Itraconazole therapy is effective for pedal onychomycosis caused by some nondermatophyte molds and in mixed infection with dermatophytes and molds: a multicenter study with 36 patients.

BACKGROUND: Onychomycosis of the toenail caused by nondermatophyte molds alone or in combination with dermatophytes is difficult to eradicate with standard antifungal therapy. OBJECTIVE: Our purpose was to determine the effectiveness of itraconazole in the treatment of toenail onychomycosis caused by molds alone or in combination with dermatophytes. METHODS: We treated 36 patients with this drug given as continuous dosing (100 or 200 mg/ day) for 6 to 20 weeks or as a 1-week pulse dosing (200 mg twice daily for 1 week per month) for two to four pulses. RESULTS: Patients with toenail onychomycosis with the following organisms were treated: Aspergillus spp. (eight patients), Fusarium spp. (four patients), Scopulariopsis brevicaulis (23 patients), and Alternaria spp. (one patient). Nineteen patients had onychomycosis with a mixed origin. At follow-up, 12 months after therapy was initiated, clinical and mycologic cure was achieved in 15 of 17 patients (88%) with onychomycosis caused by a single mold. In patients with mixed infection, a clinical cure was obtained in 16 of 19 patients (84%) and a mycologic cure in 13 of 19 patients (68%). CONCLUSION: Itraconazole appears to be effective and safe for the treatment of toenail onychomycosis caused by some nondermatophyte molds alone or in combination with dermatophytes.

Acute generalized exanthematous pustulosis induced by paracetamol. A case with severe hemodynamic disturbances.

We report on a 28-year-old Bangladesh man with acute generalized exanthematous pustulosis, induced by paracetamol. The patient presented with an erythematous and pustular eruption after taking 1 tablet of paracetamol for a sore throat. After intravenous administration of propacetamol hydrochloride (which is a prodrug of paracetamol), the rash became worse, showing a toxic epidermal necrolysis-like appearance and the patient suffered from severe hemodynamic disturbances. After discontinuation of propacetamol hydrochloride, the eruption cleared within 2 days. Prick testing performed in the patient revealed a positive reaction for propacetamol hydrochloride.

Healing of full-thickness wounds treated with lyophilized cultured keratinocyte cell lysate in genetically diabetic mice.

The effect of a lyophilized cell lysate prepared from cultured human keratinocytes on the healing of full-thickness wounds was evaluated in an impaired healing model. Full-thickness wounds (8 mm in diameter) were made on the dorsal areas of female genetically diabetic mice C57 BL/KsJ (db/db) and their normal (db/+) littermates. Wounds were covered with an occlusive polyurethane film dressing and were treated for 5 days either with the lyophilized cell lysate from cultured human keratinocytes prepared in phosphate-buffered saline solution or with phosphate-buffered saline solution. In normal (db/+) mice, all wounds were closed 16 days after wounding, and more than 90% of the wound closure was due to wound contraction. Wound contraction accounted for a similar extent of wound closure in both lyophilized cell lysate-treated and phosphate-buffered saline solution-treated wounds. In contrast, in the diabetic (db/db) mice, after histologic examination of the wounds 32 days after wounding, four of ten lyophilized cell lysate-treated wounds and four of seven phosphate-buffered saline-treated wounds were found to be closed. Moreover, applications of lyophilized cell lysate from cultured human keratinocytes to full-thickness wounds in diabetic db/db mice significantly decreased the contribution of contraction to wound closure. Day 32 after wounding, contraction contribution to wound closure amounted to 57.7%+/- 4.7% and 80.4%+/- 3.2% (mean +/- standard error of the mean, p < 0.005) of the initial wound areas, respectively, for lyophilized cell lysate-treated and phosphate-buffered saline solution-treated wounds. At this time of wound healing, the thickness of the dermis was increased 1.7-fold by the keratinocyte cell lysate treatment, but neither epithelial migration from the wound edges nor the thickness of the regenerated epithelium were significantly affected. In conclusion, in diabetic (db/db) mice the application of lyophilized cell lysate from cultured human keratinocytes influenced the healing of the dermis and wound contraction, but had no effect on reepithelialization.

