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Biomedical subjects

M van Gils

Publications and source records attributed to M van Gils.

12 recordsLinked to original sources

High throughput on-line solid phase extraction/tandem mass spectrometric determination of paclitaxel in human serum.

The feasibility of high throughput on-line solid phase extraction/tandem mass spectrometry (SPE/MS/MS) is tested for target analysis of paclitaxel in human serum. The use of a dual Prospekt system, with parallel SPE and elution directly to the mass spectrometer, resulted in a cycle time of 80 seconds for the entire, fully automated assay. The assay proved to be linear from 1 to 1000 ng/mL. Cartridges packed with small sorbent particles functioned both as SPE cartridges and as short analytical columns.

Blood Chemical Analysis↗

Technical description of the IBIS data library. Improved Monitoring for Brain Dysfunction in Intensive Care and Surgery.

The IBIS Data Library (DL) is an annotated data library that contains practically all the monitored data and other clinical information from critically ill patients during surgery and in intensive care. The data have been collected at three sites: the intensive care unit of the Kuopio University Hospital, Finland; Royal Brompton Hospital, London, UK; and St. Bartholomew's Hospital, London, UK. The purpose of the DL is to form the basis for development of biosignal interpretation methods in the Improved Monitoring for Brain Dysfunction in Intensive Care and Surgery project in the European Union (EU) BIOMED2 programme (BMH4-97-2570). The DL contains continuous electroencephalography signals, multimodal evoked potential recordings and diagnostic electrocardiography recorded during intensive care and surgery. In addition, signal types similar to those recorded during an earlier project, the EU-BIOMED1 project IMPROVE, are stored in the DL. In addition, trend data from patient monitors, laboratory data, annotations, nursing actions, and medications recorded and stored by a Patient Data Management System (PDMS) during routine care are included. The data obtained routinely are complemented by special annotations made by a physician who observes the patient during the data collection session. Annotations include, for example, assessment of the awareness of the patient and specific events during surgery not recorded routinely by the PDMS. Inclusion of information about the care plan and the aims of the care make the contents of the DL complete. The present paper describes the technical set-up used for recording of the DL and the contents of the DL. The paper also includes an appendix defining a new data format, the extended evoked potentials format, used for storage of sweep data in the DL.

Brain↗

beta-chemokines and neutralizing antibody titers correlate with sterilizing immunity generated in HIV-1 vaccinated macaques.

One of the obstacles to AIDS vaccine development is the variability of HIV-1 within individuals and within infected populations, enabling viral escape from highly specific vaccine induced immune responses. An understanding of the different immune mechanisms capable of inhibiting HIV infection may be of benefit in the eventual design of vaccines effective against HIV-1 variants. To study this we first compared the immune responses induced in Rhesus monkeys by using two different immunization strategies based on the same vaccine strain of HIV-1. We then utilized a chimeric simian/HIV that expressed the envelope of a dual tropic HIV-1 escape variant isolated from a later time point from the same patient from which the vaccine strain was isolated. Upon challenge, one vaccine group was completely protected from infection, whereas all of the other vaccinees and controls became infected. Protected macaques developed highest titers of heterologous neutralizing antibodies, and consistently elevated HIV-1-specific T helper responses. Furthermore, only protected animals had markedly increased concentrations of RANTES, macrophage inflammatory proteins 1alpha and 1beta produced by circulating CD8(+) T cells. These results suggest that vaccine strategies that induce multiple effector mechanisms in concert with beta-chemokines may be desired in the generation of protective immune responses by HIV-1 vaccines.

AIDS Vaccines↗

Framework for biosignal interpretation in intensive care and anesthesia.

Improved monitoring improves outcomes of care. As critical care is "critical", everything that can be done to detect and prevent complications as early as possible benefits the patients. In spite of major efforts by the research community to develop and apply sophisticated biosignal interpretation methods (BSI), the uptake of the results by industry has been poor. Consequently, the BSI methods used in clinical routine are fairly simple. This paper postulates that the main reason for the poor uptake is the insufficient bridging between the actors (i.e., clinicians, industry and research). This makes it difficult for the BSI developers to understand what can be implemented into commercial systems and what will be accepted by clinicians as routine tools. A framework is suggested that enables improved interaction and cooperation between the actors. This framework is based on the emerging commercial patient monitoring and data management platforms which can be shared and utilized by all concerned, from research to development and finally to clinical evaluation.

