Asymmetric activity of NetrinB controls laterality of the Drosophila brain.

Left-Right (LR) asymmetry of the nervous system is widespread across animals and is thought to be important for cognition and behaviour. But in contrast to visceral organ asymmetry, the genetic basis and function of brain laterality remain only poorly characterized. In this study, we performed RNAi screening to identify genes controlling brain asymmetry in Drosophila. We found that the conserved NetrinB (NetB) pathway is required for a small group of bilateral neurons to project asymmetrically into a pair of neuropils (Asymmetrical Bodies, AB) in the central brain in both sexes. While neurons project unilaterally into the right AB in wild-type flies, netB mutants show a bilateral projection phenotype and hence lose asymmetry. Developmental time course analysis reveals an initially bilateral connectivity, eventually resolving into a right asymmetrical circuit during metamorphosis, with the NetB pathway being required just prior symmetry breaking. We show using unilateral clonal analysis that netB activity is required specifically on the right side for neurons to innervate the right AB. We finally show that loss of NetB pathway activity leads to specific alteration of long-term memory, providing a functional link between asymmetrical circuitry determined by NetB and animal cognitive functions.

From Curves to Trees: A Tree-like Shapes Distance Using the Elastic Shape Analysis Framework.

Trees are a special type of graph that can be found in various disciplines. In the field of biomedical imaging, trees have been widely studied as they can be used to describe structures such as neurons, blood vessels and lung airways. It has been shown that the morphological characteristics of these structures can provide information on their function aiding the characterization of pathological states. Therefore, it is important to develop methods that analyze their shape and quantify differences between their structures. In this paper, we present a method for the comparison of tree-like shapes that takes into account both topological and geometrical information. This method, which is based on the Elastic Shape Analysis Framework, also computes the mean shape of a population of trees. As a first application, we have considered the comparison of axon morphology. The performance of our method has been evaluated on two sets of images. For the first set of images, we considered four different populations of neurons from different animals and brain sections from the NeuroMorpho.org open database. The second set was composed of a database of 3D confocal microscopy images of three populations of axonal trees (normal and two types of mutations) of the same type of neurons. We have calculated the inter and intra class distances between the populations and embedded the distance in a classification scheme. We have compared the performance of our method against three other state of the art algorithms, and results showed that the proposed method better distinguishes between the populations. Furthermore, we present the mean shape of each population. These shapes present a more complete picture of the morphological characteristics of each population, compared to the average value of certain predefined features.

[Comparative evaluation of quality of life in patients with schizophrenia treated with conventional versus atypical neuroleptics: results of a transversal study]. / Evaluation comparative de la qualité de vie de patients schizophrènes traités par neuroleptiques classiques et neuroleptiques atypiques: résultats d'une étude transversale.

AIM: The World Health Organization has defined quality of life as "the perception of an individual, his/her place in life, in the context of the culture and the system of values in which he/she lives and in relation to his/her objectives, expectations, standards and concerns". The quality of life of the schizophrenic patients has been largely studied for the evaluation of their medical, social and therapeutic needs. The impact of neuroleptics, in particular atypical neuroleptics, on the subjective quality of life of these patients remains to be specified. The aim of this study was to compare the subjective quality of life of schizophrenic patients treated with classical neuroleptics (CN) or atypical neuroleptics (AN). METHODS: One hundred patients meeting DSM IV criteria for the diagnosis of schizophrenia (American Psychiatric Association, 1994) were included in the study. Sixty-four schizophrenic patients were treated with CN and thirty-six with AN. The symptomatology of the patients was assessed using the Positive And Negative Syndrome Scale, (PANSS, Kay et al., 1987) and the Schedule for the Deficit Syndrome (SDS, Kirkpatrick et al., 1989). The extra-pyramidal symptoms were assessed using the Extrapyramidal Symptom Rating Scale (Chouinard et al., 1980). The Subjective quality of life was studied using the Lehman Quality of Life Interview (QOLI, Lehman, 1988) translated and validated in France. RESULTS: The patients treated by CN did not differ from the patients treated by AN in terms of severity of the positive and negative symptoms. The patients treated with AN presented significantly less extrapyramidal side effects than the patients treated with CN. No significant difference in terms of quality of life was found between both groups of patients. CONCLUSION: The kind of neuroleptic (CN vs AC) does not seem to influence the quality of subjective life of schizophrenic patients.

