The OpenLabs Project.
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Artificial Intelligence↗
Biomedical subjects
T Groth
Publications and source records attributed to T Groth.
Specifying an open clinical laboratory information system.
This paper presents an overview of the architectural infrastructure in which existing laboratory information systems can be made to interoperate with additional modules offering a range of advanced clinical laboratory functionalities. The infrastructure is based on an open distributed computing platform, and its specification is described using the open distributed processing reference model.
Clinical Laboratory Information Systems↗
Managing the operation of open distributed laboratory information systems.
This paper examines how the concepts and designs of workflow management systems and distributed systems management can be integrated and customized to manage open laboratory computing services. The paper outlines the objectives of managing laboratory computing services and identifies techniques and designs which facilitate this management. The paper also outlines the implementation of an open laboratory service management system.
Clinical Laboratory Information Systems↗
OpenLabs advanced instrument workstation services.
The advanced instrument workstation (AIW) is one of a number of system modules developed in the OpenLabs project, offering advanced services that complement the basic services available from laboratory information systems (LIS) in general. The AIW services relate to instrument interfacing, user interfacing, quality control, calibration verification, patient result validation, local and remote fault diagnosis and maintenance, and external quality assessment (EQA) by external organisations.
Clinical Laboratory Information Systems↗
Remote instrument telemaintenance.
In the past decade, great technological progress has been made in telemaintenance of mainframe and mini computers. As hardware technology is now available at an acceptable cost, computer aided trouble-shooting can be adapted to laboratory instrumentation in order to significantly improve repair time, avoid instrument downtime by taking advantage of predictive methods, and provide general diagnostic assistance. Depending on the size of the instrument, the telemaintenance facility can be dedicated to a single instrument or alternatively a telemaintenance server can manage multiple distributed small instruments through a Local Area Network. As complex failures can occur, the local diagnosis capabilities may be exceeded and automatic dialing for connection to computerized Remote Maintenance Centers is needed. The main advantages of such a centre, as compared to local diagnosis systems, are the increased access to more information and experience of failures from instrument installations, and consequently the provision of training data updates for Artificial Neural Networks and Knowledge Based Systems in general. When an abnormal situation is detected or anticipated by a diagnosis module, an automatic alert is given to the user, local diagnosis is activated, and for simple solutions, instructions are given to the operator. In the last resort, a human expert can be alerted who, with remote control tools, can attend to the failures. For both local and remote trouble-shooting, the data provided by the instrument and connected workstation is of paramount importance for the efficiency and accuracy of the diagnosis. Equally, the importance of standardization of telemaintenance communication protocols is addressed.
Clinical Laboratory Information Systems↗
Fibronectin matrix formation by human fibroblasts on surfaces varying in wettability.
The spatial organization of extracellular fibronectin on biomaterial surfaces might be important for interaction with tissue cells. In previous investigations we have demonstrated that hydrophilic materials bind preadsorbed fibronectin that can easily be reorganized by fibroblasts in a specific matrix-like structure, while on less wettable materials (possessing water contact angles above 60 deg) the cells were unable to do this. As the cells continuously produce their fibronectin matrix, we tried in this study to answer the question of how the surface wettability of biomaterials influences the endogenous fibronectin matrix formation and its subsequent organization on the substrate. We cultured fibroblasts for 72 h on five different wettable surfaces: glass, aminopropyltriethoxysilane, pellethane, polyvinylchloride, and silicone, with water-contact angles gradually ranging from 25 to 105 deg. We demonstrated that the decreasing wettability of the materials significantly reduced endogenous fibronectin deposition on the substratum. Moreover, fibrillar organization of fibronectin appeared only on relatively hydrophilic glass and APS substrate, while on more hydrophobic materials like PVC and SI, cells secreted some fibronectin but were not able to organize it into a fibronectin matrix. These results were correlated with an altered cell morphology and spreading on these materials. In addition, an ELISA method has been implemented to quantify fibronectin matrix formation as a possible measure of the biocompatibility of materials, where a clear relation has been found between fibroblast growth and fibronectin matrix formation.
Adsorption↗
Modification of poly(ether urethane)elastomers by incorporation of poly(isobutylene)glycol. Relation between polymer properties and thrombogenicity.
