Intramolecular [2 + 2] and [4 + 2] Cycloaddition Reactions of Cinnamylamides of Ethenetricarboxylate in Sequential Processes.

Intramolecular [2 + 2] and [4 + 2] cycloaddition reactions of cinnamylamides of ethenetricarboxylate in sequential processes have been studied. Reaction of 1,1-diethyl 2-hydrogen ethenetricarboxylate and trans-cinnamylamines in the presence of EDCI/HOBt/Et3N led to pyrrolidine products in one pot, via intramolecular [2 + 2], [4 + 2], and some other cyclizations. The types of the products depend on the substituents on the benzene ring and the reaction conditions. Reaction of cinnamylamines without substituents on the benzene ring and with halogens and OMe on the para position at room temperature gave cyclobutane-fused pyrrolidines as major products via [2 + 2] cycloaddition. The reaction at 80 °C in 1,2-dichloroethane gave δ-lactone fused pyrrolidines as major products, probably via ring-opening of the cyclobutanes. Interestingly, reaction of 1,1-diethyl 2-hydrogen ethenetricarboxylate and cinnamylamines bearing electron-withdrawing groups such as NO2, CN, CO2Me, CO2Et, and CF3 on ortho and para positions in the presence of EDCI/HOBt/Et3N at room temperature or at 60-80 °C gave tetrahydrobenz[f]isoindolines via [4 + 2] cycloaddition as major products. DFT studies have been performed to explained the observed [2 + 2]/[4 + 2] selectivity.

[Left atrial giant myxoma incidentally discovered during endoscopic ultrasonography; report of a case].

A 49-year-old female patient with a symptom of dysphagia underwent endoscopic ultrasonography (EUS) of the upper gastrointestinal tract, which incidentally revealed a tumor compressing the esophagus from outside. Transthoracic echocardiography performed after EUS showed a giant tumor in the left atrium. The tumor, measuring 75×68×43 mm, weighing 105 g was successfully removed, and pathologically diagnosed as myxoma. Her symptom disappeared completely. When performing clinical studies, it is important to pay every attention not to miss any abnormal findings beyond the scope of targeted areas. We also mentioned an ambiguity of the term," giant" regarding the size and weight of myxoma.

Differences in coagulation responses to vascular injury between uninterrupted dabigatran and apixaban: A clinical prospective randomized study.

BACKGROUND: The coagulation response during vascular injury with uninterrupted administration of direct oral anticoagulants has not been elucidated. OBJECTIVE: Our aim was to evaluate differences in coagulation responses after vascular injury between uninterrupted direct thrombin inhibitor and direct factor Xa inhibitor recipients. METHODS: Patients scheduled for catheter ablation for atrial fibrillation were randomly assigned to receive dabigatran or apixaban in this prospective, randomized, comparative, parallel-group study. Venous blood was collected 3 times: 180 minutes after taking the anticoagulant on the day before the procedure, before vascular punctures of the ablation procedure, and 10-15 minutes after the start of vascular punctures. RESULTS: Forty-two patients were enrolled. The prothrombin fragment 1+2 level, the primary end point, was much larger after vascular puncture in the uninterrupted dabigatran recipients (median, 83 pmol/L; interquartile range, 56-133 pmol/L) than in the uninterrupted apixaban recipients (median, 1 pmol/L; interquartile range, -3 to 19 pmol/L; P < .001). Antithrombin levels decreased after vascular puncture in dabigatran recipients, and both protein C and antithrombin levels decreased after vascular puncture in apixaban recipients. CONCLUSION: Unlike uninterrupted apixaban, uninterrupted dabigatran does not inhibit thrombin generation in response to vascular injury.

Radial Osteotomy With Callus Distraction for the Correction of Severe Madelung Deformity.

We report a case of an 11-year-old girl with bilateral severe Madelung deformity who underwent radial osteotomy with callus distraction. The distal radial articulation was corrected at surgery, and a unilateral fixator was subsequently used for callus distraction. No postoperative complication was noted. The patient did not need any additional surgeries for correction of the deformity. Forty-three months after surgery, the patient had a nearly full range of motion without any pain. Forearm deformity was not noticeable, except for surgical scar on both wrists.

