Effect of FK506 on the activation state of hepatic macrophages in Propionibacterium acnes-treated rats

Activated hepatic macrophages can provoke massive liver necrosis following endotoxin stimulation through microcirculatory disturbances due to sinusoidal fibrin deposition in rats pretreated with heat-killed Propionibacterium acnes. In these rats, FK506 (tachlorinus) administered 24 h before and at the time of endotoxin injection, significantly attenuated liver injury compared with the rats given no FK506. The effect of FK506 on hepatic macrophage activation and its action sites were studied in Propionibacterium acnes-treated rats. When rats received Propionibacterium acnes intravenously, hepatic-mRNA expression of interferon-γ-inducing factor and interleukin-2 and splenic-mRNA expression of interferon-γ were significantly increased compared with normal rats. Hepatic-mRNA expression of CD14, a receptor for lipopolysaccharide and its binding protein complex, was also increased preceding the expressions of the three cytokines in the liver and spleen. FK506 administration attenuated hepatic-mRNA expression of interleukin-2 and both superoxide anions as well as tumour necrosis factor-α production by hepatic macrophages, but did not change CD14-mRNA expression in Propionibacterium acnes-treated rats. It is suggested that a cytokine network through interferon-γ-inducing factor, interferon-γ and interleukin-2 may operate during activation of hepatic macrophages in rats treated with heat-killed Propionibacterium acnes, while CD14 expression on the cells may increase independently of this network. FK506 seems to attenuate such activation by suppressing hepatic interleukin-2 expression, without affecting CD14 expression on the cells.     

Optimal Target Site for Slow AV Nodal Pathway Ablation

INTRODUCTION: Although a variety of ablation techniques have been developed in the treatment of atrioventricular nodal reentrant tachycardia (AVNRT), there have been few reports discussing the location of the optimal target site. Based on our early experiences, we hypothesized that radiofrequency (RF) current applied around the upper margin of the coronary sinus ostium (UCSO) results in the most effective and safe treatment of AVNRT. METHODS AND RESULTS: To confirm our hypothesis, the efficacy of RF currents applied around the UCSO guided by local electrograms in 59 patients (group B: predetermined focal mapping approach) were compared with the outcomes in 60 other patients previously treated with the standard electrogram-guided mapping method starting around the lower margin of the coronary sinus ostium (group A). The precise location of ablation catheters at successful sites (S) was also evaluated. All the patients were successfully treated without complications. Significantly fewer RF pulses and lower energies were needed in group B patients (mean RF applications: 4.3 vs 1.4 applications, mean total energy delivered: 4,699 vs 2,236 J in groups A and B, respectively, P < 0.01). Detailed analyses of the anatomical locations of S using CS venography in group B patients who received only a single RF application (46 patients) revealed that the distance between His and S varied according to the length of Koch's triangle, while that between S and UCSO was relatively constant. In 85 % of these 46 patients, S was located within 5 mm above and below the level of the UCSO. CONCLUSION: RF applications around the UCSO guided by local electrograms yielded excellent outcomes in AVNRT patients with wide varieties in the size of Koch's triangle. The optimal target site was located within 5 mm above and below the level of UCSO along the tricuspid annulus.     

Ventricular Late Potential in Patients with Apparently Normal Electrocardiogram; Predictor of Brugada Syndrome

Backgrounds: Brugada syndrome can be overlooked due to its dynamic change in its electrocardiogram (ECG) manifestation. We hypothesized that positive ventricular late potential (VLP) in patients with nonspecific ECG would predict the inducible coved ST elevation (type‐1 Brugada ECG) and the patients at high risk. Methods: Thirty‐four patients of nonspecific ECG without structural heart disease were eligible for this study. All patients were referred for evaluation of syncopal episodes and/or cardiac arrest and/or frequent episodes of ventricular premature contractions. We assessed the correlation between baseline VLP and the alteration to a drug‐induced type‐1 Brugada ECG, and also evaluated the diagnostic accuracy of positive VLP in normal ECG subjects for the appearance of a drug‐induced type‐1 Brugada ECG. Results: Twenty‐one patients presented positive VLP and 13 patients showed negative VLP. Parameters of VLP (fQRSd, RMS₄₀, LAS₄₀) presented significant correlation with the alteration to a type‐1 ECG by pilsicainide. VLP demonstrated high sensitivity and negative predictive value for the prediction of type‐1 Brugada ECG. Furthermore, in their follow‐up, at least two cases of ventricular fibrillation were recognized in 21 of positive VLP patients with apparently normal ECGs. Conclusions: VLP in apparently normal ECG can predict the alteration to a drug‐induced type‐1 Brugada ECG and unmask the patients at risk. (PACE 2010; 33:266–273)     

