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2,334,000
Comparison of three fluid regimens for preloading in elective caesarean section under spinal anaesthesia.
The most common problem associated with subarachnoid block (SAB) for caesarean section remains the rapid onset of profound hypotension. This study was designed to compare the incidence of hypotension after preloading with Ringer's Lactate, Hydroxyethylstarch and combination prior to SAB in caesarean section. Ninety non-labouring ASA grade 1 and 2, aged 20-35 years, weight and height was 45-60kg and 153-165cm respectively divided randomly into three groups. Group-RL received Ringer's Lactate 20ml/kg as preloading fluid. Group-H received Hydroxyethylstarch-6% 8ml/kg and Group-RLH received preloading fluid with combination of Ringer's Lactate 10ml/kg and Hydroxyethylstarch-6% 4ml/kg. Blood pressure (Systolic, Diastolic & Mean arterial pressure) was measured every 5 minute for 20 minute and every 10 minutes thereafter. Hypotension was less in Group-RLH (6.7%) whereas in Group-H and Group-RL hypotension was 20% and 47.7% respectively. Systolic blood pressure decreased significantly in all three groups. But the decreasing was less in Group-RLH than other two groups. Less IV fluid was required in Group-RLH (403ml) and Group-H (577ml) in comparison to Group-RL (1032ml) to prevent and treat peroperative hypotension. No ephedrine was needed in Group-RLH. Variation in Pulse rate was not significant in Group-RLH (p=0.061). But in other two groups it was highly significant (Group RL p≤0.001 and Group H p=0.004). There was no significant difference in neonatal outcome between three groups. Preloading with low volume colloid (4ml/kg) plus crystalloid (10ml/kg) is superior to crystalloid or colloid alone.
2,334,001
[Anti-Ro/SSA antibodies in congenital heart block].
Describe a case of a female patient having anti-Ro/SSA antibodies without any other risk factor or collagen disease. In her first pregnancy a congenital heart block and hydrops in the fetus were diagnosed, and these caused stillbirth. In a second pregnancy an in utero treatment resulted in the succesful delivery of a normal child.
2,334,002
Posterior tibial nerve sensory blockade duration prolonged by adding dexmedetomidine to ropivacaine.
Dexmedetomidine, an &#x3b1;(2)-receptor agonist, prolongs analgesia when used in neuraxial and IV blocks. We evaluated the effect of dexmedetomidine added to ropivacaine for tibial nerve block on the duration of the sensory blockade.</AbstractText>For this prospective, randomized, controlled, double-blind, crossover trial, 14 healthy volunteers were allocated to 2 groups. All volunteers received an ultrasound-guided tibial nerve block 4 to 5 cm proximally to the medial malleolus. In group R, 10 mL of 0.5% ropivacaine was injected for the block; in group RD, 10 mL of a solution containing 0.5% ropivacaine with 1 &#x3bc;g/kg of dexmedetomidine was administered. After the injection, monitoring of vital signs, evaluation of onset and resolution of sensory block, and level of sedation (Observer's Assessment of Alertness/Sedation scale) were performed. Three weeks later, the same procedure was repeated, but the study subjects were allocated to the other group in a crossover fashion. The primary end point was the duration of sensory blockade. The time and carryover effects were also evaluated. Secondary outcomes were the onset time and the presence of adverse effects such as hypotension, bradycardia, hypoxia, and sedation.</AbstractText>Sensory blocks lasted longer in group RD than in group R (21.5 vs 16.2 hours; mean pairwise difference 5.3 hours [95% confidence interval: 3.9-6.7 hours]; P &lt; 0.0001). Onset times were similar between groups. The mean systolic and diastolic blood pressure levels were stable throughout the study period in group R. In group RD, a noticeable decrease in systolic and diastolic blood pressure was observed between 60 and 480 minutes (P &lt; 0.05); 2 volunteers experienced a 30% decrease in systolic blood pressure when compared with the baseline value as compared with none in group R. Heart rate was similar between groups except at 60 minutes (P &lt; 0.01).</AbstractText>Dexmedetomidine added to ropivacaine for tibial nerve block prolongs the duration of sensory blockade with similar onset time. However, patients should be monitored for potential adverse effects such as hypotension, bradycardia, and sedation.</AbstractText>
2,334,003
Suspected brainstem anesthesia following retrobulbar block in a cat.
A 10-year-old, male, neutered, domestic shorthair cat was anesthetised for enucleation of a perforated left globe. A retrobulbar injection of local anesthetic (lidocaine/bupivacaine) was performed prior to surgery to provide intra- and postoperative analgesia. Following administration of the injection, the cat developed apnea and heart rate increased. Mechanical ventilation was initiated and surgery went ahead as planned. At the conclusion of surgery, the cat remained apnoeic requiring positive pressure ventilation until spontaneous ventilatory effort resumed. Upon recovery, the cat demonstrated neurological signs including tremors, nystagmus and absent dazzle reflex. These signs were attributed to brainstem anesthesia from the retrobulbar block and fully resolved within 3 h. This is the first report of suspected intrathecal spread of local anesthetic following retrobulbar block in a cat to the authors' knowledge.
2,334,004
Extracardiac minimal invasive implantation of cardioverter defibrillator in young children.
Implantable cardioverter defibrillator (ICD) placement in young children remains a challenge due to device-patient size mismatch and the important choice between an endovenous or an epicardial approach for lead implantation. We treated three children, with respectively Long QT-syndrome, Brugada syndrome and Brugada syndrome with sick sinus syndrome, ranging from 9 months to 7 years with a subxyphoidal ICD and extracardiac lead implantation by minimally invasive techniques. In all cases the thresholds were excellent. The devices could be properly placed in the preperitoneal space without discomfort to the patients. The clinical course was uneventful and results were excellent.
2,334,005
Fluid-dynamics modelling of the human left ventricle with dynamic mesh for normal and myocardial infarction: preliminary study.
Pulsating blood flow patterns in the left ventricular (LV) were computed for three normal subjects and three patients after myocardial infarction (MI). Cardiac magnetic resonance (MR) images were obtained, segmented and transformed into 25 frames of LV for a computational fluid dynamics (CFD) study. Multi-block structure meshes were generated for 25 frames and 75 intermediate grids. The complete LV cycle was modelled by using ANSYS-CFX 12. The flow patterns and pressure drops in the LV chamber of this study provided some useful information on intra-LV flow patterns with heart diseases.
2,334,006
A New Anterior Approach for Fluoroscopy-guided Suprascapular Nerve Block - A Preliminary Report -.
The aim of the study was to investigate the feasibility of fluoroscopy-guided anterior approach for suprascapular nerve block (SSNB).</AbstractText>Twenty patients with chronic shoulder pain were included in the study. All of the nerve blocks were performed with patients in a supine position. Fluoroscopy was tilted medially to obtain the best view of the scapular notch (medial angle) and caudally to put the base of coracoid process and scapular spine on same line (caudal angle). SSNB was performed by introducing a 100-mm, 21-gauge needle to the scapular notch with tunnel view technique. Following negative aspiration, 1.0 ml of contrast was injected to confirm the scapular notch, and 1 % mepivacaine 2 ml was slowly injected. The success of SSNB was assessed by numerical rating scale (NRS) before and after the block.</AbstractText>The average NRS was decreased from 4.8 &#xb1; 0.6 to 0.6 &#xb1; 0.5 after the procedure (P &lt; 0.05). The best view of the scapular notch was obtained in a medial angle of 15.1 &#xb1; 2.2 (11-19&#xb0;) and a caudal angle of 15.4 &#xb1; 1.7&#xb0; (12-18&#xb0;). The average distance from the skin to the scapular notch was 5.8 &#xb1; 0.6 cm. None of the complications such as pneumothorax, intravascular injection, and hematoma formation was found except one case of partial brachial plexus block.</AbstractText>SSNB by fluoroscopy-guided anterior approach is a feasible technique. The advantage of using a fluoroscopy resulted in an effective block with a small dose of local anesthetics by an accurate placement of a tip of needle in the scapular notch while avoiding pneumothorax.</AbstractText>
2,334,007
A phenotype-genotype correlation of ADAMTS13 mutations in congenital thrombotic thrombocytopenic purpura patients treated in the United Kingdom.
ADAMTS13 mutations play a role in thrombotic thrombocytopenic purpura (TTP) pathogenesis.</AbstractText>To establish a phenotype-genotype correlation in a cohort of congenital TTP patients.</AbstractText><AbstractText Label="PATIENTS/METHODS" NlmCategory="METHODS">Clinical history and ADAMTS13 activity, antigen and anti-ADAMTS13 antibody assays were used to diagnose congenital TTP, and DNA sequencing and in vitro expression were performed to identify the functional effects of the ADAMTS13 mutations responsible.</AbstractText>Seventeen (11 novel) ADAMTS13 mutations were identified in 17 congenital TTP patients. All had severely reduced ADAMTS13 activity and antigen levels at presentation. Six patients with pregnancy-associated TTP and six patients with childhood TTP were homozygous or compound heterozygous for ADAMTS13 mutations located in the metalloprotease (MP), cysteine-rich, spacer and/or distal thrombospondin type 1 domains. The adults had TTP precipitated by pregnancy, and had overall higher antigen levels (median, 30&#x2003;ng&#x2003;mL(-1) ; range, &lt;&#x2003;10-57&#x2003;ng&#x2003;mL(-1) ) than the children (median, 14&#x2003;ng&#x2003;mL(-1) ; range, &lt;&#x2003;10-40&#x2003;ng&#x2003;mL(-1)). Presentation in the neonatal period was associated with more intensive treatment requirements. The two neonates with the most severe phenotype had mutations in the first thrombospondin type 1 motif of ADAMTS13 (p.R398C, p.R409W, and p.Q436H). Using transfected HEK293T cells, we have shown that p.R398C and p.R409W block ADAMTS13 secretion, whereas p.Q436H allows secretion at reduced levels.</AbstractText>This study confirms the heterogeneity of ADAMTS13 defects and an association between ADAMTS13 genotypes and TTP phenotype.</AbstractText>&#xa9; 2012 International Society on Thrombosis and Haemostasis.</CopyrightInformation>
2,334,008
[Application of ultrasound guidance for ilioinguinal or iliohypogastric nerve block in pediatric inguinal surgery].
To evaluate the efficacy of ultrasound guidance for ilioinguinal or iliohypogastric nerve block in pediatric outpatients undergoing inguinal surgery.</AbstractText>The present study was approved by the ethics committee of our hospital. One hundred children with ASA status I, aged 4 - 8 years old, scheduled for unilateral inguinal surgery were randomly divided into ultrasound group (Group U) and traditional group (Group T) (n = 50 each). Upon entering operation room, they were monitored by electrocardiography (ECG), heart rate (HR) and oxygen saturation (SpO(2)). After an induction of general anesthesia, intravenous access was established and laryngeal mask inserted with spontaneous breathing. Intraoperative anesthesia was maintained with 2% sevoflurane in 50% nitrous oxide with 50% oxygen. Children in Group U received an ilioinguinal or iliohypogastric block under ultrasonic guidance with a mixture of 0.8% lidocaine and 0.25% levobupivacaine at 0.2 ml/kg while those in Group T performed according to the traditional method of anatomical localization with the same local anesthetic at 0.3 ml/kg. During surgery, the vital signs of HR, respiratory rate (RR), SpO(2), partial pressure of end-tidal carbon dioxide (P(ET)CO(2)) and exhaled sevoflurane concentration were recorded. Additional intraoperative analgesic requirements were recorded. Face legs activity cry consolability (FLACC) score was used to assess the pain score postoperatively at recovery time, 2 and 4 h postoperation respectively. If the pain score was above 3, the child received acetaminophen rectally. The number of postoperative rectal acetaminophen was recorded. The degrees of parental satisfaction were investigated at 2 and 4 h postoperation. Intra-or postoperative adverse events were also recorded.</AbstractText>HR at skin incision and sac traction in Group U was significantly lower than those in Group T (P &lt; 0.05). Six children (12%) needed to increase inhaled sevoflurane concentration during operation in Group U versus 17 (34%) in Group T (P &lt; 0.05). The pain score at recovery time, 2 and 4 h postoperation in Group U was significantly lower than those in T group (P &lt; 0.05). Only 4 children (8%) needed postoperative rectal acetaminophen in Group U versus 13 (26%) in Group T (P &lt; 0.05). The degree of parental satisfaction at 2 h postoperation was significantly higher in Group U than that in Group T (P &lt; 0.05). One case in Group T had needle puncturing into blood vessels. No other adverse event was observed in two groups.</AbstractText>The method of ultrasonic guidance for ilioinguinal or iliohypogastric nerve block is both feasible and effective. It can not only enhance the effect of nerve block, reduce the occurrences of complications, lower the quantity of local anesthetic and alleviate the medicinal toxicity.</AbstractText>
2,334,009
Effect of magnesium sulfate pretreatment on onset and recovery characteristics of cisatracurium.
To determine how pretreatment with magnesium sulfate (MgSO(4)) potentiates neuromuscular blocking agents. We investigated how the onset and recovery characteristics of cisatracurium are changed by pretreatment with MgSO(4).</AbstractText>After Institutional Review Board approval, a total of 48 ASA I and II patients were devided into 2 groups. Patients in each group received either the MgSO(4) 30 mg/kg (group M) in 0.9% normal saline (total volume 100 ml) or 0.9% normal saline (control group C) alone intravenously for 15 min before induction of anesthesia with propofol, remifentanil and cisatracurium 0.15 mg/kg. Anesthesia was maintained with propofol and remifentanil. Electromyographical responses were measured by train-of-four. Lag time, onset time, total recovery time, clinical duration, recovery index, and recovery time were measured. The mean arterial blood pressure, heart rate, and ionized magnesium were also measured.</AbstractText>The lag time and onset time were significantly shorter in the MgSO(4) group than the control group (P &lt; 0.05). Recovery index, recovery time, clinical duration, and total recovery time showed no significant differences in the MgSO(4) group compared to the control group (P &gt; 0.05). Mean arterial pressure was more significantly increased in the MgSO(4) group than in the control group at the time point immediately after the administration of MgSO(4). Heart rate showed no significant changes in both groups. The concentrations of ionized magnesium were significantly more increased at the all time point (P &lt; 0.05).</AbstractText>MgSO(4) results in about 29% shortening of onset time of cisatracurium (0.15 mg/kg) without prolongation on the recovery of neuromuscular block.</AbstractText>
2,334,010
Assessing physician leadership styles: application of the situational leadership model to transitions in patient acuity.
The situational leadership model suggests that an effective leader adapts leadership style depending on the followers' level of competency.</AbstractText>We assessed the applicability and reliability of the situational leadership model when observing residents in simulated hospital floor-based scenarios.</AbstractText>Resident teams engaged in clinical simulated scenarios. Video recordings were divided into clips based on Emergency Severity Index v4 acuity scores. Situational leadership styles were identified in clips by two physicians. Interrater reliability was determined through descriptive statistical data analysis.</AbstractText>There were 114 participants recorded in 20 sessions, and 109 clips were reviewed and scored. There was a high level of interrater reliability (weighted kappa r = .81) supporting situational leadership model's applicability to medical teams. A suggestive correlation was found between frequency of changes in leadership style and the ability to effectively lead a medical team.</AbstractText>The situational leadership model represents a unique tool to assess medical leadership performance in the context of acuity changes.</AbstractText>
2,334,011
[Role of autoimmune reactions in development of cardiac arrhythmia and conduction disturbances].
Cardiac arrhythmias and conduction disturbances are an important cause of morbidity and mortality in many countries all over the world Etiology of these disorders remains unclear in many patients. Experimental and clinical studies show that autoimmune reactions may be involved in development of arrhythmias and cardiac blocks. Precise identification of an autoantibody-mediated mechanism opens new perspectives in the treatment and prevention of cardiac arrhythmias including use of immunosuppressive agents or removal of autoantibodies by absorption technique. The review focuses on cardiac autoantigens, autoantibodies and their interactions that may be involved in development of cardriac arrhythmias.
2,334,012
Intracardiac acoustic radiation force impulse imaging: a novel imaging method for intraprocedural evaluation of radiofrequency ablation lesions.
Arrhythmia recurrence after cardiac radiofrequency ablation (RFA) for atrial fibrillation has been linked to conduction through discontinuous lesion lines. Intraprocedural visualization and corrective ablation of lesion line discontinuities could decrease postprocedure atrial fibrillation recurrence. Intracardiac acoustic radiation force impulse (ARFI) imaging is a new imaging technique that visualizes RFA lesions by mapping the relative elasticity contrast between compliant-unablated and stiff RFA-treated myocardium.</AbstractText>To determine whether intraprocedure ARFI images can identify RFA-treated myocardium in vivo.</AbstractText>In 8 canines, an electroanatomical mapping-guided intracardiac echo catheter was used to acquire 2-dimensional ARFI images along right atrial ablation lines before and after RFA. ARFI images were acquired during diastole with the myocardium positioned at the ARFI focus (1.5 cm) and parallel to the intracardiac echo transducer for maximal and uniform energy delivery to the tissue. Three reviewers categorized each ARFI image as depicting no lesion, noncontiguous lesion, or contiguous lesion. For comparison, 3 separate reviewers confirmed RFA lesion presence and contiguity on the basis of functional conduction block at the imaging plane location on electroanatomical activation maps.</AbstractText>Ten percent of ARFI images were discarded because of motion artifacts. Reviewers of the ARFI images detected RFA-treated sites with high sensitivity (95.7%) and specificity (91.5%). Reviewer identification of contiguous lesions had 75.3% specificity and 47.1% sensitivity.</AbstractText>Intracardiac ARFI imaging was successful in identifying endocardial RFA treatment when specific imaging conditions were maintained. Further advances in ARFI imaging technology would facilitate a wider range of imaging opportunities for clinical lesion evaluation.</AbstractText>Copyright &#xa9; 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
2,334,013
The predictive value of anti-SS-A antibodies titration in pregnant women with fetal congenital heart block.
Fetal congenital complete heart block (CHB) is irreversible and is associated with significant mortality and morbidity. Anti-SS-A antibodies in the maternal sera are involved in its pathogenesis; however, the predictive value of the antibody titer and its role in prediction of this complication are controversial. The aim of this study was to determine the predictive value of maternal anti-SS-A antibodies on the development of fetal CHB.</AbstractText>A retrospective chart review was performed for 189 cases of positive anti-SS-A antibodies determined by the double immunodiffusion (DID) method, and included 17 patients that developed fetal CHB. The relationship between the appearance of CHB and the anti-SS-A antibodies titer was examined.</AbstractText>An anti-SS-A antibodies titer of 1:32 or higher was identified by analyzing the receiver-operating characteristics (area under curve 0.72) curve. An anti-SS-A antibodies titer of 32 or more times greater than the upper limit by DID was a risk factor for fetal CHB (odds ratio 27.77, 95% confidence interval (CI) 1.91-21.02, P &lt; 0.05) in the multivariate analysis. Among 107 cases of anti-SS-A antibodies titers of 1:32 or higher, 65 patients (60.7%) were treated with oral steroids. Of these, four patients had CHB (6.2%). This rate of CHB was significantly lower (P &lt; 0.01) than the rate in patients not treated with steroids.</AbstractText>An anti-SS-A antibodies titer of 1:32 or higher in the maternal sera by DID was an independent risk factor for fetal CHB. In these patients, either antenatally administered prednisolone or betamethasone, was associated with a lower risk of fetal CHB.</AbstractText>
2,334,014
Immediate cardiac arrest after neostigmine administration.
Many drugs used in anaesthesia have some potential fatal consequences; for example complete heart block and Q-Tc interval prolongation. Since the parasympathetic system in children is not fully developed, electrical transmission of the heart is not stable. Neostigmine is used in order to reverse neuromuscular block but it may also lead to prolongation of Q-Tc interval. We present a case of an 18-month-old male patient weighing 12kg subjected to a surgical operation because of congenital glaucoma. In order to reverse neuromuscular block at the end of operation, atropine and neostigmine were injected intravenously. However, cardiac arrest developed immediately after administration.
2,334,015
Role of Cholinergic Innervation and RGS2 in Atrial Arrhythmia.
