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Matthias Hartmann

Publications and source records attributed to Matthias Hartmann.

15 recordsLinked to original sources
PubMed2006

Effects of cardiac surgery on hemostasis.

Cardiac surgery affects both coagulation and platelet function. Revision of surgery due to bleeding has to be performed in 2% to 6% of patients undergoing cardiac surgery and is generally associated with a marked deterioration in prognosis. Factors contributing to acquired hemostatic abnormalities in cardiac surgery include the use of anticoagulants as well as the activation and consumption of coagulation factors and platelets induced by the extracorporeal circulation. Prophylactic use of antifibrinolytic agents such as aprotinin and tranexamic acid has been demonstrated to reduce the blood loss by half. Adequacy of heparin-induced anticoagulation in the perioperative setting is commonly controlled by the activated clotting time. This method also indicates the correct reversal of the heparin effect by protamine. In recent years, thrombelastography has proved to be valuable for diagnosis of coagulopathy associated with cardiac surgery. In addition, the use of thrombelastography-based algorithms has been shown to reduce transfusion requirements. In contrast to point of care methods, laboratory assessment of hemostasis is more time-consuming and, thus, often not as rapidly available as required. At this time, the therapy for perioperative hemostatic abnormalities is based mainly on the administration of blood components (fresh frozen plasma and platelet concentrates). In the future, recombinant activated factor VIIa might prove to be a therapeutic option in patients with otherwise untractable bleeding, but the efficacy of recombinant activated factor VIIa has yet to be defined for this indication.

Blood Coagulation Disorders↗
PubMed2006

Thrombelastography for the monitoring of lipopolysaccharide induced activation of coagulation.

During Gram-negative sepsis, lipopolysaccharide (LPS) activates toll-like receptor (TLR) 4 and induces complex responses of immune system and haemostasis. In the present study we investigated whether thrombelastography is suitable to monitor the LPS-induced activation of coagulation. Whole blood samples from healthy volunteers were incubated with LPS for various incubation periods (0-5 hrs), thereafter rotation thrombelastography was performed. Incubation of whole blood (>or=3 h) with LPS markedly reduced clotting time; after 5 hrs the variable was reduced from 459+/-39 sec to 80+/-20 sec while the other thrombelastography variables (angle alpha, clot formation time, maximal clot formation) remained unaltered. EC(50) of the LPS effect on whole blood clotting time was 18 microg/ml. In isolated leukocytes, diluted in platelet poor plasma, far lower LPS-concentrations were effective: 10 ng/ml LPS reduced clotting time from 439+/-68 sec to 200+/-56 sec. Experiments with the protein synthesis inhibitor cycloheximide and active site-inhibited factor VIIa revealed that LPS exerts its effects via the synthesis of tissue factor. Addition of tissue factor to whole blood samples revealed that a concentration of 100 fmol/l can be detected using thrombelastography. In whole blood samples the tissue factor concentration induced by LPS amounted up to 12 pmol/l. In summary, thrombelastography proved to be a sensitive and reliable tool for the determination of LPS-induced tissue factor mediated activation of haemostasis in whole blood samples.

Blood Coagulation↗
PubMed2006

Recombinant activated factor VII in the treatment of near-fatal bleeding during pediatric brain tumor surgery. Report of two cases and review of the literature.

Recombinant activated factor VII (rFVIIa) was successfully used in two pediatric cases to control microvascular bleeding during brain tumor surgery. The agent demonstrated a marked effect on the intraoperative blood coagulation after failure of conventional therapy with fresh-frozen plasma, platelet concentrates, and inhibition of the fibrinolytic system. Remarkably, rFVIIa was effective in the present cases in which assessment of hemostasis yielded normal results. The use of rFVIIa should be considered in otherwise untreatable microvascular bleeding in pediatric neurosurgery.

Adolescent↗
PubMed2005

Differential vesicular targeting and time course of synaptic secretion of the mammalian neurotrophins.

