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2,332,900 | In vivo implantation of 2,2'-bis(oxazoline)-linked poly-epsilon-caprolactone: proof for enzyme sensitive surface erosion and biocompatibility. | Previously, we have demonstrated that 2,2-bis(2-oxazoline) linked poly-epsilon-caprolactone (PCL-O) is degraded in vitro enzymatically by surface erosion which could enable the novel use of this material for drug delivery and other biomedical applications. In this study, degradation, erosion (weight loss) and toxicity of PCL-O poly(ester-amide)s were evaluated in vivo. PCL and three PCL-O polymers with different PCL block lengths (M(n): 1500, 3900, 7500 g/mol) were melt-pressed in the form of discs and implanted subcutaneously in Wistar rats (dose approximately 340 mg/kg) for 1, 4 and 12 weeks. With implantation for 12 weeks, up to 16.5% weight loss of polymer discs was measured for the most extensively linked PCL-O polymer (block length 1500 g/mol) whereas practically no weight loss was observed with the other polymers. NMR, DSC and SEC studies as well as SEM micrographs before and after implantation and in vitro hydrolysis studies indicate that enzyme based surface erosion of PCL-O polymers occurred in vivo. The in vivo evaluation based on results from hematology, clinical chemistry and histology of the implantation area and main organs (i.e. heart, lung, liver, kidney, spleen and brain) demonstrated that PCL-O polymers are biocompatible and safe, enzyme sensitive biomaterials. |
2,332,901 | Pharmacokinetics, pharmacodynamics, and tolerability of the dipeptidyl peptidase IV inhibitor LC15-0444 in healthy Korean men: a dose-block-randomized, double-blind, placebo-controlled, ascending single-dose, Phase I study. | LC15-0444 is a selective inhibitor of dipeptidyl peptidase (DPP) IV under investigation in Korea for the treatment of type 2 diabetes.</AbstractText>The aim of this study was to investigate the pharmacokinetic (PK), pharmacodynamic (PD), and tolerability profiles of a single dose of LC15-0444 in healthy male subjects.</AbstractText>A dose-block-randomized, double-blind, placebo-controlled, ascending single-dose, Phase I study was performed in healthy Korean male subjects assigned to receive 25, 50, 100, 200, 400, or 600 mg of LC15-0444 capsules. Blood and urine samples were collected up to 72 hours after administration. Plasma and urine drug concentrations were determined by tandem mass spectrometry coupled with high-performance liquid chromatography. DPP IV activity was measured by continuous spectrophotometric assay. An additional food effect study was performed in the 100-mg dose group; changes in PK and PD parameters after high-fat diet were evaluated. Adverse events (AEs) were detected through investigator inquiries, spontaneous reports, and clinical evaluations such as physical examinations, vital sign measurements, 12-lead electrocardiography, clinical laboratory tests (eg, hematology, blood chemistry, coagulation, urinalysis), and computerized impedance cardiography.</AbstractText>Sixty Korean men (mean age, 25.3 years [range, 19-39 years]; weight, 68.3 kg [range, 53.6-84.9 kg]) were enrolled, providing 10 subjects for each dose group. After administration, LC15-0444 reached T(max) at 0.5 to 5.1 hours, and was eliminated with a t((1/2)) of 16.7 to 21.3 hours. The mean fraction of unchanged drug excreted in urine ranged from 0.21 to 0.34 and mean renal clearance was 15.5 to 23.6 L/h. The dose-normalized AUC exhibited dose-linearity over the range of 50 to 400 mg. All doses of LC15-0444 =200 mg were found to inhibit 80% of DPP IV activity for 24 hours. High-fat diet did not significantly influence the AUC of LC15-0444. LC15-0444 was generally well tolerated. None of the subjects developed any serious clinical or laboratory AEs or discontinued the study due to an AE. All AEs were mild or moderate, and no dose-related trends were observed. Forty-six AEs were reported in 18 subjects (30.0%). AEs considered to be related to the study drug were headache (6 cases), dizziness (2), nausea (1), epistaxis (1), and increased heart rate (1). All AEs resolved spontaneously.</AbstractText>A single dose of LC15-0444 exhibited linear PK properties over the range of 50 to 400 mg in these healthy Korean male subjects. PK characteristics were not significantly influenced by food. In addition, doses >or=200 mg of LC15-0444 inhibited plasma DPP IV activity by >80% over a 24-hour dosing interval, and a 600-mg dose increased active glucagon-like peptide-1 levels after a standardized meal. LC15-0444 was generally well tolerated.</AbstractText> |
2,332,902 | Urbanization and coronary heart disease: a study of urban-rural differences in northern India. | In the West, urbanization has been accompanied by a rise in the rate of coronary heart disease. This trend has gone hand in hand with an increased consumption of processed, energy-dense food and dependence on machines for physical work. To examine whether a similar trend is underway in northern India, the prevalence of and risk factors for coronary heart disease were compared in rural, semi-urban and urban communities.</AbstractText>A total of 7,169 adults were interviewed and examined during 1995-2000 in cross-sectional cluster sample surveys from a rural area of Haryana (Raipur Rani block), two semi-urban areas of Punjab (Mandi Gobindgarh and Morinda), and Chandigarh city. The study, which covered people in the age-group of 35+ years, also estimated the lipid, glucose and insulin levels of a sub-sample of 186 persons who did not have coronary heart disease or hypertension. The prevalence of coronary heart disease among males in the villages, towns and city was 1.7%, 2.5% and 7.4%, respectively, and among females, 1.5%, 3.4% and 7.1%,respectively. The age- and sex-adjusted prevalence odds ratio of coronary heart disease, in comparison to the villages, was 1.9 (95% CI; 1.1-3.2) in the towns and 4.9 (95% CI: 2.9-8.2) in the city. Hypertension, diabetes, obesity and physical inactivity were significantly more common in the urban areas, while the rate of tobacco smoking was significantly higher in the rural areas ( p< 0.05). The alcohol consumption rates for the urban and rural communities were similar (p> 0.05). The quantity of the food items commonly consumed, as well as the frequency with which particular items were consumed, varied across the rural, semi-urban and urban areas ( p< 0.05). The urban population had significantly higher levels of lipids and serum insulin than did the rural population, but a lower level of plasma glucose ( p< 0.05).</AbstractText>The urban way of living is leading to an increase in the prevalence of the well-known risk factors for, as well as the rate of, coronary heart disease. Attempts to preserve the traditional lifestyle are necessary in order to prevent an epidemic of coronary heart disease in the developing countries.</AbstractText> |
2,332,903 | Midazolam with bupivacaine for improving analgesia quality in brachial plexus block for upper limb surgeries. | To compare the onset, duration and postoperative pain scores of supraclavicular block with bupivacaine alone and bupivacaine-midazolam combination.</AbstractText>Randomized controlled clinical trial.</AbstractText>The Postgraduate Medical Institute, Hayatabad Medical Complex, Peshawar, from April 2005 to June 2007.</AbstractText>A randomized controlled clinical trial was conducted on 50 ASA-I or II adult patients undergoing upper limb surgeries under supraclavicular brachial plexus block. Patients were randomly allocated into two groups of 25 each. Patients in group A were administered 30 ml of 0.5% bupivacaine and those in group B were given 30 ml of 0.5% bupivacaine with midazolam 50 microg x kg-1. Hemodynamic variables (heart rate, noninvasive blood pressure, oxygen saturation), pain scores, rescue analgesic requirements and sedation score were recorded for 24 hours postoperatively, and compared using ANOVA with significance at p <0.05.</AbstractText>The onset and duration of sensory and motor block was significantly faster and longer in group B compared to group A (p < 0.001). Pain scores were significantly lower in group B for 24 hours postoperatively (p < 0.001). Demand for rescue analgesic were significantly less in group B. Hemodynamics and sedation scores did not differ between the groups in the studied period.</AbstractText>Bupivacaine (0.5%) in combination with Midazolam (50 microg x kg-1) quickened the onset as well as prolonged the duration of sensory and motor blockade of the brachial plexus for upper limb surgery. It improved postoperative analgesia without producing any adverse events compared to plain bupivacaine (0.5%) in equal volume.</AbstractText> |
2,332,904 | Nitric oxide specifically inhibits integrin-mediated platelet adhesion and spreading on collagen. | Nitric oxide (NO) inhibits platelet adhesion to collagen, although the precise molecular mechanisms underlying this process are unclear.</AbstractText>Collagen-mediated adhesion is a multifaceted event requiring multiple receptors and platelet-derived soluble agonists. We investigated the influence of NO on these processes.</AbstractText>S-nitrosoglutathione (GSNO) induced a concentration-dependent inhibition of platelet adhesion to immobilized collagen. Maximal adhesion to collagen required platelet-derived ADP and TxA(2). GSNO-mediated inhibition was lost in the presence of apyrase and indomethacin, suggesting that NO reduced the availability of, or signaling by, ADP and TxA(2). Exogenous ADP, but not the TxA(2) analogue U46619, reversed the inhibitory actions of GSNO on adhesion. Under adhesive conditions NO inhibited dense granule secretion but did not influence TxA(2) generation. These data indicated that NO may block signaling by TxA(2) required for dense granule secretion, thereby reducing the availability of ADP. Indeed, we found TxA(2)-mediated activation of PKC was required to drive dense granule secretion, a pathway that was inhibited by NO. Because our data demonstrated that NO only inhibited the activation-dependent component of adhesion, we investigated the effects of NO on individual collagen receptors. GSNO inhibited platelet adhesion and spreading on alpha(2)beta(1) specific peptide ligand GFOGER. In contrast, GSNO did not inhibit GPVI-mediated adhesion to collagen, or adhesion to the GPVI specific ligand, collagen related peptide (CRP).</AbstractText>NO targets activation-dependent adhesion mediated by alpha(2)beta(1), possibly by reducing bioavailability of platelet-derived ADP, but has no effect on activation-independent adhesion mediated by GPVI. Thus, NO regulates platelet spreading and stable adhesion to collagen.</AbstractText> |
2,332,905 | Expression of cardiac alpha-actin spares extraocular muscles in skeletal muscle alpha-actin diseases--quantification of striated alpha-actins by MRM-mass spectrometry. | As with many skeletal muscle diseases, the extraocular muscles (EOMs) are spared in skeletal muscle alpha-actin diseases, with no ophthalmoplegia even in severely affected patients. We hypothesised that the extraocular muscles sparing in these patients was due to significant expression of cardiac alpha-actin, the alpha-actin isoform expressed in heart and foetal skeletal muscle. We have shown by immunochemistry, Western blotting and a novel MRM-mass spectrometry technique, comparable levels of cardiac alpha-actin in the extraocular muscles of human, pig and sheep to those in the heart. The sparing of extraocular muscles in skeletal muscle alpha-actin disease is thus probably due to greater levels of cardiac alpha-actin, than the negligible amounts in skeletal muscles, diluting out the effects of the mutant skeletal muscle alpha-actin. |
2,332,906 | Superficial versus combined (deep and superficial) cervical plexus block for carotid endarterectomy. | It is not clear if any technique of regional anesthesia for carotid endarterectomy has an advantage over another. Therefore, we analyzed analgesic efficacy side effects and complication rate in patients undergoing carotid surgery either under combined (deep and superficial) or superficial cervical block alone. Data on 324 patients that received either combined (n = 107) or superficial (n = 216) cervical block were prospectively analyzed. Data were collected on the intraoperative Verbal Analog Score (VAS), arterial pressure and heart rate. Analgesic efficacy was additionally assessed by the dose of supplemental 1% lidocaine and fentanyl and time before the first analgesic was administered at Intensive Care Unit. During surgery, VAS was slightly higher in the superficial group (median 0.6, range 0-3.9) than in the combined group (median 0.4, range 0-2.4; p < 0.001). The median supplemental lidocaine dose during the operation was higher in the superficial block group (2.4 mg/kg, range 1.1-3.5) than in the combined group (2.1, range 0.5-3.4 mg/kg; p < 0.001). Supplemental fentanyl was also higher in the superficial block group. There were no between-group differences in the time before the first postoperative analgesic, postoperative VAS and block-related complication rate. Accordingly combined block provided a slightly better analgesia during the surgery which was probably clinically irrelevant. There was no difference in postoperative analgesia and hemodynamic stability. So far, this is the largest prospective study in which superficial cervical block was found to be as efficacious as combined block which is associated with a considerably higher risk of complications. |
