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Objective This study aimed to examine the alterations in gray matter networks related to tau retention in Alzheimer's disease (AD) patients and cognitively normal (CN) older individuals. Methods Eighteen amyloid-positive AD patients and 30 age- and sex-matched amyloid-negative CN controls were enrolled. All underwent 3D T1-weighted MRI, amyloid positron-emission tomography imaging (PET) with 11C-Pittsburgh Compound B (PiB), and tau PET with 18F-THK5351. The structural networks extracted from the T1-weighted MRI data based on cortical similarities within single subjects were analyzed. Based on graph theoretical approach, global and local network properties across the whole brain were computed. Group comparisons of global and local network properties were evaluated between the groups. Then, we correlated the global and local network measures with total cerebral 18F-THK5351 retention. Results AD patients moved toward more randomized global network compared to controls and regional differences were observed in the default mode network (DMN) area. No significant correlations existed between global network properties and tau retention. On a local level, AD and controls showed opposite relationships between network properties and tau retention mainly in the DMN areas; CN controls showed positive correlations, whereas AD showed negative correlations. Conclusion We found opposite relationships between local network properties and tau retention between amyloid-positive AD patients and amyloid-negative controls. Our findings suggest that the presence of amyloid and induced exacerbated tau retention alter the relationship of local network properties and tau retention., Highlights • Correlation of structural network properties and tau retention. • Positive correlations between local network properties and tau retention in healthy elderly. • Negative correlations between local network properties and tau retention in AD.

Background and purpose Recent studies suggest that the autoantibodies against adrenergic/muscarinic receptors might be one of the causes and potential markers of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The purpose of this study was to investigate the structural network changes related to autoantibody titers against adrenergic/muscarinic receptors in ME/CFS by performing a single-subject gray matter similarity-based structural network analysis. Methods We prospectively examined 89 consecutive right-handed ME/CFS patients who underwent both brain MRI including 3D T1-wighted images and a blood analysis of autoantibodies titers against β1 adrenergic receptor (β1 AdR-Ab), β2 AdR-Ab, M3 acetylcholine receptor (M3 AchR-Ab), and M4 AchR-Ab. Single-subject gray matter similarity-based structural networks were extracted from segmented gray matter images for each patient. We calculated local network properties (betweenness centrality, clustering coefficient, and characteristic path length) and global network properties (normalized path length λ, normalized clustering coefficient γ, and small-world network value δ). We investigated the correlations between the autoantibody titers and regional gray matter/white matter volumes, the local network properties, and the global network properties. Results Betweenness centrality showed a significant positive correlation with β1-AdR-Ab in the right dorsolateral prefrontal cortex. The characteristic path length showed a significant negative correlation with β2-AdR-Ab in the right precentral gyrus. There were no significant correlations between the antibody titers and the regional gray matter/white matter volumes, and the global network properties. Conclusions Our findings suggest that β1 AdR-Ab and β2 AdR-Ab are potential markers of ME/CFS.

Aims: The identification and appropriate management of commercial motor vehicle (CMV) drivers with unrecognized obstructive sleep apnea (OSA) is a major public health concern and priority; OSA among drivers has not been fully investigated in Japan, and a better understanding of this undiagnosed disease is warranted. Therefore, we evaluated the prevalence of OSA and the factors related to apnea–hypopnea index (AHI) in Japanese CMV drivers. Methods: This retrospective study included 1309 Japanese CMV drivers aged 40–69 years. All the subjects received type IV portable sleep monitors (PMs) with Epworth Sleepiness Scale (ESS) and a periodic health check including anthropometrical and laboratory measurements, and a questionnaire of medical history, smoking status, and life style, following which variables related to AHI were analyzed. Results: Of all the subjects, 23.9% had moderate to severe OSA (AHI ≥ 15). Age, body mass index (BMI), LogeHbA1c and diastolic blood pressure (DBP) showed significance with AHI in 1309 subjects. The following factors were found to have significant odds ratio (OR) for AHI of ≥ 15 in 1309 subjects: age, ESS, DBP, and LogeHbA1c. Conclusion: Notably, drivers with undiagnosed OSA exist. In these subjects, AHI was related to obesity, hypertension, and diabetes. For the early diagnosis and intervention of OSA, BMI, blood pressure, and HbA1c measurements may be helpful, particularly for drivers. Furthermore, when performing an objective assessment of the suspected OSA, evaluating these parameters during routine medical check-ups may be useful and feasible in the detection of drivers with latent OSA.

Background— The existence of an atypical fast-slow (F/S) atrioventricular nodal reentrant tachycardia (AVNRT) including a superior (sup) pathway with slow conductive properties and an atrial exit near the His bundle has not been confirmed. Methods and Results— We studied 6 women and 2 men (age, 74±7 years) with sup-F/S-AVNRT who underwent successful radiofrequency ablation near the His bundle. Programmed ventricular stimulation induced retrograde conduction over a superior SP with an earliest atrial activation near the His bundle, a mean shortest spike-atrial interval of 378±119 milliseconds, and decremental properties in all patients. sup-F/S-AVNRT was characterized by a long-RP interval; a retrograde atrial activation sequence during tachycardia identical to that over a sup-SP during ventricular pacing; ventriculoatrial dissociation during ventricular overdrive pacing of the tachycardia in 5 patients or atrioventricular block occurring during tachycardia in 3 patients, excluding atrioventricular reentrant tachycardia; termination of the tachycardia by ATP; and a V-A-V activation sequence immediately after ventricular induction or entrainment of the tachycardia, including dual atrial responses in 2 patients. Elimination or modification of retrograde conduction over the sup-SP by ablation near the right perinodal region or from the noncoronary cusp of Valsalva eliminated and confirmed the diagnosis of AVNRT in 4 patients each. Conclusions— sup-F/S-AVNRT is a distinct supraventricular tachycardia, incorporating an SP located above the Koch triangle as the retrograde limb, that can be eliminated by radiofrequency ablation.