The heart receives sympathetic and parasympathetic efferent innervation as well as the ability to process information internally via an intrinsic cardiac autonomic nervous system (ICANS). For over a century, the role of the parasympathetics via vagal acetylcholine release was related to controlling primarily heart rate. Although in the late 1800s shown to play a role in atrial arrhythmia, the myocardium took precedence from the mid-1950s until in the last decade a resurgence of interest in the autonomics along with signaling cascades, regulators, and ion channels. Originally ignored as being benign and thus untreated, recent emphasis has focused on atrial arrhythmia as atrial fibrillation (AF) is the most common arrhythmia seen by the general practitioner. It is now recognized to have significant mortality and morbidity due to resultant stroke and heart failure. With the aging population, there will be an unprecedented increased burden on health care resources. Although it has been known for more than half a century that cholinergic stimulation can initiate AF, the classical concept focused on the M2 receptor and its signaling cascade including RGS4, as these had been shown to have predominant effects on nodal function (heart rate and conduction block) as well as contractility. However, recent evidence suggests that the M3 receptor may also playa role in initiation and perpetuation of AF and thus RGS2, a putative regulator of the M3 receptor, may be a target for therapeutic intervention. Mice lacking RGS2 (RGS2(-/-)), were found to have significantly altered electrophysiological atrial responses and were more susceptible to electrically induced AF. Vagally induced or programmed stimulation-induced AF could be blocked by the selective M3R antagonist, darifenacin. These results suggest a potential surgical target (ICANS) and pharmacological targets (M3R, RGS2) for the management of AF.
2,334,016
New anticancer agents: hormones made within the heart.
The heart is a sophisticated endocrine gland synthesizing the atrial natriuretic peptide (ANP) prohormone which contains four peptide hormones, namely atrial natriuretic peptide, vessel dilator, kaliuretic peptide and long-acting natriuretic peptide, which decrease up to 97% of human pancreatic, breast, colon, prostate, kidney and ovarian carcinomas, as well as small-cell and squamous cell lung cancer cells within 24 hours in cell culture. In vivo these four cardiac hormones eliminate up to 80% of human pancreatic adenocarcinomas, up to two-thirds of human breast cancers, and up to 86% of human small-cell lung cancers in athymic mice. Their anticancer mechanism(s) target the Rat sarcoma bound guanosine triphosphate (RAS)-mitogen activated protein kinase kinase 1/2 (MEK1/2)-extracellular signal related kinase 1/2 (ERK1/2) kinase cascade in cancer cells. These four cardiac hormones inhibit up to 95% of the basal activity of Ras, 98% of the phosphorylation of MEK1/2 kinases and 96% of the activation of basal activity of ERK1/2 kinases. They also completely block the activity of mitogens such as the ability of epidermal growth factor to stimulate ERK and RAS. In addition to inhibiting these mitogen-activated protein kinases (MAPKs) they also inhibit MAPK9, i.e. c-Jun-N-terminal kinase 2. These multiple kinase inhibitors are cytotoxic and cause cell death of cancer cells but not of normal cells.
2,334,017
Antipsychotic drugs cause bradycardia in GD 13 rat embryos in vitro.
This study investigated the effects of antipsychotic drugs on heart function of gestational day (GD) 13 rat embryos in vitro since they all block the I(Kr)/hERG potassium ion channel in addition to their main pharmacological effect on neurotransmitters. The results showed that all the tested antipsychotic drugs caused bradycardia of the rat embryonic heart in a concentration-dependent manner. However, with the possible exception of haloperidol the tested drugs did not cause arrhythmias typically seen with the highly selective I(Kr)/hERG blocking drug dofetilide. For six of the eight drugs tested the effects on the embryonic rat heart were only seen at free drug concentrations that were much greater than those likely to occur in pregnant women taking antipsychotic medication. However, the safety margins for haloperidol and quetiapine were lower.
2,334,018
Clonidine as an adjuvant in axillary brachial plexus block for below elbow orthopedic surgeries: A comparison between local and systemic administration.
Axillary brachial plexus block for below elbow orthopedic surgery provides a safe and low-cost technique with the advantage of prolonged postoperative analgesia. Clonidine, with selective partial agonist activity on &#x3b1;2 adrenergic receptors, has significantly demonstrated its role in this regard as an adjuvant to local anesthetics. The current study compares the locally administered clonidine with systemically administered control group in terms of onset and duration of sensory block, motor block, and analgesia; hemodynamic variability; sedation; and other side effect profile.</AbstractText>Seventy patients (ASA I or II) scheduled for below elbow orthopedic surgeries were randomly allocated in equal numbers to receive either 30 ml of 0.5% plain bupivacaine with 150 &#x3bc;g (1 ml) of inj. clonidine locally in the axillary sheath and 1 ml of normal saline (NS) subcutaneously (Group L) or 30 ml of 0.5% plain bupivacaine with 1 ml of NS locally and 150 &#x3bc;g (1 ml) of inj. clonidine subcutaneously (Group S). Standard monitoring of vital parameters was done. Duration of sensory and motor block, analgesia, hemodynamic changes, and any adverse effects were observed and recorded for different duration up to 24 h.</AbstractText>Duration of sensory block (625 &#xb1; 35 min), motor block (690 &#xb1; 38 min), and analgesia (930 &#xb1; 45 min) was significantly longer in Group L than in Group S [sensory block (480 &#xb1; 30 min), motor block (535 &#xb1; 25 min), and analgesia (720 &#xb1; 30 min)] (P &lt; 0.05). Significant alteration of heart rate, systolic blood pressure and diastolic blood pressure, and mean arterial pressure in Group S was observed compared to Group L (P &lt; 0.05). Side effects like nausea and vomiting were comparable, but highly significant sedation score (&#x3c7;(2) = 47.75 and 49.51 at 120 and 240 min, respectively; P &lt; 0.01) was observed between the two groups.</AbstractText>Compared to systemic administration, local clonidine as an adjuvant in axillary block resulted in significant prolongation of duration of sensory and motor blockade, and analgesia without any hemodynamic alteration, probably by locally mediated mechanism of action.</AbstractText>
2,334,019
An intron-retaining splice variant of human cyclin A2, expressed in adult differentiated tissues, induces a G1/S cell cycle arrest in vitro.
Human cyclin A2 is a key regulator of S phase progression and entry into mitosis. Alternative splice variants of the G1 and mitotic cyclins have been shown to interfere with full-length cyclin functions to modulate cell cycle progression and are therefore likely to play a role in differentiation or oncogenesis. The alternative splicing of human cyclin A2 has not yet been studied.</AbstractText><AbstractText Label="METHODOLOGY/PRINCIPAL FINDINGS" NlmCategory="RESULTS">Sequence-specific primers were designed to amplify various exon-intron regions of cyclin A2 mRNA in cell lines and human tissues. Intron retaining PCR products were cloned and sequenced and then overexpressed in HeLa cells. The subcellular localization of the splice variants was studied using confocal and time-lapse microscopy, and their impact on the cell cycle by flow cytometry, immunoblotting and histone H1 kinase activity. We found a splice variant of cyclin A2 mRNA called A2V6 that partly retains Intron 6. The gene expression pattern of A2V6 mRNA in human tissues was noticeably different from that of wild-type cyclin A2 (A2WT) mRNA. It was lower in proliferating fetal tissues and stronger in some differentiated adult tissues, especially, heart. In transfected HeLa cells, A2V6 localized exclusively in the cytoplasm whereas A2WT accumulated in the nucleus. We show that A2V6 induced a clear G1/S cell cycle arrest associated with a p21 and p27 upregulation and an inhibition of retinoblastoma protein phosphorylation. Like A2WT, A2V6 bound CDK2, but the A2V6/CDK2 complex did not phosphorylate histone H1.</AbstractText><AbstractText Label="CONCLUSION/SIGNIFICANCE" NlmCategory="CONCLUSIONS">This study has revealed that some highly differentiated human tissues express an intron-retaining cyclin A2 mRNA that induced a G1/S block in vitro. Contrary to full-length cyclin A2, which regulates cell proliferation, the A2V6 splice variant might play a role in regulating nondividing cell states such as terminal differentiation or senescence.</AbstractText>
2,334,020
Na(+)/K)+)-ATPase &#x3b1;2-isoform preferentially modulates Ca2(+) transients and sarcoplasmic reticulum Ca2(+) release in cardiac myocytes.
Na(+)/K(+)-ATPase (NKA) is essential in regulating [Na(+)](i), and thus cardiac myocyte Ca(2+) and contractility via Na(+)/Ca(2+) exchange. Different NKA-&#x3b1; subunit isoforms are present in the heart and may differ functionally, depending on specific membrane localization. In smooth muscle and astrocytes, NKA-&#x3b1;2 is located at the junctions with the endo(sarco)plasmic reticulum, where they could regulate local [Na(+)], and indirectly junctional cleft [Ca(2+)]. Whether this model holds for cardiac myocytes is unclear.</AbstractText>The ouabain-resistant NKA-&#x3b1;1 cannot be selectively blocked to assess its effect. To overcome this, we used mice in which NKA-&#x3b1;1 is ouabain sensitive and NKA-&#x3b1;2 is ouabain resistant (SWAP mice). We measured the effect of ouabain at low concentration on [Na(+)](i), Ca(2+) transients, and the fractional sarcoplasmic reticulum (SR) Ca(2+) release in cardiac myocytes from wild-type (WT; NKA-&#x3b1;2 inhibition) and SWAP mice (selective NKA-&#x3b1;1 block). At baseline, Na(+) and Ca(2+) regulations are similar in WT and SWAP mice. For equal levels of total NKA inhibition (~25%), ouabain significantly increased Ca(2+) transients (from &#x394;F/F(0)= 1.5 &#xb1; 0.1 to 1.8 &#xb1; 0.1), and fractional SR Ca(2+) release (from 24 &#xb1; 3 to 29 &#xb1; 3%) in WT (NKA-&#x3b1;2 block) but not in SWAP myocytes (NKA-&#x3b1;1 block). This occurred despite a similar and modest increase in [Na(+)](i) (~2 mM) in both groups. The effect in WT mice was mediated specifically by NKA-&#x3b1;2 inhibition because at a similar concentration ouabain had no effect in transgenic mice where both NKA-&#x3b1;1 and NKA-&#x3b1;2 are ouabain resistant.</AbstractText>NKA-&#x3b1;2 has a more prominent role (vs. NKA-&#x3b1;1) in modulating cardiac myocyte SR Ca(2+) release.</AbstractText>
2,334,021
[Basic mechanisms of the new antiarrhythmic drugs in atrial fibrillation].
Atrial fibrillation (AF) is the most common sustained arrhythmia seen in clinical practice. Despite of new technological breakthroughs and the understanding of the mechanisms underlying AF, based on animal models and ablation procedures in patients, the antiarrhythmic drugs remain the main therapeutic strategy to restore and maintain the sinus rhythm. New antiarrhythmic drugs are already available in the clinical practice and many others are under development. The new antiarrhythmic drugs have the capability to block atrial-specific ionic currents, which are involved in the maintenance of the arrhythmia. Parallel, increasing evidence supports the use of compounds to regulate the arrhythmogenic atrial substrate involved in the long-term maintenance of the arrhythmia (upstream therapies). This article reviews the new antiarrhythmic drugs and upstream therapies, based on the current knowledge of the mechanisms involved in the maintenance of AF.
2,334,022
Effect of heterogeneities in the cellular microstructure on propagation of the cardiac action potential.
Cardiac arrhythmias are initiated in regions that undergo cellular remodeling as a result of disease. Using a sub-cellular model of myocardium, we studied the mechanism of block caused by tissue microstructure remodeling: cell geometry [quantified as length/width (L/W) cell ratio] and cell-to-cell coupling (G(j)). Heterogeneities in cell L/W ratio and G ( j ) lead to block when excitability is reduced and the corresponding space constant &#x3bb; (in the direction of propagation) increases by &gt;40 %. Tissue architectures with elongated cells (i.e. large cell L/W ratios) that are better coupled (i.e. large G(j)) are less prone to block at sites of regional heterogeneities in cell geometry and/or cell coupling than tissue architectures consisting of cells with smaller L/W ratios and/or poorer coupling. Whether an increase in tissue anisotropic ratio (ANR) is arrhythmogenic or not depends on the cellular mechanism of the increase: ANR leads to an increased risk of block when G(j) decreases, but to a decreased risk of block when cell L/W ratio increases. Our findings are useful to understand the mechanisms of block in cardiac pathologies that result in tissue architecture remodeling.
2,334,023
Using the negative exponential distribution to quantitatively review the evidence on how rapidly the excess risk of ischaemic heart disease declines following quitting smoking.
No previous review has formally modelled the decline in IHD risk following quitting smoking. From PubMed searches and other sources we identified 15 prospective and eight case-control studies that compared IHD risk in current smokers, never smokers, and quitters by time period of quit, some studies providing separate blocks of results by sex, age or amount smoked. For each of 41 independent blocks, we estimated, using the negative exponential model, the time, H, when the excess risk reduced to half that caused by smoking. Goodness-of-fit to the model was adequate for 35 blocks, others showing a non-monotonic pattern of decline following quitting, with a variable pattern of misfit. After omitting one block with a current smoker RR 1.0, the combined H estimate was 4.40 (95% CI 3.26-5.95) years. There was considerable heterogeneity, H being &lt;2years for 10 blocks and &gt;10years for 12. H increased (p&lt;0.001) with mean age at study start, but not clearly with other factors. Sensitivity analyses allowing for reverse causation, or varying assumed midpoint times for the final open-ended quitting period little affected goodness-of-fit of the combined estimate. The US Surgeon-General's view that excess risk approximately halves after a year's abstinence seems over-optimistic.
2,334,024
Blocking Scn10a channels in heart reduces late sodium current and is antiarrhythmic.
Although the sodium channel locus SCN10A has been implicated by genome-wide association studies as a modulator of cardiac electrophysiology, the role of its gene product Nav1.8 as a modulator of cardiac ion currents is unknown.</AbstractText>We determined the electrophysiological and pharmacological properties of Nav1.8 in heterologous cell systems and assessed the antiarrhythmic effect of Nav1.8 block on isolated mouse and rabbit ventricular cardiomyocytes.</AbstractText>We first demonstrated that Scn10a transcripts are identified in mouse heart and that the blocker A-803467 is highly specific for Nav1.8 current over that of Nav1.5, the canonical cardiac sodium channel encoded by SCN5A. We then showed that low concentrations of A-803467 selectively block "late" sodium current and shorten action potentials in mouse and rabbit cardiomyocytes. Exaggerated late sodium current is known to mediate arrhythmogenic early afterdepolarizations in heart, and these were similarly suppressed by low concentrations of A-803467.</AbstractText>Scn10a expression contributes to late sodium current in heart and represents a new target for antiarrhythmic intervention.</AbstractText>
2,334,025
High-resolution 3-dimensional reconstruction of the infarct border zone: impact of structural remodeling on electrical activation.
Slow nonuniform electric propagation in the border zone (BZ) of a healed myocardial infarct (MI) can give rise to reentrant arrhythmia. The extent to which this is influenced by structural rather than cellular electric remodeling is unclear.</AbstractText>To determine whether structural remodeling alone in the infarct BZ could provide a substrate for re-entry by (i) characterizing the 3-dimensional (3D) structure of the myocardium surrounding a healed MI at high spatial resolution and (ii) modeling electric activation on this structure.</AbstractText>Anterior left ventricular (LV) infarcts were induced in 2 rats by coronary artery ligation. Three-dimensional BZ volume (4.1 mm(3) and 5.6 mm(3)) were imaged at 14 days using confocal microscopy. Viable myocytes were identified, and their connectivity and orientation were quantified. Preserved cell networks were observed in the subendocardium and subepicardium of the infarct. Myocyte tracts traversed the BZ, and there was heavy infiltration of collagen into the adjacent myocardium. Myocyte connectivity decreased by &#x2248;65% over 250 &#x3bc;m across the BZ. This structure was incorporated into 3D network models on which activation was simulated using Luo-Rudy membrane dynamics assuming normal cellular electric properties. Repetitive stimulation was imposed at selected BZ sites. Stimulus site-specific unidirectional propagation occurred in the BZ with rate-dependent slowing and conduction block, and reentry was demonstrated in one substrate. Activation times were prolonged because of tract path length and local slowing.</AbstractText>We have used a detailed image-based model of the infarct BZ to demonstrate that structural heterogeneity provides a dynamic substrate for electric reentry.</AbstractText>
2,334,026
Targeted therapies in breast cancer: are heart and vessels also being targeted?
The concept of 'targeted' therapies implies that such drugs only act on cells that specifically express the particular target, therefore giving rise to a low incidence of side effects. However, targeted therapies currently approved for the treatment of breast cancer have demonstrated a relatively high incidence of cardiovascular events. The anti-HER2 agents trastuzumab and lapatinib may cause left ventricular dysfunction or even congestive heart failure. Bevacizumab, an antiangiogenic drug, has been shown to increase the risk of hypertension, cardiovascular dysfunction and thromboembolic events. In addition, several anti-human epidermal growth factor receptor 2 (HER2) and antiangiogenic agents plus their combinations are currently being developed and evaluated for the treatment of breast cancer. In this review, we aim to assess the incidence of cardiac adverse events associated with targeted therapies designed to block HER2 and angiogenic pathways.
