A new, automated, four-colour interphase FISH approach for the simultaneous detection of specific aneuploidies of diagnosis and prognosis significance in high hyperdiploid ALL

In hyperdiploid acute lymphoblastic leukaemia (ALL), the simultaneous occurrence of specific aneuploidies confers a more favourable outcome than hyperdiploidy alone. Interphase (I) FISH complements conventional cytogenetics (CC) through its sensitivity and ability to detect chromosome aberrations in non-dividing cells. To overcome the limits of manual I-FISH, we developed an automated four-colour I-FISH approach and assessed its ability to detect concurrent aneuploidies in ALL. I-FISH was performed using centromeric probes for chromosomes 4, 6, 10 and 17. Parameters established for automatic nucleus selection and signal detection were evaluated (3 controls). Cut-off values were determined (10 controls, 1000 nuclei/case). Combinations of aneuploidies were considered relevant when each aneuploidy was individually significant. Results obtained in 10 ALL patients (1500 nuclei/patient) were compared with those by CC. Various combinations of aneuploidies were identified. All clones detected by CC were observed by I-FISH. I-FISH revealed numerous additional abnormal clones, ranging between 0.1 % and 31.6%, based on the large number of nuclei evaluated. Four-colour automated I-FISH permits the identification of concurrent aneuploidies of prognostic significance in hyperdiploid ALL. Large numbers of cells can be analysed rapidly by this method. Owing to its high sensitivity, the method provides a powerful tool for the detection of small abnormal clones at diagnosis and during follow up. Compared to CC, it generates a more detailed cytogenetic picture, the biological and clinical significance of which merits further evaluation. Once optimised for a given set of probes, the system can be easily adapted for other probe combinations.

An epidemiological and clinical approach to adolescent suicide. A comparison between suicidal and non-suicidal clinical groups in a health foundation center for French students.

Suicidal behaviour among young people represents a major public health problem. This study seeks to compare the major sociological, clinical, schooling and family features of suicidal and non-suicidal subgroups of adolescents hospitalised in the Health Foundation Center for French Students of neufmoutiers en Brie (France). All these adolescents suffered from the severe mental disorders. The adolescents from the suicidal subgroup presented significantly fewer psychoses and more mood disorders than those of the non-suicidal subgroup. Half of the patients from the suicidal subgroup presented some features of personality disorders, mostly borderline personality disorders. Nevertheless, their global functioning was more frequently improved between admission and discharge than was the case for the non-suicidal group.

Le soignant face au patient lombalgique chronique: l'expérience clinique de l'Unité Rachis à l'Hôpital orthopédique [The health professional's approach to chronic lumbago: clinical experience at the Spinal Cord Unit at the orthopedic hospital]

The treatment of back pain patients refers to the biopsychosocial model of care. This model includes illness in patient's personal and relational life. In this context, it is not only the physical symptom of the patient which is focused but also his psychological distress often hidden by algic complain. Clinical interviews conducted with back pain patients have highlighted psychosocial aspects able to influence the relationship between health care user and provider. Taking account of psychosocial aspects implies an interdisciplinary approach that identify and assesses patients' needs through adequate tools. As a result, the different health care providers implied with back pain patients have to collaborate in a structured network.

Dimensionality of drinking consequences - cross-cultural comparability and stability over time

Despite the long tradition for asking about the negative social and health consequences of alcohol consumption in surveys, little is known about the dimensionality of these consequences. Analysing cross-sectional and longitudinal data from the Nordic Taxation Study collected for Sweden, Finland, and Denmark in two waves in 2003 and 2004 by means of an explorative principal component analysis for categorical data (CATPCA), it is tested whether consequences have a single underlying dimension across cultures. It further tests the reliability, replicability, concurrent and predictive validity of the consequence scales. A one-dimensional solution was commonly preferable. Whereas the two-dimensional solution was unable to distinguish clearly between different concepts of consequences, the one-dimensional solution resulted in interpretable, generally very stable scales within countries across different samples and time.

Transcriptional activation of the utrophin promoter B by a constitutively active Ets-transcription factor.

Duchenne muscular dystrophy is an X-linked genetic disease caused by the absence of functional dystrophin. Pharmacological upregulation of utrophin, the autosomal homologue of dystrophin, offers a potential therapeutic approach to treat Duchenne patients. Full-length utrophin mRNA is transcribed from two alternative promoters, called A and B. In contrast to the utrophin promoter A, little is known about the factors regulating the activity of the utrophin promoter B. Computer analysis of this second promoter revealed the presence of several conserved binding motives for Ets-transcription factors. Using electrotransfer of cDNA into mouse muscles, we demonstrate that a genetically modified beta-subunit of the Ets-transcription factor GA-binding protein potently activates a utrophin promoter B reporter construct in innervated muscle fibers in vivo. These results make the GA-binding protein and the signaling cascade regulating its activity in muscle cells, potential targets for the pharmacological modulation of utrophin expression in Duchenne patients.

