[Trisomy 21 and breast cancer: A genetic abnormality which protects against breast cancer?]. / Cancer du sein et trisomie 21 : une anomalie génétique qui protège contre le cancer du sein ?

INTRODUCTION: Trisomy 21 (T21) is the most common chromosomal abnormality and one of the main causes of intellectual disability. The tumor profile of T21 patients is characterized by the low frequency of solid tumors including breast cancer. METHODS: The objective of this work was to analyze the literature to find possible clues for the low frequency of breast cancer in T21 persons with a focus on one hand to the various risks and protective factors against breast cancer for women T21, and on the other hand to changes in the expression of different genes located on chromosome 21. RESULTS: T21 women have hormonal and societal risk factors for breast cancer: frequent nulliparity, lack of breastfeeding, physical inactivity and high body mass index. The age of menopause, earlier in T21 women, has a modest protective effect against breast cancer. The low rate of breast tumors in T21 women is probably mainly linked to the reduced life expectancy compared to the general population (risk of death before the age of onset of the majority of breast cancers) and the presence of a third chromosome 21, characterizing the disease. It might lead to the increased expression of a number of genes contributing directly or undirectly to tumor suppression, decreased tumor angiogenesis and increased cell apoptosis. Moreover, changes in the mammary stroma of persons T21 could have an inhibitory role on the development of breast tumors. CONCLUSION: The low frequency of breast cancers for T21 patients may not only be explained by hormonal and societal factors, but also by genetic mechanisms which could constitute an interesting axis of research in breast cancer.

Mechanistic insights into the antileukemic activity of hyperforin.

Hyperforin is a prenylated phloroglucinol present in the medicinal plant St John's wort (Hypericum perforatum). The compound has many biological properties, including antidepressant, anti-inflammatory, antibacterial and antitumor activities. This review focuses on the in vitro antileukemic effects of purified hyperforin and related mechanisms in chronic lymphoid leukemia (CLL) and acute myeloid leukemia (AML) - conditions that are known for their resistance to chemotherapy. Hyperforin induces apoptosis in both CLL and AML cells. In AML cell lines and primary AML cells, hyperforin directly inhibits the kinase activity of the serine/threonine protein kinase B/AKT1, leading to activation of the pro-apoptotic Bcl-2 family protein Bad through its non-phosphorylation by AKT1. In primary CLL cells, hyperforin acts by stimulating the expression of the pro-apoptotic Bcl-2 family member Noxa (possibly through the inhibition of proteasome activity). Other hyperforin targets include matrix metalloproteinase-2 in AML cells and vascular endothelial growth factor and matrix metalloproteinase-9 in CLL cells - two mediators of cell migration and angiogenesis. In summary, hyperforin targets molecules involved in signaling pathways that control leukemic cell proliferation, survival, apoptosis, migration and angiogenesis. Hyperforin also downregulates the expression of P-glycoprotein, a protein that is involved in the resistance of leukemia cells to chemotherapeutic agents. Lastly, native hyperforin and its stable derivatives show interesting in vivo properties in animal models. In view of their low toxicity, hyperforin and its derivatives are promising antileukemic agents and deserve further investigation in vivo.

[Sensory disorders screening in learning disabilities]. / Interprétation du dépistage sensoriel dans les troubles des apprentissages ?

Inserm French collective expert's report describes sensory disorders screening. However, the causality link with learning disorders remains questionable. In auditory disorders, there are high-level proof recommendations: early and intensive treatment improves language development, at least partially. For visual disorders, consensus conferences recognize their high frequency in learning disorders but there is no proof of a direct causality link. Currently, in learning disorders, orthoptic treatment is not recommended as a specific therapy. In France, despite medical ignorance about orthoptic assessment, absence of reference values and lack of therapy benefits evaluation, orthoptic treatment is usually prescribed, without any objective criteria. This article makes a literature review concerning the link between learning and sensory disorders. It also describes a typical orthoptic assessment with vision and optic musculature evaluation, and reports its results in a prospective comparative study in three populations (controls, dyslexic and Developmental Coordination Disorders [DCD] children). Strabismus or binocular vision disorders are frequent in DCD. Combined ocular motor function is almost constantly disturbed in DCD (90 %), whereas 34 % of dyslexic children and only 13 % of controls are concerned. Visual disorders are therefore present in learning disorders but also in normal population. Orthoptic assessment results must be interpreted in a multidisciplinary evaluation context.