The Atrial Natriuretic Peptide-to-brain Natriuretic Peptide Ratio Predicts Left Atrial Reverse Remodeling after Rhythm Control Therapy in Patients with Persistent Atrial Fibrillation.

Objective The association between natriuretic peptide levels in atrial fibrillation (AF) patients with advanced left atrial (LA) remodeling and reverse remodeling after rhythm control therapy has not been clarified. The present study assessed the role of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) measurements to predict LA reverse remodeling after catheter ablation (CA) in persistent AF patients with LA enlargement. Methods This study included 88 persistent AF patients with LA enlargement (volume index >48 mL/m2) who underwent CA. Plasma ANP and BNP levels were analyzed before CA in all patients. The study population was divided into 2 groups according to the extent of decrease in the LA volume index (LAVI) at 6 months after CA responders were those with a ≥15% reduction in the LAVI, and all others were non-responders. Results At follow-up, 58 patients (66%) were classified as responders. The preprocedural ANP level was significantly higher in the responders than in the non-responders (p=0.03). Furthermore, the ANP-to-BNP ratio (ANP/BNP) was significantly higher in the responders than in the non-responders (p<0.01). The ANP/BNP was correlated with the percentage decrease in the LAVI (r=0.391, p<0.01). A multivariate linear regression analysis revealed that the ANP/BNP before CA was an independent predictor of LA reverse remodeling (p<0.01). Conclusion The preprocedural ANP/BNP was a robust predictor of reverse remodeling of the enlarged LA after sinus rhythm restoration by rhythm control therapy in persistent AF patients.

Integration of Microfluidic Chip and Probe with a Dual Pump System for Measurement of Single Cells Transient Response.

The integration of liquid exchange and microfluidic chips plays a critical role in the biomedical and biophysical fields as it enables the control of the extracellular environment and allows for the simultaneous stimulation and detection of single cells. In this study, we present a novel approach for measuring the transient response of single cells using a system integrated with a microfluidic chip and a probe with a dual pump. The system was composed of a probe with a dual pump system, a microfluidic chip, optical tweezers, an external manipulator, an external piezo actuator, etc. Particularly, we incorporated the probe with the dual pump to allow for high-speed liquid change, and the localized flow control enabled a low disturbance contact force detection of single cells on the chip. Using this system, we measured the transient response of the cell swelling against the osmotic shock with a very fine time resolution. To demonstrate the concept, we first designed the double-barreled pipette, which was assembled with two piezo pumps to achieve a probe with the dual pump system, allowing for simultaneous liquid injection and suction. The microfluidic chip with on-chip probes was fabricated, and the integrated force sensor was calibrated. Second, we characterized the performance of the probe with the dual pump system, and the effect of the analysis position and area of the liquid exchange time was investigated. In addition, we optimized the applied injection voltage to achieve a complete concentration change, and the average liquid exchange time was achieved at approximately 3.33 ms. Finally, we demonstrated that the force sensor was only subjected to minor disturbances during the liquid exchange. This system was utilized to measure the deformation and the reactive force of Synechocystis sp. strain PCC 6803 in osmotic shock, with an average response time of approximately 16.33 ms. This system reveals the transient response of compressed single cells under millisecond osmotic shock which has the potential to characterize the accurate physiological function of ion channels.

A force measurement platform for a vitreoretinal surgical simulator using an artificial eye module integrated with a quartz crystal resonator.

