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Flow between rotating concentric cylinders, or the Taylor Couette flow, has been studied extensively because of its rich physics, ranging from axisymmetric steady laminar flow, to fully developed turbulent flow. In the present study, we advocate the use of this problem as a benchmark case for scale-resolving simulation, such as large eddy simulation (LES) and direct numerical simulation (DNS). The problem is attractive because of its simple geometry, simple boundary conditions, and complex physics involving wall-shear induced and centrifugal instability. Unlike the well-known fully developed channel flow, this problem has a curved wall boundary, and it is unnecessary to add a source term to the governing equations to sustain the fully developed turbulent flow. A p-refinement study for Re = 4000 is performed first to establish DNS data, including the time history of enstrophy, which can be used as an accuracy and resolution indicator to evaluate numerical methods, and is orders of magnitude faster than using the mean flow quantities and Reynolds stresses to evaluate solution quality. Finally, an hp-refinement study is performed to establish the relative accuracy and efficiency of high-order schemes of various accuracy. more...

Tyrosine kinase inhibitor (TKI) discontinuation in chronic phase chronic myeloid leukemia (CML) patients has been examined in a real-life setting in the east occitania region of France. We have collected sex, age, prognostic scores, pre-TKI treatment, TKI length and response, relapse data from patients who had stopped TKI in prolonged complete molecular remission (CMR), and analyzed relapse risk factors. Sixty consecutive patients were included from january 2010 to december 2016. Sixteen received pre-TKI treatment. Fifty-three received a first-generation TKI, and seven had a second-generation TKI in first-line therapy. The median TKI time to achieve CMR was 20.5 months [5-137]. The median TKI length before discontinuation treatment was 73 months [12-158]. Twenty-two patients (37%) relapsed with a median time to relapse of 6 months [3-27]. An intermediate or high Sokal score was the only relapse risk factor (HR = 3.32, p 0.05) associated with relapse after TKI discontinuation. TKI discontinuation was possible without relapse for half of the patients in chronic phase CML. In a real-life cohort, a high-risk Sokal score at diagnosis appears to be an adverse prognosis feature for TKI discontinuation. more...

Introduction People suffering from autism spectrum disorders (ASD) provide atypical responses to sensorial stimulations, indicating specific sensory processing. These responses vary from one another and within the same individual with ASD, resulting in maladaptive functional capacities in everyday life. Factors explaining those specificities are poorly defined and need to be better identified. Objectives To examine the relationship between sensory modulation symptoms (SMSs) and maladaptive behaviors in a group of children with ASD. To study how the sensory processing patterns in ASD are related to chronological age, intensity of autistic symptoms, and associated intellectual disability. Method A transversal observational study of a group of children with ASD was conducted for 1 year in an Autism Resource Centre in Marseille, France. The SMSs were assessed using the Dunn short sensory profile. The adaptive behaviors and social quotient were assessed using the Vineland adaptive behavior scale. Results Forty-five children with ASD completed both scales. Significant correlations were found between SMS intensity and the children's adaptive behaviors. Furthermore, chronological age and intellectual disability showed a significant relationship with SMS intensity; chronological age and intellectual disability were also found to be significantly related. However, the severity of autistic symptoms was not associated with the intensity of SMSs. Conclusion These outcomes give a better understanding of sensory processing in ASD. The analysis of sensory processing is valuable during the diagnostic phase and for the development of individualized/custom-tailored interventions. more...

Introduction Acne vulgaris is a common chronic inflammatory disease of the pilosebaceous unit triggered by Propionibacterium acnes. A bakuchiol, Ginkgo biloba extract, and mannitol (BGM) complex has been developed to provide patients with acne with a specific dermocosmetic to be used adjunctively with conventional treatments. Objective The aim of these studies was to assess the antibacterial, anti-inflammatory, and antioxidative potential of BGM complex and its individual compounds as well as its impact on sebum composition. Methods The antibacterial, anti-inflammatory, and antioxidative potential of BGM complex and its compounds was assessed through in vitro, ex vivo, and clinical studies. The clinical benefit of BGM complex formulated in a cream was assessed in subjects prone to acne through sebum composition analysis and photometric assessments. Results Results from the studies showed that the BGM complex has significant antibacterial, anti-inflammatory, and antioxidative properties. At similar concentrations, bakuchiol has up to twice the antioxidative potential than vitamin E. In subjects, BGM complex regulated the sebum composition in acne patients by increasing the level of sapienic and linolenic acid and reducing the level of oleic acid. The reduced number of porphyrins on the skin surface showed that it is also effective against P. acnes. Conclusion BGM complex provides a complete adjunctive care in patients with acne by targeting etiopathogenic factors of acne: dysseborrhea, inflammation, and P. acnes proliferation. more...

