[Antifungal agents].
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Biomedical subjects
Publications and source records attributed to L Ben Slama.
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Radiotherapy continues to cause skin disorders. In this article, with the aid of our human skin model maintained in ex vivo survival conditions for 15 days, we describe the modifications caused by irradiation and their modulation by a trolamine-containing emulsion (Biafine). Normal human skin fragments were maintained in organ culture. One ionizing radiation session with 5 Gy was applied. Skin parameters were evaluated 24 h after the radiation session and were compared with a nonirradiated skin fragment: vascular modifications (histology), edema, epithelial proliferation, interleukin (IL)-1alpha and IL-6. Another series of skin fragments was maintained in survival conditions for 15 days after the radiation session to evaluate collagen neosynthesis by fibroblasts and any vascular changes (CD34). After irradiation the basal cell proliferation was reduced by approximately 50%. Extensive vasodilation occurred with altered capillary permeability accompanied by decreased CD34 transmembrane protein expression. Collagen synthesis and IL-1 secretion were increased. Biafine significantly reduced capillary alterations, restored CD34 expression as well as epithelial cell proliferation and significantly decreased collagen synthesis and IL-1 expression. With this ex vivo human skin model we confirmed the main modifications induced by radiotherapy as previously described in animal models: decreased basal cell proliferation and endothelial cell alterations and increased collagen synthesis by fibroblasts, probably under the influence of IL-1. The effect of Biafine emulsion on these histological and biochemical parameters may support its clinical efficacy.
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The aim of this exploratory study was to assess the efficacy of a natural metabolite of vitamin A, retinaldehyde 0.1%, vehicled in a gel in 17 patients with oral lichen planus and in 13 patients with oral leukoplakia, twice daily for 2 months. Our investigation was clinical, histological, immunohistochemical through the expression of markers of cell terminal differentiation and biochemical by using two-dimensional gel electrophoresis of cytokeratins (CK). In addition, the activity of retinaldehyde was studied ex vivo on surviving buccal mucosa. Retinaldehyde gel 0.1% showed good clinical efficacy, resulting in 6% disappearance and 82% improvement of the lesions in lichen planus and 17% disappearance and 75% improvement in leukoplakia. This was confirmed with immunohistochemistry, which revealed down-regulation of filaggrin and CK-10 as markers of terminal differentiation in both diseases. The effects of retinaldehyde in these two diseases were further demonstrated in the ex vivo surviving mucosal model, resulting in histological disappearance of keratinization in 80% of the lichen planus fragments and 40% of the leukoplakia fragments, associated with down-regulation of filaggrin and CK-10.
OBJECTIVES: We analyzed data in the literature in comparison with experience at the Department of Cancer and Oral pathology of the Stomatology and Maxillo-Facial Surgery division of la Salpêtrière Hospital on precancerous lesions of the oral mucosa, in order to establish definitions and describe epidemiological, clinical, histological findings as well as natural history and treatment outcome. MATERIAL AND METHODS: Three literature sources were analyzed: Medline and Current Contents searches, books and references listed in articles. The following key words were used and classed into three groups; 1) oral mucosa, epidemiology, precancerous lesions, malignant transformation, dysplasia, leucoplakia, oral lichen planus, erythroplasia, verrucous, cheilitis, candidosis, immunodepression, 2) oral mucosa, tumor markers, carcinogens, keratin, keratinocytes, gene, nuclear proteins, p53 protein, Ki-67 antigen, 3) oral mucosa, therapy, prevention, nutrients. The period chosen ran from 1980 to 1998. This automatic literature search was completed by systematic manual search of summaries in specialized journals published in 1997-1998. The lists of references in the identified articles were consulted and furnished the principal publications concerning precancerous lesions of the buccal mucosa. In all 383 references were selected and analyzed by level of scientific proof. Among these 135 are cited in the text. If data in the literature were insufficient, the physicians at the Department of Cancer and Oral pathology of the Stomatology and Maxillo-Facial Surgery division of La Salpêtrière Hospital were consulted to provide their experience-based recommendations. RESULTS AND DISCUSSION: Clear and practical definitions drawn from current knowledge were adopted. Precancerous lesions were distinguished from precancerous states. Precancerous lesions included chronic lesions of the oral cavity on which cancer of the oral cavity is known to develop. These were: leucoplakia, oral lichen planus, erythroplasia, papillomatous lesions, actinic cheilitis, submucosal fibrosis, keratotic candidosis, and tertiary syphilis. The precancerous states included cancers occasionally observed in the oral cavity: immunodepression and Plummer Vinson syndrome were analyzed. Epidemiological, clinical, histological, and evolutive data as well as therapeutic strategies were described. A decisional algorithm was elaborated for leucoplakia. The text was enriched with images available in the Department. CONCLUSION: Precancerous lesions of the oral mucosa offer a particularly interesting area of research for understanding the process of cancer formation and its prevention. The level of scientific proof available in the large majority of the published reports is low. Few recent publications provide relevant data. In practice, the experience in the management of cancer and precancerous lesions of the oral mucosa accumulated over the last 40 years at the Department of Cancer and Oral pathology of the Stomatology and Maxillo-Facial Surgery division of la Salpêtrière Hospital provides an invaluable source of information.
