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B Dreno

Publications and source records attributed to B Dreno.

At least 37 records · Page 2Linked to original sources

Expression pattern, genomic structure and evaluation of the human SLC30A4 gene as a candidate for acrodermatitis enteropathica.

Slc30a4 is the fourth and last identified member of a mammalian proteins family presumably involved in the cellular transport of zinc, solute carrier family 30. The murine homologue of the human SLC30A4 gene has previously been investigated and found responsible for the lm, a phenotype due to zinc deficiency. According to the strong homology between mouse and human SLC30A4 coding sequences, and to the very similar clinical features encountered in the murine lm and in human acrodermatitis enteropathica, SLC30A4 has appeared to us to be a good candidate for acrodermatitis enteropathica. Here we detail the genomic structure of human SLC30A4 together with its localization on chromosome 15q15-q21. We also report the mutational analysis of human SLC30A4 in ten families with acrodermatitis enteropathica, which enabled us to exclude this gene from any involvement in the disorder of the patients examined.

Acrodermatitis↗

Economic analysis of adjuvant therapy with interferon alpha-2a in stage II malignant melanoma.

Using the trial demonstrating that interferonalpha-2a (IFNalpha-2a) is efficacious as adjuvant therapy in stage II melanoma, we evaluate its outcomes and economic consequences. Using rates observed in the 5-year trial and published figures, survival and Q-TWIST (Time Without Symptoms and Toxicity) were extrapolated to a 10-year and lifetime horizon. Cost analysis was performed using the trial's data, published literature and experts' opinions from the perspective of the French Sickness Funds. Patients in the IFNalpha-2a-group have an additional 0.26 years in life-expectancy over a 5-year time period (P=0.046), 0.67 years over a 10-year period and 2.59 years over a lifetime. Cost per life-year-gained was estimated at approximately 14400 after 5 years, 6635 after 10 years and 1716 over a lifetime. Assuming that there is an improvement in disease-free survival only, cost is 26147 per Q-TWIST. Cost-effectiveness of IFNalpha-2a in stage II melanoma compares favourably with estimates for widely used therapies in the oncological field.

Adult↗

An epidemiological study of acne in female adults: results of a survey conducted in France.

BACKGROUND: Acne is usually perceived as a disease of teenagers, and most epidemiological studies have focused on adolescents. OBJECTIVE: The primary objective was to investigate the prevalence of acne in a representative sample of French females. Information about skin type, life-style factors influencing acne and quality of life were also recorded. METHODS: A self-administered questionnaire was sent to 4,000 adult women aged 25-40 years, after a validation test by three dermatologists. A definition of acne severity, according to questionnaire answers, was established before the questionnaire was sent out. RESULTS: A total of 3394 women completed the questionnaire of which 3,305 were useable. The data showed a prevalence of acne in 17% of the population, and physiological acne in 24%. Thus, the total acne prevalence was 41%. Forty-nine per cent of the acne patients had acne sequelae (scars and/or pigmented macules). Forty-one per cent of adult acne patients had not experienced acne during their adolescence. A premenstrual flare and stress was recorded as causing acne in 78% and 50%, respectively. Twenty-two per cent of acne subjects were currently receiving therapy. For most patients, acne did not severely impair their quality of life. CONCLUSION: This study shows a prevalence of acne in 41% of women in the general population. A high proportion of these acne cases are late onset acne.

Acne Vulgaris↗

Multicenter randomized comparative double-blind controlled clinical trial of the safety and efficacy of zinc gluconate versus minocycline hydrochloride in the treatment of inflammatory acne vulgaris.

BACKGROUND: In addition to tetracyclines, zinc may constitute an alternative treatment in inflammatory lesions of acne. OBJECTIVE: To evaluate the place of zinc gluconate in relation to antibiotics in the treatment of acne vulgaris. METHODS: Zinc was compared to minocycline in a multicenter randomized double-blind trial. 332 patients received either 30 mg elemental zinc or 100 mg minocycline over 3 months. The primary endpoint was defined as the percentage of the clinical success rate on day 90 (i.e. more than 2/3 decrease in inflammatory lesions, i.e. papules and pustules). RESULTS: This clinical success rate was 31.2% for zinc and 63.4% for minocycline. Minocycline nevertheless showed a 9% superiority in action at 1 month and one of 17% at 3 months, with respect to the mean change in lesion count. Regarding safety, the majority of the adverse effects of zinc gluconate and of minocycline concerned the gastrointestinal system and were moderate (5 dropouts with zinc gluconate and 4 with minocycline). CONCLUSION: Minocycline and zinc gluconate are both effective in the treatment of inflammatory acne, but minocycline has a superior effect evaluated to be 17% in our study.