[Prophylactic prescription of vitamin D in France: national multicenter epidemiological study of 3240 children under 6 years of age]. / Prescription prophylactique de la vitamine D en France : enquête épidémiologique multicentrique nationale chez 3240 enfants de moins de 6 ans.

AIMS: The aim of the study was to assess compliance with the current recommendations of prophylactic prescription of vitamin D via a multicentric cross-sectional epidemiological survey of 3240 children under 6 years of age. METHOD: Parent questionnaires and data from the health records of children presenting to the emergency departments of 25 teaching hospitals and hospital centers provided information on the children's characteristics, their prescriptions, and other vitamin D intake. Based on the currently applicable recommendations, intakes of 600-1,200 IU/day - 900-1500 IU/day for children with pigmented skin and/or premature and/or hypotrophic children - are considered adequate. RESULTS: In 1606 infants, 9.8% of the prescriptions were below and 23.7% were above the recommendations; in 1256 children between 18 months and 5 years of age, 53.4% of the prescriptions were below and 5.1% were above the recommendations. Children at risk, those from the southern half of France, and those between 18 months and 5 years of age were more likely to receive a prescription below the recommendations; their risk of receiving a prescription above the recommended guidelines was smaller. Of the children aged between 61 and 71 months, 85% had not received any prescription at all during the previous 12 months. These results were compared with the laboratory data collected from a subsample of children. There was a significant correlation between the adequacy of the prescription and the biological vitamin D status both for 25-hydroxyvitamin D (25-OH-D) serological concentrations and for calciuria. CONCLUSIONS: Only 66.6% of the prescriptions in children between 0 and 18 months of age and 41.5% in children between 19 months and 5 years of age comply with the recommendations; 53.4% of the prescriptions in the latter age group are below the current recommendations.

Design of novel BH3 mimetics for the treatment of chronic lymphocytic leukemia.

Impaired programmed cell death is an important factor in the pathogenesis of chronic lymphocytic leukemia (CLL) and in the development of resistance to chemoimmunotherapy. Hence, the reactivation of apoptotic processes is likely to be a pertinent strategy for circumventing this resistance. Proteins from the Bcl-2 family are critical elements in defective apoptosis. Some compounds induce the apoptosis of CLL cells ex vivo by downregulation of prosurvival members of this family (for example, Bcl-2 and Mcl-1), whereas others act by upregulation of proapoptotic Bcl-2 homology (BH) 3-only members (for example, Noxa and Bim). The concept of BH3 mimetics was prompted by the fact that BH3-only proteins are specific antagonistic ligands of prosurvival Bcl-2 family members. This led to the design of small molecules capable of inhibiting the activity of prosurvival Bcl-2 proteins and inducing apoptosis in leukemia cells in vitro and antileukemic effects in animal models. Several putative or actual BH3 mimetics are currently being trialed in the clinic. Two novel BH3 mimetics that can specifically bind to and antagonize Mcl-1 (a crucial antiapoptotic factor in CLL) have recently been discovered. The evaluation of this type of compound's clinical impact in CLL can now be considered.

[Attention deficit disorder: multidisciplinary observational study over 1 year]. / Le trouble déficitaire de l'attention, avec ou sans hyperactivité (TDA/H) : une approche pluridisciplinaire longitudinale croisée de 36 enfants.