Katarína Poláková,1 Aurélie Fauger,2 Michèle Sayag,2 Eric Jourdan2 1Saint Elisabeth´s Oncological Institute, Bratislava, Slovakia; 2Laboratoire Bioderma, Lyon, France Background: Acne vulgaris is an inflammatory disorder of the pilosebaceous unit. Aim: To confirm that BGM (bakuchiol, Ginkgo biloba extract, and mannitol) complex increases the established clinical efficacy of adapalene 0.1% gel in patients with acne. Methods: A clinical trial was conducted in acne patients. A total of 111 subjects received adapalene 0.1% gel and BGM complex or vehicle cream for 2 months. Assessments comprised Investigator Global Assessment (IGA), global efficacy, seborrhea intensity, inflammatory and non-inflammatory lesions, and subject perception, as well as overall safety and local tolerance and quality of life. Results: At the end of the trial, inflammatory and non-inflammatory lesions, IGA, global efficacy, and seborrhea intensity had significantly improved in both treatment groups. Differences were statistically significant (P more...

Background Sensitive skin usually manifests itself as unpleasant sensations and sometimes erythema. There are various triggering factors for this condition. Although sensitive skin may alter quality of life, its burden has not yet been explored. Objective The aim of this study was to develop and validate a specific sensitive skin burden questionnaire called the BoSS (Burden of Sensitive Skin). Methods A conceptual phase was developed, followed by a development phase, external validation, psychometric analysis, test-retest analysis and, finally, a translation, cross-cultural adaptation and cognitive debriefing. Results A total of 6471 individuals participated in the study (4614 people in the validation study). The dimensionality of items was evaluated using factor analyses, suggesting three dimensions (self-care, daily life and appearance). Unidimensionality was confirmed by higher order factor analysis. The overall Cronbach's α coefficient was high, and intradimensional coherences all demonstrated good reliability. The final instrument consisted of 14 items. The test-retest reliability demonstrated very good reproducibility. The intraclass correlation of each dimension was high. External validity was confirmed by the correlation coefficients of the BoSS vs. those of the SF-12 and the DLQI assessment tools. Conclusion BoSS is the first reliable tool to assess the burden of sensitive skin. more...

SummaryBackground Atopic dermatitis (AD) is an inflammatory and pruritic skin disorder. Objectives To assess the efficacy and tolerance of a new emollient (SBT complex) in subjects with moderate AD. Methods Subjects received twice daily for 168 days (6 months) either SBT complex or emollient base adjunctively or alternately with topical corticosteroids or calcineurin inhibitors. Evolution of AD was assessed throughout the study using usual AD assessment criteria including SCORAD and PO-SCORAD. Quality of life was assessed at Day 0 and Day 168. Results At Day 168, a significant decrease with SBT complex was observed for the SCORAD and the PO-SCORAD scores (P more...

Esthetic treatments can induce swelling and bruises. Thus, a treatment that would prevent or hasten the resolution of bruising should be very useful. Generally, the regression of bruising was conducted with patients or animals models. So we decided firstly to develop an ex vivo model in order to test antibruising properties of topical formulations and secondly to evaluate a curative effect of a cream (mixture of arnica extract and apigenin) in comparison with a positive control (vulnerary cream) and also to estimate the preventive interest of this cream. The results showed that the injection of 25 μl of blood into the dermis of skin fragments was sufficient to create a model of induced-bruise. The duration of 24 hours was chosen to compare the effects of actives on the decrease in the size of the bruise. Joint effects of a pretreatment and a treatment of a mixture of arnica extract and apigenin decreased significantly the area of bruising compared to the treatment group, the control group and the positive control group. Many topical products claim to improve bruising on their package label. Our model can demonstrate their efficacy and determinate the best topical antibruising formulation. The mechanism involved in anti-inflammatory activity of active compounds of topical formulations is often not fully understood. Our blood-induced model may bring some responses through the study of mediators of the inflammation. more...

