Biomedical subjects

T Wendt

Publications and source records attributed to T Wendt.

At least 19 recordsLinked to original sources

PubMed2006

Postprandial mononuclear NF-kappaB activation is independent of the AGE-content of a single meal.

OBJECTIVE: Dietary uptake of Advanced Glycation Endproducts (AGE) is supposed to potentially contribute to inflammatory reactions linked to vascular dysfunction and late diabetic complications. One mechanism by which dietary AGE might exert these effects is by activation of the proinflammatory transcription factor NF-kappa-B. The aim of this study was to analyze the postprandial effects of a casein meal with low or high AGE content on postprandial NF-kappaB activation in peripheral blood mononuclear cells (pBMC) of healthy volunteers. RESEARCH DESIGN AND METHODS: Casein was heated for 40 h at 50 degrees C in the presence of sorbitol or glucose, resulting in either minimal (Sorbitol [S]-casein) or large (glucose [G]-casein) amounts of AGE-modified casein. Nine healthy volunteers ate 250 g of both types of casein, whereas both meals were separated at least by 2 weeks. Plasma and pBMC were taken before and 2 h after each meal. Thereafter, the defined AGE carboxymethyllysine (CML) was determined by ELISA and Western blot. NF-kappaB activation in pBMC was assayed using Electrophoretic Mobility Shift Assays (EMSA) and Western blot analysis. RESULTS: S-casein contained only minor amounts of CML and no pentosidine, while G-casein contained large amounts of both. 2 h after ingestion, the S-casein or the G-casein-meal, both, resulted in a non-significant increase in plasma CML and in the intracellular CML-content of pBMC. This was paralleled by a highly significant increase in postprandial mononuclear NF-kappaB-binding activity. Remarkably, neither the extent of NF-kappaB induction (178% for S-casein, 188% for G-casein), nor composition of the NF-kappaB heterodimer (mainly consisting of NF-kappaB p50/p65) were significantly different after intake of S-casein or G-casein. Consistently, Western blots confirmed an increased NF-kappaBp65 nuclear translocation and a decrease of NF-kappaBp65 in the cytoplasm, while no difference in postprandial NF-kappaB nuclear translocation was observed following intake of S-casein or G-casein. CONCLUSION: Postprandial mononuclear NF-kappaB activation after a single meal is independent of the AGE-content of the ingested protein.

Active Transport, Cell Nucleus↗

PubMed2006

Modeling interdependencies between information processes and communication paths in hospitals.

OBJECTIVES: For planning hospital information systems it is important to recognize the interrelation between business processes and the communication needs between supporting application systems. We therefore present an approach to model, visualize and analyze those interdependencies. METHODS: The approach is based on the concepts defined in 3LGM2, a meta-model to describe health information systems (HIS). An information process is defined as a sequence of functions using or updating information; a communication path as a sequence of communication links between interfaces belonging to application systems. The search for communication paths belonging to an information process is interpreted as an all-pairs shortest-paths problem. To solve this problem the Floyd-Warshall algorithm is applied. RESULTS: The resulting algorithm has been implemented as function of the 3LGM2 tool, a tool to create 3LGM2 compliant models. With it, it is possible to interactively define information processes at the domain layer and to analyze step by step whether the infrastructure at the logical tool layer is sufficient to communicate necessary data between application systems. CONCLUSIONS: The presented approach enables the representation and analysis of dependencies between information processes and communication paths. With it, the HIS architecture is directly associated with the business needs. This is an important condition for the systematic planning of hospital information systems.

Algorithms↗

PubMed2004

Modeling Hospital Information Systems (Part 2): using the 3LGM2 tool for modeling patient record management.