2,332,907 | Red blood cell accumulation in a rat model of pulmonary ischemia/reperfusion injury. | Red blood cell (RBC) accumulation in lung tissue during ischemia/reperfusion has not been studied extensively. A warm lung ischemia/reperfusion-injury model was developed to determine RBC trapping.</AbstractText>Twenty-four rats were randomized into 5 groups. In 4 groups, the left lung was submitted to 20 minutes of warm ischemia followed by reperfusion for 3, 10, 30 and 60 minutes. Subsequently, both lungs were flushed. Afterwards the heart-lung block was removed and fixed endoluminally. The fifth group was the sham group, in which lungs were flushed after 20 minutes of perfusion without induction of ischemia. RBC were counted in the hilar sectional plane and expressed in area%.</AbstractText>In the left reperfused ischemic lung, already 3 minutes after reperfusion, a significant accumulation of RBC was found in the capillaries. This accumulation was accompanied by a significant vascular congestion of these vessels. After in vivo perfusion, almost all RBC were flushed out the blood vessels of the non-ischemic lung (area%=0.082). In ischemic reperfused lungs, capillaries were densely packed with RBC. Significantly more RBC were counted after 3 (area%=1.572; P=0.002) and 10 minutes (area%=1.240; P=0.011) of reperfusion compared to the sham group. After 30 (area%=0.929; P=0.054) and 60 minutes (area%=0.435; P=0.404) no significant increase in RBC was observed compared to the sham group. In the right non-ischemic lungs, no differences in RBC accumulation were observed between the sham group and ischemia-reperfusion groups.</AbstractText>After warm ischemia/reperfusion, a significant early increase in accumulation of RBC was observed.</AbstractText> |
2,332,908 | Extracellular superoxide dismutase haplotypes are associated with acute lung injury and mortality. | Extracellular superoxide dismutase (EC-SOD) is a potent antioxidant that plays an important role in controlling oxidant-mediated stress and inflammation. High levels of EC-SOD are found in the lung. Acute lung injury (ALI) frequently occurs in patients with infection, and levels of EC-SOD have been shown to modulate severity of lung injury in transgenic animal models of endotoxemia-induced ALI. An R213G single nucleotide polymorphism (SNP) has been shown to alter levels of EC-SOD and patient outcomes in chronic obstructive pulmonary disease (COPD) and ischemic heart disease.</AbstractText>To determine genetic variation in the promoter and EC-SOD gene and to examine whether EC-SOD haplotype blocks are associated with clinical outcomes.</AbstractText>We sequenced the EC-SOD promoter and gene to determine genetic variation and linkage disequilibrium (LD) patterns in a European American population. Two separate patient populations with infection-associated ALI were also evaluated to determine whether EC-SOD haplotypes were associated with clinical outcomes.</AbstractText>Sequencing resulted in the identification of 28 SNPs with relatively strong LD and 1 block consisting of 4691-5321-5360-5955-5982. This specific block was shown to be protective in two separate patient populations with infection associated ALI. In particular, patients with a GCCT haplotype had a reduced risk of time on the ventilator and mortality.</AbstractText>These results indicate that a GCCT haplotype may reduce inflammation in the lung, thereby decreasing the severity of lung injury and ultimately protecting patients from mortality associated with infection-induced ALI.</AbstractText> |
2,332,909 | Effect of neutralizing sera on factor x-mediated adenovirus serotype 5 gene transfer. | The deployment of adenovirus serotype 5 (Ad5)-based vectors is hampered by preexisting immunity. When such vectors are delivered intravenously, hepatocyte transduction is mediated by the hexon-coagulation factor X (FX) interaction. Here, we demonstrate that human sera efficiently block FX-mediated cellular binding and transduction of Ad5-based vectors in vitro. Neutralizing activity correlated well with the ability to inhibit Ad5-mediated liver transduction, suggesting that prescreening patient sera in this manner accurately predicts the efficacy of Ad5-based gene therapies. Neutralization in vitro can be partially bypassed by pseudotyping with Ad45 fiber protein, indicating that a proportion of neutralizing antibodies are directed against the Ad5 fiber. |
2,332,910 | Reverse genetic studies of mitochondrial DNA-based diseases using a mouse model. | In the situation that it would not be able to produce model animals for mitochondrial diseases caused by mitochondrial DNA (mtDNA) with pathogenic mutations, we succeeded in generating mice with pathogenic deletion mutant mtDNA (DeltamtDNA), named "mito-mice", by direct introduction of mitochondria with DeltamtDNA into mouse zygotes. In the mito-mice, accumulation of DeltamtDNA induced mitochondrial respiration defects in various tissues, resulting in mitochondrial disease phenotypes, such as low body weight, lactic acidosis, ischemia, myopathy, heart block, deafness, male infertility, and renal failure. Thus, mito-mice are the first model animal for mtDNA-based diseases, and the mice could be valuable for understanding precise pathogeneses and testing therapies of mitochondrial diseases. In the present review, we summarized reverse genetic studies using the mito-mice.(Communicated by Takao SEKIYA, M.J.A.). |
2,332,911 | Clinical pharmacology of cisatracurium during nitrous oxide-propofol anesthesia in children. | To describe, in pediatric patients, the effects of three doses of cisatracurium during nitrous oxide-propofol anesthesia and to determine if larger doses result in faster onset time.</AbstractText>College hospital.</AbstractText>75 ASA physical status I and II children, aged 15 to 60 months, undergoing surgery for hypospadias or undescendent testis.</AbstractText>Patients were randomly assigned to one of three groups according to the dose of cisatracurium: Group A = 0.1 mg/kg (two x effective dose), Group B = 0.15 mg/kg (three x effective dose), and Group C = 0.2 mg/kg (4 x effective dose).</AbstractText>Neuromuscular block was assessed with TOF-Guard (Biometer International, Odense, Denmark) accelerometry. Onset time (from cisatracurium injection to maximal depression of time to first twitch), duration of peak effect (time from cisatracurium injection to 5% recovery of time to first twitch), duration of clinical action (time from cisatracurium injection to 25% recovery of time to first twitch), and recovery index (recovery of time to first twitch from 25% to 75%) were recorded.</AbstractText>Cisatracurium had no effect on heart rate or blood pressure at any dose. Compared with Group A, onset times in Groups B and C were shorter; and durations of peak effect and clinical action in Groups B and C were longer (P < 0.01) than those in Group A. There was no difference in recovery index among the three groups. There was no difference in onset times between Groups B and C. Compared with Group B, durations of peak effect and clinical action in Group C were longer (P < 0.05 or P < 0.01).</AbstractText>Four times the effective dose of cisatracurium did not significantly shorten onset time beyond that produced with three times the effective dose in young children.</AbstractText> |
2,332,912 | Priming donor lungs with thioredoxin-1 attenuates acute allograft injury in a rat model of lung transplantation. | Lung graft dysfunction and rejection are significant causes of morbidity and mortality in transplant recipients. Thioredoxin-1, a redox-regulatory protein, functions as an antioxidant in multiple organs, including lungs. We examined whether priming of the donor lungs with thioredoxin-1 before transplantation attenuates acute lung injury.</AbstractText>Orthotopic left lung transplantation was performed from Lewis (donor) to Sprague-Dawley (recipient) rats. Donor lungs were perfused and stored in Perfadex solution (Vitrolife, Uppsala, Sweden), with or without purified thioredoxin-1. Changes in bronchoalveolar lavage (BAL) analysis, allograft oxygen exchange function, nuclear factor kappaB (NF-kappaB)/DNA binding, myeloperoxidase activities, and immunohistologic evaluation of neutrophils, macrophages, and cytotoxic T-cells (CD8(+)) infiltration were examined in post-transplant allograft (left) and native (right) lungs at Days 1 and 5.</AbstractText>BAL cell differential analysis showed significant increases in macrophages and neutrophils in allografts at Day 1 post-transplant. At Days 1 and 5, lymphocyte infiltration was significantly increased and myeloperoxidase and NF-kappaB/DNA binding activities were increased vs basal activities. Immunohistology staining revealed increased infiltration of macrophages, neutrophils, and CD8(+) T cell sub-sets. Pre-transplant priming of donor lungs with thioredoxin-1 improved oxygen exchange and attenuated NF-kappaB/DNA binding activity, and infiltration of macrophages, neutrophils, and CD8(+) T cell sub-sets in allografts at Days 1 and 5 post-transplant.</AbstractText>Priming of donor lungs with thioredoxin-1 before transplant attenuates acute allograft injury in a rat model of lung transplantation, and appears to be associated with the antioxidant function of thioredoxin-1 that limits early ischemia-reperfusion injury, NF-kappaB activation, and progressive infiltration of inflammatory and immune cells in allografts.</AbstractText> |
2,332,913 | [Clinical and genetic analysis of a pedigree of myotonic dystrophy disease]. | To investigate the clinical manifestations and to make genetic analysis in a pedigree with myotonic dystrophy disease.</AbstractText>The proband and available family members were identified by neurological examination. The clinical manifestation of 8 patients (including the proband) was analyzed; the electromyographic data of 5 patients were compared with 6 other family members. Blood samples were obtained from the 7 patients of the family (excepting II6). DM(1) and DM(2) gene were amplified by PCR, tested by agarose electrophoresis, then analyzed by genetic analyzer.</AbstractText>Myotonia and muscle weakness were the main manifestations associated with heart block (7/8) and cataract(6/7). Electromyologram showed myopathic abnormalities not only in patients but also in other members of the family (5/6). The CTG repeats in DM1 and CCTG repeats in DM2 were all in normal range.</AbstractText>There likely to be new mutants in this DM pedigree and further study is needed.</AbstractText> |
2,332,914 | The physiological effects of thoracic epidural anesthesia and analgesia on the cardiovascular, respiratory and gastrointestinal systems. | Studies of regional anesthesia are increasing in popularity not only for the purpose of technical advancement, but also to better understand the effects of neural deafferentation on the function of various organs. Thoracic epidural anesthesia (TEA) is one of the most versatile and widely utilized neural deafferentation techniques. The aim of this article is to critically review published data regarding the most relevant effects of TEA on the cardiovascular, respiratory and gastrointestinal systems. In the cardiovascular system, TEA modifies the electrical activity of the heart in addition to ventricular function and wall motion. Improvements in regional blood flow and a reduction of the major determinants of cardiac oxygen consumption lead to less severity of the ischemic injury. Although TEA negatively affects the performance of intercostal muscles, it spares diaphragmatic function and, when it is limited to the first five thoracic segments, affects pulmonary volumes to a lesser extent. TEA can be safely used in patients with compromised respiration. Splanchnic sympathetic block is achieved when thoracic fibers from T5 to T12 are affected in a dose-dependent manner. Improved gastrointestinal blood flow and motility are clear in animals, and in clinical studies, TEA has been shown to improve recovery after major abdominal surgery. TEA thus presents a powerful tool available to anesthesiologists for perioperative intervention, but its use alone cannot prevent postoperative morbidity and mortality. It is therefore necessary to address its use in the context of multimodal intervention. |
2,332,915 | Surgical stress index as a measure of nociception/antinociception balance during general anesthesia. | No validated monitoring method is available for evaluating the nociception/antinociception balance. We assessed the surgical stress index (SSI), computed from finger photoplethysmographic waveform amplitudes and pulse-to-pulse intervals, in patients undergoing shoulder surgery under general anesthesia (GA) and interscalene plexus block and in patients with GA only.</AbstractText>In this prospective, randomized study in 26 patients, increased blood pressure (BP) or heart rate, movement, and coughing were considered to be signs of intraoperative nociception and were treated with alfentanil. GA was maintained with desflurane aiming at a State Entropy level of 50. Photoplethysmographic waveforms were collected from the contra-lateral arm to the surgery and SSI values from 0 (no surgical stress) to 100 (maximal surgical stress) were calculated off-line.</AbstractText>Two minutes after skin incision, SSI had not increased in the plexus group and was lower in the plexus group (38 +/- 13) compared with the controls (58 +/- 13, P<0.005). Among the controls, 1 min before alfentanil administration, the SSI value was higher than during periods of adequate antinociception, 59 +/- 11 vs. 39 +/- 12 (P<0.01). The total cumulative need for alfentanil was higher in controls (2.7 +/- 1.2 mg) compared with the plexus group (1.6 +/- 0.5 mg; P=0.008). Tetanic stimulation to the ulnar region of the hand increased SSI significantly only among the patients with plexus block not covering the site of the stimulation.</AbstractText>SSI values were lower in patients with plexus block covering the sites of nociceptive stimuli. In detecting nociceptive stimuli, SSI had better performance than heart rate, BP, or response entropy.</AbstractText> |
