Biomedical subjects

T Groth

Publications and source records attributed to T Groth.

At least 37 records · Page 2Linked to original sources

PubMed1999

Production and elimination of hyaluronan in rheumatoid arthritis patients: estimation with a loading test.

OBJECTIVE: To evaluate the benefit of determining the maximal elimination rate (Vmax) and the endogenous production of hyaluronan (HYA) in relation to the basal HYA concentration (c0) in rheumatoid arthritis (RA) patients; and to evaluate the compatibility of a new model for HYA kinetics, taking renal elimination into separate account in the overall clearance of HYA from the blood. METHODS: The calculations of production and elimination of HYA were based on the HYA loading test, which was performed in 21 patients with RA and 15 healthy controls. A blood sample was drawn before the loading test, followed by an intravenous (i.v.) injection of HYA as a single bolus dose of 7.5 mg. Blood samples were taken regularly during the next 60 minutes. A theoretical model with computational analysis of the data collected was used for calculating HYA production and elimination. RESULTS: Patients with RA had significantly higher c0 than healthy controls, although in 10 of 21 patients c0 was within the normal range. The RA patients also had higher Vmax than healthy controls, but the difference was not significant. The calculated production of HYA was increased in RA patients (P = .001) and correlated with c0 (P < .0001). The new model for HYA kinetics, in which the renal elimination was taken separately into account, proved to be more compatible than the previous model. CONCLUSION: The HYA loading test can help determine whether the increased serum level of HYA in RA patients is due to a high production or reduced elimination of HYA or both.

Adult↗

PubMed1999

Functionalized nanoparticles for endotoxin binding in aqueous solutions.

Nanoparticles consisting of a polystyrene core and a polyglycidyl methacrylate shell were prepared by a two-step emulsion polymerization. The size and surface properties of the particles were characterized by scanning electron microscopy, dynamic light scattering and polyelectrolyte titration techniques. Particles were found to be monodisperse with a mean diameter of about 85 nm. Parent particles were modified with a number of different ligands including diamines of increasing chain length, amino acids and corresponding amines and higher molecular weight ligands like polymyxin B. The modified particles were tested for their endotoxin (ET) binding capacity in water and physiological sodium chloride solution with the Limulus amebocyte lysate (LAL) assay. It was found that the ET binding properties of the different ligands depend both on the ability of the ligand to form Coulomb- and van der Waals-interactions with the ET molecule influenced by the nature of the suspension medium. Therefore, the choice of ligands for particle modification has to consider minutely the conditions under which ET has to be removed, e.g. removal from pure water, dialysis fluids, plasma or blood.

Biocompatible Materials↗

PubMed1999

Object-oriented biomedical system modeling--the rationale.

A short tutorial and a rationale for Object-Oriented Biomedical (Continuous) System Modelling (OOBSM) are given. The paper investigates and defines what is needed in order to make the work with complex bio-medical and pathophysiological models easier, less error prone and conceptually clearer than is possible by using the existing modelling techniques. It also contains a specification of what is required in order to make such models and corresponding knowledge communicable among different research groups and in order to use such models as components in even more complex models. The work shows that hitherto available continuous system modelling languages and tools are less suitable for the construction of complex, interdisciplinary, multilevel, hierarchical models and model components and that those modelling languages do not allow for easy exchange and communication of the model knowledge between different research groups and sites. It concludes that object-oriented and distributed objects methodologies are both feasible and suitable for such modelling.

Artificial Intelligence↗

PubMed1999

Object-oriented biomedical system modelling--the language.

The paper describes a new object-oriented biomedical continuous system modelling language (OOBSML). It is fully object-oriented and supports model inheritance, encapsulation, and model component instantiation and behaviour polymorphism. Besides the traditional differential and algebraic equation expressions the language includes also formal expressions for documenting models and defining model quantity types and quantity units. It supports explicit definition of model input-, output- and state quantities, model components and component connections. The OOBSML model compiler produces self-contained, independent, executable model components that can be instantiated and used within other OOBSML models and/or stored within model and model component libraries. In this way complex models can be structured as multilevel, multi-component model hierarchies. Technically the model components produced by the OOBSML compiler are executable computer code objects based on distributed object and object request broker technology. This paper includes both the language tutorial and the formal language syntax and semantic description.