Abdominal Pain↗

Prognostic value of tyrosinase reverse-transcriptase polymerase chain reaction in metastatic melanoma.

BACKGROUND: Circulating tumor cells can now be identified in subjects with metastatic melanoma by using the reverse-transcriptase polymerase chain reaction (RT-PCR) to detect the messenger RNA of tyrosinase, a key enzyme of melanogenesis. AIM AND METHODS: The aim of this study was to determine whether the detection of positive tyrosinase cells in patients at metastatic stage was associated with a worse evolution. 32 patients were included with metastatic melanoma (AJCC IV). RESULTS: 66% had a positive tyrosinase RT-PCR and a shorter survival compared with patients with a negative RT-PCR, but this difference is not statistically significant. However, a positive test could appear indicative of rapid progression and poor prognosis. CONCLUSION: The prognostic value of this method could be improved by combining it with PCR of other melanoma markers (Melan A, Mage 3) or assays of serum markers (S 100 protein or lactate dehydrogenase).

Humans↗

[Viruses involved in allograft recipients'cutaneous carcinomas].

BACKGROUND: Cutaneous carcinomas are frequent in renal allograft recipients. Their treatment can be difficult especially in cases of multiple carcinomas. The aim of this study was to determine whether human papillomavirus are more frequent in patients group with multiple cutaneous carcinomas and whether other viruses such as Epstein-Barr virus, cytomegalovirus, and herpes simplex might be associated in this kind of tumour. PATIENTS AND METHODS: Forty-three patients were included. Twenty-two had a single carcinoma (group 1) and 21 had multiple cutaneous carcinomas (group 2). Histologic analysis and in situ hybridization were used to search for Epstein-Barr virus, human papillomavirus, herpes simplex virus and cytomegalovirus latency genes. RESULTS: In both groups, epidermoid carcinomas were more frequent than basal cell carcinomas and delay between graft and first carcinoma was similar (5 years). In situ hybridization was more often positive in group 2 (41/50) than in group 1 (13/22). Human papillomavirus DNA was detected more frequently in the group with multiple carcinomas (26/50) than in the group with a single carcinoma (6/22). Moreover, cytomegalovirus was more frequent in group 2. CONCLUSION: This study shows a higher prevalence of human papillomavirus DNA in the carcinomas of the multiple carcinoma population. Moreover, for the first time, cytomegalovirus DNA was detected in carcinomas of renal allograft recipients with a higher frequency in the patients with multiple carcinomas.

Adult↗

Delays in diagnosis and melanoma prognosis (II): the role of doctors.

A prospective survey was conducted to assess physician responsibility in melanoma prognosis. Consecutive patients with primary melanoma were interviewed and examined using a standardized questionnaire. Main outcome measures were medical components of the delay before tumor resection and tumor thickness. Of 590 melanomas, 29.1% were coincidentally detected by physicians and their tumor depth was lower than in melanomas detected by patients (p < 0.001). Physician sensitivity for melanoma diagnosis was evaluated at 86%. Median time intervals to propose resection and to perform removal of melanoma were short: 0 (mean 103) and 7 (mean 68) days, respectively. Melanomas were managed in an inappropriate way in 14.2% of cases. Location on acral areas and absence of pigmentation were associated with longer medical delays and more frequent inappropriate medical attitudes. Melanomas located on hardly visible areas were less frequently detected by physicians than those on visible areas. Medical delays were shorter, doctor's attitude was more frequently appropriate, and melanoma thickness was lower (p < 0.001) when the patient visited a dermatologist (54.7%) than when he or she visited a general practitioner (33.4%). Our study shows that doctor responsibility accounts for only a small part of the total delay before melanoma removal. However, systematic total examination and better training of doctors, especially about unusual forms of melanoma, could still improve melanoma detection.

Attitude of Health Personnel↗

Delays in diagnosis and melanoma prognosis (I): the role of patients.