Asthma outpatient education by multiple implementation strategy. Outcome of a programme using a personal notebook.

More than 10 years after publication, international guidelines remain poorly implemented. To better implement them, we need to develop new strategies adapted to the expectations of patients and health professionals outside hospital settings and to ensure better outpatient follow up in the community. We developed a bilingual education programme including a brochure designed to support an interdisciplinary health care network and measured hospitalisations (H), work absenteeism (WA), emergency visits (EV), asthma medication (AM) and quality of life (QL Juniper) before and 12 months after the intervention. All QL scores improved significantly in comparison with pre-intervention values. Health service use decreased dramatically when comparing the 12 months prior to and after the intervention(H: 35-8%, WA: 39-14%, EV: 88-53%). The final cost/benefit ratio of the programme was 1.96. Interdisciplinary implementation strategy of patient education is cost-effective, improves quality of life for asthmatics, and reduces strain on health services. Such a health care network does not require an expensive infrastructure and is better adapted to the reality and competences of clinical practice.

Bronchial asthma and self-management education: implementation of Guidelines by an interdisciplinary programme in health network.

UNLABELLED: Asthma is a chronic disease generating very high costs even for Switzerland. Self-management education (SME) is effective and recommended as an integral part of management in the most recent guidelines on asthma treatment. Its aim is to reduce morbidity [hospitalisations (H), lost workdays (LW), emergency consultations (EC)] and improve quality of life (QOL) in these patients. METHOD: Integrated programme with educational platforms (two-language booklet), SME in 66 patients (30 m, 36 f) with interdisciplinary quality team (pneumologists, primary care physicians, pharmacists, specialised nursing staff), QOL questionnaire. Measurement of morbidity parameters 12 months before and after SME. Measurement of QOL before and 12 months after SME. RESULTS: Hospitalisations fell from 35 to 8%*, EC from 88 to 53%*. and LW from 39 to 14%* (*p <0.001). Overall, SME resulted in a health cost saving of CHF 202,510 in terms of LW and CHF 131,200 in terms of days in hospital, i.e. a total of CHF 333,710. Costs saved per patient were CHF 5,056 per year. QOL improved with the following scores: overall QOL 4.5 +/- 0.9 to 5.2 +/- 0.9*; activities 4.5 +/- 0.9 to 5.2 +/- 0.9*; symptoms 4.2 +/- 1.1 to 5.2 +/- 1.1*; emotions 4.9 +/- 1.1 to 5.6 +/- 1*; environment 4.5 +/- 1.4 to 4.9 +/- 1.3* (*p <0.001). CONCLUSION: SME by interdisciplinary health network is effective. It brings a steep fall in costs for asthma treatment by cutting back hospitalisations and lost workdays and by improving the asthmatics' quality of life. It should be recognised and better supported by the health system.

p15(INK4b) in bladder carcinomas: decreased expression in superficial tumours.

The p15 gene which encodes a cyclin-dependent kinase inhibitor, is located in the 9p21 chromosomal region that is frequently deleted in human bladder transitional cell carcinomas (TCCs). The aim of the present paper is to study the potential involvement of the p15 gene in the evolution of TCCs. p15 mRNA expression was investigated by semi-quantitative RT-PCR in a series of 75 TCCs, 13 bladder cell lines and 6 normal bladder urothelia by semi-quantitative RT-PCR. p15 was expressed in the normal urothelium but p15 mRNA levels were significantly decreased in 66% of the superficial (Ta-T1) TCCs (P = 0.0015). In contrast, in muscle-invasive (T2-T4) TCCs, p15 expression differed widely between samples. p16 mRNA levels were also studied and there was no correlation between p15 and p16 mRNA levels, thus indicating that the two genes were regulated independently. Lower p15 expression in superficial tumours did not reflect a switch from quiescence to proliferative activity as normal proliferative urothelial controls did not present decreased p15 mRNA levels relative to quiescent normal urothelia. We further investigated the mechanisms underlying p15 down regulation. Homozygous deletions of the p15 gene, also involving the contiguous p16 gene, were observed in 42% of the TCCs with decreased p15 expression. No hypermethylation at multiple methylation-sensitive restriction sites in the 5;-CpG island of p15 was encountered in the remaining tumours. Our data suggest that decreased expression of p15 may be an important step in early neoplastic transformation of the urothelium and that a mechanism other than homozygous deletions or hypermethylation, may be involved in p15 down regulation.

