The effects of the selective alpha-1-adrenoceptor antagonist doxazosin on metabolic and fibrinolytic parameters were studied in hypertensive patients with various degrees of fasting plasma insulin ...levels (Group A: 22.5 +/- 3 microU/ml, Group B: 8.1 +/- 1.5 microU/ml; p <0.01) to disclose a potential link between a doxazosin-induced alteration of insulin and/or lipid metabolism and possible changes of these parameters on the fibrinolytic system. Doxazosin treatment resulted in a dose-dependent reduction of basal insulin levels in group A to 16 +/- 3 microU/ml; p <0.05. This finding was paralleled by a dose-dependent increase in t-PAmass concentration in the same patient group (basal t-PAmass from 9.7 +/- 1 to 15.5 +/- 2 ng/ml; p <0.05). As PAI-1 "active" as well as total antigen levels were not altered in parallel, the net effect on the endogenous fibrinolytic system is an increase of the fibrinolytic potential.
In present positron emission tomography (PET)/computed tomography (CT) scanners, PET attenuation correction is performed by relying on the information given by a single CT scan. The scaling of the ...linear attenuation coefficients from CT x-ray energy to PET
511
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gamma energy is prone to errors especially in the presence of CT contrast agents. Attenuation correction based upon two CT scans at different energies but performed at the same time and patient position should reduce such errors and therefore improve the accuracy of the reconstructed PET images at the cost of introduced additional noise. Such CT scans could be provided by future PET/CT scanners that have either dual source CT or energy sensitive CT. Three different dual energy scaling methods for attenuation correction are introduced and assessed by measurements with a modified NEMA 1994 phantom with different CT contrast agent concentrations. The scaling is achieved by differentiating between (1) Compton and photoelectric effect, (2) atomic number and density, or (3) water-bone and water-iodine scaling schemes. The scaling method (3) is called hybrid dual energy computed tomography attenuation correction (hybrid DECTAC). All three dual energy scaling methods lead to a reduction of contrast agent artifacts with respect to single energy scaling. The hybrid DECTAC method resulted in PET images with the weakest artifacts. Both, the hybrid DECTAC and Compton/photoelectric effect scaling resulted also in images with the lowest PET background variability. Atomic number/density scaling and Compton/photoelectric effect scaling had problems to correctly scale water, hybrid DECTAC scaling and single energy scaling to correctly scale Teflon. Atomic number/density scaling and hybrid DECTAC could be generalized to reduce these problems.
ST-elevation myocardial infarction (STEMI) results from acute thrombotic obstruction of a coronary artery. Percutaneous coronary intervention (PCI) is the treatment of choice to restore blood flow. ...The incidence of guidewire-induced reopening of the infarct-related coronary artery (IRA) and its association with post-procedural TIMI flow and long-term mortality were assessed. Angiograms of consecutive STEMI patients admitted to the catheter laboratory of the Medical University of Vienna between January 2003 and December 2005 were analysed. TIMI flow was graded prior to and after guidewire insertion into the distality of the IRA, and at the end of the procedure. Initial TIMI 0 flow was present in 476 (47.0%) of 1,012 cases. Target vessel reopening after guidewire insertion defined as any flow >TIMI 0 flow occurred in 150 patients (37.2%), and was associated with improved survival after a median of 914 (609-1,238) days (p=0.017). Reflow after guidewire insertion was an independent predictor of post-procedural TIMI flow (odds ratio=3.10, 95% confidence interval CI=1.64 - 5.86, p<0.001) and mortality (hazard ratio=0.51, CI=0.28 - 0.94, p=0.029). Target vessel reopening by guidewire insertion is a new predictor of prognosis. Target vessel flow after guidewire insertion should be assessed in a standardised fashion during PCI.
Background: Currently used methods for assessment of coronary flow reserve are invasive and require extensive laboratory equipment. Recently, noninvasive assessment of coronary flow reserve by ...transesophageal Doppler evaluation of coronary sinus (CS) or left anterior descending coronary artery (LAD) flow has been proposed. Direct comparison between these two techniques is lacking.