2,332,916 | Intracellular calcium modulation of voltage-gated sodium channels in ventricular myocytes. | Cardiac voltage-gated sodium channels control action potential (AP) upstroke and cell excitability. Intracellular calcium (Ca(i)(2+)) regulates AP properties by modulating various ion channels. Whether Ca(i)(2+) modulates sodium channels in ventricular myocytes is unresolved. We studied whether Ca(i)(2+) modulates sodium channels in ventricular myocytes at Ca(i)(2+) concentrations ([Ca(i)(2+)]) present during the cardiac AP (0-500 nM), and how this modulation affects sodium channel properties in heart failure (HF), a condition in which Ca(i)(2+) homeostasis is disturbed.</AbstractText>Sodium current (I(Na)) and maximal AP upstroke velocity (dV/dt(max)), a measure of I(Na), were studied at 20 and 37 degrees C, respectively, in freshly isolated left ventricular myocytes of control and HF rabbits, using whole-cell patch-clamp methodology. [Ca(i)(2+)] was varied using different pipette solutions, the Ca(i)(2+) buffer BAPTA, and caffeine administration. Elevated [Ca(i)(2+)] reduced I(Na) density and dV/dt(max), but caused no I(Na) gating changes. Reductions in I(Na) density occurred simultaneously with increase in [Ca(i)(2+)], suggesting that these effects were due to permeation block. Accordingly, unitary sodium current amplitudes were reduced at higher [Ca(i)(2+)]. While I(Na) density and gating at fixed [Ca(i)(2+)] were not different between HF and control, reductions in dV/dt(max) upon increases in stimulation rate were larger in HF than in control; these differences were abolished by BAPTA.</AbstractText>Ca(i)(2+) exerts acute modulation of I(Na) density in ventricular myocytes, but does not modify I(Na) gating. These effects, occurring rapidly and in the [Ca(i)(2+)] range observed physiologically, may contribute to beat-to-beat regulation of cardiac excitability in health and disease.</AbstractText> |
2,332,917 | A comparison of paracervical block with single-shot spinal for labour analgesia in multiparous women: a randomised controlled trial. | Epidural and spinal analgesia may be contraindicated or unavailable in labour. This randomised controlled study examined the suitability of paracervical block as an alternative method of labour analgesia.</AbstractText>Multiparous women in labour were randomised to receive either paracervical block or single-shot spinal analgesia. Pain was quantified using a numerical rating scale. Subsequent analgesia, progress of labour, and mode of delivery were noted. Fetal heart rate patterns were reviewed. Apgar scores and umbilical artery pH measurements were collected. Parturients' satisfaction and willingness to have the same method of labour analgesia again were recorded.</AbstractText>122 parturients were randomised with data available on 104. Median pain scores decreased significantly in both groups; this was greater with single-shot spinal analgesia (difference between means 2.7; 95% CI 1.9-3.5; P(g)<0.001). Parturients receiving paracervical block received subsequent analgesia more often (23/56 vs. 3/48, P<0.001). Progress of labour, instrumental delivery rates, detected abnormal decelerations in cardiotocography and neonatal outcome were similar between groups. Shivering (P<0.04) and pruritus (P<0.001) were more common with single-shot spinal analgesia. Parturients in the paracervical block group were less satisfied (median 7.0, IQR 3.0-8.0 vs. median 9.0, IQR 8.0-10.0; P<0.001) and less willing (28/55 vs. 39/48, P=0.002) to have the same labour analgesia again.</AbstractText>Paracervical block was less effective than single-shot spinal analgesia. Both methods were associated with a low incidence of fetal bradycardia but maternal side effects were more common with single-shot spinal analgesia.</AbstractText> |
2,332,918 | Influence of Home Monitoring on the clinical status of heart failure patients: Design and rationale of the IN-TIME study. | Despite optimal drug and device therapy, frequent hospitalisations due to decompensated heart failure remain an issue. Early detection of decompensation could prevent hospitalisation in patients with congestive heart failure. The recently introduced Home Monitoring functionality of implanted devices is a promising new telecardiology technique which provides information on the status of heart failure. Home Monitoring observation of heart failure patients could lead to early detection of preclinical decompensation, enable early intervention before clinical decompensation, and thus could prevent hospitalisations.</AbstractText>The IN-TIME study is designed to assess the impact of Home Monitoring on the early detection of worsening congestive heart failure and the clinical status of heart failure patients.</AbstractText>Approximately 620 patients will be prospectively randomised to patient management guided by Home Monitoring analysis or standard care and followed for 12 months. The endpoints committee will adjudicate events in a blinded fashion. The primary endpoint is a composite of all-cause mortality, unplanned hospitalisation due to worsening heart failure, NYHA class and patient global self assessment (Packer score). The study should complete recruitment during 2009 and report in late 2010.</AbstractText> |
2,332,919 | [Diagnostics of autoimmune diseases]. | Autoantibodies play a key role in diagnostic laboratories as markers of autoimmune diseases. In addition to their role as markers they mediate diverse effects in vivo. Autoantibodies with protective effect have been described. Natural protective IgM autoantibodies against tumour-antigens of malignant cells or their precursors may contribute to increased survival rates of carcinoma patients. In a mouse model of systemic lupus erythematosus it has been shown that anti-dsDNA IgM autoantibodies protect from glomerular damage. In contrast, a direct pathogenic role of autoantibodies has been well established e.g. in myasthenia gravis or in Goodpasture syndrome. Similarly autoantibodies against SSA Ro52 are detrimental in neonatal lupus erythematosus with congenital heart block. Moreover, putatively protective autoantibodies may become pathogenic during the course of the disease such as the onconeuronal autoantibodies whose pathogenicity depends on their compartmentalisation. In patients with paraneoplastic syndromes tumour cells express proteins that are also naturally present in the brain. Anti-tumour autoantibodies which temporarily suppress tumour growth can provoke an autoimmune attack on neurons once having crossed the blood-brain barrier and cause specific neurological symptoms. Only a restricted number of autoantibodies are useful follow-up markers for the effectiveness of treatment in autoimmune diseases. Certain autoantibodies hold prognostic value and appear years or even decades before the diagnosis of disease such as the antimitochondrial antibodies in primary biliary cirrhosis or anti-citrullinated protein (CCP)-antibodies in rheumatoid arthritis. It is crucial to know whether the autoantibodies in question recognise linear or conformational epitopes in order to choose the appropriate detection methods. Indirect immunofluorescence microscopy remains a very useful tool for confirmation of results of commercially available immunoassays and for detection of special and rare autoantibodies that otherwise often remain undetected. Standardisation of autoimmune diagnostics is still underway and requires joint efforts by laboratories, clinicians and industry. |
2,332,920 | Determinants within the turret and pore-loop domains of KCNQ3 K+ channels governing functional activity. | KCNQ1-5 (Kv7.1-7.5) subunits assemble to form a variety of functional K(+) channels in the nervous system, heart, and epithelia. KCNQ1 and KCNQ4 homomers and KCNQ2/3 heteromers yield large currents, whereas KCNQ2 and KCNQ3 homomers yield small currents. Since the unitary conductance of KCNQ3 is five- to 10-fold greater than that of KCNQ4 or KCNQ1, these differences are even more striking. To test for differential membrane protein expression, we performed biotinylation and total internal reflection fluorescence imaging assays; however, both revealed only small differences among the channels, leading us to investigate other mechanisms at work. We probed the molecular determinants governing macroscopic current amplitudes, with focus on the turret and pore-loop domains of KCNQ1 and KCNQ3. Elimination of the putative N289 glycosylation site in KCNQ1 reduced current density by approximately 56%. A chimera consisting of KCNQ3 with the turret domain (TD) of KCNQ1 increased current density by about threefold. Replacement of the proximal half of the TD in KCNQ3 with that of KCNQ1 increased current density by fivefold. A triple chimera containing the TD of KCNQ1 and the carboxy terminus of KCNQ4 yielded current density 10- or sixfold larger than wild-type KCNQ3 or KCNQ1, respectively, suggesting that the effects on current amplitudes of the TD and the carboxy-terminus are additive. Critical was the role of the intracellular TEA(+)-binding site. The KCNQ3 (A315T) swap increased current density by 10-fold, and the converse KCNQ1 (T311A) swap reduced it by 10-fold. KCNQ3 (A315S) also yielded greatly increased current amplitudes, whereas currents from mutant A315V channels were very small. The KCNQ3 (A315T) mutation increased the sensitivity of the channels to external Ba(2+) block by eight- to 28-fold, consistent with this mutation altering the structure of the selectivity filter. To investigate a structural hypothesis for the effects of these mutations, we performed homology modeling of the pore region of wild-type and mutant KCNQ3 channels, using KvAP as a template. The modeling suggests a critical stabilizing interaction between the pore helix and the selectivity filter that is absent in wild-type KCNQ3 and the A315V mutant, but present in the A315T and A315S mutants. We conclude that KCNQ3 homomers are well expressed at the plasma membrane, but that most wild-type channels are functionally silent, with rearrangements of the pore-loop architecture induced by the presence of a hydroxyl-containing residue at the 315 position "unlocking" the channels into a conductive conformation. |
2,332,921 | PPADS does not block contraction-induced prostaglandin E2 synthesis in cat skeletal muscle. | Pyridoxal-phosphate-6-azophenyl-2'-4-disulfonate (PPADS), a purinergic 2 (P2) receptor antagonist, has been shown to attenuate the exercise pressor reflex in cats. In vitro, however, PPADS has been shown to block the production of prostaglandins, some of which play a role in evoking the exercise pressor reflex. Thus the possibility exists that PPADS blocks the exercise pressor reflex through a reduction in prostaglandin synthesis rather than through the blockade of P2 receptors. Using microdialysis, we collected interstitial fluid from skeletal muscle to determine prostaglandin E2 (PGE2) concentrations during the intermittent contraction of the triceps surae muscle before and after a popliteal arterial injection of PPADS (10 mg/kg). We found that the PGE2 concentration increased in response to the intermittent contraction before and after the injection of PPADS (both, P < 0.05). PPADS reduced the pressor response to exercise (P < 0.05) but had no effect on the magnitude of PGE2 production during contraction (P = 0.48). These experiments demonstrate that PPADS does not block the exercise pressor reflex through a reduction in PGE2 synthesis. We suggest that PGE2 and P2 receptors play independent roles in stimulating the exercise pressor reflex. |
2,332,922 | Time-dependent block of ultrarapid-delayed rectifier K+ currents by aconitine, a potent cardiotoxin, in heart-derived H9c2 myoblasts and in neonatal rat ventricular myocytes. | Aconitine (ACO), a highly toxic diterpenoid alkaloid, is recognized to have effects on cardiac voltage-gated Na(+) channels. However, it remains unknown whether it has any effects on K(+) currents. The effects of ACO on ion currents in differentiated clonal cardiac (H9c2) cells and in cultured neonatal rat ventricular myocytes were investigated in this study. In H9c2 cells, ACO suppressed ultrarapid-delayed rectifier K(+) current (I(Kur)) in a time- and concentration-dependent fashion. The IC(50) value for ACO-induced inhibition of I(Kur) was 1.4 microM. ACO could accelerate the inactivation of I(Kur) with no change in the activation time constant of this current. Steady-state inactivation curve of I(Kur) during exposure to ACO could be demonstrated. Recovery from block by ACO was fitted by a single-exponential function. The inhibition of I(Kur) by ACO could still be observed in H9c2 cells preincubated with ruthenium red (30 microM). Intracellular dialysis with ACO (30 microM) had no effects on I(Kur). I(Kur) elicited by simulated action potential (AP) waveforms was sensitive to block by ACO. Single-cell Ca(2+) imaging revealed that ACO (10 microM) alone did not affect intracellular Ca(2+) in H9c2 cells. In cultured neonatal rat ventricular myocytes, ACO also blocked I(Kur) and prolonged AP along with appearance of early afterdepolarizations. Multielectrode recordings on neonatal rat ventricular tissues also suggested that ACO-induced electrocardiographic changes could be associated with inhibition of I(Kur). This study provides the evidence that ACO can produce a depressant action on I(Kur) in cardiac myocytes. |
