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B Dreno

Publications and source records attributed to B Dreno.

At least 55 records · Page 3Linked to original sources
PubMed1999

Melanoma and tumor thickness: challenges of early diagnosis.

OBJECTIVE: To test the basic assumption of campaigns for early diagnosis of melanoma, ie, prognosis is correlated with the delay in the diagnosis. DESIGN: Prospective study of the correlation between delays to diagnosis, assessed using a questionnaire, and the Breslow thickness as a prognosis marker. SETTING: Dermatology departments in France. PATIENTS: Five hundred ninety consecutive patients, referred within 12 weeks after resection of cutaneous melanoma. MAIN OUTCOME MEASURES: Assessment of 5 successive time intervals from the first time the patients realized that they had a lesion until the resection of the melanoma, and results of the correlation between each time interval and tumor thickness (Breslow). RESULTS: There is a positive but weak correlation between tumor thickness and the delay to identify a lesion as suspicious (r = 0.17; P = .009). However, this delay tends to be short for the thickest tumors. There is a negative correlation between tumor thickness and the delay to seek medical attention (r = -0.20; P<.001). This delay was shorter for nodular melanoma. No correlation is found between melanoma thickness and physicians' delays. CONCLUSIONS: Poor prognosis can be accounted for by aggressive rapidly growing tumors rather than by delays. In well-informed populations, campaigns for early diagnosis of melanoma may thus no longer have a major impact on prognosis, unless they are focused on subgroups less accessible to information and medical care.

Female↗
PubMed1999

[ECLA grading: a system of acne classification for every day dermatological practice].

BACKGROUND: Different acne gradings have been proposed: global grading, semi-global grading, quantitative grading and photographic grading. They are mainly used in clinical studies for the evaluation of acne treatment. However, it would be important for physicians to have an acne grade which would be useful for assessing acne lesions prior to treatment and following treatment efficacy. METHODS: Six French dermatologists developed an acne grading scaled called "ECLA" which only takes 2 minutes to fill out and specifically designed for use by dermatologist practitioners. In addition, the intra- and inter-observer reliability of the grading scale was assessed. RESULTS: This analysis demonstrated the excellent reliability of the ECLA grading scale both in terms of intra- and inter-observer variability except for the retentional factor. The cross physician reliability decreased with time specificity for the retention factor, indicating that previous training prior to a multicentric clinical study would be necessary. CONCLUSION: ECLA grading appears to be an interesting and useful tool in dermatology for the follow-up of acne patients.

Acne Vulgaris↗
PubMed1998

Frequency and relative fraction of tumor antigen-specific T cells among lymphocytes from melanoma-invaded lymph nodes.

Several tumor antigens have been described as candidates for immunotherapy. Our study compared HLA-A2-restricted epitopes from 5 antigens commonly expressed by melanomas, i.e., Melan-A/MART-1 peptides (26-35 and 27-35), tyrosinase (368-376), gp-100 (280-288), MAGE-3 (271-279) and NA17-A (1-10), for their relative capacity to promote the development of cytotoxic and cytokine-producing specific CD8+ lymphocytes within melanoma-invaded lymph nodes. We used short-term cultured melanoma-invaded lymph node lymphocytes (MILLs) and tested responses developed by these cells to peptide-pulsed TAP-deficient T2 cells. We measured both the lytic response developed by MILLs and the fraction of these cells that secreted interferon-gamma (IFN-gamma), as deduced from intracellular cytokine labeling. Reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze the expression of the 5 antigens within melanoma-invaded lymph nodes. Melan-A/MART-1, tyrosinase and gp-100 peptides were recognized by MILLs derived, respectively, from 8 of 20, 5 of 19 and 4 of 20 melanoma-invaded lymph nodes expressing these antigens. Most MILLs specific for Melan-A/MART-1 and tyrosinase exhibited both lysis and IFN-gamma responses, whereas most of those specific for gp-100 developed only lysis. Weak lysis without IFN-gamma secretion was developed against NA17-A and MAGE-3 peptides by MILLs from, respectively, 3 of 9 and 2 of 14 lymph nodes expressing these antigens. Our data show a prevalence of both cytotoxic and IFN-gamma-secreting effector T cells specific for differentiation antigens within HLA-A2 melanoma-invaded lymph nodes, which makes these antigens attractive targets for specific immunotherapy.

Antigens, Neoplasm↗
PubMed1998

Randomised trial of interferon alpha-2a as adjuvant therapy in resected primary melanoma thicker than 1.5 mm without clinically detectable node metastases. French Cooperative Group on Melanoma.

