ヨクボウ トシ カラ キョウカン キョウセイ ノ マチ エ : 21セイキ ニオケル オオサカ ノトシ サイセイ オ カンガエル

梅棹忠夫が「大阪は下司の町」と喝破してから半世紀近く経つが、その後の事態は都市イメージも都市格も改善にむかうことなく低落の一途をたどっている。その最大の原因のひとつが地域経済の衰退による生活の貧しさからくる、下から地域づくりを進めようという「自立と自治」意識の希薄化と空洞化である。そこで、こうした低落一途の都市イメージを払拭し都市格を高めつつ、大阪府民が広く「公共心の伝統」とあわせて誇りと自信を取りもどすためにはどうすべきか、そのための条件や可能性は一体どこにあるのか、という点を中心に検討を加える。そしてヨーロッパや日本の条件不利地域のとりくみにも学びつつ、大阪においてもsustainabilityを合言葉に、コミュニティレベルから信頼と共感の絆を形成することが不可欠であり、こうした営為の積み重ねこそが21世紀の大阪の都市再生にとって不可避な道筋であることをあきらかにする

926-24 Clinical and Electrophysiological Characteristics in Patients with Exercise Induced Idiopathic Multiform Ventricular Tachycardia. Differential Effects of Atrial Pacing and Isoproterenol Infusion on QTc Interval and Induction of Ventricular Arrhythmia

Idiopathic multiform ventricular tachycardia (VT) is characterized by normal QT interval at restand 3 or more distinct QRS configuration during VT, which has been distinguished from torsade de pointes in long QT syndrome. Facilitation by exercise and suppression by β-antagonist of this VT suggest that it may depend on rapid heart rate (HR) or increased sympathetic tone. To determine which factors is responsible, we performed atrial pacing (120/min) and isoproterenol (ISP) infusion (0.5 or 1.0μg to attain HR 120/min) in 6 patients (2 males/4 females, mean 15.8 years) and 10 control (4 males/6 females, mean 22.8 years). Inducibility of premature ventricular contraction (PVC) or VT, and response of QTc interval (QT/√RR) were evaluated during the procedures.controlmultiform VTp valuePVCNT inductionAtrial pacing0/71/6n.s.Isoproterenol0/86/60.001OTc (secl/2)Rest0.40±0.02 (n=10)0.40±0.03n.s.Atrial pacing0.43±0.02 (n=7)0.47±003<0.01Isoproterenol0.44±0.01 (n=8)0.50±0.05<0.001ConclusionAlthough both rapid HR and increased sympathetic tone may be responsible for this VT, contribution of the latter is predominant. Differential response of QT interval to atrial pacing and isoproterenol infusion may have a possible role for the occurrence of this VT

Development of a new method for assessing otolith function in mice using three-dimensional binocular analysis of the otolith-ocular reflex

In the interaural direction, translational linear acceleration is loaded during lateral translational movement and gravitational acceleration is loaded during lateral tilting movement. These two types of acceleration induce eye movements via two kinds of otolith-ocular reflexes to compensate for movement and maintain clear vision: horizontal eye movement during translational movement, and torsional eye movement (torsion) during tilting movement. Although the two types of acceleration cannot be discriminated, the two otolith-ocular reflexes can distinguish them effectively. In the current study, we tested whether lateral-eyed mice exhibit both of these otolith-ocular reflexes. In addition, we propose a new index for assessing the otolith-ocular reflex in mice. During lateral translational movement, mice did not show appropriate horizontal eye movement, but exhibited unnecessary vertical torsion-like eye movement that compensated for the angle between the body axis and gravito-inertial acceleration (GIA; i.e., the sum of gravity and inertial force due to movement) by interpreting GIA as gravity. Using the new index (amplitude of vertical component of eye movement)/(angle between body axis and GIA), the mouse otolith-ocular reflex can be assessed without determining whether the otolith-ocular reflex is induced during translational movement or during tilting movement

Sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than LQT2 forms of congenital long QT syndrome

AbstractOBJECTIVESThe study compared the influence of sympathetic stimulation on transmural and spatial dispersion of repolarization between LQT1 and LQT2 forms of congenital long QT syndrome (LQTS).BACKGROUNDCardiac events are more associated with sympathetic stimulation in LQT1 than in LQT2 or LQT3 syndrome. Experimental studies have suggested that the interval between Tpeak and Tend (Tp-e) in the electrocardiogram (ECG) reflects transmural dispersion of repolarization across the ventricular wall.METHODSWe recorded 87-lead body-surface ECGs before and after epinephrine infusion (0.1 μg/kg/min) in 13 LQT1, 6 LQT2, and 7 control patients. The Q-Tend (QT-e), Q-Tpeak (QT-p), and Tp-e were measured automatically from 87-lead ECGs, corrected by Bazett’s method (QTc-e, QTc-p, Tcp-e), and averaged among all 87-leads and among 24-leads, which reflect the potential from the left ventricular free wall. As an index of spatial dispersion of repolarization, the dispersion of QTc-e (QTc-eD) and QTc-p (QTc-pD) were obtained among 87-leads and among 24-leads, and were defined as the interval between the maximum and the minimum of the QTc-e and the QTc-p, respectively.RESULTSEpinephrine significantly increased the mean QTc-e but not the mean QTc-p, resulting in a significant increase in the mean Tcp-e in both LQT1 and LQT2, but not in control patients. The epinephrine-induced increases in the mean QTc-e and Tcp-e were larger in LQT1 than in LQT2, and were more pronounced when the averaged data were obtained from 24-leads than from 87-leads. Epinephrine increased the maximum QTc-e but not the minimum QTc-e, producing a significant increase in the QTc-eD in both LQT1 and LQT2 patients, but not in control patients. The increase in the QTc-eD was larger in LQT1 than in LQT2 patients.CONCLUSIONSOur data suggest that sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than in LQT2 syndrome, and this may explain why LQT1 patients are more sensitive to sympathetic stimulation

Effects of verapamil and propranolol on early afterdepolarizations and ventricular arrhythmias induced by epinephrine in congenital long QT syndrome

Objectives.This study used monophasic action potentials to investigate the effects of verapamil and propranolol on epinephrineinduced repolarization abnormalities in congenital long QT syndrome.Background.Early afterdepolarizations have been suggested to play a significant role in QT prolongation and ventricular arrhythmias in congenital long QT syndrome. Calcium channel blocking as well as beta-adrenergic blocking agents are reported to be effective in the management of this syndrome.Methods.Monophasic action potentials from 2 to 4 sites were recorded simultaneously in eight patients with the long QT syndrome (22 sites) and in eight control patients (23 sites) and were obtained during constant atrial pacing 1) before epinephrine infusion; 2) during epinephrine infusion (0.1 μg/kg body weight min); 3) after verapamil injection (0.1 mg/kg) during epinephrine infusion; and 4) after both propranolol (0.1 mg/kg) and verapamil injections.Results.Early afterdepolarizations were recorded in two of the eight patients (2 of 22 sites) during the control state. During epinephrine infusion, early afterdepolarizations were recorded in six patients (six sites), and ventricular premature complexes were induced in three and torsade de pointes in one. Epinephrine prolonged 90% monophasic action potential duration from 348 ± 48 (mean ± SD) to 381 ± 49 ms (22 sites, p < 0.0005) and increased the dispersion of action potential duration (difference between the longest and shortest action potential duration) from 36 ± 20 to 64 ± 34 ms (p < 0.005). Verapamil eliminated (two sites) or reduced (four sites) early afterdepolarizations and abolished ventricular premature complexes in two of the three patients as well as suppressing torsade de pointes. Verapamil shortened the action potential duration to 355 ± 28 ms (p < 0.01 vs. epinephrine) and decreased the dispersion to 44 ± 19 ms (p < 0.05 vs. epinephrine). Propranolol further eliminated (two sites) or reduced (two sites) early afterdepolarizations, abolished ventricular premature complexes in the remaining one patient and further shortened the action potential duration to 337 ± 32 ms (p = 0.09 vs. verapamil). In the control patients, none of the early afterdepolarizations, ventricular arrhythmias or marked prolongations of action potential duration were induced by epinephrine, and neither verapamil nor propranolol changed repolarization variables.Conclusions.These results indicate that both verapamil and propranolol can improve repolarization abnormalities induced by epinephrine in congenital long QT syndrome