BACKGROUND Many epidemiological studies have been performed, but a potential increase in the prevalence of sensitive skin, its relationship with age and skin type and the impact of sensitive skin on quality of life are still debated. OBJECTIVE To answer these unresolved questions. METHODS An opinion poll was conducted on a representative French 5000 person sample. RESULTS Fifty-nine per cent of the people declared very sensitive or fairly sensitive skin (together: sensitive skin), and women (66%) declared sensitive skin more frequently than men (51.9%). The results also showed that sensitive skin is more common (more than 60%) in younger people ( more...

Hyperseborrhoea has been considered as a major aetiopathogenetic factor of acne. However, changes in sebaceous gland activity not only correlate with seborrhoea but also with alterations in sebum fatty acid composition. Current findings indicate that sebum lipid fractions with proinflammatory properties and inflammatory tissue cascades are associated in the process of the development of acne lesions. The oxidant/antioxidant ratio of the skin surface lipids and alterations of lipid composition are the main players in the induction of acne inflammation. Nutrition may influence the development of seborrhoea, the fractions of sebum lipids and acne. Acne is an inflammatory disease probably triggered, among others, by proinflammatory sebum lipid fractions. more...

People suffering from autism spectrum disorders (ASD) provide atypical responses to sensorial stimulations, indicating specific sensory processing. These responses vary from one another and within the same individual with ASD, resulting in maladaptive functional capacities in everyday life. Factors explaining those specificities are poorly defined and need to be better identified.To examine the relationship between sensory modulation symptoms (SMSs) and maladaptive behaviors in a group of children with ASD. To study how the sensory processing patterns in ASD are related to chronological age, intensity of autistic symptoms, and associated intellectual disability.A transversal observational study of a group of children with ASD was conducted for 1 year in an Autism Resource Centre in Marseille, France. The SMSs were assessed using the Dunn short sensory profile. The adaptive behaviors and social quotient were assessed using the Vineland adaptive behavior scale.Forty-five children with ASD completed both scales. Significant correlations were found between SMS intensity and the children's adaptive behaviors. Furthermore, chronological age and intellectual disability showed a significant relationship with SMS intensity; chronological age and intellectual disability were also found to be significantly related. However, the severity of autistic symptoms was not associated with the intensity of SMSs.These outcomes give a better understanding of sensory processing in ASD. The analysis of sensory processing is valuable during the diagnostic phase and for the development of individualized/custom-tailored interventions. more...

Single-agent gemcitabine has shown encouraging results in patients with mantle cell lymphoma (MCL). This phase II study further explored the potential of a gemcitabine-based regimen in patients with relapsed or refractory MCL. Patients70 years old received the PDG regimen: gemcitabine (1000 mg/m(2), days 1 and 8), dexamethasone (40 mg/m(2), days 1-4), and cisplatin (100 mg/m(2), day 1). Patients/=70 years of age received dexamethasone and gemcitabine only (DG regimen). Thirty patients (12 in the DG group, 18 in the PDG group) with a median age 66.5 years (range, 47-81) received a median of six cycles in both groups. The overall response rate was 36.4% [95% confidence interval (CI), 15.2% to 64.6%] with the DG regimen and 44.4% (95% CI 24.6% to 66.3%) with the PDG regimen. The median progression-free survival was 3 months (95% CI 0.0-7.9) in the DG group and 8.5 months (95% CI 4.8-12.2) in the PDG group. With a median follow-up of 38.8 months, 13 patients (including 11 given PDG) are still alive. DG was well tolerated, and thrombocytopenia was the most prevalent toxicity in patients receiving PDG. Both regimens deserve to be further investigated as a backbone for combination chemotherapy in patients with MCL. more...

Using well-tolerated cosmetics or those with soothing effects is recommended to treat sensitive skin. However, we lack clinical studies. Two clinical trials were performed on sensitive skin in France and Thailand. The primary objective was to evaluate the preventive soothing effect. The secondary objectives were to evaluate the immediate soothing effect, product tolerance, and impact on quality of life. Evaluation methods included a stinging test and scoring erythema and stinging intensity. We also assessed tolerance, quality of life using the Dermatology Life Quality Index, and cosmetic qualities. The clinical trials were performed in France and Thailand to test efficacy in two different environments and on different ethnic skin. Interesting effects were observed in patients with sensitive skin in France and Thailand: a preventive soothing effect, a soothing effect on erythema, and an immediate soothing effect. In vivo biometrological, sodium lauryl sulfate, and capsaicin tests confirmed these data. A favorable effect on quality of life was also noted. The product was appreciated by volunteers for its efficacy, tolerance, and cosmetic qualities. A preliminary study on the effects on interleukin 8 was also included in the paper. more...

