CYP3A4＊1G基因多态性与比索洛尔药动学关系的研究

目的：研究C Y P3A4＊1G基因多态性对健康志愿者体内比索洛尔药动学的影响。方法：采用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）方法分析CYP3A4＊1G基因型。24名健康志愿者分为CC、CT、TT三组;受试者单剂量口服5mg富马酸比索洛尔片后,采用高效液相色谱法测定血药浓度,用3P97程序的一房室模型作药动学参数估算。结果：CC、CT、TT三种基因型受试者之间主要药动学参数t1/2,Cmax及AUC0-32分别为（7.79±1.57）、（7.49±0.77）、（7.88±1.21）h;（37.23±4.00）、（38.33±8.94）、（39.51±6.55）μ g/L;（386.42±91.49）,（375.53±84.51）,（406.24±87.24）μ g·h/L,通过t检验,三种基因型受试者之间的主要药动学参数差异没有显著性（P〉0.05）。结论：比索洛尔药动学在个体间的差异与CYP3A4＊1G基因型没有相关性。     

Catheter Ablation of Atrial Fibrillation in Patients With Valvular Heart Disease: Long‐Term Follow‐Up Results

AF Ablation in Patients With Valvular Heart Disease . Background: The purpose of this study is to evaluate the efficacy of atrial fibrillation (AF) ablation in patients with moderate valvular heart disease (VHD). Methods: In total, 534 consecutive patients who underwent AF ablation were enrolled. Patients with a history of valve surgery or other structural heart disease were excluded. Patients with clinically moderate VHD (group‐1, n = 45) were compared with those without VHD (control group‐2, n = 436). Ipsilateral pulmonary vein antrum isolation (PVAI) was performed with a double Lasso technique in all the patients. Left atrial (LA) linear ablation was undertaken in persistent AF patients, if AF was inducible after PVAI. Results: Patients in group‐1 were significantly older and had a larger LA. PVAI was successfully achieved in all the patients. Patients in group‐1 received LA linear ablation more frequently during the index procedure. After a median of 26 months from the index procedure, the freedom from AF was significantly lower in group‐1 than group‐2 off antiarrhythmic drugs (AADs) (47% vs 69%, P = 0.002). Although there were more number of total procedures in group‐1 than group‐2, the freedom from AF was lower at median 24 months after the last procedure (78% vs 87%, P = 0.038). There was no significant difference in the freedom from AF on AADs (91% vs 95%, P = 0.356) or complication rate between the 2 groups. Atrial tachycardia following the index procedure was observed more frequently in group‐1 (P = 0.001). Conclusion: The patients with VHD undergoing AF ablation are less likely to remain in sinus rhythm at long term without AADs than those without VHD. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1193‐1198, November 2010)     

A case of West syndrome with atypical massive gray matter heterotopia that is well controlled by ACTH therapy

A 4 month old female infant with atypical asymmetrical massive gray matter heterotopia diagnosed as West syndrome is described. Her seizure initially appeared as afebrile general tonic and clonic convulsion and progressed to typical West syndrome consisting of clusters of myoclonic spasms of the extremities, mainly on the left side, accompanied by head and eye deviation to the right side. Electroencephalogram (EEG) presented typical hypsarrhythmia and cranial computerized tomography (CT) and magnetic resonance imaging (MRI) showed massive heterotopic gray matter in the right hemisphere with the same density or intensity as cortical gray matter. Single photon emission computed tomography (SPECT), using N-isopropyl-p-¹²³I-iodoamphetamine (¹²³I-IMP), demonstrated decreased blood flow in the ectopic lesion. Although clinical response to several anti-epileptic drugs was poor, her seizures were well controlled by relatively low dose adrenocorticotropic hormone (ACTH) therapy of 0.015 mg/kg per day followed by a combination of valproic acid and clonazepam.     

Health-related quality of life after radical prostatectomy in Japanese men with localized prostate cancer

PURPOSE: We evaluated retrospectively health-related quality of life (HRQOL) after radical prostatectomy (RP) in Japanese men with localized prostate cancer. METHODS: The study was based on self-reported HRQOL of 280 patients. Patients were divided into seven groups: time 0 (T0), baseline before operation; T1, 1-3 months after RP; T2, 4-6 months after RP; T3, 7-12 months after RP; T4, 13-24 months after RP; T5, 25-36 months after RP; and T6, more than 36 months after RP. We measured the general and disease-specific HRQOL using the RAND 36-item Health Survey 1.0 (SF-36) and the University of California, Los Angeles Prostate Cancer Index (UCLA PCI). RESULTS: The general HRQOL of the postoperative groups was assessed by SF-36. The postoperative groups showed almost the same or higher scores than those of the baseline group. Urinary function scores decreased substantially after surgery. In contrast, there was no difference in urinary bother between the baseline and postoperative groups. Sexual function deteriorated substantially in all postoperative groups. Similarly, the sexual bother score significantly deteriorated after RP. The sexual bother score of men aged 65-years or younger was significantly worse than that of their counterparts in the T1-2 groups. CONCLUSION: Despite reports of problems with sexual activity and urinary continence, general HRQOL was mostly unaffected by RP. Although there was a substantial decrease in urinary function, recovery from urinary bother was rapid. Since the deterioration of sexual function was marked through the postoperative period, careful attention should be paid to this issue during preoperative counseling, especially for younger patients.     

