[Completeness assessment of the Breton registry of congenital abnormalities: A checking tool based on hospital discharge data]. / Contrôle automatisé de l'exhaustivité du registre breton des malformations congénitales à partir des données des bases médico-administratives des établissements de santé.

BACKGROUND: Exhaustiveness is required for registries. In the Breton registry of congenital abnormalities, cases are recorded at the source. We use hospital discharge data in order to verify the completeness of the registry. In this paper, we present a computerized tool for completeness assessment applied to the Breton registry. METHODS: All the medical information departments were solicited once a year, asking for infant medical stays for newborns alive at one year old and for mother's stays if not. Files were transmitted by secure messaging and data were processed on a secure server. An identity-matching algorithm was applied and a similarity score calculated. When the record was not linked automatically or manually, the medical record had to be consulted. The exhaustiveness rate was assessed using the capture recapture method and the proportion of cases matched manually was used to assess the identity matching algorithm. RESULTS: The computerized tool bas been used in common practice since June 2012 by the registry investigators. The results presented concerned the years 2011 and 2012. There were 470 potential cases identified from the hospital discharge data in 2011 and 538 in 2012, 35 new cases were detected in 2011 (32 children born alive and 3 stillborn), and 33 in 2012 (children born alive). There were respectively 85 and 137 false-positive cases. The theorical exhaustiveness rate reached 91% for both years. The rate of exact matching amounted to 68%; 6% of the potential cases were linked manually. CONCLUSION: Hospital discharge databases contribute to the quality of the registry even though reports are made at the source. The implemented tool facilitates the investigator's work. In the future, use of the national identifying number, when allowed, should facilitate linkage between registry data and hospital discharge data.

Anionic porphyrin as a new powerful cell death inducer of Tobacco Bright Yellow-2 cells.

For the first time, the behaviour of tobacco cell suspensions submitted to four porphyrins was described. The potential killer effect of these photosensitizers on tobacco cells was evaluated. Biological results were correlated with photophysical properties and the reactive oxygen species production capacity of tested compounds. Surprisingly, the anionic free-base porphyrin showed the strongest phototoxic effect.

[Obstetric data in a population with postural changes during labor and delivery]. / Données obstétricales dans une population bénéficiant de variations posturales en cours de travail et d'accouchement.

INTRODUCTION: The aim of this study was to describe the potential impact of an active birth on classical obstetrical outcomes, as labor duration, cesarean section rate, couples and team satisfactions. MATERIAL AND METHODS: This observational study was prospective, monocentric and took place between May 2007 and February 2009 at the maternity ward of the University Hospital of Caen, France. An "active birth" was defined as an active latent-phase (having a change in position and/or a bath and/or a walk) followed by at least three changes in position during the active phase. The suggested positions were: lateral or dorsal decubitus, ROSA, on all fours, seated, standing and crouch. A position must have lasted at least 20 minutes to be considered. RESULTS: Out of the 1906 women included, 828 had an active birth (43.4%). Due to our definition of an "active birth", a "non-active birth" was significantly associated with a quicker labor. An "active birth" was associated with a decreased rate of cesarean section (OR=0.71; IC95%=[0.51-0.99]). The parturients satisfaction median was 9 on a scale of 0 to 10, the spouses'one was 10. Midwives were more satisfied when it was an "active birth". CONCLUSION: Significant associations with active births were highlighted, which would require to be validated by a randomised study. This practise plenty satisfied couples and midwives. In fact, no litterature exists to date. A consensus about the definition of an active birth is still necessary in order to lead to guidelines.

Transient elastography and portal hypertension in pediatric patients with cystic fibrosis Transient elastography and cystic fibrosis.

BACKGROUND: Esophageal varices (EV) are a complication of cystic fibrosis-associated liver disease. Esophagogastroduodenoscopy (EGD) is currently used to diagnose varices but is invasive for pediatric patients. The goal of this study was to explore the relationship between transient elastography (FibroScan®) and the presence of EV in patients with liver disease defined by clinical, laboratory, sonographic, and/or endoscopic criteria. METHODS: 18 patients with cystic fibrosis underwent EGD and transient elastography. 12 patients had EV. RESULTS: Patients with EV had higher FibroScan values than those without varices with median values of 22.4 kPa (14.4-30.4 kPa) vs. 7.9 kPa (4.4-13.7 kPa) (p=0.01). Using a threshold of 12 kPa, four of six patients without EV would not have needed EGD. CONCLUSIONS: Elastography should be recommended for all cystic fibrosis patients with liver disease to follow its progression. A prospective study is needed to define an elastography threshold value that predicts the presence of EV.