Introduction Les peaux sensibles ont desormais une definition consensuelle internationale, proposee par un groupe d’experts reunis a l’initiative de la Societe internationale sur le prurit (IFSI). La seule evaluation de la prevalence de la peau sensible en France date de 2004 et il a paru pertinent de la reevaluer plus de 10 ans apres, ce d’autant plus qu’une augmentation a ete mise en evidence aux Etats-Unis. Materiel et methodes Un echantillon national de 5000 individus representatifs de la population francaise de 15 a 80 ans, a ete constitue selon la methode habituelle des quotas. Les sujets interroges ont repondu a une question ouverte sur la presence ou non d’une peau sensible, sur l’apparition de brulures, picotements ou irritation en presence de differents facteurs : emotion, froid, chaud, soleil, cosmetiques, air sec, climatisation, eau, pollution et variations de temperature. La qualite de vie etait mesuree par le DLDI chez les sujets revendiquant une peau sensible et par le SF12 chez l’ensemble des sujets. Resultats Sur 5000 personnes interrogees, 2443 etaient des hommes (48,9 %) et 2557 (51,1 %) etaient des femmes. A la question « Avez-vous une peau sensible ? », 51,9 % des hommes et 66,0 % des femmes ont repondu « assez sensible » ou « tres sensible », (p Discussion Cette etude est la premiere etude concernant les peaux sensibles dans la population francaise depuis plus de 10 ans et la premiere qui evalue la qualite de vie au travers de 2 questionnaires (specifique et non specifique). Elle montre que plus d’un Francais sur deux (51,9 % H et 66,0 %F) revendiquent une peau « assez sensible » ou « tres sensible » alors qu’en 2004 a la meme question 44 % des H et 59 % des F avaient repondu « sensible » ou « tres sensible ». Conclusion Cette difference peut avoir plusieurs niveaux d’explication : (1) la notion de peau sensible mieux connue par la population, (2) la taille de l’echantillon (4 fois superieur a celui constitue en 2004), (3) des facteurs d’environnement nouveaux ou plus agressifs. more...

Hyperseborrhea has been considered as a major etiopathogenetic factor of acne. However, changes in sebaceous gland activity not only correlate with seborrhea but also with alterations in sebum fatty acid composition. Current findings indicate that sebum lipid fractions with proinflammatory properties and inflammatory tissue cascades are associated in the process of the development of acne lesions. The oxidant/antioxidant ratio of the skin surface lipids and alterations of lipid composition are the main players in the induction of acne inflammation. Nutrition may influence the development of seborrhea, the fractions of sebum lipids, and acne. Acne is an inflammatory disease probably triggered, among others, by proinflammatory sebum lipid fractions. more...

Mobilisation of healthy donors with lenograstim and transplantation of HLA-genoidentical blood progenitors in 54 patients with hematological malignancies: a pilot study

Allogeneic BMT for patients with acute myeloid leukemia (AML) is presently a reference therapy. The indications for this therapy mainly rely upon prognostic factors, and their importance is constantly reassessed. To examine the impact of time from diagnosis to transplant on survival and leukemia-free survival (LFS), we analyzed 109 patients from the database of the SFGM comprising patients who had all received an HLA-identical allogeneic BMT for a diagnosis of AML in first complete remission (CR1) between January 1987 and December 1992. All patients were conditioned with cyclophosphamide (CY) and total body irradiation (TBI) (CYTBI), and methotrexate (MTX) + cyclosporin A (CsA) were used as graft-versus-host disease (GVHD) prophylaxis. Patient characteristics were: age = 33 +/- 9, M/F = 64/45, white blood cell count (WBC) at diagnosis = 27 +/- 42 x 10(9)/l, FAB distribution: M1 and M2 = 55; M3 = 15, M4 and M5 = 33, M0, M6 and M7 = 6. Karyotyping was carried out for 64 patients: 32 had a normal karyotype, 16 had good prognosis abnormalities (t(8;21), t(15;17), inv 16) and 16 patients had other abnormalities. Eleven patients needed two courses of induction to achieve CR. Time between diagnosis and BMT was 120 (64-287) days. Forty-nine patients developed grade > or = 2 acute GVHD (actuarial probability = 46%). With a median follow-up of 50 months (27-100), the 5-year probabilities for transplant-related mortality (TRM), relapse, overall survival and LFS are respectively 25%, 26%, 59% and 55%. A multivariate analysis showed that survival is adversely influenced by three independent factors: time to transplant (> 120 days vs 33 vs < or = 33). LFS is only influenced by the first two of these factors. The favorable impact of a shorter time from diagnosis to transplant should lead to performing the transplant as early as possible. Practically speaking, this means that when such therapy is chosen for a patient with CR1 AML, the search for an allogeneic donor should begin immediately and transplant be performed as soon as possible. more...

