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Purpose Catheter ablation is a recommended rhythm control therapy after failed or intolerant antiarrhythmic drug (AAD) treatment for patients with atrial fibrillation (AF). This study evaluates clinical performance and safety of pulmonary vein isolation (PVI) using the cryoballoon (Arctic Front Advance) in Japan. Methods Cryo AF Global Registry is a prospective, multi-center registry. Patients with paroxysmal AF (PAF) were treated at 10 Japanese hospitals. Efficacy was evaluated by freedom from a ≥ 30-s recurrence of AF/atrial flutter (AFL)/atrial tachycardia (AT), AF-related symptoms, and quality of life using the EQ-5D-3L questionnaire. The safety endpoint was serious device- and procedure-related adverse events. Results The study included 352 patients with PAF (65 ± 10 years of age, 36% female, 36% without prior failure of AAD). Mean duration since first diagnosis of AF was 3.0 ± 5.5 years. Serious device- and procedure-related adverse event rate was 2.6% (95% CI: 1.2–4.8%). Freedom from AF/AFL/AT was 88.5% (95% CI: 84.7–91.4%) at 12 months and 86.7% (95% CI: 81.1–90.8%) at 24 months. The number of patients with ≥ 1 AF symptom was significantly decreased from 88% at enrollment to 22% (p p Conclusions This study demonstrates that cryoablation used for PVI is a safe and effective treatment in real-world use for patients with PAF in Japan.

Episodes of atrial fibrillation (AF) are mainly initiated by triggers from pulmonary veins (PVs). The superior vena cava (SVC) has been identified as a second major substrate of non-PV foci, but the electrophysiologic features of the SVC have not been fully investigated. We hypothesized that SVC ectopies are suppressed by predominant features of PV ectopies and tend to appear after PV isolation (PVI). We evaluated the electrophysiological characteristics and clinical implications of SVC ectopies in patients with AF during catheter ablation using high-dose isoproterenol and the atrial overdrive pacing maneuver. The manifestation patterns and modes of onset (coupling interval and appearance interval) of ectopies from both the PVs and SVC were investigated. 205 patients were enrolled [153 males and 52 females; mean age 64 ± 10 years; paroxysmal in 143 patients (69.8 %), persistent in 40 (19.5 %), and long-standing persistent in 22 patients (10.7 %)]. Before PVI, PV ectopies were detected in 182/205 patients (89 %). SVC ectopies were rarely observed before PVI but were significantly more frequent after the completion of PVI (3/205 vs. 14/205 patients, p = 0.011). The coupling interval (CI) and % CI (CI/preceding the A-A interval × 100) of PV ectopies were significantly shorter than those of SVC ectopies (211 ± 78 vs. 282 ± 106 ms, p = 0.021, and 34 ± 9 vs. 51 ± 17 %, p

The purpose of this study was to analyze passive motion of the para- and retropharyngeal space (PRS) during swallowing using dynamic magnetic resonance imaging (MRI). We conducted a preliminary study involving 30 healthy volunteers who underwent dynamic MRI. Consecutive MRI axial images were obtained by examining the plane parallel to the hard palate at the level of the anterior inferior corner of C2. Anterior displacement of the posterior pharyngeal wall (PPW) was measured as a motion index of pharyngeal contraction. The displacement and internal angle of the bilateral external and internal carotid arteries (ECA and ICA) and the bilateral centroids of the PRS area, as well as the increase in PRS area, were calculated at rest and at maximum pharyngeal contraction. In most participants, the bilateral ECA, ICA, and centroids were anterointernally displaced by pharyngeal contraction. The normalized ECA displacement (r = 0.64, r 2 = 0.41), normalized ICA displacement (r = 0.60, r 2 = 0.37), and normalized centroid displacement (r = 0.43, r 2 = 0.19) were more than moderately positively correlated with the normalized PPW displacement. The normalized PRS area increase (r = 0.35, r 2 = 0.12) was weakly positively correlated with the normalized PPW displacement. These results revealed that PRS area increased as the ECA and ICA were drawn anterointernally via its passive motion by pharyngeal contraction.

