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Biomedical subjects

Andreas König

Publications and source records attributed to Andreas König.

At least 19 recordsLinked to original sources

Synthesis and vasorelaxant properties of hybrid molecules out of NO-donors and the beta-receptor blocking drug propranolol.

S-Nitroso-N-acetylpenicillamine (SNAP) and 3-nitrooxypivaloyl acid were combined in the form of the respective amides with propranolol, in order to obtain prodrugs (NO-propranololes) with beta-receptor blocking properties of the latter compound with nitric oxide releasing properties of the former compounds. A respective nitratoester could not be synthesized, because it immediately rearranges to the amide after deprotection of the amino group. In vitro tests on porcine pulmonary arteries showed that both types of hybrid molecules (6, 12) elicited vasorelaxation, but the nitratoamide was less potent by more than one order of magnitude. The vasorelaxant effect of SNAP was more pronounced than that of the SNAP-hybrid (12), on the other hand the nitratoamide 6 was more potent than 3-nitrooxypivaloyl acid.

Animals↗

Comparison of acute and long-term results and underlying mechanisms from sirolimus-eluting stent implantation for the treatment of in-stent restenosis and recurrent in-stent restenosis in patients in whom intracoronary radiation failed as assessed by intravascular ultrasound.

In-stent restenosis (ISR), especially after vascular brachytherapy, is a therapeutic challenge. Sirolimus-eluting stent implantation is a promising new option for the treatment of patients with ISR. The efficacy of sirolimus-eluting stent implantation for the treatment of patients with their first episodes of ISR and with recurrent ISR due to the failure of vascular brachytherapy was compared using intravascular ultrasound imaging.

Aged↗

Evolution of angiographic restenosis rate and late lumen loss after intracoronary beta radiation for in-stent restenotic lesions.

The aim of this study was to investigate the time course of angiographic restenosis rate and late loss after successful percutaneous coronary intervention and vascular brachytherapy with beta-irradiation using strontium-90/yttrium-90 in 98 patients who were prospectively enrolled into a quantitative angiographic and clinical follow-up protocol at 6, 12, and 24 months after the index procedure, regardless of their symptom status. Actuarial restenosis rates measured 11.2 +/- 5% at 6 months of follow-up, 24.5 +/- 5% at 12 months, and 28.5 +/- 6% at 24 months, respectively. Late loss of the stent segment during the first 6 months measured 0.38 +/- 0.40 mm (6 to 12 months: 0.25 +/- 0.38 mm; 12 to 24 months: 0.16 +/- 0.32 mm), of the injured segment 0.27 +/- 0.21 mm (6 to 12 months: 0.21 +/- 0.26 mm; 12 to 24 months: 0.13 +/- 0.24 mm), of the irradiated segment 0.18 +/- 0.29 mm (6 to 12 months: 0.19 +/- 0.31 mm; 12 to 24 months: 0.11 +/- 0.27 mm), and of the analysis segment 0.18 +/- 0.36 mm (6 to 12 months: 0.17 +/- 0.29 mm; 12 to 24 months: 0.11 +/- 0.20 mm). Restenosis after angioplasty and beta-irradiation of in-stent restenotic lesions is not complete within 6 months but is sustained with a gradual decrease over 24 months.

Actuarial Analysis↗

ARB: a software environment for sequence data.

The ARB (from Latin arbor, tree) project was initiated almost 10 years ago. The ARB program package comprises a variety of directly interacting software tools for sequence database maintenance and analysis which are controlled by a common graphical user interface. Although it was initially designed for ribosomal RNA data, it can be used for any nucleic and amino acid sequence data as well. A central database contains processed (aligned) primary structure data. Any additional descriptive data can be stored in database fields assigned to the individual sequences or linked via local or worldwide networks. A phylogenetic tree visualized in the main window can be used for data access and visualization. The package comprises additional tools for data import and export, sequence alignment, primary and secondary structure editing, profile and filter calculation, phylogenetic analyses, specific hybridization probe design and evaluation and other components for data analysis. Currently, the package is used by numerous working groups worldwide.

