Initial Evaluation of AF78: a Rationally Designed Fluorine-18-Labelled PET Radiotracer Targeting Norepinephrine Transporter

Molecular Imaging and Biology - Taking full advantage of positron emission tomography (PET) technology, fluorine-18-labelled radiotracers targeting norepinephrine transporter (NET) have potential...     

Leadless cardiac pacemaker implantations after infected pacemaker system removals in octogenarians

BackgroundManagement of pacemaker (PM) infections among advanced aged patients possesses particular clinical challenges due to higher rates of concurrent cardiovascular disease and medical comorbidities. Novel leadless cardiac pacemakers (LCPs) may provide new opportunities for better management options in this population, however, there is limited data especially in Asian populations to guide the decision making.MethodsWe reviewed 11 octogenarians (median age: 86 [minimum 82–maximum 90] years; male: 73%; median body mass index (BMI): 20.1 kg/m²) who received Micra Transcatheter Pacing System (Medtronic Inc, Minneapolis, MN) implantations following transvenous lead extractions (TLEs) for PM infections. ResultsAll patients had more than two medical comorbidities (average 3.7 comorbidities). The indications for LCP implantations were atrioventricular block in four patients, atrial fibrillation bradycardia in five, and sinus node dysfunction in two. Eight patients (73%) were bridged with temporary pacing using active fixation leads (median interval of 14.0 days), while one with severe dementia underwent a concomitant LCP implantation and TLE during the same procedure. Successful TLEs and LCP implantations were successfully accomplished in all without any complications. The median time from the TLE procedure to discharge was 22 days (minimum 7–maximum 136). All patients remained free of infections during a mean follow-up period of 17.2 ± 6.5 months.ConclusionsLCP implantations were safe and effective after removing the entire infectious PM system in all octogenarians. The novel LCP technology may offer an alternative option for considering a re-implantation strategy after transvenous PM infections in elderly patients, particularly those with severe frailty and PM dependency.

The incidence of cardiac pacemaker (PM) infections among patients with an advanced age has been increasing owing to the continually widening indications and growing number of generator replacements.^[1–3] In current clinical practice, there is a class l indication for removing all hardware in the case of a proven or suspected device infection, and after a recovery window, a new conventional PM is implanted in PM dependent patients.^[1,4,5] However, this management for the elderly population is one of the most sensitive issues, since they possess particular clinical challenges due to higher rates of concurrent cardiovascular disease and medical comorbidities.^[6–10]Recently, the implantation of a Micra Transcatheter Pacing System (Medtronic Inc, Minneapolis, MN) has emerged as a new option for PM re-implantations after the removal of infectious PMs.^[11–17] Without the use of leads and a device pocket, this leadless cardiac pacemaker (LCP) potentially reduces the risk of pocket infections and lead associated endocarditis.^[16,17] However, there have not been enough data supporting the feasibility of leadless PM implantations following the removal of infectious PMs in people with an older age, particularly in octogenarians. Furthermore, there has been no data regarding those therapeutic strategies in Asian populations who have a low body mass index (BMI) and are at a higher risk of a transvenous lead extraction (TLE) procedure. Therefore, in this case series, we sought to characterize the procedure for LCP implantations following TLEs of infected PMs in octogenarians at 2 Japanese high-volume centers.     

Tannin-phytobezoars with Gastric Outlet Obstruction Treated by Dissolution with Administration and Endoscopic Injection of Coca-ColaⓇ, Endoscopic Crushing,and Removal (with Video)

A 77-year-old man complained of postmeal vomiting and sustained general fatigue. An abdominal computed tomography scan showed massive gastric expansion and fluid storage. Gastroscopy revealed four gastric bezoars that were considered to have caused pyloric ring obstruction. The patient was asked to drink 500 mL per day of Coca-Cola^Ⓡ for 4 days. On the fourth day, we performed endoscopic crushing and removal by injecting Coca-Cola^Ⓡ, cutting the softened bezoar with endoscopic snares, and collecting the pieces with endoscopic nets. We herein report (with a video presentation) a rare case of tannin-phytobezoars endoscopically removed with the administration and injection of Coca-Cola^Ⓡ.     

Experimental and theoretical study on converting myoglobin into a stable domain-swapped dimer by utilizing a tight hydrogen bond network at the hinge region

Various factors, such as helical propensity and hydrogen bonds, control protein structures. A frequently used model protein, myoglobin (Mb), can perform 3D domain swapping, in which the loop at the hinge region is converted to a helical structure in the dimer. We have previously succeeded in obtaining monomer–dimer equilibrium in the native state by introducing a high α-helical propensity residue, Ala, to the hinge region. In this study, we focused on another factor that governs the protein structure, hydrogen bonding. X-ray crystal structures and thermodynamic studies showed that the myoglobin dimer was stabilized over the monomer when keeping His82 to interact with Lys79 and Asp141 through water moleclues and mutating Leu137, which was located close to the H-bond network at the dimer hinge region, to a hydrophilic amino acid (Glu or Asp). Molecular dynamics simulation studies confirmed that the number of H-bonds increased and the α-helices at the hinge region became more rigid for mutants with a tighter H-bond network, supporting the hypothesis that the myoglobin dimer is stabilized when the H-bond network at the hinge region is enhanced. This demonstrates the importance and utility of hydrogen bonds for designing a protein dimer from its monomer with 3D domain swapping.

