In vitro activity of antifungal drugs against Cladophialophora species associated with human chromoblastomycosis.

The antifungal activity of six drugs was evaluated against 41 clinical and environmental isolates of Cladophialophora carrionii and its sister species C. yegresii. Drugs tested, including their ranges, were: 16-0.016 microg/ml for amphotericin B (AMB), itraconazole (ITZ) and voriconazole (VCZ), 8-0.008 microg/ml for terbinafine (TBF), and 64-0.063 microg/ml for flucytosin (5-FC) and fluconazole (FCZ). Strains were tested according to the CLSI guidelines (M38A). The MIC Gmeans for clinical strains in microg/ml were; 0.02 for TBF and ITZ, 0.07 microg/ml for VCZ, 0.49 for 5FC, 6.14 for FCZ and 9.42 for AMB. The MFC Gmeans in microg/ml were; 0.04 for TBF, 0.13 for ITZ, 0.72 for VCZ, 18.83 for 5FC, 36.16 for FCZ and 31.35 for AMB. The most active drugs against the fungi were TBF, ITZ, VCZ and 5FC. However, for all drugs more than two dilution steps were noted between the MIC and the MFC, indicating fungistatic activity. Despite in vitro susceptibility of C. carrionii to antifungal agents, the efficacy of therapy was shown to be not optimal.

Chromoblastomycosis in children and adolescents in the endemic area of the Falcón State, Venezuela.

The present paper describes 22 cases of chromoblastomycosis (CBM) caused by Cladophialophora carrionii in children and adolescents (2-19 years old). The patients were seen between 1992 and 2004 and all resided in a CBM endemic area in the semi-arid zone of the Falcón state, Venezuela. Twelve of the 22 patients (54.55%) had close relatives who also had CBM and 19 (86.36%) were male. Lesions consisted of erythematous papules with desquamation or squamous plaques (0.12-14.19 cm in diameter), located primarily on the upper limbs (77.27% of patients). Thirteen of the patients were treated with topical 5-fluorouracil (5-FU; 1% cream), seven with topical ajoene (0.5% gel) and two had electrodesiccation and/or fulguration. Two patients who did not respond to 5-FU were treated with oral itraconazole (100 mg/day for 1 month). Complete clinical and mycological remission was achieved in 17/20 (85%) of the patients treated with 5-FC, ajoene and electrodesiccation and/or fulguration. In addition, similar results were obtained with the two patients who received itraconazole therapy. These cases emphasize the importance of early diagnosis in difficult-to-treat mycotic diseases such as CBM. By early intervention we were able to employ topical treatment with a minimum of adverse effects to achieve a high percentage of favorable therapeutic responses. The patients were thus able to avoid the evolution of the chronic, deforming and incapacitation clinical manifestations associated with CBM.

Ajoene and 5-fluorouracil in the topical treatment of Cladophialophora carrionii chromoblastomycosis in humans: a comparative open study.

Ajoene and 5-fluorouracil (5-FU) are compounds that have shown in-vitro activity against Cladophialophora carrionii, an important etiologic agent of chromoblastomycosis. An open comparative trial was conducted to assess safety and effectiveness of topical ajoene and 5-FU in the treatment of localized chromoblastomycosis. Thirty-seven patients with a clinically and mycologically confirmed diagnosis were randomly distributed into two groups allocated to ajoene (0.5% gel; n = 19) or 5-FU (1% cream; n = 18). Topical treatment was applied to localized lesions (< or = 2.5-cm diameter) once a day, with occlusion, for 12-16 weeks. Complete clinical and mycological remission was achieved in 14/19 patients (74%) treated with ajoene and 14/18 patients (78%) treated with 5-FU. All 5-FU-treated patients developed a post-treatment scar at the site of the lesion, while ajoene-treated patients showed only a slight depigmentation of the skin. The differences observed in cure rate between ajoene and 5-FU are not statistically significant. Follow-up of all patients for 4 years revealed no relapses in the ajoene-treated group, while one patient in the 5-FU-treated group had a relapse 6 months after the end of therapy. This trial represents the first clinical use of ajoene in the control of a deep mycosis.

[Chromomycosis by Rhinocladiella aquaspera: The first case in Venezuela.]. / Cromomicosis por Rhinocladiella aquaspersa: descripción del primer caso en Venezuela.