2,334,027
Limb venous distension evokes sympathetic activation via stimulation of the limb afferents in humans.<Pagination><StartPage>H457</StartPage><EndPage>H463</EndPage><MedlinePgn>H457-63</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1152/ajpheart.00236.2012</ELocationID><Abstract><AbstractText>We have recently shown that a saline infusion in the veins of an arterially occluded human forearm evokes a systemic response with increases in muscle sympathetic nerve activity (MSNA) and blood pressure. In this report, we examined whether this response was a reflex that was due to venous distension. Blood pressure (Finometer), heart rate, and MSNA (microneurography) were assessed in 14 young healthy subjects. In the saline trial (n = 14), 5% forearm volume normal saline was infused in an arterially occluded arm. To block afferents in the limb, 90 mg of lidocaine were added to the same volume of saline in six subjects during a separate visit. To examine whether interstitial perfusion of normal saline alone induced the responses, the same volume of albumin solution (5% concentration) was infused in 11 subjects in separate studies. Lidocaine abolished the MSNA and blood pressure responses seen with saline infusion. Moreover, compared with the saline infusion, an albumin infusion induced a larger (MSNA: &#x394;14.3 &#xb1; 2.7 vs. &#x394;8.5 &#xb1; 1.3 bursts/min, P &lt; 0.01) and more sustained MSNA and blood pressure responses. These data suggest that venous distension activates afferent nerves and evokes a powerful systemic sympathoexcitatory reflex. We posit that the venous distension plays an important role in evoking the autonomic adjustments seen with postural stress in human subjects.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Cui</LastName><ForeName>Jian</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Pennsylvania State University College of Medicine, Penn State Hershey Heart &amp; Vascular Institute, Hershey, PA 17033, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McQuillan</LastName><ForeName>Patrick M</ForeName><Initials>PM</Initials></Author><Author ValidYN="Y"><LastName>Blaha</LastName><ForeName>Cheryl</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Kunselman</LastName><ForeName>Allen R</ForeName><Initials>AR</Initials></Author><Author ValidYN="Y"><LastName>Sinoway</LastName><ForeName>Lawrence I</ForeName><Initials>LI</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>C06 RR016499</GrantID><Acronym>RR</Acronym><Agency>NCRR NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P01 HL-096570</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>UL1 RR-033184</GrantID><Acronym>RR</Acronym><Agency>NCRR NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P01 HL096570</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>C06 RR-016499</GrantID><Acronym>RR</Acronym><Agency>NCRR NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>UL1 TR000127</GrantID><Acronym>TR</Acronym><Agency>NCATS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2012</Year><Month>06</Month><Day>15</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Am J Physiol Heart Circ Physiol</MedlineTA><NlmUniqueID>100901228</NlmUniqueID><ISSNLinking>0363-6135</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000418">Albumins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000779">Anesthetics, Local</NameOfSubstance></Chemical><Chemical><RegistryNumber>451W47IQ8X</RegistryNumber><NameOfSubstance UI="D012965">Sodium Chloride</NameOfSubstance></Chemical><Chemical><RegistryNumber>98PI200987</RegistryNumber><NameOfSubstance UI="D008012">Lidocaine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000344" MajorTopicYN="N">Afferent Pathways</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000418" MajorTopicYN="N">Albumins</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration &amp; dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000704" MajorTopicYN="N">Analysis of Variance</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000779" MajorTopicYN="N">Anesthetics, Local</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration &amp; dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001794" MajorTopicYN="Y">Blood Pressure</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="N">Heart Rate</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007262" MajorTopicYN="N">Infusions, Intravenous</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007511" MajorTopicYN="N">Ischemia</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008012" MajorTopicYN="N">Lidocaine</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration &amp; dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D035002" MajorTopicYN="N">Lower Extremity</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018482" MajorTopicYN="N">Muscle, Skeletal</DescriptorName><QualifierName UI="Q000294" MajorTopicYN="Y">innervation</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010414" MajorTopicYN="N" Type="Geographic">Pennsylvania</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012018" MajorTopicYN="Y">Reflex</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D056152" MajorTopicYN="N">Respiratory Rate</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012965" MajorTopicYN="N">Sodium Chloride</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration &amp; dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013564" MajorTopicYN="N">Sympathetic Nervous System</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013997" MajorTopicYN="N">Time Factors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D034941" MajorTopicYN="N">Upper Extremity</DescriptorName><QualifierName UI="Q000098" MajorTopicYN="Y">blood supply</QualifierName><QualifierName UI="Q000294" MajorTopicYN="Y">innervation</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014680" MajorTopicYN="N">Veins</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014690" MajorTopicYN="N">Venous Pressure</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2012</Year><Month>6</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2012</Year><Month>6</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2012</Year><Month>10</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">22707559</ArticleId><ArticleId IdType="pmc">PMC3423143</ArticleId><ArticleId IdType="doi">10.1152/ajpheart.00236.2012</ArticleId><ArticleId IdType="pii">ajpheart.00236.2012</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Abboud FM, Thames MD. 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We have recently shown that a saline infusion in the veins of an arterially occluded human forearm evokes a systemic response with increases in muscle sympathetic nerve activity (MSNA) and blood pressure. In this report, we examined whether this response was a reflex that was due to venous distension. Blood pressure (Finometer), heart rate, and MSNA (microneurography) were assessed in 14 young healthy subjects. In the saline trial (n = 14), 5% forearm volume normal saline was infused in an arterially occluded arm. To block afferents in the limb, 90 mg of lidocaine were added to the same volume of saline in six subjects during a separate visit. To examine whether interstitial perfusion of normal saline alone induced the responses, the same volume of albumin solution (5% concentration) was infused in 11 subjects in separate studies. Lidocaine abolished the MSNA and blood pressure responses seen with saline infusion. Moreover, compared with the saline infusion, an albumin infusion induced a larger (MSNA: &#x394;14.3 &#xb1; 2.7 vs. &#x394;8.5 &#xb1; 1.3 bursts/min, P &lt; 0.01) and more sustained MSNA and blood pressure responses. These data suggest that venous distension activates afferent nerves and evokes a powerful systemic sympathoexcitatory reflex. We posit that the venous distension plays an important role in evoking the autonomic adjustments seen with postural stress in human subjects.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Cui</LastName><ForeName>Jian</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Pennsylvania State University College of Medicine, Penn State Hershey Heart &amp; Vascular Institute, Hershey, PA 17033, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McQuillan</LastName><ForeName>Patrick M</ForeName><Initials>PM</Initials></Author><Author ValidYN="Y"><LastName>Blaha</LastName><ForeName>Cheryl</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Kunselman</LastName><ForeName>Allen R</ForeName><Initials>AR</Initials></Author><Author ValidYN="Y"><LastName>Sinoway</LastName><ForeName>Lawrence I</ForeName><Initials>LI</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>C06 RR016499</GrantID><Acronym>RR</Acronym><Agency>NCRR NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P01 HL-096570</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>UL1 RR-033184</GrantID><Acronym>RR</Acronym><Agency>NCRR NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P01 HL096570</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>C06 RR-016499</GrantID><Acronym>RR</Acronym><Agency>NCRR NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>UL1 TR000127</GrantID><Acronym>TR</Acronym><Agency>NCATS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2012</Year><Month>06</Month><Day>15</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Am J Physiol Heart Circ Physiol</MedlineTA><NlmUniqueID>100901228</NlmUniqueID><ISSNLinking>0363-6135</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000418">Albumins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000779">Anesthetics, Local</NameOfSubstance></Chemical><Chemical><RegistryNumber>451W47IQ8X</RegistryNumber><NameOfSubstance UI="D012965">Sodium Chloride</NameOfSubstance></Chemical><Chemical><RegistryNumber>98PI200987</RegistryNumber><NameOfSubstance UI="D008012">Lidocaine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000344" MajorTopicYN="N">Afferent Pathways</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000418" MajorTopicYN="N">Albumins</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration &amp; dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000704" MajorTopicYN="N">Analysis of Variance</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000779" MajorTopicYN="N">Anesthetics, Local</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration &amp; dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001794" MajorTopicYN="Y">Blood Pressure</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="N">Heart Rate</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007262" MajorTopicYN="N">Infusions, Intravenous</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007511" MajorTopicYN="N">Ischemia</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008012" MajorTopicYN="N">Lidocaine</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration &amp; dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D035002" MajorTopicYN="N">Lower Extremity</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018482" MajorTopicYN="N">Muscle, Skeletal</DescriptorName><QualifierName UI="Q000294" MajorTopicYN="Y">innervation</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010414" MajorTopicYN="N" Type="Geographic">Pennsylvania</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012018" MajorTopicYN="Y">Reflex</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D056152" MajorTopicYN="N">Respiratory Rate</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012965" MajorTopicYN="N">Sodium Chloride</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration &amp; dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013564" MajorTopicYN="N">Sympathetic Nervous System</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013997" MajorTopicYN="N">Time Factors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D034941" MajorTopicYN="N">Upper Extremity</DescriptorName><QualifierName UI="Q000098" MajorTopicYN="Y">blood supply</QualifierName><QualifierName UI="Q000294" MajorTopicYN="Y">innervation</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014680" MajorTopicYN="N">Veins</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014690" MajorTopicYN="N">Venous Pressure</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2012</Year><Month>6</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2012</Year><Month>6</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2012</Year><Month>10</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">22707559</ArticleId><ArticleId IdType="pmc">PMC3423143</ArticleId><ArticleId IdType="doi">10.1152/ajpheart.00236.2012</ArticleId><ArticleId IdType="pii">ajpheart.00236.2012</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Abboud FM, Thames MD. 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Singapore: World Scientific, 1984, p. 15&#x2013;23</Citation></Reference><Reference><Citation>Yates BJ, Thompson FJ. Activation of spinal cord interneurons which process inputs from the femoral-saphenous vein. Brain Res 359: 383&#x2013;387, 1985</Citation><ArticleIdList><ArticleId IdType="pubmed">4075158</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">22706581</PMID><DateCompleted><Year>2012</Year><Month>08</Month><Day>29</Day></DateCompleted><DateRevised><Year>2021</Year><Month>10</Month><Day>21</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1940-087X</ISSN><JournalIssue CitedMedium="Internet"><Issue>62</Issue><PubDate><Year>2012</Year><Month>Apr</Month><Day>24</Day></PubDate></JournalIssue><Title>Journal of visualized experiments : JoVE</Title><ISOAbbreviation>J Vis Exp</ISOAbbreviation></Journal><ArticleTitle>A fluorescent screening assay for identifying modulators of GIRK channels.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">3850</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.3791/3850</ELocationID><Abstract>G protein-gated inward rectifier K+ (GIRK) channels function as cellular mediators of a wide range of hormones and neurotransmitters and are expressed in the brain, heart, skeletal muscle and endocrine tissue(1,2). GIRK channels become activated following the binding of ligands (neurotransmitters, hormones, drugs, etc.) to their plasma membrane-bound, G protein-coupled receptors (GPCRs). This binding causes the stimulation of G proteins (Gi and Go) which subsequently bind to and activate the GIRK channel. Once opened the GIRK channel allows the movement of K+ out of the cell causing the resting membrane potential to become more negative. As a consequence, GIRK channel activation in neurons decreases spontaneous action potential formation and inhibits the release of excitatory neurotransmitters. In the heart, activation of the GIRK channel inhibits pacemaker activity thereby slowing the heart rate. GIRK channels represent novel targets for the development of new therapeutic agents for the treatment neuropathic pain, drug addiction, cardiac arrhythmias and other disorders(3). However, the pharmacology of these channels remains largely unexplored. Although a number of drugs including anti-arrhythmic agents, antipsychotic drugs and antidepressants block the GIRK channel, this inhibition is not selective and occurs at relatively high drug concentrations(3). Here, we describe a real-time screening assay for identifying new modulators of GIRK channels. In this assay, neuronal AtT20 cells, expressing GIRK channels, are loaded with membrane potential-sensitive fluorescent dyes such as bis-(1,3-dibutylbarbituric acid) trimethine oxonol [DiBAC4(3)] or HLB 021-152 (Figure 1). The dye molecules become strongly fluorescent following uptake into the cells (Figure 1). Treatment of the cells with GPCR ligands stimulates the GIRK channels to open. The resulting K+ efflux out of the cell causes the membrane potential to become more negative and the fluorescent signal to decrease (Figure 1). Thus, drugs that modulate K+ efflux through the GIRK channel can be assayed using a fluorescent plate reader. Unlike other ion channel screening assays, such atomic absorption spectrometry(4) or radiotracer analysis(5), the GIRK channel fluorescent assay provides a fast, real-time and inexpensive screening procedure.
2,334,028
Comparison of three different formulations of local anaesthetics for cervical epidural anaesthesia during thyroid surgery.
To compare the efficacy and safety of local anaesthetics under cervical epidural anaesthesia (CEA) using lignocaine (1%), bupivacaine (0.25%) and ropivacaine (0.5%) for thyroid surgery.</AbstractText>In a prospective, randomized fashion, 81 patients were selected for thyroid surgery under CEA. They were assigned to one of three groups: Group L, B and R to receive 10 mL of 1% lignocaine, 0.25% bupivacaine and 0.5% ropivacaine, respectively. We compared their efficacy in terms of pulmonary and haemodynamic parameters, blockade quality and complications.</AbstractText>Of the total, 74 patients completed the study successfully. Sensory block attained the median dermatomal range of C2-T4/T5 in all the groups. Motor block was more pronounced in the ropivacaine group. Cardiorespiratory parameters decreased significantly in all the groups; however, none of the patients had any major complications except for bradycardia in two patients. Among the measured variables, the decrease in heart rate and peak expiratory force was more in the lignocaine group while forced vital capacity and forced expiratory volume at 1 sec declined to a greater extent in the ropivacaine group. The lignocaine group required significantly more epidural top-ups compared with the other two groups.</AbstractText>We conclude that cervical epidural route can be safely used for surgery on thyroid gland in patients with normal cardiorespiratory reserve, using either of local anaesthetics chosen for our study. Under the selected dose and concentrations, the decrease in cardiorespiratory parameters was lesser with bupivacaine.</AbstractText>
2,334,029
Mistaken identity: severe vomiting, bradycardia and hypotension after eating a wild herb.
A 53-year-old woman presented with severe vomiting 3.5 hours after eating a boiled wild herb thought to be Hosta montana. She was alert, and did not complain of diplopia or numbness of her limbs. Her vital signs were temperature of 35.9&#xb0;C, blood pressure of 84/33 mmHg, and heart rate of 59 beats/minute. There was no arrhythmia or conduction block on electrocardiogram. Her blood pressure and heart rate were decreased to 75/44 mmHg and 51 beats/minute at the minimum, respectively. Complete blood count and serum chemistry were normal. The herb was correctly identified when the patient's husband brought in the herb for identification.
2,334,030
A case of Rosai-Dorfman disease in a pediatric patient with cardiac involvement.
Rosai-Dorfman disease (RDD) involves abnormal proliferations of oddly behaving histocytes that are not derived from the Langerhan's Cell linage. These collections tend to occur within lymph nodes, with occasional extra nodal presentation. While RDD is a rare entity itself, extra nodal cases are even more so, with even fewer reporting cardiac involvement, and previously only in adults. This report describes the disease in a pediatric patient who had the unique feature of an extra nodal cardiac mass. The patient, who was known to have sickle cell disease, was initially erroneously thought to have acute chest syndrome. Sudden changes in the patient's status, including development of 3rd degree heart block, demanded investigation with additional imaging. Chest CT revealed a mass arising from the cardiac interatrial septum and encircling the entire thoracic aorta. Imaging features of Rosai-Dorfman disease are nonspecific, complicating the diagnosis. We present this case with discussion of this extremely uncommon entity. We describe the diagnostic methods, the differential diagnosis, and the treatment options.
2,334,031
Amnesia and pain relief after cardiopulmonary resuscitation in a cancer pain patient: a case report.
The mechanism of chronic pain is very complicated. Memory, pain, and opioid dependence appear to share common mechanism, including synaptic plasticity, and anatomical structures. A 48-yr-old woman with severe pain caused by bone metastasis of breast cancer received epidural block. After local anesthetics were injected, she had a seizure and then went into cardiac arrest. Following cardiopulmonary resuscitation, her cardiac rhythm returned to normal, but her memory had disappeared. Also, her excruciating pain and opioid dependence had disappeared. This complication, although uncommon, gives us a lot to think about a role of memory for chronic pain and opioid dependence.
2,334,032
Cerebellar Purkinje cell neurodegeneration after cardiac arrest: effect of therapeutic hypothermia.
The cerebellum is among the brain regions most vulnerable to damage caused by cardiac arrest, and cerebellar Purkinje cell loss may contribute to neurologic dysfunction, including post-hypoxic myoclonus. However, it remains unknown whether cerebellar Purkinje cells are protected by post-cardiac arrest therapeutic hypothermia (TH). Therefore, we examined the effect of post-cardiac arrest TH onset and duration on cerebellar Purkinje cell loss.</AbstractText>Samples from a previously published study of post-cardiac arrest TH were utilized for the present analysis. Adult male rats subjected to asphyxial cardiac arrest and cardiopulmonary resuscitation were block randomized to normothermia (37.0&#xb0;C) or TH (33.0&#xb0;C) initiated 0, 1, 4, or 8h after return of spontaneous circulation (ROSC) and maintained for 24 or 48 h. Cerebella from rats surviving 7 days after ROSC were processed for histology and immunohistochemistry. Purkinje cell density was quantified in Nissl-stained sections of the primary fissure of the cerebellar vermis.</AbstractText>With post-cardiac arrest normothermia, Purkinje cell density in the primary fissure was severely reduced compared to sham-injured controls (3.8 &#xb1; 1.8 cells mm(-1) vs. 35.9 &#xb1; 2.4 cells mm(-1), p&lt;0.001). TH moderately improved Purkinje cell survival in all groups combined (14.0 &#xb1; 5.6 cells mm(-1), p&lt;0.001 compared to normothermia). There was no statistical difference in Purkinje cell protection based on TH onset time or duration.</AbstractText>These results indicate that post-cardiac arrest TH protects selectively vulnerable cerebellar Purkinje cells within a broad therapeutic window. The potential clinical implications for improving Purkinje cell survival require further investigation.</AbstractText>Copyright &#xa9; 2012 Elsevier Ireland Ltd. All rights reserved.</CopyrightInformation>
2,334,033
Cardiac conduction block at multiple levels caused by arsenic trioxide therapy.
We present a rare case of a woman aged 62 years with refractory acute promyelocytic leukemia treated with arsenic trioxide leading to progressive, multilevel cardiac conduction block. After chelation treatment with dimercaprol, there was normalization of conduction.
2,334,034
Management of central venous gradient using excimer laser lead extraction of chronic indwelling pacemaker leads in the setting of ipsilateral arteriovenous fistula.
Device therapy is becoming common in those patients with renal insufficiency. Coexisting need for arteriovenous (AV) fistula placement is often contemplated relative to device placement. We describe the excimer laser lead extraction of a malfunctioning chronic atrial pacemaker lead ipsilateral to an AV fistula.
2,334,035
Effect of dietary inulin and phytase on mineral digestibility and tissue retention in weanling and growing swine.
The effect of dietary phytase and the prebiotic inulin on apparent mineral digestibility, bone mineralization, and tissue mineral contents was evaluated in weanling and growing pigs. In Exp. 1, inulin and phytase were incorporated in a 2 &#xd7; 3 factorial arrangement of treatments with 8 replicate pens per treatment in a randomized complete block design. There were 2 levels of phytase [0 and 1000 phytase units (FTU)/kg] and 3 levels of chicory inulin (0, 3, and 6%). Weanling pigs (17 d of age; 5 or 4 pigs per pen) with an initial BW of 6.0 &#xb1; 0.6 kg were evaluated for 35 d postweaning. Macromineral digestibility was calculated using chromic oxide as an index in fecal samples collected during the final week of the experiment in replicates 1 through 4. On d 36, 1 pig per pen was killed and the heart, liver, kidney, and left tibia were excised and weighed. Inulin did not have any effect on growth performance measurements. Phytase increased (P &lt; 0.05) BW on d 35 and ADG and ADFI during the 21-to-35-d and 0-to-35-d periods. Inulin did not result in increased tissue mineral concentrations on a per unit (mg/kg) or total tissue basis. Phytase increased (P &lt; 0.05) the concentration of Zn in the liver, Mn and Zn in the heart, and Mg and Mn in the kidney. Phytase also increased (P &lt; 0.05) total P, Mg, S, Mn, Se, and Zn in the liver as well as tibia ash. Phytase increased the digestibility of Ca (P &lt; 0.01) and P (P &lt; 0.05). Experiment 2 was conducted with growing pigs (initial BW, 41 &#xb1; 5 kg) to evaluate 2 levels of inulin (0 or 6%) and 2 levels of phytase (0 or 1000 FTU/kg) in a 2 &#xd7; 2 factorial with 6 replicates in a randomized complete block design. Total urine and feces were collected for 10 d from each of 24 barrows after a 21-d acclimation period. Inulin inclusion resulted in reduced Ca digestibility (P &lt; 0.05). Phytase increased (P &lt; 0.05) the digestibility of both Ca and P. These results indicate that dietary inulin does not affect the overall mineral status or growth performance of pigs, whereas phytase increases the utilization of Ca and several microminerals, in addition to P, and also increases growth performance. Inulin and phytase do not appear to interact to affect pig growth or mineral status.
2,334,036
Evaluation of peri-operative epidural analgesia with ropivacaine, ropivacaine and sufentanil, and ropivacaine, sufentanil and epinephrine in isoflurane anesthetized dogs undergoing tibial plateau levelling osteotomy.
The purpose of this study was to compare four epidural protocols for peri-operative analgesia in dogs undergoing tibial plateau levelling osteotomy. Forty client-owned dogs were randomly assigned to one of four treatments - groups R0.5 and R1 received 0.5mg/kg and 1mg/kg ropivacaine, respectively. Group SR0.5 received 1 &#x3bc;g/kg sufentanil plus 0.5mg/kg ropivacaine, and group SER0.5 received 1 &#x3bc;g/kg sufentanil, 0.5mg/kg ropivacaine plus 6 &#x3bc;g/kg epinephrine. Dilution, when required, was performed with saline, so that the injected volume was always 0.2 mL/kg. Intra-operatively, nociception assessment was based on the evaluation of changes in heart rate, respiratory rate and mean arterial pressure. Post-operative pain assessment was performed using the Glasgow visual analogue pain scale, and an ad hoc multifactorial pain score. Motor block was evaluated using a modified Bromage score. Intra-operatively, none of the animals was hypotensive. All groups except SER0.5 required rescue intra-operative fentanyl (40%, 30% and 40% of the animals in groups R0.5, R1 and SR0.5, respectively). Group SER0.5 showed lower post-operative pain scores, and group R1 significantly greater motor block, compared to the other treatment groups. None of the dogs had urinary retention. Epidural sufentanil-epinephrine-ropivacaine provided superior peri-operative analgesia compared to the other treatments, without producing clinically relevant side effects.
2,334,037
Octreotide-induced asystolic events in an intensive care unit patient with gastrointestinal bleeding.
Octreotide is a somatostatin analogue used to control upper gastrointestinal bleeding. We report a case of a patient with no significant cardiac history who had multiple asystolic events during an octreotide infusion at a relatively low dose. Although octreotide leading to bradycardia and heart block has been documented in several case reports, to our knowledge, octreotide-associated asystole has not been described. It is pertinent that physicians must be aware of this significant cardiac effect for vigilant cardiac monitoring and management, preferably in an intensive care setting. Furthermore, this suggests that although dose- and route-related effects have been described, some individuals may be susceptible at low doses, even in the absence of heart disease. There were no further recurrences after the drug was discontinued.
2,334,038
SU-E-J-44: Dual Energy Subtraction Imaging to Improve Tumor Visibility at Oblique Angles.
To characterize the contrast improvement of simulated tumors in an anthropomorphic phantom using Dual Energy (DE) subtraction with a clinical on-board imager (OBI) at oblique angles.</AbstractText>An Alderson lung/chest anthropomorphic phantom with simulated tumors in the thoracic cavity was imaged using a sequential DE imaging methodology. High (120kVp) and low (60kVp) planar images were obtained in pairs every 100 in a full (3600) rotation using the OBI (Varian Medical Systems, Palo Alto, CA). Optimal mAs settings for DE component images were determined byvarying the x-ray exposure time, while maintaining a constant tube current. DE images were created to best suppress the bone overlaying the simulated tumors. Tumor visibility in DE images was quantified using the Contrast-to-Noise Ratio (CNR). The ratio of the CNR from the DE image relative to a single image (standard protocol) was evaluated as a function of gantry angle.</AbstractText>CNR was improved with DE imaging by an average ratio of 1.66 over all gantry angles. The greatest improvement occurred at gantry angles where the tumor was obstructed by the ribs alone. More modest improvements were observed where the tumor overlapped other soft tissue structures (such as the heart) or the dense spine, on a given projection.</AbstractText>This study illustrates the feasibility of performing DE imaging at oblique gantry angles using a clinical on-board imaging system. Incorporating DE imaging into clinical practice may allow for verification of tumor position at oblique gantry angles, and may facilitate the development of markerless motion tracking techniques. Supported by a grant from Varian Medical Systems.</AbstractText>&#xa9; 2012 American Association of Physicists in Medicine.</CopyrightInformation>
2,334,039
SU-E-T-276: Treatment Planning Strategies for Lung Injury Studies in Rat Models in 6 MV Delivery.
