Genetics and epidemiology of Wilms' tumor: The French Wilms' tumor study

A complete family history was obtained for 501 patients with Wilms' tumor, treated in departments of pediatric oncology in whole France. The information was collected by self-questionnaire and/or by interview of parents. The proportion of bilateral cases is 4.6% and there are 12 patients (2.4%) with a positive family history of Wilms' tumor. The affected relatives are most often distant and no first degree relative was affected. Apart from the well-known associations with aniridia, hemihypertrophy, genitourinary anomalies, Beckwith-Wiedeemann, and Drash syndromes, there is also a significant excess of congenital heart defects (P = .008) which remains to be explained. Several findings support the bimutational hypothesis such as earlier diagnosis and increased parental age in bilateral cases. No particular anomalies and no increased frequency of childhood cancer were found in patients' relatives. The frequency of Wilms' tumor in relatives was estimated to be less than 0.4% in sibs, 0.06% in unclesand aunts, and 0.04% in first cousins. These figures are very different from those found in retinoblastoma and suggest that the mechanism may be more complex in Wilms' tumor. This conclusion is in agreement with molecular biology studies in tumors and linkage analysis in multiple case families which suggest that more than one locus is involved. © 1992 Wiley-Liss, Inc.     

Modeling interinformant agreement in the absence of a "gold standard"

Epidemiological surveys of child and adolescent mental disorders often rely on multiple informants to get a complete diagnostic picture. A consistent finding in the literature is that different informants often do not identify the same children as being disordered. However, because current strategies for estimating interinformant agreement often involve categorizing children using less than perfectly sensitive and/or specific symptoms, biased estimates of interinformant agreement are likely. The aim of this report was to illustrate how latent class analysis (LCA) can be used to model interinformant agreement in the absence of a "gold standard". The proposed model consists of informant-specific latent variables each made up of two or more latent classes corresponding to different levels of symptomatology. Unlike most previous applications of LCA this model allows us to model the extent to which the prevalence of the disorder is the same across informants; and, in addition, the association between informants. The data set comes from a prospective longitudinal study of 2,264 children from Quebec (1,155 boys and 1,109 girls). In grade 2, teachers and mothers independently rated each child on three physical aggression behavior symptoms. We satisfactorily accounted for the cross-classification of the behavior symptoms by postulating the existence of two latent variables--one for each informant each made up of three latent classes of children: low-, medium-, and high-aggressive. The results showed that the prevalence of low- and medium-aggressive children in the population differed from teacher to mother, but that the prevalence of high-aggressive children did not. We found that the association between teacher and mother was large and positive and did not vary according to the child's physical aggression state or gender; in contrast, the association between physical aggression and gender was not the same for mother and teacher. Limitations and other potential applications of the proposed model are discussed.     

Prognostic significance of angiogenesis evaluated by CD105 expression compared to CD31 in 905 breast carcinomas: correlation with long-term patient outcome

Our purpose was to determine the respective prognostic significance of CD105 and CD31 immunoexpression in node negative patients with breast carcinoma, since angiogenesis induces blood borne metastases and death in carcinomas. CD105 (endoglin) has been reported as expressed by activated endothelial cells and consequently should better reflect neoangiogenesis in malignant tumors. Comparison of CD31 and CD105 immunocytochemical expression was undertaken in a series of 905 breast carcinomas. Results were compared to patients' long-term (median = 11.3 years) outcome. Univariate (Kaplan-Meier) analysis showed that the number of CD105+ microvessels (cut-off 15 vessels) correlated significantly with poor overall survival (p=0.001). This correlation was less significant in node negative patients (p=0.035). The number of CD31+ microvessels (cut-off 25 vessels) similarly correlated with poor survival (p=0.032) but not in the subgroup of node negative patients. Marked CD105 expression also correlated with a high risk for metastasis in all patients (p=0.0002) and in the subset of node negative patients (p=0.001). Similarly metastasis risk in node negative patients correlated with marked CD31 immunocytochemical expression (p=0.02). Multivariate analysis (Cox model) identified CD105, but not CD31 immunoexpression, as an independent prognostic indicator. Our results suggest that: i) in breast carcinomas, immunoselection of microvessels containing activated CD105 labelled endothelial cells is endowed with a stronger prognostic significance, as compared to CD31 vessels labelling; ii) the CD105 immunoexpression may be considered as a potential tool for selecting node negative patients with a poorer outcome and higher metastasis risk; iii) in these patients specific antiangiogenic therapy targeted by anti-CD105 conjugates can be further developed.     