Les bonnes pratiques de la desinfection sont souvent mises en defaut par la presence d'agregats de microorganismes et de biofilms frequemment observes dans les environnements hydriques.Aussi, les desinfectants doivent etre testes au laboratoire en utilisant des modeles bacteriens realistes et standardises. A cet egard, afin d'evaluer l'effet de l'acide peracetique (APA) vis a vis des bacteries, des eaux usees urbaines vehiculant de nombreux agregats de microorganismes et des biofilms standards de laboratoire (formes avec des populations bacteriennes mixtes autochtones) ont ete utilises dans cette etude.Environ 99% des coliformes thermotolerants des eaux usees secondaires sont elimines par ajout de 2,5 mg/l d'acide peracetique (temps de contact de 60 minutes a la temperature de 30°C). Un tel resultat est equivalent a celui obtenu par chloration mais la toxicite des effluents traites par APA (evaluee avec le test Microtox) est quasi nulle alors que celle des effluents chlores est relativement elevee.L'activite respiratoire des populations mixtes du biofilm forme sur les parois du "reacteur-biofilm" est inhibee en presence de 2,5 mg/l d'acide peracetique applique pendant 30 minutes. Cependant l'arrachage d'une partie des cellules fixees (80%) n'est observe que pour des traitements a plus forte concentration (30 mg/l d'acide peracetique/10 minutes). Un tel effet reste cependant limite car la repetition journaliere du traitement (30 mg APA/l/10 min) pendant 4 jours consecutifs ne permet pas d'eliminer plus de 89% des cellules fixees. Aussi, une optimisation de tels traitements chocs doit etre conduite a la seule fin d'eliminer totalement le biofilm. more...

Introduction Le laser fractionne CO 2 est un traitement physique ablatif indique pour ameliorer l’aspect d’une peau lors du photo vieillissement. Il est efficace mais necessite un temps de reparation important qui peut entrainer des effets indesirables et alterer le resultat esthetique. Pour les prevenir, les praticiens associent une prescription topique a leur acte esthetique. L’objectif de ces etudes est d’evaluer l’effet d’un produit sur des lesions cutanees provoquees par un acte esthetique. Materiel et methodes Le produit teste (Matricium ® ) est un dispositif medical sterile (classe IIa) indique pour la regeneration tissulaire des peaux alterees en cas de lesions cutanees superficielles, notamment dues a des interventions dermatologiques. Une etude ex vivo a ete realisee sur des explants de peau humaine. Un jour apres la realisation d’une lesion mecanique standardisee, le produit etudie et un controle positif etaient appliques (2 mg/cm 2 ) a la surface des explants, une fois tous les deux jours. Des photographies de coupes histologiques realisees a j0, j4 et a j10 ont permis pour chaque condition de mesurer la longueur des bourgeons de croissance et d’evaluer la morphologie de l’explant. Une etude clinique a ete conduite sur 16 patients de phototype II a III, âges de 27 a 46 ans. Sur les avant-bras, 3 zones A, B et C etaient determinees de facon aleatoire, puis traitees par laser fractionne CO 2 (SmartXide DOT, Deka, Florence, Italie), selon une procedure standardisee. Les trois zones etaient ensuite respectivement traitees par de la vaseline 2 fois par jour, de la vaseline 1 fois par jour et du Matricium ® 1 fois par jour ou Matricium ® 2 fois par jour. Les differentes zones ont ete evaluees avant et apres le traitement par laser, cliniquement et grâce a des photographies acquises par microscopie confocale (Vivascope 3000 ® , MAVIG GmbH, Munich, Allemagne). Resultats Ex vivo, apres 4 jours d’application de Matricium ® , la longueur du bourgeon de croissance est significativement plus importante que celle de l’explant non traite. Des j10, le bourgeon commence a se differencier et son adherence au derme est bonne. In vivo, l’utilisation de Matricium ® permet d’accelerer le processus de reparation cutanee. La re-epidermisation est plus rapide et de meilleure qualite et la neo-synthese de collagene est acceleree. Discussion Ces etudes montrent que Matricium ® permet de reduire la duree de reparation cutanee post-lesionnelle et d’en ameliorer la qualite. Conclusion Matricium ® peut etre utilise en suite d’acte esthetique, en particulier le laser fractionne CO 2 . Il reduit en effet le temps de reparation et les risques d’effets indesirables qui y sont associes et ameliore le resultat esthetique de l’acte. more...