Methods: Doppler recordings of CS and LAD flow velocity were obtained before and after 0.6 mg/kg/5 min dipyridamole in 16 patients with significant stenosis of the LAD (Group A) and in 14 control patients (Group B). Flow recordings and all measurements were performed in a blinded manner. For assessment of coronary flow reserve, Doppler measurements after dipyridamole were divided by the respective baseline values.
Results: Doppler studies of the CS and LAD were feasible in 30 of 30 (100%) and 23 of 30 (71%) patients, respectively. Analyzing the maximum flow velocities, coronary flow reserve in Groups A and B was 1.18 ± 0.28 and 1.68 ± 0.53 with CS recordings and 1.78 ± 0.83 and 2.51 ± 0.76 with LAD recordings, respectively. Analyzing the velocity time integrals, coronary flow reserve in Groups A and B was 1.53 ± 0.68 and 2.59 ± 0.74 with CS recordings and 1.77 ± 0.38 and 2.68 ± 0.93 with LAD recordings, respectively. Correlation between LAD and CS recordings was 0.69 (p<0.001), when coronary flow reserve was calculated from the velocity time integral and 0.68 (p<0.001) when the maximum flow velocities were used.
Conclusion: Both transesophageal Doppler techniques might be useful for noninvasive assessment of coronary flow reserve.
Trotz zunehmender IMRT-Bestrahlungstechniken gibt es im klinischen Alltag der Strahlentherapie immer noch in Einzelfällen die Notwendigkeit zum Anschluss von Photonenfeldern an Photonen- oder ...Elektronenfelder. Derartige Feldanschlüsse werden in dieser Arbeit untersucht, indem in mehreren Tiefen gemessene Dosisquerverteilungen durch systematische relative Verschiebungen zueinander rechnerisch überlagert werden und die dabei entstehenden Dosisüberhöhungen und Dosiseinbrüche dargestellt werden. Es zeigt sich, dass „optimale“ Feldanschlüsse nur in seltenen Fällen zu erreichen sind. Aber die Ergebnisse können dazu dienen, die Größenordnung der zu erwartenden Dosisänderungen abzuschätzen.
Despite increasing IMRT techniques in the clinical routine of radiotherapy there is still the need of matching photon beams with either photon or electron beams in some particular cases. Such matched beams are investigated in this paper by mathematical adding of measured transverse dose profiles in different depths and shifting them systematically relative to each other. The resulting hot and cold spots are shown. As demonstrated, an “optimal” field matching is only rarely achieved. However, the results can help to estimate the order of magnitude of the expected dose variation.
Despite increasing IMRT techniques in the clinical routine of radiotherapy there is still the need of matching photon beams with either photon or electron beams in some particular cases. Such matched ...beams are investigated in this paper by mathematical adding of measured transverse dose profiles in different depths and shifting them systematically relative to each other. The resulting hot and cold spots are shown. As demonstrated, an "optimal" field matching is only rarely achieved. However, the results can help to estimate the order of magnitude of the expected dose variation.
Abstract Background Plasminogen activator inhibitor-1 (PAI-1) has been shown to increase after percutaneous coronary intervention (PCI). Whether activated platelets, local trauma with activation of ...resident vascular cells or the acute phase response is the source of this PAI-1 increase is not well defined. Therefore we examined whether intensive platelet inhibition may modulate PAI-1 levels or whether the PAI-1 increase is associated with the acute phase protein C-reactive protein (CRP). Methods We included 51 patients with stable angina who underwent elective PCI with stent implantation. At the time of study, routine pretreatment with clopidogrel before PCI was not standard of care, but left to the discretion of the referring cardiologist. We matched 17 patients with stable angina that were not pretreated with clopidogrel but received a loading dose of 300 mg immediately after stent implantation according age, sex and smoking with 34 patients that received clopidogrel at least 12 to 24 hours before PCI. Blood samples for measurement of PAI-1, t-PA and CRP were taken directly before and 24 hours after the procedure. Results PAI-1 and t-PA active antigen plasma levels before PCI were not different in patients with and without clopidogrel pretreatment. Whereas PCI induced a significant increase of PAI-1 levels in patients without pretreatment (p < 0.05), the procedure had no effect on PAI-1 active antigen in patients pretreated with clopidogrel. This resulted in significant lower PAI-1 plasma levels 24 hours after PCI in patients with pretreatment (p < 0.05). CRP was not associated with pre- or postprocedural PAI-1 levels. Conclusion Clopidogrel pretreatment completely abolishes the increase of PAI-1 active antigen after coronary stent implantation. This suggests that peri-procedural platelet activation might play a major role for the increase of PAI-1 after PCI thus increasing the risk of acute and subacute thrombus formation based on a reduced endogenous fibrinolytic system.