Randomized trial comparing cryopreserved cultured epidermal allografts with hydrocolloid dressings in healing chronic venous ulcers.

BACKGROUND: Cultured epidermal allografts have been successfully used to treat a variety of wounds. Their postulated mechanism of action is through release of cytokines that stimulate epithelialization. On the basis of previous experience we expected ulcers treated with cryopreserved cultured allografts (CCAs) to be healed by 6 weeks. Hydrocolloid dressings (HCDs) have also been reported to be effective in the treatment of venous ulcers. OBJECTIVE: Our purpose was to compare the effectiveness of CCAs with HCDs in healing chronic venous ulcers. METHODS: Forty-three patients with 47 ulcers were enrolled in a randomized controlled trial. Ulcers not healed by 6 weeks were changed to the other treatment. RESULTS: No difference in the number of healed ulcers between the two groups was observed at 6 weeks. Healing rate, percent reduction of initial ulcer size, and radial progression toward wound closure were significantly greater for CCAs than for HCDs. Pain relief was not significantly different. CONCLUSION: CCAs achieve more rapid healing and greater reduction in ulcer size than HCDs.

Allogeneic cultured epidermal grafts heal chronic ulcers although they do not remain as proved by DNA analysis.

To investigate whether allogeneic cultured keratinocytes are rejected or not, and to find out how beneficial their effect on wound healing could be, patients with chronic ulcers were grafted with allogeneic cultured human keratinocytes. In order to examine the epidermal origin of the healed wound, DNA analysis was performed and compared to donor and recipient blood-cell DNA. Healing was observed in 84% of the grafted ulcers by granulation tissue stimulation and would edge effect. In little time 60% of the grafted chronic ulcers healed completely. Although no rejection was observed, DNA analysis revealed that the grafted allogeneic keratinocytes were finally replaced by the patient's own epidermis. This study confirmed that cultured allogeneic keratinocytes that have been grafted on ulcers, play an important role in the wound healing process.

Penicillamine-induced pemphigus erythematosus.

Pemphigus erythematosus occurred in a patient with rheumatoid arthritis who was treated with D-penicillamine. The skin lesions appeared 4 months after the onset of D-penicillamine treatment and persisted 14 years after cessation of this drug. Topical betamethasone dipropionate applications resulted in complete regression of the cutaneous lesions.

Autoimmune thyroiditis and generalized granuloma annulare: remission of the skin lesions after thyroxine therapy.

A patient suffering from generalized granuloma annulare associated with mild hypothyroidism due to an atrophic autoimmune thyroiditis is presented. Treatment with thyroxine resulted in the restauration of a euthyroid state. Subsequently disappearance of the antithyroid antibodies along with a progressive decrease in the number of the skin lesions was noticed. The association between generalized granuloma annulare and autoimmune thyroiditis has been reported once previously in the literature, but it might be of more frequent occurrence.

Aleukemic leukemia cutis. An unusual presentation of acute myelomonocytic leukemia.

A patient with acute myelomonocytic leukemia is reported. He had presented erythroderma and atypical cellular infiltration of the skin 4 months prior to the detection of leukemia in the peripheral blood and bone marrow. Aleukemic leukemia cutis is a rare condition which is characterized by leukemic cells invading the skin prior to the observation of leukemic cells in the peripheral blood. The cases of aleukemic leukemia cutis reported in the literature show little or no conformity in their clinical appearance. Enzyme cytochemistry, immunocytological and electron-microscopic studies are of considerable help in differentiating the cutaneous infiltrates and in establishing early diagnosis. We report herein a patient with erythroderma which regressed spontaneously, whereas microscopic examination of a cutaneous biopsy showed atypical cells infiltrating the dermis. After a period of 3 months, during which the patient remained free of lesions, he showed recurrence of the erythroderma while developing acute myelomonocytic leukemia. We feel this unusual presentation of aleukemic leukemia cutis should be added to the evergrowing list of cutaneous manifestations of leukemia.

