Relationship between arrhythmogenic pulmonary veins and the surrounding atrial substrate in patients with paroxysmal atrial fibrillation

Arrhythmogenic PVs and the Fibrillatory Activities . Introduction: The relationship between pulmonary veins (PVs) with atrial fibrillation (AF) initiating triggers and their surrounding atrial substrate has not been elucidated. We aimed to clarify the atrial substrate properties around the PVs. Methods and Results: Twenty‐three paroxysmal AF patients were studied with the identification of PV initiating triggers. High‐density mapping of the dominant frequency (DF, 1200 Hz) and the mean degree of the complex fractionated electrograms (CFE mean interval over 6 seconds) was evaluated in 2 zones (zone 1: < 5 mm, zone 2: 5–15 mm from the PVs) and the left atrial (LA) using a NavX system prior to the PV isolation. High‐DFs (>8 Hz) and continuous CFEs (<50 ms) were identified in 1.5 ± 0.9 and 2.3 ± 1.1 regions per patient, respectively. Most of the high‐DF regions (86%) and continuous CFE regions (77%) were located within 15 mm of the PV ostia. Of those, 75% of the high‐DF regions and 54% of the continuous CFE regions were related to arrhythmogenic PVs. There was a significant DF gradient from arrhythmogenic PV zone 1 to zone 2, while the mean CFE exhibited a significant gradient between arrhythmogenic PV zone 2 and the rest of the LA. Additionally, 69% of the procedural AF termination sites were at arrhythmogenic PV zone 2. Conclusion: Evaluation of the atrial substrate properties may be useful for locating arrhythmogenic PVs during AF and defining the extent of the circumferential PV isolation. (J Cardiovasc Electrophysiol, Vol. 22, pp. 405‐410)     

Simulation Platform: A cloud-based online simulation environment

For multi-scale and multi-modal neural modeling, it is needed to handle multiple neural models described at different levels seamlessly. Database technology will become more important for these studies, specifically for downloading and handling the neural models seamlessly and effortlessly. To date, conventional neuroinformatics databases have solely been designed to archive model files, but the databases should provide a chance for users to validate the models before downloading them. In this paper, we report our on-going project to develop a cloud-based web service for online simulation called “Simulation Platform”. Simulation Platform is a cloud of virtual machines running GNU/Linux. On a virtual machine, various software including developer tools such as compilers and libraries, popular neural simulators such as GENESIS, NEURON and NEST, and scientific software such as Gnuplot, R and Octave, are pre-installed. When a user posts a request, a virtual machine is assigned to the user, and the simulation starts on that machine. The user remotely accesses to the machine through a web browser and carries out the simulation, without the need to install any software but a web browser on the user’s own computer. Therefore, Simulation Platform is expected to eliminate impediments to handle multiple neural models that require multiple software.     

Frequent spontaneous seizures followed by spatial working memory/anxiety deficits in mice lacking sphingosine 1-phosphate receptor 2

The diverse physiological effects of sphingosine 1-phosphate (S1P) are mostly mediated by its five cognate G protein-coupled receptors, S1P₁-S1P₅, which have attracted much attention as future drug targets. To gain insight into S1P₂-mediated signaling, we analyzed frequent spontaneous seizures in S1P₂-deficient (S1P₂^−/−) mice obtained after several backcrosses onto a C57BL/6N background. Full-time video recording of 120 S1P₂^−/− mice identified 420 seizures both day and night between postnatal days 25 and 45, which were accompanied by high-voltage synchronized cortical discharges and a series of typical episodes: wild run, tonic-clonic convulsion, freezing, and, occasionally, death. Nearly 40% of 224 S1P₂^−/− mice died after such seizures, while the remaining 60% of the mice survived to adulthood; however, approximately half of the deliveries from S1P₂^−/− pregnant mice resulted in neonatal death. In situ hybridization revealed exclusive s1p₂ expression in the hippocampal pyramidal/granular neurons of wild-type mice, and immunohistochemistry/microarray analyses identified enhanced gliosis in the whole hippocampus and its neighboring neocortex in seizure-prone adult S1P₂^−/− mice. Seizure-prone adult S1P₂^−/− mice displayed impaired spatial working memory in the eight-arm radial maze test and increased anxiety in the elevated plus maze test, whereas their passive avoidance learning memory performance in the step-through test and hippocampal long-term potentiation was indistinguishable from that of wild-type mice. Our findings suggest that blockade of S1P₂ signaling may cause seizures/hippocampal insults and impair some specific central nervous system functions.     

