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Biomedical subjects

W A Akers

Publications and source records attributed to W A Akers.

At least 19 recordsLinked to original sources

Percutaneous absorption and metabolism of lonapalene in psoriatic skin.

The percutaneous absorption and metabolism of lonapalene (6-chloro-2,3-dimethoxynaphthalene-1,4-diol-diacetate; RS-43179), a topically effective 5-lipoxygenase inhibitor, has been measured in six subjects with stable plaque-type psoriasis of the lower extremities. Lonapalene readily penetrates psoriatic skin, is rapidly and completely metabolized, and is almost entirely excreted in the urine. Unexpectedly we observed a trend for thigh (T) plaque skin to be more permeable than lower leg (LL) plaque skin as measured by total absorption (T, 44.8 +/- 13.4%; LL, 24.9 +/- 12.6% applied dose excreted), peak plasma levels (T, 209 +/- 107; LL, 146 +/- 81 ng Eq/ml), and peak rate of urinary excretion (T, 591.7 +/- 112.2; LL, 318.4 +/- 143.9 micrograms Eq/hr). There were also differences in the metabolic profiles between the two sites as measured by the quantity and proportion of dealkylated and conjugated products excreted in the urine.

Administration, Cutaneous↗

Sulconazole nitrate 1% cream in the treatment of chronic moccasin-type tinea pedis caused by Trichophyton rubrum.

Sulconazole nitrate 1% cream applied twice daily was compared with its vehicle in the treatment of 229 patients with chronic moccasin-type tinea pedis confirmed by positive results of a potassium hydroxide preparation. At admission in this randomized, double-blind, parallel multicenter trial, 131 patients had positive dermatophyte cultures; Trichophyton rubrum was identified in 121 (92%). After 4 weeks of treatment, patients were examined and, if necessary, were treated for an additional 2 weeks. Sulconazole cream was significantly more effective than the vehicle in the treatment of chronic T. rubrum tinea pedis; 57% of patients were cured by sulconazole, compared with 13% cured with the vehicle. Relapse rates, assessed 2 weeks after the end of treatment, were significantly lower in patients treated with sulconazole than in those receiving vehicle (27% vs 71%). The 103 patients with moccasin-type tinea pedis whose cultures were not positive for T. rubrum achieved similar results.

Adolescent↗

Intrinsic potencies of novel thiol ester corticosteroids RS-85095 and RS-21314 as compared with clobetasol 17-propionate and fluocinonide.

The intrinsic potencies of two novel topical thiol ester corticosteroids, RS-85095 and RS-21314, were compared with the high potency corticosteroids clobetasol 17-propionate and fluocinonide, using human vasoconstriction assays. In these assays, four or five concentrations (0.03 to 3 mg/L) of the corticosteroids in 95% ethanol (alcohol, USP) were applied to predetermined sites on the forearm of volunteers and were occluded following evaporation of the alcohol. The responses were scored in terms of the presence or absence of vasoconstriction and the degree of vasoconstrictive intensity. No statistically significant difference was found in the intrinsic potencies of RS-85095, RS-21314, and clobetasol 17-propionate, and all three corticosteroids were significantly more potent than fluocinonide.

Administration, Topical↗

The effect of ketorolac tromethamine in reducing postoperative inflammation: double-mask parallel comparison with dexamethasone.

Anterior chamber fluorophotometry was done after the oral administration of fluorescein sodium in patients undergoing extracapsular cataract extraction and posterior chamber intraocular lens insertion before and after surgery. The administration of ketorolac solution 0.5% eye drops before and after surgery decreased the breakdown of the blood-aqueous barrier as much as did dexamethasone sodium phosphate solution 0.1% (dexamethasone solution) eye drops at each postoperative time period as measured by fluorophotometry. Slit-lamp observations of postoperative anterior ocular inflammation were not different between treatment groups. Both ketorolac and dexamethasone solutions were well tolerated by patients. No additional corticosteroids were given to any patients during the study. Therefore, ketorolac solution was as effective as dexamethasone solution in suppressing postoperative inflammation after cataract surgery as measured by fluorophotometry and as observed by slit-lamp examinations. This study confirms prior studies that suggest ketorolac ophthalmic solution 0.5% may be effective and safe as a nonsteroidal antiinflammatory agent for topical use after cataract surgery and intraocular lens implantation and as a substitute for topically applied corticosteroids.

Adult↗

Sulconazole nitrate cream 1 percent for treating tinea cruris and corporis.

