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Biomedical subjects

L Dubertret

Publications and source records attributed to L Dubertret.

At least 73 records · Page 4Linked to original sources
PubMed1999

Immune-mediated destruction of melanocytes in halo nevi is associated with the local expansion of a limited number of T cell clones.

The beta-chain repertoire of the T cells that infiltrate spontaneously regressing nevi (the halo nevus phenomenon) was studied. In addition to the infiltration of the halo nevi by cutaneous lymphocyte-associated Ag-positive lymphocytes, oligoclonal expansion of T cells was observed in all halo nevi of all patients. T cells using the same TCR beta-chain were observed in distinct halo nevi of the same patient but not in his peripheral blood, demonstrating a local expansion of common clones that are most likely activated by the Ag(s) shared by independent halo nevi of the same patient.

Amino Acid Sequence↗
PubMed1999

Leg ulcers and hydroxyurea: forty-one cases.

BACKGROUND: Hydroxyurea is an antitumor agent used to treat chronic myeloproliferative disorders. Leg ulcerations have been reported in patients undergoing long-term hydroxyurea therapy for myeloproliferative diseases. To better define this dermatological adverse effect of hydroxyurea therapy and to try to understand the pathophysiological process of this disease, we collected medical information for such patients in a multicenter retrospective study. OBSERVATIONS: Forty-one patients (mean age, 67 years) developed leg ulcerations while undergoing hydroxyurea therapy (mean therapy duration, 5 years). The sex ratio was 1, and there was no underlying vascular disease. Hematologic abnormalities were identified. Complete recovery from the ulcerations occurred quickly after withdrawal of treatment in 33 (80%) of the cases. CONCLUSIONS: This longest-reported series of patients confirms the role of hydroxyurea therapy in the onset of leg ulcerations. Healing or improvement requires cessation of treatment. Cutaneous atrophy and impaired wound healing may explain the relationship between hydroxyurea and leg ulcers. In addition, the megaloblastic erythrocytes resulting from the presence of hydroxyurea may circulate poorly through the capillary network. A prospective study in hematologic centers would be valuable.

Adult↗
PubMed1999

Pure ocular cicatricial pemphigoid. A distinct immunopathologic subset of cicatricial pemphigoid.

OBJECTIVE: To determine whether ocular cicatricial pemphigoid (OCP) may represent a distinct immunopathologic disease when it is pure ocular cicatricial pemphigoid (POCP) (e.g., only confined to the conjunctiva) or when it is associated with skin or extraocular mucous membrane lesions or both (OCP+). DESIGN: Prospective, immunologic, and immunopathologic study with special emphasis on direct immunoelectron microscopy. PARTICIPANTS: Six patients with POCP and seven patients with OCP+. INTERVENTION: After informed consent was obtained, a conjunctival biopsy was performed in all patients. Skin and extraocular mucosa biopsy specimens were harvested in selected cases only. MAIN OUTCOME MEASURES: Results of direct immunofluorescence and direct immunoelectron microscopy without freezing on conjunctival and skin biopsy specimens, indirect immunofluorescence, and Western immunoblotting analysis were analyzed. RESULTS: Results of direct immunoelectron microscopic examination of the conjunctiva showed the presence of immune deposits in the upper lamina lucida of the basement membrane zone in the six patients with POCP, whereas the immune reactants were located in the lower part of the lamina lucida and in the lamina densa of the basement membrane zone (conjunctiva, buccal mucosa, and skin) in the seven patients with OCP+. Direct immunofluorescence was positive in the biopsy specimens of three patients with POCP (50%) and the seven patients with OCP+ (100%). Results of indirect immunofluorescence study showed circulating autoantibody levels only in two patients with OCP+, and results of Western immunoblot analysis were negative. CONCLUSIONS: Results of direct immunoelectron microscopic examination of the conjunctiva support the hypothesis that POCP may be a disease entity distinct from mucocutaneous cicatricial pemphigoid.

Aged↗
PubMed1999

Low doses of ultraviolet A radiation stimulate adhesion of human dermal fibroblasts by integrins in a protein kinase C-dependent pathway.

