The context preexposure facilitation effect in mice: a dose-response analysis of pretraining scopolamine administration.

The context preexposure facilitation effect (CPFE) is an elaboration of contextual fear conditioning and refers to enhanced contextual conditioning resulting from preexposure to the context prior to a separate, brief context-shock episode. A version of the CPFE developed by Rudy and colleagues in rats has demonstrated greater sensitivity to pre-training hippocampal insult relative to standard contextual fear conditioning preparations. Our aim was to adapt the Rudy CPFE procedures to mice. In Experiment 1 we compared performance of young adult male C57BL6/J mice on two versions of the CPFE. One version - not previously used in mice - adapted methods established by Rudy and colleagues, and the other CPFE task replicated procedures previously established in this mouse strain by Gould and colleagues. In Experiment 2 we compared the effects of pre-training intraperitoneal administration of moderate levels of scopolamine or methylscopolamine on contextual conditioning between mice trained using the Rudy CPFE method and a separate group trained using standard contextual fear procedures. Scopolamine is a muscarinic cholinergic receptor antagonist that impairs hippocampal function. Robust freezing to the conditioning context was observed in mice trained using the Rudy CPFE method (Experiment 1), and greater scopolamine-induced impairments in contextual freezing were observed using this CPFE method relative to mice trained using standard contextual fear procedures (Experiment 2). These findings support use of the Rudy CPFE task as a behavioral assay for hippocampal function in mice.

Oral phosphate binders in the treatment of pseudoxanthoma elasticum.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a systemic connective tissue disorder involving elastic fiber calcification and fragmentation with major clinical manifestations occurring in the cutaneous, ocular, and cardiovascular systems. Normalization of the serum calcium-phosphate product through hemodialysis in a previous patient with perforating periumbilical PXE and elevated serum phosphate resulted in regression of skin lesions. OBJECTIVE: We sought to study the effect of pharmacologically limiting the intestinal absorption of phosphate in patients with PXE. METHODS: Patients received baseline skin examinations, target skin lesion evaluation, and photography; renal function tests and serum calcium and phosphate levels; urine calcium, phosphate, and creatinine levels; skin biopsy; and eye examinations and indocyanine-green angiography. Patients were treated with aluminium hydroxide tablets or liquid and returned every 2 to 4 months for skin photography and lesion evaluation. Repeated skin biopsies were performed on clinically improved target sites. Ophthalmologic evaluation was obtained at yearly intervals. RESULTS: Of 6 patients, 3 showed significant clinical improvement of skin lesions and all 3 of these patients showed histopathologic regression of disease in their target lesions. No deterioration of eye disease was seen in any of the 6 patients at 1-year follow-up. CONCLUSION: Our results demonstrate that the calcification seen in PXE may be reversible in some patients. This could hold true for eye and vascular lesions and for skin. Further studies supporting these results could reveal the first real treatment option for PXE.

Long-term efficacy and safety of tretinoin emollient cream 0.05% in the treatment of photodamaged facial skin: a two-year, randomized, placebo-controlled trial.

BACKGROUND: Long-term (>1 year) placebo-controlled studies of tretinoin in the treatment of photodamaged skin have not been conducted. Recently, we conducted a 2-year placebo-controlled study of tretinoin emollient cream 0.05%, including histopathologic assessment of safety and analysis of markers of collagen deposition. OBJECTIVE: The objective of the study was to determine the long-term safety and efficacy of tretinoin emollient cream 0.05% in the treatment of moderate to severe facial photodamage. METHODS: A total of 204 subjects were treated with tretinoin or placebo (vehicle emollient cream) applied to the entire face once a day for up to 2 years. Clinical and histologic effects were assessed at regularly scheduled clinic visits. RESULTS: Treatment with tretinoin resulted in significantly greater improvement relative to placebo in clinical signs of photodamage (fine and coarse wrinkling, mottled hyperpigmentation, lentigines, and sallowness), overall photodamage severity, and investigator's global assessment of clinical response (p<0.05). Histologic evaluation showed no increase in keratinocytic or melanocytic atypia, dermal elastosis, or untoward effects on stratum corneum following treatment with tretinoin compared with placebo. Immunohistochemistry studies, conducted at three study centers, showed a significant increase relative to placebo in facial procollagen 1C terminal, a marker for procollagen synthesis, at month 12 (p=0.0074). CONCLUSION: Long-term treatment with tretinoin emollient cream 0.05% is safe and effective in subjects with moderate to severe facial photodamage.

Clobetasol propionate lotion, an efficient and safe alternative to clobetasol propionate emollient cream in subjects with moderate to severe plaque-type psoriasis.