Motor activity of vascularly perfused rat duodenum. 2. Effects of VIP, PACAP27 and PACAP38

We examined the mechanisms of effects of vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase activating polypeptide (PACAP) 27 and PACAP38 on spontaneously occurring pressure waves in ex vivo perfused rat duodenum. VIP and PACAPs dose-dependently reduced the percentage motor index of pressure waves; this reduction was not prevented by atropine, hexamethonium or tetrodotoxin (TTX). VIP and PACAPs abolished acetylcholine-induced stimulation of pressure waves, even in the presence of TTX. These findings suggest that VIP and PACAPs may exert direct inhibitory effects via VIP/PACAP receptors located on smooth muscle rather than via cholinergic receptors. The inhibitory effects of VIP and PACAPs were partially antagonized by the VIP receptor antagonists VIP(10-28), suggesting that VIP and PACAPs share common receptor sites on intestinal smooth muscle. The effects of VIP and PACAPs were completely antagonized by nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NA), suggesting that NO mediates the inhibitory effects of VIP and PACAPs on duodenal motility. Furthermore, single injection of L-NA stimulated spontaneously occurring pressure waves, while VIP(10-28) did not affect them. These findings suggest that VIP/PACAPs and NO strongly interact as an inhibitory mediator on duodenal motility, but that their modes of action in doing so may differ.     

Relationship between perceived time pressure during visits and burnout among home visiting nurses in Japan

Aim: The rapidly rising number of older people has inevitably caused an increasing demand for home visiting nurses. Nursing managers must develop a healthy workplace to recruit and retain a workforce of nurses. This study focused on home visiting nurses’ perceptions of time pressure as a changeable work demand. The aim was to investigate perceptions of time pressure and reveal the relationship between perceived time pressure and burnout among home visiting nurses. Methods: From 32 agencies in three districts, 28 home visiting nurses agreed to participate in this study. Two hundred and eight home visiting nurses received an anonymous self‐administered questionnaire by mail, and 177 (85.1%) filled out and returned the questionnaire to the researchers. The Job Demands‐Resources model for burnout, which explains the relationship between a work environment and employee well‐being, was used as a conceptual guide. Three survey instruments were employed: questions on sociodemographic variables and worksite environments, including time pressure; the Japanese burnout inventory; and a Japanese version of the job content questionnaire. Multiple regression analyses were performed to examine the relationships between time pressure and burnout inventory scores. Results: About 30% of home visiting nurses perceived time pressure frequently. When home visiting nurses perceived time pressure more frequently, they experienced higher emotional exhaustion and depersonalization. Conclusion: Time pressure was often perceived as another job demand and had a significant relationship with burnout. This indicates the importance of lessening time pressure to develop healthy work places for community health nurses.     

Neurologic toxicity associated with interferon α therapy for renal cell carcinoma

A 67-year-old man received interferon alpha (IFN alpha) therapy for lung metastases of renal cell carcinoma (RCC). Multiple pulmonary metastases disappeared completely. However, neurological toxicity was detected by magnetic resonance imaging (MRI) as abnormal brain lesions. After discontinuation of IFN alpha therapy, his neurological symptoms and abnormal lesions on MRI disappeared completely. Complete remission of RCC has continued, and results of neurological study have remained normal for 5 years after discontinuation of IFN alpha therapy.     

Electrophysiological Characteristics of Localized Reentrant Atrial Tachycardia Occurring After Catheter Ablation of Long-Lasting Persistent Atrial Fibrillation

Background: Mapping of recurrent atrial tachycardia (AT) after extensive ablation for long-lasting persistent atrial fibrillation (AF) is complex. We sought to describe the electrophysiological characteristics of localized reentry occurring after ablation of long-lasting persistent AF.
Methods: Out of 70 patients undergoing catheter ablation of long-lasting persistent AF, 9 patients (13%, 55 ± 8 years, 8 males) in whom localized reentry was demonstrated in a repeat ablation were studied. Localized reentry was defined as reentry in which the circuit was localized to a small area and did not have a central obstacle. The mechanism of AT was determined by electroanatomical and entrainment mapping.
Results: Nine localized reentries with cycle length of 243 ± 41 ms were mapped in 9 patients. The location of AT was the left atrial appendage in 4 patients, anterior left atrium in 2, left septum in 2, and mitral isthmus in 1. In all ATs, a critical isthmus of <10 mm in width was identified in the vicinity of the prior linear lesions or ostia of isolated pulmonary veins. Ablation of the critical isthmus, which was characterized by continuous low-voltage activity (median voltage: 0.15 mV, mean duration: 117 ± 31 ms), terminated AT and rendered it noninducible. Additionally, ablation was performed for all of inducible ATs. At 11 ± 7 months after the procedure, 8 of 9 patients (89%) were free from any arrhythmias.
Conclusions: After ablation of long-lasting persistent AF, localized reentry may arise from a site in the vicinity of the prior ablation lesions. Ablation of the critical isthmus eliminates the arrhythmia.