that are in development are reviewed.

Cyclosporine↗
PubMed2001

Clinical management of psoriasis: principles and practice.

A chronic condition that compromises many patients' quality of life, psoriasis is treatable with a range of agents, either alone or in combination. Clinical management strategies using these therapies can be organized as a stepped-care approach. For mild disease, corticosteroids and other topical therapies (step 1) are often appropriate. When lesions are more pronounced or extensive, phototherapy (step 2) is often the treatment of choice, and topical treatments or the step 3 agent acitretin can be added to enhance or accelerate therapeutic responses. Step 3 agents, which also include cyclosporine and methotrexate, may be contemplated when psoriasis is moderate or severe. Acitretin may cause acute adverse effects, including mucocutaneous effects, which can be avoided by reducing dosage. Methotrexate treatment can lead to bone marrow suppression and hepatotoxicity, and cyclosporine can cause nephrotoxicity. The clinical uses of these agents are illustrated in part through case presentations drawn from the authors' practices, and the supportive role of the National Psoriasis Foundation is reviewed.

Adult↗
PubMed2001

The impact of psoriasis on quality of life: results of a 1998 National Psoriasis Foundation patient-membership survey.

BACKGROUND: Psoriasis can have a profound impact on a patient's quality of life. OBJECTIVES: To assess patients' perspectives on the impact of psoriasis on their lifestyle and emotional well-being and the social ramifications of living with the disease; to determine the range of therapies available; and to ascertain patients' satisfaction with the management of their disease. DESIGN: A 4-page, self-administered questionnaire was mailed on July 13 and 14, 1998, to the entire membership of the National Psoriasis Foundation (N = 40 350), and followed by a telephone survey of responders with severe psoriasis. MAIN OUTCOME MEASURES: Patients' perspectives on the psychosocial impact of psoriasis and the effectiveness of the management of their disease. RESULTS: Of the 40 350 questionnaires mailed out, a response rate of 43% was realized. The most frequent symptoms experienced by the mail-survey respondents were scaling (94%), itching (79%), and skin redness (71%); 39% reported that psoriasis covered 10% or more of their bodies. A total of 6194 patients with severe psoriasis were entered into the database for the telephone survey. Of these, 79% reported that psoriasis had a negative impact on their lives, 40% felt frustrated with the ineffectiveness of their current therapies, and 32% reported that treatment was not aggressive enough. CONCLUSIONS: The unprecedented response to the survey provides compelling evidence that individuals with psoriasis believe that the disease has a profound emotional and social as well as physical impact on their quality of life. Many patients with psoriasis, particularly those with severe disease, are frustrated with the management of their disease and by the perceived ineffectiveness of their therapies. Physicians may need to improve communication with their patients and should reevaluate their management of psoriasis.

Activities of Daily Living↗
PubMed2001

Efficacy and safety of terbinafine 1% solution in the treatment of interdigital tinea pedis and tinea corporis or tinea cruris.

Two randomized, double-blind, vehicle-controlled, multicenter studies assessed the efficacy and safety of a new terbinafine 1% solution for the treatment of interdigital tinea pedis and tinea corporis or tinea cruris (tinea corporis/cruris). Patients with interdigital tinea pedis applied terbinafine 1% solution or vehicle twice daily for 1 week with 7 weeks of follow-up (N = 153), and patients with tinea corporis/cruris applied terbinafine 1% solution or vehicle once daily for 1 week with 3 weeks of follow-up (N = 66). Efficacy was assessed mycologically and clinically at the end of treatment and throughout follow-up. In the tinea pedis study, 66% of patients were effectively treated with terbinafine compared with 4% of the group treated by vehicle (P < .001; Mantel-Haenszel test). In the tinea corporis/cruris study, treatment was effective in 65% of the terbinafine group compared with 8% of the vehicle group (P < .001). There were no significant differences in the frequency of cutaneous adverse events between the 2 groups in either study. We conclude that one week of therapy with terbinafine 1% solution is highly effective, superior to vehicle, and safe for use in superficial fungal infections.

