A very narrow preexisting isthmus in a case with typical atrial flutter

A 61-year-old woman with typical atrial flutter underwent an electrophysiologic study and radiofrequency catheter ablation. The electroanatomic mapping revealed two contiguous lines of distinct double potentials (DPs) extending anteriorly/posteriorly from the coronary sinus ostium to the inferior vena cava (IVC) border. A large part of the anterior line of the DPs was close and parallel to the tricuspid annulus (TA). An initial discrete radiofrequency application at the very narrow preexisting isthmus between the TA and anterior line of the DPs completed the IVC-TA isthmus conduction block.     

Development of breakpoints of carbapenems for intraabdominal infections based on pharmacokinetics and pharmacodynamics in peritoneal fluid

This study aimed to develop breakpoints of carbapenems for intraabdominal infections, based on pharmacokinetics (PK) and pharmacodynamics (PD) at the target site. Imipenem, meropenem, and doripenem were each administered to 8-11 patients before abdominal surgery, and venous blood and peritoneal fluid samples were obtained. The drug concentrations in plasma and peritoneal fluid were determined and analyzed using population pharmacokinetic modeling. Using the pharmacokinetic model parameters, a Monte Carlo simulation was performed to estimate the probabilities of attaining the bacteriostatic and bactericidal targets (20% and 40% of the time above the minimum inhibitory concentration [MIC], respectively) in peritoneal fluid. The bacteriostatic and bactericidal breakpoints were defined as the highest MIC values at which the bacteriostatic and bactericidal probabilities in peritoneal fluid were 80% or more. The breakpoints for the minimum and maximum approved dosages of each drug were identical for imipenem, meropenem, and doripenem, and some of these values varied with dosing interval and infusion time. Site-specific PK-PD-based breakpoints are proposed here for the first time, and should help us to select appropriate carbapenem regimens for intraabdominal infections.     

Hypothermia attenuates apoptosis and protects contact between myelin basic protein‐expressing oligodendroglial‐lineage cells and neurons against hypoxia–Ischemia

Periventricular leukomalacia (PVL) is a major form of brain injury among preterm infants, which is characterized by extensive loss and dysfunction of premyelinating oligodendrocytes (pre‐OLs) induced by hypoxia–ischemia (HI). Therapeutic hypothermia, which is a standard treatment for term infants with HI encephalopathy, is not indicated for preterm infants because its safety and effect have not been established. Here we investigate the effectiveness and mechanism of hypothermia for the inhibition of pre‐OLs damage in PVL. For in vivo studies, 6‐day‐old rats underwent left carotid artery ligation, followed by exposure to 6% oxygen for 1 hr under hypothermic or normothermic conditions. The loss of myelin basic protein (MBP) was inhibited by hypothermia. For in vitro studies, primary pre‐OLs cultures were subjected to oxygen–glucose deprivation (OGD) under normothermic or hypothermic conditions, and dorsal root ganglion neurons were subsequently added. Hypothermia inhibited apoptosis of pre‐OLs, and, despite specific downregulation of 21.5‐ and 17‐kDa MBP mRNA expression during hypothermia, recovery of the expression after OGD was superior compared with normothermia. OGD caused disarrangement of MBP distribution, decreased the levels of phosphorylated 21.5‐kDa MBP, and disturbed the capacity to contact with neurons, all of which were restored by hypothermia. Pharmacological inhibition of ERK1/2 phosphorylation with U0126 during and after OGD significantly reduced the protective effects of hypothermia on apoptosis and myelination, respectively. These data suggest that phosphorylated exon 2‐containing (21.5‐ and possibly 17‐kDa) MBP isoforms may play critical roles in myelination and that hypothermia attenuates apoptosis and preserves the contact between OLs and neurons via ERK1/2 phosphorylation. © 2014 Wiley Periodicals, Inc.     