In this work, we have studied the modulation of fibroblast-extracellular matrix interactions by physiological doses of ultraviolet A (UV-A) radiation using an adhesion assay on collagen. We have shown that low doses of UV-A (20 kJ/m2) stimulate fibroblast adhesion while higher doses (100 and 200 kJ/m2) inhibit it. By measurement of the thiobarbituric acid reactive substances (TBARS) and use of the chain-breaking antioxidant vitamin E, no role of lipid peroxidation can be detected in these effects. By incubating fibroblasts with a specific protein kinase C (PKC) inhibitor, GF109203X, we have demonstrated that the stimulation of the adhesion by low doses of UV-A involves, at least in part, a PKC-dependent mechanism. In addition, using function-blocking antibodies of alpha 1, alpha 2 or alpha 5 integrin chains involved in extracellular matrix anchorage, we have shown that they decrease the stimulation of adhesion following low doses of UV-A radiation, demonstrating the involvement of these three integrin chains in this UV-A effect. In parallel, 20 kJ/M2 of UV-A are found to rapidly stimulate membrane expression of alpha 1, alpha 2 and alpha 5 integrin chains. This work, which underlines the involvement of integrins in UV-A effects, contributes to the evaluation of the mechanisms by which cell-matrix interactions modulate cell behaviour.

Adolescent↗
PubMed1999

Lamellar ichthyosis: further narrowing, physical and expression mapping of the chromosome 2 candidate locus.

Lamellar ichthyosis (LI) is an autosomal recessive genodermatosis which has been shown to be both clinically and genetically heterogeneous. Keratinocyte transglutaminase (or transglutaminase 1: TGM1) has been demonstrated to be the disease-causing gene in some families, whilst in others, a second unidentified LI gene was mapped to chromosome 2q33-35 (ICR2B locus). In this study, we present a physical map that encompasses the ICR2B locus, including the mapping of new microsatellite markers. Based on this new map, genotyping additional families highly suggests a reduction in size of the candidate interval. The final interval is covered by a single yeast artificial chromosome (937-H-3) which is 2.2Mb in length. Fine mapping of potential candidate transcripts was also focused on this region.

Chromosomes, Artificial, Yeast↗
PubMed1999

A prospective coagulation study including resistance to activated protein C and mutations in factors V and II in venous leg ulcers.

Hypercoagulable states have been reported to be associated with venous leg ulcers. In an attempt to investigate the prevalence of hypercoagulable states in patients with venous leg ulcers, we performed a prospective case-control study for the presence of coagulation defects in such patients, including resistance to activated protein C (APC), factor V Leiden mutation and a newly described mutation in factor II. Results were compared with those obtained in a control group. APC resistance was found in four of 33 patients tested, but only one was found to be heterozygous for the factor V Leiden mutation. Factor II mutation was found in two of 30 patients tested. Our findings show that the prevalence of coagulation abnormalities is not different in patients with venous leg ulcers from controls in our study, suggesting that only selected patients with venous ulcers and a history of recurrent deep venous thrombosis should be investigated for the presence of coagulation defects.

Activated Protein C Resistance↗
PubMed1999

Contact allergens, but not irritants, alter receptor-mediated endocytosis by human epidermal Langerhans cells.

Allergic contact dermatitis is a T-cell-mediated inflammation, induced by contact with sensitizers and occurring through the release of epidermal cytokines and the activation of epidermal Langerhans cells (LCs). The aim of this study was to analyse early events of LC activation induced either by contact allergens or by irritants devoid of any contact allergenic properties. in order to obtain an in vitro method to discriminate between these two groups of molecules. Various contact sensitizers and irritants were studied for their effects on the endocytosis of major histocompatibility complex class II (MHC-II) molecules by freshly-isolated human epidermal LCs. As observed by flow cytometry, a spontaneous decrease in the surface expression of MHC-II (HLA-DR) molecules, linked to spontaneous internalization of the MHC-II molecules by LCs, was obtained by moving freshly-isolated LCs from 4 degrees C to 37 degrees C. Pre-incubation of LCs with either sensitizers or irritants increased the spontaneous internalization of HLA-DR molecules with a similar magnitude, but no clear discrimination between sensitizer and irritant effects was obtained by flow cytometry analysis. In contrast, confocal microscopy enabled discrimination between the effects of sensitizers and irritants: sensitizer-treated samples showed internalized HLA-DR molecules aggregated in large vesicles with very bright fluorescence; irritant-treated samples were not different from untreated controls and showed compact HLA-DR molecules in small vesicles with diffuse fluorescence, and mostly localized in the submembranous zone. Electron microscopy demonstrated that sensitizer-treated LCs internalized HLA-DR molecules preferentially in lysosomes collected near the nucleus, whereas the irritant-treated and non-treated LCs internalized these molecules in the prelysosomes only near the cell membrane. We conclude that contact allergens and irritants induce distinct patterns of HLA-I)R endocytosis, which may be useful for the development of in vitro screening tests.

