Biomedical subjects

T Groth

Publications and source records attributed to T Groth.

At least 19 recordsLinked to original sources

PubMed2006

Outcome prediction of enteral levodopa/carbidopa infusion in advanced Parkinson's disease.

Two studies comparing intraduodenal infusion of a levodopa/carbidopa gel with oral treatments in advanced PD patients demonstrated improvement in UPDRS scores and in frequent clinical ratings on a global treatment response scale. Further analysis of data from these studies was performed to find predictive factors related to degree of improvement with infusion. Pearson's correlation coefficients between measures of improvement and baseline variables were calculated. Using data from one study, a prediction model was designed and was then evaluated using the other study's data. Correlations were found indicating that patients with more severe symptoms at baseline were most improved after infusion.

Adult↗

PubMed2006

On exemplary scientific conduct regarding submission of manuscripts to biomedical informatics journals.

As the Editors of leading international biomedical informatics journals, the authors report on a recent pattern of improper manuscript submissions to journals in our field. As a guide for future authors, we describe ethical and pragmatic issues related to submitting work for peer-reviewed journal publication. We propose a coordinated approach to the problem that our respective journals will follow. This Editorial is being jointly published in the following journals represented by the authors: Computer Methods and Programs in Biomedicine, International Journal of Medical Informatics, Journal of Biomedical Informatics, Journal of the American Medical Informatics Association, and Methods of Information in Medicine.

Biomedical Research↗

PubMed2005

Dynamics of beta1-integrins in living fibroblasts--effect of substratum wettability.

The dynamics of integrin receptors mobility was studied in living human fibroblasts using fluorescence-labeled beta(1)-integrin monoclonal antibodies. Time-lapse image series were obtained by confocal laser scanning microscopy when cells were adhering on model hydrophilic (clean glass) and hydrophobic (octadecyl-silanized; i.e., ODS) surfaces coated with fibronectin. Direct measurements showed approximately twice-higher velocity of integrins on glass compared to ODS, and these velocities varied in different zones of the cells. A kinetic model and algorithm for quantification of images was developed, and the analysis identified three receptor populations on glass: immobilized (82.76% of all), slow (4.16%), and fast (13.08%), while, on ODS, only two were identified: immobilized (83.36%) and fast (16.64%). Fast integrins in the peripheral zone of cells have maximal velocities of 0.353 +/- 0.02 mum/min (n = 48, four cells) on hydrophilic and 0.218 +/- 0.02 mum/min (n = 30, three cells) on hydrophobic substrata. The slow population has a velocity of 0.114 mum/min (n = 48, four cells). Further analyses show that these velocities also differ significantly in the peripheral and middle zones of cells in a substrate-dependent fashion. A well-defined circular motion of receptors around the cell center expressed mainly on hydrophobic substrata was monitored and quantified as well.

Algorithms↗

PubMed2005

Development of polymer membranes with improved haemocompatibility for biohybrid organ technology.

Biomedical technology has opened up possibilities of treating the failure of internal organs like kidney and liver by artificial organ therapy. Most of these techniques are based on polymer membranes, which allow the removal of excess of water, salts and toxins from the circulation. However, haemodialysis for the replacement of kidney function results in an increased morbidity and mortality of patients after long-term application. Conventional therapy, such as haemofiltration for the treatment of acute liver failure does not improve significantly the survival rate of patients. Biohybrid organ support as a combination of the artificial organ therapy with the functional activity of immobilised cells seems to be a solution of the problem. Membranes applied in these devices have to face both tissue cells and blood. Organ cells in biohybrid organs have to make intimate contact with the surface of membrane but must also develop close cell-cell-connections as a prerequisite for their survival and high functional activity. Blood to be detoxified will contact the other side of membrane and may not become activated by the synthetic material. New polymer membranes based on acrylonitrile were developed to address these requirements by tailoring the composition of copolymers and to be applied in a specific hollow fibre bioreactor with an outer fibre for blood contact, and an inner fibre for tissue contact or vice versa.

Animals↗

PubMed2004

Self-assembled monolayers with different terminating groups as model substrates for cell adhesion studies.

