Prevalence of dental anomalies in French orthodontic patients: A retrospective study.

OBJECTIVES: To investigate the prevalence and gender distributions of dental anomalies in French orthodontic patients. MATERIAL AND METHODS: A retrospective review of the dental files of orthodontic patients was conducted to investigate the frequencies of dental anomalies. Pretreatment intraoral photographs and panoramic radiographs were analyzed. The occurrence rates of various dental anomalies (as determined by the numbers, shapes, structures, exfoliations, and eruptions of teeth) were calculated as percentages and differences in gender distribution using Chi2 and Fisher tests. RESULTS: Five hundred fifty-one patients receiving orthodontic treatment between 2003 and 2013 at a French hospital were included in the study: 45.74% of the patients (n=252) presented at least one dental anomaly. Taurodontism was the most common (15.06%), followed by ectopic eruption (11.43%). Odontoma, macrodontia, fusion, gemination, talon cusp, dentinogenesis imperfecta, regional odontodysplasia, premature tooth eruption, and premature exfoliation were not found. No statistically significant correlations were found between gender and the occurrence of dental anomalies. CONCLUSION: French orthodontic patients exhibit a high rate of dental anomalies, indicating that dental anomalies should be carefully considered in the orodental management of French patients.

Neuropsychological improvement after posterior fossa arachnoid cyst drainage.

PURPOSE: Posterior fossa arachnoid cysts (PFAC) are mostly considered as benign lesions of the cerebellum. Although many studies have shown the major role of the cerebellum in modulating movement, language, cognition, and social interaction, there are few studies on the cognitive impact and surgical decompression of PFAC. METHODS: We present the cases of two brothers successively diagnosed with PFAC and neuropsychological delay. After multidisciplinary discussion with the boys' parents, it was decided to drain these lesions. Clinical signs, cerebral images, and neuropsychological status were assessed on admission and then 1 and 3 years after surgery. RESULTS: At presentation, both children had mild cerebellar signs, associated with cognitive and visual-motor impairments and academic regression. CT scans revealed retrovermian cysts, which were shunted. Post-operatively, both brothers demonstrated improved visual-motor skills and behavior. At follow-up, we observed disappearance of dysarthria and academic delay and significant improvement in cognition especially at the intelligence scale and in language. Fine motor skills had improved but remained slower than the average and writing skills appeared limited. CONCLUSION: Except for PFAC which impair cerebrospinal fluid circulation or which are responsible for a significant mass effect, most PFAC are usually considered as "asymptomatic" and do not require surgical treatment. The two cases reported herein suggest that these lesions might be responsible for some associated but potentially reversible neuropsychological impairment. In the future, clinical assessment should include neuropsychological evaluation to help inform decision for surgical decompression in these children with PFAC.

[Left temporal arachnoid cyst and specific learning disorders associated with Pervasive Developmental Disorders - Not Otherwise Specified (PDD-NOS): contributions of an integrative neuropsychomotor, neuropsychological, psychopathological and neurosurgical approach about a case report in a child (François)]. / Kyste arachnoïdien temporal gauche et troubles spécifiques des apprentissages associés à un trouble envahissant du développement non spécifié (TED-NoS) : apports d'une approche intégrative neuro-psychomotrice neuropsychologique, psychopathologique et neurochirurgicale à propos d'une observation chez un enfant (le cas François).