Adult↗
PubMed1999

Chronic radiodermatitis following cardiac catheterisation: a report of two cases and a brief review of the literature.

Cardiac angiography produces one of the highest radiation exposures of any commonly used diagnostic x ray procedure. Recently, serious radiation induced skin injuries have been reported after repeated therapeutic interventional procedures using prolonged fluoroscopic imaging. Two male patients, aged 62 and 71 years, in whom chronic radiodermatitis developed one to two years after two consecutive cardiac catheterisation procedures are reported. Both patients had undergone lengthy procedures using prolonged fluoroscopic guidance in a limited number of projections. The resulting skin lesions were preceded, in one case, by an acute erythema and took the form of a delayed pigmented telangiectatic, indurated, or ulcerated plaque in the upper back or below the axilla whose site corresponded to the location of the x ray tube during cardiac catheterisation. Cutaneous side effects of radiation exposure result from direct damage to the irradiated tissue and have known thresholds. The diagnosis of radiation induced skin injury relies essentially on clinical and histopathological findings, location of skin lesions, and careful medical history. Interventional cardiologists should be aware of this complication, because chronic radiodermatitis may result in painful and resistant ulceration and eventually in squamous cell carcinoma.

Aged↗
PubMed1999

Efficacy and safety of mizolastine 10 mg in a placebo-controlled comparison with loratadine in chronic idiopathic urticaria: results of the MILOR Study.

BACKGROUND: Mizolastine is a novel histamine H1-antagonist registered in Europe for the management of allergic rhinitis and urticaria. OBJECTIVES: To compare the clinical efficacy and safety of mizolastine with loratadine and placebo in patients with chronic idiopathic urticaria (CIU). METHODS: A multicentre, double-blind, parallel group study was designed in which 247 patients with CIU were randomised after a 1-week placebo run-in period to 10 mg daily mizolastine (n = 88), 10 mg daily loratadine (n = 79), or placebo (n = 80) for a 4-week treatment period. RESULTS: Mizolastine and loratadine both relieved symptoms of CIU. After 2 weeks' treatment, the severity of pruritus (visual analogue score (VAS) assessed by patients) decreased significantly in both the mizolastine and loratadine groups compared with placebo (mizolastine: -36.7 mm, P = 0.0001; loratadine: -29.8, P = 0.0071; placebo: -16.3); this improvement with both active treatments was maintained throughout the treatment period, the difference being significant only for the mizolastine group (P = 0.0090). Both active treatments were also associated with reduced weekly episodes of urticaria compared with placebo, which was significant after 2 weeks' treatment (mizolastine: 7.9 episodes, P = 0.0061; loratadine: 8.3, P = 0.0221; placebo: 13.3). Angioedema was improved to a clinically significant extent with mizolastine, and loratadine compared with placebo in those patients who had this symptom before treatment. Overall tolerability of both treatments was similar to placebo, and there were no clinically relevant effects on cardiac repolarisation with either mizolastine or loratadine. CONCLUSION: Mizolastine (10 mg daily) is confirmed as an effective and well tolerated agent, comparable to loratadine and superior to placebo, for the management of CIU. Mizolastine acted as rapidly as loratadine in improving urticarial symptoms from the first day of treatment.

Adult↗
PubMed1999

[Dermatologic consultation in a precarious situation: a prospective medical and social study at the Hôpital Saint-Louis in Paris].