To study planning strategies that can be used in small animal radiation-induced lung toxicity experiments using 6 MV accelerator with high density MLC.</AbstractText>Three different types of plans were designed on CT images of a Sprague Dawley rat model to irradiate 50% of the total lung volume (lung divided into apex and base) with a prescription dose of 24 Gy to the partial lung. Two VMAT arc therapy plans were optimized to cover to the prescription dose, either the apex or base of the lung. Two AP- PA plans were designed to completely block either lung apex or base while irradiating the remaining 50% of the lung. Finally, two AP-PA plans were designed to cover, to the prescription dose, the apex or base of the lung. The plans were designed and optimized using the Eclipse AAA algorithm and recalculated using the MMCTP/EGS/Beam Monte Carlo system.</AbstractText>When completely blocking the lung base, the apex will be underdosed by up to 30%; when completely covering the apex by the prescribed dose, the base will receive overdosing (V50%=73%). The VMAT plan leads to a more conformal dose distribution and spares unnecessary skin exposure when compared to AP-PA MV or kV delivery. Despite the small size of rat model, the 6 MV VMAT delivery is superior in terms of dose conformality and sparing of the heart and the non-irradiated 50% of the lung compared to the standard, simpler, AP-PA delivery. MC dosimetry in lung shows that the delivered dose is 10% higher than predicted by AAA because of the predominance of small fields in the delivery.</AbstractText>Clinical state-of- the-art planning and delivery techniques can be scaled down accurately to rats. The use of these techniques is essential in small animal studies to render conclusions of radiation response investigations translatable to human studies.</AbstractText>&#xa9; 2012 American Association of Physicists in Medicine.</CopyrightInformation>
2,334,040
Effects of adding dexmedetomidine to levobupivacaine in axillary brachial plexus block.
Although several studies have described effects of dexmedetomidine on peripheral nerve blocks, to date there is limited knowledge available on the impact of dexmedetomidine adjunct to levobupivacaine in axillary brachial plexus block.</AbstractText>In this study, we aimed to investigate the effects of adding dexmedetomidine to levobupivacaine for an axillary brachial plexus block.</AbstractText>A total of 64 patients of American Society of Anesthesiologists physical status I/II scheduled to undergo forearm and hand surgery, in which an axillary block was used, were enrolled. The patients were randomly divided into 2 groups: in group L patients (n = 32), an axillary block was performed with 39 mL levobupivacaine 5% plus 1 mL of isotonic sodium chloride. In group D patients (n = 32), an axillary block was performed with 39 mL levobupivacaine 5% and 1 mL dexmedetomidine 1 &#x3bc;g/kg(-1) plus isotonic sodium chloride. Demographic data, mean arterial pressure (MAP), heart rate (HR), peripheral oxygen saturation (Spo2), sensory and motor block onset times and block durations, time to first analgesic use, total analgesic need, intraoperative verbal analog scale, postoperative visual analog scale (VAS) data, and side effects were recorded for each patient.</AbstractText>There were no significant differences in patient and surgery characteristics between the 2 groups. Sensory block onset time was shorter in group D (P &lt; 0.05). Sensory and motor block duration and time to first analgesic use were significantly longer in group D (P &lt; 0.05), and the total need for analgesics was lower in group D (P &lt; 0.05). Intraoperative 5- and 10-minute verbal analog scale values and postoperative VAS value at 12 hours were significantly lower in group D (P &lt; 0.05). Intraoperative MAP and HR values, except at 5 minutes and postoperatively at 10 and 30 minutes and 1 and 2 hours, were significantly lower in group D (P &lt; 0.01). Bradycardia, hypotension, hypoxemia, nausea, vomiting, and any other side effects were not seen in any patients.</AbstractText>It was concluded in our study that adding dexmedetomidine to axillary brachial plexus block shortens sensory block onset time, increases the sensory and motor block duration and time to first analgesic use, and decreases total analgesic use with no side effects. ClinicalTrials.gov identifier ISRCTN67622282.</AbstractText>
2,334,041
Does epidural clonidine improve postoperative analgesia in major vascular surgery?
To determine the quality and duration of the analgesic and haemodynamic effects of clonidine when used as an additional analgesic for postoperative epidural analgesia in major vascular surgery.</AbstractText>The prospective, single-blinded study involved 60 patients randomised into three groups (20 patients each): Group BM- bupivacaine 0.125% and morphine 0.1 mg/ml; Group BC-bupivacaine 0.125% and clonidine 5 &#x3bc;g/ml; Group MC-morphine 0.1 mg/ml and clonidine 5 &#x3bc;g/ml continuously infused at 5 ml/h. The quality and duration of the analgesia measured by the Visual Analogue Scale (VAS) at rest and on movement, additional analgesia requirements, sedation scores, haemodynamic parameters and side effects (respiratory depression, motor block, toxic effects, nausea and pruritus) were recorded.</AbstractText>The average VAS scores at rest and on movement were significantly lower in Group MC at two, six and 24 hours following the start of epidural infusion (P&lt;0.05). The duration of the analgesic effect after finishing the epidural infusion was significantly longer in Group MC (P&lt;0.05). Patients from Group MC were intubated longer. Additional analgesia consumption, sedation scores and haemodynamic profiles were similar in all three groups. Pruritus was more frequent in morphine groups (P&lt;0.05), but other side effects were similar in all three groups.</AbstractText>Under study conditions, clonidine added to morphine, not 0.125% bupivacaine, provided significantly better pain scores at two, six and 24 hours following the start of epidural infusion and the longest-lasting analgesia following the discontinuation of epidural infusion. However, patients from the Group MC were mechanically ventilated longer than patients from other two groups. Continuous monitoring of the patient is necessary after the administration of clonidine for epidural analgesia.</AbstractText>
2,334,042
Natural history of conduction abnormalities in a patient with Kearns-Sayre syndrome.
Kearns-Sayre syndrome is a rare mitochondrial disorder characterized by large-scale deletion or rearrangement of mitochondrial DNA, which is usually not inherited but occur spontaneously probably at the germ cell level or very early in embryonic development by Mehndiratta et al. (Neurol India 50:162-167, 2002). Neuromuscular and cardiac conduction abnormalities are most commonly involved in these patients, which may have subtle presenting signs.
2,334,043
Influence of starter protein content on growth of dairy calves in an enhanced early nutrition program.
Our objectives were to determine the effect of starter crude protein (CP) content on growth of Holstein calves from birth to 10 wk of age in an enhanced early nutrition program, and to compare the enhanced program to a conventional milk replacer program. Calves (64 female, 25 male) were assigned to 3 treatments in a randomized block design: 1) conventional milk replacer (20% CP, 20% fat) plus conventional starter [19.6% CP, dry matter (DM) basis], 2) enhanced milk replacer (28.5% CP, 15% fat) plus conventional starter, and 3) enhanced milk replacer plus high-CP starter (25.5% CP, DM basis). Calves began treatments (n=29, 31, and 29 for treatments 1 to 3) at 3 d of age. Conventional milk replacer (12.5% solids) was fed at 1.25% of birth body weight (BW) as DM daily in 2 feedings from wk 1 to 5 and at 0.625% of birth BW once daily during wk 6. Enhanced milk replacer (15% solids) was fed at 1.5% of BW as DM during wk 1 and 2% of BW as DM during wk 2 to 5, divided into 2 daily feedings. During wk 6, enhanced milk replacer was fed at 1% of BW as DM once daily. Calves were weaned at d 42. Starter was available for ad libitum intake starting on d 3. Starter intake was greater for calves fed conventional milk replacer. For calves fed enhanced milk replacer, starter intake tended to be greater for calves fed enhanced starter. During the weaning period, enhanced starter promoted greater starter DM intake than the conventional starter. Over the 10-wk study, the average daily gain of BW (0.64, 0.74, and 0.80 kg/d) was greater for calves fed enhanced milk replacer with either starter and, for calves fed enhanced milk replacer, tended to be greater for calves fed high-CP starter. Rates of change in withers height, body length, and heart girth were greater for calves fed enhanced milk replacer but did not differ between starter CP concentrations. The postweaning BW for enhanced milk replacer treatments was greater for calves receiving the enhanced starter at wk 8 (73.7, 81.3, and 85.8 kg) and wk 10 (88.0, 94.9, and 99.9 kg). Starter CP content did not affect height, length, or heart girth within enhanced milk replacer treatments. Regression analysis showed that gain of BW during the first week postweaning (wk 7) increased with greater 3-d mean starter intake in the week before weaning. Starter with 25.5% CP (DM basis) provided modest benefits in starter intake (particularly around weaning) and growth for dairy calves in an enhanced early nutrition program compared with a conventional starter (19.6% CP).
2,334,044
Patients transplanted for nonalcoholic steatohepatitis are at increased risk for postoperative cardiovascular events.
Nonalcoholic steatohepatitis (NASH) is an independent predictor of coronary artery disease (CAD). Our aim was to compare the incidence of cardiovascular (CV) events between patients transplanted for NASH and alcohol (ETOH)-induced cirrhosis. This is a retrospective cohort study (August 1993 to March 2010) of 242 patients (115 NASH and 127 ETOH) with &#x2265;12 months follow-up after liver transplantation (LT). Those with hepatocellular carcinoma or coexisting liver diseases were excluded. Kaplan-Meier's and Cox's proportional hazard analyses were conducted to compare survival. Logistic regression was used to calculate the likelihood of CV events, defined as death from any cardiac cause, myocardial infarction, acute heart failure, cardiac arrest, arrhythmia, complete heart block, and/or stroke requiring hospitalization &lt;1 year after LT. Patients in the NASH group were older (58.4 versus 53.3 years) and were more likely to be female (45% versus 18%; P &lt; 0.001). They were more likely to be morbidly obese (32% versus 9%), have dyslipidemia (25% versus 6%), or have hypertension (53% versus 38%; P &lt; 0.01). On multivariate analysis, NASH patients were more likely to have a CV event &lt;1 year after LT, compared to ETOH patients, even after controlling for recipient age, sex, smoking status, pretransplant diabetes, CV disease, and the presence of metabolic syndrome (26% versus 8%; odds ratio = 4.12; 95% confidence interval = 1.91-8.90). The majority (70%) of events occurred in the perioperative period, and the occurrence of a CV event was associated with a 50% overall mortality. However, there were no differences in patient, graft, or CV mortality between groups.</AbstractText>CV complications are common after LT, and NASH patients are at increased risk independent of traditional cardiac risk factors, though this did not affect overall mortality.</AbstractText>Copyright &#xa9; 2012 American Association for the Study of Liver Diseases.</CopyrightInformation>
2,334,045
Cardioprotection from oxidative stress in the newborn heart by activation of PPAR&#x3b3; is mediated by catalase.
Regulation of catalase (CAT) by peroxisome proliferator-activated receptor-&#x3b3; (PPAR&#x3b3;) was investigated to determine if PPAR&#x3b3; activation provides cardioprotection from oxidative stress caused by hydrogen peroxide (H(2)O(2)) in an age-dependent manner. Left ventricular developed pressure (LVDP) was measured in Langendorff perfused newborn or adult rabbit hearts, exposed to 200&#x3bc;M H(2)O(2), with perfusion of rosiglitazone (RGZ) or pioglitazone (PGZ), PPAR&#x3b3; agonists. We found: (1) H(2)O(2) significantly decreased sarcomere shortening in newborn ventricular cells but not in adult cells. Lactate dehydrogenase (LDH) release occurred earlier in newborn than in adult heart, which may be due, in part, to the lower expression of CAT in newborn heart. (2) RGZ increased CAT mRNA and protein as well as activity in newborn but not in adult heart. GW9662 (PPAR&#x3b3; blocker) eliminated the increased CAT mRNA by RGZ. (3) In newborn heart, RGZ and PGZ treatment inhibited release of LDH in response to H(2)O(2) compared to H(2)O(2) alone. GW9662 decreased this inhibition. (4) LVDP was significantly higher in both RGZ+H(2)O(2) and PGZ+H(2)O(2) groups than in the H(2)O(2) group. Block of PPAR&#x3b3; abolished this effect. In contrast, there was no effect of RGZ in adult. (5) The cardioprotective effects of RGZ were abolished by inhibition of CAT. In conclusion, PPAR&#x3b3; activation is cardioprotective to H(2)O(2)-induced stress in the newborn heart by upregulation of catalase. These data suggest that PPAR&#x3b3; activation may be an effective therapy for the young cardiac patient.
2,334,046
Functional significance of M-type potassium channels in nociceptive cutaneous sensory endings.
M-channels carry slowly activating potassium currents that regulate excitability in a variety of central and peripheral neurons. Functional M-channels and their Kv7 channel correlates are expressed throughout the somatosensory nervous system where they may play an important role in controlling sensory nerve activity. Here we show that Kv7.2 immunoreactivity is expressed in the peripheral terminals of nociceptive primary afferents. Electrophysiological recordings from single afferents in vitro showed that block of M-channels by 3 &#x3bc;M XE991 sensitized A&#x3b4;- but not C-fibers to noxious heat stimulation and induced spontaneous, ongoing activity at 32&#xb0;C in many A&#x3b4;-fibers. These observations were extended in vivo: intraplantar injection of XE991 selectively enhanced the response of deep dorsal horn (DH) neurons to peripheral mid-range mechanical and higher range thermal stimuli, consistent with a selective effect on A&#x3b4;-fiber peripheral terminals. These results demonstrate an important physiological role of M-channels in controlling nociceptive A&#x3b4;-fiber responses and provide a rationale for the nocifensive behaviors that arise following intraplantar injection of the M-channel blocker XE991.
2,334,047
PKC&#x3b2;II modulation of myocyte contractile performance.
Significant up-regulation of the protein kinase C&#x3b2;(II) (PKC&#x3b2;(II)) develops during heart failure and yet divergent functional outcomes are reported in animal models. The goal here is to investigate PKC&#x3b2;(II) modulation of contractile function and gain insights into downstream targets in adult cardiac myocytes. Increased PKC&#x3b2;(II) protein expression and phosphorylation developed after gene transfer into adult myocytes while expression remained undetectable in controls. The PKC&#x3b2;(II) was distributed in a peri-nuclear pattern and this expression resulted in diminished rates and amplitude of shortening and re-lengthening compared to controls and myocytes expressing dominant negative PKC&#x3b2;(II) (PKC&#x3b2;DN). Similar decreases were observed in the Ca(2+) transient and the Ca(2+) decay rate slowed in response to caffeine in PKC&#x3b2;(II)-expressing myocytes. Parallel phosphorylation studies indicated PKC&#x3b2;(II) targets phosphatase activity to reduce phospholamban (PLB) phosphorylation at residue Thr17 (pThr17-PLB). The PKC&#x3b2; inhibitor, LY379196 (LY) restored pThr17-PLB to control levels. In contrast, myofilament protein phosphorylation was enhanced by PKC&#x3b2;(II) expression, and individually, LY and the phosphatase inhibitor, calyculin A each failed to block this response. Further work showed PKC&#x3b2;(II) increased Ca(2+)-activated, calmodulin-dependent kinase II&#x3b4; (CaMKII&#x3b4;) expression and enhanced both CaMKII&#x3b4; and protein kinase D (PKD) phosphorylation. Phosphorylation of both signaling targets also was resistant to acute inhibition by LY. These later results provide evidence PKC&#x3b2;(II) modulates contractile function via intermediate downstream pathway(s) in cardiac myocytes.
2,334,048
Improved outcomes in paediatric anaesthesia: contributing factors.
To discuss developments in paediatric anaesthesia and explore the factors which have contributed to improved anaesthetic-related patient outcomes.</AbstractText>Narrative review of findings in the literature retrieved from MEDLINE/Pubmed and manual search.</AbstractText>Adverse perioperative outcomes related to anaesthesia have been extensively debated over the past few decades, with studies implicating factors such as major human error and equipment failure. Case series and event registries have enlightened physicians on sources of error and patient risk factors such as extremes of age, comorbidity and emergent circumstances. Anaesthetic-related deaths in children fell from 6.4 per 10,000 anaesthetics in the early 1950s to as low as 0.1 per 10,000 anaesthetics by the end of the century. Advances in anaesthetic agents, techniques, monitoring technologies and training programmes in paediatric anaesthesia play a vital role in driving this downward trend.</AbstractText>Despite substantial progress, there is still much room for improvement in areas such as adverse-event reporting, anaesthetic-related risk and late neurocognitive outcomes. Systematic reviews comparing paediatric patient outcomes after neuroaxial block versus general anaesthesia are currently unavailable. The future of paediatric anaesthesia will most likely be influenced by much-needed large prospective studies, which can provide further insight into patient safety and service delivery.</AbstractText>
2,334,049
Isolated left-ventricular apical hypoplasia presenting as a left-ventricular mass on echocardiography.
Left-ventricular apical hypoplasia is a rare entity. Although it has typical imaging features on cardiovascular magnetic resonance, recognizing this condition on echocardiography can be challenging. This report describes an asymptomatic pediatric patient who initially presented with a left-ventricular mass on echocardiography.
2,334,050
How reading in a second language protects your heart.
Reading words in a second language spontaneously activates native language translations in the human bilingual mind. Here, we show that the emotional valence of a word presented in English constrains unconscious access to its Chinese translation. We asked native speakers of Chinese fluent with English to indicate whether or not pairs of English words were related in meaning while monitoring their brain electrical activity. Unbeknownst to the participants, some of the word pairs hid a sound repetition if translated into Chinese. Remarkably, English words with a negative valence such as "violence" did not automatically activate their Chinese translation, even though we observed the expected sound repetition priming effect for positive and neutral words, such as "holiday" and "theory." These findings show that emotion conveyed by words determines language activation in bilinguals, where potentially disturbing stimuli trigger inhibitory mechanisms that block access to the native language.
2,334,051
Ranolazine decreases mechanosensitivity of the voltage-gated sodium ion channel Na(v)1.5: a novel mechanism of drug action.
Na(V)1.5 is a mechanosensitive voltage-gated sodium-selective ion channel responsible for the depolarizing current and maintenance of the action potential plateau in the heart. Ranolazine is a Na(V)1.5 antagonist with antianginal and antiarrhythmic properties.</AbstractText>Mechanosensitivity of Na(V)1.5 was tested in voltage-clamped whole cells and cell-attached patches by bath flow and patch pressure, respectively. In whole cells, bath flow increased peak inward current in both murine ventricular cardiac myocytes (24&#xb1;8%) and human embryonic kidney 293 cells heterologously expressing Na(V)1.5 (18&#xb1;3%). The flow-induced increases in peak current were blocked by ranolazine. In cell-attached patches from cardiac myocytes and Na(V)1.5-expressing human embryonic kidney 293 cells, negative pressure increased Na(V) peak currents by 27&#xb1;18% and 18&#xb1;4% and hyperpolarized voltage dependence of activation by -11 mV and -10 mV, respectively. In human embryonic kidney 293 cells, negative pressure also increased the window current (250%) and increased late open channel events (250%). Ranolazine decreased pressure-induced shift in the voltage dependence (IC(50) 54 &#x3bc;mol/L) and eliminated the pressure-induced increases in window current and late current event numbers. Block of Na(V)1.5 mechanosensitivity by ranolazine was not due to the known binding site on DIVS6 (F1760). The effect of ranolazine on mechanosensitivity of Na(V)1.5 was approximated by lidocaine. However, ionized ranolazine and charged lidocaine analog (QX-314) failed to block mechanosensitivity.</AbstractText>Ranolazine effectively inhibits mechanosensitivity of Na(V)1.5. The block of Na(V)1.5 mechanosensitivity by ranolazine does not utilize the established binding site and may require bilayer partitioning. Ranolazine block of Na(V)1.5 mechanosensitivity may be relevant in disorders of mechanoelectric dysfunction.</AbstractText>
2,334,052
Symptomatic epidural gas cyst treated with epidural block and percutaneous needle aspiration -A case report-.