Summary Purpose: Zinc is released in synaptic vesicles with glutamate, and modulates glutamatergic neurotransmission. In brain, the highest amount of zinc, detected by Timm staining, is in the mossy fiber (MF) system in the hippocampus. In the intrahippocampal kainate (KA) mouse model of mesial temporal lobe epilepsy, which is elicited by intrahippocampal KA, prominent MF sprouting develops rapidly within 2 weeks post-KA. However, the intensity of Timm staining is reduced gradually thereafter. The present study is designed to determine the mechanisms underlying this reduction of Timm staining. Methods: The changes in Timm staining, and VGluT1, Synapsin-1, and zinc transporter 3 (ZnT3) immunoreactivity (IR) were examined from 4–56 days post-KA. An analysis of glutamate release in the KA-injected hippocampus was conducted by microdialysis before and during the continuous injection of midazolam (MDZ). Results: At 56 days post-KA, Timm staining disappeared completely, whereas VGluT-1-, Synapsin-1-, and ZnT3-IR were increased in the sprouted MF boutons. However, when the seizures were suppressed by a continuous perfusion of MDZ, the glutamate release in the hippocampus decreased and Timm staining was recovered. Discussion: This study showed that the reduction of Timm staining is the result of decreased zinc content but not the loss of MF itself. The reduction is the result of the enhanced release of zinc relative to storage, and it should facilitate the glutamate excitation that might be related to the epileptogenesis and rapid advancement of the morphologic changes in this model.

症例は68歳，女性．40歳時より慢性関節リウマチ（rheumatoid arthritis:以下RA）に対し治療を行っていた．腹痛を主訴に来院し，穿孔性腹膜炎の診断で緊急手術を施行した．回腸末端より10cmの小腸に直径5mmの穿孔を認め，周囲に暗赤色に虚血性変化を示す領域が多発しており，同部を含む回盲部切除術を施行した．切除小腸粘膜には多発性の潰瘍を認め，一部に穿孔が認められた．病理組織学的に，粘膜下の血管壁に広範囲にアミロイドの沈着を認め，アミロイドA蛋白と同定され，RAに続発したアミロイドーシスによる穿孔と診断した．術後は完全静脈栄養管理や消化態経腸栄養剤投与などを用いた全身管理を行い救命し，軽快退院した．消化管アミロイドーシスで穿孔をきたすことは稀であり，その予後は極めて悪い．RAに続発したアミロイドーシスによる小腸穿孔の1救命例を経験したので報告する．

International audience; PURPOSE: Granule cell dispersion (GCD) appears as a characteristic morphological feature of the mesial temporal lobe epilepsy (MTLE). It has been suggested that this phenomenon could be due to an increased neurogenesis in the dentate gyrus. However, this hypothesis is still debated and recent clinical and experimental studies have shown that neurogenesis is rather decreased in MTLE. To further determine the role of neural and astroglial cell generation in GCD we examined the consequences of aging and irradiation, which are known to reduce progenitor cells, in a mouse model of MTLE induced by intrahippocampal kainate (KA) injection. METHODS: We injected KA in hippocampus of three different types of mice; (1) young adult, (2) aged, and (3) irradiated mice. Newly generated cells were labeled by Bromodeoxyuridine (BrdU) and were characterized by immunohistochemistry. The extent of GCD was compared among the three animal groups. RESULTS: In young adult mice, BrdU-labeled neurons as well as doublecortin- and NeuroD-positive cells decreased progressively after KA injection whereas BrdU-labeled astrocytes and microglias increased. In aged and irradiated mice, where basal neurogenesis was already strongly reduced, GCD developed after KA injection to the same extent as in young adult mice. However, augmentation of the BrdU-labeled astrocytes after KA was less than 40% in irradiated mice in comparison to young and aged mice. CONCLUSIONS: Our data show that GCD occurs without neurogenesis. Furthermore GCD developed regardless of the degree of astroglial cell proliferation, suggesting that neural stem cell generation is not crucial for GCD.

A 74-year-old man presented with palpitation and 12-lead ECG exhibited atrial premature contraction (APC) at general check-up. Holter ECG demonstrated narrow QRS tachycardia with a rate of 160/min and more than 31,000/day atrial premature beats. The P wave morphology of atrial premature beats showed negative in II, III, aVF and biphasic in V1. Venography was performed and disclosed persistent left superior vena cava (LSVC) draining into the right atrium via the markedly dilated coronary sinus (CS). Electrogram recordings from LSVC and CS were obtained with an electrode catheter via the left subclavian vein. At the level where a ventricular potential disappeared, the intra-LSVC potentials began to show a discrete second sharp potential after local left atrial signals. Double potentials were obtained within the LSVC from the lower left atrium (LA) to the higher LA. A proximal-to-distal activation sequence of the second components was observed. The interval between the 1st and 2nd component ranged from 8 to 22 msec between the proximal LSVC and distal LSVC. The double potentials resulted in fusion at the lower part of the LSVC, indicating the presence of an electrical connection between the LSVC and lower LA.

目的: 流出3路起源心室頻拍 (VOT-VT) のリエントリー回路の同定, 方法と結果: 非虚血性心疾患症例 (男性3例, 女性1例) に合併したリエントリー性VOT-VTを対象.心臓電気生理学検査時, 誘発されたVOT-VT (n=5) 持続中に大動脈バルサルバ洞および心室流出路領域においてエントレインメントマッピング (EM) 施行後, カテーテルアブレーションを行った.カテーテルアブレーション成功部位 (n=5) では, 頻拍中postpacing間隔は頻拍周期と一致, あるいは刺激-QRS間隔は電位-QRS間隔と一致し, すべての成功部位はリエントリー回路上であることが示唆された, EM法によりカテーテルアブレーション成功部位を同定した, リエントリー回路出口 (exit) (n=4) は右大動脈バルサルバ洞, 大動脈弁下部, 左室流出路そして右室流出路に, 必須緩徐伝導路 (central-proximal) (n=1) は右大動脈バルサルバ洞に同定された, 総括: リエントリー性VOT-VTはEM法によりリエントリー回路出口 (exit) および必須緩徐伝導路 (central-proximal) が同定され, カテーテルアブレーション成功部位は, 大動脈バルサルバ洞および心室流出路に存在した.

We studied the modes of initiation of two types of atria] reentrant tachycardias (i.e., microreentry isthmus tachycardia and counterclockwise atrial flutter) in a 39-year-old male with typical atrial flutter. Rapid atrial pacing from proximal coronary sinus at a cycle length of 220 msec initiated micro-reentry isthmus tachycardia (non-sustained), while rapid atrial pacing at a cycle length of 210 msec initiated sustained atrial flutter circulating counterclockwise around the tricuspid annulus. It was suggested that initiation of the counterclockwise atrial flutter was associated with a pacing-induced conduction block in the entire width of the isthmus, whereas initiation of the micro-reentry isthmus tachycardia was associated with a pacing-induced conduction block in a limited segment of the isthmus (i.e., partial isthmus block).

