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Biomedical subjects

M Lebwohl

Publications and source records attributed to M Lebwohl.

At least 73 records · Page 4Linked to original sources
PubMed1998

Effect of UV-B phototherapy on plasma HIV type 1 RNA viral level: a self-controlled prospective study.

OBJECTIVE: To study the plasma human immunodeficiency virus type 1 (HIV-1) RNA levels of 12 patients seropositive for HIV who were undergoing UV-B phototherapy to determine if UV-B phototherapy upregulates HIV activity in humans. DESIGN: A self-controlled prospective cohort of HIV-infected patients seen for the treatment of a skin disorder responsive to UV-B phototherapy. Viral levels were measured weekly for 8 weeks of phototherapy. Follow-up viral levels were measured for patients who continued phototherapy beyond 8 weeks, those who had a significant change in their viral level, or both. SETTING: Outpatient clinic of an academic hospital. PATIENTS: Patients with HIV disease and a skin disorder responsive to UV-B phototherapy. Inclusion criteria for patients in this study were those receiving a stable antiviral regimen for at least 6 weeks and who had no major illness or immunization in the 2 months before starting phototherapy. Of 72 patient volunteers screened, 15 met the criteria, 2 declined to participate, and 13 entered the study. One patient was dropped from the study because an accurate baseline measurement could not be obtained. Twelve patients were analyzed, 2 of whom left the study early, 1 at 6 weeks and 1 at 7 weeks. INTERVENTIONS: Ultraviolet-B phototherapy. MAIN OUTCOME MEASURE: Plasma HIV-1 RNA viral level. RESULTS: Plasma HIV-1 RNA levels showed no significant increase or decrease in most of the patients, defined as a 3-fold change from baseline (mean fold change from baseline after 8 weeks of phototherapy, -1.1; 95% confidence interval, 2.9 to -5.0). Trend analysis indicated no significant pattern of change in viral levels (slope, -0.013 log; P > .25). The CD4+ cell counts also remained unchanged (mean before therapy, 277 x 10(9)/L; mean after therapy, 285 x 10(9)/L; P = .67). CONCLUSION: No significant effect of UV-B exposure was seen on plasma HIV-1 levels.

Adult↗
PubMed1998

Tazarotene in combination with topical corticosteroids.

The use of a topical corticosteroid in combination with tazarotene has theoretic appeal because each drug has a different mechanism of action, and it is therefore likely that combination therapy will offer additive or synergistic effects. For example, the steroid may promote a rapid initial response together with minimization of erythema during the treatment period, and tazarotene may prolong the duration of the therapeutic effect and lower the probability of relapse. The results of a large, controlled clinical trial in which corticosteroids of various potencies were added to tazarotene therapy showed that tazarotene plus a medium- or high potency corticosteroid produced greater and more rapid efficacy, and superior tolerability, than tazarotene plus placebo cream.

Administration, Cutaneous↗
PubMed1998

Calcipotriene ointment and halobetasol ointment in the long-term treatment of psoriasis: effects on the duration of improvement.

BACKGROUND: Weekend therapy with superpotent topical corticosteroids has been used for the long-term treatment of psoriasis. Recently, calcipotriene ointment has been added to this regimen for use on weekdays, but there are no long-term studies of that combination. OBJECTIVE: The purpose of this study was to determine whether the addition of weekday calcipotriene to a pulse therapy regimen of weekend superpotent corticosteroids results in a longer duration of remission of plaque psoriasis. SUBJECTS: This was a double-blind, placebo-controlled, parallel-group study. Forty-four patients with mild to moderate psoriasis were treated with calcipotriene ointment in the morning and halobetasol ointment in the evening for 2 weeks. Thereafter, 40 patients who were at least moderately (50% or greater) improved were randomized to 2 treatment groups. After 2 weeks of treatment with calcipotriene ointment in the morning and halobetasol ointment in the evening, 20 patients were randomized to receive halobetasol ointment twice daily on weekends and calcipotriene ointment twice daily on weekdays, and 20 patients were randomized to receive halobetasol ointment twice daily on weekends and placebo ointment twice daily on weekdays. RESULTS: Seventy-six percent of patients applying halobetasol ointments on weekends and calcipotriene ointment on weekdays were able to maintain remission for 6 months compared with 40% of patients applying halobetasol ointment on weekends only with the vehicle on weekdays. CONCLUSION: The addition of calcipotriene ointment applied on weekdays to a weekend pulse therapy regimen of superpotent corticosteroids can increase the duration of remission of psoriasis.

Administration, Topical↗
PubMed1998

Cyclosporine consensus conference: with emphasis on the treatment of psoriasis.

Cyclosporine has been in worldwide use for 15 years for patients who have undergone transplantation operations and is now being used to control inflammatory reactions in other organs (eg, joints, bowel, and skin). Neoral, a more consistently absorbed form of cyclosporine, has recently been approved by the Food and Drug Administration for the treatment of psoriasis. This report outlines the indications, contraindications, dosage recommendations, monitoring requirements, adverse events, drug interactions, interactions with other psoriasis treatments, and suggestions for cyclosporine's use in rotational therapy.