2,332,923 | Perspectives on interactions between antiepileptic drugs (AEDs) and antimicrobial agents. | In the treatment of seizures and epilepsy associated with central nervous system (CNS) infections, drug-drug interactions may significantly and unexpectedly impact outcome not only of epilepsy but also of the infectious disorders in both emergent and chronic care situations. A case is described in whom, the administration of the antimicrobial agent, meropenem presumably reduced serum valproate concentrations resulting in impaired seizure control. Other situations are reviewed in which interactions between antiepileptic drugs (AEDs) and antimicrobial agents may be of clinical significance. These include: (1) seizure management in individuals with neurocysticercosis, (2) management of seizures in patients with lobar tuberculomas, (3) management of seizures due to cerebral abscess, and (4) management of seizures in HIV-seropositive individuals. |
2,332,924 | The PKB inhibitor Akti-1/2 potentiates PAR-1-mediated platelet function independently of its ability to block PKB. | The role of PKB in platelet function is poorly defined due to the lack of genuinely selective small-molecule inhibitors and limiting genetic models. Recently, a selective, non-ATP-competitive PKB inhibitor, Akti-1/2 has been reported, but the efficacy and specificity against PKB activation in platelet function is unknown.</AbstractText>To determine the effect of the PKB inhibitor Akti-1/2 on PKB activation and platelet function by Western blotting and aggregometry/flow cytometry, respectively.</AbstractText>Akti-1/2 potently inhibited thrombin-mediated PKB phosphorylation on Thr(308) and Ser(473) and phosphorylation of its downstream substrate GSK3beta, with a negligible effect on the phosphorylation of pleckstrin, p38, ERK and JNK. Surprisingly, Akti-1/2 strongly potentiated PAR-1-mediated platelet aggregation. This effect persisted in the presence of PI3 kinase inhibitors, indicating a mechanism of action that is independent of PKB. Potentiation of aggregation by Akti-1/2 was associated with increased [Ca(++)](i), PKC activation and degranulation and was ablated by agents that antagonized this pathway.</AbstractText>The PKB inhibitor Akti-1/2 increases PAR-1-mediated platelet responses in a PKB-independent, Ca(++)/PKC-dependent manner. This effect is strong and rapid and may impact on the therapeutic application of Akti-1/2 and structurally related compounds.</AbstractText> |
2,332,925 | Farnesyltransferase inhibitors target multiple endothelial cell functions in angiogenesis. | Farnesyltransferase inhibitors (FTIs) are novel anticancer drugs that inhibit the secretion of pro-angiogenic factors by Ras-transformed cancer cells. FTIs also inhibit angiogenesis in a rat corneal model, suggesting that FTIs have anti-angiogenic properties that extend beyond targeting cancer cells. Our hypothesis was that FTIs may directly target endothelial cell functions in angiogenesis. We examined the effects of FTI treatment on a range of assays designed to pick apart the individual functions of endothelial cells during angiogenesis. We found that FTIs inhibit endothelial cell proliferation, causing a failure of mitosis and accumulation of binucleate cells. FTIs also block the directional migration of endothelial cells toward VEGF, the major pro-angiogenic factor in adult tissues. In a co-culture assay of angiogenesis, FTI treatment significantly inhibits tube formation, but has no effect on pre-existing structures. Defects in tube formation could be replicated by specific targeting of endothelial cell farnesyltransferase using RNA interference. Our data show that FTIs directly target endothelial cells in angiogenesis, explaining previous in vivo findings. Importantly, these results suggest that the therapeutic use of FTIs may extend beyond cancer to include the treatment of other diseases involving pathological angiogenesis. |
2,332,926 | [Effect of intrathecal administration of sufentanil at different doses on bupivacaine spinal anesthesia in gynecologic laparoscopy]. | To investigate the effect of sufentanil administered intrathecally at different doses on the clinical effect of bupivacaine spinal anesthesia in gynecologic laparoscopy.</AbstractText>Sixty patients with ectopic pregnancy undergoing elective laparoscopy (ASA class I-II) were randomized into 4 groups (groups A, B, C and D), and received spinal anesthesia with 15 mg bupivacaine and sufentanil at 0, 2.5, 5 and 7.5 microg, respectively. When the patients complained of discomforts, showed bodily movements, had heart rate over 100 beats/min, or showed blood pressure increment by 20%, additional doses of propofol were given. The onset time of sensory block, time to Bromage scale 3 motor block, time to the highest sensory block level, time of operation and recovery from anesthesia, and the total dosages of propofol were recorded along with the sedative score and the side effects.</AbstractText>The 4 groups were comparable for age, body weight, height and operation time (range 60-65 min) (P>0.05). Both the onset time of sensory block and the time of Bromage scale 3 motor block in groups C and D were significantly shorter than those in groups A and B (P<0.05). The time of the highest sensory block in group D was shorter than that in group A (P<0.05). Compared to the group A, the dose of propofol was reduced in groups B, C, and D by 7.1%, 28.1%, and 34.8%, respectively; propofol doses in groups C and D were significantly lower than those in groups A and B (P<0.05). Pruritus associated with the spinal anesthesia occurred in 4 (26.7%), 3 (20%), and 6 (40%) cases in groups B, C and D, respectively.</AbstractText>Intrathecal sufentanil dose-dependently affect the effect of bupivacaine spinal anesthesia, and larger sufentanil dose produces better effects but more side effects. According to our results, 5.0 microg is the optimal dose for sufentanil.</AbstractText> |
2,332,927 | Automated correction of room location errors in anesthesia information management systems. | Anesthesia information management systems (AIMS) and operating room information management systems (ORIMS) are both used in operating rooms (OR). Anesthesia providers use AIMS to document their care in near real-time, including milestone events, and these systems automatically record vital signs from patient monitors. Circulating nurses use ORIMS primarily to document procedural information. Because of automatic documentation, AIMS would be ideal platforms for OR managerial decision support if the correct locations of cases in progress were known accurately. Trust is diminished if recommendations are poor.</AbstractText>We compiled room location error rates from prior analyses of ORIMS data. Data from 24 consecutive 4-wk periods (45,459 cases) were analyzed from one hospital where both ORIMS and AIMS data were available. The actual location of cases was inferred from the physical location of the workstation recording the majority of pulse oximetry saturations. These were compared to the listed location in the AIMS and the final corrected location in the ORIMS. The scheduled and final ORIMS locations were compared to determine how often location changes were updated before the start of anesthesia. The location of cases was inferred in near real-time by using the identifier of the AIMS workstation transmitting pulse oximetry saturated electrocardiogram heart rate, and end-tidal CO(2) partial pressures.</AbstractText>Location error rates ranged from 0% to 7.5% at 42 hospitals. The error rate at the studied hospital was just 0.4%, showing that the hospital was suitable for investigation. The 0.4% error rate was based on cases listed as overlapping in the same OR, and thus under-estimated the actual error rate in the ORIMS (1.0%). With education, there was a decrease in the moved cases in the ORIMS whose location was not changed before the start of anesthesia (9.3%-2.0%, P < 10(-5)). Despite the significant improvement (P < 10(-5)) in the error rate between the AIMS listed and actual locations, the residual AIMS real-time error rate was 4.1% of cases. Use of vital sign data reduced errors to <0.1%.</AbstractText>Education can only modestly improve the accuracy of OR locations in ORIMS and AIMS data. The actual location can be inferred, either in near real-time or afterwards, from the AIMS workstation transmitting vital sign data. This addresses the fundamental problem of cases having more than one location during the course of anesthetic care (e.g., holding area, block room, OR, and postanesthesia care unit), which cannot be determined from scheduled ORIMS or listed AIMS locations.</AbstractText> |
2,332,928 | The acidic domain of GPIHBP1 is important for the binding of lipoprotein lipase and chylomicrons. | GPIHBP1, a glycosylphosphatidylinositol-anchored endothelial cell protein of the lymphocyte antigen 6 (Ly6) family, plays a key role in the lipolysis of triglyceride-rich lipoproteins (e.g. chylomicrons). GPIHBP1 is expressed along the luminal surface of endothelial cells of heart, skeletal muscle, and adipose tissue, and GPIHBP1-expressing cells bind lipoprotein lipase (LPL) and chylomicrons avidly. GPIHBP1 contains an amino-terminal acidic domain (amino acids 24-48) that is enriched in aspartate and glutamate residues, and we previously speculated that this domain might be important in binding ligands. To explore the functional importance of the acidic domain, we tested the ability of polyaspartate or polyglutamate peptides to block the binding of ligands to pgsA-745 Chinese hamster ovary cells that overexpress GPIHBP1. Both polyaspartate and polyglutamate blocked LPL and chylomicron binding to GPIHBP1. Also, a rabbit antiserum against the acidic domain of GPIHBP1 blocked LPL and chylomicron binding to GPIHBP1-expressing cells. Replacing the acidic amino acids within GPIHBP1 residues 38-48 with alanine eliminated the ability of GPIHBP1 to bind LPL and chylomicrons. Finally, mutation of the positively charged heparin-binding domains within LPL and apolipoprotein AV abolished the ability of these proteins to bind to GPIHBP1. These studies indicate that the acidic domain of GPIHBP1 is important and that electrostatic interactions play a key role in ligand binding. |
2,332,929 | [General anesthesia with remifentanil for a patient having sinoatrial block and constrictive pulmonary disorder]. | There is little report describing the effect of remifentanil on cardiac conduction system. We present a successful anesthetic management with remifentanil in a patient with sick sinus syndrome. A 66-year-old woman (31-kg, 121-cm) having sinoatrial (SA) block was diagnosed as having hepatic cell carcinoma, and radiofrequency ablation (RFA) was scheduled. She was also suffering from kyphosis due to the past history of tuberculous spondylitis. Preoperative examination of her respiratory function indicated a severe constrictive pulmonary disorder. Anesthesia was induced with propofol (30 mg), and maintained with sevoflurane (1-2%) and oxygen/air in combination with remifentanil (0.5 microg x kg(-1) x min(-1)). Temporary pacemaker was prepared during anesthesia. Neither remifentanil nor sevoflurane deteriorated SA block and her heart rate was well controlled. Respiratory dysfunction was not seen in the postoperative course. Our case suggests that remifentanil may be a suitable analgesic for patients with cardiac conduction abnormalities. |
2,332,930 | Transient trifascicular block complicating myocardial contusion after blunt chest trauma: a case report. | Cardiac contusion may be frequently found in patients with blunt chest trauma, and it presents clinically as a spectrum of injuries of varying severity, including transient disorders of impulse formation and propagation. A rare observation of transient trifascicular block in a previously fit 32-year-old man involved in a car accident is reported. The importance of ECG monitoring and biochemical assessment of markers to unmask myocardial contusion is discussed. |
2,332,931 | The risks and benefits of therapy with aldosterone receptor antagonist therapy. | Spironolacotone and eplerenone are mineralocorticoid-blocking agents. These compounds block both the epithelial and non-epithelial actions of aldosterone with the latter assuming increasing clinical importance. Spironolactone and eplerenone both effectively reduce blood pressure either as mono- or add-on therapy; moreover, they each offer survival benefits in diverse circumstances of heart failure and the potential for renal protection in proteinuric chronic kidney disease. However, as the use of mineralocorticoid-blocking agents has increased the hazards inherent to use of such drugs has become more apparent. Whereas; the endocrine side-effects of spironolactone are in most cases little more than a cosmetic annoyance the potassium-sparing effects of both spironolactone and eplerenone can prove fatal if sufficient degrees of hyperkalemia develop. However, for most patients the risk of developing hyperkalemia in and of itself should not discourage the sensible clinician from bringing these compounds into play. Hyperkalemia should always be considered as a possibility in any patient receiving one or the other of these medications. As such, steps should be taken to lessen the likelihood of its occurring if therapy is being contemplated with agents in this class. |