We proposed [11C]KF18446 as a selective radioligand for mapping the adenosine A2A receptors being highly enriched in the striatum by positron emission tomography (PET). In the present study, we investigated whether [11C]KF18446 PET can detect the change in the striatal adenosine A2A receptors in the rat after unilateral injection of an excitotoxin quinolinic acid into the striatum, a Huntington's disease model, to demonstrate the usefulness of [11C]KF18446. The extent of the striatal lesion was identified based on MRI, to which the PET was co-registered. The binding potential of [11C]KF18446 significantly decreased in the quinolinic acid-lesioned striatum. The decrease was comparable to the decrease in the potential of [11C]raclopride binding to dopamine D2 receptors in the lesioned striatum, but seemed to be larger than the decrease in the potential of [11C]SCH 23390 binding to dopamine D1 receptors. Ex vivo and in vitro autoradiography validated the PET signals. We concluded that [11C]KF18446 PET can detect change in the adenosine A2A receptors in the rat model, and will provide a new diagnostic tool for characterizing post-synaptic striatopallidal neurons in the stratum.

We evaluated the potential of [ 11 C]MPDX as a radioligand for mapping adenosine A 1 receptors in comparison with previously proposed [ 11 C]KF15372 in cat brain by PET. Two tracers showed the same brain distribution. Brain uptake of [ 11 C]MPDX (Ki = 4.2 nM) was much higher and washed out faster than that of [ 11 C]KF15372 (Ki = 3.0 nM), and was blocked by carrier-loading or displaced with an A 1 antagonist. The regional A 1 receptor distribution evaluated with kinetic analysis is consistent with that previously measured in vitro. [ 11 C]MPDX PET has a potential for mapping adenosine A 1 receptors in brain.

A large-scale screening involving the measurement of N-ERC/mesothelin levels in blood using an ELISA system for the early diagnosis of malignant mesothelioma (MM) was carried out in individuals with a history of employment at construction sites. Approximately 30,000 subjects were screened. Of the 80 subjects with high-risk values, one male patient was diagnosed as having MM based on a PET study and histopathology. This is the first report of the pre-clinical diagnosis of MM based on blood test screening. In addition, plasma levels of N-ERC/mesothelin may be effectively used for monitoring relapse after surgery.

An 81-year-old man with long RP narrow QRS tachycardia underwent catheter ablation. Ventricular pacing reset the atrial cycle over a retrograde slow pathway, followed by termination of the tachycardia without atrial capture, confirming the diagnosis of fast-slow atrioventricular nodal reentrant tachycardia (AVNRT). The earliest atrial activation during tachycardia was found in the noncoronary sinus of Valsalva, where the first delivery of radiofrequency energy terminated and eliminated the inducibility of the tachycardia, by retrograde conduction block over the slow pathway. This is the first report of a fast-slow AVNRT, with successful ablation of the slow pathway from a noncoronary sinus of Valsalva.

Purpose: To study the changes in the distribution of postsynaptic benzodiazepine (BDZ) and presynaptic adenosine A 1 (AA 1 ) receptors in the superior colliculus (SC) and visual cortex (VC) of rats following monocular enucleation. Methods: The right eyes of 6-week-old Long-Evans rats were enucleated and ex vivo autoradiography was performed on the SC and VC obtained at different times up to 8 weeks after the enucleation. [ 14 C]deoxyglucose was used to detect glucose metabolism, and [ 11 C]flumazenil and [1-methyl- 11 C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine ([ 11 C]MPDX) were used to map BDZ and AA 1 receptors, respectively. The receptor-specific binding for 11 C was determined, and 11 C and 14 C activities were evaluated separately in the same tissue by a double tracing method. Results: The uptake of [ 14 C]deoxyglucose in the SC was depressed immediately after enucleation and gradually recovered. The binding of [ 11 C]flumazenil to BDZ receptors in the contralateral SC was increased at week 2, and then returned to the pre-enucleation levels. The uptake of [ 11 C]MPDX by the AA 1 receptors in the contralateral SC decreased by about 67% on day 5 after enucleation and remained low thereafter. In the contralateral VC, the uptake of [ 14 C]deoxyglucose decreased immediately after the enucleation followed by a gradual recovery, whereas the uptake of [ 11 C]flumazenil and [ 11 C]MPDX was not altered. Conclusions: The axon degeneration related decrease of the AA 1 receptor density resulted in a transient up-regulation of postsynaptic BDZ receptor density in monocularly enucleated adult rats. These results suggest that these radioligands can be used to study the distribution of the postsynaptic BDZ and presynaptic AA 1 receptors in the visual system and can probably be applied to the human visual system for positron emission tomography.

Intrahippocampal injection of a subtoxic dose of kainate in mice has been shown to induce a dispersion of granule cells of the dentate gyrus, which is a characteristic morphological change often seen in human hippocampal sclerosis. In addition, it has been shown recently that such injections lead to recurrent hippocampal seizures and changes in glucose metabolism, which are reminiscent of temporal lobe epilepsy. Previous reports on human hippocampal sclerosis have shown an increase of the expression of the GluR2 α-amino-3-hydroxy-5-methylisoxazole-4-propionate subunits in the dispersed granule cell somata. However, no such changes have been observed so far in animal models of epilepsy with hippocampal sclerosis. In this study, the expression of α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor subunits was examined by immunohistochemistry following intrahippocampal injection of kainate in mice and rats. In mice, such injection induced a persistent increase of GluR2 immunoreactivity in the granule cells for up to 180 days. By contrast, GluR1 immunoreactivity was transiently increased during the first four days after the injection and progressively decreased thereafter. By contrast, intrahippocampal injection of kainate in rats did not result in granule cell dispersion and no changes in GluR1 immunoreactivity or GluR2 immunoreactivity were observed. These results show that, in addition to morphological, clinical and metabolical similarities, intrahippocampal injection of kainate results in a persistent increase of GluR2 associated with granule cell dispersion, as in human hippocampal sclerosis. These data suggest the existence of common mechanisms between granule cell dispersion and regulation of GluR2 subunits associated with hippocampal sclerosis.