Algorithms↗

PubMed1999

Investigation of plasma protein adsorption on functionalized nanoparticles for application in apheresis.

Particles with specific ligands for the adsorption of plasma proteins can be used in therapeutic or preparative apheresis. The development of these particles may benefit from an improved knowledge of the relationship between protein adsorption and the structure of ligands. Nanoparticles were functionalized with aliphatic diamines of increasing chain length; with the amino acids lysine, tryptophan, histidine, and their corresponding amines; and with tryptophan and histidine spaced with diamines of different length. Suitable protocols were developed for the washing of particles and the subsequent desorption of proteins adsorbed from human plasma. The adsorption pattern, as well as the quantification of the overall adsorption of proteins on these modified particles, was investigated with gel electrophoresis. This was followed by immunoblotting which yielded specific assessments of bound human serum albumin and fibrinogen. The comparison of protein adsorption with surface charge density and measured hydrophobicities yielded no simple correlations although in general more hydrophobic ligands bound higher quantities of protein. The detection of human serum albumin yielded similar results because it was observed for overall protein adsorption while the adsorption of fibrinogen expressed a different pattern. In this case, particular nanoparticles functionalized with aliphatic diamines bound significantly higher amounts of fibrinogen than all other ligands.

Adsorption↗

PubMed1999

Series analyses and quality specifications required for monitoring over time.

General specifications of analytical goals for biochemical monitoring have been proposed based on biological within-subject variation. As a complement to this strategy for general global quality requirements there is also a need for other methods and approaches to set more optimal requirements in specific monitoring situations, i.e. application of systems and sensitivity analysis using (i) rules for propagation of errors (uncertainty) in simple algebraic/statistical transformations of laboratory results; (ii) biochemical/pathophysiological simulation models; and (iii) formalized descriptions of clinical classification and decision support processes. The possible gain in medical outcome by improving analytical and preanalytical quality should then be related to the often more important aspects of selection and combination of "tests", period and frequency of sampling/measurement, and the use of correct conceptual and computational models for transformation of data.

Clinical Laboratory Techniques↗

PubMed1999

Cortisol responses to marital conflict depend on marital interaction quality.

A sample of 80 couples were videotaped discussing a marital conflict and were then grouped in 3 types according to their interaction behavior: both partners displaying predominantly negative behavior ( N = 36 couples); both partners showing positive behavior ( N = 26); and couples showing asymmetric behavior (one positive, one negative; N = 16). Positive o r negative in this context refers to the empirically defined quality of speaker and listener skills by the Kategoriensystem Partnerschaftlicher Interaktion. Psychophysiological responses were measured 5 times, both before and after the conflict discussion. Participants rated their overall marital quality, the number of marital problems, and their actual cognitions and emotions. Overall responses to the conflict revealed a greater cortisol response in women than in men. Couples grouped according to their interaction style showed significant differences in cortisol responses: In couples with positive interaction, cortisol increased markedly, whereas couples with negative interaction showed a nonresponse, that is, a slight decrease expected with diurnal variation, although they rated the actual conflict discussion as "stressful" like the other groups of couples. We conclude that marital interaction directly affects physiological responses to a conflict depending on interaction quality.

Journal Article↗

PubMed1998

The efficacy of a compact psychoeducational group training program for married couples.

There is a lack of psychoeducational programs for married couples who, although subjectively concerned about their marriages, do not seek marital therapy. In this study, the efficacy of a cognitive-behavioral program delivered on a weekend by 2 trainers for groups of 4 couples was investigated. Couples (n = 67) were recruited by newspaper announcements, then randomly assigned to the intervention program or a waiting-list control group. The program consisted of communication and problem-solving training, couples' discussions to clarify their relationship expectations, and exercises to enhance their sensual or sexual relationship. At postassessment, intervention couples emitted more positive verbal and nonverbal communication behaviors during a conflict discussion task than did control couples, who reported significantly more relationship problem areas and displayed more negative communication behaviors. At the 1-year follow-up, intervention couples reported fewer problem areas in comparison with preassessment.

Adult↗

PubMed1997

The influence of analytical bias on diagnostic misclassifications.