Cell shapes induced by cell-substratum interactions are linked with proliferation, differentiation or apoptosis of cells. To clarify the relevance of specific surface characteristics, we applied self-assembled monolayers (SAM) of alkyl silanes exhibiting a variety of terminating functional groups. We first characterised the SAMs on glass or silicon wafers by measuring wettability, layer thickness and roughness. Water contact angle data revealed that methyl (CH(3)), bromine (Br), and vinyl (CH=CH(2)) groups lead to hydrophobic surfaces, while amine (NH(2)) and carboxyl (COOH) functions lead to moderately wettable surfaces, and polyethylene glycol (PEG) and hydroxyl (OH) groups created wettable substrata. The surfaces were found to be molecular smooth except for one type of NH(2) surface. The SDS-PAGE analysis of proteins adsorbed from bovine serum to the SAMs showed less protein adsorption to PEG and OH than to CH(3), NH(2) and COOH. Immunoblotting revealed that a key component of adsorbed proteins is vitronectin while fibronectin was not detectable. The interaction of human fibroblasts with CH(3), PEG and OH terminated SAMs was similarly weak while strong attachment, spreading, fibronectin matrix formation and growth were observed on COOH and NH(2). The strong interaction of fibroblasts with the latter SAMs was linked to an enhanced activity of integrins as observed after antibody-tagging of living cells.

Adsorption↗

PubMed2003

Morphological studies on the culture of kidney epithelial cells in a fiber-in-fiber bioreactor design with hollow fiber membranes.

A hollow fiber-in-fiber-based bioreactor system was tested for the applicability to host kidney epithelial cells as a model system for a bioartificial kidney. Hollow fibers were prepared from polyacrylonitrile (PAN), polysulfone-polyvinylpyrollidinone (PVP) blend (PSU) and poly(acrylonitrile-N-vinylpyrollidinone) copolymer P(AN-NVP). Hollow fibers with smaller and larger diameters were prepared so that the smaller fitted into the larger, with a distance of 50-100 microm in between. The following material combinations as outer and inner fiber were applied: PAN-PAN; PSU-PSU, PSU-P(AN-NVP). Madin-Darby kidney epithelial cells (MDCK) were seeded in the interfiber space and cultured for a period up to 14 days. Light, scanning, and transmission electron microscopy were used to follow the adhesion and growth of cells, and to characterize their morphology. As a result, we found that MDCK cells were able to grow in the interfiber space in mono- and multilayers without signs of systemic degeneration. Comparison of the different materials showed that PAN and P(AN-NVP) provided the best growth conditions, indicated by a tight attachment of cells on hollow fiber membrane, and subsequent proliferation and development of structural elements of normal epithelia, such as tight junctions and microvilli. In conclusion, the fiber-in-fiber design seems to be an interesting system for the construction of a bioartificial kidney.

Acrylic Resins↗

PubMed2002

Polyetherimide: a new membrane-forming polymer for biomedical applications.

Membranes for biohybrid organs such as the biohybrid liver support system have to face 2 different environments, namely blood and tissue cells. Accordingly, the respective membrane surfaces must have optimal properties in terms of biocompatibility for blood or tissue. Flat membranes prepared by a phase inversion process from polyetherimide were modified by binding of tris-(hydroxymethyl)-aminomethane to obtain a surface with hydroxyl groups by binding of polyethylene imine to attach a hydrophilic macromolecule with amine groups useful as a spacer for later bonding of further ligands and by attachment of heparin. The binding of the different ligands was successful as monitored by different physicochemical methods. The blood response of plain polyetherimide was comparable to that of polyacrylonitrile, and it could be further improved by the binding of heparin. The tissue compatibility of polyetherimide and its different modifications was compared with commercial cell culture substrate membranes (Millicell) and found to be comparable for polyetherimide and even better after the modification with tris-(hydroxymethyl)-aminomethane. In conclusion, polyetherimide seems to be an interesting material for the production of membranes for application in biohybrid organ systems.

Complement Activation↗

PubMed2001

Surfactant Mediated Cationic and Anionic Suspension Polymerization of PEG-Based Resins in Silicon Oil: Beaded SPOCC 1500 and POEPOP 1500.