Differential effects of beta-blockade on dispersion of repolarization in the absence and presence of sympathetic stimulation between the lqt1 and lqt2 forms of congenital long qt syndrome

AbstractObjectivesThis study compared the effects of beta-blockade on transmural and spatial dispersion of repolarization (TDR and SDR, respectively) between the LQT1 and LQT2 forms of congenital long QT syndrome (LQTS).BackgroundThe LQT1 form is more sensitive to sympathetic stimulation and more responsive to beta-blockers than either the LQT2 or LQT3 forms.MethodsEighty-seven-lead, body-surface electrocardiograms (ECGs) were recorded before and after epinephrine infusion (0.1 μg/kg body weight per min) in the absence and presence of oral propranolol (0.5–2.0 mg/kg per day) in 11 LQT1 patients and 11 LQT2 patients. The Q-Tendinterval, the Q-Tpeakinterval and the interval between Tpeakand Tend(Tp-e), representing TDR, were measured and averaged from 87-lead ECGs and corrected by Bazett’s method (corrected Q-Tendinterval [cQTe], corrected Q-Tpeakinterval [cQTp] and corrected interval between Tpeakand Tend[cTp-e]). The dispersion of cQTe(cQTe-D) was obtained among 87 leads and was defined as the interval between the maximum and minimum values of cQTe.ResultsPropranolol in the absence of epinephrine significantly prolonged the mean cQTpvalue but not the mean cQTevalue, thus decreasing the mean cTp-evalue in both LQT1 and LQT2 patients; the differences with propranolol were significantly larger in LQT1 than in LQT2 (p < 0.05). The maximum cQTe, minimum cQTeand cQTe-D were not changed with propranolol. Propranolol completely suppressed the influence of epinephrine in prolonging the mean cQTe, maximum cQTeand minimum cQTevalues, as well as increasing the mean cTp-eand cQTe-D values in both groups.ConclusionsBeta-blockade under normal sympathetic tone produces a greater decrease in TDR in the LQT1 form than in the LQT2 form, explaining the superior effectiveness of beta-blockers in LQT1 versus LQT2. Beta-blockers also suppress the influence of sympathetic stimulation in increasing TDR and SDR equally in LQT1 and LQT2 syndrome

Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome Multicenter study in Japan

AbstractObjectivesWe sought to compare the arrhythmic risk and sensitivity to sympathetic stimulation of mutations located in transmembrane regions and C-terminal regions of the KCNQ1channel in the LQT1 form of congenital long QT syndrome (LQTS).BackgroundThe LQT1 syndrome is frequently manifested with variable expressivity and incomplete penetrance and is much more sensitive to sympathetic stimulation than the other forms.MethodsSixty-six LQT1 patients (27 families) with a total of 19 transmembrane mutations and 29 patients (10 families) with 8 C-terminal mutations were enrolled from five Japanese institutes.ResultsPatients with transmembrane mutations were more frequently affected based on electrocardiographic (ECG) diagnostic criteria (82% vs. 24%, p < 0.0001) and had more frequent LQTS-related cardiac events (all cardiac events: 55% vs. 21%, p = 0.002; syncope: 55% vs. 21%, p = 0.002; aborted cardiac arrest or unexpected sudden cardiac death: 15% vs. 0%, p = 0.03) than those with C-terminal mutations. Patients with transmembrane mutations had a greater risk of first cardiac events occurring at an earlier age, with a hazard ratio of 3.4 (p = 0.006) and with an 8% increase in risk per 10-ms increase in corrected Q-Tend. The baseline ECG parameters, including Q-Tend, Q-Tpeak, and Tpeak-end intervals, were significantly greater in patients with transmembrane mutations than in those with C-terminal mutations (p < 0.005). Moreover, the corrected Q-Tend and Tpeak-end were more prominently increased with exercise in patients with transmembrane mutations (p < 0.005).ConclusionsIn this multicenter Japanese population, LQT1 patients with transmembrane mutations are at higher risk of congenital LQTS-related cardiac events and have greater sensitivity to sympathetic stimulation, as compared with patients with C-terminal mutations

Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction

Cholesteatoma, which potentially results from tympanic membrane retraction, is characterized by intractable local bone erosion and subsequent hearing loss and brain abscess formation. However, the pathophysiological mechanisms underlying bone destruction remain elusive. Here, we performed a single-cell RNA sequencing analysis on human cholesteatoma samples and identify a pathogenic fibroblast subset characterized by abundant expression of inhibin βA. We demonstrate that activin A, a homodimer of inhibin βA, promotes osteoclast differentiation. Furthermore, the deletion of inhibin βA /activin A in these fibroblasts results in decreased osteoclast differentiation in a murine model of cholesteatoma. Moreover, follistatin, an antagonist of activin A, reduces osteoclastogenesis and resultant bone erosion in cholesteatoma. Collectively, these findings indicate that unique activin A-producing fibroblasts present in human cholesteatoma tissues are accountable for bone destruction via the induction of local osteoclastogenesis, suggesting a potential therapeutic target.Shimizu K., Kikuta J., Ohta Y., et al. Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction. Nature Communications 14, 4417 (2023); https://doi.org/10.1038/s41467-023-40094-3

Comparison of the efficacy of the Epley maneuver and repeated Dix–Hallpike tests for eliminating positional nystagmus: A multicenter randomized study

Background and objectivesPatients with benign paroxysmal positional vertigo of the posterior canal (pc-BPPV) exhibit BPPV fatigue, where the positional nystagmus diminishes with the repeated performance of the Dix–Hallpike test (DHt). BPPV fatigue is thought to be caused by the disintegration of lumps of otoconial debris into smaller parts and can eliminate positional nystagmus within a few minutes [similar to the immediate effect of the Epley maneuver (EM)]. In this study, we aimed to show the non-inferiority of the repeated DHt to the EM for eliminating positional nystagmus after 1 week.MethodsThis multicenter, randomized controlled clinical trial was designed based on the CONSORT 2010 guidelines. Patients who had pc-BPPV were recruited and randomly allocated to Group A or Group B. Patients in Group A were treated using the EM, and patients in Group B were treated using repeated DHt. For both groups, head movements were repeated until the positional nystagmus had been eliminated (a maximum of three repetitions). After 1 week, the patients were examined to determine whether the positional nystagmus was still present. The groups were compared in terms of the percentage of patients whose positional nystagmus had been eliminated, with the non-inferiority margin set at 15%.ResultsData for a total of 180 patients were analyzed (90 patients per group). Positional nystagmus had been eliminated in 50.0% of the patients in Group A compared with 47.8% in Group B. The upper limit of the 95% confidence interval for the difference was 14.5%, which was lower than the non-inferiority margin.DiscussionThis study showed the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week in patients with pc-BPPV and that even the disintegration of otoconial debris alone has a therapeutic effect for pc-BPPV. Disintegrated otoconial debris disappears from the posterior canal because it can be dissolved in the endolymph or returned to the vestibule via activities of daily living.Classification of evidenceThis study provides Class II evidence of the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week.Registration numberUMIN000016421