BACKGROUND: Owing to the limited efficacy of therapy on melanoma at the stage of distant metastases, a well-tolerated adjuvant therapy is needed for patients with high-risk primary melanoma. Our hypothesis was that an adjuvant treatment with low doses of interferon alpha could be effective in patients with localised melanoma. METHODS: After resection of a primary cutaneous melanoma thicker than 1.5 mm, patients without clinically detectable node metastases were randomly assigned to receive either 3x10(6) IU interferon alpha-2a, three-times weekly for 18 months, or no treatment. The primary endpoint was the relapse-free interval. FINDINGS: 499 patients were enrolled, of whom 489 were eligible. When used as part of a sequential procedure, interferon alpha-2a was of significant benefit for relapse-free interval (p=0.038). A long-term analysis, after a median follow-up of 5 years, showed a significant extension of relapse-free interval (p=0.035) and a clear trend towards an increase in overall survival (p=0.059) in interferon alpha-2a-treated patients compared with controls. There were 100 relapses and 59 deaths among the 244 interferon alpha-2a-treated patients compared with 119 relapses and 76 deaths among the 245 controls. The estimated 3-year-relapse rates were 32% in the interferon alpha-2a group and 44% in controls; the 3-year death rates were 15% and 21%, respectively. Only 10% of patients experienced WHO grade 3 or 4 adverse events. Treatment was compatible with normal daily life. INTERPRETATION: Adjuvant therapy of high-risk melanoma with low doses of interferon alpha-2a for 18 months is safe and is beneficial when started before clinically detectable node metastases develop.

Antineoplastic Agents↗
PubMed1998

Control of growth and differentiation of normal human epithelial cells through the manipulation of reactive nitrogen species.

In this work, we addressed the issue of whether exogenous NO and ONOO- (peroxynitrite) are able to alter growth, viability and/or differentiation of normal epithelial cells using cultured normal human keratinocytes as a model. 3-Morpholino-sydnonimine (SIN-1), a donor of both NO and O2(-)., leading to the production of ONOO-, dose-dependently inhibited growth of human keratinocytes without loss of viability. This inhibitory effect was lowered when SIN-1 was transformed into a pure NO donor by scavenging O2(-). with superoxide dismutase/catalase. Finally, scavenging NO release from SIN-1 with carboxy-1H-imidazol-1-yloxy,2-(4-carboxyp henyl)-4,5-dihydro-4,4,5,5 -tetramethyl-3-oxide (PTIO) resulted in a loss of the inhibitory effect of SIN-1. Together these findings suggest that both ONOO- and NO exert a growth inhibitory effect on human keratinocytes without cytotoxicity. Further support for this conclusion came from the treatment of human keratinocytes with the NO. donor propanamine 3-(2-hydroxy-2-nitroso-1-propyl hydrazino) or with authentic peroxynitrite. Moreover, only SIN-1 or peroxynitrite, and not NO, was able to trigger the expression of markers of terminal differentiation in human keratinocytes. From a physiological perspective, the ability of peroxynitrite, a known genotoxic and potentially carcinogenic agent, to direct proliferating keratinocytes towards terminal differentiation may be crucial to protect the genomic stability of this barrier epithelium.

Catalase↗
PubMed1998

Effect of long-term immunosuppression in kidney-graft recipients on cancer incidence: randomised comparison of two cyclosporin regimens.

BACKGROUND: Long-term administration of cyclosporin carries a risk of renal toxicity, and immunosuppressants are associated with an increased rate of malignant disorders. We undertook an open randomised study of the risks and benefits of two long-term maintenance regimens of cyclosporin in kidney-allograft recipients. The primary endpoint was graft function; secondary endpoints were survival and occurrence of cancer and rejection. METHODS: 231 recipients of a first allograft with at most one previous rejection episode were randomised 1 year after transplantation. Most were receiving cyclosporin and azathioprine. One group received cyclosporin doses adjusted to yield trough blood concentrations of 75-125 ng/mL (low-dose group); the second received doses that yielded trough concentrations of 150-250 ng/mL (normal-dose group). Analysis was by intention to treat. FINDINGS: At 66 months' follow-up, the low-dose and normal-dose groups were similar in mean serum creatinine (182 [SD 160] vs 184 [157] micromol/L; p=0.9) and mean creatinine clearance (47.5 [25.1] vs 45.3 (22.5] mL/min; p=0.6). Nine of 116 patients in the low-dose group and one of 115 in the normal-dose group had symptoms of rejection (p<0.02). There was no difference between the low-dose and normal-dose groups in survival (95 vs 92%; p=0.7) or graft survival (89 vs 82%; p=0.17) at 6 years. 60 patients developed cancers, 37 in the normal-dose group and 23 in the low-dose group (p<0.034); 66% were skin cancers (26 vs 17; p<0.05). INTERPRETATION: We found no evidence that halving of trough blood cyclosporin concentrations significantly changes graft function or graft survival. The low-dose regimen was associated with fewer malignant disorders but more frequent rejection. The design of long-term maintenance protocols for transplant recipients based on powerful immunosuppressant combinations should take these potential risks into account.