To provide quantitative feedback on surgical progress to ophthalmologists practicing inner limiting membrane (ILM) peeling, we developed an artificial eye module comprising a quartz crystal resonator (QCR) force sensor and a strain body that serves as a uniform force transmitter beneath a retinal model. Although a sufficiently large initial force must be loaded onto the QCR force sensor assembly to achieve stable contact with the strain body, the highly sensitive and wide dynamic-range property of this sensor enables the eye module to detect the slight forceps contact force. A parallel-plate strain body is used to achieve a uniform force sensitivity over the 4-mm-diameter ILM peeling region. Combining these two components allowed for a measurable force range of 0.22 mN to 29.6 N with a sensitivity error within -11.3 to 4.2% over the ILM peeling area. Using this eye module, we measured the applied force during a simulation involving artificial ILM peeling by an untrained individual and compensated for the long-term drift of the obtained force data using a newly developed algorithm. The compensated force data clearly captured the characteristics of several types of motion sequences observed from video recordings of the eye bottom using an ophthalmological microscope. As a result, we succeeded in extracting feature values that can be potentially related to trainee skill level, such as the mean and standard deviation of the pushing and peeling forces, corresponding, in the case of an untrained operator, to 122.6 ± 95.2 and 20.4 ± 13.2 mN, respectively.

Highly sensitive VOC detectors using insect olfactory receptors reconstituted into lipid bilayers.

This paper reports a volatile organic compound (VOC) sensor based on olfactory receptors that were reconstituted into a lipid bilayer and used in a specifically designed gas flow system for rapid parts per billion (ppb)-level detection. This VOC sensor achieves both rapid detection and high detection probability because of its gas flow system and array design. Specifically, the gas flow system includes microchannels and hydrophobic microslits, which facilitate both the introduction of gas into the droplet and droplet mixing. We installed this system into a parallel lipid bilayer device and subsequently demonstrated parts per billion-level (0.5 ppb) detection of 1-octen-3-ol in human breath. Therefore, this system extends the various applications of biological odorant sensing, including breath diagnosis systems and environmental monitoring.

Japan ablation registry: cryoablation in atrioventricular nodal reentrant tachycardia ("JARCANRET study"): results from large multicenter retrospective investigation.

PURPOSE: Cryoenergy has been demonstrated to be a safe alternative to radiofrequency ablation for catheter ablation of atrioventricular nodal reentrant tachycardia (AVNRT). This study aimed to evaluate the safety and efficacy of cryoablation in patients with AVNRT. METHODS: A multicenter retrospective study was performed. Two hundred eighty-three consecutive patients with AVNRT underwent cryoablation. Cryomapping at - 30 °C and - 80 °C was performed to predict cryoablation outcome and ascertain antegrade conduction. Cryoenergy was delivered subsequently at the same spot (cryoablation at - 80 °C) for 240 s. RESULTS: Ablation procedure was acutely successful in 281 out of 283 patients (99.3%). Of note, 22 patients (10.1%) had transient AV block during the cryoablation, but no injurious effects on AV conduction were provoked during cryomapping. During a follow-up period of 367 ± 35 days, the recurrence rate was 3.9% (11 out of 281). There were no significant differences among the patients with a complete elimination of slow pathway conduction, AH jump without an echo beat, and AH jump with a single echo beat, in terms of the long-term recurrence of AVNRT. CONCLUSIONS: Cryoablation of AVNRT appears to be effective both acutely and during the long-term with a minimal risk of unwanted injuries to the conduction system. It seems to be important to monitor the antegrade conduction during cryoenergy applications, even when cryomapping demonstrates a safe location for cryoablation. The recurrence rate of AVNRT did not differ according to the properties of the residual slow pathway conduction.

Malunion of medial condyle fracture of the humerus: a case report.

Medial condyle fracture of the humerus is extremely rare in pediatric elbow fractures. We report a rare case of malunion of medial condyle fracture in a 10-year-old boy who had an injury on the right elbow at age 4. He was referred to our clinic because of severe varus deformity (the carrying angle was 191°, unaffected side 172°) with instability. Extra-articular closing wedge osteotomy was performed. Five years after surgery, the carrying angle was 172° and the patient had no pain and no difficulties with activities of daily living.

Ventricular tachyarrhythmia associated with cardiac sarcoidosis: its mechanisms and outcome.

