[Impact on parents of cerebral palsy in children: a literature review]. / Impact sur les parents de la paralysie cérébrale chez l'enfant : revue de la littérature.

Cerebral palsy is the commonest cause of motor impairment in childhood. Parents of children with this particular neurodevelopmental disorder face many problems encountered by disabled children's parents. The aim of the present paper is to report the current knowledge on this parental impact, highlighting consensus and disagreement. A literature search was conducted using the key words "Cerebral palsy" and "Parents/Father/Mother" and "Adapt/Adjust/Cost/Economic/Impact/Well-being" in the Medline and PsycInfo databases searching for articles published between 1989 and 2009. Seven parental impact dimensions were distinguished: time spent, occupational restrictions, social relationships, family relationships, psychological well-being, physical health, and financial burden. Of 40 selected references, the studies were mostly cross-sectional, although longitudinal surveys highlighted the causal relationship between factors. Despite various methodologies, this review confirms that parents of CP children have greater risk of experiencing a sense of burden than parents of typically normally developing children. Time spent caring for the child appears to be an important factor that depends on the child's autonomy. The 7 impact dimensions seem to be related to each other and to child's and caregiver's characteristics. The severity of motor impairment is not unanimously viewed as a worsening factor: however, the child's behavioral problems influence the impact experienced by the parents. The level of intellectual impairment also has a negative influence on family relationships and on the parent's psychological well-being. The child's developmental stage seems to be related to the level of parental impact, but there is no agreement on the dimensions involved. We also observed that the mother and father do not experience this situation in the same way, probably because of the role played by each one in the family. The current literature lacks data on caregiver characteristics, identifying families at risk of burden, and the environmental context that would allow for a less negative impact on parents. In addition, the tools measuring the impact lack standardization. No questionnaire covering all 7 dimensions exists, but useful validated questionnaires for different dimensions were identified. We consider that the caregiver's occupation and physical health needs further research. The current knowledge is insufficient for proposing an overall model taking all the dimensions into account. Research is needed before a complete model of the CP child's impact on parents can be tested in view of providing guidelines to professionals for identifying families with a risk of maladaptation and suggesting solutions to decrease the negative impact.

Mathematical modeling in genetic networks: relationships between the genetic expression and both chromosomic breakage and positive circuits.

The human genome with its 23 pairs of chromosomes, is the result of evolution. This evolution has been ruled by the mutation process and also by the physiological and pathological reorganization of the genomic material inside or between the chromosomes, which are conditioning the genomic variability. This reorganization is starting at singular points on the short or long chromosomic arms, called crossing-over, or translocations, insertions, break points. In this paper, we will show that these points, also called weak points or hot spots of the genome are correlated, independently of their origin. In addition, we will give some properties of the genetic interaction matrices in terms of attractors of the genetic expression dynamics.

HC Forum: a web site based on an international human cytogenetic database.

Familial structural rearrangements of chromosomes represent a factor of malformation risk that could vary over a large range, making genetic counseling difficult. However, they also represent a powerful tool for increasing knowledge of the genome, particularly by studying breakpoints and viable imbalances of the genome. We have developed a collaborative database that now includes data on more than 4100 families, from which we have developed a web site called HC Forum (http://HCForum.imag.fr). It offers geneticists assistance in diagnosis and in genetic counseling by assessing the malformation risk with statistical models. For researchers, interactive interfaces exhibit the distribution of chromosomal breakpoints and of the genome regions observed at birth in trisomy or in monosomy. Dedicated tools including an interactive pedigree allow electronic submission of data, which will be anonymously shown in a forum for discussions. After validation, data are definitively registered in the database with the email of the sender, allowing direct location of biological material. Thus HC Forum constitutes a link between diagnosis laboratories and genome research centers, and after 1 year, more than 700 users from about 40 different countries already exist.

Cooperation of selection and meiotic mechanisms in the production of imbalances in reciprocal translocations.

We have used data from chromosomally unbalanced offspring observed at birth, as well as data from sperm chromosome analysis, to study the meiotic segregation of reciprocal translocations. Using data from a total of 1,597 unbalanced children, we have observed an excess in maternal origin for all modes of imbalance. This excess is particularly marked for the 3:1 unbalanced mode, for which we have also observed a maternal age effect, indicating a close relationship with autosomal trisomies. In addition, a statistical analysis of data from 34 different published studies using sperm chromosome analysis has demonstrated that factors which, for reasons of viability, produce a predisposition for a particular mode of imbalance at birth also appear to favor meiotic production of this type of imbalance. Thus the production of unbalanced gametes of a particular type is influenced by the size of the imbalance.

Cartographic study: breakpoints in 1574 families carrying human reciprocal translocations.