A 68-year-old woman suffered from lower back and radiating pain on her right buttock and posterior calf. Axial magnetic resonance imaging showed a 7 &#xd7; 7 mm nodular lesion (T1 and, T2 low signal intensity) at the epidural space between the L5-S1 level and computed tomography revealed it was an epidural gas cyst. The authors performed an epidural block and percutaneous needle aspiration of the epidural gas cyst. The patient showed almost complete resolution of symptoms one year later. The authors suggest that an epidural nerve block with needle aspiration of a gas cyst could be an alternative treatment option for patients with a symptomatic epidural gas cyst before surgery.
2,334,053
Regional cardiac motion and strain estimation in three-dimensional echocardiography: a validation study in thick-walled univentricular phantoms.
Automatic quantification of regional left ventricular deformation in volumetric ultrasound data remains challenging. Many methods have been proposed to extract myocardial motion, including techniques using block matching, phase-based correlation, differential optical flow methods, and image registration. Our lab previously presented an approach based on elastic registration of subsequent volumes using a B-spline representation of the underlying transformation field. Encouraging results were obtained for the assessment of global left ventricular function, but a thorough validation on a regional level was still lacking. For this purpose, univentricular thick-walled cardiac phantoms were deformed in an experimental setup to locally assess strain accuracy against sonomicrometry as a reference method and to assess whether regions containing stiff inclusions could be detected. Our method showed good correlations against sonomicrometry: r(2) was 0.96, 0.92, and 0.84 for the radial (&#x3b5;(RR)), longitudinal (&#x3b5;(LL)), and circumferential (&#x3b5;(CC)) strain, respectively. Absolute strain errors and strain drift were low for &#x3b5;(LL) (absolute mean error: 2.42%, drift: -1.05%) and &#x3b5;(CC) (error: 1.79%, drift: -1.33%) and slightly higher for &#x3b5;(RR) (error: 3.37%, drift: 3.05%). The discriminative power of our methodology was adequate to resolve full transmural inclusions down to 17 mm in diameter, although the inclusion-to-surrounding tissue stiffness ratio was required to be at least 5:2 (absolute difference of 39.42 kPa). When the inclusion-to-surrounding tissue stiffness ratio was lowered to approximately 2:1 (absolute difference of 22.63 kPa), only larger inclusions down to 27 mm in diameter could still be identified. Radial strain was found not to be reliable in identifying dysfunctional regions.
2,334,054
[Pulmonary hypertension and femoral neck fracture: interest of continuous spinal anaesthesia].
Anaesthetic management of patients with pulmonary hypertension is challenging and alternatives to general anaesthesia are encouraged. We report anaesthetic management of two patients with pulmonary hypertension admitted for femoral neck fracture. In order to reduce the risk of right-sided heart failure and systemic hypotension, it was decided to operate the patients under continuous spinal anaesthesia. Anaesthesia was induced with excellent hemodynamic tolerance. Quality and extension of the block was correct and allowed surgery. No postoperative complication was observed. These cases suggest that continuous spinal anaesthesia may be considered for the management of patients with pulmonary hypertension undergoing femoral neck fracture surgery.
2,334,055
Distinct endothelial pathways underlie sexual dimorphism in vascular auto-regulation.
Pre-menopausal females have a lower incidence of cardiovascular disease compared with age-matched males, implying differences in the mechanisms and pathways regulating vasoactivity. In small arteries, myogenic tone (constriction in response to raised intraluminal pressure) is a major determinant of vascular resistance. Endothelium-derived dilators, particularly NO, tonically moderate myogenic tone and, because the endothelium is an important target for female sex hormones, we investigated whether NO-mediated moderation of myogenic tone differed between the sexes.</AbstractText>Pressure-diameter or relaxation concentration-response curves to the NO donor spermine-NO or soluble guanylate cyclase (sGC) stimulation (BAY41-2272) were constructed before and following drug intervention in murine mesenteric resistance arteries. Hypotensive responses to activators of the NO-sGC pathway were determined. Quantitative PCR and Western blotting were used for expression analysis.</AbstractText>NO synthase inhibition enhanced myogenic tone of arteries of both sexes while block of endothelium-derived hyperpolarizing factor (EDHF) enhanced responses in arteries of females only. Spermine-NO concentration-dependently relaxed mesenteric arteries isolated from either sex. However, while inhibition of sGC activity attenuated responses of arteries from male mice only, endothelial denudation attenuated responses of arteries from females only. BAY41-2272 and spermine-NO-induced vasodilatation and hypotension were greater in males than in females.</AbstractText>NO moderated myogenic tone in arteries of male mice by a sGC-dependent pathway while EDHF was the predominant endothelial regulator in arteries of females. This is a potentially important sexual dimorphism in NO-mediated reactivity and further implicates EDHF as the predominant endothelial vasodilator in female resistance arteries.</AbstractText>&#xa9; 2012 The Authors. British Journal of Pharmacology &#xa9; 2012 The British Pharmacological Society.</CopyrightInformation>
2,334,056
Overexpression of Shp-2 attenuates apoptosis in neonatal rat cardiac myocytes through the ERK pathway.
During cardiac ischemia and end-stage heart disease, a large number of cardiac cells are apoptotic, and therefore, heart function is impaired. Although the role of Shp-2 in cell survival has been reported, its regulation of cardiac apoptosis is still undetermined. To better understand the potential role of Shp-2 in apoptosis, cell death was determined in serum-depleted cardiomyocytes. Shp-2 was inhibited by NSC87877, and apoptosis, Cyt C release and caspase 3 activation were determined. To evaluate the notion that Shp-2 plays a role in survival stimulation, wild-type and gain-of-function mutant Shp-2 adenoviruses were infected into neonatal cardiomyocytes, and ERK activation was examined. Finally, the MEK inhibitor U0126 was utilized to block the ERK pathway and determine the role of Shp-2 in this pathway. We found that Shp-2 inhibition enhanced apoptosis via regulation of mitochondrial Cyt C release and activation of caspase 3. Overexpression of Shp-2 inhibited apoptosis through activation of ERK. The MEK inhibitor U0126 abolished Shp-2's effect on apoptosis in cardiomyocytes. Our results have revealed that Shp-2 functions as an intracellular inhibitor of apoptosis. These data provide insight into the pathogenesis and the therapeutic strategies of heart diseases.
2,334,057
Intracellular spatial localization regulated by the microtubule network.
The commonly recognized mechanisms for spatial regulation inside the cell are membrane-bounded compartmentalization and biochemical association with subcellular organelles. We use computational modeling to investigate another spatial regulation mechanism mediated by the microtubule network in the cell. Our results demonstrate that the mitotic spindle can impose strong sequestration and concentration effects on molecules with binding affinity for microtubules, especially dynein-directed cargoes. The model can recapitulate the essence of three experimental observations on distinct microtubule network morphologies: the sequestration of germ plasm components by the mitotic spindles in the Drosophila syncytial embryo, the asymmetric cell division initiated by the time delay in centrosome maturation in the Drosophila neuroblast, and the diffusional block between neighboring energids in the Drosophila syncytial embryo. Our model thus suggests that the cell cycle-dependent changes in the microtubule network are critical for achieving different spatial regulation effects. The microtubule network provides a spatially extensive docking platform for molecules and gives rise to a "structured cytoplasm", in contrast to a free and fluid environment.
2,334,058
Comparative evaluation of ropivacaine and lignocaine with ropivacaine, lignocaine and clonidine combination during peribulbar anaesthesia for phacoemulsification cataract surgery.
Peribulbar block is the most common type of local anaesthesia administered for cataract surgery, and continuous efforts are on to find a long-acting local anaesthetic (LA) drug with the safest pharmacological profile.</AbstractText>A double-blind, prospective and randomized study was carried out in our institute to compare the anaesthetic effects of ropivacaine with the combination of ropivacaine and clonidine in administration of peribulbar block for phacoemulsification cataract surgery.</AbstractText>A total of 200 patients of both sexes aged 50-80 years of American Society of Anaesthesiologists grade I and II, scheduled for phacoemulsification cataract surgery under monitored anaesthesia care, were enrolled for the study. Patients were assigned into two groups of 100 each; ropivacaine group (R) and ropivacaine clonidine group (RC). Group R received 10 mL of LA solution containing 5 mL of 2% lignocaine, 5 mL of 0.75% ropivacaine and 100 units of hyaluronidase while group RC received 8 mL of a similar mixture with the addition of clonidine 1 &#x3bc;g/kg and saline to make a total volume of 10 mL. Heart rate (HR), mean arterial pressure (MAP), pulse oximetry (SpO(2)), respiratory rate (RR), intraocular pressure (IOP), eye muscle movement scores and quality of peribulbar block were observed and recorded throughout the study period at regular intervals. At the end of the research project, the data was compiled systematically and was subjected to statistical analysis using the ANOVA test with post hoc significance for continuous variables and Chi-square test for qualitative data. Value of P&lt;0.05 was considered significant and P&lt;0.0001 as highly significant.</AbstractText>Demographic characteristics, SpO(2) and RR were comparable in both the groups. Mean HR and MAP were also comparable after a significant variation in the first 2-3 min (P&lt;0.05). Onset and establishment of sensory and motor blocks were significantly earlier in the RC group (P&lt;0.05). IOP decreased significantly during the first 6-7 min in the RC group after the administration of the peribulbar block. Duration of analgesia was prolonged in the RC group (6.5&#xb1;2.1 h) as compared with the R group (4.2&#xb1;1.8 h). The side-effect profile revealed a higher incidence of nausea, vomiting, headache and dizziness in Group R, while a considerably higher incidence of dry mouth was observed in Group RC.</AbstractText>Addition of clonidine to ropivacaine not only decreases the total volume of LA to be used but also augments early onset and prolonged offset of sensory analgesia as well as provides smooth operating conditions with a good sedation level as well by providing a wider safety margin of LA.</AbstractText>
2,334,059
Antidepressants cause bradycardia and heart block in GD 13 rat embryos in vitro.
This study investigated the effects of a range of antidepressant drugs on the heart of gestation day 13 rat embryos in vitro. The general hypothesis was that the drugs would adversely affect the function of the embryonic heart since they all have some cardiac ion channel blocking activity in addition to their main pharmacological effect on neurotransmitters. The results showed that all the tested drugs caused bradycardia in a generally concentration-dependent manner. At higher concentrations most of the drugs caused some degree of heart block consistent with sodium channel blockade and some drugs also showed negative inotropy associated with blockade of the L-type calcium channel. One drug, trazodone, caused arrhythmia consistent with blockade of the hERG (human ether-a-go-go related gene) potassium channel. In general the effects on the embryonic rat heart were only seen at "free drug" concentrations much greater than those likely to occur in pregnant women taking antidepressant medication. The least margin of safety was seen with the tricyclic antidepressants and the serotonin antagonist and reuptake inhibitor trazodone.
2,334,060
Sensitivity of cloned muscle, heart and neuronal voltage-gated sodium channels to block by polyamines: a possible basis for modulation of excitability in vivo.
Spermidine and spermine, are endogenous polyamines (PAs) that regulate cell growth and modulate the activity of numerous ion channel proteins. In particular, intracellular PAs are potent blockers of many different cation channels and are responsible for strong suppression of outward K (+) current, a phenomenon known as inward rectification characteristic of a major class of KIR K (+) channels. We previously described block of heterologously expressed voltage-gated Na (+) channels (NaV) of rat muscle by intracellular PAs and PAs have recently been found to modulate excitability of brain neocortical neurons by blocking neuronal NaV channels. In this study, we compared the sensitivity of four different cloned mammalian NaV isoforms to PAs to investigate whether PA block is a common feature of NaV channel pharmacology. We find that outward Na (+) current of muscle (NaV 1.4), heart (NaV 1.5), and neuronal (NaV 1.2, NaV 1.7) NaV isoforms is blocked by PAs, suggesting that PA metabolism may be linked to modulation of action potential firing in numerous excitable tissues. Interestingly, the cardiac NaV 1.5 channel is more sensitive to PA block than other isoforms. Our results also indicate that rapid binding of PAs to blocking sites in the NaV 1.4 channel is restricted to access from the cytoplasmic side of the channel, but plasma membrane transport pathways for PA uptake may contribute to long-term NaV channel modulation. PAs may also play a role in drug interactions since spermine attenuates the use-dependent effect of the lidocaine, a typical local anesthetic and anti-arrhythmic drug.
2,334,061
The effectiveness of physical activity interventions in socio-economically disadvantaged communities: a systematic review.
Interventions to increase levels of physical activity (PA) in socio-economically disadvantaged communities are needed but little is known about their effectiveness. This review examines the effectiveness of interventions designed to increase PA in these communities and the theoretical frameworks and components used.</AbstractText>Five databases were searched for papers published in English between January 2000 and December 2010 that reported outcomes of PA interventions in socio-economically disadvantaged communities. Studies targeting individuals with pre-existing disease and not reporting a measure of free-living PA were excluded. Two reviewers independently extracted data and evaluated quality of evidence against pre-defined criteria.</AbstractText>Of 478 publications identified, 27 were included. We found that group-based interventions were effective for adults but not for children; evidence for the effectiveness of interventions targeting individuals was insufficient; limited evidence suggested that community-wide interventions produced small changes in PA. Interventions underpinned by any theoretical framework, compared to none, were more likely to be effective. Several effective interventions included education, PA and social support components.</AbstractText>Compared to other approaches, multi-component adult group-based interventions with theoretical frameworks are most effective in increasing PA in socio-economically disadvantaged communities. More robust evaluations of interventions targeting individuals in these 'hard-to-reach' communities are required.</AbstractText>Copyright &#xa9; 2012 Elsevier Inc. All rights reserved.</CopyrightInformation>
2,334,062
Persistence of perinatal mortality due to congenital malformations in resource-poor settings.
Every year, half a million babies are born with malformations, one-third of these life-threatening. The present study aims at analysing trends of perinatal mortality (PM) due to major congenital malformations (MCM) at a rural institute, for preventive possibilities. Records of all perinatal deaths due to MCM over 24 years were analysed. Perinatal deaths (PD) due to MCM were 346; overall 8.3% of PD (287 (82.94%) stillbirths; 59 (17.06%) neonatal deaths). There was a decreasing trend of contribution of MCM to PM: 9.52% in Block A to 6.95% in Block H; 26.87% of PD were due to nervous system anomalies: 3.76% in Block A to 2.02% in Block H. PM due to congenital heart disease increased from 0.87% in Block A to 6.94% in Block H. It is essential that a system exists to diagnose MCM at a gestation when abortion is possible. Research for prevention of anomalies needs to be continued.
2,334,063
Electrical coupling and propagation in engineered ventricular myocardium with heterogeneous expression of connexin43.
Spatial heterogeneity in connexin (Cx) expression has been implicated in arrhythmogenesis.</AbstractText>This study was performed to quantify the relation between the degree of heterogeneity in Cx43 expression and disturbances in electric propagation.</AbstractText>Cell pairs and strands composed of mixtures of Cx43(-/-) (Cx43KO) or GFP-expressing Cx43(+/+) (WT(GFP)) murine ventricular myocytes were patterned using microlithographic techniques. At the interface between pairs of WT(GFP) and Cx43KO cells, dual-voltage clamp showed a marked decrease in electric coupling (approximately 5% of WT) and voltage gating suggested the presence of mixed Cx43/Cx45 channels. Cx43 and Cx45 immunofluorescence signals were not detectable at this interface, probably because of markedly reduced gap junction size. Macroscopic propagation velocity, measured by multisite high-resolution optical mapping of transmembrane potential in strands of cells of mixed Cx43 genotype, decreased with an increasing proportion of Cx43KO cells in the strand. A marked decrease in conduction velocity was observed in strands composed of &lt;50% WT cells. Propagation at the microscopic scale showed a high degree of dissociation between WT(GFP) and Cx43KO cells, but consistent excitation without development of propagation block.</AbstractText>Heterogeneous ablation of Cx43 leads to a marked decrease in propagation velocity in tissue strands composed of &lt;50% cells with WT Cx43 expression and marked dissociation of excitation at the cellular level. However, the small residual electric conductance between Cx43 and WT(GFP) myocytes assures excitation of Cx43(-/-) cells. This explains the previously reported undisturbed contractility in tissues with spatially heterogeneous downregulation of Cx43 expression.</AbstractText>
2,334,064
An epidemiologic transition of cardiovascular disease risk in Carriacou and Petite Martinique, Grenada: the Grenada Heart Project, 2005-2007.
The epidemiologic transition has made chronic disease a major health threat in the Caribbean and throughout the world. Our objective was to examine the pattern of lifestyle factors associated with cardiovascular disease (CVD) in Grenada and to determine whether the prevalence of CVD risk factors differs by subgroups.</AbstractText>We conducted a cross-sectional study of adult Grenadians between 2005 and 2007. We used a population-wide, community-based approach by adapting the World Health Organization's STEPwise Approach to the Surveillance of Chronic Disease survey for a local context. We collected behavioral, anthropometric, and blood sample data to assess the prevalence of CVD risk factors.</AbstractText>An estimated 64% (n = 2,017) of 3,167 eligible adults participated in our study (60% women). With increasing age, consumption of fried foods declined, whereas fish intake increased. Adults aged 45 to 54 years had the highest obesity rate (39%). Large waist circumference was more common among women than among men. According to National Cholesterol Education Program criteria, 29% of participants had metabolic syndrome (47% &#x2265; 65 y; 36% women vs 17% men). Approximately one-fifth of participants had lived outside Grenada for more than 10 years. Participants who had migrated tended to be older and have different CVD risk factors than those who had never migrated.</AbstractText>In the midst of an epidemiologic transition in the Caribbean nation of Grenada in which CVD risk is increasing, dietary risk factors are most prevalent among women and among all adults younger than 55.</AbstractText>
2,334,065
Umbilical cord blood levels of maternal antibodies reactive with p200 and full-length Ro 52 in the assessment of risk for cardiac manifestations of neonatal lupus.
Maternal anti-Ro autoantibodies are associated with cardiac manifestations of neonatal lupus (cardiac NL), yet only 2% of women with this reactivity have an affected child. Identification of a more specific marker would channel intense monitoring to fetuses at greater risk. This study aimed to determine whether autoantibodies against Ro 52 amino acids 200-239 (p200) confer added risk over autoantibodies to full-length Ro 52, Ro 60, or La.</AbstractText>Anti-Ro-exposed pregnancies resulting in cardiac NL or no cardiac manifestations were identified from the Research Registry for Neonatal Lupus and the PR Interval and Dexamethasone Evaluation study. Umbilical cord (n = 123) and maternal (n = 115) samples were evaluated by enzyme-linked immunosorbent assay.</AbstractText>The frequencies of p200, Ro 52, Ro 60, and La autoantibodies were not significantly different between affected and unaffected children. However, neonatal anti-Ro 52 and Ro 60 titers were highest in cardiac NL and their unaffected siblings compared to unaffected neonates without a cardiac NL sibling. Although both maternal anti-Ro 52 and p200 autoantibodies were less than 50% specific for cardiac NL, anti-p200 was the least likely of the Ro autoantibodies to be false-positive in mothers who have never had an affected child. Titers of anti-Ro 52 and p200 did not differ during a cardiac NL or unaffected pregnancy from the same mother.</AbstractText>Maternal reactivity to p200 does not confer an added risk to fetal conduction defects over full-length Ro 52 or Ro 60 autoantibodies. Mothers who may never be at risk for having an affected child have lower anti-Ro 60 titers and may require less stringent echocardiographic monitoring compared to women with high-titer autoantibodies.</AbstractText>Copyright &#xa9; 2012 by the American College of Rheumatology.</CopyrightInformation>
2,334,066
Comparison of the anaesthetic efficacy of and heart rate changes after periodontal ligament or intraosseous X-Tip injection in mandibular molars: a randomized controlled clinical trial.
To compare the efficacy of supplemental anaesthesia using periodontal ligament injections (PDL) and intraosseous injections with the X-Tip system in terms of the measured heart rate and patient reported pain level.</AbstractText>In this single-blind randomized clinical trial, 40 patients (22 women, 18 men) with irreversible pulpitis who had experienced unsuccessful pain management by inferior alveolar nerve block with 2% lidocaine and 1 : 100 000 epinephrine were selected. Patients were divided equally and randomly into two groups. Supplementary anaesthesia was provided through intraosseous injection with the X-Tip system (X-Tip group) or by PDL injection (PDL group). After each step of injection, pain severity was assessed using a visual analogue scale. Patient heart rate was recorded with a pulse oximeter. Data were coded and analysed using Mann-Whitney U-test with SPSS (version 16) software.</AbstractText>Anaesthetic success was obtained in 100% of X-Tip and 70% of PDL group patients after the first supplemental injection. Compared with the first PDL injection, the first intraosseous injection resulted in a significant increase in heart rate (P = 0.001); however, this increase was short-lived (mean increase: 9-10 beats per min). No significant difference in heart rate or anaesthesia success was observed between men and women.</AbstractText>Intraosseous injection using the X-Tip system was more effective than PDL injection as a supplementary anaesthetic for pulpectomy in mandibular molars or second premolars. However, the former resulted in a transient increase in heart rate.</AbstractText>&#xa9; 2012 International Endodontic Journal.</CopyrightInformation>
2,334,067
Selective block of K(ATP) channels: why the anti-diabetic sulphonylureas and rosiglitazone have more in common than we thought.