Adolescent↗
PubMed1998

Comparative study of the in vitro inflammatory activity of three nickel salts on keratinocytes.

Nickel, the allergen of contact dermatitis, induces the in vitro production of inflammation markers such as intracellular adhesion molecule-1, interleukin-1 and tumour necrosis factor-alpha by keratinocytes. The purpose of our study was to compare the effect in vitro of different nickel salts on keratinocyte activation in order to determine whether this process depends on the nature of the salt used. Cultured keratinocytes were incubated with three nickel salts for 24 h in MCDB153 medium without hydrocortisone. Nickel gluconate, nickel sulphate and nickel chloride were each used at four concentrations: 5.10(-5) M, 1.10(-4) M and 1.10 (-3) M. Keratinocyte activation was studied through the production of three inflammation markers: intracellular adhesion molecule-1, tumour necrosis factor-alpha and very late antigen-3 (an integrin with increased expression during contact dermatitis). Marker production was detected by immunocytochemistry and flow cytometry. Tumour necrosis factor-alpha production and intracellular adhesion molecule-1 and very late antigen-3 expression increased with addition of the three nickel salts, becoming maximal for nickel gluconate 1.10(-4) M. In a subsequent experiment, zinc gluconate (an anti-inflammatory molecule) at 9 micrograms/ml reduced the very late antigen-3 expression induced by nickel gluconate 1.10(-4) M. Therefore, this study enabled us to determine the concentration of a nickel salt (nickel gluconate) inducing optimal keratinocyte activation in our culture conditions and also indicated the potential interest of very late antigen-3 as an inflammation marker.

Anti-Inflammatory Agents↗
PubMed1998

[The resistance of Propionibacterium acnes and Staphylococcus epidermidis to cyclines. The Research and Study Group on Acne].

BACKGROUND: A rising percentage of tetracycline-resistant Propionibacterium acnes strains has been reported in the English literature. PATIENTS AND METHODS: We studied a population of 16 patients with acne who had been treated with oral tetracyclines during the preceding year. A bacteriological examination of a skin biopsy was obtained in all patients to determine aerobic and anaerobic flora as wells as resistance to tetracycline and minocycline. RESULTS: Staphylococcus epidermidis strains were frequently resistant to tetracycline (87.5%) as well as minocycline (30%). Tetracycline-resistant Propionibacterium acnes were also observed (7%). Inversely, we were unable to evidence any minocycline-resistant Propionibacterium acnes strains. CONCLUSION: These findings emphasize the importance of determining whether therapeutic response is related or not to the presence of resistant strains.

Acne Vulgaris↗
PubMed1997

Optimal T cell activation by melanoma cells depends on a minimal level of antigen transcription.

We reported previously that a large fraction of melanoma cell lines induced a suboptimal activation of specific CTL clones, characterized by good tumor cell lysis but no detectable IL-2 production. Using synthetic peptides, we demonstrated recently that this was due to expression of subthreshold levels of appropriate MHC-peptide complexes. We measure here by semiquantitative reverse transcription-PCR the expression of two melanoma Ag (NA17-A and Melan-A/MART-1) mRNAs in 13 melanoma cell lines and analyze the responses to these cell lines of specific HLA-A2-restricted CTL clones. In line with the idea that the density of MHC-antigenic peptide complexes on melanoma cells is a direct function of the Ag's mRNA level, we found that CTL lysis was grossly proportional to this level. We also established that a minimal level of transcription is required for melanoma cells to induce IL-2 secretion. Interestingly, all cell lines that expressed the Ag above this minimal level, either spontaneously or after gene transfection, stimulated the secretion by tumor-infiltrating lymphocyte of IL-2 amounts proportional to Ag expression unless they exhibited a defective expression of intracellular adhesion molecule-1 or LFA-3 molecules or a low expression of the restricting HLA element. These results indicate that optimal activation and therefore, doubtless, full functionality of melanoma-specific CTL clones critically depend on the mRNA level of the Ag in tumor cells and also on a minimal expression of the HLA restriction element, intracellular adhesion molecule-1, and LFA-3. These data provide a rationale for a better selection of patients to be included in Ag-specific immunization protocols.