OBJECTIVES: We introduce the 3LGM(2) tool, a tool for modeling information systems, and describe the process of modeling parts of the hospital information system of the Leipzig University Hospital (UKL(a)). We modeled the sub information systems of five patient record archiving sections to support the creation of a proposal for governmental financial support for a new document management and archiving system. We explain the steps of identifying the model elements and their relations as well as the analyzing capabilities of the 3LGM(2) tool to answer questions about the information system. METHODS: The 3LGM(2) tool was developed on the basis of the meta model 3LGM(2) which is described in detail in [1]. 3LGM(2) defines an ontological basis, divided into three layers and their relationships. In addition to usual meta CASE tools, the 3LGM(2) tool meets certain requirements of information management in hospitals. The model described in this article was created on the base of on-site surveys in five archiving sections of the UKL. RESULTS: A prototype of the 3LGM(2) tool is available and is currently tested in some projects at the UKL and partner institutions. The model presented in this article is a structured documentation about the current state of patient record archiving at the UKL. The analyzing capabilities of the 3LGM(2) tool help to use the model and to answer questions about the information system. CONCLUSIONS: The 3LGM(2) tool can be used to model and analyze information systems. The presentation capabilities and the reliability of the prototype have to be improved. The initial modeling effort of an institution is only valuable if the model is maintained regularly and reused in other projects. Reference catalogues and reference models are needed to decrease this effort and to support the creation of comparable models.

Archives↗

PubMed2003

[Circadian rhythm of QT- and QTc-intervals in diabetics and hypertensives].

UNLABELLED: Few studies have been done on the circadian rhythm of QT- und corrected QT-interval in diabetics. METHOD: 13 type II diabetics (mean duration 10.08 yrs +/- 1.95 (SEM), 12 insulin-dependent) and 13 hypertensives, mean age 58.2 +/- 197 (SEM) and 57.3 +/- 1.4 yrs (p = n.s.), respectively, without cardiovascular events within the last 6 months before rehabilitation underwent Holter monitoring. We investigated mean and maximum QT-interval, QTc-interval (Bazett-formula), RR-interval as well as spectral parameters LF, HF, and LF/HF ratio. RESULTS: Both groups showed significant circadian variations of mean and maximum QT-intervals. No group differences were found. There was no significant circadian rhythm of mean or maximum QTc-interval. Diabetics had significantly prolonged maximum QTc-intervals during the day-time. Mean and maximum RR-intervals in diabetics were significantly shorter. Both groups showed a significant circadian rhythm. LF and HF were significantly shorter in diabetics. Only in diabetics could significant circadian rhythm of LF and HF be demonstrated. The LF/HF ratio was significantly shorter in diabetics. The hypertensive group showed a decreasing circadian trend whereas diabetics showed increasing LF/HF ratio trend. CONCLUSION: Mean and maximum QT-intervals are significantly shorter in diabetics than in hypertensives. Maximum QTc-interval prolongation is highly significant (p < 0.01) in diabetics. Spectral parameters LF and HF are reduced in comparison with hypertensives. The prolongation of the maximum QTc-interval could be expression of an increased arrythmogenic and cardiovascular risk in diabetics.

Antihypertensive Agents↗

PubMed2003

Modeling hospital information systems. Part 1: The revised three-layer graph-based meta model 3LGM2.

OBJECTIVES: Not only architects but also information managers need models and modeling tools for their subject of work. Especially for supporting strategic information management in hospitals, the meta model 3LGM2 is presented as an ontological basis for modeling the comprehensive information system of a hospital (HIS). METHODS: In a case study, requirements for modeling HIS have been deduced. Accordingly 3LGM2 has been designed to describe HIS by concepts on three layers. The domain layer consists of enterprise functions and entity types, the logical tool layer focuses on application components and the physical tool layer describes physical data processing components. In contrast to other approaches a lot of inter-layer-relationships exist. 3LGM2 is defined using the Unified Modeling Language (UML). RESULTS: Models of HIS can be created which comprise not only technical and semantic aspects but also computer-based and paper-based information processing. A software tool supporting the creation of 3LGM2 compliant models in a graphical way has been developed. The tool supports in detecting those shortcomings at the logical or the physical tool layers which make it impossible to satisfy the information needs at the domain layer. 3LGM2 can also be used as an ontology for describing HIS in natural language. CONCLUSIONS: Strategic information management even in large hospitals should be and can be supported by dedicated methods and tools. Although there have been good experiences with 3LGM2 concerning digital document archiving at the Leipzig University Hospital, which are presented in part 2, the benefit of the proposed method and tool has to be further evaluated.