Non-polar hydrophobic poly(isobutylene)glycol (PIBG) was substituted for poly(tetramethylene ether)glycol (PTMEG) in poly(ether urethanes) based on 4,4'-methylenebis-(phenylisocyanate) (MDI) and 1,4-butanediol (BD) as chain extender. Two series of polyurethanes differing in their soft segment length, polymer composition, and hard segment content were studied by dynamic mechanical analysis (DMA) and static, as well as dynamic, contact angle measurements. The thrombogenicity of these polymers was characterized by studying the adhesion and activation of platelets using ELISA for GMP 140 and fluorescence microscopy. It was found by DMA that in PIBG-containing polyurethanes (PUE) exist soft domains containing hard segments, strictly separated hard segment domains, and hard segments partially mixed with soft segments. Contact angle measurements revealed that 25% PIBG or even less, are sufficient for a remarkable enrichment of these non-polar soft segments on the polymer surface. The platelet adhesion/activation on these materials was demonstrated to increase with the rise in hard segment content, as well as with an enhancement of the PIBG content. However, comparison of PIBG-containing PUE with medical applied polypropylene and pellethane expressed that PUE with PIBG content equal or less 25% have excellent haemocompatibility.
Biocompatible Materials↗
Application of enzyme immunoassays for testing haemocompatibility of biomedical polymers.
In this study enzyme immunoassays are presented for the assessment of platelet adhesion/activation and fibrinogen adsorption/conformation. The estimation of platelet adhesion and activation was performed with two enzyme immunoassays (EIAs) using monoclonal antibodies directed against CD42b (GP lb) and CD 62 (GMP 140 or P-Selectin). The applicability of EIA was first demonstrated in microtitre plates coated with fibrinogen. The thrombogenic substrate showed that platelet adhesion and activation reached a plateau level within 30 min. The use of EIA for testing biomaterials was demonstrated with polymeric reference materials where a differentiation of materials with respect to adhesion and activation was achieved. To validate the EIA scanning electron microscopy was applied and confirmed the different extent of adhesion and activation of platelets on reference materials. In addition, polyurethaneureas, based on 4,4'-diphenylmethane diisocyanate and polytetramethylene glycols, with different hard segment content and composition were investigated. It was found that both adhesion and activation were not simply dependent on the hard segment content but also on the hard segment composition. To get more insight into the mechanism of this process, two EIAs for the binding of fibrinogen using polyclonal and monoclonal antibodies were developed. There it was shown that the adhesion and activation of platelets on polyurethaneureas was not simply dependent on the total amount of adsorbed fibrinogen but rather on its conformation, indicated by the binding of the monoclonal antibody directed vs the gamma-chain of fibrinogen.
Adsorption↗
Immobilization of heparin on polylactide for application to degradable biomaterials in contact with blood.
The poly-(D, L-lactide) RESOMER R208 (Boehringer-Ingelheim, Germany) was modified with heparin to improve the blood contacting properties of the material. The immobilization of herapin was carried out by covalent binding with glutaraldehyde as the coupling agent. The reaction conditions, such as temperature and time, were varied to optimize the binding of heparin. The efficiency of the immobilization was monitored with respect to the total amount of coupled herapin with a toluidine blue assay and the anticoagulant activity of immobilized heparin with a factor Xa assay. The hemocompatibility of the modified polylactide was estimated after blood-material contact by the activation of platelets measured with an enzyme immuno assay for GMP140. Immobilization at ambient temperature and a reaction time of 2 h resulted in maximal heparin binding, high anticoagulant activity, and low thrombogenicity. Since the remaining unsaturated aldehyde groups of the coupling agent may cause a low hemocompatibility of the material, washing of the heparinized polylactide was carried out with ethanol. However, it was shown that washing diminished the anticoagulant activity of heparin and increased the thrombogenicity. The prolonged storage of heparinized polylactide in phosphate buffered saline for 8 days demonstrated that small quantities of heparin were released but the hemocompatibility was further improved, indicated by an increasing anticoagulant potential and a decrease in platelet activation with incubation time. A comparison of polylactide, heparinized polylactide, polypropylene, and Pellethane with respect to platelet activation by GMP140 assay and scanning electron microscopy, revealed that the heparinization of polylactide substantially improved the hemocompatibility of RESOMER R208, making the material comparable to Pellethane.
Anticoagulants↗
Fibroblast spreading and proliferation on hydrophilic and hydrophobic surfaces is related to tyrosine phosphorylation in focal contacts.