Although several predictors of an electrical storm (ES) are indicated in patients with idiopathic dilated cardiomyopathy (IDCM), whether the severity of the myocardial tissue damage (SMTD) evaluated by myocardial perfusion SPECT (MPS) has an association with an ES remains unclear. The purpose of this study was to elucidate the clinical significance of SMTD for the prediction of ES in IDCM patients with an ICD. Thirty-seven (27 men, mean age 58 ± 15 years) IDCM patients receiving ICD implantations for secondary prevention with preoperative MPS were enrolled in this study. The medical history, physical and laboratory findings, electrocardiograms, echocardiograms and MPS findings were evaluated. The SMTD was assessed by the summed scores of 17 segments using a 4-point system (0, normal ~3, severe defect). During a mean follow-up of 43.9 ± 30.7 months, an ES developed in 12/37 (32.4 %) patients. The SMTD score predicted an ES with a 92 % sensitivity and 56 % specificity, at a cut-off score of 10. In addition, a multivariate analysis showed that the SMTD score remained an independent predictor of an ES (HR 1.09/score 1 increase, 95 % CI 1.01–1.19, p = 0.02). The SMTD score was significantly associated with three indices of late potentials on the signal-averaged electrocardiograms, and was significantly higher in patients with positive late potentials (p = 0.0006). SMTD score assessed by MPS has a strong correlation to the late potentials and higher SMTD score may increase the risk of ES among patients with IDCM and an ICD.

Factor XIII (FXIII) is the final enzyme in the coagulation cascade. Acquired FXIII deficiency is caused by inhibitors of FXIII or decreased synthesis and/or increased consumption of FXIII, which leads to severe bleeding. Recently, we experienced a case of hemorrhagic-acquired factor XIII deficiency that occurred during treatment with the IL-6 inhibitor tocilizumab for rheumatoid arthritis. A 48-year-old man was referred because of right hip pain due to a hematoma. Laboratory findings showed that routine coagulation tests were normal, while FXIII activity was slightly low (52.4 %). The patient was successfully treated with plasma-derived factor XIII concentrates. The time course of recovery suggests that tocilizumab might have inhibited FXIII production. To our knowledge, this is the first report of acquired factor XIII deficiency associated with administering of tocilizumab. When recurrent bleeding is seen during administering of tocilizumab, acquired factor XIII deficiency may have been induced, thus attending physicians should consider this disease in a differential diagnosis.

The atrioventricular (AV) conduction system in corrected transposition of the great arteries (cTGA) involving situs inversus remains unclear. A case of cTGA involving situs inversus, mild pulmonary stenosis, and ventricular septal defect (VSD) is reported. An electrophysiologic study using the CARTO system and angiography was performed to identify the AV conduction system before a double-switch operation with VSD enlargement. The His bundle was located at the anteroseptum of the left-sided RA. It descended along the posteroinferior margin of the VSD with cTGA involving situs inversus and a normal-sized pulmonary trunk. No AV block occurred after surgery. The combination of the CARTO system and angiography could be useful for identifying the conduction system.

Duodecapolar catheters (DPCs) have been widely used to diagnose isthmus block after ablation in patients with atrial flutters. The purpose of this study was to assess the ability of DPC to diagnose isthmus block utilizing electroanatomical mapping system (CARTO).Sixty-two patients with common atrial flutter underwent isthmus ablation during CS pacing while DPC was positioned at lateral wall of RA along tricuspid annulus (TA). When activation sequence of DPC recording changed exclusively counter-clockwise after ablation, or did not even after ablations targeting single potentials on ablation line (Ab-L), only lateral side of Ab-L was remapped using CARTO to assess whether complete block (CB) was established.After ablation, DPC recording suggested CB and incomplete block (ICB) in 53 (85%) and 9 patients (15%), respectively. In 51/53 patients (96%) with CB suggested by DPC recordings, CARTO remap also demonstrated CB, however, in the remaining two patients (4%), demonstrated ICB with residual isthmus conduction that was slow enough to allow wavefront conducting around TA to arrive at distal dipole of DPC earlier, mimicking CB. In 4/9 patients (44%) with ICB suggested by DPC recordings, CARTO remap also demonstrated ICB, however, in the remaining five patients (56%), demonstrated CB with earlier arrival of wavefront traversing posterior wall at just lateral to Ab-L than that conducting around TA, mimicking ICB. Sensitivity, specificity, positive, and negative predictive values of DPC to diagnose CB were 91, 67, 96, and 44%, respectively.Mapping using DPC would not be sufficient for diagnosis of CB and ICB.

We report a case of left accessory atrioventricular pathway (AP) which antegrade conduction was manifest during pacing from the anterior site of the atrial insertion, but absent during pacing from the posterior site. Infusion of adenosine triphosphate during pacing from the posterior site induced a conduction block of atrioventricular node without affecting the persistent antegrade conduction block of the AP. These findings suggested that the different response of the AP according to the directional change of atrial conduction was not due to a 'linking' phenomenon, but may relate to the impedance mismatch because of an oblique fashion of the pathway.

