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Background: Onychomycosis is a common nail infection that is difficult to treat successfully. The prevalence increases with age and is associated with diabetes. Oral treatments are limited by drug interactions and potential hepatotoxicity; topical treatments, by modest efficacy., Objective: We investigated the efficacy and safety of a solution using a novel topical triazole antifungal, efinaconazole, in distal lateral subungual onychomycosis (DLSO)., Methods: Multicenter, randomized, double-blind, vehicle-controlled phase 2 study in mild to moderate toenail DLSO (n=135). Subjects randomized (2:2:2:1 ratio) to receive efinaconazole 10% solution (with or without semiocclusion), efinaconazole 5% solution, or vehicle, once daily for 36 weeks, with one 4-week posttreatment follow-up (week 40). Efficacy assessments included complete cure, mycologic cure, clinical efficacy, and other assessments of overall treatment effectiveness. No efficacy variables were designated as primary., Results: At follow-up, complete cure was numerically higher in all active groups (16%-26%) compared with vehicle (9%). Mycologic cure rates with efinaconazole 10% semiocclusion, efinaconazole 10%, and efinaconazole 5% were 83%, 87%, and 87%, respectively. Efinaconazole 10% (with or without semiocclusion) demonstrated significantly greater clinical efficacy and treatment effectiveness when compared with vehicle (P=.0088 and .0064; .0056 and .0085, respectively, for both efinaconazole 10% groups). Adverse events were generally similar and mild. Local-site reactions were restricted to few subjects and did not differ meaningfully from those produced by vehicle., Conclusions: This study provided evidence that once-daily efinaconazole 10% solution (with or without semiocclusion) applied topically for 36 weeks was more effective than vehicle in treating DLSO and was well tolerated. Based on these results, efinaconazole 10% solution was chosen for the phase 3 development program.

Background: There is a need for improved medical approaches to the treatment of actinic keratosis. Ingenol mebutate, a diterpene ester extracted and purified from the plant Euphorbia peplus, is being evaluated as a topical therapy for actinic keratosis., Objective: Assess the efficacy and safety of ingenol mebutate (formerly PEP005) gel at 3 dosing regimens for the treatment of actinic keratosis., Methods: Patients with non-facial actinic keratoses applied vehicle gel for 3 days, ingenol mebutate gel, 0.025% for 3 days, or ingenol mebutate gel, 0.05% for 2 or 3 days, with an 8-week follow-up period., Results: All 3 active treatments were significantly more effective than vehicle at clearing actinic keratosis lesions, with a dose response observed. The partial clearance rate (primary efficacy end point) for patients treated with ingenol mebutate gel ranged from 56.0% to 75.4% compared with 21.7% for vehicle gel (P = .0002 to P < .0001 vs vehicle). The complete clearance rate was also significantly higher (P < or = .0006) for patients in the ingenol mebutate gel treatment groups (range: 40.0% to 54.4%) compared with vehicle (11.7%), as was the baseline clearance rate (range: 42.0% to 57.9% for ingenol mebutate gel compared with 13.3% for vehicle, P < .0001 to .0007 vs vehicle). The median percentage reduction in baseline actinic keratosis lesions for patients treated with ingenol mebutate gel ranged from 75% to 100% compared with 0% for vehicle gel (P < .0001 vs vehicle). Active treatment was well tolerated at all dosages. The mechanism of action of this agent is the localized induction of necrosis followed by a transient inflammatory response, and this was manifested in most patients as transient local skin responses consisting primarily of erythema, flaking/scaling, and crusting. There was no evidence of treatment-related scarring., Limitations: Local skin responses may have suggested active treatment to investigators., Conclusions: Short-course, field-directed therapy with ingenol mebutate gel for actinic keratoses on non-facial sites seems to be effective with a favorable safety profile and potential benefits over topical agents that require a more prolonged course of treatment.