Rosiglitazone, the thiazolidinedione class anti-diabetic withdrawn from Europe in 2010 amid reports of adverse cardiovascular effects, is revealed by Yu et al. in this issue of the British Journal of Pharmacology to be a selective blocker of ATP-sensitive potassium (K(ATP) ) channels. This seems little cause for excitement given that the closure of pancreatic K(ATP) channels is integral to insulin secretion; and sulphonylureas, which inhibit K(ATP) channels, are widely used to treat type II diabetes. However, rosiglitazone, whose primary targets are nuclear transcription factors that regulate genes involved in lipid metabolism, blocks K(ATP) channels by a novel mechanism different to that of the sulphonylureas and has a worrying preference for blood flow-regulating vascular K(ATP) channels. Identification of a new molecule that modulates K(ATP) channel gating will not only tell us more about how these complex metabolic sensors work but also raises questions as to whether rosiglitazone suppresses the cardiovascular system's ability to cope with metabolic stress - a claim that has dogged the sulphonylureas for many years.
2,334,068
2D myocardial strain assessment in the mouse: a comparison between a synthetic lateral phase approach and block-matching using computer simulation.
Estimating myocardial strain in the mouse with clinical equipment remains difficult due to the high heart rate and the small size of the mouse heart. Measuring the strain component perpendicular to the ultrasound beam is especially challenging because of the lack of phase information in that direction and the large speckle width compared to the wall thickness. In this study, the performance of a Synthetic Lateral Phase (SLP) approach was contrasted to a standard and a regularized 2D Speckle Tracking (2D ST) algorithm using simulated data sets. SLP yielded higher rms errors for the lateral strain estimates than the regularized 2D ST (Lateral rms error: 0.087&#xb1;0.012 vs. 0.052&#xb1;0.010; p&lt;0.05). No significant difference was found between the standard 2D ST and SLP. For the axial strain estimates, SLP produced higher rms errors than the standard 2D ST (Axial rms error: 0.063&#xb1;0.012 vs. 0.040&#xb1;0.008; p&lt;0.05). 2D ST combined with geometric regularization showed thus to be the most accurate method.
2,334,069
Blocked muscle fat oxidation during exercise in neutral lipid storage disease.<Pagination><StartPage>530</StartPage><EndPage>533</EndPage><MedlinePgn>530-3</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1001/archneurol.2011.631</ELocationID><Abstract><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">To determine whether impaired exercise capacity in neutral lipid storage disease with myopathy is solely caused by muscle weakness or whether a defect in energy metabolism (blocked fat oxidation) may also play a role.</AbstractText><AbstractText Label="DESIGN" NlmCategory="METHODS">We studied a 37-year-old woman with neutral lipid storage disease with myopathy, who cycled while lipid oxidation was assessed using U-(13)C palmitate tracer dilution technique. The effect of a glucose infusion during exercise was also studied.</AbstractText><AbstractText Label="SETTING" NlmCategory="METHODS">Neuromuscular research unit.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">The exercise-induced increase in fat oxidation was virtually abolished in the patient. Treatment with intravenous glucose infusion improved maximal oxygen uptake from 23 to 27 mL&#xa0;&#xd7;&#xa0;kg(-1)&#xa0;&#xd7;&#xa0;min(-1), and maximal workload from 75 to 100 W.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">These results demonstrate that in addition to fixed weakness, neutral lipid storage disease with myopathy is also characterized by a profound block in fat oxidation, which limits exercise tolerance.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lafor&#xea;t</LastName><ForeName>Pascal</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Centre de R&#xe9;f&#xe9;rence de Pathologie Neuromusculaire Paris-Est, B&#xe2;timent Babinski, Groupe Hospitalier Piti&#xe9;-Salp&#xea;tri&#xe8;re, 47-83 Boulevard de l'H&#xf4;pital, 75651 Paris CEDEX 13, France. [email protected]</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>&#xd8;rngreen</LastName><ForeName>Mette</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Preisler</LastName><ForeName>Nicolai</ForeName><Initials>N</Initials></Author><Author ValidYN="Y"><LastName>Andersen</LastName><ForeName>Grete</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Vissing</LastName><ForeName>John</ForeName><Initials>J</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Arch Neurol</MedlineTA><NlmUniqueID>0372436</NlmUniqueID><ISSNLinking>0003-9942</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001786">Blood Glucose</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002247">Carbon Isotopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D005227">Fatty Acids</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010168">Palmitates</NameOfSubstance></Chemical><Chemical><RegistryNumber>IY9XDZ35W2</RegistryNumber><NameOfSubstance UI="D005947">Glucose</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Disease" UI="C536560">Chanarin-Dorfman Syndrome</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001786" MajorTopicYN="N">Blood Glucose</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002247" MajorTopicYN="N">Carbon Isotopes</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004734" MajorTopicYN="N">Energy Metabolism</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015444" MajorTopicYN="N">Exercise</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005227" MajorTopicYN="N">Fatty Acids</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005947" MajorTopicYN="N">Glucose</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration &amp; dosage</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="N">Heart Rate</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016113" MajorTopicYN="N">Ichthyosiform Erythroderma, Congenital</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000534" MajorTopicYN="Y">rehabilitation</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007320" MajorTopicYN="N">Inspiratory Capacity</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D050356" MajorTopicYN="N">Lipid Metabolism</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008052" MajorTopicYN="N">Lipid Metabolism, Inborn Errors</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000534" MajorTopicYN="Y">rehabilitation</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009135" MajorTopicYN="N">Muscular Diseases</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000534" MajorTopicYN="Y">rehabilitation</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010084" MajorTopicYN="N">Oxidation-Reduction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010168" MajorTopicYN="N">Palmitates</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013997" MajorTopicYN="N">Time Factors</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2012</Year><Month>4</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2012</Year><Month>4</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2012</Year><Month>6</Month><Day>1</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">22491199</ArticleId><ArticleId IdType="doi">10.1001/archneurol.2011.631</ArticleId><ArticleId IdType="pii">69/4/530</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">22491016</PMID><DateCompleted><Year>2012</Year><Month>06</Month><Day>29</Day></DateCompleted><DateRevised><Year>2021</Year><Month>10</Month><Day>21</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1940-087X</ISSN><JournalIssue CitedMedium="Internet"><Issue>61</Issue><PubDate><Year>2012</Year><Month>Mar</Month><Day>29</Day></PubDate></JournalIssue><Title>Journal of visualized experiments : JoVE</Title><ISOAbbreviation>J Vis Exp</ISOAbbreviation></Journal>In vivo electroporation of morpholinos into the regenerating adult zebrafish tail fin.
Certain species of urodeles and teleost fish can regenerate their tissues. Zebrafish have become a widely used model to study the spontaneous regeneration of adult tissues, such as the heart, retina, spinal cord, optic nerve, sensory hair cells, and fins. The zebrafish fin is a relatively simple appendage that is easily manipulated to study multiple stages in epimorphic regeneration. Classically, fin regeneration was characterized by three distinct stages: wound healing, blastema formation, and fin outgrowth. After amputating part of the fin, the surrounding epithelium proliferates and migrates over the wound. At 33 &#xb0;C, this process occurs within six hours post-amputation (hpa, Figure 1B). Next, underlying cells from different lineages (ex. bone, blood, glia, fibroblast) re-enter the cell cycle to form a proliferative blastema, while the overlying epidermis continues to proliferate (Figure 1D). Outgrowth occurs as cells proximal to the blastema re-differentiate into their respective lineages to form new tissue (Figure 1E). Depending on the level of the amputation, full regeneration is completed in a week to a month. The expression of a large number of gene families, including wnt, hox, fgf, msx, retinoic acid, shh, notch, bmp, and activin-betaA genes, is up-regulated during specific stages of fin regeneration. However, the roles of these genes and their encoded proteins during regeneration have been difficult to assess, unless a specific inhibitor for the protein exists, a temperature-sensitive mutant exists or a transgenic animal (either overexpressing the wild-type protein or a dominant-negative protein) was generated. We developed a reverse genetic technique to quickly and easily test the function of any gene during fin regeneration. Morpholino oligonucleotides are widely used to study loss of specific proteins during zebrafish, Xenopus, chick, and mouse development. Morpholinos basepair with a complementary RNA sequence to either block pre-mRNA splicing or mRNA translation. We describe a method to efficiently introduce fluorescein-tagged antisense morpholinos into regenerating zebrafish fins to knockdown expression of the target protein. The morpholino is micro-injected into each blastema of the regenerating zebrafish tail fin and electroporated into the surrounding cells. Fluorescein provides the charge to electroporate the morpholino and to visualize the morpholino in the fin tissue. This protocol permits conditional protein knockdown to examine the role of specific proteins during regenerative fin outgrowth. In the Discussion, we describe how this approach can be adapted to study the role of specific proteins during wound healing or blastema formation, as well as a potential marker of cell migration during blastema formation.
2,334,070
Qualitative and quantitative characteristics of the electroencephalogram in normal horses after sedation.
The administration of certain sedatives has been shown to promote sleep in humans. Related agents induce sleep-like behavior when administered to horses. Interpretation of electroencephalograms (EEGs) obtained from sedated horses should take into account background activity, presence of sleep-related EEG events, and the animal's behavior.</AbstractText>Sedatives induce states of vigilance that are indistinguishable on EEGs from those that occur naturally.</AbstractText>Six healthy horses.</AbstractText>Digital EEG with video was recorded after administration of 1 of 4 sedatives (acepromazine, butorphanol, xylazine, or detomidine). Serum drug concentrations were measured. Recordings were reviewed, states were identified, and representative EEG samples were analysed. These data were compared with data previously obtained during a study of natural sleep.</AbstractText>Butorphanol was associated with brief episodes resembling slow wave sleep in 1 horse. Acepromazine led to SWS in 3 horses, including 1 that also exhibited rapid eye movement sleep. Periods of SWS were observed in all horses afer xylazine or detomidine administration. Normal sleep-related EEG events and heart block, occurred in association with SWS regardless of which sedative was used. Spectral data varied primarily by state, but some differences were observed between sedative and natural data.</AbstractText>Qualitatively, EEG findings appeared identical whether sedation-induced or naturally occurring. The startle response and heart block associated with some sedatives may be related to sleep. Alpha(2) agonists can be used to obtain high quality EEGs in horses, but acepromazine does not promote a relaxed state in all animals.</AbstractText>Copyright &#xa9; 2012 by the American College of Veterinary Internal Medicine.</CopyrightInformation>
2,334,071
The effect of intravenous morphine on the level of spinal anesthesia with lidocaine.
One of the major concerns in spinal anesthesia with lidocaine is its short duration of action. Enhancement is necessary in some situations during surgery, because surgeons encounter with unexpected events and need more time. Therefore there is a need to increase anesthesia duration in these situations. Many studies investigated various additives with different administration routes to enhance spread and duration of spinal block with lidocaine. Because we only have morphine sulfate in our clinics and the sulfate compounds are neurotoxic, we cannot prescribe it by intrathecal route; for this reason we investigated effects of intravenous morphine on the spinal anesthesia with lidocaine.</AbstractText>This double blinded randomized clinical trial study was performed on 36 patients who were allocated to two groups. All patients underwent spinal anesthesia with lidocaine by the same method. Patients in the case group received morphine plus midazolam intravenously as the additive medication and in the control group received normal saline plus midazolam. Duration, spinal block level, recovery time, sedation score and adverse effects were compared between the two groups.</AbstractText>This study showed that although intravenous morphine can provide better safe sedation (p-value &lt; 0.01), it has no effect on the level (p-value: 0.42) and duration of spinal block (p-value: 0.26). Although heart rate and blood pressure had significant decrease in the case group (p-value &lt; 0.01 and &lt; 0.05 respectively) but the need for administration of ephedrine was completely similar in both groups.</AbstractText>Although some studies had proved the efficacy of systemic use of other opioids including fentanyl and sufentanil, morphine had no effect on the level and duration of spinal block. It can be due to differences in the chemical structures of these substances. However, intravenous morphine as an additive to spinal anesthesia with lidocaine can provide acceptable sedation with no major side effects.</AbstractText>
2,334,072
Reduced models for unidirectional block conduction and their geometrical setting.
This article revisits a reduced model of cardiac electro-physiology which was proposed to understand the genesis of unidirectional block pathology and of ectopic foci. We underline some specificities of the model from the viewpoint of dynamical systems and bifurcation theory. We point out that essentially the same properties are shared by a simpler system more accessible to analysis. With this simpler system, it becomes possible to give a new presentation of the phenomenon in a phase plane with time moving slow manifolds. This presentation can be of interest both for cardiac electro-physiologists and for mathematicians.
2,334,073
Cultural challenges to secondary prevention: implications for Saudi women.
Like other highly developed countries, cardiovascular disease (CVD) and coronary heart disease (CHD) are major health problems in Saudi Arabia. The aetiology of cardiovascular disease (CVD) burden within the Saudi population is similar to Western countries with atherosclerosis, hypertension, ischemic heart disease and diabetes highly prevalent with the main risk factors being smoking, obesity and inactivity. There are differences between Saudi men and women in epidemiology, risk factors and health service provision for CHD. These sex and gender based factors are important in considering the health and well-being of Saudi women. Currently, there is Limited focus on the cardiovascular health of Saudi women. The aim of this paper is to examine culturally specific issues for Saudi women and the implications for secondary prevention.
2,334,074
The effect of poloxamer 407 on the functional properties of HDL in mice.
There is an inverse relationship between high-density lipoprotein (HDL) and heart disease. HDL possesses not only both antioxidant and anti-inflammatory properties, but also anti-thrombotic and endothelial function-promoting qualities. However, it is not only the serum concentration of HDL that is important, but also the 'functional' quality of the HDL. The objective was to determine the functional status of HDL in a well-established mouse model of dyslipidaemia and atherosclerosis induced by the administration of a block copolymer (poloxamer 407; P-407).</AbstractText>C57BL/6 mice were administered a single intraperitoneal dose of P-407 (0.5g/kg) and blood was collected at 24h post-dosing. HDL was isolated from controls (control HDL) and P-407-treated (P-407 HDL) mice and used to test its anti-inflammatory properties in vitro. Additionally, antioxidant enzymes associated with HDL, namely, platelet activating factor-acetylhydrolase (PAF-AH) and paraoxonase (PON), were evaluated for any potential reduction in their biological activity.</AbstractText>A single injection of P-407 in C57BL/6 mice resulted in a marked decrease in the levels of HDL-cholesterol and phospholipids. HDL particle size significantly increased, primarily due to remodelling of HDL with triglyceride. It was demonstrated that (i) long-chain saturated fatty acids were higher and the n-3/n-6 fatty acid ratio was significantly lower for P-407 HDL compared with control HDL, and (ii) P-407 HDL lost its capacity to inhibit tumour necrosis factor-&#x3b1; (TNF-&#x3b1;)-induced vascular cell adhesion molecule-1 (VCAM-1) expression compared with control HDL. Additionally, P-407 HDL was not able to neutralize lipopolysaccharide and inhibit subsequent TNF-&#x3b1; production compared with control HDL. The biological activity of platelet-activating factor acetylhydrolase (PAF-AH) and paraoxonase (PON) decreased in direct proportion to the circulating levels of both HDL-cholesterol and apolipoprotein (apoA-1).</AbstractText>Combination of previously reported findings in P-407-treated mice, such as (i) production of both oxidized LDL and malondialdehyde, and (ii) profound elevations in the soluble forms of intercellular adhesion molecule-1 (ICAM-1), VCAM-1, and E-selectin, with the present results, would strongly suggest that HDL in P-407-treated mice is rendered dysfunctional. Thus, these findings help to explain why P-407-treated mice begin to form aortic atherosclerotic lesions about one month after initiating P-407 treatment.</AbstractText>&#xa9; 2012 The Authors. JPP &#xa9; 2012 Royal Pharmaceutical Society.</CopyrightInformation>
2,334,075
Pedestrian accident analysis with a silicone dummy block.
When a car is parked in an inclined plane in a parking lot, the car can roll down the slope and cause a pedestrian accident, even when the angle of inclination is small. A rolling car on a gentle slope seems to be easily halted by human power to prevent damage to the car or a possible accident. However, even if the car rolls down very slowly, it can cause severe injuries to a pedestrian, especially when the pedestrian cannot avoid the rolling car. In an accident case that happened in our province, a pedestrian was injured by a rolling car, which had been parked on a slope the night before. The accident occurred in the parking lot of an apartment complex. The parking lot seemed almost flat with the naked eye. We conducted a rolling test with the accident vehicle at the site. The car was made to roll down the slope by purely gravitational pull and was made to collide with the silicone block leaning against the retaining wall. Silicone has characteristics similar to those of a human body, especially with respect to stiffness. In the experiment, we measured the shock power quantitatively. The results showed that a rolling car could severely damage the chest of a pedestrian, even if it moved very slowly.
2,334,076
Time-based compression and classification of heartbeats.
Heart function measured by electrocardiograms (ECG) is crucial for patient care. ECG generated waveforms are used to find patterns of irregularities in cardiac cycles in patients. In many cases, irregularities evolve over an extended period of time that requires continuous monitoring. However, this requires wireless ECG recording devices. These devices consist of an enclosed system that includes electrodes, processing circuitry, and a wireless communication block imposing constraints on area, power, bandwidth, and resolution. In order to provide continuous monitoring of cardiac functions for real-time diagnostics, we propose a methodology that combines compression and analysis of heartbeats. The signal encoding scheme is the time-based integrate and fire sampler. The diagnostics can be performed directly on the samples avoiding reconstruction required by the competing finite rate of innovation and compressed sensing. As an added benefit, our scheme provides an efficient hardware implementation and a compressed representation for the ECG recordings, while still preserving discriminative features. We demonstrate the performance of our approach through a heartbeat classification application consisting of normal and irregular heartbeats known as arrhythmia. Our approach that uses simple features extracted from ECG signals is comparable to results in the published literature.
2,334,077
Combining psychosocial data to improve prediction of cardiovascular disease risk factors and events: The National Heart, Lung, and Blood Institute--sponsored Women's Ischemia Syndrome Evaluation study.
There is overlap among psychosocial predictors of cardiovascular disease (CVD). The usefulness of combining psychosocial variables as risk markers for CVD needs investigation.</AbstractText>Participants were 493 women in the NHLBI WISE study. Multivariate combination of Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Social Network Index (SNI), and Cook-Medley hostility subscales was evaluated, and principal components analysis also conducted. Relationships of composite psychosocial risk markers to CVD events and risk factors were assessed.</AbstractText>The multivariate block of SNI, Cook-Medley Hostile Affect subscale, STAI, and BDI predicted CVD events (&#x3c7;(2) = 27.8, df = 6, p &lt; .001). Scalewise factor analysis revealed 2 factors: negative affectivity (NA) and hostility (explained variance, 45.6% and 17.1%, respectively). NA was associated with BMI (&#x3b2; [SE] = 0.18 [0.09], p = .04), hostility with metabolic syndrome (exp(&#x3b2;) = 0.60 [0.28], p = .04). Both factors were associated with blood pressure (BP): NA with SBP (&#x3b2; = 2.53 [1.04], p = .02) and DBP (&#x3b2; = 1.66 [0.60], p = .02); hostility with SBP (&#x3b2; = 2.72 [1.13], p = .02) and DBP (&#x3b2; = 1.83 [0.65], p = .005). Neither factor predicted CVD events. Original scales predicted CVD events: lower SNI (HR = 0.74, CI = 0.57-0.96), lower Hostile Affect (HR = 0.80, CI = 0.56-1.03), and higher BDI (HR = 1.33, CI = 1.08-1.74).</AbstractText>In women with suspected ischemia, multivariate combination of psychosocial risk markers predicts CVD events; derived psychosocial factors were associated with CVD risk factors but not events. Measuring common variance among psychosocial variables may be a useful research strategy.</AbstractText>
2,334,078
Effects of intrathecally administered fentanyl on duration of analgesia in patients undergoing spinal anaesthesia for elective caesarean section.