Hospital Information Systems↗

PubMed2002

RAGE is a multiligand receptor of the immunoglobulin superfamily: implications for homeostasis and chronic disease.

Receptor for AGE (RAGE) is a member of the immunoglobulin superfamily that engages distinct classes of ligands. The biology of RAGE is driven by the settings in which these ligands accumulate, such as diabetes, inflammation, neurodegenerative disorders and tumors. In this review, we discuss the context of each of these classes of ligands, including advance glycation end-products, amyloid beta peptide and the family of beta sheet fibrils, S100/calgranulins and amphoterin. Implications for the role of these ligands interacting with RAGE in homeostasis and disease will be considered.

Alzheimer Disease↗

PubMed2001

Three-dimensional image reconstruction of dephosphorylated smooth muscle heavy meromyosin reveals asymmetry in the interaction between myosin heads and placement of subfragment 2.

Regulation of the actin-activated ATPase of smooth muscle myosin II is known to involve an interaction between the two heads that is controlled by phosphorylation of the regulatory light chain. However, the three-dimensional structure of this inactivated form has been unknown. We have used a lipid monolayer to obtain two-dimensional crystalline arrays of the unphosphorylated inactive form of smooth muscle heavy meromyosin suitable for structural studies by electron cryomicroscopy of unstained, frozen-hydrated specimens. The three-dimensional structure reveals an asymmetric interaction between the two myosin heads. The ATPase activity of one head is sterically "blocked" because part of its actin-binding interface is positioned onto the converter domain of the second head. ATPase activity of the second head, which can bind actin, appears to be inhibited through stabilization of converter domain movements needed to release phosphate and achieve strong actin binding. When the subfragment 2 domain of heavy meromyosin is oriented as it would be in an actomyosin filament lattice, the position of the heads is very different from that needed to bind actin, suggesting an additional contribution to ATPase inhibition in situ.

Animals↗

PubMed2001

Point-of-care testing apparatus. Measurement of coagulation.

Point-of-care testing of coagulation parameters provides a more rapid assessment of test results compared with laboratory testing. A new coagulation monitor (GEM PCL, Instrumentation Laboratory, Kirchheim, Germany) was evaluated. Point-of-care data for activated partial thromboplastin time and prothrombin time (expressed as the international normalised ratio) and turn-around-time were compared. Coagulation parameters were compared in the blood of 57 patients with and without heparin therapy. The point-of-care and laboratory test results showed a bias (SD) of -0.26 (4.55) s for activated partial thromboplastin time and -0.011 (0.150) s for prothrombin time. The average turn-around-time was 3 min for point-of-care testing vs. 52 min for laboratory testing. We conclude that the reliability of point-of-care testing is sufficient for clinical use.

Blood Coagulation Disorders↗

PubMed2001

Structure and assembly of intracellular mature vaccinia virus: isolated-particle analysis.