Anesthesia↗

Modelling techniques and their application for monitoring in high dependency environments--learning models.

This paper reviews the use of learning models including Bayesian classifiers and artificial neural networks in monitoring and interpreting biosignals. Generally learning models applied for analysis of biosignals are "black-box' types trained on the basis of measured signals. It is illustrated that the training and application of learning models more or less follow the same sequences. The main focus is the interpretation of electrical signals from the brain (electroencephalogram (EEG) and evoked potentials (EP)). Current analysis of these signals often reveals sudden changes in the EEG or evoked potentials to be the earliest discernible signs of inadequate perfusion of the brain. They may reflect problems such as systemic arterial oxygen desaturation or hypotension arising from other body system failures during critical illness. It is suggested that these brain signals should be recorded in the critical care unit, and that they should form part of the annotated database of biosignals established during the IMPROVE project. This would allow for the development of new methods for on-line warning of impending damage to the central nervous system, such that corrective actions could be taken before permanent damage occurred.

Auscultation↗

Functional and molecular characterization of B cell-responsive V delta 1+ gamma delta T cells.

Cells expressing the V delta 1+ gene segment are a minor gamma delta T cell population in human peripheral blood but predominate in epithelial and (inflamed) tissues. The characteristic dendritic-like morphology of these gamma delta T cells is consistent with their putative immune surveillance role in epithelia. Their function, however, remains unknown. We and others previously reported that a subset of V delta 1+ gamma delta T cells proliferates after stimulation with Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines (LCL), but not with fresh peripheral blood-derived B cells. These responses were independent of the type of T cell receptor (TcR) gamma chain co-expressed with the V delta 1 chain. The in vivo relevance of this LCL-mediated activation as well as the nature of the stimulatory ligand on the LCL is not well established. In this study, we tested the proliferative response of V delta 1+ LCL-responsive T cells against non-EBV-transformed B cells, activated through CD40 by murine EL4 B5 cells, and to a panel of B cell lines differing in the expression of EBV nuclear antigen proteins and adhesion/co-stimulatory molecules. The role of the Epstein-Barr virus-derived antigen in the induction of this response could be excluded as the activated (non-EBV-transformed) peripheral blood B cells were also able to induce a proliferative response in the LCL-responsive V delta 1+ T cells. Therefore, the stimulatory ligand on B cells is of cellular rather than of viral origin, and its expression is up-regulated upon activation of B cells. The expression of B7 and CD39 molecules on the surface of activated B cells appeared to be crucial since antibodies to these structures could block the induction of proliferation of the V delta 1+ T cells. Finally, we investigated the diversity of the responding V delta 1+ gamma delta T cell clones by sequence analysis of the TcR delta junctional regions. No restricted V-D-J sequences were found among the LCL-responsive V delta 1+ T cell clones, arguing strongly against a mono- or oligoclonal V delta 1+ gamma delta T cell response to LCL. These findings may explain the presence of polyclonally activated V delta 1+ T cells in inflamed tissues where activated B cells are often present.

Adenosine Triphosphatases↗

Efforts to broaden HIV-1-specific immunity by boosting with heterologous peptides or envelope protein and the influence of prior exposure to virus.

In two previous studies, we have demonstrated the successful protection of human immunodeficiency virus type 1 (HIV-1)-vaccinated rhesus macaques from challenge with SHIV(SF13) with envelop immunogens derived from the closely related HIV-1(SF2) strain. Here we report on two follow-up studies in which we aimed to broaden immunity in order to elicit protection from a more diverse heterologous challenge with SHIV(SF33). In the first study, animals were boosted once with HIV-1(SF33) V2 and V3 peptides that were cross-linked to influenza immune-stimulating complexes (ISCOMs). In the second study, monkeys were boosted twice at 12-week intervals, using a heterologous recombinant gp120 derived from HIV-1(SF33) that was either incorporated into ISCOMs or mixed with the MF59 adjuvant. In both studies, the animals were challenged with 50 monkey infectious doses of SHIV(SF33) 4 weeks after the final boost. All controls became readily infected with the heterologous challenge virus SHIV(SF33). Neither boosting with heterologous SF33 peptides or gp120 afforded protection from infection to SF2-vaccinated animals that had previously resisted SHIV(SF13) challenge. These results demonstrate the importance of developing vaccine strategies that are capable of generating broad immune responses early in the immunization protocol. Furthermore, these findings may illustrate the potential pitfalls of early antigenic sin.

AIDS Vaccines↗