Data Display↗

Are high doses of intracoronary adenosine an alternative to standard intravenous adenosine for the assessment of fractional flow reserve?

BACKGROUND: Achievement of maximal hyperemia of the coronary microcirculation is a prerequisite for the measurement of fractional flow reserve (FFR). Intravenous adenosine is considered the standard method, but its use in the catheterization laboratory is time consuming and expensive compared with intracoronary adenosine. Therefore, this study compared different high, intracoronary doses of adenosine for the potential to achieve a maximal hyperemia equivalent to the standard intravenous route. METHODS: FFR was assessed in 50 patients with 50 intermediate lesions during cardiac catheterization. FFR was calculated as the ratio of the distal coronary pressure to the aortic pressure at hyperemia. Different incremental doses of intracoronary adenosine (60, 90, 120, and 150 microg as boli) and a standard intravenous infusion of 140 microg/kg/min were administered in a randomized fashion. RESULTS: Different incremental doses of intracoronary adenosine were well tolerated, with fewer systemic adverse effects than intravenous adenosine. At baseline, there were no significant differences for mean aortic and distal coronary pressure or heart rate in the different adenosine doses and routes. FFR decreased with increasing adenosine doses, with the lowest values observed with the 150-microg intracoronary bolus and 140-microg/kg/min dose of intravenous adenosine. All intracoronary doses, except the 150-microg bolus, resulted in mean FFR values that were significantly (P <.05) higher than FFR after the administration intravenous adenosine. Furthermore, 5 patients (10%) with a FFR value >0.75 and 3 subjects (6%) with a FFR value >0.80 who received a 60-microg intracoronary bolus reached a value below the cutoff point of 0.75 with the intravenous administration. CONCLUSIONS: This study suggests a dose-response relationship on hyperemia for intracoronary adenosine doses >60 microg. The administration of very high intracoronary adenosine boli is safe and associated with fewer systemic adverse effects than standard intravenous adenosine. However, intravenous adenosine administration with 140 microg/kg/min produced a more pronounced hyperemia than intracoronary adenosine in most patients and should be the preferred mode of application for the assessment of FFR.

Adenosine↗

Impact of barotrauma on acute and late angiographic and clinical outcomes following angioplasty and beta-irradiation of coronary in-stent restenotic lesions.

INTRODUCTION: The aim of this study was to prospectively evaluate the impact of different degrees of vessel barotrauma on the acute and 1-year clinical and angiographic outcomes of percutaneous coronary intervention (PCI) and adjunctive vascular brachytherapy (VBT) with 90Sr/90Y for in-stent restenotic lesions (ISR) in 118 patients. METHODS AND RESULTS: Sixty consecutive patients were treated according to an aggressive PCI strategy (group 1); fifty-eight were treated non-aggressively (group 2). Irradiation was performed with a manual afterloader. Clinical and angiographic baseline characteristics did not differ between groups. Group 1 yielded a higher acute lumen gain (2.3 +/- 1.2 mm versus 1.7 +/- 1.3 mm; p=0.005) and a higher prevalence of additional stent implantation (48.3% versus 22.4%; p=0.003). At follow-up, net gain (1.8 +/- 0.7 mm versus 1.4 +/- 0.8 mm; p=0.102) was equalized by a higher late loss in group 1 (0.6 +/- 0.8 mm versus 0.3 +/- 0.7 mm; p=0.036). Remaining target vessel late loss, due to edge effects, was considerably higher in group 1 than in group 2 (0.5 +/- 0.8 mm versus 0.2 +/- 0.5 mm; p<0.001), leading to a higher rate of binary angiographic restenosis (23.3% versus 6.9%; p=0.013) and target vessel revascularization (16.7% versus 5.2%; p=0.046). After excluding patients who received additional stents, the angiographic differences between groups were attenuated. CONCLUSION: Our study does not support the use of oversized balloons and high inflation pressures for the treatment of ISR when combined with VBT. Additional stent implantation combined with VBT carries a high risk of repeat revascularization in the setting of ISR and should be avoided.

Adult↗

The varicella-zoster virus induces apoptosis in vitro in subpopulations of primary human peripheral blood mononuclear cells.