Neurotrophins are a family of secreted neuronal survival and plasticity factors comprising NGF, BDNF, neurotrophin-3 (NT-3), and NT-4. Whereas synaptic secretion of BDNF has been described, the routes of intracellular targeting and secretion of NGF, NT-3, and NT-4 in neurons are poorly understood. To allow for a direct comparison of intracellular targeting and release properties, all four mammalian neurotrophins were expressed as green fluorescent protein fusion proteins in cultured rat hippocampal neurons. We show that BDNF and NT-3 are targeted more efficiently to dendritic secretory granules of the regulated pathway of secretion (BDNF, in 98% of cells; NT-3, 85%) than NGF (46%) and NT-4 (23%). For all NTs, the remaining cells showed targeting to the constitutive secretory pathway. Fusing the BDNF pre-pro sequence to NT-4 directed NT-4 more efficiently to the regulated pathway of secretion. All neurotrophins, once directed to the regulated secretion pathway, were detected near synapsin I-positive presynaptic terminals and colocalized with PSD-95-DsRed (postsynaptic density-95-Discosoma red), suggesting postsynaptic targeting of the neurotrophins to glutamatergic synapses. Depolarization-induced release of all neurotrophins from synaptic secretory granules was slow (delay in onset, 10-30 s; tau = 120-307 s) compared with transmitter release kinetics monitored with FM4-64 [N-(3-triethylammoniumpropyl)-4-(6-(4-diethylamino)phenyl)hexatrienyl)pyridinium dibromide] destaining (onset, <5 s; tau = 13 +/- 2 s). Among the neurotrophins, NT-4 secretion was most rapid but still proceeded 10 times more slowly than transmitter secretion. Preincubation of neurons with monensin (neutralizing intragranular pH, thus solubilizing the peptide core) increased the speed of secretion of BDNF, NGF, and NT-3 to the value of NT-4. These data suggest that peptide core dissolution in secretory granules is the critical determinant of the speed of synaptic secretion of all mammalian NTs and that the speed of release is not compatible with fast transmitter-like actions of neurotrophins.

Animals↗
PubMed2004

Truncated TrkB receptor-induced outgrowth of dendritic filopodia involves the p75 neurotrophin receptor.

The Trk family of receptor tyrosine kinases and the p75 receptor (p75NTR) mediate the effects of neurotrophins on neuronal survival, differentiation and synaptic plasticity. The neurotrophin BDNF and its cognate receptor tyrosine kinase, TrkB.FL, are highly expressed in neurons of the central nervous system. At later stages in postnatal development the truncated TrkB splice variants (TrkB.T1, TrkB.T2) become abundant. However, the signalling and function of these truncated receptors remained largely elusive. We show that overexpression of TrkB.T1 in hippocampal neurons induces the formation of dendritic filopodia, which are known precursors of synaptic spines. The induction of filopodia by TrkB.T1 occurs independently of neurotrophin binding and of kinase activity of endogenous TrkB.FL. Coexpression of a p75NTR lacking an intracellular domain inhibits the TrkB.T1-induced effect in a dominant negative manner. Steric hindrance of extracellular p75NTR interactions with a specific antibody, or absence of p75NTR with an intact extracellular domain also inhibit this TrkB.T1-induced effect. We thus propose a novel signalling pathway initiated by neurotrophin-independent extracellular or intramembrane interaction of TrkB.T1 with the p75NTR receptor, which modulates dendritic growth via p75NTR signalling cascades.

Animals↗
PubMed2004

Verification of IMRT: techniques and problems.