Introduction Avant de realiser un acte esthetique sur le visage, un nettoyage/demaquillage prealable est generalement necessaire. Suite a l’acte, un nettoyant doux et bien tolere est conseille sur la peau lesee. Pour cette raison, nous avons decide de mener une etude clinique sur une solution micellaire, specifiquement concue pour apaiser et ameliorer le confort cutane des peaux sensibles ou fragilisees, en pre- et post-acte esthetique. Patients et methodes Quatre-vingt-dix sujets asiatiques, âges en moyenne de 34,3 ans, ont ete inclus dans cette etude clinique multicentrique, apres avoir donne leur consentement eclaire. Les principaux actes realises etaient le laser et le peeling (dans 85,6 % des cas), pour une rejuvenation cutanee, une hyperpigmentation et une acne dans la majorite des cas. A j0, avant l’acte esthetique, les investigateurs ont evalue le pouvoir nettoyant/demaquillant de la solution micellaire, ainsi que ses qualites cosmetiques. Apres 28 jours, les sujets ont egalement evalue ces criteres ainsi que les effets apaisant et decongestionnant du produit et egalement l’effet preventif contre les sensations d’irritation souvent liees au nettoyage/demaquillage. Resultats En pre-acte, les investigateurs ont juge le pouvoir nettoyant/demaquillant du produit au niveau du visage tres bon. L’appreciation globale du produit, son apparence, sa texture, sa couleur et son parfum sont consideres comme tres bons a excellents. Tous les investigateurs ont considere les qualites cosmetiques de la solution satisfaisantes a tres satisfaisantes par rapport au produit nettoyant/demaquillant habituellement utilise. En post-acte, les sujets ont evalue le pouvoir nettoyant/demaquillant tres bon. Les qualites cosmetiques ont ete jugees tres bonnes a excellentes. L’effet apaisant de la solution etait satisfaisant a tres satisfaisant dans 97,8 % des cas, l’effet decongestionnant dans 89,9 % des cas et l’effet preventif contre les sensations d’irritation associees au nettoyage/demaquillage dans 90,9 % des cas. Tous les sujets etaient globalement satisfaits de la solution micellaire. Le produit etudie a ete bien tolere dans 96,6 % des cas. Discussion Selon une precedente enquete menee sur 262 medecins esthetiques en France (source interne – 2008), les solutions micellaires sont largement utilisees en pre-acte (dans 60 % des cas) et sont largement prescrites en post-acte (dans 62 % des cas). L’hygiene avant et apres un acte esthetique tient donc une place importante. Une etude menee en France sur 322 sujets a egalement mis en evidence l’effet benefique d’une eau micellaire en pre- et post-acte. Conclusion Ces resultats montrent que la solution micellaire, destinee aux peaux sensibles ou fragilisees, presente un interet avant et apres un acte esthetique pour nettoyer/demaquiller le visage et egalement pour son effet apaisant, decongestionnant et preventif. more...

Agressees par l’environnement, les peaux les plus sensibles deviennent parfois intolerantes et reagissent de facon excessive a des stimuli normalement bien toleres. La peau intolerante est caracterisee par une alteration de la barriere cutanee ce qui favorise la penetration des agresseurs. Il en resulte une reponse permanente de type inflammatoire, faisant intervenir principalement deux types cellulaires : les keratinocytes et les cellules nerveuses. Notre but etait de trouver des actifs capables de cibler biologiquement et simultanement les 2 types cellulaires responsables de la regulation de la sensibilite cutanee. Dans une premiere etude in vitro, des keratinocytes humains normaux en monocouche ont ete mis en presence de nos actifs (rhamnose, mannitol, xylitol) et de TNFα, puis un dosage d’IL-8 a ete realise par un test Elisa. Ensuite, dans une seconde etude in vitro, des neurones sensitifs ont ete incubes 30 minutes avec les memes actifs et un tetrapeptide puis stimules par de la capsaicine. Le flux calcique a alors ete mesure par fluorescence et la secretion d’un neuromediateur pro-inflammatoire, CGRP, par un test Elisa. Les resultats demontrent que nos actifs reduisent significativement la secretion d’IL-8 par les keratinocytes de 23 %, inhibent de 71 % le flux calcique et de 41 % la secretion de CGRP dans des neurones sensitifs actives par la capsaicine. Ainsi, notre complexe d’actifs permet de reguler biologiquement la cascade neuro-inflammatoire, en ciblant les deux types cellulaires impliques dans l’apparition de l’intolerance cutanee, afin de reduire les demangeaisons et apporter apaisement et confort aux peaux intolerantes. more...