Reciprocal translocations (rcp) are among the most common constitutional chromosomal aberrations in man. Using a European database of 1574 families carrying autosomal rcp, a cartographic study was done on the breakpoints involved. The breakpoints are non-randomly distributed along the different chromosomes, indicating "hot spots". Breakpoints of rcp that result in descendants that are unbalanced chromosomally at birth are more frequent in a distal position on chromosomal arms, and 65% of them are localised in R-bands. Among the R-bands, bands rich in GC islands and poor in Alu repetitive sequences are more frequently the site of breakpoints, as well as bands that include a fragile site. This result suggests that the variation in degree of methylation in GC islands could be involved in chromosomal breakage and hence in chromosomal rearrangements. The heterogeneity of the human chromosomal structure has been demonstrable by metaphase banding techniques since 1970. In contrast to G-bands, R-bands are sites of high gene concentration (Korenberg et al. 1978), are relatively rich in cytosine plus guanine (GC), and in Alu repetitive DNA sequences (Korenberg and Rykowski 1988). More recently Holmquist (1992) has proposed four types of R-bands, depending on their relative richness in GC and Alu DNA sequences. R-bands rich in GC correspond almost exactly to T-bands (Dutrillaux 1977). They contain 65% of all genes while they represent only 15% of the genome (Holmquist 1992). The aim of this study is to analyse the distribution of the breakpoints along chromosomes from a European database of autosomal rcp in order to relate it to the specificity of different chromosomal regions.

[Human familial autosomal reciprocal translocations]. / Les translocations réciproques autosomiques familiales humaines.

Reciprocal translocations are one of the most frequently observed structural chromosome abnormalities. They are defined by a segment exchange between two non-homologous chromosomes. A great number of different translocations exist since any chromosome can be involved in the translocation and the position of the breakpoint can vary. Though generally silent these translocations can be expressed in the form of reproduction failure or, more seriously, as offspring showing mental retardation/malformation syndromes. Since the risk of malformation varies from one translocation to the next, genetic counselling and prenatal diagnosis strategies should be adopted to suit the particular malformation risks of each individual translocation. This is currently not the case. Different prediction methods (for the most probable mode of unbalance at birth, the risk of unbalance at term) are presented. A computer system, called Reci-Conseil brings these different functionalities together to create a new aid for genetic counselling. The data base on which it is founded (approx 2000 families) offers interesting perspectives for genomic mapping of partial trisomies and monosomies.

Viability thresholds for partial trisomies and monosomies. A study of 1,159 viable unbalanced reciprocal translocations.

From a data base of 1,590 independent families with autosomal reciprocal translocations, 1,159 viable unbalances were studied and the lengths of their trisomy/monosomy segments measured according to the method proposed by Daniel. About 5% of cases were found not to comply with Daniel viability criteria. The thresholds of viability vary with the mode of unbalance and with the sex of the carrier. Thus, new viability criteria are proposed as a guide for genetic counseling and prenatal diagnosis.

Logistic regression model to estimate the risk of unbalanced offspring in reciprocal translocations.

The aim of this study was to estimate the risk of viable unbalanced offspring for a parental carrier of reciprocal translocation. On a large computerized database of reciprocal translocations we used logistic regression to model this risk. The status of the progeny is the outcome variable. Explanatory covariates are cytogenetic characteristics of the translocation, age and sex of the parental carrier, and potential viability of the gametes. The results obtained by the logistic model demonstrate the important role of certain variables such as the sex of the parental carrier and the R band length of the translocated segments. Within the group of lower risk (risk of viable unbalanced offspring less than 5%), 97% of the individuals are correctly classified with this model. For this group, the choice prenatal diagnosis can be best discussed by considering both the risk for viable unbalanced offspring and the risk of induced abortion following prenatal diagnosis.

Human reciprocal translocations: is the unbalanced mode at birth predictable?

Two methods of prediction for the risk of unbalance at birth were tested on a large data base of reciprocal translocation (1376 families): the pachytene diagram predictive method (PDP method) and the discriminant method (D method). These method succeeded in correctly predicting the segregation mode in 66% of the data for the PDP method and in 80% of the data for the D method. The quality of chromosome material (in particular R bands) must be taken into account for more accurate prediction. Some difficulties still exist in predicting the 3:1 tertiary segregation mode, which can frequently be incorrectly classified as the adjacent 1 mode.

Human reciprocal translocations: a new computer system for genetic counseling.

A new computer system for genetic counseling in reciprocal translocations is described. This system, namely RCPc (RCP counseling) is a knowledge base extracted from a data base called SCD (Structural Chromosome Data) which contains 1376 families carrying reciprocal translocations. RCPc gives key information for each translocation which allows an evaluation of the risk of unbalance at birth and a prediction of the characteristics of potential unbalances. This information could provide a useful basis for deciding whether a prenatal diagnosis is required and if so, the preferred sampling method i.e. amniocentesis or chorionic villus sampling (CVS).

Value of cytoprognostic classification in breast carcinomas.