ASTI: a guideline-based drug-ordering system for primary care.

Existing computer-based ordering systems for physicians provide effective drug-centered checks but offer little assistance for optimizing the overall patient-centered treatment strategy. Evidence-based clinical practice guidelines have been developed to disseminate state-of-the-art information concerning treatment strategy but these guidelines are poorly used in routine practice. The ASTI project aims to design a guideline-based ordering system to enable general practitioners to avoid prescription errors and to improve compliance with best therapeutic practices. The " critic mode " operates as a background process and corrects the physician's prescription on the basis of automatically triggered elementary rules that account for isolated guideline recommendations. The " guided mode " directs the physician to the best treatment by browsing a comprehensive guideline knowledge base represented as a decision tree. A first prototype, applied to hypertension, is currently under development.

Synergistic regulation of immunoreceptor signaling by SLP-76-related adaptor Clnk and serine/threonine protein kinase HPK-1.

Recently, the identification of Clnk, a third member of the SLP-76 family of adaptors expressed exclusively in cytokine-stimulated hemopoietic cells, has been reported by us and by others. Like SLP-76 and Blnk, Clnk was shown to act as a positive regulator of immunoreceptor signaling. Interestingly, however, it did not detectably associate with known binding partners of SLP-76, including Vav, Nck, and GADS. In contrast, it became complexed in activated T cells and myeloid cells with an as yet unknown tyrosine-phosphorylated polypeptide of approximately 92 kDa (p92). In order to understand better the function of Clnk, we sought to identify the Clnk-associated p92. Using a yeast two-hybrid screen and cotransfection experiments with Cos-1 cells, evidence was adduced that p92 is HPK-1, a serine/threonine-specific protein kinase expressed in hemopoietic cells. Further studies showed that Clnk and HPK-1 were also associated in hemopoietic cells and that their interaction was augmented by immunoreceptor stimulation. A much weaker association was detected between HPK-1 and SLP-76. Transient transfections in Jurkat T cells revealed that Clnk and HPK-1 cooperated to increase immunoreceptor-mediated activation of the interleukin 2 (IL-2) promoter. Moreover, the ability of Clnk to stimulate IL-2 promoter activity could be blocked by expression of a kinase-defective version of HPK-1. Lastly we found that in spite of the differential ability of Clnk and SLP-76 to bind cellular proteins, Clnk was apt at rescuing immunoreceptor signaling in a Jurkat T-cell variant lacking SLP-76. Taken together, these results show that Clnk physically and functionally interacts with HPK-1 in hemopoietic cells. Moreover, they suggest that Clnk is capable of functionally substituting for SLP-76 in immunoreceptor signaling, albeit by using a distinct set of intracellular effectors.

Release of trace elements in wetlands: role of seasonal variability.

Dissolved concentrations were determined for Fe, Mn, Al, Cu, Zn, La, U, Th, Cd and As in a wetland and its recipient stream to reveal the effect of seasonal changes in environmental conditions on the cycling and transfer of trace elements at the transition between terrestrial and aquatic ecosystems. These preliminary results from the wetland show marked seasonal changes in dissolved concentration for all elements except Zn and Cu. Concentrations are found to be low until about mid-February and then increase abruptly. The onset of trace element release appears to coincide with a marked decline in redox potential and increase of organic carbon content. Because this decline is itself correlated with a pronounced increase in temperature and dissolved Fe. Mn and organic carbon content, we suggest that the microorganisms which use soil iron and manganese oxy-hydroxides as electron acceptors catalyzed the change in redox conditions and induced an increase of DOC. Temporal changes were also observed in the recipient stream which showed marked positive concentration peaks during stormflow events (except Zn). The seasonal processes occurring in the wetland appear to play a major role in determining the amount of trace elements which are transferred from the wetland to the river.

Cloning and molecular characterization of three members of the NBS-LRR subfamily located in the vicinity of the Co-2 locus for anthracnose resistance in Phaseolus vulgaris.