Nocardia veterana isolated from ascitic fluid of a patient with human immunodeficiency virus infection

Nocardia veterana is a recently characterized species within the genus Nocardia, and only three human clinical isolates have been reported for this species. We describe a case of ascitic fluid infection in an immunocompromised patient due to N. veterana. To our knowledge, this is the first report of a Nocardia sp. strain from ascitic fluid and the fourth report of N. veterana isolated from human samples. Chemotaxonomic methods showed the strain to belong to the genus Nocardia, and identification to the species level was done by 16S ribosomal DNA gene sequencing. The antibiotic susceptibility profile of N. veterana is reported here for the second time. The strain was deposited in the Collection of the Pasteur Institute and in the Culture Collection of the University of G?teborg (CIP 107497 and CCUG 46576). The corresponding 16S ribosomal DNA gene sequence is available from the GenBank database under accession number AY149599. A phylogenetic analysis was conducted and showed that N. veterana was most closely related to the recently characterized species Nocardia africana rather than to Nocardia vaccinii, as previously reported.     

Long-term adiposity changes are related to a glucocorticoid receptor polymorphism in young females

Male and female preadolescents and adolescents who participated in phase 1 of the Québec Family Study, and who were retested about 12 yr later, were recruited and subdivided on the basis of a genetic variant within the intron 2 of the glucocorticoid receptor (GRL IVS2-BclI). The increase in sc adiposity over the 12-yr follow-up period in the 4.5/2.3 genotype female subgroup was more than twice that observed in the 4.5/4.5 and the 2.3/2.3 genotype subgroups (P < 0.01). The statistical significance of this difference was essentially unchanged after adjusting for changes, over time, in percent dietary energy as fat, alcohol consumption, and participation in vigorous physical activity. In male subjects, the same trend was found, but it did not reach statistical significance. In conclusion, this study suggests that a significant interaction effect exists between variation in the glucocorticoid receptor gene and body fat gain in female subjects experiencing the transition between adolescence and adulthood. Further research will, however, be necessary to characterize the lifestyle factors promoting fat accumulation, over time, among genetically susceptible individuals.     

Cell therapies for inherited myopathies

PURPOSE OF REVIEW: Cell therapies for inherited myopathies are based on the implantation of normal or genetically corrected myogenic cells into the body. This review summarizes the recent progress in this field, systematized according to the factors important for success. RECENT FINDINGS: In the choice of donor cells, myoblasts derived from satellite cells remain the best choice.Some studies on the population of muscle-derived stem cells in mice suggested that these cells may have some advantages over myoblasts; however, no results supporting this advantage have been presented in a primate model. Recent studies on bone marrow transplantation as a systemic source of myogenic precursors for the treatment of myopathies were disappointing. Concerning donor cell delivery, intramuscular myoblast injection remains the only way that can significantly introduce exogenous myogenic cells into the muscles. A recent study in primates showed some parameters of myoblast injection that could be useful in the human. Progress was made in mice to understand the factors that could favor the migration of the donor myoblasts in the host muscles. Concerning donor cell survival, analysis of immune cell infiltration dynamics allowed a better understanding of the factors implicated in early donor cell death. Progress was made on the control of acute rejection for myoblast transplantation in primates. So far, few mouse experiments have advanced the field of tolerance induction toward myogenic cells. SUMMARY: Myoblast transplantation (intramuscular injection of satellite cell-derived myoblasts) currently remains the only cell-based therapy that has produced promising results in the context of a preclinical model such as the nonhuman primate.     