2,332,932 | An evaluation of the psychometric properties of the Smoking Self-Efficacy Questionnaire (SEQ-12) among Chinese cardiac patients who smoke. | Smoking cessation can reduce both morbidity and mortality among patients who have heart disease. China has the largest number of smokers in the world, and most smokers have low motivation to quit. Regular smoking cessation services are almost nonexistent in China, and little is known about the psychometric properties of instruments in assessing smoking self-efficacy in Chinese, whose cultures differ greatly from those of Westerners. The present study tested the psychometric properties of the Chinese version of the Smoking Self-Efficacy Questionnaire (SEQ-12) among 1,841 Chinese smokers who had heart disease, including (a) factorial structure using confirmatory factor analysis, (b) reliability with Cronbach's alpha, (c) concurrent validity, and (d) predictive validity of successful quitting. Confirmatory factor analysis of the SEQ-12 revealed a modified two-factor model that provided a good fit to the data; item 6 ("urge to smoke") was an indicator for the external stimuli subscale rather than for the internal stimuli subscale. Internal consistency coefficients (.77 for external stimuli and .88 for internal stimuli) were acceptable. Baseline self-efficacy scores were significantly associated positively with stage of readiness to quit, and negatively with cigarettes smoked per day and Fagerstrom Test for Nicotine Dependence (FTND) score. Multivariate logistic regression analysis showed that successful quitting at 1 month and at 3 months were predicted by higher external stimuli score, fewer cigarettes smoked per day, lower FTND scores, and being in the intervention group. We concluded that the Chinese version of the SEQ-12 is a valid and reliable instrument for Chinese cardiac patients who smoke. The SEQ-12 can be used to assess smokers' self-efficacy so that appropriate smoking cessation interventions can be provided. |
2,332,933 | Dietary tryptophan helps to preserve tryptophan homeostasis in pigs suffering from lung inflammation. | In pigs, inflammation modifies Trp metabolism and consequently could impact on Trp requirement for growth. In this study, the effects of lung inflammation, induced by the intravenous injection of complete Freund's adjuvant, and dietary Trp content on Trp metabolism and availability were investigated. Two dietary Trp contents, one corresponding to a low-Trp diet (1.5 g of Trp/kg of diet, Basal diet) and the second to an adequate-Trp diet (2 g of Trp/kg of diet, TRP diet), were used. Ten blocks of 4 littermate piglets were selected at 40 d of age. Within each block, piglets were randomly assigned to 1 of the 4 experimental treatments: (1) healthy control and Basal diet, (2) inflammation and Basal diet, (3) inflammation and Basal diet + antioxidant, and (4) inflammation and TRP diet. Inflammation induced an increase in indoleam-ine 2,3 dioxygenase (IDO) activity, an enzyme involved in Trp catabolism, in lung, lymph nodes, heart, and spleen (P < 0.01). Contrary to piglets fed the TRP diet, pigs suffering from inflammation did not maintain their plasma Trp concentrations when they were fed the Basal diet. Furthermore, pigs fed the TRP diet had decreased plasma haptoglobin concentrations, IDO activity, and lung weight than those fed the Basal diet, indicating that the inflammatory response was moderated with the greater Trp supply. Antioxidant addition in the Basal diet decreased the effects of inflammation on plasma Trp concentrations and IDO activity. These results indicated that inflammation increases Trp catabolism and thus may decrease Trp availability for growth. |
2,332,934 | RXP-E: a connexin43-binding peptide that prevents action potential propagation block. | Gap junctions provide a low-resistance pathway for cardiac electric propagation. The role of GJ regulation in arrhythmia is unclear, partly because of limited availability of pharmacological tools. Recently, we showed that a peptide called "RXP-E" binds to the carboxyl terminal of connexin43 and prevents chemically induced uncoupling in connexin43-expressing N2a cells. Here, pull-down experiments show RXP-E binding to adult cardiac connexin43. Patch-clamp studies revealed that RXP-E prevented heptanol-induced and acidification-induced uncoupling in pairs of neonatal rat ventricular myocytes. Separately, RXP-E was concatenated to a cytoplasmic transduction peptide (CTP) for cytoplasmic translocation (CTP-RXP-E). The effect of RXP-E on action potential propagation was assessed by high-resolution optical mapping in monolayers of neonatal rat ventricular myocytes, containing approximately 20% of randomly distributed myofibroblasts. In contrast to control experiments, when heptanol (2 mmol/L) was added to the superfusate of monolayers loaded with CTP-RXP-E, action potential propagation was maintained, albeit at a slower velocity. Similarly, intracellular acidification (pH(i) 6.2) caused a loss of action potential propagation in control monolayers; however, propagation was maintained in CTP-RXP-E-treated cells, although at a slower rate. Patch-clamp experiments revealed that RXP-E did not prevent heptanol-induced block of sodium currents, nor did it alter voltage dependence or amplitude of Kir2.1/Kir2.3 currents. RXP-E is the first synthetic molecule known to: (1) bind cardiac connexin43; (2) prevent heptanol and acidification-induced uncoupling of cardiac gap junctions; and (3) preserve action potential propagation among cardiac myocytes. RXP-E can be used to characterize the role of gap junctions in the function of multicellular systems, including the heart. |
2,332,935 | [Arrhythmia triggered by stretching rabbit left ventricles and the block effect of streptomysin]. | To observe the effect of stretching left ventricles in the end of action potential on rabbit cardiac activity, and to investigate its possible mechanisms.</AbstractText>Stretch (120 mmHg, 50 ms) was applied in the end of action potential by the pressure-clamp technique to observe if there would be any changes in rabbit cardiac activity and streptomycin (500 micromol/L) was used to identify the mechanism.</AbstractText>Stretch in the end of action potential caused arrhythmia (P < 0.05) and streptomycin blocked the above effect (P < 0.05).</AbstractText>Streptomycin could block the effect of stretching left ventricles in the end of action potential on rabbit cardiac activity, which indicates that stretch-activated ion channels involve it.</AbstractText> |
2,332,936 | Thirty-year trends (1975-2005) in the magnitude and hospital death rates associated with complete heart block in patients with acute myocardial infarction: a population-based perspective. | The contemporary magnitude and prognostic implications of complete heart block (CHB) in patients with acute myocardial infarction (AMI) are unknown. As part of a community-based study of patients hospitalized with AMI in the Worcester, MA, metropolitan area, changes over time in the incidence rates of CHB complicating AMI and the prognostic impact of CHB on short-term survival were examined.</AbstractText>The study population consisted of 13,663 residents of the Worcester metropolitan area who were hospitalized with AMI at all greater Worcester medical centers during 15 annual periods between 1975 and 2005.</AbstractText>The average age of the hospitalized study sample was 69 years, and 58% were men. The overall proportion of patients with AMI who developed CHB was 4.1%. The incidence rates of CHB complicating AMI declined appreciably over time, with the greatest decline in these incidence rates occurring during the most recent years under study. In 2005, 2.0% of patients hospitalized with AMI developed CHB compared to 5.1% in the initial study year of 1975. Patients with AMI who developed CHB had higher inhospital death rates (43.2%) than did those who did not develop CHB (13.0%) (P < .001). The hospital death rates associated with CHB declined appreciably over time, particularly during the most recent years under study. Several patient characteristics were associated with an increased risk for developing CHB during hospitalization for myocardial infarcation.</AbstractText>Our findings indicate recent encouraging declines in the incidence rates of CHB complicating AMI and improving trends in the hospital prognosis of these patients.</AbstractText> |
2,332,937 | The influence of permanent cardiac pacing on plasma levels of B-type natriuretic peptide in patients with sick sinus syndrome. | Unequivocal data presenting the impact of different pacing modes on B-type natriuretic peptide levels has never been published. The aim of the study was to assess changes of plasma B-type natriuretic peptide (BNP) during permanent cardiac pacing in patients with sick sinus syndrome (SSS).</AbstractText>Patients with SSS undergoing routine pacemaker implantation were enrolled. Each subject underwent medical history and examination, echocardiography and blood sampling. Analysis was performed on 12 females (42.9%) and 16 males (57.1%), mean age 71.3 +/- 9.03 years, range 49-90 years. There were 11 pacemakers with AAIR pacing mode (39.3%; AAI group) and 17 with DDDR mode (60.7%; DDD group) implanted. There were no significant differences in age, concomitant diseases or echocardiographic parameters between the groups in baseline characteristics or plasma BNP levels (94.05 +/- 54.1 vs. 73.57 +/- 70.13 pg/mL; p > 0.2).</AbstractText>During six months follow-up no significant changes in plasma BNP levels in AAI group (94.05 +/- 54.1 vs. 94.05 +/- 54.1 pg/mL; p > 0.5) as well as in DDD group (73.57 +/- 70.1 vs. 82.39 +/- 58.9 pg/mL; p > 0.5) were noticed.</AbstractText>Atrial (AAIR) and dual chamber (DDDR) pacing did not influence plasma BNP levels in patients with SSS and preserved left ventricular systolic function.</AbstractText> |
2,332,938 | ECGs in the ED.<Pagination><StartPage>499</StartPage><EndPage>500</EndPage><MedlinePgn>499-500</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1097/PEC.0b013e3181823a8c</ELocationID><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tanel</LastName><ForeName>Ronn E</ForeName><Initials>RE</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>Pediatr Emerg Care</MedlineTA><NlmUniqueID>8507560</NlmUniqueID><ISSNLinking>0749-5161</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002037" MajorTopicYN="N">Bundle-Branch Block</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004562" MajorTopicYN="Y">Electrocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004636" MajorTopicYN="Y">Emergency Service, Hospital</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004868" MajorTopicYN="N">Equipment Failure</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010138" MajorTopicYN="Y">Pacemaker, Artificial</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2008</Year><Month>7</Month><Day>18</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2008</Year><Month>9</Month><Day>10</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2008</Year><Month>7</Month><Day>18</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">18633315</ArticleId><ArticleId IdType="doi">10.1097/PEC.0b013e3181823a8c</ArticleId><ArticleId IdType="pii">00006565-200807000-00018</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">18633148</PMID><DateCompleted><Year>2008</Year><Month>09</Month><Day>25</Day></DateCompleted><DateRevised><Year>2014</Year><Month>07</Month><Day>30</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">1512-0112</ISSN><JournalIssue CitedMedium="Print"><Issue>159</Issue><PubDate><Year>2008</Year><Month>Jun</Month></PubDate></JournalIssue><Title>Georgian medical news</Title><ISOAbbreviation>Georgian Med News</ISOAbbreviation></Journal>[Heart rhythm abnormalities in middle-aged veteran elite athletes]. | Disrrhythmia is frequent finding in high competitive athletes. Majority of heart rhythm abnormalities in athletes, suggested being benign, however, prognostic value of it is not yet well established. Purpose of the present study was to investigate heart rhythm and relationship of heart rhythm abnormalities with LV mass in veteran elite athletes. 30 veteran elite athletes (16 soccer players and 14 water-polo players) aged 30-50 were studied. They formed main group.</AbstractText>>10 years of active sports activity and >5 years after competitive sports cessation. All athletes were symptom free. Control group consists of 30 age - matched sedentary healthy individuals. In all study subjects ambulatory 24 hour ECG was recorded and, LV mass, dimensions and function by ultrasound-Doppler technique was evaluated. LV mass by Devereux formula was calculated and indexed to body surface area. Student's t-test for continuous variables, Descriptive statistics and Fisher's exact test for categorical variables were used. A P-value of <0.05 was considered to be statistically significant. Mean heart rate in former athletes group was 62+/-6 ,and 69+/-9, in control group. Night HR in athletes group was 48+/-8 and 55+/-5 in control group. Differences between groups were statistically significant (p<0,01). Complex arrhythmias were found in 4 athletes and none in control group First degree AV block presented in 6 athletes and in 2 controls. Second degree AV block (Mobitz II) was found in 4 athletes and none in controls. LV mass index was higher in ex-athletes (91,42 g/m, than in controls (84,02 g/m ) .differences between groups was statistically significant - p<0,05. Profound Bradycardia and heart conductivity abnormalities as well as complex arrhythmias were more frequent findings in athletes as compared with healthy sedentary subjects. Heart Rhythm abnormalities were associated with enhanced LV mass in Veteran athletes. Hence, veteran elite athletes may be at increased risk of life threatening arrhythmias. However, prognostic value of heart rhythm disturbances in veteran athletes has to be studied.</AbstractText> |