Co-2 is one of the R-genes against anthracnose identified in common bean. A RAPD marker, cloned as PvH20, was previously shown to contain 6 imperfect leucine-rich-repeats and to reveal a family of related sequences in the vicinity of the Co-2 locus. Using PvH20 as probe, a genomic clone and 2 partial cDNAs were isolated. DNA sequencing revealed that the 6.1 kb genomic fragment contains sequences encoding both NBS-LRR (ORF1) and kinase-like (ORF2) products. The 2 partial cDNAs (cD7 and cD8) belong to the NBS-LRR subfamily as do most of the resistance genes cloned to date. The LRR domain of ORF1 is interrupted by 2 stop codons suggesting that it corresponds to a non-functional member of the multigene family and ORF2 appears to be a kinase pseudogene. The 3 NBS-LRR polypeptides share a high level of amino acid identity and represent different members of a related family. By genetic mapping ORF1, cD7, and cD8 were found to span a genetic distance of 3 cM: cD8 maps at 2 cM from Co-2 and 3 cM from ORF1, cD7 maps at 1 cM from ORF1 and co-segregates with Co-2, thus cD7 might be a putative candidate for the Co-2 R-gene.

A computer-assisted drug prescription system: the model and its implementation in the ATM knowledge base.

Informatisation of drug prescription is an important topic in medical informatics. For several years now, computerized drug databases have been implemented. Usually only a small part of the prescriptions can be stored in prescription systems because of the format of the included information; prescriptions contain essentially free text without any structure and homogeneity of the used vocabulary. In this article a model is presented for knowledge representation in a computerized drug prescription system. The model should be applicable to clinical practice and be didactic for medical students. The problem of standardization of terminology had to be solved. A computer-assisted drug prescription program has been developed. The next step is its validation by clinicians. The program can also be used in a consultation mode.

Susceptibility of differentiated thyrocytes in primary culture to undergo apoptosis after exposure to hydrogen peroxide: relation with the level of expression of apoptosis regulatory proteins, Bcl-2 and Bax.

Thyrocytes, that generate and use hydrogen peroxide (H2O2) to synthesize thyroid hormones, undergo apoptosis, as do most cell types, when exposed in vitro to H2O2. We have studied 1) the kinetics and the amplitude of the apoptotic response to H2O2 and 2) the relationship between the extent of the apoptosis-inducing effect of H2O2, the H2O2 degradation activity, and the level of expression of apoptosis regulatory proteins, Bcl-2 and Bax, in pig thyrocytes in primary culture. Cells were seeded at high density to obtain confluent monolayers and were cultured in the presence of TSH to maintain the expression of differentiation. H2O2 (10-300 microM) induced the appearance of cells with fragmented DNA (terminal transferase deoxy-UTP-fluorescein isothiocyanate nick end labeling-positive cells) at a maximum of 3-4 h after H2O2 addition and then the detachment of apoptotic cells from the cell monolayer. The proportion of detached cells increased with H2O2 concentration and amounted to up to 30% of the initial cell number after 24 h. The transient effect of H2O2 was related to its rapid degradation by cells and culture medium components (rate constant, approximately 0.1 min(-1)). Iterative additions of H2O2 produced cumulative apoptotic waves. The amplitude of the apoptotic response of thyrocytes to H2O2 progressively increased with the time of culture, up to 4-fold from days 1-8. This was not related to a change in the capacity of thyrocytes to degrade H2O2. During the same period of culture, the Bcl-2 cell content progressively decreased, whereas that of Bax concomitantly increased; thus, the Bcl-2/Bax ratio varied from about 6 on day 1 to 0.5 on day 10. These data show that the susceptibility of thyrocytes to undergo apoptosis increases with the time of culture and that the pronounced changes in the apoptotic status ofthyrocytes might be linked to coordinate modifications of the level of expression of pro- and antiapoptotic regulatory proteins.

A first evaluation of a pedagogical network for medical students at the University Hospital of Rennes.

A pedagogical network has been developed at University Hospital of Rennes from 1996. The challenge is to give medical information and informatics tools to all medical students in the clinical wards of the University Hospital. At first, nine wards were connected to the medical school server which is linked to the Internet. Client software electronic mail and WWW Netscape on Macintosh computers. Sever software is set up on Unix SUN providing a local homepage with selected pedagogical resources. These documents are stored in a DBMS database ORACLE and queries can be provided by specialty, authors or disease. The students can access a set of interactive teaching programs or electronic textbooks and can explore the Internet through the library information system and search engines. The teachers can send URL and indexation of pedagogical documents and can produce clinical cases: the database updating will be done by the users. This experience of using Web tools generated enthusiasm when we first introduced it to students. The evaluation shows that if the students can use this training early on, they will adapt the resources of the Internet to their own needs.