Background: Actinic keratoses (AKs) are the most common epithelial precancerous lesions, especially among individuals with light complexions. AKs are believed to progress to in situ squamous cell carcinoma (SCC) and potentially, to invasive SCC. AKs and invasive SCCs share certain histopathological features and both share genetic tumour markers and p53 mutations. Given these facts, the treatment and management of AKs are integral components to quality dermatological health care., Objectives: Topical aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has been extensively studied over the last several years. This study seeks to characterize further the efficacy and safety of ALA-PDT by extending previous work to: (i) assess the long-term recurrence rate of AKs that have resolved after ALA-PDT; (ii) to characterize the histopathology of treated AK lesions that do not completely respond to ALA-PDT or recur in long-term follow up; (iii) to characterize the histopathology of untreated clinically diagnosed AK lesions in the study population at baseline; and (iv) to evaluate ALA-PDT in darker skin types than previously studied., Methods: Patients enrolled in this study had six to 12 discrete AK lesions, either on the face or the scalp. Individual AK lesions designated for treatment were graded as either grade 1 (lesions slightly palpable and more easily felt than seen) or grade 2 (moderately thick AKs, easily seen and felt). Patients with grade 3 (very thick and/or hyperkeratotic) lesions were excluded. For each subject, two lesions at baseline were randomized to biopsy, and were not followed as part of the study while the remaining lesions (target lesions) were treated with ALA-PDT (baseline and month 2, if required) and followed for 12 months., Results: Of the 110 patients enrolled, 101 completed the study. The target AK lesions in the per-protocol population clearing completely in the first and second months following a single ALA-PDT treatment (baseline) were 76% and 72%, respectively. Sixty per cent of the patients received a second ALA-PDT treatment, limited to the target AKs still present at month 2. The percentage of treated target lesions that cleared completely peaked at 86% at month 4 then decreased gradually over time to 78% at month 12. The overall recurrence rate for all lesions that were noted to be cleared at some visit during the 12-month period was 24% (162/688). Of the 162 recurrent lesions 16 were lost to follow up, seven spontaneously cleared and 139 were biopsied. With respect to the lesions biopsied, 91% (127/139) were diagnosed histopathologically as AK, with the balance of lesions being SCC (nine of 139: 7%), basal cell carcinoma (one of 139: 0.7%) and other non-AK diagnoses (two of 139: 1%). The recurrence rate for histologically confirmed AKs was 19%. The clinical diagnosis of AK by investigators appeared to be accurate, with 91% (200/220) of the untreated clinically diagnosed AK lesions being histopathologically confirmed to be AK (AK, 142/220: 65%; advanced AK, 29/220: 13%; macular AK, 29/220: 13%). Despite concentrated efforts to recruit patients with Fitzpatrick skin types IV-VI, the distribution was as follows: I, 11%; II, 36%; III, 41%; IV, 11%; V, 2%. The demographics of this study population are typical of a patient population with AK., Conclusions: ALA-PDT was shown to be an effective and safe therapy for the treatment of AKs of the face and scalp in skin types I-V, with an acceptable rate of recurrence over 12 months of histologically confirmed AKs of 19%. Phototoxicity reactions were all expected, nonserious and had essentially resolved after 1 month post-treatment independent of skin type.

Background: Adverse changes in bone have been reported for patients undergoing high-dose, long-term (several years) isotretinoin therapy for disorders of cornification. The effect of short-term (4-5 months) therapy at the lower dose recommended for acne on bone development in younger, growing adolescent (12-17 years) patients has not been well studied., Objective: The purpose of the study was to evaluate the effect of a standard, single course of isotretinoin (Accutane) therapy on bone mineral density (BMD) of the lumbar spine and hip in adolescents ages 12 to 17 years with severe, recalcitrant, nodular acne., Methods: In this open-label, multicenter study, 217 adolescents (81 girls) with severe, recalcitrant, nodular acne were enrolled and treated with isotretinoin twice daily with food at the recommended total dose of approximately 1 mg/kg for 16 to 20 weeks. BMD in the lumbar spine and hip was measured at baseline and at the end of therapy by dual energy radiograph absorptiometry., Results: There was no clinically significant mean change in BMD measured at the lumbar spine (+1.4%, range: -4.9% to +12.3%) or total hip (-0.26%, range: -11.3% to +15.0%). Hyperostosis was not observed in any patient. Typical efficacy expected in the treatment of acne was observed., Conclusions: A 16- to 20-week course of isotretinoin treatment at the recommended dose for severe acne has no clinically significant effect on lumbar spine and total hip BMD in the adolescent (12-17 years) population.