BACKGROUND: Various formulations of clobetasol propionate are currently used to treat psoriasis due to its anti-inflammatory, anti-pruritic, vasoconstrictive and immunomodulating properties. OBJECTIVE: To assess the efficacy, safety and remission profile of clobetasol propionate lotion compared to that of clobetasol propionate emollient cream and lotion vehicle in subjects with moderate to severe plaque-type psoriasis. METHODS: Multicentre, investigator-blind, randomized, active- and vehicle-controlled, parallel-group study. RESULTS: A total of 192 subjects were treated: 82 with clobetasol propionate lotion, 81 with clobetasol propionate cream and 29 with the vehicle. Clobetasol propionate lotion was significantly more effective than vehicle lotion and was comparable in efficacy to the emollient cream after 4 weeks of treatment. Treatment success was higher for subjects in the clobetasol propionate lotion group than in the emollient cream group after 4 weeks of a treatment-free follow-up period. Clobetasol propionate lotion was safe and well tolerated. CONCLUSION: The present study demonstrates that clobetasol propionate lotion is an efficacious, safe and well-tolerated alternative to the currently available emollient cream formulation, while showing a better remission profile after 4 weeks of treatment-free follow-up period.

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.

A randomized, double-blind, placebo-controlled study of clobetasol propionate 0.05% foam in the treatment of nonscalp psoriasis.

BACKGROUND: Topical corticosteroids are the primary treatment for mild to moderate psoriasis. Foam preparations of corticosteroids offer potential cosmetic and pharmacodynamic advantages over cream and ointment vehicles. A clobetasol propionate foam product is as effective as clobetasol propionate solution in the treatment of scalp psoriasis. AIM: To evaluate the safety and efficacy of clobetasol propionate foam in the treatment of psoriasis involving sites other than the scalp. METHODS: Eighty-one subjects with mild to moderate psoriasis were randomized in a 3 : 1 ratio to receive clobetasol propionate foam vs. placebo foam treatment in this double-blind study of psoriasis involving nonscalp sites. The investigator's and subject's global assessment of the response at week 2 (or at the end of treatment) and at week 4 (follow-up) and the severity of erythema, scaling, and plaque thickness were assessed. Safety was assessed from reported adverse events. RESULTS: After 2 weeks of treatment, there was significantly greater improvement with clobetasol propionate foam compared with placebo foam in both investigator's and subject's global assessment of the response (P < 0.0005). The improvement with clobetasol propionate foam was still present at the 4-week follow-up visit. Adverse effects were generally limited to mild to moderate application site reactions. No subjects withdrew because of adverse events. CONCLUSIONS: Clobetasol propionate foam is more effective than placebo in the treatment of nonscalp psoriasis. Twice-daily applications are well tolerated, compliance exceeds 90%, cosmetic characteristics are acceptable, and the medication may eliminate the need for separate scalp and body prescriptions.

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.

Successful treatment of acne vulgaris using a new method: results of a randomized vehicle-controlled trial of short-contact therapy with 0.1% tazarotene gel.

CONTEXT: Short-contact application of 0.1% tazarotene gel for acne was devised to minimize local adverse effects. Its efficacy and safety are unknown. OBJECTIVES: To assess acne improvement and tolerability during 12 weeks of short-contact treatment with 0.1% tazarotene gel vs a nonmedicated gel control. DESIGN: A randomized, masked, vehicle-controlled trial. SETTING: Outpatient facilities at an urban medical school and an affiliated suburban office practice. PARTICIPANTS: Ninety-nine volunteers with facial acne were enrolled; 81 completed the study. INTERVENTION: Thirty-three patients were randomly assigned to each of 3 groups: T + T applied 0.1% tazarotene gel twice daily, T + V applied 0.1% tazarotene gel once daily and vehicle gel once daily, and V + V applied vehicle gel twice daily. Patients adjusted the contact period as tolerated, between 30 seconds and 5 minutes per application. MAIN OUTCOME MEASURES: Acne efficacy by reduction in acne lesions, treatment success (50%-100% improvement in global response to treatment) and improvement in overall disease severity. Local adverse effects, scored from none to severe. RESULTS: By week 12, T + T and T + V achieved significantly greater improvement in acne than V + V based on mean percentage reduction in noninflammatory lesions (46% and 41% vs 2%; P =.002) and inflammatory lesions (38% and 34% vs 9%; P =.01), percentage of treatment successes (64% and 61% vs 15%; P<.001), and reduction in overall disease severity (30% and 29% vs 3%; P<.001). Local adverse effects did not differ significantly among the 3 groups after week 4. CONCLUSION: Short-contact 0.1% tazarotene gel therapy is a safe and effective new method of acne treatment.