Sprouting of axonal collaterals after spinal cord injury is prevented by delayed axonal degeneration.

After an incomplete spinal cord injury (SCI), partial recovery of locomotion is accomplished with time. Previous studies have established a functional link between extension of axon collaterals from spared spinal tracts and locomotor recovery after SCI, but the tissular signals triggering collateral sprouting have not been identified. Here, we investigated whether axonal degeneration after SCI contributes to the sprouting of collaterals from axons spared after injury. To this end, we evaluated collateral sprouting from BDA-labeled uninjured corticospinal axons after spinal cord hemisection (SCI(H)) in wild type (WT) mouse and Wld(S) mouse strains, which shows a significant delay in Wallerian degeneration after injury. After SCI(H), spared fibers of WT mice extend collateral sprouts to both intact and denervated sides of the spinal cord distant from the injury site. On the contrary, in the Wld(S) mice collateral sprouting from spared fibers was greatly reduced after SCI(H). Consistent with a role for collateral sprouting in functional recovery after SCI, locomotor recovery after SCI(H) was impaired in Wld(S) mice compared to WT animals. In conclusion, our results identify axonal degeneration as one of the triggers for collateral sprouting from the contralesional uninjured fibers after an SCI(H). These results open the path for identifying molecular signals associated with tissular changes after SCI that promotes collateral sprouting and functional recovery.

Integration of medical applications: the 'mediator service' of the SynEx platform.

Interoperability is a key issue and a long-term domain of research for distributed healthcare information systems. The SynEx European project provides open and standard integration platform for both new and legacy medical applications. It aims to provide access to hospital information services, patient records, and to medical knowledge, in a seamless way, hiding the distribution aspects and the heterogeneity of the underlying systems. In this study, we describe the SynEx 'mediator service', a software engineering component, that is used to facilitate the development of mediators between any pair of SynEx components and to manage the corresponding interchange messages. Both a C++ library and a Java package of a generic mediator model are provided with several ready-to-use specialisations for well-defined use. The use of the XML technology as a powerful data interchange format and as an efficient data structure converter is proposed and discussed.

The "mediator service", a component to ease the integration of medical applications in the SynEx framework.

Interoperability is a key issue and a long-term domain of research for distributed healthcare information systems. The European project SynEx provides an open and standard integration platform for both new and legacy medical applications. It allows the collaboration of distributed and heterogeneous healthcare records and services. It aims to provide access to Hospital Information Services, to remote sources of medical data and to medical knowledge, in a seamless way, hiding the distribution aspects and the heterogeneity of systems. In this project, the Medical Informatics Department of the Broussais University Hospital is responsible for the development of the "Mediator Service". It is a software component of the SynEx platform which is used as a "glue" mechanism to provide a flexible way to facilitate the interchange between any pair of systems, with different nomenclatures and data structures. The Mediator Service uses a generic model of mediators to create, through specialization, specific mediators for practical cases. Based on this model, it offers a C++ library to be used as the tool case by the programmers, to reduce the development effort. The use of XML as a powerful data interchange format and as a data structure descriptor is proposed and evaluated.

Effects of fatty acids on human platelet glutathione peroxidase: possible role of oxidative stress.

Highly polyunsaturated fatty acids of the n-3 family are known to be inhibitors of platelet functions, but these fatty acids (FA) may alter the platelet antioxidant status, depending on their concentrations. The present study was aimed to investigate the effect of various FA on glutathione-dependent peroxidase (GPx), the required antioxidant enzyme for degrading FA hydroperoxides. Human platelets were enriched in vitro with either n-3 (18:3, 20.5, or 22.6), n-6 (18:2 or 18:3) FA, 18:1 n-9 or 16:0, and the GPx activity was then measured. It was found that n-3 FA enhanced the GPx activity whereas the others did not affect the enzyme activity. The increased GPx activity was associated with an increased amount of the enzyme measured by Western blotting. The enhanced activity and amount of GPx induced by 22:6n-3, the most potent activator among the n-3 FA, was completely abolished in the presence of cycloheximide at a concentration known to inhibit platelet protein synthesis. Because platelets are devoid of nucleus, which rules out the involvement of transcriptional factors, this suggests that 22:6n-3 might act at a translational level. On the other hand, 22:6n-3 treatment increased the malondialdehyde formation and decreased the vitamin E level in platelets, both events that could be prevented by the antioxidant epicatechin. Because epicatechin also suppressed the enhancement of both the activity and amount of GPx induced by 22:6n-3, we conclude that the increased GPx activity (possibly via protein synthesis) might be associated with an oxidative stress induced by 22:6n-3 and/or 20:4n-6 released from the platelet endogenous pool in the course of the 22:6n-3 enrichment.