Background: Topical minoxidil solution 2% stimulates new hair growth and helps stop the loss of hair in individuals with androgenetic alopecia (AGA). Results can be variable, and historical experience suggests that higher concentrations of topical minoxidil may enhance efficacy., Objective: The purpose of this 48-week, double-blind, placebo-controlled, randomized, multicenter trial was to compare 5% topical minoxidil with 2% topical minoxidil and placebo in the treatment of men with AGA., Methods: A total of 393 men (18-49 years old) with AGA applied 5% topical minoxidil solution (n = 157), 2% topical minoxidil solution (n = 158), or placebo (vehicle for 5% solution; n = 78) twice daily. Efficacy was evaluated by scalp target area hair counts and patient and investigator assessments of change in scalp coverage and benefit of treatment., Results: After 48 weeks of therapy, 5% topical minoxidil was significantly superior to 2% topical minoxidil and placebo in terms of change from baseline in nonvellus hair count, patient rating of scalp coverage and treatment benefit, and investigator rating of scalp coverage. Hair count data indicate that response to treatment occurred earlier with 5% compared with 2% topical minoxidil. Additionally, data from a patient questionnaire on quality of life, global benefit, hair growth, and hair styling demonstrated that 5% topical minoxidil helped improve patients' psychosocial perceptions of hair loss. An increased occurrence of pruritus and local irritation was observed with 5% topical minoxidil compared with 2% topical minoxidil., Conclusion: In men with AGA, 5% topical minoxidil was clearly superior to 2% topical minoxidil and placebo in increasing hair regrowth, and the magnitude of its effect was marked (45% more hair regrowth than 2% topical minoxidil at week 48). Men who used 5% topical minoxidil also had an earlier response to treatment than those who used 2% topical minoxidil. Psychosocial perceptions of hair loss in men with AGA were also improved. Topical minoxidil (5% and 2%) was well tolerated by the men in this trial without evidence of systemic effects.

Adapalene gel 0.1% is approved for use in the treatment of acne vulgaris. A new cream formulation, adapalene cream 0.1%, has been developed. Our objective was to evaluate the efficacy and tolerability of adapalene cream 0.1% in comparison with its cream vehicle, applied once daily for 12 weeks to patients with facial acne vulgaris. We used a 12-week, multicenter, randomized, double-blind, vehicle-controlled, comparative phase 3 study of adapalene cream 0.1% and cream vehicle. The study enrolled 237 patients (125 males and 112 females), aged 12 through 30 years, with mild-to-moderate acne vulgaris. Adapalene cream 0.1% demonstrated superior efficacy compared with its cream vehicle. Significantly lower numbers of total inflammatory and noninflammatory lesion counts were observed at the end of the study period in patients using adapalene cream 0.1% as opposed to those using cream vehicle (P<.05 compared with baseline, for all 3 parameters). Adapalene cream 0.1% caused more cutaneous side effects than the cream vehicle, but these were tolerated in most patients. In summary, the results of this study indicate that adapalene cream 0.1% demonstrates superior efficacy over cream vehicle for the treatment of acne vulgaris. Adapalene cream 0.1% also has excellent tolerability and is associated with a low incidence of cutaneous adverse events.

A topical gel combining 5% benzoyl peroxide and 1% clindamycin as phosphate was evaluated in a 10-week randomized double-blind trial involving 287 patients with moderate to moderately severe acne. The combination agent demonstrated significantly greater reductions in inflammatory lesions than either of its active constituents (5% benzoyl peroxide and 1% clindamycin) or vehicle when used alone. Significantly greater reductions in comedos and improvements, as measured by both physicians' and patients' global evaluations, were obtained with the combination agent than with clindamycin or vehicle. The reduction in comedos and the global improvements were similar between the combination agent and benzoyl peroxide. The combination agent was well tolerated; the incidence of dry skin was similar to that found with benzoyl peroxide, and other adverse events were similar to that with vehicle. The improved efficacy obtained with combination therapy was accompanied by a safety profile similar to that of either constituent used alone.