Technical developments in cardiac CT: 2000 update.

Preliminary results of the new generation CT scanners in the study of the heart and coronary arteries, are reported, after an overview of basic anatomy, physiology and main technical problems. Comparison is made with the other conventional procedures. The clinical validation of cardiac CT is under way while preliminary results are very encouraging. However, for cardiac CT to become an examination of first choice in the study of the heart and coronary arteries, spatial resolution should be improved and acquisitions of 15 cm volume with less than 15 sec breath-hold should be feasible. The improvement in cardiac synchronization and temporal resolution will allow a kynetic systolic as well as diastolic study. This is going to be possible with the new generation CT scanners able of 16 or 32 sections per second.

Month of birth in deficit and non-deficit schizophrenic patients.

In order to test the hypothesis that an excess of summer births is a risk factor for deficit syndrome, the month of birth was studied in 53 deficit schizophrenic patients compared to 158 non-deficit patients. No significant difference in terms of month of birth or season of birth was observed between deficit and non-deficit patients, suggesting that summer births might not be a risk factor for deficit schizophrenia.

["Polydipsia, intermittent hyponatremia and psychoses" syndrome: a diagnosis and therapeutic management of a case]. / Le syndrome "polydipsie, hyponatrémie intermittence et psychoses": diagnostic et conduite thérapeutique à propos d'un cas.

Polydipsia can be defined as an impulsive behavior leading to absorption of large amounts of water (4 to 20 litres a day), without any underlying organic disease. Its prevalence in a population of chronic psychiatric patients can be as high as 6 to 17%. Schizophrenia represents 80% of cases reported. Some patients with polydipsia may develop hyponatremia, leading to a PIP syndrome (Polydipsia intermittent hyponatremia and psychosis). Hyponatremia or water intoxication appears when three conditions are present: an abnormal regulation of thirst, an inappropriate ADH secretion and/or an excessive renal sensitivity to ADH, with an increased sensitivity of the central nervous system to hyponatremia. The clinician must first identify patients at risk to develop water intoxication and start treatment before any severe physical complication occurs. Pharmacological treatments aiming at an increase of renal free-water excretion--do not show a constant efficacy in the correction of hyponatremia, they have no action on polydipsia. The new atypical neuroleptics such as clozapine and risperidone seem to open new perspectives in the treatment of polydipsia. Controlled studies should be performed in this field.

Identifying subtypes of schizophrenia by cluster analyses.

The existence of two subtypes of schizophrenia (positive and negative) is well established. The evidence in favor of other subtypes, particularly a disorganized subtype, is still the subject of some debate. The aim of the study reported in this article is to investigate the possibility of further subtypes of schizophrenia by applying a particular method of cluster analysis to a particular set of data. Ward's method of cluster analysis was applied to the Positive and Negative syndrome Scale (PANSS) scores of 138 patients, defined as having schizophrenia by one of four diagnostic criteria. The validity of the cluster solution was assessed both by examining differences between clusters on a number of clinical characteristics recorded for each patient and by comparing the results obtained from the PANSS with those derived from a cluster analysis using two other instruments (the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms). Results from the cluster analysis suggest the existence of at least four subtypes of schizophrenia: positive, negative, mixed, and disorganized. A fifth subtype includes patients with few symptoms, suggesting the simple schizophrenia named by Bleuler. Evidence for the validity of these subtypes was provided by the differences observed between the clusters on a number of clinical characteristics and by the similarity of the cluster solution obtained from the different instruments. In conclusion, the negative-positive dichotomy in schizophrenia is an oversimplification, and the existence of a more complex structure needs to be taken into account in future research.

[A contribution of brain imaging techniques to the diagnosis of psychiatric emergencies]. / Apports des techniques d'imagerie cérébrale au diagnostic de certaines urgences psychiatriques. A propos de deux observations.

