Mechanisms of vascular dysfunction in the interleukin-10–deficient murine model of preeclampsia indicate nitric oxide dysregulation

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Low-permeability Gore Excluder device versus the original in abdominal aortic aneurysm size regression

We sought to compare the efficacy of a low-permeability version of the Gore Excluder™ device with that of the original device. We used volumetric analysis and maximum transverse diameter measurements to examine abdominal aortic aneurysm size regression after endovascular aneurysm repair.From November 2002 through April 2007, 101 patients (82% men; mean age, 71.5 ± 8.9 yr) underwent endovascular aneurysm repair with the Excluder stent-graft: 34 with the original device, and 67 with the low-permeability device. Only patients without endoleak and with preprocedural and 1- and 2-year follow-up computed tomographic scans were included. Eight patients with type II endoleak and 2 with type I endoleak were excluded. Maximum abdominal aortic aneurysm diameter and volume were measured before endovascular aneurysm repair and annually thereafter. Postprocessing, multiplanar computed tomography, and 3-dimensional reconstructions were compared with baseline measurements. Diameter and volume changes that were greater than 5 mm or that exceeded 10% were considered significant.At 12 months, the mean maximum transverse diameter had decreased by −0.16 ± 12.1 mm in recipients of the original device and by −4.8 ± 5.9 mm in recipients of the low-permeability device (P = NS). In addition, mean reduction in volume had changed by −17 ± 16 mL in original-device recipients and by −36.1 ± 37.9 mL in low-permeability device recipients (P < 0.01).One-year follow-up revealed that the low-permeability stent-graft resulted in a greater decrease in abdominal aortic aneurysm volume than did the original stent-graft.Key words: Aortic aneurysm, abdominal/exclusion/repair; blood vessel prosthesis; endoleak; stent-grafts; stents; tomography, x-ray computed; treatment outcomeEndovascular aortic repair (EVAR) has become an accepted treatment technique for patients with abdominal aortic aneurysm (AAA). Compared with surgery, EVAR is associated with less operative blood loss, shorter hospital and intensive care unit stays, fewer major postoperative complications, and more rapid convalescence.^1–3 In addition, EVAR has proved beneficial in the treatment of high-risk patients who cannot undergo standard surgical AAA repair. Two recent prospective, randomized trials have shown that, compared with surgery, EVAR is associated with a reduction in 30-day perioperative mortality.^4,5 The GORE® EXCLUDER® AAA Endoprosthesis (W.L. Gore & Associates, Inc.; Flagstaff, Ariz) is currently 1 of 5 endografts approved by the U.S. Food and Drug Administration for clinical use in the treatment of infrarenal AAA. The Excluder endograft is a bifurcated endoprosthesis composed of a trunk-ipsilateral endoprosthesis and a contralateral leg endoprosthesis. The graft material consists of expanded polytetrafluoroethylene (ePTFE) and fluorinated ethylene propylene. The material is supported by nitinol (nickel-titanium alloy) wire along its external surface, which is attached to the graft by a bonding film.In the mid-term Excluder Pivotal Trial, the original Excluder device was associated with a higher aneurysm expansion rate than that observed with other commercially available devices.^6,7 Some patients in this trial had aneurysm expansion without an identifiable endoleak, a phenomenon termed endotension. As the trial showed, the causes of aneurysm enlargement are multifactorial and include both endoleaks and endotension due to the material''s high permeability by plasma. As a result, several patients in this trial had to undergo late conversion to open surgical intervention.⁸ In an effort to resolve this issue, in June 2004, W.L. Gore & Associates modified the Excluder graft material to reduce its permeability. The purpose of the present study was to compare the efficacy of the new, low-permeability (LP) Excluder device with that of the original device by using volumetric analysis and measuring maximum transverse diameter to examine regression in AAA size after EVAR.     

Image quality of mammography in Croatian nationwide screening program: comparison between various types of facilities

Purpose

The study was aimed to provide objective evidence about the mammographic image quality in Croatia, to compare it between different types of MG facilities and to identify the most common deficiencies and possible reasons as well as the steps needed to improve image quality.

Materials and methods

A total of 420 mammographic examinations collected from 84 mammographic units participating in the Croatian nationwide breast cancer screening program were reviewed in terms of four image quality categories: identification of patient and examination, breast positioning and compression, exposure and contrast, and artifacts. Those were rated using image evaluating system based on American College of Radiology and European Commission proposals. The results were compared among different types of mammographic units, and common image quality deficiencies were identified.

Results

Total image quality scores of 12.8, 16.1, 13.0 and 13.7 were found for general hospitals, university hospitals, private clinics and public healthcare centres, respectively. Average score for all mammographic units was 13.5 (out of 25 points). University hospitals were significantly better than all other mammography units in overall image quality, which was mostly contributed by better breast positioning practices. Private clinics showed the worst results in identification, exposure, contrast and artifacts.