A novel surfactant has been synthesized for use in cationic and anionic ring-opening suspension polymerization of PEG-based macromonomers in silicon oil. A polymer of acrylate esters containing pentamethyldisiloxane and PEG was prepared by radical polymerization. The surfactant can stabilize an emulsion of PEG-based macromonomers, initiator, and solvent in silicon oil such that polymer beads are obtained by ring-opening polymerization, initiated either by a Lewis acid (cationic ring opening) or potassium tert-butoxide (anionic ring opening). The average bead size could be controlled by varying the stirring rate and the amount of surfactant and solvent. The surfactant does not interfere with the polymerization and can be removed together with residual silicon oil by a simple washing procedure.

Journal Article↗

PubMed2001

Growth hormone secretion and sensitivity in men with idiopathic osteoporosis.

Previous studies have suggested that insulin-like growth factor-I (IGF-I) and its binding proteins (IGFBPs) have a pathogenetic role in idiopathic osteoporosis. To investigate this question further we compared 20 men with idiopathic osteoporosis with 12 healthy, age-matched men regarding growth hormone (GH) secretion and sensitivity. GH samples were drawn every 30 minutes for 24 hours from 12 of the patients and all controls, and cumulated GH secretion (24 hGH) was derived. Peak GH secretion (peakGH) was provoked by an insulin tolerance test. There were no differences between the groups in serum IGF-I (162 +/- 30 vs 163 +/- 47 micrograms/liter, mean +/- SD), IGFBP-3 (2474 +/- 263 vs 2568 +/- 197 micrograms/liter), 24 hGH (1.34 +/- 1.26 vs 0.79 +/- 0.43 U), or peakGH (53.0 +/- 21.5 vs 44.1 +/- 19.8 mU/liter). Patients and controls were given GH (2.4 U/day) for 1 week. Serum levels of markers for bone turnover increased significantly in both groups, with no difference in response to GH between the groups. The increase in urinary bone resorption markers was only significant in the controls. In the patients, but not in the controls, there were significant positive correlations between indices for GH secretion and markers for bone turnover at baseline and significant negative correlations with relative changes in bone markers during GH treatment. In this study no difference in GH secretion was found between men with idiopathic osteoporosis and controls, but the findings suggest that the GH/IGF-I axis could play a regulatory role in bone metabolism in men with this condition.

Adult↗

PubMed2001

Anticoagulant potential of regioselective derivatized cellulose.

Regioselective derivatization was carried out introducing sulfate, phosphate or quaternary ammonia groups in C2-, C3- and C6-position of the anhydroglycose unit of cellulose. The anticoagulant potential of these derivatives was estimated with common clotting assays, such as thrombin time and partial thromboplastin time. It was found that a pronounced anticoagulant activity of cellulose derivatives could be achieved if the degree of substitution (DS) with sulfate was above 1.0. The anticoagulant activity was maximal at a DS of about 1.5 and then decreased again. Further, it was detected that particularly sulfation in C2-position resulted in a pronounced anticoagulant activity of cellulose derivatives. Development and application of assays specific for thrombin and factor Xa indicated that the anticoagulant potential of these cellulose derivatives was mainly due to anti-thrombin activity. The comparison of cellulose sulfates and cellulose derivatized with phosphate and quaternary ammonium groups demonstrated that the negative charge and type of the substituent is an important prerequisite for the anticoagulant activity of cellulose derivatives. Indeed, derivatization with sulfate produced superior activity in comparison with phosphate.

Anticoagulants↗

PubMed2001

A new module arrangement for plasmapheresis.

On-line plasmapheresis using microporous membranes for filtration normally requires two external circulations (double treatment) before the detoxified plasma can be returned to the patient. The duomodule, a new filter arrangement developed by our group, integrates both steps in one equipment module using only one external circuit. Separations of aqueous polyethylene glycol (PEG) solutions as well as human plasma were carried out using the duomodule arrangement. The results revealed a considerable decrease of higher molecular substances in the feed solutions and a significant increase of these components in the permeate solution accumulated in the external compartment of the module. In conclusion, the duomodule arrangement seems to be an useful tool for the therapeutic apheresis.

Chemical Fractionation↗

PubMed2001

Errors in estimating neonatal production of glucose with stable isotopes during "approximate steady state".