This study was performed in the psychiatric emergency unit of René-Dubos General Hospital (Pontoise, France). Two cases of female patients with motor deficiencies suggesting a diagnosis of conversion disorder because of preceding psychological stressors and lability of symptoms, are presented. In both cases, the diagnosis was reconsidered after the use of RMI for multiple sclerosis in one case, HIV related encephalopathy in the other. Recent studies have shown that organic diseases with a psychiatric presentation represent 1,2 to 4% of patients examined in emergency setting. Criteria for the diagnosis of conversion disorders are discussed (they are classified as dissociative disorders in ICD-10 and as somatoform disorders in DMS-IV). A diagnosis of conversion disorder should not be made before a thorough clinical and neurological evaluation has been performed.

[French translation of the Chapman Social and Physical Anhedonia Questionnaire: validation of the French translation in controls and schizophrenic patients]. / Traduction française des questionnaires d'anhédonie sociale et physique de Chapman: validation de la traduction française à partir de témoins et de patients schizophrènes.

Whereas Chapman's social and physical scales are the most used instruments for the assessment of anhedonia in schizophrenia, no French translation has been still validated by the authors. Therefore, the aim of this study was first to translate into French the both scales, and after back translation, to obtain the agreement of the original authors. Second, the aim was to establish values and to establish the cut-off beyond of which French subjects could be considered as anhedonic. One hundred and twenty-three subjects were included: 72 control subjects without mental disorders and 51 stable schizophrenic patients defined by the DSM III-R, ICD 9, ICD 10, RDC or Feighner criteria. According to the literature, schizophrenic patients had higher scores for both scales than control subjects (p < 0.001; Student t test). The social anhedonia scores are different due to cultural variations. The distribution of physical anhedonia scores in control subjects or in schizophrenic patients differed from normal distributions (respectively, p < 0.05; p < 0.0001; Shapiro-Wilks test). The distribution of social anhedonia scores differed from normal distributions (p < 0.01) only in schizophrenic patients but not in control subjects. By maximising the Younden indice [Sensitivity + Specificity -1], the cut-off of the physical anhedonia score was 18 (Younden indice = 0.45), and the cut-off of the social anhedonia score was 12 (Younden indice = 0.24). In using this cut-off, the French physical anhedonia scale had a good positive predictive value (evaluated by logistic regression) for schizophrenia. Therefore, a patient with a physical anhedonia score beyond 18 have a probability of 64% to be schizophrenic. In contrast, the social anhedonia scale was less discriminant for schizophrenia. Indeed, patient with a social anhedonia score beyond 12 have a probability of 52% to be schizophrenic. This French version of Chapman's anhedonia scales could be considered as an useful instrument to assess anhedonia, in particular physical anhedonia, in schizophrenic patients.

[Depressive symptoms and negative symptoms during schizophrenia]. / Symptômes dépressifs et symptômes négatifs au cours des schizophrénies.

Taking into account the wellknown frequency of depressive and extrapyramidal symptoms in schizophrenia and the rare studies about their evolution, several questions can be raised: How do these different symptoms move? Are there specific characters of each of them? First, stability of negative symptoms evaluated by the Scale for the Assessment of Negative Symptoms (SANS) was studied among 57 schizophrenic patients at admission and at discharge. The course of negative symptoms was compared to that of depressive MADRS (Montgomery et Asberg Depression Rating Scale) and akinetic symptoms (Extrapyramidal Symptom Rating Scale). All the subscores of the SANS decreased significantly but 4 items belonging to the affective flattening subscale and one item belonging to the alogia subscale did not vary significantly, showing the necessity of taking into account the individual items of the SANS rather than the subscale scores to evaluate the course of negative symptoms. Changes in all the SANS subscores except the alogia and anhedonia subscores were associated with variations in scores of other scales. Correlations between the changes of negative symptoms and the changes of depressive symptoms showed the necessity to do more specific scales, for example, scales for depression in schizophrenia. Langlois-Théry et al. (1994) evaluated among 53 schizophrenic patients stabilized with neuroleptic treatment, depressive symptomatology with Echelle de Ralentissement Dépressif (ERD, Widlöcher, 1983) and MADRS, negative symptomatology (Positive and Negative Syndrome Scale) and akinesia (ESRS), to determinate whether ERD composed of 3 subscores (motor, ideic and subjective) could be able to evaluate the depressive symptomatology, independently of the measures of negative and akinetic symptomatology.(ABSTRACT TRUNCATED AT 250 WORDS)

[Magnetic resonance in the study of patients of short stature of the hypothalamo-hypophyseal origin. Report on 29 cases]. / La risonanza magnetica nello studio dei pazienti con bassa statura di origine ipotalamo-ipofisaria. Rapporto su 29 casi.