Outlet obstruction of the ratbladder induces hypertrophy/hyperplasiacharacterized by increases in bladder mass,smooth muscle content, and collagen deposition.In order to understand the mechanism of theoutlet obstruction-induced hypertrophy andhyperplasia, we first determined the temporalpattern of changes in bladder mass afterinducing the outlet obstruction. Histologicalanalysis revealed that the smooth muscle cellswith hypertrophy and hyperplasia, fibroblastsand connective tissue were increased in atime-dependent manner, corresponding to thetemporal pattern observed in the changes inbladder mass, although the phase of changes inthese tissue components was somewhat different.In order to further determine whether anyproliferation-stimulatory factors were releasedfrom the bladder with obstruction incorrespondence with increased bladder mass,soluble fractions were prepared from thebladders with outlet obstruction for 3–30weeks, and their effects on proliferation ofsmooth muscle cells were examined. The solublefractions prepared from the bladders at 3 to 14weeks after obstruction slightly butsignificantly facilitated the proliferation ofcultured smooth muscle cells, while the solublefractions released after 20 weeks rathersuppressed the proliferation. These resultssuggest that the initial increase in bladdermass might be in part due to the facilitatedproliferation of smooth muscle cells of thebladder body induced by growth factors releasedinto the soluble fractions, and thathypertrophy might then play a role in theincreased bladder mass at later phases.

Pellet injection and repetitive laser illumination are key technologies for realizing inertial fusion energy. Numerous studies have been conducted on target suppliers, injectors, and tracking systems for flying pellet engagement. Here we for the first time demonstrate the pellet injection, counter laser beams' engagement and neutron generation. Deuterated polystyrene (CD) bead pellets, after free-falling for a distance of 18 cm at 1 Hz, are successfully engaged by two counter laser beams from a diode-pumped, ultra-intense laser HAMA. The laser energy, pulse duration, wavelength, and the intensity are 0.63 J per beam, 104 fs, and 811 nm, 4.7 × 10(18) W/cm(2), respectively. The irradiated pellets produce D(d,n)(3)He-reacted neutrons with a maximum yield of 9.5 × 10(4)/4π sr/shot. Moreover, the laser is found out to bore a straight channel with 10 μm-diameter through the 1-mm-diameter beads. The results indicate potentially useful technologies and findings for the next step in realizing inertial fusion energy.

Transurethral injection of Teflon paste (TUI) was carried out in 24 ureters of 16 patients with vesicoureteral reflux (VUR) secondary to neurogenic bladder dysfunction at an age ranging from 4 to 77 years, and the results were compared with those of conventional open surgery. During the mean follow-up period of 20.1 months, reflux disappeared in 19 ureters (79%), so that the success rate of endoscopic operation was considered to be satisfactory as compared with that of conventional open surgery, in which reflux disappeared in 16 (80%) of 20 ureters in 16 patients with neurogenic bladder dysfunction at our department. No exacerbation of hydronephrosis was observed postoperatively, and no complication was noted. This procedure, which is minimally invasive and technically simple, may be regarded as the first choice for VUR secondary to neurogenic bladder dysfunction.

The growth fraction of bladder tumors was immunohistochemically assessed in situ using anti-DNA polymerase (Pol alpha) monoclonal antibody. This enzyme is known to be present in the nucleus of the cells in G1, S, and G2 phases. The percentage of labeled cells was expressed as the labeling index (LI). The average LI was 6.0% in normal epithelium and 17.8% in bladder tumors, this difference being significant. The labeled cells were distributed throughout both the basal and surface layers of bladder tumors. However, in some bladder tumors, the distribution of Pol alpha-labeled cells varied from area to area. The higher fraction of labeled cells was found in high grade or invasive tumors. Papillary and nodular bladder tumors showed a greater rate of cell proliferation than papillary tumors. These findings suggest that Pol alpha immunostaining could be a potent tool for easy and quick evaluation of proliferating cells in bladder tumors, thereby providing a supplement to conventional histological findings.

The relationship between the degree of metabolic acidosis and calcium phosphate stone formation was studied. Furthermore, the reasons why renal tubular acidosis (RTA) and primary hyperparathyroidism (PHPT) dominantly occur in women, and female stone formers more often produce calcium phosphate stone are discussed. Blood was slightly more acidotic in women than in men in both the urolithiasis and the control groups. Likewise, blood was significantly more acidotic and urinary pH significantly higher in patients with PHPT. Patients with RTA had severe metabolic acidosis, and urinary pH was highest among all groups. Calcium phosphate concentration was significantly higher in women than in men, and was also higher in patients with PHPT than in those with urolithiasis. All patients with RTA had pure calcium phosphate stones. The reasons why females are more acidotic and have more calcium phosphate in stones are suspected to be related to progesterone and urinary tract infection.