Administration, Cutaneous↗
PubMed2000

A 500-kb region on chromosome 16p13.1 contains the pseudoxanthoma elasticum locus: high-resolution mapping and genomic structure.

We have recently mapped the genetic defect underlying pseudoxanthoma elasticum (PXE), an inherited disorder characterized by progressive calcification of elastic fibers in skin, eye, and cardiovascular system, to chromosome 16p 13.1. Here we report further data on the fine-mapping and genomic structure of this locus. Haplotype analysis of informative PXE families narrowed the locus to an interval of less than 500 kb located between markers D16B9621 and D16S764. Three overlapping YAC clones were found to cover this region through YAC-STS content mapping. An overlapping BAC contig was then constructed to cover this interval and the surrounding region. About 80% of this chromosomal region has been fully sequenced using the BAC shotgun technique. Gene content and sequence analysis predicted four genes (MRP1, MRP6, PM5, and a novel transcript) and two pseudogenes (ARA and PKDI) within this interval. By screening a somatic cell hybrid panel we were able to precision-map the breakpoint of Cy185 and the starting point of a chromosomal duplication within 20 kb of BAC A962B4. The present data further refine the localization of PXE, provide additional physical cloning resources, and will aid in the eventual identification of the genetic defect causing PXE.

Adult↗
PubMed2000

Effects of administration of a single dose of a humanized monoclonal antibody to CD11a on the immunobiology and clinical activity of psoriasis.

BACKGROUND: CD11a/CD18 comprise subunits of leukocyte function associated antigen (LFA-1), a T-cell surface molecule important in T-cell activation, T-cell emigration into skin, and cytotoxic T-cell function. OBJECTIVE: We explored the immunobiologic and clinical effects of treating moderate to severe psoriasis vulgaris with a single dose of humanized monoclonal antibody against CD11a (hu1124). METHODS: This was an open label study with a single dose of hu1124 at doses of 0.03 to 10 mg/kg. Clinical (Psoriasis Area and Severity Index [PASI]) and immunohistologic parameters (epidermal thickness, epidermal and dermal T-cell numbers, and keratinocyte intercellular adhesion molecule 1 [ICAM-1] expression) were followed. RESULTS: Treatment with hu1124, at doses higher than 1.0 mg/kg (group III), completely blocks CD11a staining for at least 14 days in both blood and psoriatic plaques. At 0.3 to 1.0 mg/kg, T-cell CD11a staining was completely blocked; however, blockade lasted less than 2 weeks (group II). Only partial saturation of either blood or plaque cellular CD11a was observed at doses of hu1124 between 0.01 and 0.1 mg/kg (group I). This pharmacodynamic response was accompanied by decreased numbers of epidermal and dermal CD3(+) T cells, decreased keratinocyte and blood vessel expression of ICAM-1, and epidermal thinning. Statistically significant drops in PASI compared with baseline were observed in group II patients at weeks 3 and 4 and in group III patients at weeks 2 through 10. No significant drop in PASI score was observed in group 1. Adverse events were mild at doses of 0.3 mg/kg or less and included mild chills, abdominal discomfort, headache, and fever. At a single dose of 0.6 mg/kg or higher, headache was the most common dose-limiting toxicity observed. CONCLUSION: Targeting CD11a may improve psoriasis by inhibiting T-cell activation, T-cell emigration into the skin, and cytotoxic T-cell function.

Antibodies, Monoclonal↗
PubMed2000

Advances in psoriasis therapy.

New uses of older drugs, new combinations of treatments, and new phototherapeutic modalities are enabling clinicians to offer patients safer and more effective treatments. New vehicles for topical delivery of older treatments have created more cosmetically elegant preparations that are better accepted by patients. This article discusses new developments in topical therapy, phototherapy, oral therapy, and injectable therapy for psoriasis.

Administration, Oral↗