Antigens, Neoplasm↗
PubMed1997

Clinical efficacy and safety comparison of adapalene gel and tretinoin gel in the treatment of acne vulgaris: Europe and U.S. multicenter trials.

BACKGROUND: Adapalene is a new chemical entity that exhibits tretinoin-like activities in the terminal differentiation process. OBJECTIVE: We evaluated a dose range effect of two concentrations of adapalene gel as acne treatment and compared adapalene 0.1% gel with tretinoin 0.025% gel in the treatment of acne patients in two large multicenter studies. METHODS: Multicenter, investigator-masked, parallel group studies including 89 acne patients in the dose range study and 591 patients in the concurrent controlled studies were conducted. RESULTS: Adapalene gel 0.1% was significantly more effective in treating acne lesions than 0.03% adapalene gel. Adapalene gel 0.1% was significantly more effective than 0.025% or tretinoin gel in one study and of the same effectiveness in the other study. Adapalene gel was always better tolerated than tretinoin gel. CONCLUSION: Adapalene 0.1% gel is a safe and effective treatment of acne vulgaris.

Adapalene↗
PubMed1997

[Detection of circulating neoplastic cells by reverse transcriptase and polymerase chain reaction in melanoma].

BACKGROUND: Circulating melanocytes can be detected in peripheral blood of patients with malignant melanoma by means of tyrosinase messenger RNA amplification. In this study we especially examined peripheral blood from patients with stage II melanoma before and after lymph node dissection for the detection of these circulating melanoma cells. Indeed the presence of regional nodal metastasis is one of the most important prognostic factors in patients with cutaneous melanoma. PATIENTS AND METHODS: Blood samples were collected from 20 normal patients, 42 patients with stage I melanoma and 23 patients with stage III melanoma. Twenty patients with stage II melanoma were tested 3 days before lymph node dissection and 2 à 8 weeks after. To identify circulating melanocytes, we used coupled reverse-transcription and polymerase chain reaction to target tyrosinase messenger RNA. RESULTS: None of the 20 patients with stage II melanoma had detectable circulating melanocytes before lymph node dissection. By contrast, 7 of them became transiently PCR positive in the 8 weeks following surgery. We observed no evidence of correlation between the presence of circulating melanocytes after lymph node dissection and the risk of relapse within 6 months after surgery or the presence of capsule breaking or the number of involved lymph nodes. Sixty-nine percent of stage III patients and none of stage I patients were found to have circulating melanocytes. DISCUSSION: Our study suggests that melanoma cells could circulate transiently after lymph node dissection. Confrontation of our results with literature data, despite important discrepancies related in part to sensibility technique, shows that the presence of circulating melanoma cells is correlated to the clinical stage. Prognostic value of these circulating cells need to be further assessed by prospective studies with large number of patients and long follow-up.

Gene Expression Regulation, Enzymologic↗
PubMed1996

Long-term interferon-alpha therapy induces autoantibodies against epidermis.

BACKGROUND: While interferon (IFN) is known for its immunoregulatory properties, it has also been shown to induce autoimmune disorders such as lupus erythematosus, hypothyroidism, antiphospholipid syndrome and, recently, bullous pemphigus-like eruptions. OBJECTIVE: The purpose of this study was to determine the percentage of antibodies against epidermis induced by IFN-alpha therapy, as detected by indirect immunofluorescence and Western blotting (WB). METHOD: We have studied the sera of 47 patients treated with low doses of IFN-alpha 2a for malignant melanoma or cutaneous T cell lymphoma for a period of 12 months. These sera were tested by standard IIF and WB. RESULTS: 32% of patient sera were positive after 6 months of treatment. Antibodies against epidermis were most often of the pemphigus type as confirmed by WB. Two types of labeling were noted for anti-basement membrane antibodies: basal cytoplasmic pattern in 4 sera and along the dermal side of the basal keratinocytes in 2 sera. CONCLUSION: This study brings biological arguments to confirm the direct role of IFN-alpha in the development of pemphigus-like eruption, and emphasizes the need for clinical follow-up of patients treated with IFN-alpha over a long period of time.

Adult↗
PubMed1996

[Cutaneous and neurologic vasculitis disclosing EBV-selective immunodeficiency].