2,332,939 | Correlations between clinical and physiological consequences of the novel mutation R878C in a highly conserved pore residue in the cardiac Na+ channel. | We compared the clinical and physiological consequences of the novel mutation R878C in a highly conserved pore residue in domain II (S5-S6) of human, hNa(v)1.5, cardiac Na(+) channels.</AbstractText>Full clinical evaluation of pedigree members through three generations of a Chinese family combined with SCN5A sequencing from genomic DNA was compared with patch and voltage-clamp results from two independent expression systems.</AbstractText>The four mutation carriers showed bradycardia, and slowed sino-atrial, atrioventricular and intraventricular conduction. Two also showed sick sinus syndrome; two had ST elevation in leads V1 and V2. Unlike WT-hNa(v)1.5, whole-cell patch-clamped HEK293 cells expressing R878C-hNa(v)1.5 showed no detectable Na(+) currents (i(Na)), even with substitution of a similarly charged lysine residue. Voltage-clamped Xenopus oocytes injected with either 0.04 or 1.5 microg microL(-1) R878C-hNa(v)1.5 cRNA similarly showed no i(Na), yet WT-hNa(v)1.5 cRNA diluted to 0.0004-0.0008 ng microL(-1)resulted in expression of detectable i(Na). i(Na) was simply determined by the amount of injected WT-hNa(v)1.5: doubling the dose of WT-hNa(v)1.5 cRNA doubled i(Na). i(Na) amplitudes and activation and inactivation characteristics were similar irrespective of whether WT-hNa(v)1.5 cRNA was given alone or combined with equal doses of R878C-hNa(v)1.5 cRNA therefore excluding dominant negative phenotypic effects. Na(+) channel function in HEK293 cells transfected with R878C-hNa(v)1.5 was not restored by exposure to mexiletine (200 microM) and lidocaine (100 microM). Fluorescence confocal microscopy using E3-Nav1.5 antibody demonstrated persistent membrane expression of both WT and R878C-hNa(v)1.5. Modelling studies confirmed that such i(Na) reductions reproduced the SSS phenotype.</AbstractText>Clinical consequences of the novel R878C mutation correlate with results of physiological studies.</AbstractText> |
2,332,940 | Cardiovascular magnetic resonance of the charcoal heart. | We report a case of malignant melanoma metastasis to the heart presenting as complete heart block. The highlight of the case is to demonstrate that silent cardiac metastasis is not uncommon and CMR has the potential to characterize these cardiac metastases and should be used routinely as a screening tool for those cancers with a high chance of cardiac involvement. |
2,332,941 | Feasibility of concurrent treatment with the scanning ultrasound reflector linear array system (SURLAS) and the helical tomotherapy system. | To evaluate the feasibility of concurrent treatment with the scanning ultrasound reflector linear array system (SURLAS) and helical tomotherapy (HT) intensity modulated radiation therapy (IMRT).</AbstractText>The SURLAS was placed on a RANDO phantom simulating a patient with superficial or deep recurrent breast cancer. A megavoltage CT (MVCT) of the phantom with and without the SURLAS was obtained in the HT system. MVCT images with the SURLAS were obtained for two configurations: (1) with the SURLAS's long axis parallel and (2) perpendicular to the longitudinal axis of the phantom. The MVCT simulation data set was then transferred to a radiation therapy planning station. Organs at risk (OAR) were contoured including the lungs, heart, abdomen and spinal cord. The metallic parts of the SURLAS were contoured as well and constraints were assigned to completely or directionally block radiation through them. The MVCT simulation data set and regions of interest (ROI) files were subsequently transferred to the HT planning station. Several HT plans were obtained with optimization parameters that are usually used in the clinic. For comparison purposes, planning was also performed without the SURLAS on the phantom.</AbstractText>All plans with the SURLAS on the phantom showed adequate dose covering 95% of the planning target volume (PTV D95%), average dose and coefficient of variation of the planning target volume (PTV) dose distribution regardless of the SURLAS's orientation with respect to the RANDO phantom. Likewise, all OAR showed clinically acceptable dose values. Spatial dose distributions and dose-volume histogram (DVH) evaluation showed negligible plan degradation due to the presence of the SURLAS. Beam-on time varied depending on the selected optimization parameters.</AbstractText>From the perspective of the radiation dosage, concurrent treatment with the SURLAS and HT IMRT is feasible as demonstrated by the obtained clinically acceptable treatment plans. In addition, proper orientation of the SURLAS may be of benefit in reducing dose to organs at risk in some cases.</AbstractText> |
2,332,942 | Comparative study between bupivacaine heavy vs pethidine intrathecally to study early haemodynamic changes and postoperative analgesia in patients undergoing caesarean section. | To study early hemodynamic changes and duration of postoperative analgesia between two study groups of intrathecal pethidine and bupivacaine heavy in patients undergoing caesarean section.</AbstractText>Total number of 60 patients of ASA I and II, undergoing caesarean section were enrolled in the study. All the patients were divided into two groups: Pethidine and Bupivacaine heavy. The dose of pethidine for subarachnoid block was 1mg/kg and in Bupivacaine group 2.2 ml of 0.5% bupivacaine heavy was given intrathecally. Heart rate and blood pressure of all the patients were recorded before subarachnoid block. After giving spinal anesthesia, the heart rate and blood pressure were monitored and recorded in different time intervals. The duration of postoperative analgesia in all patients was recorded in postoperative ward. The APGAR Scores of the babies were recorded in 1 and 5 minutes after delivery. The data were statistically compared using independent sample t-test.</AbstractText>The hemodynamic parameters (HR & BP) were compared in different time intervals. The difference in heart rate and blood pressure at different time intervals in the two study groups were statistically insignificant as (p > 0.05). The total duration of postoperative analgesia in patients receiving sole intrathecal pethidine was 8 hours and 30 minutes. Where as, in Bupivacaine group the duration was 2 hrs and 36 minutes. This has been found statistically significant (p<0.05).</AbstractText> |
2,332,943 | Acid-sensing ion and epithelial sodium channels do not contribute to the mechanoreceptor component of the exercise pressor reflex. | Amiloride, injected into the popliteal artery, has been reported to attenuate the reflex pressor response to static contraction of the triceps surae muscles. Both mechanical and metabolic stimuli arising in contracting skeletal muscle are believed to evoke this effect, which has been named the exercise pressor reflex. Amiloride blocks both acid-sensing ion channels, as well as epithelial sodium channels. Nevertheless, amiloride is thought to block the metabolic stimulus to the reflex, because this agent has been shown to attenuate the reflex pressor response to injection of lactic acid into the arterial supply of skeletal muscle. The possibility exists, however, that amiloride may also block mechanical stimuli evoking the exercise pressor reflex. The mechanical component of the reflex can be assessed by measuring renal sympathetic nerve activity during the first 2-5 s of contraction. During this period of time, the sudden tension developed by contraction onset briskly discharges mechanoreceptors, whereas it has little effect on the discharge of metaboreceptors. We, therefore, examined the effect of amiloride (0.5 microg/kg) injected into the popliteal artery on the renal sympathetic and pressor responses to static contraction of the triceps surae muscles in decerebrated cats. We found that amiloride significantly attenuated the pressor and renal sympathetic responses to contraction; for the latter variable, the attenuation started 10 s after the onset of contraction. Our findings lead us to conclude that acid-sensing ion channels and epithelial sodium channels play little, if any, role in evoking the mechanical component of the exercise pressor reflex. |
2,332,944 | Effect of ropivacaine skull block on perioperative outcomes in patients with supratentorial brain tumors and comparison with remifentanil: a pilot study. | Skull blockade for craniotomy may result in the reduction of sympathetic stimulation associated with the application of head pins ("pinning"), improvement in intraoperative hemodynamic stability, and a decrease in intraoperative anesthetic requirements. Postoperative benefits may include a decrease in pain, in analgesic requirements, and in the incidence of nausea and vomiting. The authors examined the potential benefits of a skull block in patients in whom a maintenance anesthetic consisting of sevoflurane and a titratable remifentanil infusion was used. In other studies examining the ability of a skull block to improve perioperative outcomes, investigators have not used remifentanil.</AbstractText>Thirty patients presenting for resection of a supratentorial tumor were prospectively enrolled. Patients were randomized into 2 groups as follows: 14 patients (skull block group) received a skull block with 0.5% ropivacaine at least 15 minutes prior to pinning, whereas the remaining 16 patients (control group) did not.</AbstractText>Patients in the skull block group did not have a significant increase in blood pressure or heart rate with placement of head pins, whereas patients in the control group did. Nevertheless, there was no difference in blood pressure variability between the groups. The mean intraoperative concentration of sevoflurane (1.0% in both groups, p = 0.703) and remifentanil (0.163 microg/kg/min compared with 0.205 microg/kg/min, p = 0.186) used was similar in both groups. During the postoperative period, there was no difference in the 1-, 2-, or 4-hour visual analog scale scores; in the need for postoperative narcotic analgesia (0.274 morphine equivalent mg/kg compared with 0.517 morphine equivalent mg/kg, p = 0.162); or in the incidence of nausea or vomiting.</AbstractText>Prospective analysis of perioperative skull blockade failed to demonstrate significant benefit in patients treated with a remifentanil infusion.</AbstractText> |
2,332,945 | [+]-Huperzine A treatment protects against N-methyl-D-aspartate-induced seizure/status epilepticus in rats. | The toxicity of organophosphorous (OP) nerve agents is attributed to their irreversible inhibition of acetylcholinesterase (AChE), which leads to excessive accumulation of acetylcholine (ACh) and is followed by the release of excitatory amino acids (EAA). EAAs sustain seizure activity and induce neuropathology due to over-stimulation of N-methyl-d-aspartate (NMDA) receptors. Huperzine A (Hup A), a blood-brain barrier permeable selective reversible inhibitor of AChE, has been shown to reduce EAA-induced cell death by interfering with glutamate receptor-gated ion channels in primary neuronal cultures. Although [-]-Hup A, the natural isomer, inhibits AChE approximately 38-fold more potently than [+]-Hup A, both [-]- and [+]-Hup A block the NMDA channel similarly. Here, we evaluated the protective efficacy of [+]-Hup A for NMDA-induced seizure in a rat model. Rats implanted with radiotelemetry probes to record electroencephalography (EEG), electrocardiography (ECG), body temperature, and physical activity were administered various doses of [+]-Hup A (intramuscularly) and treated with 20 microg/kg NMDA (intracerebroventricular) 20-30 min later. For post-exposure, rats were treated with [+]-Hup A (3 mg/kg, intramuscularly) 1 min after NMDA (20 microg/kg). Our data showed that pre- and post-exposure, [+]-Hup A (3 mg/kg) protects animals against NMDA-induced seizures. Also, NMDA-administered animals showed increased survival following [+]-Hup A treatment. [+]-Hup A has no visible effect on EEG, heart-rate, body temperature, or physical activity, indicating a reduced risk of side effects, toxicity, or associated pathology. Our results suggest that [+]-Hup A protects against seizure and status epilepticus (SE) by blocking NMDA-induced excitotoxicity in vivo. We propose that [+]-Hup A, or a unique combination of [+]- and [-]-Hup A, may prove to be effective for pre- and post-exposure treatment of lethal doses of OP-induced neurotoxicity. |
2,332,946 | Sedative and cardiorespiratory effects of acepromazine or atropine given before dexmedetomidine in dogs. | To test the hypothesis that acepromazine could potentiate the sedative actions and attenuate the pressor response induced by dexmedetomidine, the effects of acepromazine or atropine were compared in six healthy adult dogs treated with this alpha2-agonist. In a randomised block design, the dogs received intravenous doses of either physiological saline, 0.05 mg/kg acepromazine or 0.04 mg/kg atropine, 15 minutes before an intravenous dose of 5 microg/kg dexmedetomidine. The dogs' heart rate was reduced by 50 to 63 per cent from baseline and their mean arterial blood pressure was increased transiently from baseline for 20 minutes after the dexmedetomidine. Atropine prevented the alpha2-agonist-induced bradycardia and increased the severity and duration of the hypertension, but acepromazine did not substantially modify the cardiovascular effects of the alpha2-agonist, except for a slight reduction in the magnitude and duration of its pressor effects. The dexmedetomidine induced moderate to intense sedation in all the treatments, but the dogs' sedation scores did not differ among treatments. The combination of acepromazine with dexmedetomidine had no obvious advantages in comparison with dexmedetomidine alone, but the administration of atropine before dexmedetomidine is contraindicated because of a severe hypertensive response. |
