Human antibody against C domain of tenascin-C visualizes murine atherosclerotic plaques ex vivo.

Targeting proteins that are overexpressed in atherosclerotic plaques may open novel diagnostic applications. The C domain of tenascin-C is absent from normal adult tissues but can be inserted during tumor progression or tissue repair into the molecule by alternative splicing. We tested the ability of the human antibody G11, specific to this antigen, to reveal murine atherosclerotic plaques ex vivo. The antibody directed against the extra domain B of fibronectin (L19) was used as a reference. METHODS: We intravenously injected (125)I-labeled G11 or L19 antibodies into apolipoprotein E-deficient (ApoE(-/-)) mice and harvested the aortae 4 or 24 h later. En face analyses of distal aortae and longitudinal sections of the aortic arch were performed to compare antibody uptake using autoradiography with plaque staining using oil red O. Plaque macrophages were detected by immunohistochemistry (anti-CD68 staining). Biodistribution of injected antibodies was investigated in aortae and blood at 4 and 24 h. RESULTS: En face analyses revealed a significant correlation between radiolabeled G11 and fat-stained areas, increasing from 4 to 24 h, with a correlation coefficient of 0.92 (P < 0.0001) and an average signal-to-noise ratio of 104:1 at 24 h. Plaque imaging using L19 showed similar results (r = 0.86; P < 0.0001; signal-to-noise ratio, 72:1 at 24 h). Uptake of radiolabeled antibodies in histologic sections colocalized with fat staining and activated macrophages in aortic plaques. Biodistribution analyses confirmed specific accumulation in aortic plaques as well as rapid blood pool clearance of the antibodies 24 h after injection. Immunofluorescence analyses revealed increased expression of tenascin and fibronectin isoforms in macrophage-rich plaques. CONCLUSION: The antibody G11, specific to the C domain of tenascin-C, visualizes murine atherosclerotic plaques ex vivo. In conjunction with the increased expression of the C domain of tenascin-C in macrophage-rich plaques, the colocalization of G11 uptake with activated macrophages, and the favorable target-to-blood ratio at 24 h, this antibody may be useful for molecular imaging of advanced atherosclerotic plaques in the intact organism.     

The Static Stiffness Index: A Simple Method to Assess the Elastic Property of Compression Material In Vivo

BACKGROUND: The efficacy of compression therapy depends mainly on the exerted pressure and on the stiffness of the material. OBJECTIVE: To propose a simple method by which pressure and stiffness can be assessed in the individual patient. MATERIAL AND METHODS: Using a pressure transducer (Kikuhime small probe, MediTrade, Soro, Denmark) the sub-bandage pressure is measured on the medial aspect of the lower leg at the transition of the gastrocnemius muscle into the Achilles' tendon. The pressure difference between active standing and lying is defined as the static stiffness index (SSI). Results: The accuracy and precision of the probe are good. Unna boot bandages (Lohmann-Rauscher, Vienna, Austria) and multilayer short-stretch bandages show a significantly higher SSI than long-stretch bandages and round-knitted class II stockings. The SSI values are lower than 10 mm Hg for elastic, long-stretch material and higher than 10 mm Hg for inelastic, short-stretch material. CONCLUSION: In future compression trials, pressure and stiffness measured in vivo should be declared.     

Remote-controlled catheter ablation of accessory pathways: results from the magnetic laboratory.

AIMS: This study evaluates feasibility, safety, and efficacy of magnetic remote-controlled accessory pathway (AP) ablation. METHODS AND RESULTS: The novel magnetic navigation system (MNS) (Niobe, Stereotaxis) creates a steerable magnetic field (0.08 T) controlling the distal magnetic tip of an ablation catheter. In conjunction with a catheter advancer system (Cardiodrive, Stereotaxis) remote catheter ablation is enabled. Conventional electrophysiology study identified AP conduction in 59 patients (37 males, 36+/-14 years, 60 APs). First generation 1-magnet tip (1-M) (group I, n=18), second generation bipolar 3-magnet tip (3-M) (group II, n=27), and third generation quadripolar 3-magnet tip catheters (3-M quad.) (group III, n=14) were used for magnetic remote-controlled ablation. Successful AP ablation was achieved in 67% (group I), 85% (group II), and 92% (group III). A significant decrease of median [IQR: Q1-Q3] fluoroscopy time and dosage was observed: 21.2 [12.1-33.8] min, 1110 [395-3234] microGym2 (group I); 6.5 [4.4-15.4] min, 290 [129-489] microGym2 (group II), and 4.9 [3.4-8.0] min, 129 [74-270] microGym2 (group III). Mean procedure time (217+/-67 min; 182+/-68 min, and 172+/-90 min) significantly decreased in group III. Median number [Q1-Q3] of radiofrequency current applications in groups I, II, and III was 4 [2-9], 4 [2-6], and 2 [2-4], respectively. No complications occurred. CONCLUSION: Remote AP ablation is safe and feasible using the novel MNS. Introduction of the 3-magnet quadripolar ablation catheter significantly improved the efficacy of the procedure.     

The frozen elephant trunk technique for the treatment of extensive thoracic aortic aneurysms: operative results and follow-up.