Purification, characterization, and substrate specificity of a novel highly glucose-tolerant beta-glucosidase from Aspergillus oryzae.

Aspergillus oryzae was found to secrete two distinct beta-glucosidases when it was grown in liquid culture on various substrates. The major form had a molecular mass of 130 kDa and was highly inhibited by glucose. The minor form, which was induced most effectively on quercetin (3,3',4',5,7-pentahydroxyflavone)-rich medium, represented no more than 18% of total beta-glucosidase activity but exhibited a high tolerance to glucose inhibition. This highly glucose-tolerant beta-glucosidase (designated HGT-BG) was purified to homogeneity by ammonium sulfate precipitation, gel filtration, and anion-exchange chromatography. HGT-BG is a monomeric protein with an apparent molecular mass of 43 kDa and a pI of 4.2 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing polyacrylamide gel electrophoresis, respectively. Using p-nitrophenyl-beta-D-glucoside as the substrate, we found that the enzyme was optimally active at 50 degreesC and pH 5.0 and had a specific activity of 1,066 micromol min-1 mg of protein-1 and a Km of 0.55 mM under these conditions. The enzyme is particularly resistant to inhibition by glucose (Ki, 1. 36 M) or glucono-delta-lactone (Ki, 12.5 mM), another powerful beta-glucosidase inhibitor present in wine. A comparison of the enzyme activities on various glycosidic substrates indicated that HGT-BG is a broad-specificity type of fungal beta-glucosidase. It exhibits exoglucanase activity and hydrolyzes (1-->3)- and (1-->6)-beta-glucosidic linkages most effectively. This enzyme was able to release flavor compounds, such as geraniol, nerol, and linalol, from the corresponding monoterpenyl-beta-D-glucosides in a grape must (pH 2.9, 90 g of glucose liter-1). Other flavor precursors (benzyl- and 2-phenylethyl-beta-D-glucosides) and prunin (4',5,7-trihydroxyflavanone-7-glucoside), which contribute to the bitterness of citrus juices, are also substrates of the enzyme. Thus, this novel beta-glucosidase is of great potential interest in wine and fruit juice processing because it releases aromatic compounds from flavorless glucosidic precursors.

H2O2 induces apoptosis of pig thyrocytes in culture.

Apoptosis might be involved in the reduction of the thyroid cell population in physiopathological situations such as goitre involution and autoimmune deleterious processes. Up to now, little attention has been paid to the apoptotic phenomenon in the normal thyroid gland the specialized metabolism of which is expected to generate reactive oxygen species. Indeed, thyroid cells have the capacity to synthesize H2O2. In this study, we have analyzed the capacity of H2O2 to trigger apoptosis of pig thyrocytes in culture to try to determine whether thyrocytes exhibit a particular resistance to apoptosis induced by an oxidative stress. We show that exposure of thyrocytes cultured as monolayers to exogenous H2O2 induced cell death with characteristics of apoptosis. The effect of H2O2 was concentration-dependent; apoptotic cells were already observed after exposure to 50 micro M H2O2. At high concentrations (millimolar range), H2O2 exerted toxic effects leading to rapid cell disruption. Within the first hour after the onset of exposure to 50-300 micro M H2O2, early signs of apoptosis, i.e. DNA fragmentation, appeared in a low (0.1-1%) but definite fraction of thyrocytes. The proportion of adherent cells exhibiting DNA fragmentation remained fairly constant after 6, 15 and 24 h. During the 24-h period, an increasing number of cells detached from the culture dish and up to 30-40% of cells in suspension displayed apoptotic features. The fraction of cells that lost contact with the culture dish amounted to up to 25% 24 h after addition of 300 micro M H2O2. In conclusion, as reported for other cell types, low H2O2 concentrations are capable of triggering apoptosis in thyrocytes cultured as monolayers. Thyrocytes that undergo apoptosis secondarily lose contact with neighbour cells and the substratum; cell detachment from the monolayer probably happens within 1-2 h after initiation of DNA fragmentation. Our data show that the apoptotic commitment can take place many hours after initiation of the oxidative stress.

A network of web multimedia medical information servers for a medical school and university hospital.