Left temporal arachnoid cyst and specific learning disorders associated with pervasive developmental disorders - not otherwise specified (PDD-NOS): contributions of an integrative neuro-psychomotor, neuropsychological, psychopathological and neurosurgical approach about a case report in a child (François). With DSM-IV and DSM-IV-TR, the terminology of pervasive developmental disorders (PDD) covers two main categories of infantile disorders: disorders of "strictly" autistic nature and pervasive developmental disorders - not otherwise specified (PDD-NOS). Under the terminology of multiple complex developmental disorder (MCDD), it is proposed to classify children presenting symptoms approaching the psychotic disharmonies and usually diagnosed as PDD-NOS. Such a category of developmental disorders is now included without nosographic distinction in the autistic spectrum in the Diagnostic and Statistical Manual of mental disorders (DSM-V). CASE REPORT: We are reporting a case report of a 6-year-old boy which shows a PDD-NoS/MCDD complex symptomatology type. This child presents multiple disorders: minor neurological signs (soft signs), neuro-psychomotor disorders, developmental coordination disorder (DCD), communication, thought, and regulation of emotions disorders, attention deficit disorders (ADD); in the presence of a high verbal intellectual potential, which makes it difficult to establish a clear diagnosis. A cerebral magnetic resonance imaging (MRI) was carried out due to the presence of minor neurological signs (soft signs) and of neurodevelopmental multiple disorders. The MRI revealed a voluminous arachnoid temporo-polar left cyst with a marked mass effect on the left temporal lobe. DISCUSSION: A neurosurgical intervention allowed to observe the gradual disappearance of the specific symptomatology (in particular soft signs, neuro-psychomotor functions and autistic symptoms) secondary to the interference of the cyst's pressure with intracranial areas involving neurological and psychopathological abnormalities, underlying at the same time the reversibility of the disorders after decompression as demonstrated in some studies. There are always, with a quantitative and qualitative decrease, an emotional dysregulation, a DCD, an ADD as well as impairments in the executive functions. CONCLUSION: This clinical case underlines the necessity of an evaluation in a transdisciplinary way and to follow the developmental evolution of the child in order to focus adapted therapeutics. Furthermore, with neurodevelopmental disorders not specified, it is important to examine the presence of soft signs with standardized neuro-psychomotor assessment, and then, to propose an MRI investigation. To our knowledge, this is the first report in the literature with a school age child of an unusual association between a temporal arachnoid cyst associated with PDD-NOS/MCDD.

Fruit juice authentication by 1H NMR spectroscopy in combination with different chemometrics tools.

To discriminate orange juice from grapefruit juice in a context of fraud prevention, (1)H NMR data were submitted to different treatments to extract informative variables which were then analysed using multivariate techniques. Averaging contiguous data points of the spectrum followed by logarithmic transformation improved the results of the data analysis. Moreover, supervised variable selection methods gave better rates of classification of the juices into the correct groups. Last, independent-component analysis gave better classification results than principal-component analysis. Hence, ICA may be an efficient chemometric tool to detect differences in the (1)H NMR spectra of similar samples, and so may be useful for authentication of foods.

Evolving window zone selection method followed by independent component analysis as useful chemometric tools to discriminate between grapefruit juice, orange juice and blends.

This study investigates the use of high resolution 1H NMR as a suitable alternative to the standard chromatographic method for the determination of adulteration of orange juice (Citrus sinensis) with grapefruit juice (Citrus paradisi) based on flavonoid glycoside content. Fifty-nine orange juices (OJ), 23 grapefruit juices (GJ) and 10 blends (OG), obtained from local retail outlets were used to assess the performance of the 1H NMR method. The work presented here introduces the Evolving Window Zone Selection (EWZS) function that holds promise for the automatic detection of spectral regions tailored to discriminate predefined groups. This technique was applied on the pre-processed 1H NMR spectra of the 92 juices. Independent Component Analysis (ICA) is a good alternative to Principal Component Analysis (PCA) for recovering linearly-mixed unobserved multidimensional independent signals and has been used in this study to build supervised models that classify the samples into three categories, OJ, GJ, OG. The regions containing the known flavonoid glycoside markers were selected as well as another zone containing the signals of sucrose, alpha-glucose and other components that were tentatively attributed. ICA was applied on three different groups of selected variables and showed good results for both discrimination and interpretation of the signals. Up to 97.8% of the juices were correctly attributed. This method gave better results than the commonly used PCA method. In addition, the time required to carry out the 1H NMR analysis was less than half the time of the standard chromatographic method.

Small-animal models for testing macroporous ceramic bone substitutes.