INTRODUCTION: The aim of our study was to evaluate the outcomes and the cost of the dermatological consultation for poor and destitute patients, in Saint-Louis Hospital. PATIENTS AND METHODS: We carried out a prospective study from May to October 1996. One hundred and eighty-nine patients (237 consultations) who had no social welfare, were examined. RESULTS: They revealed that 82 p. 100 were male, 63.7 p. 100 were French, 13.9 p. 100 came from Maghreb, 9.7 p. 100 from Sub-Saharan Africa, 73 p. 100 were homeless and 25.7 p. 100 were alcoholic. The average age was around 37.6. The main medical disorders: scabies (56.5 p. 100), lice (22.4 p. 100) and cutaneous infections (7.2 p. 100) were related to the patients' living conditions and their social and economic situation. The other diseases observed were identical to the ones detected in regular health care centers. Complementary laboratories were necessary in 9.3 p. 100 consultations. Only 2 p. 100 of patients were admitted in Hospital. Local treatment was applied by nurses in 67 p. 100 of cases. Drugs were delivered free of charge by the Hospital's pharmacy in 64 p. 100 of cases. The cost of drugs was 83 FF per patient. The mean of duration of treatment was 10.5 days. DISCUSSION: Social workers are a key element in helping the patients to recover their social rights (49 p. 100 of patients have recovered social rights after 6 months). The frequency of skin diseases is higher in this population than in general population, especially in homeless persons. Access to health care is a problem of public health.

Adult↗
PubMed1998

Oligoclonal expansion of HIV-specific cytotoxic CD8 T lymphocytes in the skin of HIV-1-infected patients with cutaneous pseudolymphoma.

A massive infiltration of the skin by activated CD8+ T lymphocytes involving both the dermis and the epidermis has been found in HIV-1-infected patients presenting with a chronic skin rash. We characterized the T cell receptor (TCR) BV-BJ junctional diversity of the skin-infiltrating lymphocytes (SILs) in four patients. The SILs expressed a limited set of TCRBV gene segments. Complementarity determining region 3 length analysis further emphasized their oligoclonality, suggesting that antigen stimulation might be responsible for the cutaneous T cell expansion. Furthermore, independent skin biopsies obtained from the same individual were shown to harbor distinct T cell repertoires, possibly reflecting the spatial heterogeneity of the antigenic stimuli. The CD8+ cytotoxic T lymphocyte (CTL) lines isolated from the skin rash in one patient exhibited a specific, class I MHC-restricted cytotoxic activity against HIV-1 Gag- and Pol-expressing target cells, whereas CTL lines derived from the skin lesions of a second patient were shown to be predominantly Env-specific. Taken together, these data demonstrate the infiltration of HIV-specific CTLs in the skin of HIV-infected patients, and suggest that in addition to their known role in controlling the retroviral infection, these CTLs may also be involved in the pathogenesis of cutaneous inflammatory disorders occurring during the course of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Topical tacrolimus is not effective in chronic plaque psoriasis. A pilot study.

BACKGROUND: Cyclosporine for the treatment of psoriasis constitutes a new approach. Alternative systemic cyclosporine derivatives have been studied to find an immunosuppressive drug with fewer adverse effects. Tacrolimus is one of these new immunosuppressive drugs. Systematically, it has been proven effective in treating psoriasis. A topical formulation of tacrolimus is attractive because it has fewer adverse effects and is useful for a large group of patients. We report for the first time on the efficacy of nonocclusive topical tacrolimus in the treatment of psoriasis. OBSERVATIONS: After a washout phase of 2 weeks, patients were randomized to receive 0.005% calcipotriol ointment twice daily, placebo ointment once daily, or 0.3% tacrolimus ointment once daily. One psoriatic plaque was treated with a surface area of 40 to 200 cm2. Efficacy was estimated using the local psoriasis severity index. The reduction in the local psoriasis severity index score after 6 weeks was 62.5% in the calcipotriol group, 33.3% in the tacrolimus group, and 42.9% in the placebo group. CONCLUSIONS: There was no statistically significant difference between the efficacy of tacrolimus and placebo ointment (P = .77). Calcipotriol ointment, applied twice daily, had a better effect than tacrolimus ointment and placebo ointment once daily.

Administration, Cutaneous↗