In a series of papers, we have provided evidence that during its assembly vaccinia virus is enveloped by a membrane cisterna that originates from a specialized, virally modified, smooth-membraned domain of the endoplasmic reticulum (ER). Recently, however, Hollinshead et al. (M. Hollinshead, A. Vanderplasschen, G. I. Smith, and D. J. Vaux, J. Virol. 73:1503-1517, 1999) argued against this hypothesis, based on their interpretations of thin-sectioned material. The present article is the first in a series of papers that describe a comprehensive electron microscopy (EM) analysis of the vaccinia Intracellular Mature Virus (IMV) and the process of its assembly in HeLa cells. In this first study, we analyzed the IMV by on-grid staining, cryo-scanning EM (SEM), and cryo-transmission EM. We focused on the structure of the IMV particle, both after isolation and in the context of viral entry. For the latter, we used high-resolution cryo-SEM combined with cryofixation, as well as a novel approach we developed for investigating vaccinia IMV bound to plasma membrane fragments adsorbed onto EM grids. Our analysis revealed that the IMV is made up of interconnected cisternal and tubular domains that fold upon themselves via a complex topology that includes an S-shaped fold. The viral tubules appear to be eviscerated from the particle during viral infection. Since the structure of the IMV is the result of a complex assembly process, we also provide a working model to explain how a specialized smooth-ER domain can be modulated to form the IMV. We also present theoretical arguments for why it is highly unlikely that the IMV is surrounded by only a single membrane.

Dithiothreitol↗

PubMed2001

Prospective controlled evaluation of the influence of an excursion to a health resort on medical students' opinion about chances for outpatient rehabilitation at a health resort.

OBJECTIVE: To assess the influence of an excursion to a health resort on students' opinion on the chances for outpatient rehabilitation at a health resort for cardiac and rheumatic diseases. METHODS: A group of 17 medical students went on a 1-day excursion to Bad Orb (near Frankfurt/M.) where mainly patients with heart diseases are treated. Another group of 44 students went on a 5-day excursion to Bad Gastein (Austria) where mainly patients with rheumatic diseases are treated. Before and after the excursion students completed a questionnaire asking their opinion on the chances for outpatient rehabilitation at a health resort for acute and chronic cardiac and rheumatic diseases. RESULTS: Students judged the chances for beneficial effects of outpatient rehabilitation at a health resort for chronic rheumatic diseases to be significantly better after the excursion to Bad Gastein than before, whereas there was no difference after the excursion to Bad Orb. CONCLUSION: Students' opinion of chances for outpatient rehabilitation at a health resort can be influenced by an excursion to a spa, but a single 1-day excursion may not be sufficient.

Adult↗

PubMed2001

Receptor for advanced glycation end products mediates inflammation and enhanced expression of tissue factor in vasculature of diabetic apolipoprotein E-null mice.

Advanced glycation end products (AGEs) and their cell surface receptor, RAGE, have been implicated in the pathogenesis of diabetic complications. Here, we studied the role of RAGE and expression of its proinflammatory ligands, EN-RAGEs (S100/calgranulins), in inflammatory events mediating cellular activation in diabetic tissue. Apolipoprotein E-null mice were rendered diabetic with streptozotocin at 6 weeks of age. Compared with nondiabetic aortas and kidneys, diabetic aortas and kidneys displayed increased expression of RAGE, EN-RAGEs, and 2 key markers of vascular inflammation, vascular cell adhesion molecule (VCAM)-1 and tissue factor. Administration of soluble RAGE, the extracellular domain of the receptor, or vehicle to diabetic mice for 6 weeks suppressed levels of VCAM-1 and tissue factor in the aorta, in parallel with decreased expression of RAGE and EN-RAGEs. Diabetic kidney demonstrated increased numbers of EN-RAGE-expressing inflammatory cells infiltrating the glomerulus and enhanced mRNA for transforming growth factor-beta, fibronectin, and alpha(1) (IV) collagen. In mice treated with soluble RAGE, the numbers of infiltrating inflammatory cells and mRNA levels for these glomerular cytokines and components of extracellular matrix were decreased. These data suggest that activation of RAGE primes cells targeted for perturbation in diabetic tissues by the induction of proinflammatory mediators.

Animals↗

PubMed2001

A UML-based ontology for describing hospital information system architectures.

To control the heterogeneity inherent to hospital information systems the information management needs appropriate hospital information systems modeling methods or techniques. This paper shows that, for several reasons, available modeling approaches are not able to answer relevant questions of information management. To overcome this major deficiency we offer an UML-based ontology for describing hospital information systems architectures. This ontology views at three layers: the domain layer, the logical tool layer, and the physical tool layer, and defines the relevant components. The relations between these components, especially between components of different layers make the answering of our information management questions possible.