Gerdy tubercle osteotomy in surgical approach of posterolateral corner of the knee.

Posterolateral corner (PLC) injuries of the knee are uncommon injury patterns that may result in significant degrees of functional disability. When surgery is necessary to address this injury a good knowledge of anatomy and a good surgical exposure is the mainstay. This report reviews the complex anatomy of the posterolateral corner (PLC) of knee and describes the osteotomy of Gerdy tubercle as a technical variant to approach this anatomical region. This surgical step allowing a good mobilisation of the multiple layers of ilio-tibial tract from distal to proximal makes an excellent exposure of the PLC structures with absence of morbidity.

On the use of IRMS in forensic science: proposals for a methodological approach.

The flourishing number of publications on the use of isotope ratio mass spectrometry (IRMS) in forensicscience denotes the enthusiasm and the attraction generated by this technology. IRMS has demonstratedits potential to distinguish chemically identical compounds coming from different sources. Despite thenumerous applications of IRMS to a wide range of forensic materials, its implementation in a forensicframework is less straightforward than it appears. In addition, each laboratory has developed its ownstrategy of analysis on calibration, sequence design, standards utilisation and data treatment without aclear consensus.Through the experience acquired from research undertaken in different forensic fields, we propose amethodological framework of the whole process using IRMS methods. We emphasize the importance ofconsidering isotopic results as part of a whole approach, when applying this technology to a particularforensic issue. The process is divided into six different steps, which should be considered for a thoughtfuland relevant application. The dissection of this process into fundamental steps, further detailed, enablesa better understanding of the essential, though not exhaustive, factors that have to be considered in orderto obtain results of quality and sufficiently robust to proceed to retrospective analyses or interlaboratorycomparisons.

Appropriate treatment for Crohn's disease: methodology and summary results of a multidisciplinary international expert panel approach--EPACT.

BACKGROUND/AIMS: For many therapeutic decisions in Crohn's disease (CD), high-grade evidence is lacking. To assist clinical decision-making, explicit panel-based appropriateness criteria were developed by an international, multidisciplinary expert panel. METHODS: 10 gastroenterologists, 3 surgeons and 2 general practitioners from 12 European countries assessed the appropriateness of therapy for CD using the RAND Appropriateness Method. Their assessment was based on the study of a recent literature review of the subject, combined with their own expert clinical judgment. Panelists rated clinical indications and treatment options using a 9-point scale (1 = extremely inappropriate; 9 = extremely appropriate). These scenarios were then discussed in detail at the panel meeting and re-rated. Median ratings and disagreement were used to aggregate ratings into three assessment categories: appropriate (A), uncertain (U) and inappropriate (I). RESULTS: 569 specific indications were rated, dealing with 9 clinical presentations: mild/moderate luminal CD (n = 104), severe CD (n = 126), steroid-dependent CD (n = 25), steroid-refractory CD (n = 37), fistulizing CD (n = 49), fibrostenotic CD (n = 35), maintenance of medical remission of CD (n = 84), maintenance of surgical remission (n = 78), drug safety in pregnancy (n = 24) and use of infliximab (n = 7). Overall, 146 indications (26%) were judged appropriate, 129 (23%) uncertain and 294 (52%) inappropriate. Frank disagreement was low (14% overall) with the greatest disagreement (54% of scenarios) being observed for treatment of steroid-refractory disease. CONCLUSIONS: Detailed explicit appropriateness criteria for the appropriate use of therapy for CD were developed for the first time by a European expert panel. Disease location, severity and previous treatments were the main factors taken into account. User-friendly access to EPACT criteria is available via an Internet site, www.epact.ch, allowing prospective evaluation and improvement of appropriateness of current CD therapy.

Landscape genetics of the Alpine newt (Mesotriton alpestris) inferred from a strip-based approach

Habitat destruction and fragmentation are known to strongly affect dispersal by altering the quality of the environment between populations. As a consequence, lower landscape connectivity is expected to enhance extinction risks through a decrease in gene flow and the resulting negative effects of genetic drift, accumulation of deleterious mutations and inbreeding depression. Such phenomena are particularly harmful for amphibian species, characterized by disjunct breeding habitats. The dispersal behaviour of amphibians being poorly understood, it is crucial to develop new tools, allowing us to determine the influence of landscape connectivity on the persistence of populations. In this study, we developed a new landscape genetics approach that aims at identifying land-uses affecting genetic differentiation, without a priori assumptions about associated ecological costs. We surveyed genetic variation at seven microsatellite loci for 19 Alpine newt (Mesotriton alpestris) populations in western Switzerland. Using strips of varying widths that define a dispersal corridor between pairs of populations, we were able to identify land-uses that act as dispersal barriers (i.e. urban areas) and corridors (i.e. forests). Our results suggest that habitat destruction and landscape fragmentation might in the near future affect common species such as M. alpestris. In addition, by identifying relevant landscape variables influencing population structure without unrealistic assumptions about dispersal, our method offers a simple and flexible tool of investigation as an alternative to least-cost models and other approaches.