We demonstrated the distribution of adenosine A1 receptors in the anesthetized monkey brain with positron emission tomography (PET) using [(11)C]KF15372 ([1-propyl-(11)C]8-dicyclopropylmethyl-1, 3-dipropylxanthine). [(11)C]KF15372 was injected intravenously. The regional standardized uptake values and the distribution volume were calculated. We also investigated the effect of carrier on the uptake and regional brain distribution of [(11)C]KF15372. The use of [(11)C]KF15372 with dynamic PET scanning could be an appropriate method to analyze the regional binding potential of adenosine A1 receptors in living brain.

A case of atypical AV nodal reentrant tachycardia (AVNRT) with eccentric retrograde left-sided activation, masquerading as tachycardia using a left-sided accessory pathway, is reported. Initially, it appeared that the tachycardia was a typical slow-fast form of AVNRT. The earliest retrograde activation, however, was registered at a site approximately 3 cm from the coronary sinus orifice (left atrial free wall), indicating atypical AVNRT. Atrial tachycardia and orthodromic AV reciprocating tachycardia using an accessory AV pathway were excluded. Slow pathway ablation at the posteroseptal right atrium eliminated the tachycardia. It was suggested that the anterograde limb of the tachycardia circuit was a slow AV nodal pathway with typical posteroseptal location, whereas the retrograde limb was a long atrionodal pathway connecting the compact AV node and the left atrial free wall near the mid-coronary sinus.

本研究の目的は, イヌ心臓に誘発される房室結節エコー (AV Nodal echo=AVNe) に関する電気生理学的所見およびAVNeに対する右房前中隔fast pathwayアブレーション効果より, イヌAVNeの旋回回路の電気生理学的および解剖学的多様性の有無, ヒトAVNRTとの関連性について検討を加えることである.【方法】麻酔開胸犬16頭において, 針電極を右心耳, 冠状静脈洞開口部付近 (CSos) , 右心室基部に刺入した.また大腿静脈より挿入した電極カテーテルをヒス東電位記録部位 (HBE) に留置した.洞房結節挫滅後, 心室プログラム刺激を実施し, AVNeの誘発の有無を検討した.この際AVNe出現時の心房exit部位よりAVNeの分類をした.続いて前方exit (=fast AVnodal pathway) のアブレーションのため, 右房前中隔部の心外膜側で, 大きな心房電位と小さく鋭いヒス東電位が記録される部位に電極力テーテルを留置し, 高周波通電を行った.再度心室刺激を実施し, アブレーションのAVNeに対する効果について検討を加えた.【結果】室房伝導は全16頭に存在した, 高周波通電により∬～皿度房室ブロックが誘発された3頭を除く13頭において, PR間隔は有意に延長し (115±13msec: 115±16msec, p

Para-Hisian pacing, a useful method to differentiate conduction over an accessory pathway from conduction over the AV node, is assessed essentially by comparing the timing of local atrial electrograms between His-bundle captured beats and His-bundle noncaptured beats. We describe the case of a patient with a permanent form of junctional reciprocating tachycardia, in whom an atrial double potential was recorded only during the tachycardia at the right posterior septum. During para-Hisian pacing, a morphologic change in the atrial electrogram at the posterior septum was also identified, as well as a change in the retrograde atrial sequence. Since the morphologic change of atrial electrograms during para-Hisian pacing cannot be demonstrated in a patient without an accessory pathway, this new finding could be considered a new additional diagnostic criterion suggesting the presence of an accessory pathway.

Objective To identify target sites for radiofrequency ablation of ventricular tachycardia (VT) by entrainment mapping techniques in patients with arrhythmogenic right ventricular dysplasia. Methods Entrainment mapping and radiofrequency ablation of eight VTs was performed in seven patients. Radiofrequency ablation was applied at 31 reentry circuits sites that were classified based on findings during entrainment. Results By entrainment criteria the 31 sites were classified as: exit sites (n = 12), proximal sites (n = 6), and outer loop sites (n = 13). Radiofrequency current application terminated VT at 7 of 31 sites: 2 of 12 exit sites (17%), 4 of 6 proximal sites (67%), and 1 of 13 outer loop sites (8%). Conclusion Radiofrequency ablation terminated VTs most often at sites proximal to the exit as opposed to outer loop sites and exit sites (P = 0.05). The critical isthmus for ablation of VT in right ventricular dysplasia often may be distant to the exit.

During the past decade, many neuroreceptors in humans and other animals have been visualized in vivo by positron emission tomography (PET) with corresponding radioligands. Because adenosine is a neuromodulator, PET assessment of the adenosine receptor system offers Is an opportunity to understand the neurotransmission system in general. The 11 C-labeled selective adenosine A 1 antagonists KF15372 ([3-propyl- 11 C]8-dicyclopropylmethyl-1, 3-dipropylxanthine) and a 11 C-methyl derivative [ 11 C]KF26345 and selective adenosine A 2A antagonist KF17837 ([7-methyl- 11 -(E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine) and KF18446 ([7-methyl- 11 C]-(E)-8-3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine were evaluated in vivo as potential PET ligands for mapping CNS adenosine A 1 and A 2A receptors. [ 11 C]KF15372 and [ 11 C]KF263345: Tissue sampling and ex vivo autoradiography (ARC) suggest that the regional brain distribution of [ 11 C]KF15372 and [ 11 C]KF26345 is consistent with that of the adenosine A 1 receptors found in mice and rats. The brain uptake was competitively reduced by the coadministration of A 1 , but not by A 2A antagonists. The ex vivo ARG on the rat model with unilateral orbital enucleation, visualized the A 1 receptor deficiency in the presynaptic terminals. PET with these ligands visualized the A 1 receptors in the monkey and cat brain. [ 11 C]KF17837 and [ 11 C]KF18446: In mice, a high uptake of two ligands was found in the striatum in which A 2A receptors are highly enriched. The uptake was decreased by coinjection of carrier KF17837 or other xanthine-type A 2A antagonists, but not by four nonxanthine-type A 2A antagonists or A 1 antagonists. In the rat brain, ex vivo ARG showed the A 2A receptor-specific uptake of two ligands in the striatum. In PET studies of the monkey and cat brain, the A 2A receptors in the striatum was clearly visualized. These pieces of evidence demonstrated the potential of 11 C-labeled selective xanthine-type adenosine antagonists as PET ligands for mapping CNS adenosine A 1 and A 2A receptors.