Hospital Information Systems↗

PubMed2000

Time course of cytokine mRNA expression in kidneys of rats with unilateral ureteral obstruction.

The development of renal interstitial fibrosis (RIF) is related to the expression and excretion of cytokines and growth factors. Thus, we investigated the time course of mRNA expression of cytokines known as causative factors in a model of RIF in rats before and on day 10 after unilateral ureteral obstruction (UUO), when first signs of fibrosis were visible, as well as during progressive RIF. UUO causes a fivefold increase in mRNA expression of monocyte chemoattractant protein 1 15 days after surgery as compared with contralateral kidneys. The level remains elevated about three-fold up to day 25. The mRNA of the fibrogenic cytokine transforming growth factor beta 1 (TGF-beta1) is increased two- to threefold during the time course, whereas the mRNAs of platelet-derived growth factor B chain (PDGF-B) and its receptor beta (PDGF-Rbeta) increase after UUO, reaching their maxima on days 10-15. PDGF-B mRNA increase up to day 15, marking the onset of fibrosis, and decreases thereafter, whereas the expression of the PDGF-Rbeta mRNA remains elevated more than threefold over the entire study period. Incubation of cultured renal fibroblasts with TGF-beta1 and/or PDGF-B suggests that their specific action on cell growth and proliferation is maintained even when they are used in combination. The sustained elevation of TGF-beta1 and PDGF-B/PDGF-Rbeta mRNA levels confirms the assumption of a particular involvement of these cytokines in the pathogenesis of RIF. The mRNA expression of the gap junctional protein connexin 43 in ureteral ligated kidneys is increased sixfold already 5 days after UUO. In this way, the increased connexin 43 mRNA levels indicate a possible function in the remodeling of the kidney tissue after tubular damage and fibrosis.

Animals↗

PubMed2000

Decision support in medicine: a survey of problems of user acceptance.

Computer-based clinical decision support systems (CDSSs) are still today not in widespread use, although there has been extensive research and development for several decades. We have, based on the literature of the last years, summarised some of the problems that may lead to low user acceptance and that should be addressed more extensive in future developments of CDSSs. We describe different aspects of the usefulness of CDSSs according to the elements (relevance, validity, and work) of a formula of usefulness of information, and, in a short section, refer to the discussion about clinical guidelines.

Attitude of Health Personnel↗

PubMed1999

Visualization of head-head interactions in the inhibited state of smooth muscle myosin.

The structural basis for the phosphoryla- tion-dependent regulation of smooth muscle myosin ATPase activity was investigated by forming two- dimensional (2-D) crystalline arrays of expressed unphosphorylated and thiophosphorylated smooth muscle heavy meromyosin (HMM) on positively charged lipid monolayers. A comparison of averaged 2-D projections of both forms at 2.3-nm resolution reveals distinct structural differences. In the active, thiophosphorylated form, the two heads of HMM interact intermolecularly with adjacent molecules. In the unphosphorylated or inhibited state, intramolecular interactions position the actin-binding interface of one head onto the converter domain of the second head, thus providing a mechanism whereby the activity of both heads could be inhibited.

Animals↗

PubMed1999

Influence of methotrexate and azathioprine on radiologic progression in rheumatoid arthritis.