Intrathecal opioids have gained popularity in obstetrics; they augment the analgesia produced by local anaesthetic agents. The aim of this study is to determine the duration of analgesia following addition of fentanyl to bupivacaine during elective Caesarean section.</AbstractText>This is a prospective randomized study comparing the effect of addition of 25 microg of fentanyl to 2.5 mls of 0.5% hyperbaric bupivacaine intrathecally on sixty healthy women of American Society ofAnaesthesiologist (ASA) physical status I scheduled for elective Caesarean section at the UCH, Ibadan. Patients were randomized to group B, n=30 and group FB, n=30. Maternal heart rate, blood pressure, respiratory rate, sensory level, motor block, pain score (NRS) and side effects were observed every 2 minutes for first 15 minutes, then at 5 minutes interval for the remainder of the operation. Thereafter at 30 minutes interval until the first complaint of pain.</AbstractText>Complete analgesia (time from injection of intrathecal drug to first report of pain) lasted longer in group FB (240 +/- 29 minutes) than group B (99 +/- 12 minutes) with a p-value of 0.002. The duration of effective analgesia (time from injection of intrathecal drug to first request for analgesic) in group FB (276 +/- 26 minutes) while group B was (121 +/- 10 minutes) with a p-value of 0.001. Both were statistically significant.</AbstractText>We conclude that the addition of 25 microg of fentanyl to bupivacaine intrathecally for elective Caesarean section increases the duration of complete and effective analgesia thereby reducing the need for early postoperative use of analgesics.</AbstractText>
2,334,079
Sick sinus syndrome and orthostatic hypotension in Parkinson's disease.
We present a case of Parkinson's disease patient whose initial symptoms were sick sinus syndrome and orthostatic hypotension. Our case illustrates difficulties in distinguishing syncope of primary cardiac or neurological origin and highlights the importance of a diagnostic workup including neurological examination.
2,334,080
Cyclosporine treatment improves cardiac function and systemic hemodynamics during resuscitation in a newborn piglet model of asphyxia: a dose-response study.
Asphyxiated neonates often have myocardial depression, which is a significant cause of morbidity and mortality. Cardioprotective effects of cyclosporine have been observed in adult patients and animals with myocardial infarction. However, the cardioprotective effect of cyclosporine in neonates has not yet been studied. We hypothesize that cyclosporine will improve cardiac function and reduce myocardial injury in asphyxiated newborn piglets.</AbstractText>Thirty-six piglets (1-4 days old, weighing 1.4-2.5 kg) were acutely instrumented for continuous monitoring of cardiac output and systemic arterial pressure. After stabilization, normocapnic alveolar hypoxia (10% to 15% oxygen) was instituted for 2 hrs followed by reoxygenation with 100% oxygen for 0.5 hrs and then 21% for 3.5 hrs. A nonasphyxiated, sham-operated group was included (n = 4) to control for effects of the surgical model. Plasma troponin and myocardial lactate concentrations were determined as well as morphologic examinations.</AbstractText>Neonatal asphyxia and reoxygenation.</AbstractText>Newborn (1-4 days old) piglets.</AbstractText>Piglets were block-randomized to receive intravenous boluses of cyclosporine A (2.5, 10, or 25 mg/kg) or normal saline (control) at 5 mins of reoxygenation (n = 8/group).</AbstractText>Cardiac index, heart rate, systemic oxygenation, plasma troponin, and left ventricular lactate were measured. Hypoxic piglets had cardiogenic shock (cardiac output 40% to 48% of baseline), hypotension (mean arterial pressure 27-31 mm Hg), and acidosis (pH 7.04). Cyclosporine treatment caused bell-shaped improvements in cardiac output, stroke volume, and systemic oxygen delivery (p &lt; .05 vs. controls). Plasma troponin and left ventricle lactate were higher in controls than that of 2.5 and 10 mg/kg cyclosporine-treated groups (p &lt; .05). Although histologic features of myocardial injury were not different among groups, severe damage was observed in mitochondria of control piglets but attenuated in that of cyclosporine (10 mg/kg) treatment.</AbstractText>Postresuscitation administration of cyclosporine causes preservation of cardiac function and attenuates myocardial injury in newborn piglets after asphyxia-reoxygenation.</AbstractText>
2,334,081
Myotonic Dystrophy Type 1 or Steinert's disease.
Myotonic Dystrophy Type 1 (DM1) is the most common worldwide autosomal dominant muscular dystrophy due to polynucleotide [CTG]( n ) triplet expansion located on the 3'UTR of chromosome 19q13.3. A toxic gain-of-function of abnormally stored RNA in the nuclei of affected cells is assumed to be responsible for several clinical features of the disease. It plays a basic role in deregulating RNA binding protein levels and in several mRNA splicing processes of several genes, thus leading to the multisystemic features typical of DM1. In DM1, the musculoskeletal apparatus, heart, brain, eye, endocrine, respiratory and gastroenteric systems are involved with variable levels of severity. DM1 onset can be congenital, juvenile, adult or late. DM1 can be diagnosed on the grounds of clinical presentation (distal muscular atrophy and weakness, grip and percussion myotonia, ptosis, hatchet face, slurred speech, rhinolalia), EMG myotonic pattern, EKG (such as AV-blocks) or routine blood test abnormalities (such as increased CK values or hypogamma-globulinemia) and history of cataract. Its confirmation can come by DNA analysis. At present, only symptomatic therapy is possible and is addressed at correcting hormonal and glycemic balance, removing cataract, preventing respiratory failure and, above all, major cardiac disturbances. Efficacious therapies targeted at the pathogenic mechanism of DM1 are not yet available, while studies that seek to block toxic RNA intranuclear storage with specific molecules are still ongoing.
2,334,082
Thoracic epidural analgesia via the lumbosacral approach using multiport catheters with a low concentration of bupivacaine and morphine in sheep.
To determine the analgesic and systemic effects of thoracic epidural administration of bupivacaine (BP) and morphine (MP) in conscious sheep.</AbstractText>Randomized, crossover, experimental study.</AbstractText>Six healthy castrated sheep weighing between 40 and 50 kg.</AbstractText>Each sheep received, via the lumbosacral approach, BP (0.5 mg kg(-1)), MP (0.1 mg kg(-1)), and BP plus MP (BPMP; 0.25 mg kg(-1) + 0.05 mg kg(-1)) in a randomized order. Heart rate, blood pressure, respiratory rate, blood gas analysis, skin temperature, rectal temperature, analgesia, sedation, and motor blockade were determined before treatment and at predetermined intervals until analgesia had disappeared.</AbstractText>The main areas of complete analgesia for the BP and BPMP treatments were the thorax and forelimb bilaterally. The median duration of analgesia was shorter with MP treatment (45 minutes; score 2) than with BP treatment (70 minutes) and BPMP treatment (140 minutes; p &lt; 0.05). The BP and BPMP treatments caused motor block, and MP and BPMP treatments showed mild sedation. Significant decreases in systolic and diastolic arterial blood pressures were observed only with the BP treatment (p &lt; 0.05). Epidural MP combined with the BP local anesthetic depressed ventilation but within acceptable limits in these clinically healthy sheep.</AbstractText>Thoracic epidural administration of BPMP to sheep resulted in longer duration of analgesia of the thorax and forelimbs bilaterally in conscious sheep than the administration of MP or BP alone. The incidence of complications was low, but side-effects such as depressed ventilation and muscle paralysis occurred and require appropriate management.</AbstractText>This technique should be considered as another method for the relief of postoperative pain after thoracic surgery in sheep.</AbstractText>&#xa9; 2012 The Authors. Veterinary Anaesthesia and Analgesia. &#xa9; 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.</CopyrightInformation>
2,334,083
Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial.
By contrast with many observational studies, women in the Women's Health Initiative (WHI) trial who were randomly allocated to receive oestrogen alone had a lower incidence of invasive breast cancer than did those who received placebo. We aimed to assess the influence of oestrogen use on longer term breast cancer incidence and mortality in extended follow-up of this cohort.</AbstractText>Between 1993 and 1998, the WHI enrolled 10,739 postmenopausal women from 40 US clinical centres into a randomised, double-masked, placebo-controlled trial. Women aged 50-79 years who had undergone hysterectomy and had expected 3-year survival and mammography clearance were randomly allocated by a computerised, permuted block algorithm, stratified by age group and centre, to receive oral conjugated equine oestrogen (0&#xb7;625 mg per day; n=5310) or matched placebo (n=5429). The trial intervention was terminated early on Feb 29, 2004, because of an adverse effect on stroke. Follow-up continued until planned termination (March 31, 2005). Consent was sought for extended surveillance from the 9786 living participants in active follow-up, of whom 7645 agreed. Using data from this extended follow-up (to Aug 14, 2009), we assessed long-term effects of oestrogen use on invasive breast cancer incidence, tumour characteristics, and mortality. We used Cox regression models to estimate hazard ratios (HRs) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00000611.</AbstractText>After a median follow-up of 11&#xb7;8 years (IQR 9&#xb7;1-12&#xb7;9), the use of oestrogen for a median of 5&#xb7;9 years (2&#xb7;5-7&#xb7;3) was associated with lower incidence of invasive breast cancer (151 cases, 0&#xb7;27% per year) compared with placebo (199 cases, 0&#xb7;35% per year; HR 0&#xb7;77, 95% CI 0&#xb7;62-0&#xb7;95; p=0&#xb7;02) with no difference (p=0&#xb7;76) between intervention phase (0&#xb7;79, 0&#xb7;61-1&#xb7;02) and post-intervention phase effects (0&#xb7;75, 0&#xb7;51-1&#xb7;09). In subgroup analyses, we noted breast cancer risk reduction with oestrogen use was concentrated in women without benign breast disease (p=0&#xb7;01) or a family history of breast cancer (p=0&#xb7;02). In the oestrogen group, fewer women died from breast cancer (six deaths, 0&#xb7;009% per year) compared with controls (16 deaths, 0&#xb7;024% per year; HR 0&#xb7;37, 95% CI 0&#xb7;13-0&#xb7;91; p=0&#xb7;03). Fewer women in the oestrogen group died from any cause after a breast cancer diagnosis (30 deaths, 0&#xb7;046% per year) than did controls (50 deaths, 0&#xb7;076%; HR 0&#xb7;62, 95% CI 0&#xb7;39-0&#xb7;97; p=0&#xb7;04).</AbstractText>Our findings provide reassurance for women with hysterectomy seeking relief of climacteric symptoms in terms of the effects of oestrogen use for about 5 years on breast cancer incidence and mortality. However, our data do not support use of oestrogen for breast cancer risk reduction because any noted benefit probably does not apply to populations at increased risk of such cancer.</AbstractText>US National Heart, Lung, and Blood Institute; Wyeth.</AbstractText>Copyright &#xa9; 2012 Elsevier Ltd. All rights reserved.</CopyrightInformation>
2,334,084
Deletion of Siah-interacting protein gene in Drosophila causes cardiomyopathy.
Drosophila is a useful model organism in which the genetics of human diseases, including recent advances in identification of the genetics of heart development and disease in the fly, can be studied. To identify novel genes that cause cardiomyopathy, we performed a deficiency screen in adult Drosophila. Using optical coherence tomography to phenotype cardiac function in awake adult Drosophila, we identified Df(1)Exel6240 as having cardiomyopathy. Using a number of strategies including customized smaller deletions, screening of mutant alleles, and transgenic rescue, we identified CG3226 as the causative gene for this deficiency. CG3226 is an uncharacterized gene in Drosophila possessing homology to the mammalian Siah-interacting protein (SIP) gene. Mammalian SIP functions as an adaptor protein involved in one of the &#x3b2;-catenin degradation complexes. To investigate the effects of altering &#x3b2;-catenin/Armadillo signaling in the adult fly, we measured heart function in flies expressing either constitutively active Armadillo or transgenic constructs that block Armadillo signaling, specifically in the heart. While, increasing Armadillo signaling in the heart did not have an effect on adult heart function, decreasing Armadillo signaling in the fly heart caused the significant reduction in heart chamber size. In summary, we show that deletion of CG3226, which has homology to mammalian SIP, causes cardiomyopathy in adult Drosophila. Alterations in Armadillo signaling during development lead to important changes in the size and function of the adult heart.
2,334,085
Community based needs assessment in an urban area: a participatory action research project.
Community assessment is a core function of public health. In such assessments, a commitment to community participation and empowerment is at the heart of the WHO European Healthy Cities Network, reflecting its origins in health for all and the Ottawa Charter for Health Promotion. This study employs a participation and empowerment plan in order to conduct community assessment.</AbstractText>The method of participatory action research (PAR) was used. The study was carried out in an area of high socio-economic deprivation in Ardabil, a city in the northwest of Iran, which is currently served by a branch of the Social Development Center (SDC). The steering committee of the project was formed by some university faculty members, health officials and delegates form Farhikhteh non-governmental organization and representatives from twelve blocks or districts of the community. Then, the representatives were trained and then conducted focus groups in their block. The focus group findings informed the development of the questionnaire. About six hundred households were surveyed and study questionnaires were completed either during face-to-face interviews by the research team (in case of illiteracy) or via self-completion. The primary question for the residents was: 'what is the most important health problem in your community? Each health problem identified by the community was weighted based on the frequency it was selected on the survey, and steering committee perception of the problem's seriousness, urgency, solvability, and financial load.</AbstractText>The main problems of the area appeared to be the asphalt problem, lack of easy access to medical centers, addiction among relatives and unemployment of youth. High participation rates of community members in the steering committee and survey suggest that the PAR approach was greatly appreciated by the community and that problems identified through this research truly reflect community opinion.</AbstractText>Participatory action research is an effective method for community assessments. However, researchers must rigorously embrace principles of mutual cooperation, respect for public ideas, and a robust belief in community empowerment in order to pave the way for responsible and active citizen participation in the various stages of research.</AbstractText>
2,334,086
In vitro cardiovascular effects of dihydroartemisin-piperaquine combination compared with other antimalarials.
The in vitro cardiac properties of dihydroartemisinin (DHA) plus piperaquine phosphate (PQP) were compared with those of other antimalarial compounds. Results with antimalarial drugs, chosen on the basis of their free therapeutic maximum concentration in plasma (C(max)), were expressed as the fold of that particular effect with respect to their C(max). The following tests were used at 37 &#xb0;C: hERG (human ether-&#xe0;-go-go-related gene) blockade and trafficking, rabbit heart ventricular preparations, and sodium and slow potassium ion current interference (I(Na) and I(Ks), respectively). Chloroquine, halofantrine, mefloquine, and lumefantrine were tested in the hERG studies, but only chloroquine, dofetilide, lumefantrine, and the combination of artemether-lumefantrine were used in the rabbit heart ventricular preparations, hERG trafficking studies, and I(Na) and I(Ks) analyses. A proper reference was used in each test. In hERG studies, the high 50% inhibitory concentration (IC(50)) of halofantrine, which was lower than its C(max), was confirmed. All the other compounds blocked hERG, with IC(50)s ranging from 3- to 30-fold their C(max)s. In hERG trafficking studies, the facilitative effects of chloroquine at about 30-fold its C(max) were confirmed and DHA blocked it at a concentration about 300-fold its C(max). In rabbit heart ventricular preparations, dofetilide, used as a positive control, revealed a high risk of torsades de pointes, whereas chloroquine showed a medium risk. Neither DHA-PQP nor artemether-lumefantrine displayed an in vitro signal for a significant proarrhythmic risk. Only chloroquine blocked the I(Na) ion current and did so at about 30-fold its C(max). No effect on I(Ks) was detected. In conclusion, despite significant hERG blockade, DHA-PQP and artemether-lumefantrine do not appear to induce potential torsadogenic effects in vitro, affect hERG trafficking, or block sodium and slow potassium ion currents.
2,334,087
Pediatric flecainide toxicity from a double dose.
A 23-month-old boy was brought to the emergency department of an adult and pediatric tertiary care center 1 hour after an inadvertent &#x201c;double dose&#x201d; of 120 mg flecainide (9.2 mg/kg). His electrocardiogram revealed sinus rhythm with a terminal R wave in aVR greater than 7 mm, a bifascicular block, and prolonged QRS and QTc intervals. A dramatic improvement in the bifascicular block and terminal R wave occurred after the administration of sodium bicarbonate. He was discharged after 36 hours with no complications. This case demonstrates that flecainide can cause significant cardiac conduction disturbances in doses much lower than previously described. All supratherapeutic ingestions should be assessed in hospital.
2,334,088
Histopathologic characterization of chronic radiofrequency ablation lesions for pulmonary vein isolation.<Pagination><StartPage>930</StartPage><EndPage>938</EndPage><MedlinePgn>930-8</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jacc.2011.09.076</ELocationID><Abstract><AbstractText Label="OBJECTIVES" NlmCategory="OBJECTIVE">This study describes the histopathologic and electrophysiological findings in patients with recurrence of atrial fibrillation (AF) after pulmonary vein (PV) isolation who underwent a subsequent surgical maze procedure.</AbstractText><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">The recovery of PV conduction is commonly responsible for recurrence of AF after catheter-based PV isolation.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">Twelve patients with recurrent AF after acutely successful catheter-based antral PV isolation underwent a surgical maze procedure. Full-thickness surgical biopsy specimens were obtained from the PV antrum in areas of visible endocardial scar. Before biopsy, intraoperative epicardial electrophysiological recordings were taken from each PV using a circular mapping catheter.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Twenty-two PVs were biopsied from the 12 patients 8 &#xb1; 11 months after ablation. Eleven of the 22 specimens (50%) revealed transmural scar, and 11 (50%) showed viable myocardium with or without scar. Each biopsy specimen demonstrated evidence of injury, most commonly endocardial thickening (n = 21 [95%]) and fibrous scar (n = 18 [82%]). Seven of the 22 specimens (32%) showed conduction block at surgery. Transmural scar was more likely to be seen in the biopsy specimens from the PVs with conduction block than in specimens from the PVs showing reconnection. However, viable myocardium alone or mixed with scar was seen in 2 specimens from PVs with conduction block.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">PVs showing electrical reconnection after catheter-based antral ablation frequently reveal anatomic gaps or nontransmural lesions at the sites of catheter ablation. Nontransmural lesions are noted in some PVs with persistent conduction block, suggesting that lesion geometry may influence PV conduction. The histological findings show that nontransmural ablation can produce a dynamic cellular substrate with features of reversible injury. Delayed recovery from injury may explain late recurrences of AF after PV isolation.</AbstractText><CopyrightInformation>Copyright &#xc2;&#xa9; 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kowalski</LastName><ForeName>Marcin</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Clinical Cardiac Electrophysiology, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Grimes</LastName><ForeName>Margaret M</ForeName><Initials>MM</Initials></Author><Author ValidYN="Y"><LastName>Perez</LastName><ForeName>Francisco J</ForeName><Initials>FJ</Initials></Author><Author ValidYN="Y"><LastName>Kenigsberg</LastName><ForeName>David N</ForeName><Initials>DN</Initials></Author><Author ValidYN="Y"><LastName>Koneru</LastName><ForeName>Jayanthi</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Kasirajan</LastName><ForeName>Vigneshwar</ForeName><Initials>V</Initials></Author><Author ValidYN="Y"><LastName>Wood</LastName><ForeName>Mark A</ForeName><Initials>MA</Initials></Author><Author ValidYN="Y"><LastName>Ellenbogen</LastName><ForeName>Kenneth A</ForeName><Initials>KA</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016448">Multicenter Study</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Am Coll Cardiol</MedlineTA><NlmUniqueID>8301365</NlmUniqueID><ISSNLinking>0735-1097</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D001281" MajorTopicYN="N">Atrial Fibrillation</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001706" MajorTopicYN="N">Biopsy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017115" MajorTopicYN="Y">Catheter Ablation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002908" MajorTopicYN="N">Chronic Disease</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004562" MajorTopicYN="N">Electrocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005500" MajorTopicYN="N">Follow-Up Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006329" MajorTopicYN="N">Heart Conduction System</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009206" MajorTopicYN="N">Myocardium</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011667" MajorTopicYN="N">Pulmonary Veins</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012189" MajorTopicYN="N">Retrospective Studies</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2011</Year><Month>4</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2011</Year><Month>8</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2011</Year><Month>9</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2012</Year><Month>3</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2012</Year><Month>3</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2012</Year><Month>5</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">22381429</ArticleId><ArticleId IdType="doi">10.1016/j.jacc.2011.09.076</ArticleId><ArticleId IdType="pii">S0735-1097(11)05269-7</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">22379909</PMID><DateCompleted><Year>2012</Year><Month>03</Month><Day>20</Day></DateCompleted><DateRevised><Year>2018</Year><Month>12</Month><Day>01</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>6</Issue><PubDate><Year>2011</Year><Season>Nov-Dec</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal>[Spinal anesthesia with various anesthetic agents due to endoscopic urological procedure in patient over 60 years old].