Retinoids reverse the abnormal pattern of keratinization seen in acne vulgaris. Tazarotene is the first of a novel family of topical receptor-selective acetylenic retinoids. This study evaluates the safety and efficacy of topical tazarotene 0.1% and 0.05% gels, in comparison to vehicle gel, applied once daily for 12 weeks, in the treatment of mild-to-moderate facial acne vulgaris. A total of 446 patients with facial acne vulgaris were enrolled, and 375 patients, ranging in age from 14 to 44 years, were evaluable in this multicenter, double-blind, randomized study. In comparison to vehicle gel, treatment with tazarotene 0.1% gel resulted in significantly greater reductions in noninflammatory and total lesion counts at all follow-up visits, and inflammatory lesion counts at Week 12. Tazarotene 0.05% gel resulted in significantly greater reductions in noninflammatory and total lesion counts than vehicle gel at Weeks 8 and 12. At Week 12, treatment success rates were 68% and 51% for tazarotene 0.1% and 0.05%, respectively (40% for vehicle gel). Tazarotene gel was an effective, safe, and generally well-tolerated therapy for the treatment of acne vulgaris.

Background: Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of fungal infections., Objective: The purpose of this study was to assess the safety and efficacy of oral fluconazole 150, 300, and 450 mg administered once weekly compared with placebo in the treatment of distal subungual onychomycosis of the fingernail caused by dermatophytes., Methods: This was a multicenter, randomized, double-blind, placebo-controlled study enrolling 349 patients with onychomycosis of the fingernails. Clinical and mycologic efficacy as well as measures of safety were assessed monthly for a maximum of 9 months of treatment, with additional safety visits occurring at weeks 2 and 6. For inclusion, patients were required to have clinically and mycologically documented onychomycosis of the fingernail caused by dermatophytes with at least 25% involvement of the target fingernail. After end of therapy, patients with improved or cured fingernails entered a blinded 6-month follow-up without drug treatment during which efficacy was assessed every 2 months. Efficacy was assessed by clinical (visual) and mycologic (microscopic and culture) measures. Clinical measures included assessments of the percentage of target nail involvement, measurement of the distance from the nail fold to the proximal onychomycotic border, and signs and symptoms of onychomycosis., Results: Fluconazole was significantly superior to placebo in eradicating clinical and mycologic symptoms of onychomycosis, both at the end of active treatment and at 6 months after treatment (p=0.0001 for all efficacy measures). At the end of therapy, 91% to 100% of patients in the fluconazole groups were judged clinical successes, defined as reduction of the affected area of the target nail to less than 25% or cure, compared with 8% for placebo. Clinical cure rates at end of therapy were 76%, 85%, and 90% for fluconazole 150, 300, and 450 mg, respectively, compared with 3% for placebo. These clinical success and cure rates were largely maintained or improved during follow-up. Clinical relapse in cured patients during the follow-up period was very low (1.5% to 3.3%). Fluconazole demonstrated mycologic eradication rates of 89% to 100% at the end of treatment and 90% to 99% at the end of follow-up; for placebo the rates were 8% and 12%, respectively., Conclusion: Fluconazole administered once weekly is safe and effective in eradicating distal subungual onychomycosis of the fingernail caused by dermatophytes.

Background: Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens of onychomycosis, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of superficial fungal infections., Objective: The purpose of this study was to compare the efficacy and safety of three different doses of fluconazole (150, 300, and 450 mg) given orally once weekly to that of placebo in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes., Methods: In this multicenter, double-blind study, 362 patients with mycologically confirmed onychomycosis were randomized to treatment with fluconazole, 150, 300, or 450 mg once weekly, or placebo once weekly for a maximum of 12 months. To enter the study, patients were required to have at least 25% involvement of the target nail with at least 2 mm of healthy nail from the nail fold to the proximal onychomycotic border. Patients who were clinically cured or improved at the end of treatment were further evaluated over a 6 month follow-up period. At both the end of therapy and the end of follow-up, clinical success of the target nail was defined as reduction of the affected area to less than 25% or cure., Results: At the end of therapy, 86% to 89% of patients in the fluconazole treatment groups were judged clinical successes as defined above compared with 8% of placebo-treated patients. Clinical cure (completely healthy nail) was achieved in 28% to 36% of fluconazole-treated patients compared with 3% of placebo-treated patients. Fluconazole demonstrated mycologic eradication rates of 47% to 62% at the end of therapy compared with 14% for placebo. The rates at the end of follow-up were very similar, indicating that eradication of the dermatophyte was maintained over the 6-month period. All efficacy measures for the fluconazole groups were significantly superior to placebo (p=0.0001); there were no significant differences between the fluconazole groups on these efficacy measures. The clinical relapse rate among cured patients over 6 months of follow-up was low at 4%. Fluconazole was well tolerated at all doses over the 12-month treatment period, with the incidence and severity of adverse events being similar between the fluconazole and placebo treatment groups. Mean time to clinical success in the fluconazole treatment groups was 6 to 7 months. This time frame may be used as a guideline for fluconazole treatment duration., Conclusion: The results of this study support the use of fluconazole in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. Doses between 150 to 450 mg weekly for 6 months were clinically and mycologically effective as well as safe and well tolerated.