Sulconazole nitrate 1 percent cream, a new imidazole derivative, was tested in 117 Colombian Army soldiers with tinea cruris/corporis under hot, humid conditions. The results of two clinical trials demonstrate that sulconazole applied once daily was as effective as clotrimazole applied twice daily. After three weeks of therapy 100 percent of the patients treated either once or twice daily with sulconazole showed negative findings on potassium hydroxide preparations and cultures from lesions. Although sulconazole was well tolerated and caused no adverse reactions, four of twenty-seven clotrimazole-treated patients showed reactions consisting of erosive primary irritation. Sulconazole nitrate 1 percent cream appears to be highly effective in the treatment of tinea cruris/corporis when applied once or twice daily and may be very useful in hot and humid conditions where contact irritation reactions occur more often.

Adolescent↗

Measurements of friction injuries in man.

Repetitive frictional insults over years to human skin result in lichenification, callosites, and clavi (corns). No measurements of the forces involved have been made for callosites or corns. Two reports deal with lichenification produced by repeated rubbing over weeks. By contrast, friction blisters have been seriously studied because they can be produced in minutes and because foot blisters can disable soldiers. Three devices to measure the coefficient of friction of materials on man's skin and eight machines to rub man's skin are reviewed.

Biophysical Phenomena↗

Risks of unoccluded topical steroids in clinical trials.

Data were reviewed on the beneficial responses and adverse reactions among 2,849 patients in 14 paired-comparison studies with eight unoccluded topical corticosteroids in six steroid-responsive dermatoses. Adverse reactions were found to be mild, transient, and, for the most part, rare. Of 5,698 treatment exposures, 249 (4.39%) adverse reactions were reported, including irritation (1.3%), itching (0.95%), burning (0.81%), dryness (0.46%), scaling (0.30%), and vesicle formation (0.16%). Other reactions occurred in less than one in 1,000 treatment exposures. No severe reactions were observed. Five subjects (0.17%) terminated treatment early because of adverse reactions. The incidence of adverse reactions to vehicle alone was 6.7%. The benefit-risk ratio for mild reactions was 17:1. Therefore, long lists of adverse reactions are inappropriate in written consent forms for prospective volunteers for clinical trials. Al alternative warning statement is proposed.

Administration, Topical↗

Percutaneous absorption of carbon 14 labeled insect repellents in hairless dogs.

The percutaneous penetration of three insect repellents was determined in hairless dogs. Each compound was administered intravenously and topically to three dogs. Urine, feces and blood samples were assayed for radioactivity by scintillation counting. The percent penetration for N,N-diethyl-m-toluamide (m-deet, the most widely used insect repellent), its isomer N,N-diethyl-p-toluamide and 2-ethyl-1,3-hexanediol were 7.9%, 7.6%, and 10.3% respectively. The results for m-deet penetration in the hairless dog are comparable to those in man.

Administration, Topical↗

Allergic contact hypersensitivity to nickel, neomycin, ethylenediamine, and benzocaine. Relationships between age, sex, history of exposure, and reactivity to standard patch tests and use tests in a general population.

A study population of 1,158 paid adult volunteers was obtained. Prior to patch testing, a history of previous exposure to four allergens also was obtained. Prevalence of positive reactions to patch tests was nickel, 5.8%; neomycin, 1.1%; ethylenediamine, 0.43%; and benzocaine, 0.17%. Nine percent of women reacted to nickel compared with 0.9% of men. There was a strong correlation of nickel sensitivity with a history of pierced ears, earlobe rash, and jewelry rash. Ten of 12 neomycin-positive subjects used neomycin for one week or longer on an inflammatory dermatosis, compared with six of 36 age-, race-, and sex-matched controls. By history, 85% were exposed to benzocaine, 48% to neomycin, and 15% to Mycolog (ethylenediamine). Of 127 patients referred to clinics for evaluation of contact dermatitis, 11% yielded positive tests to nickel, 6.3% to neomycin, 3.1% to ethylenediamine, and 1.6% to benzocaine. Data obtained from testing contact dermatitis patients are not applicable to the general population.

Adult↗

Temperature dependence of water content of stratum corneum.

The water content of human stratum corneum has been measured gravimetrically in vitro in relation to relative humidity (RH) and temperature. Water content increased with increasing RH. Stratum corneum water content increased 50% when the temperature was raised from 20 to 35 degrees C at RH below 60%. Temperature dependence decreased with increasing RH until there was essentially no temperature dependence at 90% RH. The conclusion is that temperature changes could significantly affect water content in vivo and pliability of skin at RH below 60%.

Elasticity↗