INTRODUCTION: In France, attention deficit disorder (ADHD) has traditionally met with two opposing approaches (biological and psychoanalytic). This conflict led us to conduct a multidisciplinary observational study, on a group of 36 children over a period of 1 year. METHODS: Thirty-six children with ADHD diagnostic (DSM IV), not treated by MPH were included. Initial "multi-field" evaluation (T0) consisted of: neuro-paediatric consultation (Conners questionnaire, Child Behaviour Checklist, reading and writing scores by French tests); semi-structured child psychiatric interview (DSM-IV axis I), structural hypothesis (CFTMEA), existence of narcissistic fragility, parents/child interactions; neuropsychological standardized evaluation (attention and executive functions); psychodynamic interview and projective tests (Rorscharch, CAT or TAT). A therapeutic project is proposed combining MPH and psychotherapy according to the results. A new evaluation 1 year later (T1) included a consultation and a neuropsychological evaluation. RESULTS T0: All parental questionnaires appreciating attention deficit and hyperactivity/impulsivity were significantly pathological. The neuropsychological evaluation showed usual characteristics of ADHD with individual differences. The psychiatric evaluation revealed the frequency of comorbidity in axis I (23% of children with more than two diagnoses, 57% with anxiety disorder, 23 and 3% with oppositional and conduct disorder). FOLLOW UP (T1): Thirty-one children were re-examined (20 treated by MPH and 11 not treated because of parental refusal or particular psychopathological situations). Psychoanalytical psychotherapy, proposed to 28 children, was undertaken with only 19. An improvement in scores for attention and executive tests was registered only in the treated group. DISCUSSION: The tests confirm deficits of attention and executive functions without correlation with the scores of questionnaires, underlining the need for a neuropsychological evaluation to objectify attention disorders. Projective tests refine and enrich psychiatric evaluation and showed that half of the children had borderline organization. However, structural hypotheses were heterogeneous, suggesting the need for specific therapeutic projects to be devised according to each child. The treated children were the only ones to improve attention deficit. On the other hand, the scores of anxiety are not improved by MPH, emphasizing the indications of psychotherapy if comorbidity is present. Psychotherapeutic care was carried out only among part of the population, because of parental reservations, exacerbated by differences of opinion among professionals and lack of access. CONCLUSION: This study is innovative, providing precise data on ADHD from a multidisciplinary perspective. Psychopathological comorbidity is high in this population, so the concept of ADHD cannot be limited to a cognitive point of view. These elements and doubts regarding the efficacy of behavioural therapies suggest the need for a rigorous evaluation of analytical psychotherapies independent of MPH to treat attention deficit.

[Dyslexia: clinical characteristics]. / Clinique de la dyslexie.

Dyslexia is characterized by a severe, persistent reading disorder occurring in an intelligent child. In the large field of learning disabilities, dyslexia is related to a cerebral dysfunction well described with Imagery and genetic studies. Nevertheless the diagnosis of dyslexia cannot be done by another way than clinical symptoms. Optimizing the management of children with dyslexia is a critical issue and is now possible, thanks to the improvement of neurosciences data and the mobilization of the key stakeholders. The knowledge of the precise symptoms is essential in order to lead the child's doctor able to improve coordination and harmonization of teaching and care and guidance of parents.

[Evolution of competence in reading, spelling and comprehension levels in low socioeconomic environments and impact of cognitive and behavioral factors on outcome in two years]. / Evolution des compétences en lecture, compréhension et orthographe en environnement socioéconomique défavorisé et impact des facteurs cognitifs et comportementaux sur le devenir à deux ans.