OBJECTIVE: The 'frozen' elephant trunk technique allows for single-stage repair of combined aortic arch and descending aortic aneurysms using a 'hybridprosthesis' with a stented and a non-stented end. This report summarizes the operative- and follow-up data (mean follow-up 14 months) with this new treatment. METHODS: Between 09/01 and 4/04, 22 patients (62+/-9 years; 9 female) with different aortic pathologies (15 aortic dissections, 7 aneurysms) were operated on after approval from the local institutional review board. The stented end of the hybridprosthesis was deployed in the descending aorta through the opened aortic arch during hypothermic circulatory arrest and selective antegrade cerebral perfusion. RESULTS: All patients survived the procedure but one patient died of acute hemorrhage due to rupture of the false lumen in the descending aorta on the second postoperative day. Two patients required reexploration of the chest for bleeding complications. In 2 of 4 patients who developed neurological dysfunction, symptoms resolved completely. In one of them, the descending aorta was perforated intraoperatively due to misplacement of the stented end of the hybridprosthesis. In all follow-up CT-scans thrombus formation in the descending aortic aneurysm excluded by the stented end of the hybridprosthesis has been observed. CONCLUSIONS: This procedure is performed through median sternotomy and combines the concepts of the elephant trunk operation and endovascular stenting of descending aortic aneurysms. Favourable intraoperative and postoperative results during follow-up with regard to thrombus formation around the stented descending aortic segment encourage us to evaluate all patients with thoracic aneurysms extending to proximal and distal of the left subclavian artery for this treatment.     

Risk stratification with cardiac troponin I in patients undergoing elective coronary artery bypass surgery.

OBJECTIVE: Cardiac troponin I (cTnI) is a highly sensitive and specific marker for postoperative prediction of patients outcome after coronary artery bypass surgery (CABG). Whether preoperatively elevated cTnI levels similarly predict the outcome in patients scheduled for elective CABG is currently unknown. METHODS: Therefore, a possible correlation between preoperative cTnI levels and perioperative major adverse events and in-hospital mortality after CABG was investigated. CTnI was measured within 24h before surgery in 1405 out of 3124 consecutive elective CABG patients. Out of these patients, 1178 had a preoperative cTnI level below 0.1ng/ml (group 1), 163 patients had a cTnI level between 0.11 and 1.5ng/ml (group 2), and 64 patients had a cTnI level above 1.5ng/ml (group 3). CTnI levels, electrocardiograms, clinical data, adverse events and in-hospital mortality were recorded prospectively. Patients with ST-elevation myocardial infarction less than 7 days before surgery were excluded from the study. RESULTS: Perioperative myocardial infarction (PMI) occurred in 69/1178 patients (5.9%) in group 1, 14/163 patients (8.6%; odds ratio (OR) 1.5, 95% confidence interval (CI): 0.8-2.8) in group 2, and 11/64 patients (17.2%; OR 3.3, CI: 1.6-7.0) in group 3 (overall: P<0.001, Cochran-Armitage trend test). Low cardiac output syndrome (LCOS) occurred in 19/1178 patients (1.6%), 9/163 (5.5%; OR 3.6, CI: 1.5-8.5), and 7/64 patients (10.9%; OR 7.5, CI: 2.7-19.8) (overall: P<0.001, group 1 vs. group 2: P<0.002), respectively. In-hospital mortality was 1.7% in group 1 and 3.1% in group 2, but 6.3% (OR 3.9, CI: 1.1-12.5) in group 3 (overall: P<0.01, group 1 vs. group 2: P=NS). Intensive care and hospital stay were significantly longer in group 3 compared to groups 1 and 2. Univariate and multivariate logistic regression analysis confirmed the statistically significant relationship between cTnI and PMI, LCOS and in-hospital mortality, respectively (P<0.001). CONCLUSIONS: Risk stratification by measurement of cTnI levels within 24h before elective CABG clearly identifies a subgroup of patients with increased risk for postoperative adverse outcome and in-hospital mortality.     

Precision of Image-Guided Radiotherapy (IGRT) in Six Degrees of Freedom and Limitations in Clinical Practice

PURPOSE: To evaluate the precision of image-guided radiotherapy (IGRT) using cone-beam computed tomography (CB-CT) for volume imaging and a robotic couch for correcting setup errors in six degrees of freedom. PATIENTS AND METHODS: 47 consecutive patients with 372 fractions were classified according to whether a patient fixation device was used (pat(fix): n = 28) or not (pat(non-fix): n = 19). Prior to treatment a CB-CT was acquired and translational and rotational setup errors were corrected online without an action level using a robotic couch (HexaPOD). A second CB-CT was acquired after the correction process and after treatment in 134 and 238 fractions, respectively. RESULTS: In 17 fractions (4.6%) rotational errors > 3 degrees exceeded the motion range of the HexaPOD. Errors (3D vector) after the correction process were significantly smaller for pat(fix) compared to pat(non-fix) (p < 0.001): 0.9 mm +/- 0.5 mm and 1.6 mm +/- 0.8 mm, respectively. For pat(non-fix) the correction of rotational errors resulted in displacements of the patients on the angled couch of 0.6 mm/1 degree. Intrafractional motion further decreased precision in pat(non-fix) but not in pat(fix). CONCLUSION: Very high precision in cranial and extracranial treatment of immobilized patients was demonstrated. Without application of adequate immobilization the correction of rotational errors and intrafractional patient motion significantly decreased the accuracy of the online correction protocol.