Background: Fluconazole has proven to be safe and effective for a variety of superficial and systemic fungal infections. Preliminary analysis of extensive Phase III studies suggests that it is very effective for the treatment of onychomycosis. Its pharmacokinetic properties, including low molecular weight and high water-solubility, suggest a unique ability to penetrate the nail. This feature is likely to account in part for fluconazole's effectiveness in the treatment of onychomycosis., Objective: Determinations of plasma and fingernail concentrations of fluconazole were performed as part of a larger study comparing the safety and efficacy of once-weekly fluconazole (150, 300, and 450 mg) to placebo in the treatment of distal subungual onychomycosis of the fingernails caused by dermatophytes. The relationship between fluconazole concentrations and efficacy was also examined., Methods: Pharmacokinetic studies were performed by means of plasma and fingernail samples from 133 patients, a subset of 349 patients participating in a double-blind, placebo-controlled clinical trial of fluconazole administered in once-weekly doses of 150, 300, or 450 mg until cure of onychomycosis or for a maximum of 9 months. Blood and fingernail samples for pharmacokinetic analysis were taken at baseline, at week 2, and at monthly intervals during the treatment phase of the study. Patients considered clinically cured or improved also participated in a 6-month follow-up study. During this phase, patients were monitored and samples taken every 2 months., Results: Significant amounts of fluconazole were detected in the earliest fingernail samples taken (after 2 weeks of treatment). After two weekly doses, 30% to 33% of steady-state concentrations had been achieved in healthy nails and 22% to 29% in affected nails. Steady state was achieved in 3 to 5 months. Fluconazole concentration in nails as well as plasma followed dose-proportional pharmacokinetics. Nail:plasma ratios in affected nails were 0.4 to 0.6 at 2 weeks and 1.7 to 1.8 at 6 months. Fluconazole concentrations fell slowly after drug discontinuation and were still detectable 4 months after end of treatment. A statistically significant correlation was found between steady-state concentration and clinical and global outcomes., Conclusion: Fluconazole rapidly penetrates the fingernail, where it is retained at detectable levels for at least 4 months after drug discontinuation. A significant correlation exists between fluconazole concentration in the fingernails and clinical and global outcomes.

Background: Preliminary clinical data suggest that fluconazole is effective in the treatment of patients with onychomycosis. To design optimum dosage regimens, a better understanding of fluconazole's distribution into and elimination from nails is needed., Objective: The purpose of this study was to determine plasma and toenail concentrations of fluconazole., Methods: In this multicenter, randomized, double-blind investigation, fluconazole (150 mg, 300 mg, or 450 mg) or matching placebo was administered once a week for a maximum of 12 months to patients with onychomycosis of the toenail. A total of 151 subjects participated in the pharmacokinetic assessment. Blood samples and distal toenail clippings from both affected and healthy nails were obtained for fluconazole concentration determinations at baseline, at the 2-week visit, at each monthly visit until the end of treatment, and then at 2, 4, and 6 months (nail samples only at the latter two) after fluconazole was discontinued., Results: Fluconazole was detected in healthy and affected nails at the 2-week assessment in nearly all subjects. The median time to reach steady-state fluconazole concentrations in healthy nails was 4 to 5 months in the three fluconazole dose groups. In affected nails, steady-state fluconazole concentrations were achieved more slowly, with a median time of 6 to 7 months. At the 8-month assessment, affected toenail fluconazole concentrations were higher than corresponding plasma fluconazole concentrations, with ratios of 1.31 to 1.50 in the three active treatment groups. Toenail concentrations of fluconazole declined slowly after treatment was discontinued, with elimination half-lives of 2.5, 2.4, and 3.7 months for the 150, 300, and 450 mg doses, respectively. Measurable fluconazole concentrations were still present in toenails at 6 months after treatment in most subjects., Conclusion: Fluconazole penetrates healthy and diseased nails rapidly, yielding detectable concentrations after two weekly doses. Once it penetrates nail, fluconazole persists for up to 6 months or longer after therapy is stopped. These favorable pharmacokinetic characteristics support a once-weekly fluconazole dosage regimen for the treatment of patients with onychomycosis.