Adverse events in therapeutic apheresis: a single center survey of various therapies

The aim of the study was to review the adverse events associated with various treatment modalities performed in a single apheresis facility. A total of 854 sessions with 10 types of apheresis therapies were performed and 154 (18.0%) adverse events were observed over a four-year period. Of the adverse events, 77 were related to operational problems and another 77 were complications associated with treatment. A transmembranous pressure abnormality constituted more than 80% of the operational problems. Nausea was the most frequent complication, accounting for 19 of the 77 treatment-related events. A total of 26 (16.9%) adverse events occurred in the early stage of the sessions, 40 (26.0%) in the middle stage, and 88 (57.1%) in the late stage. The information in this study can be used to improve the safety and efficacy of apheresis therapy.     

Plasma concentration of propofol was 4.4 microg x ml(-1), 4.5 hours after completion of its administration

Propofol is one of the most commonly used intravenous anesthetic drugs because its distribution, metabolism and excretion are rapid. Recovery from anesthesia using propofol infusion is generally smooth. We have therefore taken this opportunity to report on a case of delayed recovery from anesthesia in a 58-year-old man who underwent removal of a light maxillary sinus mucocele. General anesthesia was performed with propofol 3-7 mg x kg(-1) x hr(-1) associated with intermittent injection of fentanyl, total of 450 microg. He was not obese, and his preoperative liver function was within normal limits. Any intracranial hematomas, brain edema, cerebral infarction, acid-base abnormalities, hypo- and hyperglycemia and hypothermia were not detected in the early postoperative period. The administration of naloxone hydrochloride and flumazenil failed to improve delayed recovery from anesthesia. It was 16 hours after the end of operation and the administration of propofol had been completed before the trachea could be extubated. His plasma concentration of propofol was 4.4 microg x ml(-1), 4.5 hours after administration. In this patient we could not prove a metabolic abnormality with propofol, but it was strongly suspected.     

A case of paracecal hernia

A 63-year-old male patient suddenly suffered right lower abdominal pain. The patient had tenderness and rebound tenderness at the right lower abdomen. Marked small bowel dilatation and an intestinal obstruction were evident upon abdominal X-ray and abdominal computed tomography (CT) imaging. CT imaging also revealed a dilated small bowel cluster in a wrapped round shape in the right lower abdomen. The cecum and the ascending colon were displaced inward. Strangulation in the ileocecal region was suspected, and emergency surgery was performed. A part of the small bowel was incarcerated within the retrocecal recess, and the intestinal tract was strangulated in the hernia orifice, by which paracecal hernia was diagnosed. The strangulated intestinal tract was repositioned, and the orifice to the hernia was closed. Paracecal hernia is a rare disease; an internal hernia should always be considered in patients with ileus without a history of surgery.     

Subchondral Insufficiency Fracture of the Femoral Head may be Associated with Hip Dysplasia: A Pilot Study

Background  

Subchondral insufficiency fracture of the femoral head occurs mainly in elderly patients with osteoporosis. Spontaneous resolution is observed after nonoperative treatment in some patients whereas other show progressive joint destruction requiring THA. Several studies report the occurrence of subchondral insufficiency fracture of the femoral head in dysplastic hips.     

Absence of High-Risk Human Papillomavirus (HPV) Detection in Endocervical Adenocarcinoma with Gastric Morphology and Phenotype