Involvement of lipid peroxidation in platelet signalling.

A well-known signalling pathway in blood platelets consists in the release of arachidonic acid (AA) from membrane phospholipids and its specific oxygenation into bioactive derivatives. In particular, cyclic prostaglandin endoperoxides and thromboxane A2 are potent inducers of platelet functions and are produced in greater amounts when the level of lipid hydroperoxides is higher than normal, as 'physiological concentrations' of such peroxides activate the cyclooxygenation of AA. In this context, a lower activity of platelet glutathione peroxidase (GPx), the key-enzyme for the degradation of lipid hydroperoxides, has been reported in aging, which will ensure a longer life span to those peroxides. Accordingly, the biosynthesis of pro-aggregatory prostanoids is elevated in platelets from the elderly. On the other hand, fatty acids from marine origin have been recognized as inhibitors of platelet functions, and they may alter the redox status of cells. They may for instance increase the platelet GPx activity, an effect that can be prevented by antioxidants. Overall, these data point out the relevance of the redox status in platelet functions.

N-3 fatty acid-induced lipid peroxidation in human platelets is prevented by catechins.

The effects of catechins were studied in both unstimulated platelets and platelets submitted to a mild oxidative stress induced by docosahexaenoic acid (DHA). Human unstimulated platelets were incubated in the presence of catechin or epicatechin (1, 10 or 100 microM) for 2 h at 37 degrees C. Treatment by 1 microM epicatechin was sufficient to induce a significant inhibition (-30%) of basal thromboxane B2 formation. This result is consistent with the observed inhibitory effects of flavonoids on platelet aggregation. DHA treatment of platelets decreased the amount of alpha-tocopherol and increased the malondialdehyde (MDA) formation. The presence of epicatechin or catechin prevented the oxidative stress induced by DHA. Indeed, the platelet alpha-tocopherol level was significantly increased when compared to that of platelets treated by DHA alone, to reach the control level, whereas MDA was depressed to a level even lower than the control one. Our results indicate that catechin and especially epicatechin protect platelets from a peroxidative stress.

[Activation of T-lymphocytes in Crohn disease and in ulcerative hemorrhagic rectocolitis. Therapeutic implications]. / Activation des lymphocytes T dans la maladie de Crohn et dans la rectocolite ulcéro-hémorragique. Implications thérapeutiques.

Inflammatory bowel disease (IBD) encompasses two forms of intestinal inflammation: ulcerative colitis and Crohn's disease. Besides abnormalities of immunoglobulins production and complement activation, T lymphocytes play an important role in pathogeny of these diseases. Although T-cells number is increased in intestinal mucosa of such patients, CD4/CD8 ratio of T lymphocytes subsets is normal in mucosa. Activated T-cells expressing interleukin-2 receptors (CD25) are increased in lamina propria from patients with IBD. Cytokines induce abnormal expression of class II antigens of major histocompatibility complex by epithelial cells which may act as antigen presenting cells to CD4 T-cells. Better understanding of pathogenic mechanisms in IBD might justify new immunosuppressive therapeutics to treat these patients.

Tracheal colonization with Sphingomonas paucimobilis in mechanically ventilated neonates due to contaminated ventilator temperature probes.

Sphingomonas paucimobilis was isolated from tracheal secretions of a total of 85 mechanically ventilated babies in a neonatal intensive-care unit (NICU) during a two-year-period. None of the neonates developed pneumonia or sepsis. After each increase in the fluctuating number of S. paucimobilis isolates, extra attention was paid to hand hygiene and to the maintenance of the ventilation equipment. This resulted in a reduction of the frequency of isolation each time. Cultures of all liquids in use and of the ventilation equipment were negative on several occasions. Fifteen months after the start of the outbreak, the NICU was moved to another building, and some older ventilation equipment was abandoned. After a period of six weeks without problems, S. paucimobilis was isolated in association with at least four ventilators. A new investigation showed that the ventilator temperature probes were the source of contamination. Once effective sterilization procedures for the temperature probes were introduced no new cases appeared, until a spare ventilator with an unautoclaved temperature probe was accidentally used and this caused contamination of one child. After correction, no further cases have occurred to date. The clonal relatedness of the outbreak isolates from patients and from ventilator temperature probes was documented by fingerprinting with the arbitrarily primed polymerase chain reaction.

The number needed to treat: a clinically useful nomogram in its proper context.

The number needed to treat is a meaningful way of expressing the benefit of an active treatment over a control. It can be used either for summarising the results of a therapeutic trial or for medical decision making about an individual patient, but its use at the bedside has been impeded by the need for time consuming calculations. A nomogram has therefore been devised that will greatly simplify the calculations. Since calculations are now easy, the number needed to treat can be used to access the value of several interventions, although it does have its limitations. In particular it should not be used when it is not known whether the relative risk reduction associated with an intervention is constant for all levels of risk, or for periods of time longer than that studied in the original trials.