Magnitude of ornithine decarboxylase induction by epidermal mitogens: effect of the assay technique.

The polyamines, putrescine, spermidine and spermine, as well as ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis, are increased in the blood, urine and skin of psoriasis patients. A study of the association between stimulated epidermal cell proliferation and induction of ODC activity was done using both an intact, living cell ODC assay and the routinely used homogenized cell supernate assay. 10(-6) to 10(-8) mol/l of the tumor promoter, tetradecanoyl phorbol acetate (TPA), 10(-3) mol/l 8-BrcAMP, 10(-6) mol/l cholera toxin and 10(-3) mol/l MIX, which are epidermal cell mitogens, were used to stimulate basal cells in short-term suspension cultures, freshly plated monolayers, or up to 8-day-old cultures. The results showed that the ODC enzyme must be assayed in supernates from disrupted epidermal cells in order for significant ODC induction by hyperplastic agents to be observed.

Epidermal keratinocytes actively maintain their intracellular polyamine levels.

Increased cellular polyamine levels are thought to be essential for epidermal keratinocyte proliferation. However, a number of studies report that the induction of keratinocyte proliferation and of ornithine decarboxylase, the rate-limiting enzyme of putrescine, spermidine and spermine biosynthesis, is not concordantly expressed. The relationship between epidermal keratinocyte polyamine synthesis and proliferation was studied in neonatal mouse keratinocyte cultures using specific inhibitors of ODC activity to decrease the intracellular polyamine levels. The ODC inhibitors alpha-methyl ornithine (alpha-Me-Orn), alpha-hydrazino ornithine (alpha-HO) and difluoro-alpha-methylornithine (alpha-DFMO) did not significantly inhibit epidermal keratinocyte proliferation at 5 X 10(-3) to 10(-4) M concentrations. At these doses, only alpha-DFMO was seen to decrease (by 70%) the cellular levels of putrescine, but not of spermidine or spermine. Epidermal keratinocyte growth in the higher dose of 20 mM alpha-DFMO, however, did not decrease the cellular levels of putrescine. Polyamine analyses of the spent medium showed that growth in 10 mM alpha-DFMO decreased the normal epidermal cell transport of putrescine and spermidine into the medium. At 20 mM alpha-DFMO concentration, the keratinocytes actually transported, intracellularly, the putrescine and spermidine that are naturally found in the foetal bovine component of the growth medium. We conclude from these studies that epidermal keratinocyte polyamine levels are determined by both the rate of synthesis, and of the transport of these amines into the extracellular medium. Since epidermal keratinocytes actively maintain specific polyamine levels, it appears that these molecules are essential for epidermal keratinocyte function.

Intact epidermal cell assay for ornithine decarboxylase activity.

A procedure measuring the ornithine decarboxylase (ODC) activity and polyamine formation of intact neonatal mouse epidermal cells in culture has been developed and tested. Basal cells prepared from neonatal mouse epidermis were plated on round 15-mm Lux coverslips, placed in Costar 24 well culture clusters and grown at 32 degrees C in M-199 + 13% fetal bovine serum. Before assay the cells were rendered permeable to ornithine 14C and ODC inhibitors using the buffer described by Berger et al. [3]. The slides, covered with adhering cell layers, were then placed in vials, covered with assay buffer and assayed intact for ODC activity. The ODC reaction was terminated by addition of citric acid to the buffer and the amount of 14CO2 released was determined by scintillation counting of a center well filled with trapping agent. The baseline ODC activity of the intact cells was 500-1,000 pmol 14CO2/mg protein/45 min. The validity of this ODC assay procedure using intact neonatal mouse keratinocytes was tested by use of three specific ODC inhibitors and by measuring the formation of polyamines from uniform labeled ornithine. The results indicated that authentic ODC activity was measured and preserved in this intact neonatal mouse epidermal cell assay. This technique holds promise for future studies of epidermal cell regulation of ODC and polyamine synthesis and studies of the multiple ornithine metabolites and conjugates formed, using a highly manipulable in vitro system.