A prospective survey was conducted to assess the role of patients in the melanoma prognosis. Consecutive patients with primary melanoma were interviewed and examined using a comprehensive questionnaire including a psychological instrument. Main outcome measures were the delay before medical intervention and the tumor thickness. Of 590 melanomas, 70.8% were detected by patients and this proportion was higher in females. Relatives were involved in the detection of half of the cases. Median delays before the patient realized he had a suspicious lesion, before this lesion was seen by a doctor, and before the melanoma was removed were 4 months, 2 months, and 1 week, respectively. Delays up to several years were observed in some cases. The rate of self-detection tended to be lower, the delays before seeking medical advice to be longer, and the tumor thickness to be higher in old people, in males, in lower-educated individuals, in those living out of towns, and in people with a low awareness about melanocytic tumors than in other cases. Conversely, individuals with a high number of atypical nevi, those who were aware to be at risk, and those who regularly visited a dermatologist tended to detect their melanoma more rapidly. No specific psychological traits were associated with a late reaction, although negligence and anxiety tended to prolong the delays. Knowledge about melanoma was poor in many patients, especially in males, and wrong beliefs were widespread. This study provides the targets of future education programs.

Adolescent↗

Melanoma screening: report of a survey in occupational medicine.

BACKGROUND: Epidemiological studies concerning melanoma are most often performed by general practitioners and dermatologists in patients previously aware of the risk of nevi. OBJECTIVE: To determine the efficiency of early detection of melanoma by occupational medicine specialists trained in the use of ABCDE criteria during annual systematic examination of workers. METHODS: A total of 370 subjects with suspect lesions that demonstrated at least 2 of 5 ABCDE criteria were selected from 65000 employees examined; these subjects were requested to see their physician about possible excision. Of the 370 subjects, 273 (73.8%) were seen at a second-year follow-up visit to determine their outcome. RESULTS: Among the 273 subjects who were seen again, 172 (63.0%) had consulted a physician. For the 101 subjects who had not seen a physician, the main reason was the negligence (86.1%). A total of 353 atypical nevi were observed. The mean number of ABCDE criteria noted per lesion was 2.6. Lesion diameter greater than 6 mm was the most frequent (80.5%) and enlargement the least frequent criteria seen; heterochromous coloration and diameter greater than 6 mm was the most common association (54.5%). Five histologically confirmed melanomas were found among nevi excised in 78 subjects. CONCLUSION: This screening approach seems efficient for the early detection of melanoma, demonstrating an incidence of 7.7 per 100000 vs. 9 per 100000 in the general French population.

Adolescent↗

Zinc, copper and manganese enhanced keratinocyte migration through a functional modulation of keratinocyte integrins.

The migration of keratinocytes plays an important role in the re-epithelialization of cutaneous wounds. Zinc, copper and manganese are used in vivo for their healing properties and their mechanism of action is still only partially known. Thus, they have been shown both to promote keratinocyte proliferation and to modulate integrins expression. The aim of this study was to determine if trace elements induce an increase of the migration of keratinocytes and if this effect is related to the modulation of integrins. Two independent migration assays were used to study keratinocyte migration: the scratch assay using normal human keratinocytes and the modified Boyden chamber using HaCaT cells. Inhibition studies using function-blocking antibodies directed to alpha3, alpha6, alpha(v) and beta1 subunits were performed to investigate the modulator effect of trace elements on integrin function. In this way, zinc and copper gluconates increased alpha3, alpha(v) and beta1 function whereas manganese gluconate seems mainly able to modulate the function of alpha3 and beta1. The stimulating effect of these trace elements on keratinocyte migration does not appear related to alpha6 subunit. Thus, zinc, copper and manganese enhanced keratinocyte migration and one of the mechanisms was going through a modulation of integrin functions.

3T3 Cells↗

Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma.