Objective: This study evaluated the effects of fluticasone cream 0.05% on the hypothalamopituitary-adrenal (HPA) axis in patients with extensive psoriasis or eczema., Patients: Six inpatients in a hospital setting, three with extensive eczema and three with extensive psoriasis of at least 30% body surface involvement, were enrolled in this study., Methods: In an open-label design, all patients received fluticasone cream 0.05%, 15g applied twice daily without occlusion for 7 consecutive days. The primary outcome measures were HPA-axis suppression (determined by morning plasma cortisol and 24-hour urinary free cortisol concentrations), selected blood chemistries, urinalysis and haematology profile., Results: During the treatment phase, four of the six patients studied experienced insignificant changes in morning plasma cortisol concentrations. In one patient, a decrease in plasma cortisol concentrations occurred following several days of treatment; these concentrations recovered after 6 to 7 days of treatment. In the remaining patient, a marked decrease in morning plasma cortisol concentrations occurred, which may have been attributed to consumption of alcohol by this patient., Conclusion: Fluticasone cream 0.05% was well tolerated in patients with extensive eczema or psoriasis and had a low potential for suppressing endogenous cortisol secretion, even when applied to extensive areas of diseased skin for 7 days.

Background: Topical therapy providing initial improvement and maintenance of effect after treatment of the large majority of patients with limited, mild to moderate psoriasis is not presently available. Previous topical retinoids have generally been either ineffective or too irritating for therapy of psoriasis., Objective: Our purpose was to evaluate a new topical retinoid, tazarotene, in the treatment of stable plaque psoriasis during treatment and posttreatment periods., Methods: In a double-blind manner, 324 patients were randomly selected to receive tazarotene 0.1% or 0.05% gel, or vehicle control, once daily for 12 weeks and were then followed up for 12 weeks after treatment., Results: Of the total, 318 patients could be evaluated. Tazarotene gels were superior (p < 0.05) to vehicle, often as early as treatment week 1, in all efficacy measures: plaque elevation, scaling, and erythema; treatment response; percentage treatment success (patients with > or = 50% improvement); and time to initial success. Efficacy was equivalent on target lesion sites (trunk or limbs and knees or elbows) and overall. A sustained therapeutic effect was observed for 12 weeks after treatment. Tazarotene gel was cosmetically acceptable. There was low systemic absorption, limiting toxicity to local irritation., Conclusion: Once-daily tazarotene was effective and safe as a topical monotherapy for plaque psoriasis, providing rapid reduction of signs and symptoms.

Adult Swiss webster mice were injected with 3 x 10(6) colony-forming units (cfu) of group G or 2.5 x 10(6) cfu of group A streptococci at intradermal injection sites on the right and left paralumbar areas of the back. The mice were sacrificed at intervals between 4 hours and 14 days post-injection (p.i.) and full thickness biopsies of skin 10 mm in diameter encompassing the sites of injection were taken. One tissue specimen was homogenized in PBS and plated to determine the number of cfu, while another was used for histopathological studies. The number of viable group A and group G streptococci in the tissue increased to 3 x 10(9) cfu by 96 hours p.i.: after 192 hours p.i. the group A cells had declined to 2.7 x 10(6) cfu compared to 1.1 x 10(8) cfu for group G cells. No streptococci of either group were detected at 336 hours (14 days p.i.). Gross edematous lesions induced by either streptococcus group were evident on all animals at 24 hours (p.i.). Group G streptococci lesions were larger and persisted longer than lesions induced by group A. Histological examination consistently revealed more inflammation and necrosis in tissue sections from mice injected with group G streptococci.

Cutaneous cysticercosis in humans is an uncommon parasitic infestation. When few nodules are present, surgical excision is effective therapy. For multiple nodules, diverse forms of treatment have been employed. We describe herein a patient with myriad nodules of cysticercosis who showed dramatic improvement after two six-day courses of metrifonate (an organophosphorous compound) administered one month apart. These encouraging results could be of help to other patients, especially those with CNS involvement, although the use of this compound is not without risk.