Two hundred and four cases of breast carcinoma were classified according to cytological features, and these were related to prognosis. A disease free interval of seven years was 95% for patients with grade I, 70% for those with grade II, and 45% for those with grade III tumours. The risk of recurrence was also related to tumour size and the presence or absence of steroid receptors in the tumour. Cytological classification of breast carcinoma based on fine needle aspiration provides valuable information concerning the prognosis of patients, which is relevant to their clinical management.

[Importance of the systematic cytologic examination of breast secretions: 60 cancers diagnosed in 2120 discharges examined]. / Intérêt de l'examen cytologique systématique des sécrétions mammaires: 60 cancers diagnostiqués sur 2 120 écoulements examinés.

The systematic collection of breast secretions by manual expression of the breast and nipple in 2 120 patients examined for breast diseases has led to the following results: 529 (25%) disclose epithelial papillary hyperplasia, 136 of which underwent surgical control. Epithelial hyperplasia without cellular atypias was found in 9 fibroadenomas, 42 fibrocystic diseases, 29 papilloma/papillomatosis and 21 cancers. Atypical or malignant hyperplasia was observed in 42 cases. Out of 60 cancers, thus investigated, 31 (51%) had malignant cells in such induced nipple discharge, 8 (13%) atypical cells and 21 (35%) concomitant papillary hyperplasia. Systematic cytological examination of breast secretion allows to control intraductal epithelial hyperplasia and to eventually disclose malignant tumor.

Tamoxifen-induced fluorescence as a marker of human breast tumor cell responsiveness to hormonal manipulations: correlation with progesterone receptor content and ultrastructural alterations.

The fluorescent binding of tamoxifen to eosin is used on Papanicolaou-stained smears as a marker of cell responsiveness to the antiestrogen molecule. Forty-two cases of human breast carcinomas were submitted to tamoxifen treatment between first diagnosis and surgery (4 to 30 days). Tamoxifen-induced fluorescence is observed in 17 of 42 cases (40%). There is a highly significant correlation between progesterone receptor content of the tumor and cellular fluorescence (0.01 greater than p greater than 0.001). Ultrastructural changes of such tumors (820 cells observed in 28 treated patients and 840 cells in 32 untreated controls) are observed in 42% of treated cells versus 10% of untreated cells. These ultrastructural alterations can be significantly correlated with cellular fluorescence induced by tamoxifen treatment and with progesterone receptor content of human breast cancers. These data suggest that a short pretreatment with tamoxifen before surgery can give useful additional information at the biochemical, cytochemical, and ultrastructural levels regarding cell responsiveness to hormonal manipulation.

Differential nucleolar staining affinity with a modified Papanicolaou staining procedure.

A modified Papanicolaou staining procedure using diluted Harris' hematoxylin with potassium alum is described. Nucleolar staining varies from blue to bright red. This technique has been applied to mammary tumor cell lines in vitro under several conditions of hormonal stimulation known to induce protein synthesis and cell differentiation. Blue nucleoli are observed in control resting cells, while bright red nucleoli are seen after hormonal stimulation.

Long-term tissue cultures of human pleural effusions: a cytological follow-up.

A cytological follow-up was performed on long-term cultures of 53 metastatic pleural effusions and 34 cases of mesothelial hyperplasia. Cells were grown in Leighton tubes with up to 11 changes of cover slip in the same tube. Cell morphology and arrangement was followed for up to 1 year. Morphological criteria are of no use in recognizing malignant cells with any degree of certainty. As to cell distribution, several types of heaping up are observed both in benign and malignant pleural effusions. In malignant cases, patches of cells in an epithelial-like arrangement are seen heaping up from their substrate. They can be recovered from the used medium by cytocentrifugation. Such behavior may explain the numerous unsuccessful attempts to establish epithelial cell lines, as the clusters of epithelial cells are progressively lost in the supernates.

[Short and long term behaviour of pleural effusion cultures. (Report of 200 cases) (author's transl)]. / Comportement "in vitro" à court et a long terme de cultures d'épanchements pleuraux. A propos de 200 cas

Pleural effusions from 200 patients with benign or malignant pleural involvement have been cultured in vitro and observed from 48 hours to 9 months. The morphology and "social behavior" of the different types of cells are described. Mesothelial cells settle down quickly and come into contact with each other by long cytoplasmic processes. The tendency of epithelial malignant cells is to clump and grow in clusters. These "balls" of varying size are freed into the culture medium. Similar clusters may be found in benign effusions showing mesothelial hyperplasia. In case of malignant primary tumor of the pleura, the morphology of cultured cells is similar to that of mesothelial cells. In 3 cases, typical malignant epithelial cells have allowed us to discard the diagnosis of malignant mesothelioma. Discrepancies between conventional cytology and cell culture were found in 13 cases: in 6 cases, positive for malignant cells using conventional cytology, cell culture was negative. In 7 cases with negative routine techniques, cell culture disclosed malignant cells. Large multinucleated syncytia were observed in 15 cultures. They suggest a cytopathic effect similar to that seen in myxovirus infected cells. Correlation with the etiology of pleural effusions in these cases is described.