BACKGROUND: The prevalence of poor reading skills is particularly high among children from low socioeconomic backgrounds, but no longitudinal studies have been conducted so far in France to determine whether poor reading in a socioeconomically challenged population is persistent and warrants preventive action. DESIGN: One hundred and fifty-four children were divided into three groups according to their reading skills: poor, intermediate and typical readers. They were followed over a period of 2 years. Reading levels, spelling and comprehension were assessed by standardized measurement scales in order to determine reading outcome and predictive variables. RESULTS: The reading skills in each group progressed at similar rates, but the differences between the three groups remained relatively constant over the 2 years. The gap between good and poor readers actually increased for the poorest readers. Spelling scores followed a similar pattern and remained weak. Comprehension scores followed a different pattern. Most of the initially poor readers with low comprehension scores almost caught up and reached the level of the typical readers. The best predictive variables of reading and spelling outcome were phonological awareness, rapid naming and attention deficit. The strongest predictive variables for comprehension were IQ, lexical level and attention. CONCLUSIONS: Our results confirm the relative stability of reading measurement across time in poor readers from low socioeconomic backgrounds. Their behavior are similar to the classic dyslexic population. The predictive variables are different depending on whether reading or spelling or comprehension is considered. These results provide a clear agenda for preventive literacy action in children with low socioeconomic levels (SES): phonological decoding and oral language skills in early grades, and screening and treatment of attention disorders.

[Specific language impairment and electroencephalogram: which recommendations in clinical practice? A cohort of 24 children]. / Troubles spécifiques du langage oral et électroencéphalogramme : quelles indications ? Quelle interprétation ? A propos d'une cohorte de 24 enfants.

AIM OF THE STUDY: Electroencephalographic recording (electroencephalogram [EEG]) is frequent in specific language impairment (SLI), whereas the relations between epileptiform activity (EA) and language disorders remain uncertain and the therapeutic approach undetermined. The aim of this prospective study was to clarify EEG indications and interpretation in SLI. METHODS: We present a prospective study of cognitive (speech-language measures, psychological assessments) and electroencephalographic data on 24 children (20 males, 4 females; mean age: 4 years 5 months; range: 3 years to 4 years 8 months) with a diagnosis of SLI, defined as a pathologic score on at least 2 speech-language measures and IQ performance of at least 80 points, within epileptic seizures. All participants had an EEG after partial deprivation of sleep at night. When nonsporadic EA was found, 24-h EEG was performed. Antiepileptic treatment was prescribed depending on the frequency of discharges and the SLI profile. The follow-up lasted 2 years. RESULTS: All patients reached stage II sleep during their EEG. Seven children had abnormal electroencephalography results, including 5 children with EA. Two patients with mixed SLI prevailing on expression presented a left centrotemporal spike focus on EEG becoming subcontinuous during sleep. In the first case, the language progressed without antiepileptic treatment. The 2nd case was treated with ethosuximide; the EEG normalized on subsequent recordings, but the language disorder remained severe. The lexical and syntactic understanding and syntactic production scores were not different for children presented EA (5 cases) or without (19 cases) (Wilcoxon's test). Finally, the progression of the various linguistic skills was similar whether or not the children had EA (p<0.1). CONCLUSION: Abnormal electroencephalographic activity is more frequent in SLI than in normal children. It can be seen in all types of SLI but preferentially in the mixed forms. The longitudinal systematic evaluation of all the children with or without EA has never been reported in the literature, which confirms that there is no parallel between EEG progression and language development, contrary to Landau-Kleffner's syndrome. Systematic EEG recording is not recommended in SLI. It is indicated in cases of fluctuation or stagnation of language development or if there is a family history of cognitive disorders or epilepsy. Antiepileptic treatment is justified in cases with fluctuation or stagnation in language development after 6 months of progression associated with frequent EA. However, when the EA is particularly diffuse and dense, an additional moderate aggravating effect on language development cannot be eliminated. The method most likely to clarify this question is to compare a child's baseline phase followed by a treatment phase, with the same double follow-up.

Types I and II interferons upregulate the costimulatory CD80 molecule in monocytes via interferon regulatory factor-1.

