Treatment of recalcitrant psoriasis with daclizumab.
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Biomedical subjects
Publications and source records attributed to K M Taube.
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Vulvodynia is a complex syndrome of chronic vulvar pain. It is divided into several subtypes: 1. cyclic vulvovaginitis (pain occurs after coitus), 2. vulvar vestibulitis syndrome (pain mainly with intercourse), 3. dysaesthetic vulvodynia (psychosomatic; diagnosis of exclusion), 4. vulvar dermatoses (e.g. pemphigus vulgaris, contact dermatitis). Additional causes have been described in single cases. Though vulvodynia is often accompanied by psychological distress, somatic causes have to be considered in each case.
OBJECTIVE: To assess the safety, tolerability and efficacy of a new cyclosporin A (CyA) microemulsion formulation, Sandimmun Neoral (Neoral), in patients with severe psoriasis that was stable on CyA administered as Sandimmun (SIM). METHODS: In this 24-week, open, randomized, prospective, multicentre trial, 28 patients continued on the same dosage of SIM, while 30 converted to Neoral at 2.5 mg/kg/day or a dosage equivalent to their pre-conversion SIM dosage. During the study, dosages could be adjusted to maintain efficacy, because of adverse events or after disease stabilization. The maximum permitted dosage for either formulation was 5.0 mg/kg/day. Primary efficacy criteria were change in Psoriasis Area and Severity Index (PASI) from baseline and time to relapse. RESULTS: The dosage was increased to maintain efficacy in 22 patients (Neoral 13; SIM 9) and 20 dose reductions for safety were required (Neoral 14, SIM 6). In both groups, PASI scores remained stable throughout and relapses were primarily a result of dosage reduction after disease stabilization. No significant difference was found between groups in the proportion of patients remaining relapse-free. Adverse events were recorded in 20 patients receiving Neoral and 14 receiving SIM. Most drug-related events were of mild or moderate severity and reflected the known CyA side-effect profile. Dose titration guidelines ensured that mean blood pressure and serum creatinine concentrations remained stable in both groups. CONCLUSIONS: If the guidelines for CyA use are followed and the Neoral dosage does not exceed 5 mg/kg/day, conversion of stable patients with severe psoriasis from SIM to Neoral should present no clinically relevant safety or tolerability problems and efficacy of treatment is maintained.
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Urea ointments and emulsions are excellently suited for the care and supportive therapy of neurodermatitis patients. In treating children and in the case of acutely irritated skin conditions, we have arrived at a concentration of 5% urea. All other dermatological conditions can be easily and effectively treated with a 10% urea preparation. It goes without saying that galenics also play an important role. An unbalanced composition can lead to poor results. In a short-term test (180 minutes) and in a long-term test (7 days), we tested the moisture level of the corneal layer with the corneometer in a climate-controlled room. We were able to show that urea in hydrous topical agents ensures acceleration of corneal hydration and helps retain water in the corneal layer. Thus, urea preparations can also be especially recommended for use in patients with neurodermatitis.
A polychemotherapy (DTIC, vincristine, ftorafur, hydroxycarbamide) devised with reference to the results of short-term sensitivity tests in cell culture is compared with single-agent chemotherapy with DTIC in malignant melanoma. Effectiveness was investigated in a randomized prospective study in cases of high-risk melanoma in clinical stage I, in clinical stage II after lymphadenectomy and in clinical stage III after tumour debulking. The results recorded allow no positive effects of either form of chemotherapy in stage I disease compared with surgical treatment only in a control group. In contrast, a statistically significant advantage of the polychemotherapy was noted in stage II compared with a control group. There was no significant difference in the results of treatment between the two forms of chemotherapy in stage III. No complete remissions of long duration have been achieved.
Using a multilayer membrane system and human horny layer the difference in the penetration of salicylic acid (SA) and its sodium (Na-S) and choline (Ch-S) salts from topical formulations was studied. It was found Na-S and Ch-S were markedly accumulated in the first membrane of the three layer membrane system used. In contrast, a rapid penetration into all three membranes was observed when SA was used. Similar penetration profiles were obtained in human horny layer. Hence, the use of the salts of SA appears to be more suitable for the application as keratolytic.
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Several attempts have been made to optimize the efficiency of topical glucocorticoids (GC) and, at the same time, to minimize their side effects. In this respect, we should first consider attenuated GC. Dependent on the urea concentration, hydrocortisone (HC) in combination with urea results in both a considerable increase of the HC liberation from the ointment base, as well as an increased penetration rate of HC into the individual skin layers. If we apply these mechanisms to a preparation containing low HC concentrations, a given therapeutic effect can be obtained with definitely reduced HC concentrations. On the other hand, the therapeutic efficiency or the penetration rate of GC can not be deduced from the galenic formulation, the drug concentration, or the amount of urea.
Malignant atrophic papulosis (Degos'disease) is very rare and shows characteristic clinical symptoms. We report on a patient with Degos'disease who died as a result of intestinal involvement. The clinical and histological changes are indicative of a systemic disease.
73 patients with fungal infections due to dermatophytes (49), yeasts (16) and Malassezia furfur (8) could be cured clinically in 71% and mycologically in 88% of cases by the application of Mycontral-Lotion or -cream twice daily for 33 days on average. In 28% improvement could be reached, in one patient the therapy failed. Treatment is simple, clean and well acceptable. Side-effects occurred as slight redness, transient burning and pruritus on the eroded skin in the initial phase in 8 patients (11%). Mykontral contains 1% tioconazole as a modern imidazol compound. It has been characterized as an effective topical broad spectrum antimycotic agent. Its introduction and application in the GDR is to be recommended.
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With the liposomal incorporated hydrocortisone a very much improved concentration-time profile was obtained in the different layers of human skin after topical application when compared with conventional hydrocortisone in the ointment. The increased hydrocortisone penetration into human skin correspond with the degree of blanching results by vasoconstriction test. Under in vivo conditions the influence of liposomal hydrocortisone on percutaneous resorption was investigated. In guinea pigs a decreased serum concentration and urinary excretion of hydrocortisone could be demonstrated. Thus, hydrocortisone-loaded liposomes, when applied topically, act as a selective drug delivery system, it can be provide increased therapeutic efficacy and, simultaneously, decreased unwanted systemic effects. The significance of liposomal incorporated attenuative and higher potent glucocorticoids in external therapy is discussed.
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The initial steps of any topical therapy are characterized by the degree of liberation of the agent from the ointment base and their penetration into different skin layers. A high percentage of the topically applied prednisolone does not penetrate into the skin and may be removed from the skin surface even after some time. By altering the functional structure of the horny layer and considerably increase of prednisolone liberation from ointment bases urea is a effective penetration promotor also for prednisolone. The increased prednisolone penetration into human skin from urea containing ointment correspond with the degree of blanching results by vasoconstriction test under in vivo conditions. The resulting penetration optimation of prednisolone has two possible applications in topical therapy: an increased therapeutic effect for a given prednisolone concentration and a given therapeutic effect could be obtained with a reduced prednisolone concentration.