BACKGROUND: Cardiac sarcoidosis is increasingly recognized and is associated with poor prognosis. Ventricular tachycardia (VT) associated with cardiac sarcoidosis is the most likely cause of sudden death in most patients, but the mechanism has not been well established. HYPOTHESIS: This study investigated the mechanisms and outcome of VT associated with cardiac sarcoidosis. METHODS: The study included eight consecutive patients (five men, three women, aged 54 +/- 19 years) who had sustained monomorphic VT associated with cardiac sarcoidosis in our hospital. RESULTS: The average ejection fraction was 43 +/- 11%. Twenty-two VTs were observed in these patients, and mean heart rate during VT was 192 +/- 29 beats/min (range 144-259). The phenomenon of transient entrainment was documented in 10 of 22 (45%) VTs by ventricular pacing (eight in the active phase). Another five (23%) VTs could not be entrained, but could be initiated by programmed stimulation and terminated by rapid pacing, reproducibly. In 3 of the 22 (14%) VTs, cardioversion was required urgently because of the fast rate, while the remaining 4 (18%) could be induced during electrophysiologic study. CONCLUSIONS: In this study, there was a high possibility that the mechanism of 15 (68%) VTs was reentry. Reentrant substrate is formed not only in association with the healing of cardiac granulomas in the inactive phase of cardiac sarcoidosis but also in the active phase. Ventricular tachycardia with cardiac sarcoidosis, even if this mechanism is reentry, has different inducibility between the active and inactive phases in an electrophysiologic study. This makes the therapy for cardiac sarcoidosis (e.g., corticosteroids, antiarrhythmic agents, and catheter ablation) difficult. The implantable cardioverter-defibrillator is an effective treatment for ventricular tachyarrythmia with cardiac sarcoidosis.

Ventricular tachycardia late after repair of congenital heart disease: efficacy of combination therapy with radiofrequency catheter ablation and class III antiarrhythmic agents and long-term outcome.

OBJECTIVE: This study investigated the treatment of ventricular tachycardia (VT) after repair of tetralogy of Fallot or double outlet of the right ventricle. BACKGROUND: The ideal antiarrhythmic therapy for VT in patients after repair of congenital heart disease, especially without left ventricular dysfunction, has not yet been established. METHODS: Seven consecutive patients (2 women and 5 men) with stable monomorphic sustained VT were investigated. The mean age was 25 +/- 7 years (range, 16-35 years). Four patients had undergone surgical repair of tetralogy of Fallot, and 3 had surgical correction of double outlet of the right ventricle at the mean age of 18 +/- 7 years (range, 9-27 years) before documentation of the arrhythmia. RESULTS: The mean ejection fraction of the left ventricle was 60% +/- 8% (range, 50-72). Fourteen sustained monomorphic VTs were induced in 7 patients using programmed electrical stimulation. The mean cycle length of tachycardia was 346 +/- 77 milliseconds (range, 260-480 seconds). The site of the surgical correction of the right ventricle was associated with the origin of VT in all patients. Radiofrequency catheter ablation was attempted in 8 VTs in 7 patients: 7 clinical and 1 nonclinical VTs. In 6 patients, class III antarrhythmic agents were added because VT remained inducible after ablation. During a follow-up of 61 +/- 29 months (range, 15-110 months), there were no recurrences of VT. CONCLUSION: In patients with drug-refractory VT originating from the right ventricle late after congenital heart disease, and when their left ventricular function do not deteriorate, combined therapy for radiofrequency catheter ablation with class III antiarrhythmic agents might effective and should be considered as a therapeutic option.

Comparison of efficacy of sotalol and nifekalant for ventricular tachyarrhythmias.

BACKGROUND: Suppression of implantable defibrillator discharges associated with ventricular tachyarrhythmia (VTA) has been reported for sotalol. This study aimed to investigate the efficacy of intravenous nifekalant hydrochloride in predicting the effects of oral sotalol. METHODS AND RESULTS: The present study included 14 patients who had sustained VTA associated with structural heart disease. All patients also had inducible VTA. To compare the effects of nifekalant and sotalol, programmed electrical stimulation was performed, in the basal state, after nifekalant administration, and after sotalol administration. Nifekalant and sotalol similarly prolonged the corrected QT interval and ventricular effective refractory periods, but the heart rate was slowed by sotalol only. In 4 of 5 patients whose VTA became non-inducible by nifekalant, subsequent treatment with sotalol also suppressed the inducible VTA. In all of the 9 patients non-responding to nifekalant, VTA remained inducible during sotalol treatment. Nifekalant accurately predicted the response to sotalol during electrophysiologic study in 13 of 14 patients. Of 11 patients who remained on sotalol, VTA recurred in 3 non-responders during a follow-up of 46 +/- 11 months. CONCLUSIONS: Nifekalant and sotalol had similar effects on inducible VTA. The response of inducible VTA to nifekalant may predict the clinical efficacy of sotalol.