In studies of glucose metabolism in neonates, a commonly used approach is based on constant rate infusion of glucose labelled with a stable isotope in order to reach an approximate steady state with regard to isotopic enrichment in plasma. Under presumed conditions of a glucose steady state, the rates of appearance and disappearance of glucose can, in principle, be calculated with use of a simple steady-state formula. However, in the neonate, steady-state conditions do not generally prevail and results derived on such assumptions are questionable. In the present study, we have taken a pragmatic approach and compared estimates obtained from the conventional formula with values calculated with Steele's non-steady-state method. The results show that the estimated glucose appearance and disappearance rates change more or less over the observed time period in all the typical cases studied, and that "steady-state estimates" may differ from the corresponding non-steady-state values by up to 37%. In a sensitivity analysis, the value of the distribution volume factor was found to be non-critical, a circumstance that supports the use of Steele's method. Thus, even though the classical Steele pool-fraction method for computation of rates of appearance and disappearance under non-steady-state conditions has been criticized, it is still the most realistic alternative to the frequently used simple steady-state formula in applications to newborns.

Deuterium↗

PubMed2000

Isolation and characterization of an Achromobacter xylosoxidans strain B3 and other bacteria capable to degrade the synthetic chelating agent iminodisuccinate.

Three bacterial strains were isolated, which used the synthetic chelating agent iminodisuccinate (IDS) as sole carbon source for growth in mineral salts media (MSM). Taxonomic analysis and 16S rDNA sequence analysis identified one of these isolates (B3), which was isolated from sewage sludge, as a strain of Achromobacter xylosoxidans subsp. xylosoxidans. It exhibited a doubling time of approximately 3 h in liquid MSM supplemented with IDS and grew even in the presence of 1.0% (w/v) IDS. Since photometric and high performance liquid chromatography analysis showed that IDS, which came onto the market only recently as an alternative for ethylenediaminetetraacetate, was completely degraded by axenic cultures of bacteria; it will probably be readily degraded in the environment.

Alcaligenes↗

PubMed2000

Modulating the biocompatibility of polymer surfaces with poly(ethylene glycol): effect of fibronectin.

A novel approach described earlier for improving polymer substratum biocompatibility(1) is further elucidated. Polysulfone (PSf) spin-coating films were modified by covalent end-on grafting of hydrophilic and sterically demanding photo-reactive poly(ethylene glycol) (PEG) conjugates (ABMPEG; 10 kDa). The degree of grafting density was varied systematically, yielding a wide spectrum of attained surface characteristics monitored by air-water contact angles (captive bubble method). Fibronectin (FN) adsorption was studied by in situ ellipsometry and found to decrease monotonically as ABMPEG grafting density increased. The adhesive interaction of human skin fibroblasts with these substrata and, in particular, the effect of FN precoating were investigated in detail. A clear optimum of cell-substratum interactions was found for mildly modified substrata, employing well established microscopic and immunofluorescence techniques, namely the monitoring of cell adhesion and spreading, overall cell morphology, organization of FN receptors, and focal adhesions as well as FN matrix formation. The results suggest that cell interactions with hydrophobic polymer substrata are enhanced considerably when modified with hydrophilic and sterically demanding PEG moieties at a low surface coverage due to enhanced biologic activity of adsorbed and intercalated adhesive proteins such as FN.

Biocompatible Materials↗

PubMed2000

Development of membranes for the cultivation of kidney epithelial cells.

The development of biohybrid organs (BHO) will benefit from improved membranes regarding transport and cell contacting properties. Here we describe in a first study the development and testing of membranes made of polyacrylonitrile (PAN) and polysulfone (PSU) for the immobilisation of kidney epithelial cells. Comparative investigations on overall polymer toxicity tested with 3T3 fibroblasts, and morphology and proliferation of Madin-Darby canine kidney (MDCK) cells cultured on the membranes could show that these materials have comparable cell contacting properties like Millicell membranes. Since PAN and PSU have superior membrane forming properties with regard to membrane geometry, i.e. for the preparation of hollow fibres, and porosity, i.e. for immuno isolation, both materials or modifications thereof seem to be suitable for the application in BHO such as biohybrid kidney.

3T3 Cells↗

PubMed2000

Transferability of neural network-based decision support algorithms for early assessment of chest-pain patients.