Although growth hormone (GH) deficiency is a very common cause of short stature, many cases are still diagnosed as idiopathic. Magnetic Resonance Imaging (MRI), more clearly than CT, reveals the anatomy of the hypothalamic-hypophyseal region and of the possible alterations (pituitary hypoplasia, interruption of the stalk) causing hormonal deficit. Twenty-nine patients with short stature underwent MRI examinations of the hypothalamic-pituitary region to assess the significance of the correlation between hormonal test and MR patterns. Five patients had normal variants of short stature (NVSS), 7 had multiple pituitary hormone defects (MPHD) and 17 had isolated growth hormone deficiency (IGHD). In patients with MPHD or with severe isolated growth hormone deficit MRI shows interruption of the pituitary stalk with ectopy of the neurohypophysis or a mass. In patients with less severe IGHD and in NVSS, MRI demonstrates a normal pituitary region or a slightly hypoplastic gland, the neurohypophysis being normally situated. MRI may provide an ethiological classification in short stature patients. Typical MR patterns can be demonstrated in cases of dwarfism secondary to a mass in the hypothalamic-pituitary region or to morphological changes of the pituitary stalk, while in transient GH deficit no anatomical abnormalities are observed.

[Polydiagnostic approach to schizophrenia. Validation of a computerized checklist (Diagnostic and Prognostic Scales)]. / Approche polydiagnostique de la schizophrénie. Validation d'une "checklist" informatisée (LIDE: Liste d'Items à visée Diagnostique et Evolutive).

With a polydiagnostic approach of schizophrenia in mind, the authors present, in french language, a computer-diagnostic instrument, essential for any research at the present time. This includes a 183-item checklist constructed from 14 diagnostic systems for schizophrenia and from Chronic Hallucinatory Psychosis (CHP), a typically french diagnostic entity, not recognized by English-speaking countries which do not individualize it from schizophrenia. This study tested the reliability in interviewing the patients simultaneously by 2 examiners with the checklist. The interrater agreement was excellent (Kappa from 0.75 to 1) for schizophrenic diagnoses under the systems CATEGO, DSM III-R, Feighner, ICD9, Langfeldt, Pull, Schneider and Taylor-Abrams. It was good (Kappa from 0.40 to 0.75) for the 6 other schizophrenic systems, Bleuler (k = 0.52; p > 0.01), Carpenter with a cut-off at 6 (k = 0.52; p < 0.05), ICD10 (k = 0.70; p < 0.01), New-Haven (k = 0.58), RDC (k = 0.59; p < 0.01), Vienne (k = 0.68; p < 0.01), and the Chronic Hallucinatory Psychosis (Pull) (k = 0.71; p < 0.01). The validity of the computer program was tested by the concordance (Cohen's Kappa) between the diagnoses established by a medical examiner and by computer, both obtained from the same collected data (the checklist). The tests show that the concordances were excellent for the 15 diagnoses for schizophrenia and CHP (Kappa form 0.75 to 1) and always above those obtained by the tests of interreliability.

Quantitative metabolic PET imaging of a plasma cell granuloma.

We report a patient who underwent surgical resection of two lung nodules that proved to be recurrent plasma cell granuloma, also known as inflammatory pseudotumor. Prior to surgery, positron emission tomography (PET) was performed with 18F-labeled fluoro-2-deoxy-D-glucose (18FDG) and rubidium-82 (82Rb). The 18FDG PET scan revealed that the nodules corresponded to two areas of intense uptake. PET imaging with 82Rb, the marker of flow, also showed intense uptake. Thus, PET demonstrated both a high degree of metabolic activity and increased perfusion. These features suggest a lesion with high cellular activity rather than a simple reparative process. The true nature of this lesion remains unknown.