The aim of this study was to compare the bone colonization of a macroporous biphasic calcium phosphate (MBCP) ceramic in different sites (femur, tibia, and calvaria) in two animal species (rats and rabbits). A critical size defect model was used in all cases with implantation for 21 days. Bone colonization in the empty and MBCP-filled defects was measured with the use of backscattered electron microscopy (BSEM). In the empty cavities, bone healing remained on the edges, and did not bridge the critical size defects. Bone growth was observed in all the implantation sites in rats (approximately 13.6-36.6% of the total defect area, with ceramic ranging from 46.1 to 51.9%). The bone colonization appeared statistically higher in the femur of rabbits (48.5%) than in the tibia (12.6%) and calvaria (22.9%) sites. This slightly higher degree of bone healing was related to differences in the bone architecture of the implantation sites. Concerning the comparison between animal species, bone colonization appeared greater in rabbits than in rats for the femoral site (48.5% vs. 29.6%). For the other two sites (the tibia and calvaria), there was no statistically significant difference. The increased bone ingrowth observed in rabbit femurs might be due to the large bone surface area in contact with the MBCP ceramics. The femoral epiphysis of rabbits is therefore a favorable model for testing the bone-bonding capacity of materials, but a comparison with other implantation sites is subject to bias. This study shows that well-conducted and fully validated models with the use of small animals are essential in the development of new bone substitutes.

Relating genotype and phenotype in breast cancer: an analysis of the prognostic significance of amplification at eight different genes or loci and of p53 mutations.

Breast cancer heterogeneity can be related directly to its variability at the genetic level. Thus, tumor genotyping could be a valuable approach to define breast tumor subtypes. It has been shown that it is possible to delineate subgroups of breast tumors according to specific sets of DNA amplifications. The aim of the present work was to study the prognostic significance of these DNA amplifications. We studied DNA amplification at eight genes or loci (AIB1, CCND1, EMS1, ERBB2, FGFR1, MDM2, MYC, and RMC20C001) as well as p53 mutations in a series of 640 breast cancer patients who had not received presurgical therapy and analyzed the correlations with survival DNA amplification was assessed by Southern blotting and was scored positive when exceeding three to five copies. Mutations in the p53 gene were searched by four-color fluorescent single. strand conformational polymorphism, using an automated sequencer. Of the nine genetic alterations tested, four (CCND1, EMS1, FGFR1, and p53 mutations) showed a significant association with reduced disease-free (DFS) and/or overall survival (OVS) in the unselected set of patients by univariate test. Correlations for p53 were found only when selecting mutations in exons 5 or 7. Analysis of node-negative and -positive subgroups of patients showed that MDM2 amplification and p53 mutations bore prognostic significance in node-negative patients, whereas amplification of CCND1, EMS1, and FGFR1 correlated with poor outcome in node-positive patients. Multivariate analysis on an unselected set of patients retained significance for the amplification of EMS1, FGFR1, and MDM2 with DFS, of CCND1 with OVS, and of RMC20C001 with both DFS and OVS. Interestingly, stratified analysis according to nodal status confirmed results obtained in the univariate tests: significance of MDM2 amplification and p53 mutations in node-negative and that of CCND1, EMS1, and FGFR1 in node-positive patients. We also observed an association between the number of genetic alterations observed in a tumor and poor prognosis. Patients with two or more amplified loci had a worsened outcome. Strongly correlating coamplifications such as CCND1 and FGFR1, as well as ERBB2 and MYC, were associated with a significant reduction of patient survival, thus indicating cooperative effects. Our data support the idea that genetic alterations in breast cancer are not only helpful for phenotyping purposes, but can also represent powerful prognostic indicators in the clinical practice.

17q21-q25 aberrations in breast cancer: combined allelotyping and CGH analysis reveals 5 regions of allelic imbalance among which two correspond to DNA amplification.