INTRODUCTION: Purtilo's syndrome or X-linked lymphoproliferative syndrome (XLP) is a rare genetic disorder affecting boys who have a selective immunodeficit towards Epstein Barr Virus (EBV) and who develop extremely severe forms of EBV infection, of which there are four major types: severe or fatal infectious mononucleosis (60 p. 100), lymphoma (23 p. 100), acquired hypo- or agamaglobulinemia (25 p. 100) and anemia or pancytopenia. We report a case of vasculitis (cutaneous and neurologic) which led to the discovery of a selective immunodeficit towards EBV, similar to Purtilo's syndrome. CASE REPORT: A 17 year-old male with no significant past medical history presented with an eruption initially felt to be consistent with pityriasis lichenoid. Treatment with erythromycin was initiated, this did not prevent the subsequent eruptions of cutaneous vasculitis lesions which were severe, prolonged, debilitating, and associated with fever and general deterioration of the patient condition. All etiologic studies were negative. A course of systemic corticosteroids was begun, but the cutaneous eruptions persisted; and in addition the patient developed signs of polyneuropathy in the lower extremities secondary to neurologic vasculitic lesions. New studies revealed an abnormal EBV serology (absence of anti-EBNA antibodies) as well as hypogammaglobulinemia, suggestive of a selective immunodeficit towards EBV resembling Purtilo's syndrome. DISCUSSION: In our patient, the development of an extensive vasculitis, characterized histologically by an intense lymphocytic infiltrate, positive for EBV, associated with hypogammaglobulinemia, and with abnormal serology suggests an anomaly in the immune response to EBV. Although the age of the patient and absence of family history make the Purtilo's syndrome uncertain, the nature of the immunodeficit is very similar and the patient could well develop a lymphoma. This case is significant in that the disease initially manifested itself as a cutaneous vasculitis, which was not been described previously.

Adolescent↗
PubMed1996

[Cardiac metastasis of melanoma disclosed by tamponade].

INTRODUCTION: Melanoma is the most frequent cause of neoplastic metastasis to the heart. The diagnosis is however usually made after the patient's death as clinical signs are discrete, non-specific or masked by other visceral metastases. CASE REPORT: A 50-year-old man who was given chemotherapy for metastatic melanoma limited to the mediastinal lymph nodes suddenly developed acute dyspnea due to cardiac tamponnade. Puncture biopsy of the pericardium revealed melanoma cells and nodular infiltration of the pericardium. A pleuro-percardial window gave functional relief. The patient died 5 months later due to a recurrent episode of cardiac tamponnade. DISCUSSION: The diagnosis of metastasis to the heart of a malignant melanoma may be suspected in patients developing heart failure, rhythm or conduction disorders or pericardial effusion. The diagnosis can usually be confirmed with transthoracic sonography. Endocavitary or transmural tumors may require transesophageal echography or magnetic resonance imaging before surgery to determine extension and myocardial infiltration. Despite the severe prognosis, in case of immediate life-threatening emergencies or isolated cardiac metastases, a surgical treatment may be considered.

Cardiac Tamponade↗
PubMed1996

[Combination of dacarbazine, cisplatin and interferon alpha in the treatment of metastatic melanoma].

INTRODUCTION: The aim of this work was to study the effectiveness and safety of a combined therapy with dacarbazine, cisplatin and interferon alpha in the treatment of metastatic melanoma. PATIENTS AND METHODS: Sixteen patients, including 15 with one or more visceral metastases, were treated with dacarbazin 400 mg/m2, cisplatin 100 mg/m2 repeated every 28-day and interferon alpha-2a 3.10(6) IU subcutaneously 3 times weekly. Fifty percent of patients had at least 3 different sites of metastases. Ten patients had previously received one or more specific treatment for their melanoma. RESULTS: The overall response was 25 p. 100 (2 complete responses and 2 partial responses). The two complete responses were obtained on liver, lung and cutaneous metastases and remain in sustained, unmaintained remission for 22 and 24 months. Administration of this treatment was well tolerated, the most prevalent toxicity being hematologic. At present, responding patients have a median survival of 26 months+ since the beginning of the treatment, compared to 7 months for non responding patients. DISCUSSION: Dacarbazine and cisplatin combined chemotherapy has been used at various doses with an overall response rate of 14 to 37 p. 100, similar to our results. However, duration of complete response in our study (22 months+ and 24 months+) seem more prolonged than in studies using dacarbazine and cisplatin at dose of 100 mg/m2/21 d (7 to 9 months) and comparable to studies using dacarbazine and cisplatin at dose of 150 mg/m2/28 d or more (15 months+ to 19 months+ and 24 months+) but with less toxicity. Therefore addition of interferon alpha might be of interest in the maintain of complete remissions and perhaps in the prolongation of survival of responding patients as it has already been suggested with the dacarbazine-interferon alpha combination.

Adult↗