Single dose treatment of fungal nail disease.
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Biomedical subjects
Publications and source records attributed to S Shuster.
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It has recently been shown that antimycotic drugs have unexpectedly rapid access to distal nail, which we have suggested occurs through the site of continuous ventral nail formation along the nail bed. To exclude the alternative possibility of diffusion through the nail plate, we have measured the effect of topical terbinafine cream in onychomycosis. Sustained outward movement of the fungally affected distal segment was seen in only 2 of 10 measured nails, and there was no change in the mean severity of clinical involvement in 53 nails under study. This excludes significant diffusion of drugs through the nail plate, and we conclude that the route of rapid access is indeed through the nail bed.
In 167 unselected patients with renal allografts, after a lag of 3.5 years the prevalence of dysplastic keratotic lesions increased linearly by 6.8%/yr and number of lesions also increased. There was no relationship to sun exposure or skin type. Malignancies occurred in 5 patients after 9 years. Viral warts occurred in 42% but prevalence and extent were not related to time after transplantation or keratoses. Comparison with other drugs and diseases suggests malignant keratoses are initiated in two stages by the cytotoxic effect of azathioprine, the role of immunosuppression remaining unproved. Psoriasis and eczema remitted and the prevalence of zoster and fungal disease increased. P. orbiculare (but not P. ovale) infection increased, unlike in other states of immunosuppression, suggesting the organisms are distinct, not transitional, and differently influenced by the different immunodeficient states induced by drugs and disease.
To test our hypothesis that, by laying down a fungicidal barrier in the growing nail, a short course of antifungal therapy should be effective against onychomycosis, we treated 8 subjects with Trichophyton rubrum nail infection with terbinafine 125 mg b.d. for 14 days. All but one patient showed marked improvement, and 80% of fingernails and 37% of toenails were clinically cured after 6 months. Although this confirmed our prediction, the onset of response measured by outward movement of affected nail and negative cultures from distal nail clippings occurred after as little as 4 weeks. This was too soon for a fungicidal barrier to have grown out and indicates that the drug must have been carried directly into the diseased distal nail, presumably from newly formed ventral nail beneath it. The findings show that 1) short duration therapy, perhaps even a single dose, is possible in fungal nail infections; 2) the ventral nail provides unexpectedly rapid access of drugs to the site of distal disease.
Cyclosporin A is an effective drug but its use is limited by its side effects. Since oral ketoconazole inhibits the metabolism of oral cyclosporin, we set out to find out whether topical ketoconazole would enhance the effect in the skin of oral cyclosporin. Five patients with contact allergic dermatitis (CAD) were given a 6-day course of cyclosporin (1 mg/kg/day) and applied 2% ketoconazole cream to an area on one arm and the inert base to the other. Serial dilutions of the relevant allergen were applied to the arms at 3 days for 48 hours, and the responses were measured objectively a day later. There was no significant difference between responses at the two sites, indicating that topical ketoconazole does not enable the dose of oral cyclosporin to be reduced in CAD.
Nail thickness and mass (dry weight/unit surface area) of 21 toenails, removed from 19 patients after accidental injury, were measured over the mid point of the lunula, at the nail plate immediately distal to the lunula and at the distal end of the nail bed. Nail thickness increased from 43% of the final thickness over the mid-point of the lunula to 81% at its distal margin, the remaining increase in thickness being formed by the nail bed. The changes in nail mass were comparable. We conclude that ventral nail produced by the nail bed comprises about one-fifth of the terminal nail thickness and mass.
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Fourteen patients with severe chronic atopic dermatitis were treated with cyclosporin A (CyA, Sandimmun; 5 mg/kg/day) for 7-16 weeks. All showed a marked clinical improvement and half could omit topical corticosteroid treatment during therapy. Adverse effects were minor, but two patients relapsed despite continued treatment. In the others, the disease recurred soon after stopping CyA. Serum IgE levels and prick-test responses were unchanged by CyA. Immediate and late-phase cutaneous responses to intradermal house dust mite antigen (HDM) were significantly increased during treatment; but a delayed response, present at 24 and 48 h, was unaffected. Four of six patients challenged with HDM patch tests to tape-stripped skin during treatment showed eczematous reactions at 48 h. Thus, cyclosporin A has a powerful therapeutic effect in atopic dermatitis but does not reduce allergic responses to inhalant antigens.
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Cimetidine, 1g orally per day, partially inhibited sebum excretion in patients with acne. Whether this was the result of H2-receptor blockade or an antiandrogen action is unknown.
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The incidence of skin cancer in patients with psoriasis seems to be low, despite repeated use of known carcinogens in treating the disorder. This may be due to a reduced capacity of psoriatic skin to metabolise precarcinogens because of impaired arylhydrocarbon hydroxylase (AHH) activity. If this hypothesis is correct, and impaired AHH activity in psoriatic skin is shared by other tissues, the incidence of cancers associated with environmental carcinogens may also be reduced in patients with psoriasis. Since the disease is probably genetically transmitted as a dominant trait, it may have persisted because it confers genetic advantage. This hypothesis, though speculative, provides a basis for further study.
A two-centre trial has been carried out on 224 patients with chronic plaque psoriasis randomly allocated to treatment with a standard dithranol regimen of 8-methoxypsoralen and long-wave ultraviolet light (P.U.V.A.). Lesions in 91% of the 113 in the P.U.V.A. group cleared satisfactorily compared with 82% of 111 in the dithranol group, but clearing took longer (34.4 +/- 1.8 S.E. days) with P.U.V.A. than with dithranol (20.4 +/- 0.9 S.E. days). P.U.V.A. treatment took less patient-time and nurse-time and was more convenient and acceptable to the patients. Patients in whom lesions had failed to clear with dithranol, and some who had needed methotrexate for control, responded satisfactorily to P.U.V.A. A few patients who had failed on P.U.V.A. were treated with dithranol and responded to it. There is a case for the use of P.U.V.A. for patients who would otherwise require methotrexate and those who cannot be managed successfully with dithranol. There is also no reason to withhold P.U.V.A. in patients of 60 years or above with chronic plaque psoriasis. However, despite its superiority in terms of cost and patient acceptability, P.U.V.A. cannot be recommended as the first line of treatment for patients with uncomplicated, dithranol-responsive plaque psoriasis until there is more information on relapse-rate and toxicity.