Rituximab (chimeric anti-CD20 IgG1 monoclonal antibody) is effective in the treatment of relapsed/refractory low-grade lymphomas of B-cell origin as well as in diffuse large B-cell lymphoma. Several reports also demonstrated the efficacy of rituximab for the treatment of autoimmune cytopenia, especially for cold agglutinin disease. We report the first case, to our knowledge, of rituximab-related autoimmune hemolytic anemia. The pathophysiological mechanisms remain unknown, although the drug could act through massive cytokines liberation after destruction of CD20 positive cells by rituximab. more...

There is a need in the management of non-Hodgkin's lymphoma (NHL) for tumor-targeted therapy. Immunotherapy with monoclonal antibodies can be used to reach this goal. These treatments have however often produced disappointing efficacy and so have not been broadly applicable to patients. MODIFIED MONOCLONAL ANTIBODIES: Technological advances have been used to alter mouse monoclonal antibodies genetically, leading to the development of mouse/human chimeric or humanized antibodies with demonstrated advantages of reduced immunogenicity and enhanced ability to interact with human effector cells. Initial phase I/II trials of monoclonal antibodies for relapse or refractory NHL, especially with chimeric anti-CD20 rituximab, demonstrated encouraging results. FURTHER ASSESSMENT: Randomized trials are now necessary to compare these agents with standard regimens and to determine their optimal use. more...

Allogeneic BMT for patients with acute myeloid leukemia (AML) is presently a reference therapy. The indications for this therapy may likely rely upon prognostic factors, and their importance are constantly investigated. To examine the impact of time from diagnosis to transplant on survival and Leukemia Free Survival (LFS), we analyzed 109 patients from the data base of the SFGM, patients who all had received an HLA-identical allogeneic BMT for a diagnosis of AML in First Complete Remission (CR1) between January 1987 and December 1992. All patients were prepared with cyclophosphamide (Cy) and Total Body Irradiation (TBI) (Cy — TBI), and Methotrexate (MTX) + Cyclosporine A (CSA) was used as Graft-vs.-Host Disease (GVHD) prophylaxis. Eleven patients needed 2 courses of induction to achieve CR. Time between diagnosis and BMT was 120 (64–287) days. Forty nine patients developed a grade 2 acute GVHD (Actuarial probability = 46%). With a median follow-up of 52 months (30–100), the 5 year probabilities for transplant related mortality (TRM), relapse, overall survival and LFS are respectively 25, 26, 59%, and 55%. A multivariate analysis showed that survival is adversely influenced by 3 independent factors: time to transplant (>120 days vs.≤120 days), acute GVHD (grade 2–4 vs. grade 0–1) and age (>33 vs.≤33). LFS is influenced by only the first two of these factors. The favorable impact of less time from diagnosis to transplant should lead to proceeding to the transplant as soon as possible. Practically speaking, this means that when such therapy is chosen for a patient with CR1 AML, the search for an allogeneic donor should be immediately investigated and transplant performed as soon as possible. more...

We conducted a phase I–II trial of escalating dose of carboplatin (CB) 0.750, 0.875, 1000 g/m2 (level 1, 2, 3 respectively) given over 5 days as continuous infusion (CI) in association with ARAC 5 g/m2 and VP16 0.5 g/m2, to assess the limiting toxicity and the response rate of this combination. Twenty eight patients entered the study (19 phase I, 9 phase II) median age 42 years (22–55),14 males, 13 females, 9 ALL, 19 AML (16 without antecedent of MDS or CML, 1 acutisation of CML, 2 acutisation of MDS). 3 patients received the therapy as primary treatment for AML. Four patients were refractory, 21 were in relapse. more...