Acute Effects of Different Atrial Pacing Sites in Patients with Atrial Fibrillation: Comparison of Single Site and Biatrial Pacing

It has been reported that a trial single site or biatrial pacing can suppress the occurrence of AF. However, its mechanism remains unclear. The study population included 32 patients with AF (n = 20: AF group), or without paroxysmal AF (n = 12: control group). The mechanism and efficacy of atrial pacing were investigated by electrophysiological studies to determine which was more effective for suppressing AF induction; single site pacing of the right atrial appendage (RAA) or distal coronary sinus (CS-d), or biatrial (simultaneous BAA and CS-d) pacing. In the AF group, AF inducibility was significantly higher with BAA extrastimulus during RAA (12/20; P < 0.0001) or biatrial paced drive (7/20; P < 0.01) than during CS-d paced drive (0/20). In the control group, AF was not induced at any site paced. In the AF group, the conduction delay and other parameters of atrial vulnerability significantly improved during CS-d paced drive. The atrial recovery time (ART) at RAA and CS-d was measured during each basic pacing mode. ART was defined as the sum of the activation time and refractory period, and the difference between ARTs at RAA and CS-d was calculated as the ART difference (ARTD). The ARTD was significantly longer during BAA pacing in the AF group than in control group (155.0 +/- 32.8 vs 128.8 +/- 32.9 ms, P < 0.05). In the AFgroup, ARTDs during biatrial (52.0 +/- 24.2 ms) and CS-d pacing (51.7 +/- 26.0 ms) were significantly shorter than ARTD during RAA pacing. The CS-d paced drive was more effective for suppressing AF induction than biatrial or RAA paced drive by alleviating conduction delay. CS-d and biatrial pacing significantly reduced ARTD compared with RAA pacing.     

A negative component on event related potential recorded in the drowsy state

Abstract Behavior of event related potential (ERP) components in the drowsy state was examined in nine subjects using oddball paradigm. A component with peak latency of 300 msec, N300, was superimposed on ERP in the drowsy state. N300 appeared also in stage 1 of NREM sleep and closely resembled vertex sharp wave evoked by sound stimulation in both scalp distribution and peak latency. It was suggested that N300 recorded in the drowsy state and vertex sharp wave recorded in stage 1 of NREM sleep are generated by the identical synchronizing mechanism in the brain.     

Bladder cancer discovered by ovarian metastasis: Cytokeratin expression is useful when making differential diagnosis

A 49-year-old woman underwent hysterectomy and bilateral adnexectomy after the diagnosis of a right ovarian tumor with paraaortic and pelvic lymph node metastases. The pathological diagnosis was undifferentiated carcinoma of the ovary. After the operation, a bladder tumor was discovered during the evaluation for microscopic hematuria. The bladder tumor was pathologically diagnosed as transitional cell carcinoma, pT1b, G3. Although the pathological findings of the bladder cancer and ovarian cancer were very similar, we could diagnose primary bladder cancer with ovary and lymph node metastases according to the immunohistochemical staining pattern of cytokeratins 7 and 20. Herein, the clinical usefulness of immunohistochemical staining using cytokeratins for making a differential diagnosis of the origin of a tumor in the pelvic cavity is demonstrated.     

Asthenozoospermia: Possible association with long-term exposure to an anti-epileptic drug of carbamazepine

Little attention has been paid to infertility in men with epilepsy and little information exists about the mechanisms by which anti-epileptic drugs affect spermatogenesis or sperm function. We report a case of a male infertility patient with asthenozoospermia during long-term treatment with anti-epileptic drugs. A 29-year-old man had continued treatment with anti-epileptic drugs under the diagnosis of epilepsy for 13 years. He and his wife had been examined and treated as an infertile couple for 3 years. The patient was found to have no motile sperm with a normal sperm count, while taking a dose of 400 mg/day of carbamazepine. On suspicion of an adverse effect of carbamazepine, he was switched to phenytoin monotherapy. One month after that, sperm motility was vastly improved (65%) and they conceived a child 5 months after that. One must be cautious in extrapolating from a case report, but these findings strongly suggest a direct effect of carbamazepine on spermatic function.