Varicella-zoster virus (VZV), a member of Herpesviridae, subfamily alpha-Herpesvirinae, is pathogenic exclusively in the human. Chickenpox is the result of primary infection of VZV. During the viremic stage, VZV infects peripheral blood mononuclear cells (PBMC) and spreads to the periphery. In skin cells it causes typical lesions. Apoptosis has been demonstrated in different cell types by other alpha-herpesviruses. VZV-infected T lymphocytes, B lymphocytes, and monocytes, respectively, were examined in this in vitro study by flow cytometry, immunofluorescence and electron microscopy. All infected cell types showed signs of apoptosis: a lower DNA content, DNA fragmentation, loss of membrane integrity, and an altered nuclear morphology. The results observed led to the suggestion that VZV can induce apoptosis during infection in vivo in the PBMC subpopulations.

Annexin A5↗

Stent design-related coronary artery remodeling and patterns of neointima formation following self-expanding and balloon-expandable stent implantation.

The self-expanding Wallstent (WS) and balloon-expandable Palmaz-Schatz stents (PS) display different mechanical and dynamical stent properties. We analyzed the impact of the respective stent design on coronary wall geometry using quantitative coronary angiography (QCA) and intracoronary ultrasound (ICUS) measurements. Serial measurements were performed within the stent and within reference segments of 50 patients (25 WS, 25 PS). Relative changes for each parameter in both stent designs were calculated (Mann-Whitney U-test; 95% CI). The luminal net gain in WS was not significantly higher in WS compared with PS (1.63 +/- 1.11 vs. 1.44 +/- 0.63 mm; P = 0.2554). The respective loss indexes were also similar (0.38 +/- 0.42 vs. 0.36 +/- 0.23; P = 0.8578). The WS segments showed significant postinterventional stent expansion with positive vessel remodeling. The neointima formation was significantly higher in WS segments (4.23 +/- 2.07 vs. 2.22 +/- 2.22 mm(2)). The coronary wall morphology and stent geometry after 6.5 +/- 1.2 months are related to the stent design. In WS segments, the neointima formation was balanced by postinterventional stent expansion, resulting in a comparable relative lumen loss in both stent types. The respective stent design had no impact on the vessel reference segments.

Coronary Angiography↗

Microbial sensors on a respiratory basis for wastewater monitoring.

In respect of their rapidity, their online capabilities, and their moderate costs, biosensing systems generally offer an attractive alternative to the existing methods of water analysis. Additionally, one particular advantage of microbial biosensors is the ability to measure direct effects on living cells, e.g., their respiratory activity and its alteration caused by environmental pollutants. It is true that microbial sensors, often do not provide the optimum solution for the determination of individual analytes when compared to established physico-chemical analysis methods. However, these biosensing devices are predestined for the summary determination of environmentally relevant compounds and their complex effects, respectively. For this reason, microbial sensors allow an integral evaluation of the degree of environmental pollution including the interaction of various compounds. Moreover, in some cases specific metabolic pathways in microorganisms are used, resulting in the development of microbial sensors for the more selective analysis for those compounds or pollutants, which cannot be measured by simple enzyme reactions, e.g., the determination of aromatic compounds and heavy metals. This chapter gives an overview of microbiological biosensors on respiratory basis for the measurement of the following environmentally relevant compounds: inorganic N-compounds, heavy metals, organic xenobiotics and the estimation of sum parameters or so-called complex parameters such as BOD, ADOC, N-BOD, and the inhibition of nitrification.

Bacteria↗

Serial intravascular ultrasound analysis after intracoronary beta-radiation in long in-stent restenotic lesions.