CD80/B7.1 expressed on monocytes plays a prominent role in the activation of T cell-mediated immunity and its level is reduced in monocytes from cancer patients. Type I (alpha/beta) and type II (gamma) IFNs are widely administered as adjuvant therapy. We show here that both classes of IFNs upregulate CD80 mRNA and protein in primary monocytes ex vivo. The stimulatory action of IFN-alpha/beta on CD80 is accompanied by the activation of both interferon regulatory factors IRF-1 and IRF-7, whereas IFN-gamma stimulating effect is associated only with IRF-1 induction. IFNs concomitantly upregulate the transcription of CD40 costimulatory molecule whose activation is known to require IRF-1. In monocytic U937 cells, IRF-1 is activated by IFN-gamma but not by IFN-alpha/beta, whereas it is the reverse for IRF-7; in the latter cells, only IFN-gamma is capable of stimulating CD80 transcription emphasizing the essential role of IRF-1. Moreover, siRNA against IRF-1 prevents IFN-gamma-mediated CD80 activation. In AML cells, IFNs upregulate CD40, CD80 and IRF-1 in the FAB-M4/M5 subtypes but not in the less differentiated M1/M2 subtypes. Monitoring the expression of CD80 on AML cells and its modulation by IFNs could help to predict the patients more susceptible to benefit from therapeutic strategies aimed at eliciting specific T cell responses to leukemia-associated antigens.

[Deficits in reading acquisition in primary school: cognitive, social and behavioral factors studied in a sample of 1062 children]. / Troubles d'acquisition de la lecture en cours élémentaire : facteurs cognitifs, sociaux et comportementaux dans un échantillon de 1062 enfants.

BACKGROUND: Reading impairment is the major learning disability in children. While research on illiteracy has mainly been conducted from a sociological perspective, research on dyslexia has typically been studied from a cognitive-linguistic perspective. Studies that jointly investigate sociological, behavioral and cognitive factors in predicting reading outcome are rare and limited to English-speaking populations. The goal of the present study was to screen second grade children with reading impairment in French urban elementary schools and to pin down the factors that explain the various facets of reading failure and success. METHODS: A total of 1062 children from 20 different schools in the city of Paris participated in the study. Different aspects of reading were assessed individually for children with a suspected impairment in reading acquisition. Subsequently, 131 poor readers and 50 typically developing readers were matched for sex, age, and school. For these children, medical, cognitive, behavioral and individual socioeconomic data were obtained. Group differences were examined and multiple regression analyses were conducted to examine how much variance in reading was explained by the various variables. RESULTS: The prevalence of poor reading skills in grade 2 was highly influenced by neighborhood socioeconomic status (SES) (ranging from 3.3% in high SES to 20.5% in low SES areas). Among the SES variables, employment of the father was a significant predictor of poor reading. Among the cognitive variables, phonological awareness and rapid naming were the most significant factors, much more than verbal or nonverbal intelligence. Among the behavioral variables, attention was an important factor but not externalized symptoms. Multiple regression analyses showed that reading outcome was best predicted by phonological awareness skills and attention deficits. CONCLUSION: The majority of children with reading disability come from low SES areas. As in the English literature, the most robust predictor for reading impairment is phonological awareness, even when SES is taken into account. In addition, attention deficits seemed to aggravate reading impairments for children with weak phonological awareness skills. Successful early prevention should focus on reinforcing phonological awareness, recoding and attention skills.

[The rapid development of child neuropsychology]. / L'essor de la neuropsychologie de l'enfant.

The past few years have seen important progress and new developments in the field of child neuropsychology. Children can exhibit acquired or learning disorders, but in all cases such deficits take place in a developmental trajectory that requires taking into account cerebral maturation and plasticity processes. Child neuropsychology finds its specificity in the perspective of developmental neuropsychology and has close connections with health and education. This article focuses on two pathologies - childhood epilepsies and developmental dyslexia - that highlight the recent progress in this specialty and its perspectives.

Apoptotic effects on B-cell chronic lymphocytic leukemia (B-CLL) cells of heterocyclic compounds isolated from Guttiferaes.