In earlier work, we demonstrated that 0.1 p. 100 topical tretinoin is clinically effective and well tolerated compared with placebo for the treatment of oral leukoplakia and oral keratosic or erythematous lichen planus. Here we aimed to complete this clinical protocol with histological and biochemical analyses comparing the biopsy specimens collected at inclusion and those collected after 4 months of treatment. Histological results were based on changes in keratinization observed between onset of treatment and 4 months treatment. Biochemical studies included the use of antibodies (anti-cytokeratins 10-11, anti-filaggrine) for the immunohistochemical evaluation of keratinization and 2-dimensional gel electrophoresis for measuring cytokeratins. In patients with lichen planus, histological changes during treatment showed that, in the 10 patients in the tretinoin group, keratinization disappeared in 6 and decreased significantly in 3. Immunohistochemistry revealed that cytokeratins 10-11 and filaggrin disappeared in 57 p. 100 of the patients treated with tretinoin versus 25 p. 100 in the patients given placebo. Bidimensional gel electrophoresis showed that cytokeratins 1, 2, 10 and 11 disappeared only in the tretinoin group (60 p. 100 of the cases). In patients with leukoplakia, histological changes during treatment showed that, in the tretinoin group, keratinization disappeared in 5 cases and decreased in 5 others. Immunohistochemistry revealed that cytokeratins 10-11 disappeared in 30 p. 100 of the patients treated with tretinoin versus 25 p. 100 in the placebo group. Bidimensional electrophoresis demonstrated that cytokeratins 1, 2, 10 and 11 disappeared in 43 p. 100 of the patients treated with tretinoin.
A randomized study was conducted to evaluate the effect of tretinoin and patient tolerance to treatment with topical applications in series of 20 cases of smoking-related or traumatic oral keratoses leukoplakia and of 20 cases of lichen planus. In each group, patients applied the topical ointment containing tretinoin (10 patients) or placebo (10 patients) twice daily. Clinical outcome was evaluated on the basis of the surface area of the lesion, measured monthly during treatment, as compared with the area observed at treatment onset. After 4 months treatment, there was a significant decrease in the surface area of the lesion in the patients with lichen planus (p < 0.02): 94 p. 100 in the tretinoin group versus 21.4 p. 100 in the placebo group. In patients with leukoplakias, there was also a very significant reduction in the surface area of the lesion after 4 months of treatment (p < 0.001): 80 p. 100 in the tretinoin group and 16 p. 100 in the placebo group. Tolerance to treatment was generally good despite a few complaints of quite temporary burning sensation at application rapidly resolutive.
Malignant changes in oral lichen planus lesions are still the subject of controversy. Two new cases provide supportive data for this thesis. Case 1: A 64 year old non smoking diabetic woman presented with combined atrophic lichen planus and erythroplasia lesions of the right buccal mucosa and a unique reticular lichen planus lesion of the left buccal mucosa. Both lesions were histologically confirmed. Despite treatment, degeneration of the Bowen's type lesion into an epidermoid carcinoma was noted within 11 months. Case 2: A 47 year old non smoking woman consulted for combined cutaneous and oral lichen planus lesions. Clinical examination showed an "acute" oral lichen planus associated with extensive ulcerative, atrophic and reticular lesions involving almost the total oral mucosa. Histology of a left buccal biopsy confirmed the diagnosis. Systemic and local corticotherapy produced marked improvement in her condition and she was not seen for five years. Follow up examination then detected a proliferative ulcerative type of epidermoid carcinoma on the left buccal mucosa. These findings appear to fulfil the clinical and histologic criteria suggestive of development of epidermoid carcinoma on a lichen planus lesion.
In order to investigate whether or not a racial factor plays a role in modulating the pattern of autoimmune response associated with human malaria infection, we studied the frequencies of anti-nuclear (ANA) and anti-smooth muscle (SMA) antibodies in sera of 152 Caucasians, Africans and Asians with acute malaria. No significant differences were observed in the frequency of these autoantibodies (AAb) between malarial individuals of different racial groups even if we considered subjects of different races infected by the same plasmodial species (P. falciparum) and submitted to similar degrees of exposure to malaria infection, indicating that the pattern and frequency of the malaria induced AAb do not seem to be determined or modulated by racial factors.