Quality specifications for analytical imprecision and bias based on the state of the art; 'biology' and 'analysis of clinical situations' have been proposed by several scientists. Most interesting is the assessment of 'diagnostic misclassifications' based on direct evaluation of the consequences of analytical bias on the percentage of false positives and false negatives from a clinical decision situation, or based on the percentage of healthy individuals outside each reference limit when common reference intervals are used. With use of graphical or computer simulations assuming increasing (positive or negative) analytical bias, the expected percentage of misclassifications can be estimated- and, for the error for which the outcome (the fraction of misclassifications) is considered unacceptable, the maximum allowable analytical bias can be defined. An overview is given of previous proposals for specification of allowable analytical bias, and new examples are presented: (i) for S-transferrin. an analytical bias of +10% will increase the percentage of healthy individuals with measured concentration values above the upper reference limit from 2.5 to 10% (ii) the percentage of healthy men with concentration values for S-cholesterol above 6.2 mmol/l (240 mg/dl) will vary between 25 and 85% for analytical bias from - 1.0 to +1.0 mmol/l (+/- 16%): (iii) for glycated haemoglobin, two examples are given which illustrate the effect of analytical bias on the risk of retinopathy and so-called 'microalbuminuria' for measured values identical to the target 7.5% and 10.1% glycated haemoglobin, respectively. It is concluded that analytical bias may have significant impact on diagnostic performance, better standardization is needed, and quality specifications for allowable analytical bias should be based on medical usefulness criteria or, if such data are not available, on biological criteria.

Bias↗

PubMed1997

Covalent immobilization of hirudin improves the haemocompatibility of polylactide-polyglycolide in vitro.

A biodegradable polymer, poly(D,L-lactide-co-glycolide) RESOMER RG756, was modified by surface immobilization of recombinant hirudin (r-Hir) with glutaraldehyde as coupling reagent to improve the blood contacting properties of the polymer. The activity of immobilized hirudin on the polymer was estimated by a chromogenic assay to about 2.5 ATU r-Hir cm-2. The improvement of the haemocompatibility of the modified RG756 was evaluated in terms of platelet adhesion/activation, whole blood clotting times and clot formation rate. Fluorescence microscopy revealed that surface modification with r-Hir resulted in decreased platelet adhesion and activation. An ELISA for P-selectin, a marker of platelet activation, was used to confirm this result. Clotting time experiments demonstrated significantly prolonged non-activated partial thromboplastin times, and a decreased clot formation rate of whole blood in contact with r-Hir modified RG756 compared with the plain polymer. Comparison of immobilized r-Hir with bound heparin yielded equivalent improvement of blood-contacting properties of the investigated polymers. These in vitro investigations indicate that the immobilization of r-Hir on RG756 is a useful method to improve the blood contacting properties of polylactides/polyglycolides and other polymers as well.

Antithrombins↗

PubMed1997

Evaluation of various models of hyaluronan kinetics for assessment of liver function.

The purpose of this study of various models of hyaluronan kinetics has been to find the most appropriate model for estimation of parameters which characterize liver endothelial cell function. Five theoretical models for serum hyaluronan distribution and elimination were evaluated by computer analysis of serial measurements of the mass concentration of hyaluronan in serum following an intravenous bolus dose. Three of the models were based on one-compartment distribution of intravenously injected hyaluronan. Model 1A, with assumed first-order elimination, was found to be compatible with measured data and had identifiable parameters. Model 1B, with assumed non-linear Michaelis-Menten kinetics, was also found to be compatible but the Michaelis-Menten constant (K(m)) was not well determined. In model 1C, with non-linear Michaelis-Menten elimination kinetics, K(m) was set to a fixed value of 340 micrograms l-1, and the remaining parameters were well determined and the model was found to be compatible. Two models with an assumed two-compartment distribution of intravenously injected hyaluronan, were not acceptable due to unidentified parameters not discriminating between patients and healthy persons. In conclusion, model 1C, with one-compartment distribution and non-linear Michaelis-Menten kinetics, best fulfilled the criteria of validity and was accepted for further evaluation of clinical materials.

Adult↗

PubMed1997

Contact activation of plasmatic coagulation on polymeric membranes measured by the activity of kallikrein in heparinized plasma.