Conclusions

Serious deficiencies in identification and breast positioning, which might compromise breast cancer screening outcome, were detected in our material. They occur mainly due to subjective reasons and could be corrected through additional staff training and improvement of working discipline.     

Benefits of Catheter Thrombectomy during Carotid Stenting: A Preliminary Study

Despite the use of distal embolic protection devices (DEPs) in carotid artery (CA) stenting, an appreciable risk of stroke exists, particularly in symptomatic patients. The mechanism of embolic events is possibly related to microembolization of atherothrombotic débris that remains or forms on the stent struts. This study evaluated the safety of using thrombus-extraction catheters in the setting of CA stenting.From August 2006 through June 2008, 43 symptomatic and asymptomatic patients with severe CA stenosis (>90%) underwent CA stenting with DEPs. After stenting and before removal of the DEP, an extraction catheter was passed through the stented segment. The extracted volume and the filtered extracted volume were visually examined for débris. The primary outcome was a composite of stroke and death at 30 days. Outcomes were compared with those in a control population of 783 patients who underwent CA stenting with a DEP, but without prophylactic thrombus aspiration. Retrospective analysis was performed on prospectively gathered data.Substantial amounts of atherothrombotic débris were extracted from the stented segment in all 43 thrombectomy patients, none of whom died or experienced periprocedural stroke. In the control group, 3.9% of patients experienced these outcomes. Differences in primary outcome did not reach statistical significance.We conclude that the prophylactic use of extraction catheters is safe and does not incur periprocedural events. The results of this preliminary study are encouraging, although larger, randomized trials (optimally using diffusion-weighted magnetic resonance imaging) are needed in order to evaluate this technique''s potential benefits in reducing neurologic complications.Key words: Angioplasty, balloon/instrumentation/methods; atherosclerosis/therapy; balloon dilatation/instrumentation/methods; carotid arteries/surgery; carotid stenosis/complications/therapy; catheterization; equipment design; stents; stroke/prevention & control; survival rate; treatment outcomeAdvances in the endovascular treatment of carotid arterial (CA) occlusive disease have led to a reduction in treatment-related adverse events. Distal embolic protection devices (DEPs), lower-profile sheaths and stent-delivery systems, and more aggressive periprocedural antiplatelet therapy have all contributed to this improvement.^1,2Despite the improved procedural safety afforded by these technical advances, the risk of periprocedural stroke consequent to CA stenting is not negligible.³ This risk is particularly high in symptomatic patients, in octogenarians, and in subsets of patients with certain lesions, such as those with critical stenosis and ulcerated lesions.^3,4 Observational data from a prospective multicenter registry that was compiled in order to assess outcomes of CA stenting revealed that 4.8% of the patients who underwent neuroprotected carotid stenting experienced a stroke.⁵ In addition to symptomatic strokes, subclinical microinfarctions after CA stenting range from 22% to as high as 41.5%.^6–8 During intermediate-term follow-up, these microinfarctions have been associated with cognitive decline.⁹ Observational data also suggest that most neurologic events (77%) occur after the procedure has been completed.⁵ The mechanisms that underlie late occurrence of neurologic events remain undefined; however, they may be secondary to embolization of atherothrombotic débris after a DEP has been removed. Consequently, we surmised that the use of an aspiration catheter might reduce distal embolization of atherothrombotic material after stenting, via the aspiration of friable atherothrombotic débris from the stent struts while the DEP is still deployed.We sought to investigate the safety of this novel technique by using the PRONTO® Extraction catheter (Vascular Solutions, Inc.; Minneapolis, Minn) or the QuickCat™ Extraction Catheter (Kensey Nash Corporation; Exton, Pa) as an adjunct to filter-based DEPs in the setting of CA stenting.     

Expression of leukocyte adhesion-related glycosyltransferase genes in acute coronary syndrome patients

Introduction

Acute coronary syndrome (ACS) is caused by destabilization and rupture of atherosclerotic plaque in the coronary artery via mechanisms affecting leukocyte signaling, rolling, adhesion, extravasation and inflammation-promoting factors. The majority of cellular communication takes place on the membrane surface that is covered with glycoproteins and glycolipids synthesized by glycosyltransferases. The aim of this study was to determine the mRNA expression of leukocyte adhesion-related glycosyltransferases in patients during the onset and the chronic phase of ACS and to compare the expression with matching subjects without coronary disease.

Subjects and methods

The study included 26 ACS patients and 26 ACS-free matched-pair controls. Blood samples were collected at the time of hospital admittance and 8 days later. Expression analysis of six fucosyltransferases and six sialyltransferases was performed by a real-time polymerase chain reaction.