The determination of ABH blood group antigens for the prognosis of superficial bladder tumours was evaluated. A total of 114 cases of superficial bladder tumours were studied, and all cases were treated by transurethral resection (TUR). The 5-year recurrence rate was 42%. The ABH antigenicity provided more useful information than the grade in predicting recurrence of the tumours. The period from the initial TUR till the first recurrence in antigen-negative tumours was 17.5 months, which was shorter, though not significantly, than the corresponding period in antigen-positive tumours of 25.2 months. In addition, the presence or absence of isoantigens of tumours having two or more recurrences was examined individually.

The anti-tumor effect of OK432 instilled into the bladder was evaluated in rat bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). In experiment I, the rate of the natural killer (NK) activity was determined with cells from spleen and mesenteric lymph nodes. Intravesical OK432 instillation enhanced NK activity; however, this activity was not dose-dependent and was not augmented by OK432 inoculation into the foot pad. In experiment 2, the therapeutic effect of intravesical OK432 instillation was examined in rat bladder tumors induced by BBN. OK432 was instilled weekly for six weeks. Rats given BBN for 10 weeks were divided into six groups: 1) control; 2) saline; 3) OK432 0.05 KE/ml; 4) OK432 0.05 KE/ml bladder instillation with 0.01 KE/ml foot pad inoculation; 5) OK432 0.05 KE/ml, every other week; and 6) OK432 0.5 KE/ml. Weekly OK432 instillation significantly reduced tumor weight and the incidence of tumor development; however, this inhibition was not dose-dependent and was not enhanced by OK432 inoculation into the foot pad. In rats given OK432 weekly, the augmentation of NK activity and increase in tissue infiltrating lymphocytes were significant. These results suggest that intravesical OK432 instillation is effective in the management of superficial bladder tumors. The study further emphasizes that the dose and method of administration are critical variables in determining the efficacy of immunotherapy.

High-performance liquid chromatography (HPLC) monitoring with an ultraviolet detector was carried out to measure urinary oxalate levels in urolithiasis. Interfering substances in urine were removed by anion exchange prior to chromatography. This procedure was found excellent with respect to sensitivity, reproducibility, and analytical recovery. The findings were in agreement with colorimetric date. The mean oxalate level in 24-hour urine was 30.5 +/- 15.1 mg in patients with a single episode and 36.3 +/- 9.8 mg in recurrent stone formers. The latter values was significantly higher than the normal control level (27.4 +/- 3.8 mg).

Factors relating alterations in plasma and urine composition to recurrence of urinary stones during drug therapy were investigated by using a multiple regression analysis technique. These factors were influenced not only by the efficacy of the drugs but also by other factors (plasma or urinary constituents and overall health of the patients, etc.). In order to study the effect of drug therapy or other treatment on the alteration of plasma and urine constituents, multiple regression analysis is more appropriate than Student's paired t-test which has been used by some workers. These two analytical methods yield different results even if used on the same data.

Serum osteocalcin, also called bone gla protein, is one of sensitive and specific markers for metabolic bone diseases. Current evidence suggests that the protein may be involved in the regulation of calcium homeostasis in bone. We measured serum osteocalsin levels by radioimmunoassay in 100 patients with urolothiasis, especially in calcium containing stone formers and evaluated the influence of bone metabolism on the formation of calcium-containing stones. Although serum osteocalcin levels in most patients were normal, those of two male and four female patients were high. We considered that they were patients with renal hypercalciuria and secondary hyperparathyroidism and in them the formation of calcium containing stones were influenced by disorder of bone metabolism. In addition, we suggest that serum osteocalcin levels may be available index for the effect of treatment in stone formers with renal hypercalciuria and bone disease.

Plasminogen activator was recovered from bladder tumors by 30% ammonium sulfate precipitation, acid treatment and concanavalin A-Sepharose affinity chromatography to a purification factor of about 80,000. The pooled fraction from the binding protein to concanavalin A-Sepharose revealed a single enzymatically active band with molecular weight of 55,000, which lost its enzymatic activity in the absence of plasminogen. The enzymatic activity was inactivated by DFP. The purified plasminogen activator reacted with antibody against UK, and not with that against t-PA. The purified plasminogen activator cleaved S-2288 to a greater extent than S-2444, although UK cleaved S-2444 to a greater extent that S-2288. The enzymatic activity was strongly inhibited by basic pancreatic trypsin inhibitor, and benzamidine. These results suggest that the plasminogen activator in bladder tumors may belong to a different category of plasminogen activator.