Increased Sensitivity to the Anticonvulsant Effect of Valproate in Aging BN/BiRij Rats

The aim of the present investigations was to study the influence of increasing age on the pharmacodynamics of valproate in BN/BiRij rats, applying a threshold for electrically induced localized seizure activity as a measure of the anticonvulsant effect. Seven groups of healthy male BN/BiRij rats were used, aged 3, 6, 12, 19, 25, 31, and 37 months. Individual plasma concentration versus anticonvulsant effect relationships were determined during a continuous intravenous infusion of sodium valproate at a rate of 5.5 mg/min/kg. The infusion was terminated when the anticonvulsant effect intensity had reached the maximum attainable level or at a total infusion time of three hours. A nonlinear relationship between valproate concentration and anticonvulsant effect intensity was observed with no maximal effect in the concentration range up to 1200 mg · L^–1. With increasing age a parallel shift in the concentration versus anticonvulsant effect relationships toward lower concentrations occurred. Thus increasing age appears to be associated with an increased sensitivity to the anticonvulsant effect of valproate.Suzanne Hovinga: Deceased January 30, 1991.     

Tetraspanins: molecular organisers of the leukocyte surface

Tetraspanins are a large superfamily of cell surface membrane proteins characterised by their four transmembrane domains. They are expressed in a wide variety of cell types and have functional roles in processes, such as cellular adhesion, motility, activation and tumour invasion. Leukocytes express 相似文献   

Regulating the gene: From genetic consumption to regulatory trust

In this article, we examine the changing terms on which genetics-based technologies in two areas agriculture (Genetically Modified Organism, GMOs) and health (genetic diagnostics) have been regulated. These are used to illustrate and examine the proposition that shifts in the politics of governance and regulation (associated in part with the advent of the negotiation state) have meant that the responsibility for the social management of new technology is increasingly shared between the state and the consumer. However, this redistribution of the social management of risk, we argue, fails to establish a sufficient basis for a legitimate regulatory trust. We suggest that trust will depend on embedding broad social values and a self-critical agenda within the regulatory regime itself.     

Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8+ T-cell responses.

PURPOSE: To measure the CD8+ T-cell response to a melanoma peptide vaccine and to compare an every-2-weeks with an every-3-weeks vaccination schedule. PATIENTS AND METHODS: Thirty HLA-A2-positive patients with resected stage I to III melanoma were randomly assigned to receive vaccinations every 2 weeks (13 vaccines) or every 3 weeks (nine vaccines) for 6 months. The synthetic, modified gp100 peptide, g209-2M, and a control peptide, HPV16 E7, were mixed in incomplete Freund's adjuvant and injected subcutaneously. Peripheral blood mononuclear cells obtained before and after vaccination by leukapheresis were analyzed using a fluorescence-based HLA/peptide-tetramer binding assay and cytokine flow cytometry. RESULTS: Vaccination induced an increase in peptide-specific T cells in 28 of 29 patients. The median frequency of CD8+ T cells specific for the g209-2M peptide increased markedly from 0.02% before to 0.34% after vaccination (P <.0001). Eight patients (28%) exhibited peptide-specific CD8+ T-cell frequencies greater than 1%, including two patients with frequencies of 4.96% and 8.86%, respectively. Interferon alfa-2b-treated patients also had significant increases in tetramer-binding cells (P <.0001). No difference was observed between the every-2-weeks and the every-3-weeks vaccination schedules (P =.59). CONCLUSION: Flow cytometric analysis of HLA/peptide-tetramer binding cells was a reliable means of quantifying the CD8+ T-cell response to peptide immunization. This assay may be suitable for use in future trials to optimize different vaccination strategies. Concurrent interferon treatment did not inhibit the development of a peptide-specific immune response and vaccination every 2 weeks, and every 3 weeks produced similar results.     

Hepatitis E Virus: Current Concepts and Future Perspectives

For many years, hepatitis E was considered a disease found only in certain developing countries. In these geographical settings, hepatitis E virus (HEV) causes a self-limiting hepatitis in young adults, except in pregnant females, in whom the mortality is 25 %. Our understanding of HEV has changed radically in the past decade. It is now evident that HEV is a threat to global health. This review article considers the current concepts and future perspectives of HEV and its effects on human health, with particular reference to developed countries.     

Differences in presentation and follow-up between HIV-1 antibody positive teenagers and adults: the need for a more focused approach to care?

Our findings show a high rate of loss to follow-up in HIV-positive teenagers compared with adults. Of concern is the fact that this group also have high rates of sexually transmitted infections, unprotected sex and pregnancy. There is an urgent need to examine the reasons for this and adopt strategies to minimize risk-taking behaviour and to improve access to appropriate healthcare.     

Reliability and sources of variation of the ABILHAND-Kids questionnaire in children with cerebral palsy

Purpose: To determine reliability of the ABILHAND-Kids, explore sources of variation associated with these measurement results, and generate repeatability coefficients.

Method: A reliability study with a repeated measures design was performed in an ambulatory rehabilitation care department from a rehabilitation center, and a center for special education. A physician, an occupational therapist, and parents of 27 children with spastic cerebral palsy independently rated the children’s manual capacity when performing 21 standardized tasks of the ABILHAND-Kids from video recordings twice with a three week time interval (27 first-, and 25?second video recordings available). Parents additionally rated their children’s performance based on their own perception of their child's ability to perform manual activities in everyday life, resulting in eight ratings per child.

Results: ABILHAND-Kids ratings were systematically different between observers, sessions, and rating method. Participant?×?observer interaction (66%) and residual variance (20%) contributed the most to error variance (9%). Test–retest reliability was 0.92. Repeatability coefficients (between 0.81 and 1.82 logit points) were largest for the parents’ performance-based ratings.

Conclusion: ABILHAND-Kids scores can be reliably used as a performance- and capacity-based rating method across different raters. Parents’ performance-based ratings are less reliable than their capacity-based ratings. Resulting repeatability coefficients can be used to interpret ABILHAND-Kids ratings with more confidence.

• Implications for Rehabilitation

• The ABILHAND-Kids is a valuable tool to assess a child's unimanual and bimanual upper limb activities.

• The reliability of the ABILHANDS-Kids is good across different observers as a performance- and capacity-based rating method.

• Parents' performance-based ratings are less reliable than their capacity-based ones.

• This study has generated repeatability coefficients for clinical decision making.