PURPOSE: IMRT (intensity-modulated radiotherapy) verification techniques are reviewed together with investigations demonstrating the intrinsic verification problems. MATERIAL AND METHODS: Different IMRT verification procedures for either class solutions or individual patients are demonstrated. Among the latter are techniques like fluence or three-dimensional (3-D) dose distribution verification within a transfer phantom. Different radiographic films and absolute dose probes are investigated for their suitability. Finally, Monte Carlo techniques (XVMC/VEF) are used for error detection and IMRT verification. RESULTS: During introduction of clinical IMRT for head and neck (H and N) tumors, we concurrently applied fluence, relative, and absolute dose measurement. While fluence and relative dose are in rather good agreement with calculations, absolute dose is always low when compared to the TPS (TMS 6.1A, Nucletron B.V.) by 5-7%. This deviation seems to depend not on the number of segments, but can strongly depend on MLC misalignment. Further investigations have revealed the importance of a detailed commissioning of the TPS down to the small-field range using diamond or diode probes and its detailed verification. In addition, simple tests have shown that dose calculation approximations in the IMRT option of TMS are one major source of the dose deviation. XVMC/VEF does not use such approximations. CONCLUSION: The procedure starts with a detailed TPS commissioning and verification process. Different verification methods are recommended during clinical IMRT implementation phase, in order to locate sources of error. Later on, a minimal program could consist of a fluence or relative dose verification procedure with few films and absolute dose measurement, followed by an intensive MLC quality assurance (QA). Inverse Monte Carlo systems, like IMCO(++)/IKO or Hyperion, seem to be able to reduce the effort.

Head and Neck Neoplasms↗
PubMed2004

Growth factor production in human endothelial cells after Chlamydia pneumoniae infection.

Seroepidemiological and histopathological studies have suggested a link of atherosclerosis with chronic Chlamydia pneumoniae infection. The present study was designed to examine the effect of C. pneumoniae on expression of basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) in human endothelial cells. Using reverse transcription-polymerase chain reaction, immunoblotting and enzyme-linked immunosorbent assay we found stimulation of bFGF expression depending on the number of infecting bacteria and the time of infection as well. This stimulatory effect was diminished by heat and UV light treatment of the chlamydial inoculum, suggesting that viable bacteria but not bacterial LPS may be essential for eliciting this growth factor. In contrast, the expression of both PDGF-A and PDGF-B was not increased following C. pneumoniae infection. This study demonstrates that C. pneumoniae activates endothelial cells to produce bFGF, a growth factor which is linked to the development of atherosclerotic plaques.

Arteriosclerosis↗
PubMed2003

Increased production of matrix metalloproteinases 1 and 3 by smooth muscle cells upon infection with Chlamydia pneumoniae.

Atherosclerosis has been linked to Chlamydia pneumoniae infection. In atherosclerotic arteries chlamydiae infect macrophages, endothelial cells, and smooth muscle cells (SMC). It has been suggested that the proteolysis of the extracellular matrix by matrix metalloproteinases (MMPs) is involved in the destabilisation and rupture of atherosclerotic plaques. In this study we investigated the expression of several MMPs and tissue inhibitors of MMP (TIMPs) in C. pneumoniae-infected SMC using reverse transcription-polymerase chain reaction analysis. Chlamydial infection of SMC up-regulated the mRNA levels of MMP-1 (interstitial collagenase) and MMP-3 (stromelysin) but did not affect the expression of MMP-2 and -9 (gelatinases). Additionally, the levels of TIMP-1 and -2 mRNA remained unchanged upon infection. Cells infected with C. pneumoniae secreted increased quantities of MMP-1 and -3 proteins as demonstrated by enzyme-linked immunosorbent assays. The ability of C. pneumoniae to stimulate the production of MMP-1 and -3 by SMC may be important for its pathogenic role in the progression of atherosclerotic disease.

Arteriosclerosis↗
PubMed2003

R 56865 exerts cardioprotective properties independent of the intracellular Na(+)-overload in the guinea pig heart.