Treatment of calcifying tendinitis of the shoulder by acetic acid iontophoresis: a double-blind randomized controlled trial

OBJECTIVE: To assess the effects of acetic acid iontophoresis on the treatment of calcifying tendinitis of the shoulder. DESIGN: Double-blind randomized controlled trial. SETTING: Ambulatory academic hospital in Quebec, Canada. PARTICIPANTS: Thirty-six subjects with a calcifying tendinitis of the shoulder. INTERVENTIONS: Subjects were randomized into 1 of 2 groups: physiotherapy during 6 weeks (10 sessions) plus acetic acid iontophoresis for the treatment group (n=18) and sham acetic acid iontophoresis for the control group (n=18). MAIN OUTCOME MEASURES: The Shoulder Pain and Disability Index (SPADI), shoulder range of motion (ROM); and radiologic evaluation of shoulder calcifications. RESULTS: Nine patients dropped out, leaving 27 assessable subjects for analysis. Interim analysis showed that, in both groups, treatment led to improvement, as measured by the SPADI score (P=.004), ROM of the shoulder for abduction (P<.001), internal rotation (P=.001), external rotation (P<.001), and the mean number of calcifications per subject (P=.010). Although no formal significant intervention effects (P=.13) were found for the primary endpoint (SPADI), exploratory analyses suggest a greater improvement in the treatment group (P=.001) than in the control group (P=.33). CONCLUSIONS: Despite a trend toward greater improvement in the SPADI score in the treatment group, the use of acetic acid iontophoresis and physiotherapy for the treatment of calcifying tendinitis of the shoulder did not result in better clinical and radiologic effects than those observed in subjects treated by physiotherapyalone.     

Child abuse: behavioral aspects and other associated problems

Although researchers in psychology and the social sciences will need to continue to identify the behavioral consequences of abuse and treatment strategies, pediatricians may still be the first line professionals to suspect and intercept victims. Remember that, especially in cases where there have been threats or falsification of illness, it is wise to enlist integrated multidisciplinary services to ensure the safety of the child before confronting any potential perpetrators. Physicians have become better trained to be more vigilant in detecting signs of physical abuse, but it seems that psychologic and sexual maltreatment may cause more long-term problems but are more difficult to detect. Although a book by Everett and Gallop is written for mental health professionals, the chapters on why a history of childhood trauma is often missed, recognizing signs and symptoms, and asking about abuse, are all helpful for pediatricians and other health care professionals. In certain situations, physicians should attempt to talk to children privately, so that those who are old enough might have an opportunity to relate events that are traumatic, and so that abusive parents will not have an opportunity to interrupt, instill additional fear in the child, or abruptly change providers. Children need someone to ask them directly about their experiences and act on any suspicions. Asking once may not be enough, because a frightened child may initially deny physical or sexual abuse, but be ready to tell at another time. A vocal adult survivor of Munchausen syndrome by proxy and severe physical abuse explains: The dilemma is how to be loved and accepted. Even once a child recognizes that it is wrong, victims may be afraid to speak up for fear of anger and more abuse at the hand of the abuser. By the time I reached eleven, I was angry enough at what my mother had gotten away with, I would have been more truthful. It would have been a relief to have someone else voice their own suspicions. But, no one ever asked and I could not be the one to give away my mother or the love of my family. Although society is still struggling with its ability to prevent abuse, it must also be concerned with dealing with its consequences. The problem seems overwhelming in its enormity and the resources do not seem to be adequate to tackle these issues so basic to the care and nurturing of children. Nonetheless, physicians must keep their eyes open to behaviors that signal distress, recognize and strive to eliminate the underlying cause, and make certain that children receive treatment to minimize the myriad of behavioral and other long-term problems that are associated with child abuse.     

Life course turning points: the effect of grade retention on physical aggression

Our objective is to advance the life course analytical framework by demonstrating a model for testing two of its tenets. The first is whether the individual's developmental history conditions the response to a turning point event. The second is whether the influence of a major life event upon an individual's developmental course depends upon the timing of the event. We test both propositions in an analysis of the effect of grade retention on a child's trajectory of physical aggression. Our analysis is based on data from a longitudinal study of 1,037 boysfrom schools in the lowest socioeconomic areas in Montreal, Canada. We find clear evidence that a developmental history of physical aggression conditions the child's response to grade retention. The evidence on whether the timing of retention affects this response is less clear.