Introduction: Rapid atrial pacing in sinus rhythm may directly induce atrial flutter without provoking intervening atrial fibrillation, or initiate atrial flutter indirectly, by a conversion from an episode of transient atrial fibrillation provoked by rapid atrial pacing. The present study was performed to examine whether or not the direct induction of clockwise or counterclockwise atrial flutter was pacing-site (right or left atrium) dependent. Methods and Results: We analyzed the mode of direct induction of atrial flutter by rapid atrial pacing. In 46 patients with a history of atrial flutter, rapid atrial pacing with 3 to 20 stimuli (cycle length=500 − 170 ms) was performed in sinus rhythm to induce atrial flutter from 3 atrial sites, including the high right atrium, the low lateral right atrium, and the proximal coronary sinus, while recording multiple intracardiac electrograms of the atria. Direct induction of atrial flutter by rapid atrial pacing was a rare phenomenon and was documented only 22 times in 15 patients: 3, 11, and 8 times during stimulation, respectively, from the high right atrium, low lateral right atrium, and the proximal coronary sinus. Counterclockwise atrial flutter (12 times) was more frequently induced with stimulation from the proximal coronary sinus than from the low lateral right atrium (8 vs 1, P = .0001); clockwise atrial flutter (10 times) was induced exclusively from the low lateral right atrium ( P = .0001 for low lateral right atrium vs proximal coronary sinus, P = .011 for low lateral right atrium vs high right atrium). Conclusions: Direct induction of either counterclockwise or clockwise atrial flutter was definitively pacing-site dependent; low lateral right atrial pacing induced clockwise, while proximal coronary sinus pacing induced counterclockwise atrial flutter. Anatomic correlation between the flutter circuit and the atrial pacing site may play an important role in the inducibility of counterclockwise or clockwise atrial flutter.

The typical fourth criterion for transient entrainment is defined when both a sudden shortening in conduction interval to and a distinct change in electrogram morphology at a bipolar recording site are demonstrated while performing overdrive pacing of a reentrant tachycardia from a single pacing site at two different constant rates. The purpose of this article was to test the hypothesis that if an intracardiac recording site showing both orthodromic and antidromic capture with entrainment pacing is located suitably distant from the circuit, sudden shortening in conduction interval to that site may occur without any significant change in the bipolar electrogram morphology (i.e., atypical form of the fourth criterion). Atrial overdrive pacing of orthodromic tachycardia was performed in 20 patients with either left anterior (12 patients) or left posterior (8 patients) accessory pathways. We investigated the effects of overdrive pacing from the proximal or distal coronary sinus, specifically effects on the electrogram interval and the electrogram morphology at the right atrial appendage. Overdrive pacing of orthodromic tachycardia from the proximal coronary sinus was performed in 10 of the 12 patients with left anterior accessory pathways; those 10 patients demonstrated the first entrainment criterion at the right atrial appendage site. Overdrive pacing of orthodromic tachycardia at still shorter cycle lengths demonstrated a sudden shortening in conduction interval to the right atrial appendage site. Despite shortening in conduction interval the morphology of the right atrial appendage electrogram was completely or almost identical to that during orthodromic tachycardia, indicating an atypical form of the fourth criterion. This criterion was not demonstrated in patients with left posterior accessory pathways. Thus, atypical fourth entrainment criterion was demonstrated during overdrive pacing of orthodromic tachycardia from the proximal coronary sinus only in patients with left anterior accessory path ways. Demonstration of atypical fourth criterion seems largely dependent on the location of the accessory pathway, the pacing, and the recording sites.

Virchowならびに大動脈周囲リンパ節転移を有した進行S状結腸癌に対して根治度Bの切除術を施行し, 術後6年現在, 無再発生存が得られた症例を経験したので報告する.症例は48歳の女性で, 1991年9月左鎖骨上窩の腫瘍にて来院した. リンパ節生検および注腸検査よりVirchowリンパ節転移を伴った進行S状結腸癌と診断された. 11月8日S状結腸切除ならびにD4郭清を施行した. 病理組織診断は中分化型腺癌, ss, n4 (+), P0, H0, M (+), ow (-), aw (-), ly (3), v (3), stage IVであった. リンパ節転移 (合計16/48) を認め, 特に腹部大動脈周囲には多数の転移 (9/30) が認められた. 術後補助療法として, 5年間UFT600mgの内服を行ったが, 現在術後6年, 無再発生存中である.n4症例の予後は一般的に不良とされているが, 自験例のように積極的な手術および補助療法により予後が改善される症例も認められると思われたので報告した.

胃静脈瘤を合併した特発性門脈圧亢進症の手術前後に肝血行動態を検討し, 術後肝内門脈血流の改善が示唆された症例を経験した.症例は41歳の女性で, 特発性門脈圧亢進症・胃静脈瘤に対してHassab手術を施行した. 術前の血管造影X線検査では脾腫, 脾静脈から門脈本幹の拡張, 肝内末梢門脈の造影不良ならびに側副血行路である臍静脈の開存・拡張がみられたが, 術後は門脈本幹・臍静脈の径は軽減し, 肝内末梢門脈枝の描出が良好となった. 99mTc in-vivo標識赤血球肝動脈門脈血流シンチでの肝右葉/門脈臍部血流比は術前門脈臍部優位であったが, 術後肝右葉優位に逆転した. 術前の123I-IMP経直腸門脈シンチではほとんどの123I-IMPは門脈から大循環へshuntされていたが, 術後はshunt量が低下し, 肝内に集積された.以上よりHassab手術後門脈大循環shunt量の低下および肝内門脈血流の改善が示唆された特発性門脈圧亢進症の1例を経験したので報告する.