A subset of endocervical-type mucinous adenocarcinomas (ACs) of the uterine cervix exhibit a gastric phenotype and morphology, as reported in cases of minimal deviation AC in which the presence of human papillomavirus (HPV) has been rarely detected. To investigate the HPV-independent pathway of carcinogenesis in cases of gastric-type AC, we investigated the common high-risk HPV (hr-HPV) status in 52 nonsquamous cell carcinomas, using a PCR-based typing method and immunohistochemistry of p16^INK4a (a cyclin-dependent kinase inhibitor that is overexpressed in both cancerous and precancerous cervical tissue, making it an ideal biomarker for cervical cancer cases). Using novel morphological criteria, seven of 52 (13.5%) carcinomas were designated as gastric-type ACs, all of which were negative for both hr-HPV DNA and p16^INK4a. Nongastric-type ACs were frequently positive for both hr-HPV DNA (90%, 28/31) and p16^INK4a (94%, 29/31) with adenosquamous and neuroendocrine carcinomas demonstrating the presence of hr-HPV DNA in 86% (6/7) and 83% (5/6) of cases, respectively. In these two types of carcinoma, 86% (6/7) and 100% (6/6) were positive for p16^INK4a, respectively. Our data suggests that gastric-type AC appears to represent an oncogenic hr-HPV–independent neoplasm and therefore is a potential pitfall of HPV DNA testing and vaccination.The incidence of uterine cervical cancer has been declining for the past three decades, largely due to widespread mass screening with Pap smears. This declining trend reflects the dramatic decrease of squamous cell carcinomas (SCCs), but recent studies have demonstrated an increase in both relative incidence and absolute number of adenocarcinoma (AC),^1,2,3,4,5 with its incidence approaching 20% of all cervical cancers.^1,4,5,6,7 This fact suggests that conventional sampling methods for Pap smears are not necessarily optimal for the early detection of ACs, and an effective tool is required for this particular purpose.⁸ The cause of the absolute increase of patients with ACs remains unknown.High-risk human papillomavirus (hr-HPV) is currently considered to be implicated in the carcinogenesis of most ACs as well as SCCs of the cervix, with a detection rate reaching 85% in the former.^9,10,11,12 Therefore, a combination of HPV DNA tests and cytology has been expected to contribute to improving sensitivity and specificity for the early detection of endocervical AC. On the other hand, however, some investigators have shed light on the existence of hr-HPV–negative endocervical ACs, which could be a serious diagnostic concern, and also indicates that endocervical AC is a heterogeneous group of neoplasms. Such putative hr-HPV–independent AC includes uncommon subtypes of AC, such as clear cell adenocarcinoma, mesonephric adenocarcinoma, and minimal deviation adenocarcinoma (MDA).^12,13 Based on accumulated data in the literature,^{12,13,14,15,16} hr-HPV DNA is only rarely detected in cases of MDA, a well-differentiated variant of mucinous AC with a deceptively benign appearance but significantly aggressive clinical course.^17,18A subset of mucinous AC shares gastric phenotype with MDA as evidenced by immunoreactivity for HIK1083 and anti-MUC6, antibodies recognizing pyloric gland mucin of the stomach, and incidence of p16^IKN4a immunoreactivity is significantly low in both MDA and the mucinous AC with gastric immunophenotype.^19,20 Additionally, both neoplasms can be associated with lobular endocervical glandular hyperplasia (LEGH),¹⁹ which represents a pyloric gland metaplasia²¹ and has also been shown to be hr-HPV DNA–negative.^16,22 These facts suggest that the mucinous AC with gastric immunophenotype, incorporating MDA as its well-differentiated form in the morphological spectrum, is a distinct entity arising via a hr-HPV–independent pathway. In a previous investigation we demonstrated that mucinous AC with gastric immunophenotype was morphologically distinct with a good interobserver reproducibility, characterized by neoplastic cells with conspicuous cell borders and clear and/or pale eosinophilic voluminous cytoplasm, and aggressive clinical behavior.^20,23 MDA is not a common neoplasm, accounting for 1–3% of all endocervical ACs, but the gastric-type adenocarcinoma (GAC) appears in 10–30% of all endocervical ACs^19,20 and thus may not be a negligible pitfall of HPV DNA tests and vaccination, and therapeutic strategy.Following World Health Organization classification, GAC has been hitherto recognized as an endocervical-type mucinous AC because of a lack of definite criteria, and the exact hr-HPV DNA detection rate in this tumor is unknown. We conducted this study to investigate the HPV DNA status in cases of histopathologically defined GAC using novel diagnostic criteria and literature reviews on HPV detection rate in cases of AC published by Japanese investigators.