Chromosome 17q is frequently rearranged in breast cancer. Allelotyping studies have proposed the existence of at least four regions of allelic imbalance (AI). Here we present a study combining allelotyping using 19 CA repeat markers mapping in the 17q21-25 region and molecular cytogenetics (CGH and FISH). Allelotyping was undertaken on 178 pairs of cognate tumor and normal DNA in order to determine the number of regions of AI and define the shortest overlaps. AI ranged from 34-54% of the informative cases according to the marker and, overall, 66% of the tumors presented AI at one of the markers tested. Analysis of the patterns of imbalances revealed at least five common regions of imbalance respectively defined by markers: D17S855, which is intragenic of BRCA1 (SRO 1), D17S1607 (SRO 2), D17S1855 (SRO 3), between D17S789 and D17S785 (SRO 4) and D17S784 (SRO 5). In order to characterize the nature of the genetic events revealed by allelotyping we performed CGH analysis on a subset of 43 tumors presenting variable patterns of imbalance. CGH showed that AI at 17q could represent four different types of genetic events: loss of chromosome 17, gain of 17q, gain of 17q22-q24, loss of 17q11-q21 and/or 17q25-qter. Some of these anomalies could occur concomitantly within the same tumor. Since 35% of the tumors analysed by CGH presented gains, these data indicated that AI at 17q were not solely indicative of losses of genetic material and could also represent DNA amplification. Gains were most commonly observed in the 17q23-q24 regions. This suggested that AI in SRO 2 and SRO 3 corresponded to DNA amplification. To assess this, we isolated BAC clones by PCR screening for markers D17S1607 and D17S1855 and used these in FISH experiments on six breast tumor cell lines and 14 breast cancer specimens. FISH results showed that both D17S1607 and D17S1855 were frequently involved in DNA amplification (8-30 copies). Altogether, our data show that allelotyping can be efficiently used in amplicon mapping. Clinico-pathological correlations indicated that imbalance at 17q preferentially occurred in high grade, PR- and ERBB2 amplified tumors.

Consortium study on 1280 breast carcinomas: allelic loss on chromosome 17 targets subregions associated with family history and clinical parameters.

The pattern of loss of heterozygosity (LOH) on chromosome 17 in human breast cancer is complicated and shows many different regions of loss. In an attempt to narrow down the relevant regions of LOH on chromosome 17, we have studied the deletion pattern and its association with clinical parameters in 1280 breast carcinoma-venous blood lymphocyte pairs. In total, 42 different chromosome 17 loci were investigated, and between 25 and 625 cases were analyzed at each locus. The frequency of LOH observed on the p arm was much higher than that observed on the q arm. The opposite effect was observed in 52 ovarian cancer cases investigated, with less LOH on 17p than on 17q. Patterns of loss consistent with interstitial and terminal deletions, as well as loss of either the p or q arm or monosomy 17 were observed. To determine whether loss at particular loci may be associated with biological features of breast tumors, clinical data including age of onset, family history of breast cancer, tumor histopathology, tumor size, estrogen receptor (ER) status, and occurrence of lymph node or distant metastases were collected for each case. Overall, large-sized, ER-negative, lymph node-positive ductal tumors showed the highest frequencies of LOH, with ER-negative and ductal tumors showing LOH for markers along the majority of the chromosome. Eight regions of chromosome 17 appear to be associated with human breast cancer, two on 17p and six on 17q. These regions were not necessarily in the areas exhibiting the highest frequencies of LOH but were defined by interstitial and terminal deletions in multiple independent cases. Seven of these regions showed statistically significant differences in LOH associated with clinical parameters. These data strongly suggest that loci on chromosome 17 may determine aspects of tumor presentation and disease behavior in human breast cancer and pinpoint candidate tumor suppressor gene loci.

Variation of bcl-2 expression in breast ducts and lobules in relation to plasma progesterone levels: overexpression and absence of variation in fibroadenomas.

Some women with benign breast disease eventually develop breast cancer. The mammary gland undergoes tissue remodelling according to hormonal influences, involving a balance between quiescence, proliferation, and mechanisms of cell death. Proliferation and/or apoptotic events could therefore be investigated to help understand the mechanisms of benign lesion formation and identify mastopathies with a poor prognosis. bcl-2 expression was analysed by immunohistochemistry in 75 benign mastopathies. Protein levels were quantitated with an image analyser in various epithelial structures on frozen sections, including adenoses, fibroadenomas, ductal epithelial hyperplasias, cysts, and apparently normal surrounding lobules and ducts. bcl-2 levels were equivalent in apparently normal lobules and ducts, as well as in cysts and ductal hyperplasias. bcl-2 staining was significantly higher in fibroadenomas, known to be of lobular origin [mean = 10.1, quantitative immunochemistry score (QIC) arbitrary units (AU), n = 19], than in normal lobules (mean = 5.1 AU, n = 43, P = 7 x 10(-5). bcl-2 levels in normal lobules and ducts varied according to the menstrual cycle, being higher during the follicular than the luteal phase (P = 1.8 x 10(-2) and P = 1.7 x 10(-2), respectively). This was further supported by a statistical link (P = 5 x 10(-3) between high levels of circulating progesterone and weak bcl-2 staining in lobules and ducts. This progesterone-dependent variation was absent in fibroadenomas. No statistical correlation was found between bcl-2 expression and circulating levels of oestradiol, and follicle-stimulating or luteotrophic hormones. Although these are only preliminary results, they suggest an influence of progesterone on bcl-2 expression which might be lost in fibroadenomas. A hypothesis is proposed concerning the potential involvement of altered regulation of the apoptotic process in the formation of such benign lesions.