We investigated the effects of KF19514 (5-phenyl-3-(3-pyridyl)methyl-3H-imidazo[4,5-c][1,8]naphthyridin-4 (5H)-one) on bronchoconstriction and allergic inflammation in guinea pigs and on tumor necrosis factor-alpha production in mice. KF19514 inhibited phosphodiesterase 4 (IC50 = 0.40 microM) and phosphodiesterase 1 (IC50 = 0.27 microM) derived from canine tracheal smooth muscles. KF19514 relaxed contracted tracheal smooth muscle and had a potent inhibitory effect on antigen-induced bronchoconstriction (EC50 = 0.058 microM) in vitro. Intravenous administration of KF19514 inhibited histamine-induced bronchoconstriction (ID50 = 2.8 microg/kg i.v.). Moreover, oral administration of KF19514 inhibited anaphylactic bronchoconstriction (ID50 = 0.2 mg/kg p.o.), and eosinophil infiltration in airway stimulated with platelet-activating factor (PAF) or antigen. KF19514 also produced a significant inhibition of tumor necrosis factor-alpha production in mice (ID50 = 0.023 mg/kg p.o.). Finally, KF19514 completely inhibited antigen-induced hyperreactivity at 0.1 mg/kg p.o. These results demonstrate that KF19514 may have efficacy in the treatment of asthma.

A 6-hr continuous infusion of 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenos ine (CGS21680), a selective A2a-adenosine agonist, into the subarachnoid space underlying the ventral surface region of the rostral basal forebrain, which has been defined as the prostaglandin (PG) D2-sensitive sleep-promoting zone, at rates of 0.02, 0.2, 2.0, and 12 pmol/min increased slow-wave sleep (SWS) and paradoxical sleep (PS) in a dose-dependent manner up to 183% and 202% of their respective baseline levels. The increments produced by the infusion of CGS21680 at 0.2 and 2.0 pmol/min were totally diminished when the rats had been pretreated with an i.p. injection of (E)-1,3-dipropyl-7-methyl-8-(3,4-dimethoxystyryl)xanthine (KF17837; 30 mg/kg of body weight), a selective A2-adenosine antagonist. In contrast, the infusion of N6-cyclohexyladenosine (CHA), a selective A1-adenosine agonist, at 2 pmol/min significantly suppressed SWS before causing an increase in SWS, and a decrease in PS was also markedly visible. Essentially the same effects of CGS21680 and CHA were observed when these compounds were administered to the parenchymal region of the rostral basal forebrain through chronically implanted microdialysis probes. Thus, we clearly showed that stimulation of A2a-adenosine receptors in the rostral basal forebrain promotes SWS and PS. Furthermore, i.p. injections of KF17837 at 30 and 100 mg/kg of body weight dose-dependently attenuated the magnitude of the SWS increase produced by the infusion of PGD2 into the subarachnoid space of the sleep-promoting zone, thus indicating that the A2a-adenosine receptors are crucial in the sleep-promoting process triggered by PGD2.

An 11C-labeled selective adenosine A2A antagonist, (E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-[11C]-methylxanthine ([11C]KF17837), was prepared by reaction of (E)-8-(3,4-dimethoxystyryl)-1,3-dipropylxanthine and [11C]methyl iodide with decay-corrected radiochemical yield of 19-50%, radiochemical purity of99%, sp. act. of 17-100 GBq/mumol and preparation time of 20-25 min. In mice, the myocardium showed the highest (13.4% ID/g) at 5 min after i.v. injection, which decreased gradually with time. The specific myocardial uptake was visualized by gamma-camera. In the brain region the radioactivity level was higher in the A2A receptors-rich striatum than in the cortex and cerebellum. The specific striatal uptake in rats was clearly demonstrated by PET. These results have shown that [11C]KF17837 is a potential PET radioligand for mapping the adenosine A2A receptors in the heart and brain.

A patient with reentrant ventricular tachycardia exhibited both the orthodromic and antidromic resetting responses at a single intracardiac recording site during programmed extrastimulation of ventricular tachycardia. The transition from orthodromic to antidromic resetting with extrastimulation demonstrated a sudden shortening in conduction interval to an electrogram recording site and unexpected identical morphology of the spontaneous and captured electrograms at that site, indicating atypical antidromic resetting. This newly observed resetting phenomenon with programmed extrastimulation suggests that the fourth entrainment criterion with overdrive pacing may likely be demonstrated in an atypical form; that is, a sudden shortening in conduction interval to an electrogram recording site may occur without any significant change in the bipolar electrogram morphology at that site when overdrive pacing is performed during tachycardia from a single pacing site at two different constant rates.

His-Purkinje系及び副伝導路の逆伝導においていわゆる過常伝導現象が観察された潜在性WPW症候群の1例を報告する.症例は55歳の女性で動悸発作の精査のため入院となった.電気生理学的検査時, 右房, 左房刺激では△波の出現をみなかった.心房頻回刺激法, 心房期外刺激法により通常型房室結節リエントリー性頻拍と右前中隔部位の潜在性Kent束を介する房室リエントリー性頻拍が誘発された.心室期外刺激法の際, 予期せぬ室房伝導時間の短縮現象が観察された.連結期500msec～380msecでは逆行性His束波までの伝導時間 (S2-H2時間) の短縮に伴い室房伝導時間が短縮し, また連結期330msec～320msecでは, S2-H2'時間は延長していたが室房伝導時間は短縮していた.前者はHis-Purkinje系の逆伝導における過常伝導が, 後者は副伝導路の逆行性過常伝導が推測された.副伝導路の逆行性過常伝導は稀に報告されているが, His-Purkinje系における逆行性過常伝導はいまだ報告がなく, 極めて稀な現象であると考えられた.

PURPOSE The objective of this assessment is to identify prognostic factors of recurrence and disease progression of primary superficial transitional cell carcinoma of the bladder. PATIENTS AND METHODS TUR-Bt was performed in 150 patients with initial superficial bladder cancer, of which pathological diagnosis was pTa or pT1 transitional cell carcinoma. The recurrence and progression free survival was examined. The clinicopathological factors analyzed were as follows: grade, pT, tumor size, tumor number and tumor form. RESULTS Median follow-up period was 39 months (range 3-184). The age distribution was from 25 to 98 years old with the average of 67. The patients were 122 males and 28 females. Recurrence was observed in 72 patients. The 5-year recurrence free rate for all cases were 41.6%. The factors found to be of significance for the prognosis for recurrence were tumor size (1 cm

