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Biomedical subjects

M Lebwohl

Publications and source records attributed to M Lebwohl.

At least 37 records · Page 2Linked to original sources
PubMed2000

Two considerations for patients with psoriasis and their clinicians: what defines mild, moderate, and severe psoriasis? What constitutes a clinically significant improvement when treating psoriasis?

The definitions of psoriasis severity and clinically significant improvement in psoriasis are used to classify treatments, obtain Food and Drug Administration approval, and determine product labeling and reimbursement. The Medical Advisory Board of the National Psoriasis Foundation has addressed these issues because of their importance in the clinical trials that are conducted to gain FDA approval of indications. Narrow indications, which are without a sound rational basis, will-in this era of constant oversight by third party payers-affect physicians' ability to manage patients with psoriasis. Body surface area (BSA) is usually used to define severity for clinical trials. It is not optimal for defining psoriasis severity because there are some patients with low BSA involvement who have very severe psoriasis and some patients with high BSA involvement who have mild psoriasis. We conclude that a quality of life (QOL) standard is better than BSA measurement for identifying patients with severe psoriasis. The second issue is what defines clinically significant improvement for patients with psoriasis. Setting an arbitrarily high criterion of clinical efficacy for new psoriasis treatments will likely limit the development and approval of useful treatments. To maximize the availability of useful psoriasis treatments, it is our thesis that psoriasis treatments should be approved when they have been shown to produce a statistically significant level of improvement in well-designed clinical trials.

Humans↗
PubMed2000

Pseudoxanthoma elasticum and calcinosis cutis.

A 42-year-old white woman presented with clinical and histologic manifestations of both calcinosis cutis and pseudoxanthoma elasticum: discrete milia-like calcifications at the anterior aspect of the neck, a funduscopic examination with classic eye findings, peripheral vascular disease, and a mottled appearance of the skin at the axillae, groin, and lateral aspects of the neck. A younger sibling had similar skin lesions and deteriorating visual acuity. The patient was normocalcemic and normophosphatemic. This case may represent the coincidental occurrence of two rare entities in the same person or may be suggestive of a pattern of dystrophic calcification associated with pseudoxanthoma elasticum.

Adult↗
PubMed2000

Anti-CD4 monoclonal antibody treatment of moderate to severe psoriasis vulgaris: results of a pilot, multicenter, multiple-dose, placebo-controlled study.

BACKGROUND: OKTcdr4a (IMUCLONE) is a humanized anti-CD4 IgG4 monoclonal antibody that retains the binding and in vitro immunosuppressive properties of the parent murine antibody. Psoriasis is a chronic disease for which treatment with multiple doses of monoclonal antibodies is likely to be required for adequate control. OBJECTIVE: This study was performed to test the efficacy and safety of OKTcdr4a, given in sequential courses over a period of several weeks, in the treatment of moderate to severe psoriasis vulgaris. METHODS: Twenty-eight patients (45.6 +/- 10.1 years of age) were studied, with a mean pretreatment Psoriasis Area and Severity Index (PASI) score of 18.3. In the first double-blind phase of the study, patients were randomized to receive OKTcdr4a as a 225 mg/course (low dose), 750 mg/course (high dose), or placebo divided into 3 identical infusions over a 5-day period. After 42 days, patients who met the criteria for re-treatment with OKTcdr4a were re-treated with the 750 mg/course in an open phase of the study. RESULTS: After the double-blind course of treatment, the mean PASI decreased by 11% in the placebo group, by 4% in the low-dose group, and by 17% in the high-dose group at 15 days. Twenty patients met the criteria for re-treatment (ie, did not experience a decrease in PASI score of 50% at 42 days). They were re-treated with OKTcdr4a at 43 days with the 750 mg/course in the open phase of the study. By day 99, the mean PASI score decreased from 19.9 at baseline to 17 in those patients who had received either placebo or low-dose OKTcdr4a followed by high-dose OKTcdr4a. In contrast, the mean PASI score decreased from 17.4 at baseline to only 7.7 in those patients who had received high-dose OKTcdr4a for both courses. Sustained CD4 saturation was not necessary for sustained clinical response. No patients had significant changes in circulating CD4(+) T-cell counts. The infusions were well tolerated. CONCLUSION: Targeting CD4 using sequential treatments with a humanized monoclonal antibody (OKTcdr4a) may offer another therapeutic option for the treatment of moderate to severe psoriasis.

Adult↗
PubMed2000

Strategies to optimize efficacy, duration of remission, and safety in the treatment of plaque psoriasis by using tazarotene in combination with a corticosteroid.