Legacy systems: managing evolution through integration in a distributed and object-oriented computing environment.

Legacy systems are crucial for organizations since they support key functionalities. But they become obsolete with aging and the apparition of new techniques. Managing their evolution is a key issue in software engineering. This paper presents a strategy that has been developed at Broussais University Hospital in Paris to make a legacy system devoted to the management of health care units evolve towards a new up-to-date software. A two-phase evolution pathway is described. The first phase consists in separating the interface from the data storage and application control and in using a communication channel between the individualized components. The second phase proposes to use an object-oriented DBMS in place of the homegrown system. An application example for the management of hypertensive patients is described.

ARTEMIS-2: an application development experiment with the HELIOS environment.

A medical application is a highly complex system that embraces many data types and a very large number of data processing functions and methods. The development of integrated software engineering environments has deeply changed the conception of applications and the profile of the application developers. In this paper, we address the problem of the development process of a specific multimedia application, called ARTEMIS, within the distributed HELIOS environment. The application is intended to manage information about hypertensive patients, in particular, retrieval and display of administrative, clinical and biological data and display and analysis of digital angiography images and medical reports. The objective is to show how the developer can use, customize and organize the services HELIOS provides. A particular focus is set on reuse strategies and integration during the development process. A scenario has been realized and illustrates the current state of the application. The discussion focuses on the advantages of such distributed environments in medical application development.

The HELIOS Unification Bus: a toolbox to develop client/server applications.

In the medical domain, new developments commonly rely on client/server architectures. But face to distributed environments, the software developers encounter a tremendously increasing complexity when building integrated applications. This paper presents the HELIOS Unification Bus (HUB), a communication integration framework for the HELIOS medical software engineering environment that allows the exchange of data between components that can be hosted on heterogeneous machines linked by a network. The HUB is developed as a C++ toolbox over UNIX and TCP/IP. It includes a message routing entity called router and a generic application programming interface (API), implemented as a C++ library, that allows to build easily software components compliant with the standardised HELIOS language. Messages conveyed by the bus are composite objects that are serialized to be transmitted over the bus using the ASN.1 ISO presentation protocol. The article describes the use of the bus to ease the development and execution of distributed medical applications and its role from the communication integration standpoint.

Analysing and developing object-oriented medical applications with HELIOS.

The HELIOS project promotes systematic reuse of existing software in a valuable methodological context. In order to reach this goal, the Analysis and Design Development Environment (ADDE) has been realized as a HELIOS component. This component includes the Analysis and Design sub-component (ADT), which supports the Rumbaugh's object-oriented methodology and the Insertion Retrieval Tool (IRT), which implements the reuse. The ADT sub-component enhances the quality of software development permitting a correct analysis, and design and a satisfactory documentation. The IRT Tool is dedicated to reuse by retrieving parts of existing applications (retrieve) and by qualifying elements just created or updated (insertion). A faceted system adapted to the medical domain allows an efficient search among the object database. Both tools contribute to reducing the cost of software development. This paper presents the design and the implementation of these tools in the HELIOS framework.

A software engineering approach for medical workstations development.

Multimedia medical workstations represent the natural tool for accessing the hospital information system environment. They are complex medical systems that have to gather, in a single framework, a large collection of components dealing with multimedia medical objects. To remain current with both medical practice and with advances in the computer science field, they have to allow the iterative addition of new functions to the set of existing ones. In this paper, after a survey of commonly required medical workstation functional components, we shall try to discuss how a software engineering approach can streamline the development of a medical workstation. Different software engineering tools needed to build the functional components of a workstation are described. Their integration in a single dedicated environment is considered through four perspectives: data, presentation, communication and control. Benefits and limitations of an object-oriented approach are discussed.

[3 pediatric cases of leptospirosis]. / Trois observations pédiatriques de leptospirose.

Three children presented with an association of pains, infectious syndrome, acute renal failure, hepatitis and meningitis, that lead to the diagnosis of leptospirosis. The clinical spectrum of this rare disease are recalled.

[Peripheral facial paralysis. Experience of a multidisciplinary approach]. / La paralysie faciale périphérique. Expérience d'une approche pluridisciplinaire.

The authors report the evolution of 54 patients suffering from complete paralysis of the seventh cranial nerve. They point out the interest of a good diagnose and a multidisciplinary treatment including: drugs, infiltration, kinesitherapy and electrotherapy. A good repair (77%) is obtained if the treatment is early and regular. This therapy will be used according the results of clinical and electrophysiological examinations.