We investigated 43 patients with seropositive rheumatoid arthritis (RA) under a therapy with methotrexate (MTX) or azathioprine (AZA). All patients fulfilled the American Rheumatism Association criteria. It has been a retrospective study over 2.6 years (MTX: 26 patients, average age 54 +/- 14.6 years, female/male 19:7, AZA: 17 patients, average age 59.4 +/- 12.5 years, female/male 12:5). The mean duration of disease was 8 years (+/- 5.3) in the MTX-group and 7 years (+/- 7.3) in the AZA-group. The mean dose of MTX was 13. 3mg/week and of azathioprine 142.6mg/ daily. The drugs were administered orally. - Radiographs of hands, wrists and feet obtained at enrollment and at review were scored by a rheumatologist according to a modified Larsen score. Radiographic damages were counted in 25 joints of each hand and in 25 joints of each foot. The change in radiological score was calculated by subtracting the joint damage scores at follow up with first damage score at inclusion. The rate of radiological progression (YP) was calculated by dividing the change in radiological score by the number of years during the period of study. - Only 3 patients with MTX showed no radiologic progression. All other patients of both groups showed progressive radiological changes. - The study demonstrated no significant difference in the rate of radiologic progression between the different treatment-groups. However, there was a trend that MTX treated patients (YP 5 +/- 4.4) had a slower radiographic progression compared with those treated with AZA (YP 8.5 +/- 7.7). MTX may be more effective in patients at an earlier stage of rheumatoid arthritis. - When we started a therapy with AZA or MTX in a later period of disease we revealed a better influence of radiologic progression under AZA and a trend towards an increase of the radiologic progression under MTX. - Probably there is a decreasing effect of MTX in later periods of the disease. - The corticoid dose reduction was higher under AZA (AZA: Reduction about 58.6%, MTX: 25%) over the study duration. - Our investigation demonstrated a trend towards reduced radiological progression in MTX treated patients compared to AZA, however statistic analysis showed no significant difference in the rate of radiologic progression. At an earlier stage of the disease there is a better influence of MTX in radiologic progression, at the later stage we showed a slowing of radiological deterioration in AZA treated group.

Adult↗

PubMed1999

Structure of the insect troponin complex.

Isolated troponin-tropomyosin complex from Lethocerus indicus asynchronous flight muscle forms paracrystals on a positively charged lipid monolayer. Single particle analysis was carried out on individual complexes selected from electron micrographs of negatively stained paracrystals. By a combination of correlation and classification techniques, different average projections of the object were obtained. An initial three-dimensional model was calculated by determining the Euler angles for the different views using a common line approach. This starting model was then used as a reference for the further three-dimensional refinement of the model using the original data set. The refined model of the troponin complex has a diameter of approximately 90 A and a volume corresponding with a molecular mass of about 120 kDa for the globular domain. The resolution of the reconstruction was determined to be 32 A using the differential phase residual method and 26 A using the Fourier shell correlation criterion.

Animals↗

PubMed1999

[Ambulatory phase II rehabilitation of heart patients in the Rhine-Main district hospital: the Frankfurt model].

In the early 90s the German approach to phase II cardiac rehabilitation differed markedly from that which was usually practiced in the anglosaxon countries, as it covered almost exclusively a 4-week comprehensive, residential program far away from home in an often idyllic spa. However as many as approximately 60% of the cardiac patients did not take advantage of this offer, mainly because they felt separated from their families in residential programs. Therefore, because of good experiences with outpatient programs in other countries and in order to minimize costs, the so-called Frankfurt model, an outpatient phase II rehabilitation program, was performed at the University hospital in Frankfurt. The aim of this innovative program was to find out, whether it was as effective as the German "gold standard" of residential rehabilitation and whether is was practicable at a hospital. The program was carried out in a pilot phase over 1 year according to the standards of comprehensive cardiac rehabilitation in 41 patients, who had a follow-up examination 6 months later. The outcomes were compared with results of residential programs, which, however, were not collected in a controlled way. The short- and medium-term results concerning somatic outcomes, e.g. the risk factor profile or the improvement of the maximum work capacity, were equal to the residential programs. The percentage and timing of return-to-work, however, was much higher in the outpatient program obviously due to selection phenomena. The rehabilitation program at the hospital was practicable and safe. Under given conditions and meeting the standards for comprehensive cardiac rehabilitation an outpatient phase II rehabilitation program is practicable and safe with good short- and medium-term results also at a hospital. Such a program offers a good alternative to patients who do not want to rehabilitate under strictly residential conditions far away from home.

Adult↗