Increased expression of plasminogen activator inhibitor-1 (PAI-1) mRNA in atherosclerotic human arteries suggests a linkage between PAI-1 gene expression and cellular proliferation, the fundamental ...feature of atherosclerosis. To investigate whether smooth muscle cell (SMC) proliferation influences overall fibrinolytic properties of the vascular wall, we examined the effect of serial in vitro passaging of human SMCs on tissue plasminogen activator (TPA) and PAI-1 synthesis levels as well as the ability to modulate TPA and PAI-1 synthesis of human umbilical vein endothelial cells (HUVECs). As in vivo correlates for such late-passage cells in culture, SMCs derived from human atherosclerotic plaques were used, because they are thought to have already undergone numerous cell doublings. We observed an increase of PAI-1 secretion (from 591 +/- 106 to 2952 +/- 290 ng PAI-1.10(5) cells-1.24 h-1) with a concomitant fourfold to fivefold increase of PAI-1 mRNA levels, as well as a decrease of TPA secretion (from 118 +/- 34 to 8 +/- 1.3 ng TPA.10(5) cells-1.24 h-1) and a twofold to threefold decrease of TPA mRNA levels with increasing in vitro passage number (from passage 3 to 11) of normal pulmonary artery smooth muscle cells (PASMCs) (P < .05). SMCs derived from atherosclerotic plaques of coronary arteries (CASMCs) displayed higher levels of PAI-1 antigen synthesis (3093 +/- 507 ng PAI-1.10(5) cells-1.24 h-1) with an approximately twofold increase of PAI-1 mRNA levels, as well as decreased levels of TPA antigen synthesis (10 +/- 1.6 ng TPA.10(5) cells-1.24 h-1) with an approximately 1.5- to 2-fold decrease of TPA mRNA levels in passage 1, compared with their counterparts derived from normal-appearing arterial tissue of the same vessel (1794 +/- 525 ng PAI-1.10(5) cells-1.24 h-1; 17 +/- 5 ng TPA.10(5) cells-1.24 h-1) (P < .001; P < .01). Incubation of HUVEC cultures with the 24-hour conditioned media (CM) of early-passage PASMCs decreased endothelial PAI-1 antigen synthesis by approximately 42% (P < .001) and endothelial PAI-1 mRNA levels about twofold to threefold (P < .001), whereas by incubation with the 24-hour CM of late-passage PASMCs, endothelial PAI-1 antigen synthesis was upregulated by 68% (P = .001), with a concomitant twofold increase of endothelial PAI-1 mRNA levels (P < .001). The apparent MW of this heat- and acid-stable PAI-1 upregulating factor appears to be between 50 and 100 kD, as judged by ultrafiltration. Incubation of HUVEC cultures with the 24-hour CM of early-passage CASMCs derived from normal-appearing arterial tissue showed no significant influence on endothelial PAI-1 synthesis, whereas incubation with late-passage normal CASMCs, as well as early-passage atherosclerotic CASMCs from the same vessel, increased endothelial PAI-1 antigen secretion by 45% and 48% (P < .001), with a concomitant 1.5 fold to 2-fold increase of endothelial PAI-1 mRNA levels (P < .05). No significant change in endothelial TPA synthesis was observed by incubation with CM of either PASMCs (early or late passage) or CASMCs (atherosclerotic or normal). These data suggest that SMC proliferation is associated with (1) increased SMC PAI-1 synthesis as well as decreased TPA synthesis and (2) upregulation of endothelial PAI-1 synthesis by SMC CM. This phenomenon is observed with either late passages of normal PASMCs and CASMCs or early passages of atherosclerotic plaque CASMCs. This suggests that proliferating SMCs are a major regulator of the fibrinolytic potential within the vessel wall, thereby contributing to the thrombotic risk associated with the development of atherosclerosis.
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