2,332,947 | [Night cardiac rhythm and conduction disturbances revealing obstructive sleep apnoea syndrome]. | There is a strong prevalence of sleep apnoea syndrome in general population. Cardiac arrhythmia and conduction disturbances during sleep may complicate this syndrome. We report the case of a 73-year-old patient to whom the sleep apnoea syndrome was diagnosed after varied heart blocks during the sleep. A treatment by continuous positive airway pressure (CPAP) permitted to correct these conduction disturbances and to avoid pacemaker implantation. |
2,332,948 | The efficacy of the psoas compartment block versus the intrathecal combination of morphine, fentanyl and bupivacaine for postoperative analgesia after primary hip arthroplasty: a randomized single-blinded study. | Intrathecal morphine and psoas compartment block represent two accepted techniques to provide postoperative analgesia after hip arthroplasty. We designed a prospective, randomized, single-blinded study to compare these two techniques.</AbstractText>Forty patients scheduled for primary hip arthroplasty under general anesthesia were randomized to receive either an intrathecal administration of 0.1 mg morphine, 0.015 mg fentanyl and 15 mg hyperbaric bupivacaine (Group I, n = 20) or a psoas compartment block with ropivacaine 0.475% 25 mL (Group II, n = 20). Pain scores, morphine consumption, associated side-effects were assessed for 48 hr postoperatively. In addition, patient's satisfaction and acceptance of the postoperative analgesic technique were also recorded.</AbstractText>During the first 24 hr, pain scores (12 +/- 27 vs 24 +/- 25 at H + 12, 12 +/- 46 vs 20 +/- 26 mm at H + 24, 16 +/- 19 vs 20 +/- 29 mm at H + 36) and tramadol consumption (30 +/- 70 vs 210 +/- 400 mg at H + 12, 180 +/- 120 vs 320 +/- 100 mg at H + 24) were slightly lower in Group I than in Group II, but there were no statistically significant differences. Itching was the most frequent side-effect occurring in 45% of cases in Group I vs 10% in Group II (P < 0.05). No major complication occurred. There was no difference in satisfaction scores between the two groups.</AbstractText>Intrathecal administration of a combination of morphine, fentanyl and bupivacaine and single-shot psoas compartment block both provide very good postoperative analgesia after primary hip arthroplasty.</AbstractText> |
2,332,949 | The 5-HT2 antagonist ketanserin is an open channel blocker of human cardiac ether-à-go-go-related gene (hERG) potassium channels. | Ketanserin, a selective 5-HT receptor antagonist, prolongs the QT interval of ECG in patients. The purpose of the present study was to determine whether ketanserin would block human cardiac ether-à-go-go-related gene (hERG) potassium channels.</AbstractText>Whole-cell patch voltage-clamp technique was used to record membrane currents in HEK 293 cells expressing wild type or mutant hERG channel genes.</AbstractText>Ketanserin blocked hERG current (I(hERG)) in a concentration-dependent manner (IC50=0.11 microM). The drug showed an open channel blocking property, the block increasing significantly at depolarizing voltages between +10 to +60 mV. Voltage-dependence for inactivation of hERG channels was negatively shifted by 0.3 microM ketanserin. A 2.8 fold attenuation of inhibition by elevation of external K+ concentration (from 5.0 to 20 mM) was observed, whereas the inactivation-deficient mutants S620T and S631A had the IC50s of 0.84 +/- 0.2 and 1.7 +/-0.4 microM (7.6 and 15.4 fold attenuation of block). In addition, the hERG mutants in pore helix and S6 also significantly reduced the channel block (2-59 fold) by ketanserin.</AbstractText>These results suggest that ketanserin binds to and blocks the open hERG channels in the pore helix and the S6 domain; channel inactivation is also involved in the blockade of hERG channels. Blockade of hERG channels most likely contributes to the prolongation of QT intervals in ECG observed clinically at therapeutic concentrations of ketanserin.</AbstractText> |
2,332,950 | Repression of prespliceosome complex formation at two distinct steps by Fox-1/Fox-2 proteins. | Precise and robust regulation of alternative splicing provides cells with an essential means of gene expression control. However, the mechanisms that ensure the tight control of tissue-specific alternative splicing are not well understood. It has been demonstrated that robust regulation often results from the contributions of multiple factors to one particular splicing pathway. We report here a novel strategy used by a single splicing regulator that blocks the formation of two distinct prespliceosome complexes to achieve efficient regulation. Fox-1/Fox-2 proteins, potent regulators of alternative splicing in the heart, skeletal muscle, and brain, repress calcitonin-specific splicing of the calcitonin/CGRP pre-mRNA. Using biochemical analysis, we found that Fox-1/Fox-2 proteins block prespliceosome complex formation at two distinct steps through binding to two functionally important UGCAUG elements. First, Fox-1/Fox-2 proteins bind to the intronic site to inhibit SF1-dependent E' complex formation. Second, these proteins bind to the exonic site to block the transition of E' complex that escaped the control of the intronic site to E complex. These studies provide evidence for the first example of regulated E' complex formation. The two-step repression of presplicing complexes by a single regulator provides a powerful and accurate regulatory strategy. |
2,332,951 | Serpins show structural basis for oligomer toxicity and amyloid ubiquity. | Many disorders, including Alzheimer's, the prion encephalopathies and other neurodegenerative diseases, result from aberrant protein aggregation. Surprisingly, cellular toxicity is often due not to the highly-ordered aggregates but to the oligomers that precede their formation. Using serpins as a paradigm, we show how the active and infective interface of oligomers is inherently toxic and can promiscuously bind to unrelated peptides, including neurotransmitters. Extension of the oligomer and its eventual sequestration as amyloid can thus be seen as a protective response to block the toxic interface. We illustrate how the preferential self-association that gives this protection has been selectively favoured. |
2,332,952 | Complex temporal patterns of spontaneous initiation and termination of reentry in a loop of cardiac tissue. | A two-component model is developed consisting of a discrete loop of cardiac cells that circulates action potentials as well as a pacing mechanism. Physiological properties of cells such as restitutions of refractoriness and of conduction velocity are given via experimentally measured functions. The dynamics of circulating pulses and the pacer's action are regulated by two threshold relations. Patterns of spontaneous initiations and terminations of reentry (SITR) generated by this system are studied through numerical simulations and analytical observations. These patterns can be regular or irregular; causes of irregularities are identified as the threshold bistability (T-bistability) of reentrant circulation and in some cases, also phase-resetting interactions with the pacer. |
2,332,953 | [Loco-regional analgesia]. | The epidural analgesia is one of the most effective techniques for pain relief when it is indicated, but it can present potentially serious complications that must precociously be diagnosed and be treated. In the Critical Care setting, epidural analgesia is used for pain control after surgery or major trauma. The technique is simple, a catheter is placed into a virtual cavity, so the administered drugs are absorbed through the epidural space into nerve roots. The administration of local anesthetics, opioids or the combination of both by epidural route (administered in continuous infusion or bolus), provides better analgesia. Also the clonidine can be used. In order to diagnose and to treat suitably the possible complications (pain, urinary retention, nauseas and vomits, itching, motor block, infection, respiratory depression, hypotension) a series of safety measures must be adopted (respiratory and heart rate, blood pressure, sedation score, sensory and motor level assessment, rate of diuresis, temperature and signs of infection). |
2,332,954 | Comparison of potency of ephedrine and mephentermine for prevention of post-spinal hypotension in caesarean section. | The dosages and potency of intravenous mephentermine for prevention of post-spinal hypotension are not available in English literature. This study was designed to determine the minimum effective dose (ED50) of mephentermine and to compare its potency with that of ephedrine for prevention of post-spinal hypotension in parturients undergoing caesarean section. Dixon's up-down method of sequential allocation was used for vasopressor doses. Following administration of spinal anaesthesia, patients received a prophylactic infusion with 50 mg infused over a period of 30 minutes as the initial dose and dose intervals of 5 mg, of either ephedrine or mephentermine. The ED50 of ephedrine was 25.0 mg (95% CI 15.5 to 40.4 mg). For mephentermine, the up-down method was abandoned due to the success of the minimum dose possible but the ED50 appeared to be less than 5 mg. In conclusion, the minimum effective dose of mephentermine is much less than that of ephedrine for prevention of post-spinal hypotension. Another trial with a lower starting dose and smaller dose interval of mephentermine is required to determine the potency ratio of mephentermine and ephedrine. |
2,332,955 | Endoscopic thoracic sympathectomy: at what level should you perform surgery? | Several interventions are possible on the sympathetic chain and the nomenclature has been confusing. The authors propose a uniform nomenclature for each procedure, mainly, sympathectomy for resection or ablation of the ganglion, sympathicotomy for the transaction of the chain, ramicotomy for the procedure preserving the chain and ganglia and severing the rami, and finally, sympathetic block for clipping above and below the ganglia. They recommend intervention on the T2 ganglia for facial hyperhidrosis and rubor, on the T3 ganglia for palmar hyperhidrosis, and on the T3 and T4 ganglia for axillary hyperhidrosis. |
2,332,956 | In vivo PET imaging of cardiac presynaptic sympathoneuronal mechanisms in the rat. | The sympathetic nervous system of the heart plays a key role in the pathophysiology of various cardiac diseases. Small-animal models are valuable for obtaining further insight into mechanisms of cardiac disease and therapy. To determine the translational potential of cardiac neuronal imaging from rodents to humans, we characterized the rat sympathetic nervous system using 3 radiotracers that reflect different subcellular mechanisms: (11)C-meta-hydroxyephedrine (HED), a tracer of neuronal transport showing stable uptake and no washout in healthy humans; (11)C-phenylephrine (PHEN), a tracer of vesicular leakage and intraneuronal metabolic degradation with initial uptake and subsequent washout in humans; and (11)C-epinephrine (EPI), a tracer of vesicular storage with stable uptake and no washout in humans.</AbstractText>We used a small-animal PET system to study healthy male Wistar rats at baseline, after desipramine (DMI) pretreatment (DMI block), and with DMI injection 15 min after tracer delivery (DMI chase). The rats were kept under general isoflurane anesthesia while dynamic emission scans of the heart were recorded for 60 min after radiotracer injection. A myocardial retention index was determined by normalizing uptake at 40 min to the integral under the arterial input curve. Washout rates were determined by monoexponential fitting of myocardial time-activity curves.</AbstractText>At baseline, HED showed high myocardial uptake and sustained retention, EPI showed moderate uptake and significant biphasic washout, and PHEN showed moderate uptake and monoexponential washout. The average (+/- SD) left ventricular retention index for HED, PHEN, and EPI was 7.38% +/- 0.82%/min, 3.43% +/- 0.45%/min, and 4.24% +/- 0.59%/min, respectively; the washout rate for HED, PHEN, and EPI was 0.13% +/- 0.23%/min, 1.13% +/- 0.35%/min, and 0.50% +/- 0.24%/min, respectively. The DMI chase resulted in increased washout only for HED. DMI block decreased myocardial uptake of all tracers by less than 90%.</AbstractText>Kinetic profiles of HED in the rat myocardium were similar to those of HED in humans, suggesting comparable neuronal transport density. Unlike in humans, however, significant washout of EPI and faster washout of PHEN were encountered, consistent with high intraneuronal metabolic activity, high catecholamine turnover, and reduced vesicular storage. This evidence of increased neuronal activity in rodents has implications for translational studies of cardiac neuronal biology in humans.</AbstractText> |