Allogeneic BMT for patients with acute myeloid leukemia (AML) is presently a reference therapy. The indications for this therapy mainly rely upon prognostic factors, and their importance is constantly reassessed. To examine the impact of time from diagnosis to transplant on survival and leukemia-free survival (LFS), we analyzed 109 patients from the database of the SFGM comprising patients who had all received an HLA-identical allogeneic BMT for a diagnosis of AML in first complete remission (CR1) between January 1987 and December 1992. All patients were conditioned with cyclophosphamide (CY) and total body irradiation (TBI) (CYTBI), and methotrexate (MTX) + cyclosporin A (CsA) were used as graft-versus-host disease (GVHD) prophylaxis. Patient characteristics were: age = 33 +/- 9, M/F = 64/45, white blood cell count (WBC) at diagnosis = 27 +/- 42 x 10(9)/l, FAB distribution: M1 and M2 = 55; M3 = 15, M4 and M5 = 33, M0, M6 and M7 = 6. Karyotyping was carried out for 64 patients: 32 had a normal karyotype, 16 had good prognosis abnormalities (t(8;21), t(15;17), inv 16) and 16 patients had other abnormalities. Eleven patients needed two courses of induction to achieve CR. Time between diagnosis and BMT was 120 (64-287) days. Forty-nine patients developed gradeor = 2 acute GVHD (actuarial probability = 46%). With a median follow-up of 50 months (27-100), the 5-year probabilities for transplant-related mortality (TRM), relapse, overall survival and LFS are respectively 25%, 26%, 59% and 55%. A multivariate analysis showed that survival is adversely influenced by three independent factors: time to transplant (120 days vsor = 120 days), acute GVHD (grade 2-4 vs grade 0-1) and age (33 vsor = 33). LFS is only influenced by the first two of these factors. The favorable impact of a shorter time from diagnosis to transplant should lead to performing the transplant as early as possible. Practically speaking, this means that when such therapy is chosen for a patient with CR1 AML, the search for an allogeneic donor should begin immediately and transplant be performed as soon as possible. more...

Double autologous bone marrow transplantation (ABMT) has been reported as an efficient form of consolidation for patients with multiple myeloma (MM). However, few data are available about feasibility and efficacy of a third ASCT in case of relapse. Here we report two patients with MM who received a third ASCT for late relapse (74 and 52 months) after a double ABMT. Both patients were male with IgG gamma MM (stage IIIA according to the Durie Salmon classification). The two patients were in PR50% after a first-line treatment. A double ABMT was performed after relapse and patients remained in PR50% after double intensification, lasting 71 and 49 months, respectively. The third ASCT was performed 7 and 10 months, after second relapse. One patient needed 15 months to reach 50 000 platelets, however he did not receive any transfusion after day 14. He was in PR50%. The other patient was in PR50%, 4 months after ABMT with a full hematological reconstitution. For patients with late relapse of MM after double ABMT, a third ABMT was a feasible treatment and patients seem to remain sensitive to high-dose therapy. more...

Allogeneic BMT is presently recognized as one of the reference anti-leukemic treatments for AML patients. It could be a very useful therapy in CR1 AML if it is efficient as an early form of consolidation after induction therapy. Later procedures may be of lesser importance since they concern a population which may have already been cured by chemotherapy. Alternatively it is not solved if very early BMT gives patients sufficient therapy and provides lower toxicity. To answer this question we analyzed data from the Société Française de Greffe de Moelle (SFGM) on a sub-group of patients according to the following criteria: (1) Allogeneic BMT carried out on patients with AML in CR1; (2) after January 1985; (3) conditioning with CyTBI; (4) GVHD prophylaxis with MTX-CsA; (5) interval between diagnosis and BMT100 days. Forty-two fulfilled all criteria. Age was 31 +/- 8 years and M/F ratio was 19/23. WBC at diagnosis were 36 +/- 49 x 10(9)/l and four patients needed two induction courses to achieve CR1. Median follow-up is now 51 (24-116) months. Twenty-two patients developed a gradeor = 2 acute GVHD. Early transplant mortality at 1 year is no higher than 14%. Two patients died of secondary malignancies at 3.5 and 6.5 years after BMT. Finally 5-year (and 7-year) probabilities for relapse, survival, leukemia and event-free survival are respectively 17% (17%), 71% (62%), and 71% (71%) and 68% (59%). These data indicate the feasibility of such an approach with low mortality and low relapse rates providing a good long-term outcome. This should prompt an invitation to initiate the search for an HLA-identical sibling when AML is diagnosed in a young patient eligible for allo-BMT. more...

8069 Background: PKC overexpression is observed in relapsed/refractory DLBCL. Enzastaurin (ENZ), an oral serine/threonine kinase inhibitor, targets PKCβ, and showed preclinical and clinical activit... more...