Contact urticaria developed in a patient after topical application of paraben-containing compounds. Positive open patch test results and a positive passive transfer (Prausnitz-Küstner reaction) test demonstrated an immunologic mechanism for the patient's skin reaction. The importance of parabens to contact urticaria is described.

A 32-week-old (gestational age) female infant with epidermolysis bullosa letalis (EBL) (confirmed by light and electron microscopy) had a gastric-outlet obstruction on routine roentgenographic examination. An autopsy showed a fibrous cord connecting the stomach and first part of the duodenum in the area of the pylorus. A review of the literature indicated 12 additional cases of epidermolysis bullosa (EBL where type was confirmed) associated with pyloric atresia. The possibility of coexistent pyloric atresia should be considered in a newborn who has suspected EBL.

The Klippel-Trénaunay-Weber syndrome is a congenital angiodysplasia most often characterized by a triad of symptoms: varicose veins, port-wine cutaneous hemangiomas, and symmetrical hypertrophy of the affected limb. We report a case in a 37-year-old man and present a review of the literature.

Erythema multiforme occurred in a 31-year-old woman as a complication of BCG immunotherapy administered by scarification for a Clark's level IV malignant melanoma. This is an unusual complication of the scarification technique.

To evaluate the relative effectiveness of the treatment of tinea pedis, we performed a double-blind study comparing undecylenic acid ointment, tolnaftate cream, and a placebo. Ninety patients with clinically and mycologically proven tinea pedis took part in this clinical trial. Our results showed both agents to be superior to the placebo, but there was no significant difference in effectiveness between the two active agents. We observed no side effects with the preparations used.

Toxic shock syndrome (TSS) is a recently recognized condition associated with toxin-producing strains of Staphylococcus aureus. Patients affected with this syndrome are frequently young and have multisystemic complaints such as fever, headache, edema, myalgia, scarlatiniform rash, conjunctival injection, confusion, diarrhea, oliguria, hypotension and shock, This is followed by desquamation of the skin, especially the palms and soles. The majority of cases reported have been in menstruating women who used vaginal tampons regularly. Because similarities exist between toxic shock syndrome and Kawasaki's disease (mucocutaneous lymph node syndrome), as well as other conditions, proper diagnosis and management are of the utmost importance.

Topical aluminum sulfate was not effective in relieving pain and stinging from the imported fire ant, contrary to a previous uncontrolled study.

The activity of interferons was tested in ultraviolet light-induced skin tumors in mice. After the tumors were well established, they were injected and measured daily for 19 days. Mouse virus type (IF-alpha + IF-beta) and immune (IF-gamma) interferons were injected intralesionally into three groups of test animals and compared with a fourth group which received mock interferon (control). When used separately, virus type and immune interferons did not affect tumor growth; however, we observed regression in tumor size when the two interferons were used in combination.

Before stains were available, pathologists had to rely on unstained sections viewed through crude microscopes, but they still were able to make diagnoses and discoveries. Unstained sections may still be used to advantage in making diagnoses of skin lesions quickly, accurately, and easily on the basis of negative image patterns. Low-power scanning by conventional microscopy of freshly cute and mounted, still wet, paraffin sections of skin specimens enables the histotechnologist and dermatopathologist to accomplish three things: 1) to check orientation of the sections at an early stage, 2) to cut complete sections, and 3) to find the area or areas of pathology to cut. Furthermore, because diagnoses can be made from unstained sections, extra cuts for special stains may be ordered in advance of routine staining. The dermato-pathology laboratory is able, therefore, to produce slides of better quality and diagnoses more accurately and quickly.

Two patients, a father and son, with pachyonychia congenita were treated with orally administered isotretinoin because the extreme deformity and discomfort associated with their massive keratoderma interfered with their work and school, respectively. While clinical benefits could not be sustained, electron microscopic findings compatible with suppression of abnormal keratinization were observed. In addition, skin biopsy samples were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the gels were then subjected to a lectin overlay technique with concanavalin A labeled with iodine 125. The distribution of specific glycoproteins was found to be different for lesional as against normal epidermis. The procedure was repeated after oral treatment with isotretinoin. The labeled glycoprotein pattern of the lesional epidermis was clearly distinguishable from both the pretreatment lesional and the normal epidermis; it was mostly intermediate between the two. The normal epidermis was virtually unaffected by the retinoid treatment.