Modern medicine requires a rapid access to information including clinical data from medical records, bibliographic databases, knowledge bases and nomenclature databases. This is especially true for University Hospitals and Medical Schools for training as well as for fundamental and clinical research for diagnosis and therapeutic purposes. This implies the development of local, national and international cooperation which can be enhanced via the use and access to computer networks such as Internet. The development of professional cooperative networks goes with the development of the telecommunication and computer networks and our project is to make these new tools and technologies accessible to the medical students both during the teaching time in Medical School and during the training periods at the University Hospital. We have developed a local area network which communicates between the School of Medicine and the Hospital which takes advantage of the new Web client-server technology both internally (Intranet) and externally by access to the National Research Network (RENATER in France) connected to the Internet network. The address of our public web server is http:(/)/www.med.univ-rennesl.fr.

Stationary-phase gene expression in Saccharomyces cerevisiae during wine fermentation.

Genetic engineering of wine yeast strains requires the identification of gene promoters specifically activated under wine processing conditions. In this study, transcriptional activation of specific genes was followed during the time course of wine fermentation by quantifying mRNA levels in a haploid wine strain of Saccharomyces cerevisiae grown on synthetic or natural winery musts. Northern analyses were performed using radioactive probes from 19 genes previously described as being expressed under laboratory growth conditions or on molasses in S. cerevisiae during the stationary phase and/or under nitrogen starvation. Nine genes, including members of the HSP family, showed a transition-phase induction profile. For three of them, mRNA transcripts could be detected until the end of the fermentation. Expression of one of these genes, HSP30, was further studied using a HSP30::lacZ fusion on both multicopy and monocopy expression vectors. The production of beta-galactosidase by recombinant cells was measured during cell growth and fermentation on synthetic and natural winery musts. We showed that the HSP30 promoter can induce high gene expression during late stationary phase and remains active until the end of the wine fermentation process. Similar expression profiles were obtained on five natural winery musts.

Identification of atypical strains of Staphylococcus epidermidis by use of molecular tools.

Four atypical coagulase-negative staphylococcal (CNS) isolates from clinical sources were compared with Staphylococcus epidermidis strains by ribotyping. The ribotypes of the four strains shared close rDNA restriction profiles with those of the S. epidermidis strains used. The DNA sequence encoding 16S rRNA demonstrated 99.9% homology with S. epidermidis. S1 nuclease experiments showed that these atypical strains formed a homogeneous genomic group. DNA-DNA homologies between the S. epidermidis type strain CCM 2124 and the four CNS isolates ranged from 70 to 89%. The guanine-plus-cytosine content of the deoxyribonucleic acid of the four strains ranged from 31 to 32 mol%.

Computer assisted medical diagnosis using the Web.

The ADM (Aide au diagnostic Medical) project was started 15 years ago and was the first telematic project for physicians in France using the MINITEL terminal. The knowledge base contains information on more than 10000 diseases from all pathological fields, using more than 100000 signs or symptoms. The ADM system has two main functionalities for physicians: consultation of diseases descriptions and list of diseases containing one or more symptoms. The ADM knowledge base is supported by a relational database management system (DBMS ORACLE) and we developed a Web interface using the Perl language to produce HTML pages for the web server. We will describe our experience on redesigning a large existing medical knowledge base for diffusion on the web Internet.

Using World Wide Web multimedia in medicine.

The development of the Internet [1] has given us many types of information servers in the research and academic communities: anonymous FTP [2], Gopher [3], Wais [4], News [5], and the World Wide Web [6], which is now the most used multimedia information system on the Internet. It is user-friendly and can be used to interface existing information systems and to build new information services in the medical field. We propose to investigate (not exhaustively) the functionalities and applications of the system in medicine; we also present our own experiences of using WWW to distribute medical information.

An intelligent Computer-Assisted Instruction system for clinical case teaching.

The use of computers in the field of medical education is common. Our purpose is to present a Computer-Assisted Instruction system which has been developed over ten years at the University of Compiègne and the University of Rennes Medical School. This system can be used to help the student to solve clinical cases by analyzing and critiquing their answers and by using a knowledge base which has been previously structured in a rule network. It is an intelligent Computer-Assisted Instruction system comprising an author module, a pedagogical module and a student module. The CAI system can be used as a simulation model for any type of diagnostic or therapeutic problem. In this paper we present the author and pedagogical module which have been built using our previous work on intelligent computer-assisted instruction systems.