A promising new treatment for solar lentigines.

The purpose of this open-label study was to determine the adverse event rate of topical 4HA/tretinoin when used twice daily for up to 24 weeks with concomitant sunscreen in the treatment of solar lentigines and related hyperpigmented lesions. There were two treatment areas: bilateral dorsal forearms, including the back of the hands; and the face, including the forehead and cheek areas. Each treatment area had a target lesion at least 5 mm in diameter and was moderately darker than the surrounding skin. A nine-point bipolar scale was used for evaluation of Target Lesion Pigmentation (0 = extremely lighter than pigment of the surrounding skin, 4 = equal with pigment of surrounding skin, 8 = extremely darker than pigment of surrounding skin). The other solar lentigines present in the treatment areas also had to have an overall pigmentation grade of at least Grade 6. Twice daily applications to individual lesions in each treatment area were made for up to 24 weeks followed by a 4-week follow-up phase. Sunscreen applications (sunscreen with sun protection factor (SPF) 25 or greater) were made every morning and reapplied after six hours if additional sun exposure was expected. Clinical evaluations were performed at weeks 0, 4, 8, 16, 24 and 28. The clinical signs of Target Lesion Pigmentation and Overall Lesion Pigmentation were evaluated at each visit. A total of 96 subjects were enrolled at four study centers; 77 (80%) subjects completed the study. Treatment-related adverse events (AEs) for 4HA/tretinoin included erythema, burning/stinging/tingling, desquamation, pruritus, skin irritation, halo hypopigmentation and hypopigmentation. Five (5%) subjects discontinued from the study due to adverse events considered to be related to study medication. When used with sunscreen of SPF 25 or greater, 4HA/tretinoin was safe and well tolerated and did not produce any unexpected or unusual adverse events.

The combination of 2% 4-hydroxyanisole (Mequinol) and 0.01% tretinoin is effective in improving the appearance of solar lentigines and related hyperpigmented lesions in two double-blind multicenter clinical studies.

BACKGROUND: Solar lentigines are a chronic condition of the aging population resulting from years of cumulative sun exposure. A topical treatment that is both safe and effective would be welcome and useful. Combinations of therapeutic agents are often used and allow synergy of mechanisms with tolerability. A tyrosinase inhibitor in use in Europe, 4-hydroxyanisole (Mequinol), and the retinoid tretinoin have been used singly as depigmenting agents. OBJECTIVE: The efficacy and safety of the combination product of 2% 4-hydroxyanisole (4HA [mequinol]) /0.01% tretinoin solution (tradename Solagé) were evaluated in two phase III, randomized, controlled, double-blind trials. METHODS: Subjects were randomized to treatment with 4HA/tretinoin solution, one of the active components (4HA or tretinoin), or vehicle. Subjects applied the test solution with a wand applicator twice daily to all solar lentigines and related hyperpigmented lesions on the face, forearms, and backs of hands for up to 24 weeks. Trial 1 had a 24-week no-treatment regression phase and trial 2 had a 4-week no-treatment regression phase. Information collected included clinical assessments of Target Lesion Pigmentation, Physician's Global Assessment of Improvement/Worsening, an Assessment of Overall Cosmetic Effect, and a Subject's Self-Assessment Questionnaire. RESULTS: The 4HA/tretinoin combination was clinically superior to each of its active components and to the vehicle in the treatment of solar lentigines. At the end of treatment, in trial 1 and trial 2, 4HA/tretinoin was statistically superior to each of its active components and vehicle on the forearms and face (P

Platelet factor 4 (PF4) and heparin-released platelet factor 4 (HR-PF4) in patients with cardiovascular disorders.

The recent introduction of the determinations of platelet factor 4 (PF4) and beta-thromboglobulin (beta TG) by radioimmunoassay provided a new tool to obtain knowledge of in vivo platelet activation. We evaluated the plasma level of PF4 and beta TG in 14 normal subjects (mean PF4 7.7 ng/ml; beta TG 28.8 ng/ml), in 29 patients with chronic stable cardiovascular disorders (mean PF4 9.8 ng/ml; beta TG 32.6 ng/ml) and in 15 diabetics with vascular disease (mean PF4 14.5 ng/ml; beta TG 41.8 ng/ml). The great majority had normal values and no statistical differences were noted among the three groups (p greater than 0.05). Fifteen days of treatment with 150 mg daily of dipyridamole produced a significant reduction in the levels of both proteins (p less than 0.01), in contrast of the daily administration of 650 mg of aspirin, which failed to produce any significant change (p greater than 0.5). The patients and the normal subjects were also administered 3,000 USP units intravenously of porcine heparin. The values of the heparin released-platelet factor 4 (HR-PF4), evaluated 5 minutes after the injection, showed a good correlation between platelet concentration and HR-PF4 levels (z = 2.37, p less than 0.02) in the patients. The determination of standard residual following linear regression analysis of HR-PF4 indicated the presence of two distinct patient populations. One group, including the vast majority of patients, did not differ from the control (patients mean HR-PF4 111.1 ng/ml; controls: mean HF-PF4 136 ng/ml). The other group, with severe cardiovascular disease, but with normal levels of PF4 and beta TG in almost all patients and similar platelet concentrations, showed a significantly higher HR-PF4 (219 ng/ml). Neither aspirin nor dipyridamole had any effect on the level of HR-PF4. This HR-PF4 could represent a possible marker of the interaction of platelets with a seriously damaged atherosclerotic vessel wall.