PURPOSE: To compare, in 305 patients with advanced metastatic melanoma, temozolomide and dacarbazine (DTIC) in terms of overall survival, progression-free survival (PFS), objective response, and safety, and to assess health-related quality of life (QOL) and pharmacokinetics of both drugs and their metabolite, 5-(3-methyltriazen-1-yl)imidazole-4-carboximide (MTIC). PATIENTS AND METHODS: Patients were randomized to receive either oral temozolomide at a starting dosage of 200 mg/m(2)/d for 5 days every 28 days or intravenous (IV) DTIC at a starting dosage of 250 mg/m(2)/d for 5 days every 21 days. RESULTS: In the intent-to-treat population, median survival time was 7.7 months for patients treated with temozolomide and 6.4 months for those treated with DTIC (hazards ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.52). Median PFS time was significantly longer in the temozolomide-treated group (1.9 months) than in the DTIC-treated group (1.5 months) (P =.012; hazards ratio, 1.37; 95% CI, 1.07 to 1.75). No major difference in drug safety was observed. Temozolomide was well tolerated and produced a noncumulative, transient myelosuppression late in the 28-day cycle. The most common nonhematologic toxicities were mild to moderate nausea and vomiting, which were easily managed. Temozolomide therapy improved health-related QOL; more patients showed improvement or maintenance of physical functioning at week 12. Systemic exposure (area under the curve) to the parent drug and the active metabolite, MTIC, was higher after treatment with oral temozolomide than after IV administration of DTIC. CONCLUSION: Temozolomide demonstrates efficacy equal to that of DTIC and is an oral alternative for patients with advanced metastatic melanoma.

Adult↗

[Melanoma in organ transplant patients].

OBJECTIVE: The incidence of cutaneous melanoma has rapidly increased in the white population over the last decades. It has been estimated that the incidence doubles world-wide every 10 years. Different risk factors have been identified, including immunosuppression. The aim of our study-was to determine the relative risk of developing melanoma in the organ transplant population and the clinical and histological features of their melanomas. PATIENTS AND METHODS: This retrospective study was conducted with the collaboration of 9 University Hospital Centers: Besançon, Brest, Caen, Dijon, Lille, Lyon, Nantes, Paris (Pitié-Salpétrière) and Rennes. A questionnaire was sent to the different departments of dermatology of these hospitals to obtain information on patients who had presented a melanoma after a transplantation between 1971 and 1997. During this period, there were 12,477 organ transplant recipients in the transplantation units of these 9 hospitals. Average follow-up for these patients was about 5 years and the average duration of immunosuppressive therapy was about 4.5 years. RESULTS: Among 12,477 organ transplant recipients, we found 17 cases of melanoma but no data could be obtain on one case: 14 occurred in renal transplant recipients and 3 in cardiac transplant recipients. Clinical and histological data were only available in 16 patients. The average time between transplantation and diagnosis of melanoma was 63 months, but it was 5 times shorter for 2 patients who had a past history of melanoma before transplantation. Two patients had a mucosal melanoma; for the cutaneous melanomas, 2 appeared on Dubreuilh melanosis, 2 were in situ melanomas, 7 were superficial spreading melanomas and 3 were nodular melanomas. The histological review of 11 cutaneous melanomas revealed a precursor nevus in 6 cases and a weak or no stroma reaction in 7/7 cases. Complete excision of the melanoma was performed in all patients except one with anorectal melanoma. Four patients died of visceral metastasis within a mean 15 months. The other 12 patients are still alive with a mean 3 year course since tumor treatment. We tried to determine the relative risk of developing melanoma in the renal transplant population (14 cases). The number of expected cases of melanoma was 5.54, giving a relative risk of 2.5. DISCUSSION: Only 4 studies have shown an increase in the incidence of melanoma in the renal transplant population: approximately 2 to 5-fold. In our study, the 2.5-fold increase in melanoma was estimated with an average 5 year follow-up and an average 5 year immunosuppressive therapy. This is probably an underestimation of risk because we were unable to make an exhaustive collection of cases of melanomas even though transplant recipients undergo more physical examinations than a reference population. The mean latency period from transplantation to melanoma diagnosis was 63 months, as in other studies. Histological examination showed that a precursor nevus is frequent with weak host cellular response to the tumor. The prognosis of these melanomas remains difficult to predict, but in our study, it would not appear to be as poor as expected. Discontinuation of immunosuppressive therapy would not appear to be necessary except in the presence of metastasis. Finally, our study demonstrates the importance of good patient follow-up, even after graft rejection due to the persistent risk of melanoma.

Adult↗

High avidity melanoma-reactive cytotoxic T lymphocytes are efficiently induced from peripheral blood lymphocytes on stimulation by peptide-pulsed melanoma cells.