Aim of the study is to compare efficiency and safety of method of spinal anesthesia with isobaric bypivacain (5 mg/ml) and ropivacain 5 (mg/ml) during performing transurethral resection of the prostate in patients over 60 years old. Methods 38 patients (68-82 years old ASAII-ASAIII) with hyperplasia of prostate gland were examined in randomized clinical study. Two methods of anesthetic management were compared. In first group of 19 patients was administrated intrathecal with isobaric bypivacain (5mg/ml), second group of 19 patients were administrated with ropivacain (5mg/ml). The efficiency of spinal anesthesia was estimated. Monitoring: Harvard standard of monitoring, ectodermic activity, characteristic of heart rhythm, medical audit. All patients in both groups were same age, physical status, anthropometric information, had equal duration of surgery and dose of local anesthetic agent (15mg). However difference between efficiency of spinal anesthesia was discovered. In group with bypivacain sensory block developed in 1.35 times faster it lasted on 1.22 time longer and motor block developed in 1.4 times faster with a longer duration in 1.32 times than group with ropivacain. Hemodynamic and condition of vegetatic homeostasis in both groups were almost equal but analyzed data presented that ropivacain (5 mg/ml) influenced hemodynamic less. Results of retrospective study demonstrates that it is safer to use isobaric ropivacain (5 ml/mg) in elderly patients for spinal anesthesia in 1.5 times p = 0,007). In conclusion spinal anesthesia with isobaric bypivacain (5mg/ml) more efficient because of duration and time of development of neuroaxial block on the other hand isobaric ropivacain 5 mg/ml is safer to use in patients older than 60 years old.
2,334,089
Lumbosacral epidural magnesium prolongs ketamine analgesia in conscious sheep.
To determine the analgesic, motor, sedation and systemic effects of lumbosacral epidural magnesium sulphate added to ketamine in the sheep.</AbstractText>Six healthy adult male mixed-breed sheep; weighing 43 &#xb1; 5 kg and aged 20-36 months. Each sheep underwent three treatments, at least 2 weeks apart, via epidural injection: (1) ketamine (KE; 2.5 mg/kg), (2) magnesium sulphate (MG; 100 mg), and (3) KE + MG (KEMG; 2.5 mg/kg + 100 mg, respectively). Epidural injections were administered through the lumbosacral space. Analgesia, motor block, sedation, cardiovascular effects, respiratory rate, skin temperature, and rectal temperature were evaluated before (baseline) and after drug administration as needed.</AbstractText>The duration of analgesia with the lumbosacral epidural KEMG combination was 115 &#xb1; 17 min (mean &#xb1; SD), that is, more than twice that obtained with KE (41 &#xb1; 7 min) or MG (29 &#xb1; 5 min) alone. KE and KEMG used in this experiment induced severe ataxia. The heart rate and arterial blood pressures changes were no statistical difference in these clinically health sheep.</AbstractText>The dose of magnesium sulphate to lumbosacral epidural ketamine in sheep is feasible, and can be used in procedures analgesics in sheep.</AbstractText>
2,334,090
Adverse cardiovascular effects of antirheumatic drugs: implications for clinical practice and research.
Clinical manifestations of most rheumatic diseases have changed over the past few decades, largely due to advances in therapies targeting autoimmune and (auto)inflammatory pathways. Improvements in the management of rheumatic diseases have also now brought to the fore the issue of comorbidities. It has become evident that the burden of cardiovascular morbidity and mortality is increased in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and the spondyloarthropathies, amongst other conditions. As a result, efforts have switched toward investigating the effects of conventional antirheumatic and new biologic agents on inflammationinduced atherothrombosis. Evidence is accumulating suggesting a beneficial cardiovascular profile of some antirheumatic drugs, such as methotrexate and hydroxychloroquine, but it also indicates the possibility of a variety of adverse events developing in the short- and long-term. The aim of this review is to highlight cardiovascular adverse effects of the drugs widely used in the treatment of rheumatic diseases. The literature search was performed through PubMed, the Cochrane Library, Scopus, and Web of Science databases using the following terms: "antirheumatic drugs", "inflammation", "rheumatic diseases", "cardiovascular diseases", "adverse events", "toxicity", "drug design", and "drug interactions". Adverse events ranging from infusion-related hypertension and myocardial ischemia, to restrictive cardiomyopathy and congestive heart failure have been reported in large trials and case series on most antirheumatic drugs. Clinicians should be alert of the wide variety of cardiovascular adverse effects of individual antirheumatic drugs, and should carefully monitor blood pressure and markers of inflammation, thrombosis, myocardial ischemia, electrolytes, and lipid disturbances while administering these drugs. Future prospective studies should specifically investigate the cardiovascular safety of most antirheumatic drugs as part of mono- or combination therapy in relation to different dosage regimens, duration of therapy, age, and gender.
2,334,091
Application of human stem cell-derived cardiomyocytes in safety pharmacology requires caution beyond hERG.
Human embryonic stem cell-derived cardiomyocytes (hESC-CM) have been proposed as a new model for safety pharmacology. So far, a thorough description of their basic electrophysiology and extensive testing, and mechanistic explanations, of their overall pro-arrhythmic ability is lacking. Under standardized conditions, we have evaluated the sensitivity of hESC-CM to proarrhythmic provocations by blockade of hERG and other channels. Using voltage patch clamp, some ion current densities (pA/pF) in hESC-CM were comparable to adult CM: I(Kr) (-12.5 &#xb1; 6.9), I(Ks) (0.65 &#xb1; 0.12), I(Na,peak) (-72 &#xb1; 21), I(Na,late) (-1.10 &#xb1; 0.36), and I(Ca,L) (-4.3 &#xb1; 0.6). I(f) density was larger (-10 &#xb1; 1.1) and I(K1) not existent or very small (-2.67 &#xb1; 0.3). The low I(K1) density was corroborated by low KCNJ2 mRNA levels. Effects of pro-arrhythmic compounds on action potential (AP) parameters and provocation of early afterdepolarizations (EADs) revealed that Chromanol293B (100 &#x3bc;mol/l) and Bay K8644 (1 &#x3bc;mol/l) both significantly prolonged APD(90). ATX-II (&lt;1 &#x3bc;mol/l ) and BaCl(2) (10 &#x3bc;mol/l ) had no effect on APD. The only compound that triggered EADs was hERG blocker Cisapride. Computer simulations and AP clamp showed that the immature AP of hESC-CM prevents proper functioning of I(Na)-channels, and result in lower peak/maximal currents of several other channels, compared to the adult situation. Lack of functional I(K1) channels and shifted I(Na) channel activation cause a rather immature electrophysiological phenotype in hESC-CM, and thereby limits the potential of this model to respond accurately to pro-arrhythmic triggers other than hERG block. Maturation of the electrical phenotype is a prerequiste for future implementation of the model in arrhythmogenic safety testing.
2,334,092
A comparison of the effectiveness of predictors of caudal block in children-swoosh test, anal sphincter tone, and heart rate response.
To study the effectiveness of three predictors of successful caudal block in children, viz. swoosh test, heart rate response to injection, and laxity of anal sphincter tone.</AbstractText>To improve the success rates of caudal block in children by identifying the best predictor.</AbstractText>Caudal blocks in children are placed after induction of anesthesia. Although simple to learn and perform, the success rate of the blocks may be variable especially in teaching hospitals where trainee anesthetists perform these blocks.</AbstractText>223 patients, aged 2-12 years, undergoing lower abdominal and urologic surgery were studied. 0.25% Bupivacaine was administered after induction of general anesthesia according to the Armitage regimen.</AbstractText>The sensitivity and specificity were highest with the sphincter tone test (sensitivity 95.22%, specificity 92.86%), followed by the heart rate response (sensitivity 92.82%, specificity 78.57%) and the swoosh test (sensitivity 66.51%, specificity 35.71%). The anal sphincter tone test had the highest positive predictive value (99.5%) and positive likelihood ratio (13.33). The heart rate response had a positive predictive value of 98.48% and a positive likelihood ratio of 4.33. The swoosh test, in our study, had a positive predictive value of 93.92% and a positive likelihood ratio of 1.035.</AbstractText>The anal sphincter tone test was the best predictor of successful caudal block. We recommend the use of these additional simple predictors of accurate needle placement to increase the success rate of caudal block especially in teaching hospitals.</AbstractText>
2,334,093
Protective effects of pinacidil hyperpolarizing cardioplegia on myocardial ischemia reperfusion injury by mitochondrial KATP channels.
Many studies have indicated that hyperpolarizing cardioplegia is responsible for myocardial preservation and researchers have suggested that the adenosine triphosphate-sensitive potassium channels (K(ATP)) were the end effectors of cardio-protection. But whether mitochondrial K(ATP) plays an important role in hyperpolarizing cardioplegia is not apparent. The present study investigated the effect of hyperpolarizing cardioplegia containing pinacidil (a nonselective K(ATP) opener) on ischemia/reperfusion injury in rat hearts, especially the role of mitochondrial K(ATP) in pinacidil hyperpolarizing cardioplegia.</AbstractText>Sprague-Dawley rat hearts were Langendorff-perfused for 20 minutes with Krebs-Henseleit buffer at 37&#xb0;C before equilibration. Cardiac arrest was then induced in different treatments: there was no arrest and ischemia in the normal group, the control group were arrested by clamping the aorta, depolarizing caidioplegia (St. Thomas solution containing 16 mmol/L KCl) and hyperpolarizing cardioplegia groups used St. Thomas solution containing 0.05 mmol/L pinacidil and 5 mmol/L KCl to induce cardiac arrest in group hyperkalemic and group pinacidil, in group hyperkalemic + 5-hydroxydecanote (5HD) and Pinacidil + 5HD, 5HD (0.1 mmol/L) was added to the above two solutions to block mitochondria K(ATP) channels. Global ischemia was then administrated for 40 minutes at 37&#xb0;C, followed by 30 minutes of reperfusion. At the end of equilibration and reperfusion, hemodynamics, ultrastructure, and mitochondrial function were measured.</AbstractText>In the control group, ischemia/reperfusion decreased the left ventricular developed pressure, heart rate, coronary flow, mitochondrial membrane potential, impaired mitochondrial respiratory function, increased reactive oxygen species and left ventricular end diastolic pressure. Damage to myocardial ultrastructure was also evident. Both depolarized arrest and especially hyperpolarized cardioplegia significantly reduced these lesions. 5HD partially blocked the beneficial effects of pinacidil cardioplegia but showing no effects on hyperkalemic arrest.</AbstractText>Pinacidil cardioplegia provides better cardioprotection with preservation of hemodynamics, ultrastructure, and mitochondrial function than traditional cardioplegia. The mitochondria K(ATP) channels may play an important role in the protection mechanism.</AbstractText>
2,334,094
[The in-hospital mortality and its determinants for very elderly patients with acute myocardial infarction].
To explore the in-hospital mortality and its determinants for very eldly (80+ years of age) patients with acute myocardial infarction (AMI).</AbstractText>A retrospective cohort method was used. The 499 study subjects were very eldly patients with newly diagnosed AMI consecutively admitted into our department between January 1, 2002 and February 22, 2010.</AbstractText>Ninety-seven out of 499 patients died during hospitalization period, with total in-hospital mortality of 19.4%. Multivariable logistic regression analysis showed the independent determinants for mortality of very elderly AMI patients were cardiac Killip grades, complete A-V block, renal dysfunction, stent implant, and the type of AMI.</AbstractText>The independent determinants for mortality of elderly AMI patients are as following, cardiac Killip grade, complete A-V block, renal dysfunction, stent implant, and the type of MAI. Urgent PCI is safe and effective for some very elderly with AMI, which could improve their survival rate within hospitalization period.</AbstractText>
2,334,095
Correlates of global area strain in native hypertensive patients: a three-dimensional speckle-tracking echocardiography study.
The present study aimed to test the capability of real-time three-dimensional echocardiography (RT3DE) in characterizing early abnormalities of left ventricular (LV) structure and function in native, untreated hypertensive patients.</AbstractText>Thirty-eight newly diagnosed, never-treated hypertensives (H) and 38 healthy controls (C) underwent both standard echo-Doppler and RT3DE assessment. LV volumes and ejection fraction (EF), sphericity index, LV mass index (LVMi), global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were calculated by RT3DE. The two groups were comparable for age and heart rate. Body mass index and blood pressure (BP) were significantly higher in H. LV volumes, EF, and sphericity index calculated by RT3DE did not differ significantly between the two groups, while LVMi was higher in H than in C (P&lt; 0.0001). GAS (-29.1 &#xb1; 2.5% in H vs. -33.6 &#xb1; 3.4% in C), GLS, and GRS (all P&lt; 0.0001) were lower in H, but GCS was not significantly different between the two groups. Among the different 3D strain components, GAS showed the best independent associations with mean BP (&#x3b2; = -0.502, P&lt; 0.0001) and LVMi (&#x3b2; = -0.385, P&lt; 0.001; cumulative R(2) = 0.55, P&lt; 0.0001) in the pooled population.</AbstractText>RT3DE identifies early functional LV changes in native hypertensive patients. GAS is precociously reduced, and longitudinal and radial strain impaired, while circumferential strain is still preserved, supporting a normal LV chamber systolic function. Reduction of GAS is independently associated with both pressure overload and magnitude of the LV mass.</AbstractText>
2,334,096
Actin cytoskeleton rest stops regulate anterograde traffic of connexin 43 vesicles to the plasma membrane.
The intracellular trafficking of connexin 43 (Cx43) hemichannels presents opportunities to regulate cardiomyocyte gap junction coupling. Although it is known that Cx43 hemichannels are transported along microtubules to the plasma membrane, the role of actin in Cx43 forward trafficking is unknown.</AbstractText>We explored whether the actin cytoskeleton is involved in Cx43 forward trafficking.</AbstractText>High-resolution imaging reveals that Cx43 vesicles colocalize with nonsarcomeric actin in adult cardiomyocytes. Live-cell fluorescence imaging reveals Cx43 vesicles as stationary or traveling slowly (average speed 0.09 &#x3bc;m/s) when associated with actin. At any time, the majority (81.7%) of vesicles travel at subkinesin rates, suggesting that actin is important for Cx43 transport. Using Cx43 containing a hemagglutinin tag in the second extracellular loop, we developed an assay to detect transport of de novo Cx43 hemichannels to the plasma membrane after release from Brefeldin A-induced endoplasmic reticulum/Golgi vesicular transport block. Latrunculin A (for specific interference of actin) was used as an intervention after reinitiation of vesicular transport. Disruption of actin inhibits delivery of Cx43 to the cell surface. Moreover, using the assay in primary cardiomyocytes, actin inhibition causes an 82% decrease (P&lt;0.01) in de novo endogenous Cx43 delivery to cell-cell borders. In Langendorff-perfused mouse heart preparations, Cx43/&#x3b2;-actin complexing is disrupted during acute ischemia, and inhibition of actin polymerization is sufficient to reduce levels of Cx43 gap junctions at intercalated discs.</AbstractText>Actin is a necessary component of the cytoskeleton-based forward trafficking apparatus for Cx43. In cardiomyocytes, Cx43 vesicles spend a majority of their time pausing at nonsarcomeric actin rest stops when not undergoing microtubule-based transport to the plasma membrane. Deleterious effects on this interaction between Cx43 and the actin cytoskeleton during acute ischemia contribute to losses in Cx43 localization at intercalated discs.</AbstractText>
2,334,097
On-pump inhibition of es-ENT1 nucleoside transporter and adenosine deaminase during aortic crossclamping entraps intracellular adenosine and protects against reperfusion injury: role of adenosine A1 receptor.
The inhibition of adenosine deaminase with erythro-9 (2-hydroxy-3-nonyl)-adenine (EHNA) and the es-ENT1 transporter with p-nitro-benzylthioinosine (NBMPR), entraps myocardial intracellular adenosine during on-pump warm aortic crossclamping, leading to a complete recovery of cardiac function and adenosine triphosphate (ATP) during reperfusion. The differential role of entrapped intracellular and circulating adenosine in EHNA/NBMPR-mediated protection is unknown. Selective (8-cyclopentyl-1,3-dipropyl-xanthine) or nonselective [8-(p-sulfophenyl)theophyline] A1 receptor antagonists were used to block adenosine A1-receptor contribution in EHNA/NBMPR-mediated cardiac recovery.</AbstractText>Anesthetized dogs (n = 45), instrumented to measure heart performance using sonomicrometry, were subjected to 30 minutes of warm aortic crossclamping and 60 minutes of reperfusion. Three boluses of the vehicle (series A) or 100 &#x3bc;M EHNA and 25 &#x3bc;M NBMPR (series B) were infused into the pump at baseline, before ischemia and before reperfusion. 8-Cyclopentyl-1,3-dipropyl-xanthine (10 &#x3bc;M) or 8-(p-sulfophenyl)theophyline (100 &#x3bc;M) was intra-aortically infused immediately after aortic crossclamping distal to the clamp in series A and series B. The ATP pool and nicotinamide adenine dinucleotide was determined using high-performance liquid chromatography.</AbstractText>Ischemia depleted ATP in all groups by 50%. The adenosine/inosine ratios were more than 10-fold greater in series B than in series A (P &lt; .001). ATP and function recovered in the EHNA/NBMPR-treated group (P &lt; .05 vs control group). 8-Cyclopentyl-1,3-dipropyl-xanthine and 8-(p-sulfophenyl)theophyline partially reduced cardiac function in series A and B to the same degree but did not abolish the EHNA/NBMPR-mediated protection in series B.</AbstractText>In addition to the cardioprotection mediated by activation of the adenosine receptors by extracellular adenosine, EHNA/NBMPR entrapment of intracellular adenosine provided a significant component of myocardial protection despite adenosine A1 receptor blockade.</AbstractText>Copyright &#xa9; 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.</CopyrightInformation>
2,334,098
Effect of warmed ropivacaine solution on onset and duration of axillary block.
Bicarbonate, as an adjunct increasing the non-ionized form of local anesthetics, can reduce latency and prolong duration of regional nerve block. Warming of local anesthetics decreases pKa and also increases the non-ionized form of local anesthetics. We warmed ropivacaine to body temperature (37&#x2103;) and evaluated the sensory block onset time, motor block onset time and analgesic duration of axillary block.</AbstractText>Patients were consecutively allocated to two groups of 22 patients each. Ropivacaine 150 mg (30 ml) at 20&#x2103; (room temperature) and 150 mg (30 ml) at 37&#x2103; (body temperature) was injected in group 1 and group 2, respectively. Sensory block and motor block was assessed every 5 minutes, for 30 minutes after injection. The duration of analgesia was recorded after operation.</AbstractText>In group 2, the onset times of both sensory and motor block of the radial, ulnar, median and musculocutaneous nerves were significantly reduced, compared to group 1. Also, the number of blocked nerves was increased in group 2, within 30 minutes after injection. Analgesia lasted for 2 hours longer in group 2, compared to group 1, but the difference was not statistically significant (P &gt; 0.05).</AbstractText>Warming of ropivacaine to 37&#x2103; can reduce the onset time of both sensory and motor block, during axillary block.</AbstractText>
2,334,099
Noradrenergic &#x3b1;&#x2081; receptor antagonist treatment attenuates positive subjective effects of cocaine in humans: a randomized trial.
Preclinical research implicates dopaminergic and noradrenergic mechanisms in mediating the reinforcing effects of drugs of abuse, including cocaine. The objective of this study was to evaluate the impact of treatment with the noradrenergic &#x3b1;(1) receptor antagonist doxazosin on the positive subjective effects of cocaine.</AbstractText>Thirteen non-treatment seeking, cocaine-dependent volunteers completed this single-site, randomized, placebo-controlled, within-subjects study. In one study phase volunteers received placebo and in the other they received doxazosin, with the order counterbalanced across participants. Study medication was masked by over-encapsulating doxazosin tablets and matched placebo lactose served as the control. Study medication treatment was initiated at 1 mg doxazosin or equivalent number of placebo capsules PO/day and increased every three days by 1 mg. After receiving 4 mg doxazosin or equivalent number of placebo capsules participants received masked doses of 20 and 40 mg cocaine IV in that order with placebo saline randomly interspersed to maintain the blind.</AbstractText>Doxazosin treatment was well tolerated and doxazosin alone produced minimal changes in heart rate and blood pressure. During treatment with placebo, cocaine produced dose-dependent increases in subjective effect ratings of "high", "stimulated", "like cocaine", "desire cocaine", "any drug effect", and "likely to use cocaine if had access" (p&lt;.001). Doxazosin treatment significantly attenuated the effects of 20 mg cocaine on ratings of "stimulated", "like cocaine", and "likely to use cocaine if had access" (p&lt;.05). There were trends for doxazosin to reduce ratings of "stimulated", "desire cocaine", and "likely to use cocaine if had access" (p&lt;.10).</AbstractText>Medications that block noradrenergic &#x3b1;&#x2081; receptors, such as doxazosin, may be useful as treatments for cocaine dependence, and should be evaluated further.</AbstractText>Clinicaltrials.gov NCT01062945.</AbstractText>