Kallikrein is involved in the generation of bradykinin during extracorporal circulation, that is believed to play an important role in cases of anaphylactic shock during hemodialysis. Therefore, a method for the assessment of kallikrein generation was developed, based on the chromogenic substrate S-2302. Comparison of kallikrein-like activity on glass using citrate or heparinized plasma demonstrated enhanced activity in the presence of heparin. The applicability of the assay, and the time course of kallikrein generation was demonstrated with glass and cuprophan. Membranes based on pure polyacrylonitrile, or its copolymers differing in their content of acrylic acid, 2-hydroxyethyl acrylate, and allylsulphonate were investigated with respect to kallikrein-like activity, and physicochemical surface properties. It was found that high content in 2-hydroxyethyl acrylate, and acrylic acid caused a substantial activation of the contact system while low content in allylsulphonate (less than 2 mol%) did not result in enhanced kallikrein-like activity. The activating materials were characterized to be highly wettable, and had the most negative zeta potentials.

Acrylates↗

PubMed1997

Morphological evidence for a different fibronectin receptor organization and function during fibroblast adhesion on hydrophilic and hydrophobic glass substrata.

A polyclonal antibody against the beta 1 subunit of the fibronectin (FN) receptor was used to mimic the early events of integrin receptor functioning to study the initial cellular processes during the organization of FN matrix on biomaterials. Hydrophilic glass and hydrophobic octadecylsilane (ODS) surfaces have been applied as models for different biocompatible materials. By immunofluorescence we could demonstrate that FN receptors organize on the dorsal cell surface of adhering fibroblasts in a specific linear pattern along with actin filaments, but only if the cells were attached to hydrophilic glass. In contrast, FN receptors were not reorganized on hydrophobic octadecylsilane (ODS). In parallel experiments, FN matrix formation after 72 h of incubation on the same substrata has been analyzed microscopically, and quantified by cell ELISA, in order to be further correlated with the integrin receptor functioning in contact with the biomaterials. It was found that FN structuring and the amount of FN matrix have been significantly diminished on ODS that was related to the observed changes in integrin receptor functioning. To learn more about the mechanism of this phenomenon, desorption of 125I-FN from these substrata was studied and found to be significantly decreased on hydrophobic ODS. As a consequence, FN receptor (function) might be arrested on the ventral cell surface, thus the important role of beta 1 integrins in the positional organization of the FN matrix may be disturbed. In light of these facts, antibody-induced clustering of FN receptor can be considered as a useful model for studying the early steps of FN matrix formation on biomaterials.

Adsorption↗

PubMed1997

Neural network analysis of biochemical markers for early assessment of acute myocardial infarction.

Neural network analysis was applied for early diagnosis/exclusion of acute myocardial infarction and prediction of infarct size. Eighty-eight patients admitted with onset of chest pain within 8 hours were included. Frequent blood samples for measurement of myoglobin, CK-MB and troponin-T were obtained and used in the development of a set of neural network components of a decision support system. The results indicate that this approach could provide useful support for assessment of patients with suspected AMI.

Biomarkers↗

PubMed1997

Early assessment of patients with suspected acute myocardial infarction by biochemical monitoring and neural network analysis.

Neural network analysis was applied for early diagnosis/exclusion of acute myocardial infarction (AMI), prediction of infarct size, and estimation of "time from onset of infarction." Eighty-eight patients admitted within 8 h after onset of chest pain were included. Blood samples for measurement of myoglobin, creatine kinase isoform MB, and troponin T were obtained every 30 min during the first 3 h and then after successively longer intervals. Data from 50 patients were used to train a set of neural network components of a decision support system. The performance of the system was evaluated and compared with experienced clinicians for the remaining 38 patients. The computer system detected myocardial infarction and predicted infarct size earlier than the clinicians, but did not differ significantly in terms of diagnostic sensitivity, specificity, and predictive values when disregarding time for diagnosis. With a cross-validation procedure the cumulated sensitivities of the computer system for the first five measurements were estimated to be (mean +/- 2SEM, n = 100): 0.77 +/- 0.03, 0.89 +/- 0.02, 0.94 +/- 0.02, 0.97 +/- 0.01, and 0.99 +/- 0.01, respectively, with corresponding cumulated specificities between 0.93 +/- 0.01 and 0.91 +/- 0.01. We concluded that neural network analysis of serial measurements of biochemical markers might provide useful support for the early assessment of patients with suspected AMI.