To design an efficient procedure to expand high avidity melanoma reactive T cells and to perform immunotherapies, we compared conditions of peripheral blood lymphocyte (PBL) stimulation by Melan-A/MART-1 peptides. Avidity of induced CTLs was evaluated by measuring their lysis and cytokine secretion to peptide-pulsed transporter-associated protein-deficient cells and to melanoma cells. In side-by-side experiments, we show that melanoma cells, either allogeneic or autologous, induced the growth of high avidity Melan-A-reactive CTLs from all donors, whereas essentially low avidity T cells were induced by peptide-pulsed PBLs. We also show that at least two cytokines, interleukin-6 and interleukin-2, were required to promote the growth of high avidity CTLs. Once sorted by tetramer labeling or cloning, the specificity and reactivity to tumor cells of peptide-specific T cells induced by allogeneic melanoma cells were confirmed. We then describe a relatively simple and efficient procedure that allowed us to obtain systematically high amounts (in the range of billion) of high avidity Melan-A/ MART-1-specific T cells from the PBLs of HLA-A2 melanoma patients and healthy donors in 3 months. Because this antigen is expressed by most melanoma tumors, this procedure should be useful for checking the efficiency of adoptive immunotherapy of melanoma tumors and using functionally well-defined Melan-A/MART-1-specific CTLs in a large group of patients.

Amino Acid Sequence↗

[Descriptive epidemiological study of acne on scholar pupils in France during autumn 1996].

BACKGROUND: Acne is the most common symptom prompting patients to consult a dermatologist. No previous study has been conducted in France to determine the prevalence of acne and describe the main epidemiological features. SUBJECTS AND METHODS: A cross sectional study was conducted in November 1996 and included 913 school children aged 11 to 18 years. This sample was statistically representative of the entire secondary school population in France during the 1996-1997 school year. The subjects were stratified by 5 criteria: age, sex, rural or urban residence, sun exposure, type of school. RESULTS: Taking the clinical diagnosis made by the dermatologist investigator as the main criteria, the overall prevalence of acne was 72 p. 100. It was 76.1 p. 100 using the new ECLA grading system previously described. The prevalence of acne was sex and age dependent: highest scores were found for girls aged 14-16 years and for boys aged 16-17 years. Genetic factors were very important for the outcome of acne. Finally, 41 p. 100 of the acneic subjects were following a treatment, prescribed by a dermatologist in two-third of the cases. DISCUSSION: These results are in agreement with those previously published in the literature although some differences were disclosed. It would appear important to distinguish between minimal acne with a few retentional pimples occuring during adolescence and severe acne (more than 20 pimples on the face) requiring early medical care to avoid scarring.

Acne Vulgaris↗

White blood cell count: a prognostic factor and possible subset indicator of optimal treatment with low-dose adjuvant interferon in primary melanoma.

AlphaIFN has recently been recognized as an adjuvant therapy to surgery in melanoma patients. A major issue is to select patients who will benefit from this therapy and to avoid toxicity in those who will not respond. The aim of this exploratory analysis was to identify the predictive factors of response to alphaIFN. The French cooperative group has recently shown that adjuvant therapy of melanoma patients with low-dose alphaIFN provides a benefit on disease-free interval (DFI). Using this database, predictors of DFI were investigated using Cox models and treatment-covariate interactions were sought. Gender, age, Breslow thickness, and baseline WBC count, given an alphaIFN-WBC interaction, were independent predictors of DFI. Baseline WBC count was the only variable for which there was an interaction with alphaIFN, whatever the Breslow: patients with low WBC count (<6.8 x 10(9)/liter = median) did not benefit from alphaIFN (HR=1.27 (95%CI: 0.84-1.91); P = 0.26) whereas the DFI of patients with high WBC was prolonged (P = 0.0001) with a hazard ratio of 0.50 (95% confidence interval, 0.35-0.71). The estimated values of WBC count for which IFN was significantly superior to no-treatment were those > or = 7.2 x 10(9)/liter. The baseline WBC count was correlated to baseline neutrophils but not to Breslow thickness or to time since last melanoma surgery. AlphaIFN prolonged DFI in patients with a high WBC count but not in those with a low WBC count. The results of this exploratory analysis, if confirmed by other studies, may help to identify patients who are most likely to benefit from alphaIFN.

Age Factors↗