Heart rate variability is a useful parameter for evaluation of anticholinergic effect associated with inducibility of atrial fibrillation.

BACKGROUND: Disopyramide is thought to have an advantageous effect for atrial fibrillation (AF) associated with vagal activity because of its anticholinergic effect. METHOD: We used a canine vagal nerve stimulation (VNS) model. The monophasic action potential (MAP) duration at 90% repolarization (MAP(90)), the intraatrial conduction time, the induciblity of AF by electrical stimulation, and the amplitude of high-frequency component (HF-amp) of the heart rate variability (HRV) were evaluated before and after the administration of disopyramide (1 mg/kg) (group D, n = 8) or pilsicainide (1 mg/kg) (group P, n = 5). RESULTS: In group D, HF-amp decreased in the baseline condition from 1.1 +/- 0.6 to 0.6 +/- 0.4 ms and the degree of VNS-induced augmentation of HF-amp was attenuated from +492% to +127%. VNS-induced shortening of MAP(90) was also attenuated in the right atrium (from -30 +/- 15% to -10 +/- 6%) and in the left atrium (from -15 +/- 9% to -6 +/- 6%). In group P, little effect was shown in these parameters. The vagotonic AF became noninducible in all eight experiments in group D, while in only one of five in group P. CONCLUSION: The beneficial effect of disopyramide for vagotonic AF is based on the decrease of basal vagal tone and attenuation of the effect of vagal stimulation in the atrial myocardium. HRV is a useful parameter for evaluation of the effect of antiarrhythmic drugs on the autonomic nerve system, and the evaluation of variability may be useful for testing drug efficacy for arrhythmias.

Effects of intravenous magnesium in a prolonged QT interval model of polymorphic ventricular tachycardia focus on transmural ventricular repolarization.

BACKGROUND: This study was performed to clarify the antiarrhythmic effects of magnesium sulfate (Mg(++)) in a prolonged QT interval canine model of polymorphic ventricular tachyarrhythmia (VTA). METHODS: In six experiments in a canine model of prolonged QT by anthopleurin-A, Mg(++) was administered in boluses of 0.2 mL/kg during repetitive episodes of self-terminating polymorphic VTA or frequent premature ventricular complexes (PVCs). The distribution of ventricular repolarization across the left ventricular(LV) wall and dispersion of transmural repolarization were analyzed before, and 30 and 120 seconds after Mg(++) administration, during ventricular pacing at 100 bpm. Transmural unipolar electrograms were recorded from multipolar needle electrodes, and local activation-recovery intervals (ARI) were measured. RESULTS: Mg(++) rapidly eliminated self-terminating polymorphic VTA and all isolated PVCs. During ventricular pacing at 100 bpm, Mg(++) caused modest shortening of ARI at all recording sites. Since the magnitude of ARI shortening was greater at mid-myocardial sites than at other ventricular sites, mean transmural ARI dispersion decreased from 80 +/- 22 to 45 +/- 18 ms within 30 seconds after Mg(++) injection. However, this effect was transient, and, at 120 seconds after Mg(++) administration, ARI had increased all sites and transmural ARI dispersion lengthened to 65 +/- 18 ms. Besides suppression of triggered premature activity, homogenization of transmural ventricular repolarization was associated with the antiarrhythmic effects of intravenous Mg(++) in this model. CONCLUSION: Since these effects were transient, a continuous intravenous infusion of Mg(++) is preferred to prevent recurrences of VTA.