Contraindications↗
PubMed1998

Once-daily tazarotene gel versus twice-daily fluocinonide cream in the treatment of plaque psoriasis.

BACKGROUND: A new class of topical receptor-selective acetylenic retinoids, the first of which is tazarotene, has been developed. OBJECTIVE: Our purpose was to compare the safety, efficacy, and duration of therapeutic effect of 12 weeks of once-daily tazarotene 0.1% and 0.05% gel with that of twice-daily fluocinonide 0.05% cream in the treatment of patients with plaque psoriasis. METHODS: Three hundred forty-eight patients with plaque psoriasis were enrolled and 275 patients completed a multicenter, investigator-masked, randomized, parallel-group clinical trial. RESULTS: Both tazarotene gels were as effective as fluocinonide in reducing plaque elevation after 1 week of treatment, and tazarotene 0.1% gel was similar to fluocinonide in reducing scaling of trunk/limb lesions at all study weeks except week 4. Tazarotene 0. 1% gel was similar to fluocinonide in reducing scaling of knee/elbow lesions at weeks 8 and 12. Fluocinonide had a significantly greater effect on erythema than tazarotene at weeks 2 through 8. However, treatments were not significantly different at week 12, and tazarotene demonstrated significantly better maintenance of therapeutic effect after cessation of therapy. CONCLUSION: Tazarotene 0.1% and 0.05% gels were safe and effective in the treatment of mild-to-moderate plaque psoriasis.

Administration, Cutaneous↗
PubMed1998

Differential regulation of P53 and Bcl-2 expression by ultraviolet A and B.

The induction of apoptosis by ultraviolet (UV) radiation and other DNA damaging agents plays a critical role in monitoring the accumulation of genetic damage and the suppression of tumor development. We hypothesize that UVA and UVB induce apoptosis by modulating balances between p53 and/or bcl-2 genes. Using MCF-7 cells that express both wild-type P53 and Bcl-2 proteins, we demonstrated that UVA and UVB induced apoptosis through regulating expression of apoptosis promoting or inhibiting genes. UVA induced immediate apoptosis and downregulated bcl-2 expression. Bcl-2 expression was reduced by approximately 40% at 4 h post-150 kJ UVA irradiation per m2 with a maximum downregulation (over 70%) at 24 h. The dose-response studies revealed that significant reduction of bcl-2 expression was observed at UVA doses ranging from 50 to 200 kJ per m2; however, p53 levels were not affected by UVA. In contrast, UVB exhibited a entirely different action than UVA in that UVB substantially induced p53 expression, but had no effect on bcl-2 expression. The induction of P53 by UVB was dose and time dependent with the maximum expression at 24 h post-2 and post-4 kJ UVB irradiation per m2. Down-regulation of bcl-2 and fragmentation of DNA induced by UVA occurred earlier (approximately at 4 h) than upregulation of p53 and DNA fragmentation by UVB (12-24 h). These results suggest that UVA and UVB cause cell damage through different mechanisms and that the balances between the expression of p53 and bcl-2 may play an important role in regulating the apoptosis induced by UV irradiation.

Apoptosis↗
PubMed1998

Inhibition of ultraviolet B (UVB)-induced c-fos and c-jun expression in vivo by a tyrosine kinase inhibitor genistein.

We reported the inhibitory effects of genistein, an inhibitor of tyrosine protein kinase (TPK), on ultraviolet B (UVB)-induced expression of c-fos and c-jun in SENCAR mouse skin. UVB irradiation substantially increased transcript levels of c-fos and c-jun mRNA in mouse skin. Topical application of genistein 60 min before UVB radiation reduced c-fos and c-jun expression in the mouse skin in dose-dependent manner. Inhibition was more pronounced in skin exposed to the low dose (5 kJ/m2) than to the high dose (15 kJ/m2) of UVB radiation. In addition, genistein exhibited more inhibition of c-fos than that of c-jun. Post-application of genistein after UVB exposure down-regulated the expressions of c-fos and c-jun, but to a lesser extent compared with pre-application. A431 human epidermoid carcinoma cells, which excessively express epidermal growth factor receptors (EGF-R), were used to investigate the possible mechanism of genistein's action. The results showed that genistein down-regulated the UVB-mediated phosphorylation of TPK-dependent EGF-R in a dose-dependent manner. We concluded that inhibition of UVB-induced c-fos and c-jun expression in mouse skin by genistein may, at least in part, result from the inhibition of TPK activities and down-regulation of EGF-R phosphorylation. Suppression of UVB-induced proto-oncogene expression in mouse skin suggests that genistein may serve as a potential preventative agent against photodamage and photocarcinogenesis.

Animals↗
PubMed1998

Tamoxifen reduces endogenous and UV light-induced oxidative damage to DNA, lipid and protein in vitro and in vivo.