In the treatment of plaque psoriasis with corticosteroids, long-term efficacy and safety are often compromised by tachyphylaxis, steroid rebound, and adverse effects. However, the results of recent studies demonstrate that the use of tazarotene in conjunction with a corticosteroid can help to optimize the efficacy, the duration of remission, and the safety of corticosteroid treatment. In one study, the adjunctive use of tazarotene with a mid-potency corticosteroid promoted greater efficacy, more rapid efficacy, and more prolonged remission after treatment than corticosteroid monotherapy. In another study, after the induction of remission with tazarotene plus a superpotent corticosteroid, maintenance therapy with tazarotene, with or without the superpotent corticosteroid, achieved more sustained remissions than vehicle. In a third study, tazarotene reduced the degree of epidermal atrophy induced by repeated applications of a superpotent corticosteroid on normal skin in healthy volunteers.

Adrenal Cortex Hormones↗
PubMed2000

Topical antipsoriatics.

Topical corticosteroids are important in psoriasis therapy. However, there are other worthwhile options available including tar, anthralin, tazarotene, calcipotriol, topical PUVA, and topical porphyrin derivatives. With growing public reluctance to use systemic medications, topical treatments for psoriasis could become increasingly important in the future.

Administration, Topical↗
PubMed2000

In vitro compatibility of tazarotene with other topical treatments of psoriasis.

Tazarotene is the first receptor-selective retinoid indicated for the topical treatment of plaque psoriasis. It is being used clinically in combination with other topical antipsoriatic treatments, although its stability in the presence of these products has not been examined extensively. This study examines the compatibility of tazarotene 0.05% gel with 17 other topical products used in the treatment of psoriasis, assessed over a 2-week period. Tazarotene showed minimal degradation (<10%) at 0, 8, 24, and 48 hours after compounding with each of the 17 products. In addition, after 1 and 2 weeks, degradation of tazarotene remained less than 10% for 15 of the 17 products tested. Tazarotene appeared to have minimal impact on the stability of the other products. These results suggest that tazarotene gel can be successfully coprescribed with a range of commonly used topical psoriasis treatments without adversely affecting the chemical stability of either agent.

Administration, Topical↗
PubMed1999

Finasteride in the treatment of men with frontal male pattern hair loss.

BACKGROUND: Finasteride, a specific inhibitor of type II 5alpha-reductase, decreases serum and scalp dihydrotestosterone and has been shown to be effective in men with vertex male pattern hair loss. OBJECTIVE: This study evaluated the efficacy of finasteride 1 mg/day in men with frontal (anterior/mid) scalp hair thinning. METHODS: This was a 1-year, double-blind, placebo-controlled study followed by a 1-year open extension. Efficacy was assessed by hair counts (1 cm2 circular area), patient and investigator assessments, and global photographic review. RESULTS: There was a significant increase in hair count in the frontal scalp of finasteride-treated patients (P < .001), as well as significant improvements in patient, investigator, and global photographic assessments. Efficacy was maintained or improved throughout the second year of the study. Finasteride was generally well tolerated. CONCLUSION: In men with hair loss in the anterior/mid area of the scalp, finasteride 1 mg/day slowed hair loss and increased hair growth.

5-alpha Reductase Inhibitors↗
PubMed1999

Interactions between tazarotene and ultraviolet light.

Tazarotene in combination with phototherapy is being used clinically for the treatment of plaque psoriasis. This study investigates the dose of UVB light required to induce minimal erythema and the dose of UVA light required to induce immediate pigment darkening, with and without pretreatment with tazarotene 0.1% gel. The photostability of tazarotene is also assessed. Pretreatment with tazarotene 0.1% gel 3 times per week for 2 weeks before phototherapy significantly reduced the mean minimal erythema dose (MED) for UVB from 56.25 to 42.50 mJ/cm(2) (P <.01), and significantly reduced the mean UVA exposure required to induce immediate pigment darkening from 20.18 to 18.50 J/cm(2) (P <.05). A thin application of tazarotene gel immediately before phototherapy had no significant effect on the mean MED for UVB, whereas a thick application of the gel increased the MED slightly, from 56.25 to 62.50 mJ/cm(2) (P =.1). Tazarotene remained chemically stable when used in conjunction with UVB or UVA phototherapy. To reduce the patient's potential to burn or tan, we recommend initiating UVB phototherapy at 50% to 75% of the MED when it is used in combination with tazarotene. We also recommend initiating PUVA therapy at slightly lower doses than usual. Lower total doses of UVA or UVB may be needed when patients with psoriasis are treated concomitantly with tazarotene.

Adult↗
PubMed1999

Acitretin in combination with UVB or PUVA.