Fibroblasts adhesion, spreading, and proliferation was investigated in this study using glass and octadecyl glass (ODS) as models for hydrophobic substrata in the absence or presence of preadsorbed fibronectin (FN). To learn more about the underlying mechanism of the biocompatibility of materials, the organization of the beta 1 integrin and the phosphorylation of tyrosine residues in focal contacts was investigated by immunofluorescence microscopy. The diminished adhesion and spreading of fibroblasts on hydrophobic ODS in comparison to clean glass was indicated by a diffuse presence of actin and by the absence of focal contacts and phosphotyrosine activity. In contrast, on hydrophilic glass, initial stress fibres and focal adhesions appeared accompanied by a moderate phosphotyrosine activity. The preadsorption of FN improved the interaction of fibroblast with both surfaces as indicated by the formation of prominent actin stress fibres and the clusterization of beta 1 integrins in the focal contacts which was co-localized with an increased phosphotyrosine activity. The proliferation of fibroblasts measured after 72 h was inhibited on ODS in comparison to glass. Preadsorption of FN, however, increased the cell proliferation index on both surfaces, which was higher than on pure glass. The improved cell adhesion, spreading, and proliferation of fibroblasts run in parallel with an increased total tyrosine phosphorylation activity measured by an enzyme immuno assay (EIA). It was concluded that the signalling via integrins might be a decisive event during the cell-biomaterial interaction.
Adsorption↗
The OpenLabs approach to clinical laboratory computing.
This paper describes the architectural infrastructure to support a number of advanced functionalties for the clinical laboratory developed by OpenLabs. This infrastructure is based on an open distributed computing platform. A brief overview is given of the advanced functionalities provided by the OpenLabs modules through the novel application of knowledge-based systems, databases, and telematics; we also describe the communications architecture which allows these modules to interoperate with each other and with existing Laboratory Information Systems and instruments. The OpenLabs approach to the provision of generic interfaces to such existing systems is described, together with the OpenLabs Service Manager which supports the automated management of the laboratory in this distributed computing environment.
Artificial Intelligence↗
Adhesion of human peripheral blood lymphocytes is dependent on surface wettability and protein preadsorption.
The influence of surface wettability and preadsorption of plasma proteins on cell adhesion was studied using human peripheral blood lymphocytes (PBL). Hydrophilic glass and hydrophobic octadecyl glass were used as model surfaces with known wettability. The adhesion of PBL was investigated under non-flow conditions that are considered as a model for the adhesion of migrating lymphocytes in the tissue. Furthermore, adhering lymphocytes were exposed to increasing shear forces to investigate the detachment under laminar flow conditions to simulate the situation during blood flow. The proteins used in this study were attachment proteins such as fibrinogen, fibronectin and vitronectin. Human serum albumin was used as a control. It was found under both conditions (static and dynamic) that PBL adhesion was strongly influenced by the wettability of the surfaces. Furthermore, it was shown that the properties of the underlying surface influenced the interaction between preadsorbed attachment proteins and PBL.
Blood Proteins↗
OpenLabs: the application of advanced informatics and telematics for optimization of clinical laboratory services.
OpenLabs has four major objectives: to improve the efficiency and effectiveness of clinical laboratory services by the integration of Knowledge Based Systems (KBSs) with Laboratory Information Systems (LISs) and equipment; to provide and implement standard solutions for Electronic Data Interchange (EDI) between laboratories and other medical systems; to specify a fully Open architecture for an integrated Clinical LIS and demonstrate the integration of various KBS modules on the open architecture platform; and to demonstrate the integration of OpenLabs modules with existing LISs.
Clinical Laboratory Information Systems↗
The effects of different intravenous feeding regimens on the rates of synthesis of alpha1-antitrypsin after surgery.
The effects of two nutritional regimens on the synthesis of alpha-1 antitrypsin were investigated postoperatively in gynaecological cancer patients. Total parenteral nutrition (TPN) or a hypocaloric amino acid mixture was administered on the day of surgery and continued for 3 days. The rate of synthesis of alpha-1 antitrypsin was estimated by a computer model from serial plasma concentrations of this protein and a reference protein, albumin. The hypocaloric amino acid mixture resulted in a more negative nitrogen balance than that produced during administration of TPN containing the same amount of nitrogen but more non-protein energy. Urinary excretion of 3-methylhistidine was significantly greater (p = 0.017) in the hypocaloric amino acid group (350 +/- 40 mumol/day; mean +/- SE) on the third postoperative day, as compared to the TPN group (240 +/- 20 mumol/day). In spite of this the synthesis of alpha-1 antitrypsin was apparently greater in the hypocaloric amino acid than in the TPN group. The accumulated plasma appearance rate of alpha-1 antitrypsin was significantly higher (p = 0.0465) in HAA group, at 70 h it was 490 +/- 40 compared to 400 +/- 20 times the pre-operative synthesis in the TPN group.
Journal Article↗
Estimation of growth hormone secretory patterns in children with use of a numerical deconvolution technique: experimental design with use of computer simulation.