We have investigated the effect of tamoxifen (TAM) on endogenous or ultraviolet radiation (UVR)-induced oxidative damage to macromolecules in vitro and in vivo. In a system containing calf thymus DNA exposed to a germicidal UV lamp, both TAM and 4-hydroxytamoxifen (4-OH-TAM) inhibited UVR-induced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA in a dose-dependent manner. At low concentrations, 4-OH-TAM quenched 8-OHdG more potently than TAM. However, the reduction of 8-OHdG by TAM and 4-OH-TAM became similar at a concentration of 10 microM. In contrast, ascorbic acid had the similar effect to TAM, whereas glutathione exhibited little effect on UVR-induced 8-OHdG. The order of quenching efficacy was: 4-OH-TAM > TAM approximately = ascorbic acid > glutathione. We have further determined the effect of TAM on endogenous 8-OHdG formation, lipid peroxidation, and protein oxidation in the skin of SENCAR mice. Topical application of 5 micromol TAM significantly reduced the level of 8-OHdG in mouse epidermis by approximately 27% (P < 0.05). Endogenous lipid peroxidation and protein oxidation, measured as malondialdehyde (MDA) and carbonyl groups, were also substantially reduced by topical TAM. Further study was conducted to evaluate the effect of TAM on UVR-induced 8-OHdG and MDA in skin of hairless mice. In mice subacutely exposed to low dose (3.4 kJ/m2 x six doses) and high dose (16.8 kJ/m2 x three doses) of UVB irradiation, TAM significantly blocked the formation of 8-OHdG in mouse epidermis by 57-81% and MDA by 37-65%, respectively. Our studies suggest that reduction of oxidative damages to biological macromolecules in vitro and in vivo may at least in part explain the anti-carcinogenic and chemopreventive actions of tamoxifen.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

Isoflavone genistein inhibits the initiation and promotion of two-stage skin carcinogenesis in mice.

Isoflavone genistein is a specific inhibitor of protein tyrosine kinase (PTK) and has been shown to have a variety of anticancer activities in cultured cells and animal models. We report here that genistein significantly inhibits 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-promoted skin tumorigenesis in a two-stage carcinogenesis model. In an initiation study, 10 micromol genistein was applied daily to female SENCAR mouse skin for 1 week, followed by initiation with 10 nmol DMBA. Mice were then treated with twice weekly 4 microg TPA. Genistein was shown to reduce tumor incidence and multiplicity in DMBA-initiated skin tumors by approximately 20 (P < 0.05) and 50% (P < 0.01), respectively. Two promotion studies were conducted using CD-1 and SENCAR mice. In experiment 1, CD-1 mice were initiated with 100 nmol DMBA and followed by a twice weekly regimen of 1 and 5 micromol genistein/4 microg TPA. In experiment 2, SENCAR mice were initiated with 10 nmol DMBA and followed by a regimen of 5, 10 and 20 micromol genistein/2 microg TPA. Both studies consistently showed that genistein substantially inhibited TPA-promoted skin tumorigenesis by reducing the tumor multiplicity by approximately 60 and 75%, respectively (P < 0.01). However, the tumor incidence appeared to be less affected. Mechanistic studies showed that genistein inhibited DMBA-induced bulky DNA adduct formation and substantially suppressed TPA-stimulated H2O2 and inflammatory responses in mouse skin by >60% (P < 0.01). In contrast, genistein only exhibited a moderate inhibition of TPA-induced ornithine decarboxylase activity (P > 0.05). Our results suggest that genistein exerts its anti-initiational and anti-promotional effects on skin carcinogenesis probably through blockage of DNA adduct formation and inhibition of oxidative and inflammatory events in vivo.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

Dermatologic manifestations of systemic disease.

As the body's point of contact with the weight-bearing surface, the foot resists abrasive forces and is constantly bombarded with dermatologic insults. It is the site of a variety of local and systemic afflictions, some which even indicate a state of relative emergency. Paying careful attention to the consideration and exclusion of serious or systemic conditions, this article presents an algorithmic approach that is useful in a clinical setting.

Foot Dermatoses↗
PubMed1998

Clinical efficacy and safety of tazarotene: optimizing clinical results.

Tazarotene is the first topical retinoid demonstrated to be both effective and tolerable in the treatment of psoriasis. The clinical efficacy and safety of topical tazarotene have been investigated in vehicle-controlled and active-controlled studies. Ongoing studies are evaluating its use in combination with other antipsoriasis medications. Tazarotene has been demonstrated to be significantly more effective than vehicle, and comparable in efficacy to fluocinonide 0.05%, but with a more sustained therapeutic effect after treatment is stopped. Its adverse effects consist primarily of mild to moderate local irritation with no reports of treatment-related systemic adverse effects. Combining tazarotene with a mid- to high-potency corticosteroid gives greater efficacy with fewer adverse effects than either agent used alone. The use of tazarotene in combination with phototherapy or calcipotriene is currently being investigated. Overall, topical tazarotene is a highly useful addition to the array of options available for the topical treatment of mild to moderate plaque psoriasis.

Administration, Topical↗