In-stent restenosis (ISR) represents the major limitation of stent implantation. Treatment, although of relative technical ease, is unsatisfactory due to the high incidence of recurrent restenosis. Long ISR lesions are especially prone to restenosis. Vascular brachytherapy (VBT) has emerged as a powerful adjunct therapeutic modality to treat ISR. However, VBT may be less effective in very long, diffuse ISR lesions. The present study investigated serial changes of the extent and distribution of neointima formation after beta-radiation as assessed by intravascular ultrasound (IVUS). Following interventional procedures of long ISR in 30 patients, a 40 mm or 60 mm non-centered 90Sr/90Y seed train was used for VBT. Serial (post radiation (PR) and follow-up (FU)) quantitative coronary angiography (QCA) measurements of minimal lumen diameter (MLD) and late lumen loss (LLL) and intravascular ultrasound measurements (IVUS) of cross-sectional areas of the lumen (L-CSA), stent (S-CSA) and intimal hyperplasia (IH-CSA) were performed and compared with historic controls. LLL (0.34 +/- 0.27 mm; p = 0.196), mean decrease of L-CSA (-1.0 +/- 0.8 mm2; p = 0.024) and mean increase of IH-CSA (0.5 +/- 1.3 mm2; p = 0.038) in long ISR were comparable with previously reported results of short ISR. In conclusion the average changes of lumen and intimal hyperplasia after beta-radiation of long ISR are similar to those of short ISR.

Adult↗

Influence of stent design and deployment technique on neointima formation and vascular remodeling.

A variety of different stent types is available for the treatment of coronary stenosis. However, in-stent restenosis remains the major limitation for the use of these devices. Intracoronary ultrasound (ICUS) in addition to coronary angiography provides precise measurements of coronary wall dimensions during stent implantation and of intimal hyperplasia during follow-up. The extent of coronary injury during stent implantation was shown to play an important role in neointima formation. It is characterized by endothelial exposure, intima laceration, and media permeation. Stent-induced coronary injury has been considered to depend on stent design and stent strut size with consecutive deep wall laceration. ICUS analysis showed a correlation between the stent design and the amount of neointimal tissue proliferation. The role of adventitial remodeling in the process of restenosis is discussed controversially. Post-procedural stent expansion may provoke adventitial remodeling. The stent design and stenting strategy determines the extent of peri- and post-procedural coronary injury. Post-procedural coronary morphologic changes and changes of the stent geometry depend upon the stent design. Beside further modifications as the use of drug-eluting stents the decrease of stent-related vessel injury should be an important criterion for the development of future stent design.

Angioplasty, Balloon, Coronary↗

Fractional flow reserve predicts major adverse cardiac events after coronary stent implantation.

OBJECTIVES: Determination of fractional flow reserve (FFR) allows the functional assessment of coronary stenoses before and after an intervention. Preliminary data suggest that a FFR > or = 0.94 is associated with an excellent clinical outcome after stent implantation. However, these results were limited both by the number of patients included and the use of non-contemporary stent designs. We sought to determine the prognostic value of FFR measurements in a large patient cohort undergoing coronary stent implantation. METHODS: Eighty-nine consecutive patients were enrolled in whom a stent implantation was performed and a pressure wire was used as a guide wire. Patients were followed for at least 6 months. Death, myocardial infarction (MI) and target vessel revascularization (TVR) were considered cardiac events. A FFR > or = 0.94 was regarded as an optimal functional result. RESULTS: A complete follow-up was available in all patents. Pre-interventional FFR increased from 0.66 +/- 0.16 to 0.95 +/- 0.05 (p < 0.0001) after stent implantation. Sixteen (18%) events occurred during follow-up including 10 (11.2%) TVR. Final FFR was significantly higher in patients without compared to patients with an event (0.92 +/- 0.06 vs. 0.96 +/- 0.05, p < 0.003). By univariate analysis, the presence of diabetes mellitus, left ventricular function, residual diameter stenosis and final FFR were associated with a worse clinical outcome. In the multivariate analysis, only the final FFR and left ventricular function remained as significant predictors for cardiac events (relative risk, 3.50; 95% CI: 1.29-9.52, P < 0.014, and 0.97; 95% CI: 0.93-1.00, p = 0.047). CONCLUSION: These results demonstrate in a nonselected patient cohort a strong correlation between FFR values after coronary stenting and subsequent cardiac events. Further studies have to investigate whether outcome after stenting might be improved by guiding the procedure with a pressure guide wire.

Aged↗