Mapping of DNA amplifications at 15 chromosomal localizations in 1875 breast tumors: definition of phenotypic groups.

DNA amplification is frequent in breast cancer and has been associated with specific clinicopathological parameters and/or worsened course of the disease. In the present work, we were interested in further defining the association linking the occurrence of DNA amplification to the emergence of specific breast tumor phenotype. To this aim, we studied by Southern blotting a total of 1875 breast tumor DNAs with 26 probes mapping at 15 distinct chromosomal localizations. Of the 26 loci tested, 11 loci showed elevated levels of amplification, 9 loci showed occasional and/or low level of DNA copy number increase, and 6 loci showed very rare or no variation. This allowed us to define six amplified domains mapping at 8p12, 8q24, 11q13, 12q13, 17q12, and 20q13.2, respectively. Over 60% of the tumors analyzed presented at least one amplification at one of these localizations. Amplifications often covered large regions of DNA and bore complex patterns involving coamplification of several colocalized markers. Statistical analysis revealed correlations associating DNA amplification with breast tumor phenotype, as well as sets of preferential coamplifications. Based on these correlations, we defined three subsets of breast cancer according to their patterns of DNA amplification. The first subset (group A) was organized around the amplifications at 11q13 and/or 8p12 and was predominantly composed of estrogen receptor-positive tumors and presented a large proportion of lobular cancers. The second subset (group B) was organized around the amplifications of ERBB2 and/or MYC. These tumors were mostly estrogen receptor-negative and of the ductal invasive type. The third subset (group C) corresponded to tumors in which no amplification was detected in the present screen. Tumors in this group were largely diploid and of low histopathological grading.

DNA amplifications at 20q13 and MDM2 define distinct subsets of evolved breast and ovarian tumours.

DNA amplification seems to be particularly frequent in human breast tumours and has been associated with cancer evolution and aggressiveness. Recent data indicate that new events should be added to the list, such as the amplifications at chromosome 20q13 or the MDM2 gene. The present work aimed at determining the incidence and clinicopathological signification of these amplifications in a large series of breast and ovarian tumours. We tested 1371 breast and 179 ovarian tumours by Southern blotting and observed amplification of 20q13 in 5.4% breast and 2.8% ovarian carcinomas, whereas MDM2 was found amplified in 5.3% and 3.8% of breast and ovarian tumours respectively. MDM2 RNA expression levels were analysed in a subset of 57 breast tumours and overexpression was observed in 4/57 (7%) of the tumours. Elevated expression levels coincided with amplification of the gene. In breast cancer, 20q13 and MDM2 amplifications seem to define subsets of aggressive tumours. Indeed, 20q13 was correlated to axillary nodal involvement and occurred preferentially in younger patients (< 50 years). Furthermore, 20q13 correlated, as did MDM2 amplification, to aneuploidy. In parallel, we had also tested our tumour DNAs for amplification of CCND1, ERBB-2 and MYC, which made it possible to test for correlations with 20q13 or MDM2 amplifications. Whereas 20q13 showed a very strong correlation to CCND1 amplification, that of MDM2 was prevalent in MYC-amplified tumours. Interestingly, 20q13 and MDM2 amplifications showed some degree of correlation to each other, which may possibly be owing to the fact that both events occurred preferentially in aneuploid tumours. In ovarian cancer, no statistically significant correlation was observed. However, 20q13 amplification occurred preferentially in stage 3 tumours and MDM2 was correlated to ERBB-2 amplification. This may suggest that in ovarian tumours also, 20q13 and MDM2 amplifications occur in late or aggressive cancers.