Aged↗

PubMed1996

A new clinical laboratory information system architecture from the OpenLabs project offering advanced services for laboratory staff and users.

The OpenLabs project aims to improve the efficiency and effectiveness of clinical laboratory services by integrating decision support systems with laboratory information systems and equipment. Standards for electronic data interchange between laboratories and other medical systems using the EUCLIDES/OpenLabs coding scheme and an open architecture for clinical laboratory information systems have been specified. This article gives an account of the proposed architecture and outlines new software applications being developed using the architecture which provide advanced services for ordering and reporting of laboratory tests, advanced instrument workstation and laboratory management services, including an OpenLabs Service Manager application which co-ordinates the available services.

Chemistry, Clinical↗

PubMed1996

Studies on the biocompatibility of materials: fibroblast reorganization of substratum-bound fibronectin on surfaces varying in wettability.

The ability of human fibroblasts to remove and reorganize fibronectin (FN) bound on material surfaces was studied as a novel feature of material surface biocompatibility. Other traditional parameters of biocompatibility analyzed included cell spreading, clustering of fibronectin receptors into focal adhesions, development of stress fibers, and cell growth. Five different materials with surface wettability ranging from hydrophilic (underwater contact angle 25 degrees) to hydrophobic (underwater contact angle 111 degrees) were used, i.e., clean glass (GLASS), aminopropylsilane (APS), octadecylsilane (ODS), polylactate (PL), and silicone (SI). When cells were cultured on these materials in serum-containing medium, formation of FN receptor-rich focal adhesions and actin stress fibers were more evident on the hydrophilic surfaces (GLASS and APS) compared to the hydrophobic ones (PL, ODS, and SI). Cell growth showed a similar pattern, that is, increased cell proliferation with increasing material surface wettability. Preadsorption of FN on the material surfaces increased subsequent cell spreading and cytoskeletal reorganization on hydrophobic surfaces except SI. Removal and reorganization of FN from the material surfaces into extracellular matrixlike structures occurred on GLASS but not on less wettable surfaces, suggesting that this removal/reorganization process may be more sensitive to changes in surface wettability than other parameters of biocompatibility.

Actins↗

PubMed1996

Studies on cell-biomaterial interaction: role of tyrosine phosphorylation during fibroblast spreading on surfaces varying in wettability.

In a previous study we observed that protein tyrosine phosphorylation was significantly diminished in the focal adhesions of human fibroblasts attached on a hydrophobic surface in comparison with hydrophilic glass. This result raises the possibility that the tyrosine phosphorylation pathway may be involved in the regulation of cell-biomaterial interaction. To learn more about the interaction of anchorage-dependent cells with biomaterials, four different materials with wettability ranging from hydrophilic (water contact angle 25 degrees) to hydrophobic (water contact angle 111 degrees) were investigated, i.e. clean glass (glass), aminopropylsilane (APS), octadecylsilane (ODS) and silicone (SI). Immunofluorescence microscopy revealed increased stress formation and fibronectin (FN) receptor-rich focal adhesions for fibroblasts attached on more hydrophilic surfaces (glass and APS) in comparison to the relatively hydrophobic materials (ODS and SI). Phosphorylation of tyrosine residues, also studied by immunofluorescence microscopy, was considerably higher on glass and APS, lower for ODS, negligible for SI, and was found to colocalize with FN receptor-rich focal adhesions. Preadsorption of FN tended to restore cell adhesion and spreading on the hydrophobic ODS and SI. Quantitative data on cell proliferation and tyrosine phosphorylation showed moderate wettable material maximum values for APS, followed by glass. ODS and SI, demonstrating a non-linearity of these parameters with the wettability of materials. Interestingly, the preadsorption of FN increased both parameters, particularly for the hydrophobic materials ODS and SI. Phosphorylation of tyrosine on FN-coated substrata was corroborated by the accessibility of binding sites estimated by ELISA using polyclonal and monoclonal FN antibodies. Our results suggest that measurement of the phosphotyrosine activity of cells may be a sensitive parameter for the ability of biomaterials to support the attachment and proliferation of cells.

Adsorption↗