Evacuated feces after intraperitoneal administration of selective adenosine receptor antagonists were evaluated in rats. The selective adenosine A 1 receptor antagonists, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (100–300 μg/kg i.p.) and ( R )-7,8-dihydro-8-ethyl-2-(3-noradamantyl)-4-propyl-1 H -imidazo[2,1- i ]purin-5(4 H )-one (KF20274) (30–300 μg/kg i.p.), significantly increased defacation, whereas the selective adenosine A 2 receptor antagonist 4-amino-8-chloro-1-phenyl[1,2,4]triazolo[4,3- a ]quinoxaline (CP-66,713) failed to cause a significant increase at up to 10 mg/kg i.p. The defacation caused by DPCPX (100 μg/kg) was markedly alleviated by (2 S )- N 6 -(2- endo -norbornyl)adenosine (( S )-ENBA) (30–300 μg/kg s.c.), a selective adenosine A 1 receptor agonist, but not influenced by 2-[ p -(2-carboxyethyl)phenethylamino]-5′- N -ethylcarboxamidoadenosine (CGS 21680) (30–1000 μg/kg s.c.), a selective adenosine A 2 receptor agonist. These results suggest that endogenous adenosine plays a physiological role in sustained inhibition of defecation via adenosine A 1 receptors.

Objectives. This study attempted to determine the prevalence and electrocardiographic (ECG) lead distribution of T wave “humps” (T2, after an initial T wave peak, T1) among families with long QT syndrome and control subjects.Background. T wave abnormalities have been suggested as another facet of familial long QT syndrome, in addition to prolongation of the rate-corrected QT interval (QTc), that might aid in the diagnosis of affected subjects.Methods. The ECGs from 254 members of 13 families with long QT syndrome (each with two to four generations of affected members) and from 2,948 healthy control subjects (age ≥ 16 years, QTc interval 0.39 to 0.46 s) were collected and analyzed. Tracings from familes with long QT syndrome were read without knowledge of QTc interval or family member status (210 blood relatives and 44 spouses).Results. We found that T2 was present in 53%, 27% and 5% of blood relatives with a “prolonged” (≥ 0.47 s), “borderline” (0.42 to 0.46 s) and “normal” (≤0.41 s) QTc interval, respectively (p < 0.0001), but in only 5% and 0% of spouses with a borderline and normal QTc interval, respectively (p = 0.06 vs. blood relatives). Among blood relatives with T2, the mean [±SD] maximal T1T2 interval was 0.10 ± 0.03 s and correlated with the QTc interval (p < 0.01); a completely distinct U wave was seen in 23%. T2 was confined to leads V2and V3in 10%, whereas V4, V5, V6or a limb lead was involved in 90% of blood relatives with T2. Among blood rotatives with a borderline QTc interval, 50% of those with versus 20% of those without major symptoms manifested T2 in at least one left precordial or limb lead (p = 0.05). A T2 amplitude > 1 mm (grade III) was observed, respectively, in 19%, 6% and 0% of blood relatives with a prolonged, borderline and normal QTc interval with T2 in at least one left precordial or limb lead. Among the 2,948 control subjects, 0.6% exhibited T2 confined to leads V2and V3, and 0.9% had T2 involving one or more left precordial lead (but none of the limb leads). Among 37 asymptomatic adult blood relatives with QTc intervals 0.42 to 0.46 s, T2 was found in left precordial or limb leads in 9 (24%; 5 with limb lead involvement) versus only 1.9% of control subjects with a borderline QTc interval (p < 0.0001).Conclusions. These findings are consistent with the hypothesis that in families with long QT syndrome, T wave humps involving left precordial or (especially) limb leads, even among asymptomatic blood relatives with a borderline QTc interval, suggest the presence of the long QT syndrome trait.

KF17837 is a novel selective adenosine A2A receptor antagonist. Oral administration of KF17837 (2.5, 10.0 and 30.0 mg/kg) significantly ameliorated the cataleptic responses induced by intracerebroventricular administration of an adenosine A2A receptor agonist, CGS 21680 (10 micrograms), in a dose-dependent manner. KF17837 also reduced the catalepsy induced by haloperidol (1 mg/kg i.p.) and by reserpine (5 mg/kg i.p.). These anticataleptic effects were exhibited dose dependently at doses from 0.625 and 2.5 mg/kg p.o., respectively. Moreover, KF17837 (0.625 mg/kg p.o.) potentiated the anticataleptic effects of a subthreshold dose of L-3,4-dihydroxyphenylalanine (L-DOPA; 25 mg/kg i.p.) plus benserazide (6.25 mg/kg i.p.). These results suggested that KF17837 is a centrally active adenosine A2A receptor antagonist and that the dopaminergic function of the nigrostriatal pathway is potentiated by adenosine A2A receptor antagonists. Furthermore, KF17837 may be a useful drug in the treatment of parkinsonism.

In patients with dual atrioventricular (AV) nodal pathways, double ventricular responses to a single atrial depolarization have been shown to occur, but virtually only during a trial pacing in sinus rhythm. We report on a patient with a slow-fast form of AV nodal reentrant tachycardia who exhibited double ventricular responses following extrastimulation during AV nodal reentrant tachycardia. The phenomenon of double ventricular responses during the tachycardia was demonstrated by ex trastimulation from the proximal coronary sinus. Retrograde unidirectional block in the slow pathway, and an anterograde effective refractory period that was shorter in the fast pathway than that in the slow pathway, are suggested.

左上大静脈遺残, 心房中隔欠損症および肺静脈還流異常と診断された52歳の女性に, 動悸の精査を目的として心臓電気生理学的検査を施行したところ, 機序の異なる2種類のlongRP′頻拍 (SVTI, SVT2) が誘発された.SVT1は基本周期450msecの右室期外刺激法により誘発され, 頻拍周期は370msecで, 最早期心房興奮部位はヒス東電位図上の下位中隔右房であった.室房伝導曲線は減衰伝導を示した.頻拍中右室単一刺激法で, ヒス束の不応期に加えられた刺激が心房を捕捉したことにより, 前中隔部位に存在する減衰伝導性の“slowKent”束を経由する房室リエントリー性頻拍 (AVRT) と診断した.SVT2は右房連続刺激法により誘発され, 頻拍周期340mseGで, 最早期心房興奮部位は冠静脈洞入口部近位であった.頻拍中右室単一刺激はすべての連結期で頻拍をリセットしなかった.本例は二重房室結節伝導路を示し, SVT2の機序として稀有型房室結節リエントリー性頻拍が強く示唆されたが, 後中隔部位の“slowKent”束を介するAVRTの可能性は完全には否定し得なかった.