The tight H-bond network enhanced the helices at the hinge region and stabilized the myoglobin dimer, providing a unique example of using H-bonds in the design of a dimeric protein through 3D domain swapping.     

Pharmacological priming of adipose‐derived stem cells for paracrine VEGF production with deferoxamine

Adipose‐derived stem cells (ASCs) show great potentials in applications such as therapeutic angiogenesis, regenerative medicine and tissue engineering. Pharmacological preconditioning of stem cells to boost the release of cytoprotective factors may represent an effective way to enhance their therapeutic efficacy. In this study, the aim was to determine whether deferoxamine can enhance the release of vascular endothelial growth factor (VEGF) from in vitro expanded ASCs. It is demonstrated that deferoxamine (50–300 μm ) upregulated VEGF expression in a concentration‐ and time‐dependent fashion. At the concentrations used, deferoxamine did not show any cytotoxic effects. The stimulatory effect of deferoxamine on VEGF expression was mediated by augmentation of hypoxia inducible factor‐1 in ASCs, but independent of its antioxidant properties. Moreover, deferoxamine enhanced the paracrine effects of ASCs in promoting the regenerative functions of endothelial cells (migration and in vitro wound healing activities). This study provides evidence that deferoxamine might be a useful drug with low cell toxicity for pharmacological preconditioning of ASCs to enhance their capacity of VEGF production. Copyright © 2013 John Wiley & Sons, Ltd.     

Tissue Doppler imaging and strain Doppler imaging as modalities for predicting clinical improvement in patients receiving biventricular pacing.

BACKGROUND: The purpose of this study was to determine the utility and efficacy of tissue Doppler imaging (TDI) and strain Doppler imaging (SDI) for evaluating ventricular synchrony and function, and for predicting the long-term clinical improvement in patients undergoing biventricular pacing (BVP). METHODS AND RESULTS: TDI and SDI were performed before and <1 month after initiating BVP in 17 patients with advanced heart failure. An intraventricular conduction delay between the left ventricular (LV) septal and lateral walls was measured by TDI. The average LV strain (LV-strain) was calculated from data obtained at the center of 6 regions of the LV (base and mid-point between the basal and apical portions, and the mid-point between these 2 points on the septal and lateral walls). During a 23+/-7 month follow-up period, 12 patients improved clinically and did not require re-hospitalization for heart failure (responder group), but the remaining 5 did not improve (nonresponder group). Before BVP, the intraventricular conduction delay was greater in the responder group than in the nonresponder group (p<0.01), but after BVP, it did not differ between the 2 groups. LV-strain improved after BVP in the responder group but not in the nonresponder group (p<0.05). CONCLUSION: A high intraventricular conduction delay before BVP and decreased strain shortly after BVP may predict long-term clinical improvement in patients undergoing this treatment.     

Neurotoxicity induced by tacrolimus after liver transplantation: relation to genetic polymorphisms of the ABCB1 (MDR1) gene

BACKGROUND: Tacrolimus is a substrate of P-glycoprotein (PGP) encoded by the multidrug resistant (MDR)1 gene (ABCB1). PGP, a multidrug efflux pump, restricts the distribution of tacrolimus in the brain. In this study, we investigate the correlation of ABCB1 gene polymorphism with tacrolimus-induced neurotoxicity in patients after liver transplantation. METHODS: The genotype of 6 patients with neurotoxic events and 11 patients without neurotoxic events was analyzed by polymerase chain reaction (PCR), and 8 mutations were detected. In addition to laboratory findings and patient characteristics, the contribution of mutations in the ABCB1 gene was evaluated with stepwise discriminant function analysis. RESULTS: High tacrolimus concentration, liver dysfunction, and mutation at position 2677 in exon 21 were demonstrated as positive predictors of tacrolimus-induced neurotoxicity. CONCLUSION: It is indicated that blood concentrations, liver function, graft weight, and polymorphism in the ABCB1 gene are important factors in tacrolimus-induced neurotoxicity.     

Identification of the anterior ethmoid arteries on thin-section axial images and coronal reformatted orbit images by means of multidetector row CT

AIM: The aim of this study was to identify anterior ethmoid arteries on thin-section axial images and coronal reformatted images of the orbits using multidetector row computed tomography (CT). MATERIALS AND METHODS: One hundred and thirty-two patients underwent paranasal CT using a 16-row detector CT (n=59) or a 6-row detector CT machine (n=73) at 1 or 1.25 mm section width, respectively. Coronal images were reformatted at section widths of 3 and 1 mm. The anterior ethmoid arteries were identified for each patient. Differences were assessed using the chi-square test. RESULTS: All CT images were of approximately average diagnostic quality. Anterior ethmoid arteries were identified in 97.5 and 96.6% at section thicknesses of 1 and 1.25 mm on the axial images, respectively. There was no statistically significant difference in the detection rate (p=0.89). On the coronal images, anterior ethmoid arteries were presented tangentially in 75.4 and 90.2% at section widths of 3 and 1 mm, respectively. The visibility of the anterior ethmoid arteries was rated significantly better on coronal images at a section width of 1 mm than on those at section widths of 3 mm (p<0.001). CONCLUSION: Thin-section axial images and coronal reformatted images using multi-detector row CT mostly depict anterior ethmoid arteries, and are useful to identify anterior ethmoid arteries for preoperative evaluation of paranasal sinuses.