Quantification of ERBB2 protein expression in breast cancer: three levels of expression defined by their clinico-pathological correlations.

Activation of the ERBB2 oncogene seems to be an early event in breast cancer progression and prevalent in in situ carcinomas. However, its prognosis value, albeit recognized for node-positive patients, remains controversial for those without apparent nodal involvement. One possible reason for this problem is likely to be the difficulty of defining threshold levels for ERBB2 protein overexpression. ERBB2 protein expression was therefore analyzed in primary invasive breast tumors. Quantification of the gene product by a commercial ELISA test was compared to results obtained by immunohistochemistry and western blotting, as well as to gene amplification status determined by Southern blotting. Correlations between results obtained by the different techniques were highly significant (P value < 10(-6)). Nevertheless, ELISA permitted us to determine three levels of protein expression corresponding to distinct tumor subsets. 1) Tumors with p185/ERBB2 expression levels exceeding 10 U/microgram exhibited in most cases amplification of the gene (83% of cases), DNA aneuploidy (81%) and absence of estrogen receptor (ER) (44%). Such high levels of protein expression were exclusively observed in invasive ductal carcinomas and were prevalent in those showing a significant in situ component. 2) "Intermediate" levels of expression (3-10 U/micrograms) were rarely observed in tumors exhibiting gene amplification (9%), but were preferentially found in cancers of more favorable prognosis (only 49% were aneuploid and 9% estrogen receptor negative). 3) Levels of p185/ERBB2 below 3 U/micrograms were detected in benign mastopathies and, thus, carcinomas presenting such levels were scored ERBB2 negative. Interestingly, invasive lobular carcinomas were rarely ERBB2 positive, and if so, only at intermediate levels. Moreover, our data show a complex interrelationship between p185/ERBB2 expression and ER levels. Indeed, tumors with more than 10 U/micrograms of p185 were prevalently ER, whereas those with p185 ranging from 3 to 10 U presented elevated levels of ER.

Role of RNA structures in c-myc and c-fos gene regulations.

Proto-oncogenes c-myc and c-fos are subjected to a complex set of controls operating both at the transcriptional and post-transcriptional levels. We report here that: (i) antisense transcription occurs at the murine c-myc locus. However, its biological significance remains to be established; (ii) transcription of both genes is regulated in various situations by a block to elongation of nascent RNA chains. In the case of c-myc, the blockade involves a RNA structure whose nature remains unknown; (iii) elements responsible for the high degree of instability of c-myc and c-fos mRNAs reside in their 3' non-coding regions. A U-rich region, reminiscent of that present in the granulocyte-monocyte colony-stimulating factor mRNA destabilizer, is likely to be involved in the rapid degradation of c-fos mRNA; (iv) exon 1 substitution by intron 1-derived sequences lessens or negates the effect of the 3' destabilizer in abnormal c-myc RNAs from Burkitt's lymphomas and mouse plasmacytomas.

Sequence determinants of c-myc mRNA turn-over: influence of 3' and 5' non-coding regions.

Normal c-myc RNAs are very unstable with a half-life of less than 30 min whereas those rearranged in 5', as found in Burkitt's lymphomas and mouse plasmacytomas, are significantly more stable. To learn about the sequence determinants controlling their turnover, we have studied naturally occurring and artificially constructed c-myc RNAs rearranged in 5' or 3'. The first conclusion is that sequences necessary for rapid c-myc RNAs turnover are localized in their 3' untranslated region. The second conclusion is that stabilization of truncated c-myc RNAs in tumors does not result from deletion of the non-coding first exon but rather from its replacement by intronic and/or exogenous sequences. This latter conclusion rests on two lines of evidence: (i) deleting the 5' rearranged sequences from the relatively stable MOPC 315 RNA restores its complete instability (pSV c-myc 1); (ii) reciprocally, appending intron 1 sequences 5' to otherwise unstable germline c-myc exons 2 and 3 have a dramatic stabilizing effect (pIM 0).