All comers 5 french transfemoral percutaneous coronary intervention without sheath

There is an interest to keep the arterial access site for percutaneous coronary interventions (PCI) small. Using sheaths for introduction of arterial catheters is standard. The effective outer diameter of the usual introducer sheaths is about 1.5 French (F) larger than the labeled size. Omitting the sheath affords a smaller access without loss of working lumen.

Temporal changes of coronary artery plaque located behind the struts of the everolimus eluting bioresorbable vascular scaffold

Implantation of a coronary stent results in a mechanical enlargement of the coronary lumen with stretching of the surrounding atherosclerotic plaque. Using intravascular ultrasound virtual-histology (IVUS-VH) we examined the temporal changes in composition of the plaque behind the struts (PBS) following the implantation of the everolimus eluting bioresorbable vascular scaffold (BVS). Using IVUS-VH and dedicated software, the composition of plaque was analyzed in all patients from the ABSORB B trial who were imaged with a commercially available IVUS-VH console (s5i system, Volcano Corporation, Rancho Cordova, CA, USA) post-treatment and at 6-month follow-up. This dedicated software enabled analysis of the PBS after subtraction of the VH signal generated by the struts. The presence of necrotic core (NC) in contact with the lumen was also evaluated at baseline and follow-up. IVUS-VH data, recorded with s5i system, were available at baseline and 6-month follow-up in 15 patients and demonstrated an increase in both the area of PBS (2.45 ± 1.93 mm(2) vs. 3.19 ± 2.48 mm(2), P = 0.005) and the external elastic membrane area (13.76 ± 4.07 mm(2) vs. 14.76 ± 4.56 mm(2), P = 0.006). Compared to baseline there was a significant progression in the NC (0.85 ± 0.70 mm(2) vs. 1.21 ± 0.92 mm(2), P = 0.010) and fibrous tissue area (0.88 ± 0.79 mm(2) vs. 1.15 ± 1.05 mm(2), P = 0.027) of the PBS. The NC in contact with the lumen in the treated segment did not increase with follow-up (7.33 vs. 6.36%, P = 0.2). Serial IVUS-VH analysis of BVS-treated lesions at 6-month demonstrated a progression in the NC and fibrous tissue content of PBS.

Active regulation of cerebral venous tone: simultaneous arterial and venous transcranial Doppler sonography during a Valsalva manoeuvre

The aim of this study was to analyse the cerebral venous outflow in relation to the arterial inflow during a Valsalva manoeuvre (VM). In 19 healthy volunteers (mean age 24.1 +/- 2.6 years), the middle cerebral artery (MCA) and the straight sinus (SRS) were insonated by transcranial Doppler sonography. Simultaneously the arterial blood pressure was recorded using a photoplethysmographic method. Two VM of 10 s length were performed per participant. Tracings of the variables were then transformed to equidistantly re-sampled data. Phases of the VM were analysed regarding the increase of the flow velocities and the latency to the peak. The typical four phases of the VM were also found in the SRS signal. The relative flow velocity (FV) increase was significantly higher in the SRS than in the MCA for all phases, particularly that of phase IV (p < 0.01). Comparison of the time latency of the VM phases of the MCA and SRS only showed a significant difference for phase I (p < 0.01). In particular, there was no significant difference for phase IV (15.8 +/- 0.29 vs. 16.0 +/- 0.28 s). Alterations in venous outflow in phase I are best explained by a cross-sectional change of the lumen of the SRS, while phases II and III are compatible with a Starling resistor. However, the significantly lager venous than the arterial overshoot in phase IV may be explained by the active regulation of the venous tone.

Nuclear cysteine cathepsin variants in thyroid carcinoma cells

The cysteine peptidase cathepsin B is important in thyroid physiology by being involved in thyroid prohormone processing initiated in the follicular lumen and completed in endo-lysosomal compartments. However, cathepsin B has also been localized to the extrafollicular space and is therefore suggested to promote invasiveness and metastasis in thyroid carcinomas through, e.g., ECM degradation. In this study, immunofluorescence and biochemical data from subcellular fractionation revealed that cathepsin B, in its single- and two-chain forms, is localized to endo-lysosomes in the papillary thyroid carcinoma cell line KTC-1 and in the anaplastic thyroid carcinoma cell lines HTh7 and HTh74. This distribution is not affected by thyroid stimulating hormone (TSH) incubation of HTh74, the only cell line that expresses a functional TSH-receptor. Immunofluorescence data disclosed an additional nuclear localization of cathepsin B immunoreactivity. This was supported by biochemical data showing a proteolytically active variant slightly smaller than the cathepsin B proform in nuclear fractions. We also demonstrate that immunoreactions specific for cathepsin V, but not cathepsin L, are localized to the nucleus in HTh74 in peri-nucleolar patterns. As deduced from co-localization studies and in vitro degradation assays, we suggest that nuclear variants of cathepsins are involved in the development of thyroid malignancies through modification of DNA-associated proteins.