To determine the optimal temperature for catheter heat mapping without damaging cardiac tissue, we studied the electrophysiologic and histologic responses of the atrioventricular (AV) conduction system exposed to a specific range of temperatures. In 18 closed-chest dogs, an electrode catheter with a thermistor, tip was positioned transvenously at the AV junction. Radiofrequency current (RFC) was applied in incremental temperature steps until transient 2nd-degree AV block was induced. Catheter tip temperature (CTT) was measured at each step. RFC was immediately discontinued when AV block occurred. AV conduction was evaluated before and 4 weeks after the procedure. Acute transient 2nd-degree AV block was induced in 45 applications, during which the average CTT was 48.7 +/- 2.7 degrees C. In another 40 applications in which 2nd degree AV block was not induced, the average CTT was significantly lower [46.3 +/- 2.5 degrees C] (p0.001). Eleven of 16 dogs showed acute 2nd-degree AV block, but had normal AV conduction at 4 weeks (Group A). In the other 5 dogs, 1st-degree AV block was seen at 4 weeks (Group B). The lowest CTTs in Groups A and B were 45 and 49 degrees C, respectively. Histologic findings in 2 dogs from Group A revealed that 10-15% (by area) of the AV node was fibrotic. These findings suggest that the induction of fully reversible AV block can be achieved by titration of RFC, during the application of RFC to the AV junction. In conclusion, RF energy was used to produce a tip temperature of between 45 degrees C and 49 degrees C, which induced reversible and significant interruption of conduction of in tissue in the AV junction, and presumably also in target sites in clinical RF ablation.

A series of quinolinecarboxylic acid derivatives has been previously described as a new class of 5-HT3 receptor antagonists due to deviation of a carbonyl moiety from the place of an aromatic ring in their minimum-energy conformations. These derivatives were evaluated in a wrap-restraint stress-induced defecation model in rats. Reference compounds, ondansetron (1), granisetron (2), and YM060 (4), potently inhibited a stress-induced increase in stools excreted from fed rats (ID50 = 0.27, 0.12, and 0.0052 mg/kg, po, respectively). However, quinoline derivatives exhibited different activities depending on structural class. 4-Hydroxyquinoline-3-carboxylic acid derivatives 5 and 6a possess high affinity for the 5-HT3 receptor (Ki = 6.1 and 1.5 nM, respectively) and exhibit potent activity in the Bezold-Jarisch (B-J) reflex test (ED50 = 0.0017 and 0.000 10 mg/kg, i.v., respectively), but they did not effectively inhibit the increase in fecal pellet output at the dose of 1 mg/kg, po. On the other hand, most of 1-substituted 2-oxoquinoline-4-carboxylates 10 showed less potent activity in the B-J reflex test than 1 or 2 but inhibited restraint stress-induced defecation more potently than 1 or 2. The ID50 value of endo-8-methyl-8- azabicyclo[3.2.1]oct-3-yl 1-isobutyl-2-oxo-1,2-dihydro-4- quinolinecarboxylate 10e was 0.013 mg/kg, po. With respect to the selected compounds 6a and 10e, effects of 5-HT- and thyrotropin-releasing hormone (TRH)-induced defecation, castor oil-induced diarrhea and wrap-restraint stress-induced colonic propulsion in rats were examined. These 5-HT3 receptor antagonists did not effectively inhibit castor oil-induced diarrhea, which has been reported not to be mediated via the 5-HT3 receptor. Although 10e showed 800-fold decreased potency compared with 4 in the B-J reflex test, 10e exhibited activity as potent as 4 in 5-HT- and TRH-induced defecation assays; 10e exhibited 7-fold increased potency compared with 4 in wrap-restraint stress-induced colonic propulsions. From these results, 10e appears to interact selectively with 5-HT3 receptors in the gastrointestinal system and might be effective in the therapy of irritable bowel syndrome (IBS).

Adenosine A2a receptors have been localized to GABAergic striatopallidal neurons, but their functional role is unknown. To address this question, the modulation of endogenous GABA release by adenosine A2a receptors was examined in slices of rat globus pallidus. The selective adenosine A2a receptor agonist CGS-21680 (3.0-10 nM) significantly increased electrically stimulated release (overflow) of GABA, with 10 nM CGS-21680 resulting in a 44% increase compared with the control. Both the nonselective adenosine receptor antagonist 8-phenyltheophylline (10 microM) and the selective A2a receptor antagonist KF-17837 (100 nM) abolished the CGS-21680-induced increase in GABA overflow. Higher concentrations of CGS-21680 (0.10-1.0 microM) decreased GABA overflow by approximately 25%. 8-Phenyltheophylline (10 microM) antagonized these effects, whereas KF-17837 (100 nM) did not, suggesting actions of CGS-21680 on other adenosine receptors at these concentrations. These results demonstrate that activation of adenosine A2a receptors augments electrically stimulated release of GABA from globus pallidus slices and suggest a mechanism by which adenosine may modulate GABAergic output from the striatopallidal efferent system.

Although the anterior and posterior boundaries of cavotricuspid isthmus-dependent atrial flutter (AFL) are reported to be located at the tricuspid annulus and sinus venosa region or crista terminalis, the exact upper turnaround point of the AFL circuit remains unclear. The aim of this study was to determine the upper turnaround site of the AFL circuit by means of three-dimensional (3D) mapping and entrainment pacing.Subjects were 21 patients with counter-clockwise AFL in whom high-density mapping of the high right atrium (RA) and superior vena cava (SVC) orifice was performed with an electroanatomical or non-contact mapping system. Entrainment pacing was performed around the SVC-RA junction.In 20 of the 21 patients, the wavefront from the septal RA split into two wavefronts: one that traveled anterior to the SVC and another that traveled to the posterior RA where it was blocked. In the remaining patient, the wavefront from the septal RA split into two wavefronts: one that propagated through the anterior portion of the SVC orifice and another that propagated transversely across the posterior portion of the SVC orifice. The two wavefronts joined in the lateral RA. Entrainment pacing from the SVC-RA junction demonstrated that the anterior boundary was within the circuit in all patients, but the posterior boundary also constituted a circuit in four patients.We surmise that the upper turnaround site of the AFL circuit is located in the anterior portion of the SVC-RA junction in the majority of patients with AFL.