Reducing intracellular Na(+)-accumulation during ischemia exerts cardioprotective effects in reperfusion in a variety of models. Since slowly-inactivating Na(+)-channels may contribute to Na(+)-influx in ischemia, we investigated whether the ischemia-protective properties of R 56865, an inhibitor of slowly inactivating Na(+)-channels, are mediated by inhibition of the ischemic Na(+)-overload. Monitoring intracellular Na(+) (Na(+)(i)) by (23)Na-NMR-spectroscopy revealed a continuous rise of Na(+)(i) during ischemia in the isolated perfused guinea pig heart. Within 30 and 60 min of ischemia, respectively, Na(+)(i) had risen 2.6+/-0.2- and 4.4+/-0.2-fold compared to baseline ( n=6). R 56865 (1 microM) did not influence the time course of the Na(+)(i)-accumulation at any point of the ischemic period. R 56865, however, showed marked cardioprotective properties: in the reperfusion period the agent markedly improved the restoration of left ventricular developed pressure (29.1+/-6.8 mm Hg vs. 2.4+/-2.0 mm Hg), ATP (2.8+/-0.3 mM vs. 1.7+/-0.6 mM) and phosphocreatine (10.9+/-2.2 mM vs. 6.8+/-1.1 mM), furthermore contracture development was reduced. The present study strongly suggests slowly-inactivating Na(+)-channels being at best a minor port of Na(+)-entry in the ischemic guinea pig heart. It clearly demonstrates that the potent cardioprotective properties of R 56865 are unrelated to intracellular sodium homeostasis.

Animals↗
PubMed2002

[IMCO(++)--a Monte Carlo based IMRT system].

The application of intensity modulated radiotherapy (IMRT) to dose escalation in the target volume sets particular demands in terms of accuracy of dose calculation. Dose calculation errors due to approximations are compensated by the optimization algorithm, a procedure that ultimately leads to incorrect fluence modulation. Such inaccuracies affect particularly the dose distribution in areas with secondary electron disequilibrium. In case tissues heterogeneity predominates, conventional dose calculation methods (such as Pencil Beam) can produce relative errors up to more than 10%. The accuracy can be significantly improved by the application of a Monte-Carlo (MC) algorithm. This paper describes a MC-based inverse treatment planning algorithm (IMCO++), based on a non-iterative approach with a feedback-controlling process. The convergence behavior of IMCO++ was investigated and the used MC dose-calculation codes MMms and XVMC were compared by means of a heterogeneous phantom. IMCO++ plans were optimized in various phantoms. All plans showed conformity in terms of dose distribution of the target volume and dose reduction in risk organs (according to the requirements of the target parameter), as well as a very fast convergence of the algorithm (in less than 10 optimization steps).

Humans↗
PubMed2002

Role of interferon-stimulated gene factor 3gamma and beta interferon in HLA class I enhancement in synovial fibroblasts upon infection with Chlamydia trachomatis.

Chlamydia trachomatis infection can cause reactive arthritis that is associated with the persistence of chlamydial organisms in the joint. Fibroblasts of the synovial membrane represent host cells for Chlamydia during articular infection. In this study we investigated the expression of HLA class I molecules in synovial fibroblasts following infection with C. trachomatis D. The expression of HLA class I heavy chain (HLA-I) was up-regulated in infected cultures as shown by reverse transcription-PCR and immunoblotting. The increase in cell surface expression of HLA-I and beta(2) microglobulin on infected fibroblasts was demonstrated by flow cytometric analysis. Suppression of enhanced production of interferon-stimulated gene factor 3gamma (ISGF3gamma) in infected cell cultures by antisense oligonucleotide treatment reduced the level of HLA-I. Blocking antibodies to beta interferon (IFN-beta) inhibited the Chlamydia-induced enhancement of both ISGF3gamma and HLA-I. These findings show that the up-regulation of HLA-I in synovial fibroblasts infected with C. trachomatis is caused by the induction of IFN-beta, which in turn stimulates the synthesis of ISGF3gamma, a transcription factor participating in the regulation of the HLA-I gene. The IFN-beta-mediated expression of HLA-I on Chlamydia-infected cells may be a regulatory factor in the immune response in chlamydial infections.

Cells, Cultured↗