Five-Year Clinical and Angiographic Outcomes of a Randomized Comparison of Sirolimus-Eluting and Paclitaxel-Eluting Stents: Results of the Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization LATE Trial

Background—Long-term comparative data of first-generation drug-eluting stents are scarce. We investigated clinical and angiographic outcomes of sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) at 5 years as part of the Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization (SIRTAX) LATE study. Methods and Results—A total of 1012 patients were randomly assigned to SES or PES. Repeat angiography was completed in 444 of 1012 patients (43.8%) at 5 years. Major adverse cardiac events occurred in 19.7% of SES- and 21.4% of PES-treated patients (hazard ratio, 0.89; 95% confidence interval, 0.68 to 1.17; P=0.39) at 5 years. There were no differences between SES and PES in terms of cardiac death (5.8% versus 5.7%; P=0.35), myocardial infarction (6.6% versus 6.9%; P=0.51), and target lesion revascularization (13.1% versus 15.1%; P=0.29). Between 1 and 5 years, the annual rate of target lesion revascularization was 2.0% (95% confidence interval, 1.4% to 2.6%) for SES and 1.4% (95% confidence interval, 0.9% to 2.0%) for PES. Among patients undergoing paired angiography at 8 months and 5 years, delayed lumen loss amounted to 0.37±0.73 mm for SES and 0.29±0.59 mm for PES (P=0.32). The overall rate of definite stent thrombosis was 4.6% for SES and 4.1% for PES (P=0.74), and very late definite stent thrombosis occurred at an annual rate of 0.65% (95% confidence interval, 0.40% to 0.90%). Conclusions—Long-term follow-up of first-generation drug-eluting stents shows no significant differences in clinical and angiographic outcomes between SES and PES. The continuous increase in late lumen loss in conjunction with the ongoing risk of very late stent thrombosis suggests that vascular healing remains incomplete up to 5 years after implantation of first-generation drug-eluting stents.

Teat anatomy affects requirements for udder preparation in Mediterranean buffaloes

The present study was conducted to assess the interrelation between teat anatomy and machine milking in dairy buffaloes raised in Switzerland. A 3-min pre-stimulation induced milk ejection before cluster attachment in most cases and caused an optimal milk removal during machine milking. In an additional experiment, longitudinal cross-section ultrasound was obtained before and after a 3-min pre-stimulation. Teat wall thickness, teat diameter, cisternal diameter and teat canal length were evaluated. It was observed that 3-min pre-stimulation dramatically reduced teat canal length whereas all the other anatomical parameters remained unchanged. The vacuum needed to open the teat canal was also measured before and after a 3-min pre-stimulation by using a special teat cup with only the mouthpiece of the liner remaining on the top of the teat cup (no liner, no pulsation). Without pre-stimulation but after wetting the teat canal by stripping one squirt of milk out of the teat, no milk could be withdrawn with a vacuum up to 39 kPa. However, after pre-stimulation, milk flow occurred in all buffaloes at a vacuum between 16 and 38 kPa. In the last experiment, the teat tissue was examined in slaughtered buffaloes and compared with teat tissue of cows. No difference was noted in histological sections and teat canal length was similar in cows and buffaloes. Proximal to the teat canal, the teat did not pass into an open cistern but the lumen was collapsed. In conclusion, buffaloes need to be well pre-stimulated because the tissue above the teat canal provides additional teat closure before milk ejection. Therefore, milk can only be obtained after pre-stimulation.

Analysis of 1 year virtual histology changes in coronary plaque located behind the struts of the everolimus eluting bioresorbable vascular scaffold

Serial intravascular ultrasound virtual histology (IVUS-VH) after implantation of metallic stents has been unable to show any changes in the composition of the scaffolded plaque overtime. The everolimus-eluting ABSORB scaffold potentially allows for the formation of new fibrotic tissue on the scaffolded coronary plaque during bioresorption. We examined the 12 month IVUS-VH changes in composition of the plaque behind the struts (PBS) following the implantation of the ABSORB scaffold. Using IVUS-VH and dedicated software, the composition of the PBS was analyzed in all patients from the ABSORB Cohort B2 trial, who were imaged with a commercially available IVUS-VH console (s5i system, Volcano Corporation, Rancho Cordova, CA, USA), immediately post-ABSORB implantation and at 12 month follow-up. Paired IVUS-VH data, recorded with s5i system, were available in 17 patients (18 lesions). The analysis demonstrated an increase in mean PBS area (2.39 ± 1.85 mm(2) vs. 2.76 ± 1.79 mm(2), P = 0.078) and a reduction in the mean lumen area (6.37 ± 0.90 mm(2) vs. 5.98 ± 0.97 mm(2), P = 0.006). Conversely, a significant decrease of 16 and 30% in necrotic core (NC) and dense calcium (DC) content, respectively, were evident (median % NC from 43.24 to 36.06%, P = 0.016; median % DC from 20.28 to 11.36%, P = 0.002). Serial IVUS-VH analyses of plaque located behind the ABSORB struts at 12-month demonstrated an increase in plaque area with a decrease in its NC and DC content. Larger studies are required to investigate the clinical impact of these findings.

Tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent vs. a fluoropolymer-coated everolimus-eluting stent at 13-month follow-up: an optical coherence tomography substudy from the RESOLUTE All Comers trial

Aims To compare the tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent (ZES) vs. a fluoropolymer-coated everolimus-eluting stent (EES) at 13 months, using optical coherence tomography (OCT) in an ‘all-comers' population of patients, in order to clarify the mechanism of eventual differences in the biocompatibility and thrombogenicity of the devices. Methods and results Patients randomized to angiographic follow-up in the RESOLUTE All Comers trial (NCT00617084) at pre-specified OCT sites underwent OCT follow-up at 13 months. Tissue coverage and apposition were assessed strut by strut, and the results in both treatment groups were compared using multilevel logistic or linear regression, as appropriate, with clustering at three different levels: patient, lesion, and stent. Fifty-eight patients (30 ZES and 28 EES), 72 lesions, 107 stents, and 23 197 struts were analysed. Eight hundred and eighty-seven and 654 uncovered struts (7.4 and 5.8%, P= 0.378), and 216 and 161 malapposed struts (1.8 and 1.4%, P= 0.569) were found in the ZES and EES groups, respectively. The mean thickness of coverage was 116 ± 99 µm in ZES and 142 ± 113 µm in EES (P= 0.466). No differences in per cent neointimal volume obstruction (12.5 ± 7.9 vs. 15.0 ± 10.7%) or other areas–volumetric parameters were found between ZES and EES, respectively. Conclusion No significant differences in tissue coverage, malapposition, or lumen/stent areas and volumes were detected by OCT between the hydrophilic polymer-coated ZES and the fluoropolymer-coated EES at 13-month follow-up.

NOD2 gene variants are a risk factor for culture-positive spontaneous bacterial peritonitis and monomicrobial bacterascites in cirrhosis

Spontaneous bacterial peritonitis (SBP) is considered as result of bacterial translocation from the gastrointestinal lumen to the mesenteric lymph nodes and subsequent circulation. Variants of the NOD2 gene contribute to bacterial translocation and were associated with SBP in a recent study.

The "Embowire" Technique: Concept and Description of a Novel Embolization Technique for Narrow Vessels

We describe a new, useful embolization technique applied to occlude narrow vessel branches (≤1.5 mm (0.06″) in diameter) by deployment of one hydrocoil, through a microcatheter, in a way similar to the way in which one might navigate through the vascular lumen with a guidewire.

Regulation of Cx45 hemichannels mediated by extracellular and intracellular calcium

Connexin45 (Cx45) hemichannels (HCs) open in the absence of Ca(2+) and close in its presence. To elucidate the underlying mechanisms, we examined the role of extra- and intracellular Ca(2+) on the electrical properties of HCs. Experiments were performed on HeLa cells expressing Cx45 using electrical (voltage clamp) and optical (Ca(2+) imaging) methods. HCs exhibit a time- and voltage-dependent current (I(hc)), activating with depolarization and inactivating with hyperpolarization. Elevation of [Ca(2+)](o) from 20 nM to 2 μM reversibly decreases I(hc), decelerates its rate of activation, and accelerates its deactivation. Our data suggest that [Ca(2+)](o) modifies the channel properties by adhering to anionic sites in the channel lumen and/or its outer vestibule. In this way, it blocks the channel pore and reversibly lowers I(hc) and modifies its kinetics. Rapid lowering of [Ca(2+)](o) from 2 mM to 20 nM, achieved early during a depolarizing pulse, led to an outward I(hc) that developed with virtually no delay and grew exponentially in time paralleled by unaffected [Ca(2+)](i). A step increase of [Ca(2+)](i) evoked by photorelease of Ca(2+) early during a depolarizing pulse led to a transient decrease of I(hc) superimposed on a growing outward I(hc); a step decrease of [Ca(2+)](i) elicited by photoactivation of a Ca(2+) scavenger provoked a transient increase in I(hc). Hence, it is tempting to assume that Ca(2+) exerts a direct effect on Cx45 hemichannels.