A series of 10 heterocyclic compounds purified from Allanblackia were tested on two B cell lines, ESKOL and EHEB, and on cells from B-CLL patients. Several molecules inhibited the proliferation of both cell lines and promoted apoptosis of B-CLL cells through different mechanisms, some of them elicited a dissipation of the mitochondrial transmembrane potential, other triggered caspase-3 activation and cleavage of the inducible nitric oxide synthase. Blood mononuclear cells and B-lymphocytes from healthy donors appeared less sensitive than B-CLL cells. These results indicate that these molecules may be of interest in the development of new therapies for B-CLL.

[Study of causal factors of reading impairment in a sample of 1062 7 to 8-year-old children]. / Etude des facteurs liés aux difficultés d'apprentissage de la lecture. A partir d'un échantillon de 1062 enfants de seconde année d'école élémentaire.

OBJECTIVE: From an original large sample of 1062 7 to 8-year-old children, reading skills were assessed and found to be highly linked with socioeconomic status (SES). The purpose of the present study was to further determine underlying medical, sociocultural, cognitive and behavioural factors explaining the diversity of reading skills and the influence of SES. METHOD: Individual testing among low-SES children identified 100 poor readers, 50 typical readers and 31 children with intermediate reading scores. All 3 groups underwent a thorough assessment, including a medical evaluation, a full cognitive battery, a structured parental interview and behavioural questionnaire. Logistic regression was used to demonstrate the variables predicting reading score outcome. RESULTS: None of the medical factors studied was statistically related to reading scores. Due to the methodology buffering the impact of SES sociocultural variables, such as parental levels of education, parental occupation, as well as familial income were weak, but statistically significant predictors. The strongest variables were phonological abilities and symptoms of attention disorders. In a final regression model, phonological awareness, level of mother's education and attention explained the differences in reading skills. CONCLUSIONS: These results, which are unique in France, are similar to existing data in the literature. They support the need to conceptualize an early screening programme to detect reading difficulties and to promote an intervention based on phonological processing and decoding in low-SES environments.

[Prevalence of reading disabilities in early elementary school: impact of socioeconomic environment on reading development in 3 different educational zones]. / Prévalence des troubles d'apprentissages du langage écrit en début de scolarité : l'impact du milieu socioéconomique dans 3 zones d'éducations distinctes.

OBJECTIVE: Socioeconomic status (SES) has a known influence on academic achievement. Most studies, however, were conducted in English-speaking countries. Because recent cross-linguistic studies suggest that reading English is much harder to learn than reading other languages, an epidemiological study was conducted in French investigating the impact of socioeconomic background on early reading development. DESIGN: One thousand and twenty second-grade children (476 girls and 544 boys) from 20 different schools participated in the study. Approximately 1/3 of the children lived and were schooled in a high SES area, 1/3 in an intermediate SES area, and one final third in a very low SES area. Assessment of reading, writing and mathematical skills was conducted initially in small groups. Children with suspected learning difficulties were further tested individually. Forty-two children of equivalent age who repeated the first grade received similar individual testing. RESULTS: Average reading scores were in accordance with chronological age, without gender differences. Children from low SES schools had academic performances significantly lower than their peers. Boys exhibited superior arithmetic skills than girls. A significant reading delay was observed in 12.7% of children. The prevalence of poor reading was highly correlated with the area of schooling, varying from 3.3% in the high SES area to 24.2% in low SES area. CONCLUSION: The high rate of children from our sample with a significant delay in reading depended on general socioeconomic environment. An understanding of the origin of such differences is mandatory for defining and coordinating preventive actions and appropriate interventions.

[Heart and freezer: about one case of hypereosinophilia and coronary spasm]. / Coeur et congélateur: a propos d'un cas d'hyperéosinophilie et de spasme coronaire.

We report the case of a 41-year-old woman, non-smoker, without cardiovascular risk, hospitalised for acute ST elevation myocardial infarction. The coronarography showed no significant coronary stenosis and a methylergometrine test performed was positive. After the discovery of a moderate chronic hypereosinophilia, a review of the literature about eosinophile and coronary pathology was realised in order to make a link between hypereosinophilia and coronary spasm.