Results

At the time of admittance ACS subjects had lower expression levels of FUT4, ST6GalNac4, ST6Gal1 and GM3 synthase (p < 0.05) than the control subjects, and moreover, after 8 days down-regulation of FUT7 and ST6GalNac3 was also observed (p < 0.05). When compared to the initial gene expression, after treatment and stabilization of ACS subjects, FUT7, ST6GalNac2 and ST6GalNac3 were down-regulated, whereas ST6GalNac1 was up-regulated. Expression levels of FUT7, ST6GalNac1, ST6GalNac2 and ST6GalNac3 were predicted by several drugs and medical history.

Conclusion

Expression of glycosyltransferase genes differs in ACS and control subjects. During the course of the ACS study we established further changes in gene expression levels. Medical history was predictive of gene expression levels while drugs were shown to modulate expression levels.     

Astrocytic high-mobility group box 1 promotes endothelial progenitor cell-mediated neurovascular remodeling during stroke recovery

Crosstalk between the brain and systemic responses in blood is increasingly suspected of playing critical roles in stroke. However, how this communication takes place remains to be fully understood. Here, we show that reactive astrocytes can release a damage-associated molecular-pattern molecule called high-mobility-group-box-1 (HMGB1) that promotes endothelial progenitor cell (EPC)-mediated neurovascular remodeling during stroke recovery. Conditioned media from reactive astrocytes increase EPC proliferation in vitro. siRNA suppression of HMGB1 in astrocytes or blockade of the HMGB1 receptor for advanced glycation endproducts in EPCs prevents this effect. In a mouse model of focal cerebral ischemia, reactive astrocytes in the peri-infarct cortex up-regulate HMGB1 at 14 d poststroke, along with an accumulation of endogenous EPCs. In vivo siRNA suppression of HMGB1 blocks this EPC response, reduces peri-infact angiogenesis, and worsens neurological deficits. Taken together, these molecular and in vivo findings support a previously undescribed mechanism of crosstalk between reactive astrocytes and EPCs wherein HMGB1 promotes neurovascular remodeling and functional recovery after stroke and brain injury.     

Precise nail tip positioning after tibial intramedullary nailing prevents anterior knee pain

Purpose

Anterior knee pain (AKP) is a common complication following intramedullary nailing of tibial shaft fractures. Our aim was, by analysing the postoperative lateral knee X-rays and clinical status (VAS score), to find the best intramedullary tip position of a non protruded nail that will provide the best postoperative outcome avoiding AKP.

Methods

We evaluated the postoperative outcome of 221 patients, from the last four years, with healed fractures initially treated with intramedullary reamed nails with two or three interlocking screws proximally and distally through a medial paratendinous incision for nail entry portal. Our aim was to analyse a possible relationship between AKP according to the VAS scale, and nail position marked as a distance from tip of nail to tibial plateau (NP) and to tibial tuberosity (NT), measured postoperatively on lateral knee X-rays.

Results

Two groups of patients were formed on the basis of presence of pain related to AKP (the level of pain was neglected): group A were patients with pain and group B without pain. The difference between the two groups concerning NP and NT measurements appeared to be statistically significant concerning NT measurement (p < 0.05), with high accuracy according to the classification tree.

Conclusions

We presume that the position of the proximal tip of the nail and its negative influence on the innervation pattern of the area dorsal to patellar tendon could be the key factor of AKP. We conclude that the symptoms of AKP will not appear if the tip of the nail position is more than 5.5 mm from the tibial plateau (NP) and more than 2.5 mm from the tibial tuberosity (NT).     

HN-10200 causes endothelium-independent relaxations in isolated canine arteries

Summary HN-10200, a nonselective inhibitor of phosphodiesterase, has positive inotropic and vasodilator activity. The present study was designed to determine the role of endotheliumin in causing relaxation to HN-10200 in isolated canine femoral and basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in Krebs-Ringer bicarbonate solution bubbled with 94% O₂, 6% CO₂ (t=37°C; pH=7.4). HN-10200 and another nonselective phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine (IBMX), caused similar concentration-dependent relaxations in femoral arteries with and without endothelium. In femoral arteries without endothelium, HN-10200 and IBMX significantly augmented relaxations to prostacyclin, but did not affect relaxations to a nitric oxide donor 3-morpholinosydnonimine (SIN-1) or endothelium-derived relaxing factor (EDRF) released by bradykinin. In basilar arteries, relaxations to HN-10200 were augmented by the removal of endothelium, whereas relaxations to IBMX were not affected. Relaxations to prostacyclin, SIN-1, and EDRF were not affected by the presence of phosphodiesterase inhibitors. The results of the present study suggest that HN-10200 causes endothelium-independent relaxations. In addition, it may augment relaxations to prostacyclin but does not affect relaxations to EDRF.