The present investigation concerns methodological and epidemiological aspects of the transferability of artificial neural network-based algorithms, as key-components for classification in decision support systems (DSS). The prevalence of pathological conditions to be detected must be known in order to tune an artificial neural networks (ANN)-decision algorithm so that the predictive values of the outcome fulfil medical requirements. Another aspect of transferability, when clinical laboratory results are used, concerns differences in analytical performance of measuring instruments. The relative bias between two instruments is not known exactly, but must be estimated and corrected for. A general method, based on original measured data sets and statistical modeling, was developed for simulating the impact of various correction procedures when using different analytical instruments. The simulation methodology was applied to a real clinical problem of ruling-in/ruling-out of patients with suspected acute myocardial infarction (AMI) by biochemical monitoring. The recommended correction procedure was based on method comparison with use of five duplicate measurements on a common set of patient samples covering the relevant measuring interval. Transferability of laboratory data over time was also studied. The design of quality assurance procedures should be based on analytical quality requirement specifications related to medical needs. Limits of critically sized systematic errors were assessed by calculating the decrease in diagnostic performance of the ANN-algorithm as a result of temporary analytical disturbances. The consequences for the design of QA procedures was illustrated. It is concluded that the actual ANN-decision algorithm for early assessment of chest-pain patients should be possible to transfer to new sites under realistic conditions.

Algorithms↗

PubMed2000

Methods for selection of adequate neural network structures with application to early assessment of chest pain patients by biochemical monitoring.

A methodology for selecting, training and estimating the performance of adequate artificial neural network (ANN) structures and incorporating them with algorithms that are optimized for clinical decision making is presented. The methodology was applied to the problem of early ruling-in/ruling-out of patients with suspected acute myocardial infarction using frequent biochemical monitoring. The selection of adequate ANN structures from a set of candidates was based on criteria for model compatibility, parameter identifiability and diagnostic performance. The candidate ANN structures evaluated were the single-layer perceptron (SLP), the fuzzified SLP, the multiple SLP, the gated multiple SLP, the multi-layer perceptron (MLP) and the discrete-time recursive neural network. The identifiability of the ANNs was assessed in terms of the conditioning of the Hessian of the objective function, and variability of parameter estimates and decision boundaries in the trials of leave-one-out cross-validation. The commonly used MLP was shown to be non-identifiable for the present problem and available amount of data, despite artificially reducing the model complexity with use of regularization methods. The investigation is concluded by recommending a number of guidelines in order to obtain an adequate ANN model.

Algorithms↗

PubMed1999

Altered vitronectin receptor (alphav integrin) function in fibroblasts adhering on hydrophobic glass.

Function of integrins is crucial for adhesion, movement, proliferation, and survival of cells. In a recent study we found impaired fibronectin receptor function on hydrophobic substrata (G. Altankov et al. J Biomater Sci Polym Edn 1997;8:712-740). Here, we have studied the distribution and function of the vitronectin receptor (alphav integrin) in fibroblasts adhering on hydrophilic glass and hydrophobic octadecyl glass (ODS). The morphology of fibroblasts and the organization of actin cytoskeleton were studied and found to be altered on ODS, where the cells did not spread and possessed condensed actin. Pretreatment of the surfaces with serum or pure vitronectin improved cell morphology on both substrata, resulting in the development of longitudinal actin stress fibers. It was found with biotinylated vitronectin that comparable quantities of vitronectin were adsorbed from single vitronectin solutions or serum on glass and on hydrophobic ODS. The organization of the vitronectin receptors on the ventral cell surface was investigated in permeabilized cells showing normal focal adhesions in fibroblasts plated on glass but none of these structures on ODS. The distribution of alphav integrin on the dorsal cell surface was studied on nonpermeabilized living cells after antibody tagging. While fibroblasts adhering on plain or serum-treated glass developed a linear organization of alphav integrin, cells on plain and serum-treated ODS were not able to reorganize the vitronectin receptor. Studies on signal transduction with antiphosphotyrosine antibodies revealed co-localization of alphav integrin and phosphotyrosine in focal adhesions on glass and serum-treated glass. However, signaling was almost absent on plain ODS and weak on serum-treated ODS. It was concluded that alterations in vitronectin receptor function on the ventral cell surface caused by the hydrophobic material surface inhibit signal transfer and subsequent intracellular events that are important for the organization and function of integrins.

Actins↗