A case of chromomycosis induced by Rhinocladiella aquaspersa is decribed in Falcon State, which is considered as the first case in Venezuela, and the fifth one in the whole world of this species of Rhinocladiella. The case was observed in a five year-old child from the south part of Falcon State. The child presented wounds of two years of duration, in his upper left limb. These wounds were characterized by queloide cicatrices, and contiguous nodules, with a scalyo-scab surface. The disease was diagnosed through direct observation of cells extracted from the wounds and cleared with potassium hydroxide at 10%. The identification of R. aquaspersa was made by 1) The isolation in culture, using Lactritmel, Sabouraud-agar and Sablac as culture media; and 2) By observation, in slide culture, of dissemination structures characterized by erect conidiophores which were either simple or branched. The thermo-tolerance test applied indicate an optimum development temperature of 28 degrees C. It was not possible to reproduce the illness in Balb/c mice. The patient showed an unsatisfactory response to Itraconazol medication and improvement to an external local application therapy. Up to the present time, 370 cases of chromomycosis have been studied in Falcon State, with 21 cases in children. The suggests the existence of a susceptibility to this kind of mycosis from childhood.

[Mycetoma: report of 3 cases in Falcón State, Venezuela]. / Micetoma: reporte de tres casos en el Estado Falcón, Venezuela.

This is a report of three cases of mycetome studied in our laboratory during the last four years. We also informed about the evolution of the first case produced by Pyrenochaeta romeroi nova species reported by Borelli in 1959. All the patients were farmer men, 18, 42 and 54 years old, from the semiarid and subhumid zones of Falcon State, located on the northwest region of Venezuela. Clinically, all patients presented the mycetome syndrome (subcutaneous edema, sinus tract and "granules"), with a evolution of six months to three years. The lesions were localized in the inferior limbs in two of the patients and in the thorax in one of them. The clinical diagnose was confirmed by microbiological and mycological studies, isolating Nocardia brasiliensis in two cases and Madurella grisea in one. Two patients treated with Sulfas showed remission of the disease in a two years follow up. Including this report, 15 cases of mycetome have been reported in the Falcon State (Venezuela) in a period of thirty five years, representing only 9, 14% of the national casuistic. Actinomadura madurae and N. brasiliensis have been the most frequently isolated agents in this region. In order to determine the real endemicity of the mycetome in Venezuela, multidisciplinary clinical, inmunological, microbiological and epidemiological studies are recommended. According to the reported casuistic (15 cases), the mycetome should be a low frequency disease in Falcon State, Venezuela. We confirm that early diagnosis favors an efficient therapy.

[Histopathology and ultrastructure of chromomycosis caused by Cladosporium carrionii]. / Histopatología y ultraestructura de la cromomicosis causada por Cladosporium carrionii.

Light and electron microscopic study of chromomycosis caused by C. carrionii was undertaken. Biopsies from 10 patients were taken and processed by means of conventional histopathologic techniques of hematoxylin and eosine and by transmission electron microscopy. Granulomatous and suppurative components of the infection process were observed by the histological procedure, other cellular elements such as lymphocytes, plasma cells, eosinophils and Langerhans cells were present. The fungus was observed free or within phagocyticcells. Ultrastructural evidence revealed that it was surrounded by a wide multilayered and electron dense cell wall. Its cytoplasmic membrane presented invaginations and vacuoles containing the electron-dense material. We suggest the existence of a secretion-excretion process of a melanin-like dark pigment, which is accumulated on the cell wall of fungus, increasing the resistance of fungal cell to its destruction by phagocytic cell. It is necessary to determine the exact role of Langerhans cells in chromomycosis caused by C. carrionii.

[Effect of temperature and humidity on the frequency of pityriasis versicolor. Epidemiological study in the state of Falcón, Venezuela]. / Influencia de la temperatura y la humedad en la frecuencia de pitiriasis versicolor. Estudio epidemiológico en el Estado Falcón, Venezuela.

The survey covers 1546 people from three towns of Falcón, which present different climatological characteristics. The diagnostic of P.V. was confirmed through microscopic observation. It is demonstrated a notable increase of the frequency of P.V. during and after the puberty. Significative differences were found between the frequencies of P.V. in the semiarid zone (9%) and the sub-humid zone (12%). The lowest frequency (4%) corresponds to the temperate climate of La Sierra de Falcón. The study shows, for the first time, that a hot and humid climate favors the parasitism by Malassezia sp.

Cytological diagnosis of breast cancer.

One hundred thirty-one fine-needle aspirations and 85 nipple discharge smears were evaluated cytologically and correlated with histological diagnoses and with clinical impressions. This study demonstrates that cytological diagnosis of breast lesions is a useful and clinically accurate procedure.