Combination therapy of psoriasis with acitretin and phototherapy (psoralen-ultraviolet A [PUVA] or ultraviolet B [UVB]) offers multiple advantages over use of either modality alone. As monotherapy, acitretin in doses of 50 mg/day is moderately effective, but is associated with numerous side effects. Single modality treatment with UVB or PUVA involves multiple visits over a period of months and is also associated with dose-limiting side effects. When used in combination, lower doses of both modalities can be used more effectively, helping to reduce side effects. In addition, clearing occurs much more quickly, reducing treatment time and number of phototherapy visits. Moreover, patients whose psoriasis does not clear with monotherapy will often achieve significant clearing with the combination of acitretin and phototherapy.

Acitretin↗
PubMed1999

Duration of remission of psoriasis therapies.

The armamentarium of therapies for psoriasis continues to expand with drugs such as tazarotene, calcipotriene, and acitretin approved in recent years. New forms of old treatments such as cyclosporine and anthralin have also been introduced. Frequently, inadequate attention is devoted to duration of remission. The purpose of this article is to examine the duration of remission reported with many therapies currently used for psoriasis. Studies examining duration of remission are included. Among our conclusions were the following: the definitions of remission/relapse used in various studies differ, duration of remission is influenced by the natural history of each patient's disease, among topical monotherapies anthralin and tazarotene appear to induce longer remissions than calcipotriene and corticosteroids, among systemic agents longer remissions occur with etretinate than cyclosporine or methotrexate but compared with the remission rate of phototherapeutic modalities, especially Goeckerman and PUVA therapy, the remission rates are much less.

Humans↗
PubMed1999

Photoinduced dermal pigmentation in patients taking tricyclic antidepressants: histology, electron microscopy, and energy dispersive spectroscopy.

Two patients had been taking long-term tricyclic antidepressant therapy. Each developed a blue to slate-gray hyperpigmentation in sun-exposed areas. On histologic examination there were refractile golden brown granules free in the dermis along collagen bundles. Similar pigment was present in macrophages and along the basement membrane zone. The granules stained for melanin, but not for iron, and were bleached by the permanganate method. Electron microscopy showed varying size and shaped electron-dense granules within lysosomes and free in the dermis, which, in unstained sections, showed a less dense peripheral halo. This peripheral halo was also evident on light microscopy. Energy dispersive spectroscopy showed these granules to be rich in copper and sulfur (elements present in tyrosinase and pheomelanin, respectively). We believe that this represents a drug-melanosome complex, which is most likely caused by chronic photoactivation.

Antidepressive Agents, Tricyclic↗
PubMed1999

Scavenging of hydrogen peroxide and inhibition of ultraviolet light-induced oxidative DNA damage by aqueous extracts from green and black teas.

Aqueous extracts of green and black teas have been shown to inhibit a variety of experimentally induced animal tumors, particularly ultraviolet (UV) B light-induced skin carcinogenesis. In the present study, we compared the effects of different extractable fractions of green and black teas on scavenging hydrogen peroxide (H2O2), and UV irradiation-induced formation of 8-hydroxy 2'-deoxyguanosine (8-OHdG) in vitro. Green and black teas have been extracted by serial chloroform, ethyl acetate and n-butanol, and divided into four subfractions designated as GT1-4 for green tea and BT1-4 for black tea, respectively. The total extracts from green and black teas exhibited a potent scavenging capacity of exogenous H2O2 in a dose-dependent manner. It appeared that the total extracts from black tea scavenged H2O2 more potently than those from green tea. When tested individually, the potency of scavenging H2O2 by green tea subfractions was: GT2 > GT3 > GT1 > GT4, whereas the order of efficacy for black tea was: BT2 > BT3 > BT4 > BT1. In addition, we demonstrated that total fractions of green and black teas substantially inhibited the induction of 8-OHdG in calf thymus by all three portions of UV spectrum (UVA, B and C). Consistent with the capacity of scavenging H2O2, the subfractions from black tea showed a greater inhibition of UV-induced 8-OHdG than those from green tea. At low concentrations, the order of potency of quenching of 8-OHdG by green tea subfractions was: GT2 > GT3 > GT4 > GT1 and the efficacy of all subfractions became similar at high concentrations. All subfractions of the black tea except BT1 strongly inhibited UV-induced 8-OHdG and the order of potency was: BT2 > BT3 > BT4 > BT1. Addition of (-)-epigallocatechin gallate (EGCG), an ingredient of green tea extract, to low concentration of green and black tea extracts substantially enhanced the scavenging of H2O2 and quenching of 8-OHdG, suggesting the important role of EGCG in the antioxidant activities of tea extracts. The potent scavenging of oxygen species and blocking of UV-induced oxidative DNA damage may, at least in part, explain the mechanism(s) by which green/black teas inhibit photocarcinogenesis.

Carcinogenicity Tests↗