Determinants of reflux perception in patients with non-erosive reflux disease who have reflux-related symptoms on potassium-competitive acid blocker therapy

Esophagus - This study investigated potential determinants of reflux perception in patients with non-erosive reflux disease (NERD) who had reflux-related symptoms on potassium-competitive acid...     

Saliva secretion is reduced in proton pump inhibitor-responsive non-erosive reflux disease patients

Esophagus - There is no consensus on the relationship between saliva secretion and non-erosive reflux disease (NERD). In this study, saliva secretion and salivary epidermal growth factor (EGF) in...     

Stimulated saliva secretion is reduced in proton pump inhibitor-resistant severe reflux esophagitis patients

Esophagus - Salivary secretion in patients with proton-pump inhibitor (PPI)-resistant severe reflux esophagitis has not been examined. In this study, saliva secretion and salivary epidermal growth...     

New protocol to detect coronary spastic angina without fixed stenosis

A new combined test, accelerated exercise following mild hyperventilation (HV), was examined to determine whether it is effective at detecting a positive response in patients with pharmacologically-induced coronary vasospasm and near normal coronary arteries. Fifty-eight consecutive patients who underwent both triple non-invasive spasm provocation tests and diagnostic coronary angiography were enrolled. They all had pharmacologically-induced coronary vasospasms and no significant organic stenosis. In these patients, an HV test was performed first, followed by a treadmill exercise test (TET), and finally the new combined test under no medication within 3 days. Of the 58 patients, positive responses were observed in 9 patients to the HV, in 15 to the TET, and in 35 to the newly combined test. The remaining 21 patients had negative responses although the triple sequential tests were perfomed. Thus, the sensitivities of the HV test, TET, and newly combined test were 16% (9/58), 26% (15/58), and 63% (35/56), respectively. Forty-six subjects with near normal coronary arteries and no ACh-provoked spasm served as controls. None of these subjects had positive responses to any of these three tests, and thus their specificity was all 100%. No serious or irreversible complications were seen in this study. We recommend this newly-combined protocol for the induction of coronary artery spasm in patients with vasospastic angina pectoris and without significant stenosis as a diagnostic tool.     

Insulin-induced activation of phosphoinositide 3-kinase in Fao cells

Summary Phosphoinositide 3-kinase (PI3-kinase) plays a crucial role in insulin signal transduction. We studied the molecular mechanism of the insulin-induced activation of PI3-kinase in rat hepatoma Fao cells using an antibody against the 110-kDa catalytic subunit (p110) and two against the 85-kDa regulatory subunit (p85). PI3-kinase activity increased 1.6-fold in anti-p85 immunoprecipitates after insulin stimulation, whereas it did not increase when cell lysates were first immunoprecipitated with anti-phosphotyrosine or anti-insulin receptor substrate-1 (IRS-1), then with anti-p85, suggesting that the PI3-kinase which associates with tyrosyl phosphoproteins including IRS-1 is responsible for the increase in kinase activity. The activated PI3-kinase molecules constituted 4–6% of the total PI3-kinase, and their specific activity was 11–14 times higher than that of the basal state. Anti-p110 recognized the catalytically active form of p110, and immunoprecipitated p110 only after exposure to insulin. Hence, the epitope of anti-p110, P200-C215, seems to be included in the portion of p110, the conformation of which is changed by insulin stimulation. We conclude that, in response to insulin stimulation, only a small fraction of p85 in the PI3-kinase pool associates with tyrosyl phosphoproteins including IRS-1, and that the specific activity of p110 is increased presumably through a conformational change including the P200-C215 region.Abbreviations PI3-kinase Phosphoinositide 3-kinase - p85 85-kDa subunit of PI3-kinase - p110 110-kDa subunit of PI3-kinase - IRS-1 insulin receptor substrate-1 - SH2 src homology 2 - SH3 src homology 3 - BCR breakpoint cluster region - PMSF phenylmethylsulphonyl fluoride - HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid - PIP phosphatidylinositol phosphate - TLC thin layer chromatography - IP (in figures) immunoprecipitation with the indicated antibody - TBS Tris-buffered saline