Growth hormone (GH) secretion rates were estimated from 24-hour plasma GH concentration profiles using a model-based numerical deconvolution method. The basic kinetic parameters describing GH distribution and elimination were obtained from studies using single intravenous injections in GH-deficient children. Computer simulation techniques were used to produce 24-hour GH secretion profiles, which could serve as reference curves for analysis of the impact of certain practical aspects of the estimation of GH secretion, such as the method of blood sampling (discrete or integrated), sampling frequency and analytical errors. The results show that sampling intervals of 20 min are acceptable even in the presence of analytical errors, and that with this sampling interval, discrete blood sampling does not seem to be preferable to continuous withdrawal of blood.
Blood Specimen Collection↗
The effect of shear rate on the adhesion/activation of human platelets in flow through a closed-loop polymeric tubular system.
Three polymers, produced as reference materials of a European Communities program, namely PE, PP, and PVC, in tubular form, were comparatively evaluated for their hemocompatibility. In particular, the following parameters: platelet retention index, beta-thromboglobulin (beta-TG) release from activated platelets, and expression of the platelet protein GMP 140 (PADGEM) were measured as a function of time for whole anticoagulated human blood flowing in a closed-loop system under two different shear rates of 2000 and 500 s-1. Data up to 20 min (afterwards there was hemolysis) showed a fluctuating platelet retention index as time increased for PE and PVC and an increasing value for PP. Platelet aggregation and dislodgment from the surface could not be differentiated. Activation of platelets as expressed with beta-TG release were higher for both PE and PP in both shear rates in comparison to PVC which elicited a higher response at the high shear rate. Finally, PADGEM estimations seem to indicate a more stable platelet retention layer for PP than PE or PVC.
Humans↗
Protein adsorption, lymphocyte adhesion and platelet adhesion/activation on polyurethane ureas is related to hard segment content and composition.
Segmented polyurethane ureas with different hard segment content and composition were synthesized using 4,4'-diphenylmethane diisocyanate and polytetramethylene glycols. Using polyols with different molecular weights, it was possible to synthesize polyurethane ureas with either: (i) a constant ratio of urethane to urea bonds; (ii) a constant urethane content; or (iii) a constant urea content. Bulk properties were assessed by dynamic mechanical analysis. Surface properties were estimated by contact angle measurements and streaming potential measurements. Haemocompatibility was evaluated in vitro by measuring the adsorption of human serum albumin (HSA) and fibrinogen (Fg), the adhesion of human peripheral blood lymphocytes (PBL), and the presence of activated platelets on the biomaterial surfaces. Enzyme immuno assays (EIA) have been specially developed for this purpose for the detection of antibody-recognizable plasma proteins and platelet surface membrane proteins. No simple correlation between chemical structure of the polymers and surface properties was found. Parameters of haemocompatibility correlated more closely with hard segment content and chemical composition than with the surface characteristics of the polymers. Adsorption of plasma proteins, adhesion of lymphocytes and the adhesion/activation of platelets were found to increase with increasing hard segment content of the polyurethane ureas. However, the monoclonal-antibody recognisable fibrinogen and the platelet activation were nearly constant with increasing hard segment content, if the urea content was kept constant.
Adsorption↗
Adhesion of human peripheral lymphocytes on biomaterials preadsorbed with fibronectin and vitronectin.
The adhesion of human peripheral lymphocytes (HPL) was studied after preadsorption of fibronectin (FN) and vitronectin (VN) on hydrophilic glass and hydrophobic octadecyl glass. The adhesion of HPL was shown to be dependent not only on the wettability but also on the protein preadsorbed. Vitronectin expressed not only a higher extent of adhesion under static conditions but also a stronger interaction with HPL, indicated by the low detachment under shear stress. The flow experiments also demonstrated that FN adsorbed on octadecyl glass may undergo conformational changes because HPL could be easily removed. Scanning electron microscopy revealed that HPL on both FN- and VN-coated glass spread well whereas particularly on FN-coated octadecyl glass less cell spreading was observed; moreover, some round cells were detected. The typing of adherent HPL by immunofluorescence microscopy showed that on FN- and VN-coated glass about 70% of all HPL were T-cells (CD 3+). However, on octadecyl glass, particularly on VN, a smaller percentage of CD 3+ cell was observed. The testing for the beta 1 integrin--the receptor for FN and the alpha v integrin--the receptor for VN demonstrated that about 70% of all cells on FN-coated glass were positive for the beta 1 integrin. On VN-coated glass, however, only 5% of HPL were positive for the beta 1 integrin. Although on VN a high adhesion and strong binding of HPL was observed, no presence of the alpha v integrin was detected.
Adsorption↗