In Vitro and In Vivo Imaging Characteristics Assessment of Polymeric Coils Compared with Standard Platinum Coils for the Treatment of Intracranial Aneurysms

BACKGROUND AND PURPOSE:Conventional platinum coils cause imaging artifacts that reduce imaging quality and therefore impair imaging interpretation on intraprocedural or noninvasive follow-up imaging. The purpose of this study was to evaluate imaging characteristics and artifact production of polymeric coils compared with standard platinum coils in vitro and in vivo.MATERIALS AND METHODS:Polymeric coils and standard platinum coils were evaluated in vitro with the use of 2 identical silicon aneurysm models coiled with a packing attenuation of 20% each. DSA, flat panel CT, CT, and MR imaging were performed. In vivo evaluation of imaging characteristics of polymeric coils was performed in experimentally created rabbit carotid bifurcation aneurysms. DSA, CT/CTA, and MR imaging were performed after endovascular treatment of the aneurysms. Images were evaluated regarding visibility of individual coils, coil mass, artifact production, and visibility of residual flow within the aneurysm.RESULTS:Overall, in vitro and in vivo imaging showed relevantly reduced artifact production of polymeric coils in all imaging modalities compared with standard platinum coils. Image quality of CT and MR imaging was improved with the use of polymeric coils, which permitted enhanced depiction of individual coil loops and residual aneurysm lumen as well as the peri-aneurysmal area. Remarkably, CT images demonstrated considerably improved image quality with only minor artifacts compared with standard coils. On DSA, polymeric coils showed transparency and allowed visualization of superimposed vessel structures.CONCLUSIONS:This initial experimental study showed improved imaging quality with the use of polymeric coils compared with standard platinum coils in all imaging modalities. This might be advantageous for improved intraprocedural imaging for the detection of complications and posttreatment noninvasive follow-up imaging.

Homeland security: IgA immunity at the frontiers of the body

IgA is the most abundant immunoglobulin produced in mammals, and is mostly secreted across mucous membranes. At these frontiers, which are constantly assaulted by pathogenic and commensal microbes, IgA provides part of a layered system of immune protection. In this review, we describe how IgA induction occurs through both T-dependent and T-independent mechanisms, and how IgA is generated against the prodigious load of commensal microbes after mucosal dendritic cells (DCs) have sampled a tiny fraction of the microbial consortia in the intestinal lumen. To function in this hostile environment, IgA must be induced behind the 'firewall' of the mesenteric lymph nodes to generate responses that integrate microbial stimuli, rather than the classical prime-boost effects characteristic of systemic immunity.

α-Ketoglutarate regulates acid-base balance through an intrarenal paracrine mechanism

Paracrine communication between different parts of the renal tubule is increasingly recognized as an important determinant of renal function. Previous studies have shown that changes in dietary acid-base load can reverse the direction of apical α-ketoglutarate (αKG) transport in the proximal tubule and Henle's loop from reabsorption (acid load) to secretion (base load). Here we show that the resulting changes in the luminal concentrations of αKG are sensed by the αKG receptor OXGR1 expressed in the type B and non-A-non-B intercalated cells of the connecting tubule (CNT) and the cortical collecting duct (CCD). The addition of 1 mM αKG to the tubular lumen strongly stimulated Cl--dependent HCO3- secretion and electroneutral transepithelial NaCl reabsorption in microperfused CCDs of wild-type mice but not Oxgr1-/- mice. Analysis of alkali-loaded mice revealed a significantly reduced ability of Oxgr1-/- mice to maintain acid-base balance. Collectively, these results demonstrate that OXGR1 is involved in the adaptive regulation of HCO3- secretion and NaCl reabsorption in the CNT/CCD under acid-base stress and establish αKG as a paracrine mediator involved in the functional coordination of the proximal and the distal parts of the renal tubule.

Penetration of ASM 981 in canine skin: a comparative study

ASM 981 has been developed for topical treatment of inflammatory skin diseases. It specifically inhibits the production and release of pro-inflammatory cytokines. We measured the skin penetration of ASM 981 in canine skin and compared penetration in living and frozen skin. To make penetration of ASM 981 visible in dog skin, tritium labelled ASM 981 was applied to a living dog and to defrosted skin of the same dog. Using qualitative autoradiography the radioactive molecules were detected in the lumen of the hair follicles until the infundibulum, around the superficial parts of the hair follicles and into a depth of the dermis of 200 to 500 microm. Activity could not be found in deeper parts of the hair follicles, the dermis or in the sebaceous glands. Penetration of ASM 981 is low in canine skin and is only equally spread in the upper third of the dermis 24 hours after application. Penetration in frozen skin takes even longer than in living canine skin but shows the same distribution.