2,332,957 | Efficacy and safety of morphine-6-glucuronide (M6G) for postoperative pain relief: a randomized, double-blind study. | The aim of the study was to assess analgesia and safety effects of a range of intravenous doses of M6G (10, 20 and 30 mg/70 kg), compared to placebo, in postoperative patients.</AbstractText>In a randomized, multicentre, double-blind study, patients undergoing knee replacement surgery under spinal anaesthesia were administered one of three doses of M6G, or placebo, 150 min after spinal nerve block. Morphine rescue medication was available via a PCA pump. The key index of analgesic activity was determined as the amount of morphine consumed by the patient over 12 and 24 h after M6G administration. Time to first use of rescue medication, VAS and global pain assessment scales were also recorded. Safety was assessed by monitoring supine blood pressure, heart rate, respiratory rate and body temperature and typical opioid side-effects of PONV and sedation.</AbstractText>A total of 170 patients were dosed with study medication. M6G induced a dose-related reduction in morphine use over 24-h that reached statistical significance compared to placebo at M6G 30 mg/70 kg. There was no clear relationship between M6G dose and time to first use of PCA morphine. Pain relief was similar in all groups. M6G showed small, but inconsistent effects on the cardiovascular system and on sedation and no effects were observed on respiration or PONV.</AbstractText>M6G induced long-lasting dose-related analgesic effects in postoperative patients with limited effects on cardiorespiratory systems or of opioid-like side-effects. M6G is an effective opioid for the treatment of moderate to severe postoperative pain.</AbstractText> |
2,332,958 | Quantitative overload: a source of stress in data-entry VDT work induced by time pressure and work difficulty. | It is hypothesized that quantitative overload impacts psycho-physiological attributes of data-entry operators, although previous research has focused primarily on different aspects of VDT work, such as working time and environment, work station, keyboards and so forth. The objective of this study was to examine the influence on psycho-physiological responses of time pressure, task demand and their combined effect as underlying causes of quantitative overload while typing. A total of 12 subjects completed four 1-h typing tasks representing two levels of time pressure and task demand. Levels were manipulated by requiring participants to achieve a least number of character strings during each block, and by changing the number of letters in the character strings. Outcomes were measured in subjective assessment of workload, performance-related and physiological measures. Overall, increased time pressure increased perceived workload, productivity rate and heart rate, and decreased initial response time and typing duration. However, increased task demand increased error rate and initial response time with no change in heart rate. Heart rate variability did not indicate increased levels of time pressure or task demand. Quantitative overload as a consequence of time pressure and task demand influenced the subjective and psycho-physiological measures of data-entry operators to some extent. |
2,332,959 | Emotional catharsis and aggression revisited: heart rate reduction following aggressive responding. | The authors tested two components of the catharsis theory of aggression: physiological tension reduction and aggressive drive reduction. On the basis of work in the stress-aggression literature, they also examined the moderating effect of impersonal stress exposure on cathartic reductions in heart rate following aggressive responding. Participants were instructed to administer nonaggressive (correct button) or aggressive (shock button) responses to a frustrating confederate in a laboratory aggression paradigm, and half the participants were exposed to an impersonal stressor (aversive air blasts) during the procedure. Heart rate was recorded before and after the participants administered the aggressive or nonaggressive response. Analyses revealed that participants exhibited reductions in heart rate following aggressive but not nonaggressive responding, but this was the case only for those not exposed to the impersonal stressor. Heart rate reductions during the experimental blocks actually predicted the most intense aggression in a subsequent block of trials. The results are considered in light of different theories of aggression by J. E. Hokanson (1974) and L. Berkowitz (1990) and have implications for interventions with anger-prone individuals. |
2,332,960 | Angiotensin II-dependent loss of cardiac function: mechanisms and pharmacological targets attenuating this effect. | Pharmacological inhibition of components of the renin-angiotensin-system is one of the major therapeutically options to treat patients with heart failure. This study hypothesized that angiotensin II (Ang II) directly depresses contractile function (cell shortening) by activation of transforming growth factor-beta(1) (TGF-beta(1)). Moreover, we hypothesized that an inhibition of glycogen synthase kinase 3-betaGSK will compensate for this depressive effect by increasing SERCA2 expression. Isolated adult ventricular rat cardiomyocytes were used and cultured in the presence of Ang II (100 nM) for 24 h. Cell shortening and contractile dynamics were recorded at 2 Hz. Immunoblot techniques and gel mobility shift assays were used to demonstrate NFAT activation caused by inhibition of GSK and to demonstrate increases in the expression of SERCA2. Ang-II caused a nearly 20% decrease in cell shortening. This Ang II-dependent effect was mimicked by TGF-beta(1) (10 ng/ml), attenuated by addition of aprotinin, that was used to block the proteolytic activation of TGF-beta(1), or by application of a neutralizing antibody directed against TGF-beta(1). Inhibition of GSK activated NFAT, increased SERCA2 expression and improved cell function. In conclusion, the study identified a paracrine mechanism for the Ang II-dependent loss of cardiac function that occurs independently of hemodynamic changes. Furthermore, it characterized the differences between Ang II and alpha-adrenoceptor stimulation with respect to the maintenance of cellular function explaining cellular events contributing to the difference between adaptive (physiological) and mal-adaptive (patho-physiological) hypertrophy. |
2,332,961 | Alternans of cardiac calcium cycling in a cluster of ryanodine receptors: a simulation study. | Mechanical alternans in cardiac muscle is associated with intracellular Ca(2+) alternans. Mechanisms underlying intracellular Ca(2+) alternans are unclear. In previous experimental studies, we produced alternans of systolic Ca(2+) under voltage clamp, either by partially inhibiting the Ca(2+) release mechanism, or by applying small depolarizing pulses. In each case, alternans relied on propagating waves of Ca(2+) release. The aim of this study is to investigate by computer modeling how alternans of systolic Ca(2+) is produced. A mathematical model of a cardiac cell with 75 coupled elements is developed, with each element contains L-type Ca(2+) current, a subspace into which Ca release takes place, a cytoplasmic space, sarcoplasmic reticulum (SR) release channels [ryanodine receptor (RyR)], and uptake sites (SERCA). Interelement coupling is via Ca(2+) diffusion between neighboring subspaces via cytoplasmic spaces and network SR spaces. Small depolarizing pulses were simulated by step changes of cell membrane potential (20 mV) with random block of L-type channels. Partial inhibition of the release mechanism is mimicked by applying a reduction of RyR open probability in response to full stimulation by L-type channels. In both cases, systolic alternans follow, consistent with our experimental observations, being generated by propagating waves of Ca(2+) release and sustained through alternation of SR Ca(2+) content. This study provides novel and fundamental insights to understand mechanisms that may underlie intracellular Ca(2+) alternans without the need for refractoriness of L-type Ca or RyR channels under rapid pacing. |
2,332,962 | Rapid resensitization of purinergic receptor function in human platelets. | Adenosine diphosphate (ADP) is a critical regulator of platelet activation, mediating its actions through two G protein-coupled receptors (GPCRs), the P2Y(1) and P2Y(12) purinergic receptors. Recently, we demonstrated that both receptors desensitize and internalize in human platelets by differential kinase-dependent mechanisms.</AbstractText>To demonstrate whether responses to P2Y(1) and P2Y(12) purinergic receptors resensitize in human platelets and determine the role of receptor traffic in this process.</AbstractText>These studies were undertaken either in human platelets or in cells stably expressing epitope-tagged P2Y(1) and P2Y(12) purinergic receptor constructs.</AbstractText>In this study we show for the first time that responses to both of these receptors can rapidly resensitize following agonist-dependent desensitization in human platelets. Further, we show that in human platelets or in 1321N1 cells stably expressing receptor constructs, the disruption of receptor internalization, dephosphorylation or subsequent receptor recycling is sufficient to block resensitization of purinergic receptor responses. We also show that, in platelets, internalization of both these receptors is dependent upon dynamin, and that this process is required for resensitization of responses.</AbstractText>This study is therefore the first to show that both P2Y(1) and P2Y(12) receptor activities are rapidly and reversibly modulated in human platelets, and it reveals that the underlying mechanism requires receptor trafficking as an essential part of this process.</AbstractText> |
2,332,963 | B cell apotopes of the 60-kDa Ro/SSA and La/SSB autoantigens. | Apoptosis has been proposed to influence the initiation and diversification of autoimmunity to the Ro (SSA)/La (SSB) ribonucleoprotein (RNP) particle and serve as a target for autoantibody-mediated tissue injury. We have developed a new approach to B cell epitope mapping which identifies "apotopes," defined as epitopes expressed on the surface of apoptotic cells. Preliminary studies support a role for apotopes as diagnostic markers in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome. For example, apotopes within the NH(2)-terminal and central regions of La react with the majority of sera from mothers of infants with congenital heart block. Furthermore, a Ro60 apotope is specific for a subset of SLE with isolated anti-Ro60 responses. The mapping of B cell apotopes may prove superior to standard epitope mapping by suggesting novel pathways of autoantibody production and identifying pathogenic species of autoantibodies. |
2,332,964 | Molecular analysis of early host cell infection by Trypanosoma cruzi. | Trypanosoma cruzi, the causative agent of Chagas heart disease, infects heart and other cells leading to cardiac arrest frequently followed by death. The disease affects millions of individuals in the Americas and is posing health problems because of blood transmission in the US due to large Latin American immigration. Since the current drugs present serious side effects and do not cure the chronic infection, it is critically important to understand the early process of cellular infection at the molecular and structural levels to design novel inhibitors to block T. cruzi infection. In this review, the authors critically analyze the molecular and cellular basis of early T. cruzi infection and discuss the future directions in this area. The candidate T. cruzi invasive genes and host genes involved in the process of early infection are just beginning to be understood. The trypanosome invasive proteins are excellent targets for intervention. The progress made in the cell biology of T. cruzi infection will also facilitate the development of novel cell-based therapies to ameliorate the disease. |
2,332,965 | Scientific review and recommendations on preclinical cardiovascular safety evaluation of biologics. | Biological therapeutic agents (biologicals), such as monoclonal antibodies (mAbs), are increasingly important in the treatment of human disease, and many types of biologicals are in clinical development. During preclinical drug development, cardiovascular safety pharmacology studies are performed to assess cardiac safety in accord with the ICH S7A and S7B regulations that guide these studies. The question arises, however, whether or not it is appropriate to apply these guidelines, which were devised primarily to standardize small molecule drug testing, to the cardiovascular evaluation of biologicals. We examined the scientific literature and formed a consensus of scientific opinion to determine if there is a rational basis for conducting an in vitro hERG assay as part of routine preclinical cardiovascular safety testing for biologicals. We conclude that mAb therapeutics have very low potential to interact with the extracellular or intracellular (pore) domains on hERG channel and, therefore, are highly unlikely to inhibit hERG channel activity based on their targeted, specific binding properties. Furthermore, mAb are large molecules (>140,000 Da) that cannot cross plasma membranes and therefore would be unable to access and block the promiscuous inner pore of the hERG channel, in contrast with typical small molecule drugs. Consequently, we recommend that it is not appropriate to conduct an in vitro hERG assay as part of a preclinical strategy for assessing the heart rate corrected QT interval (QTc) prolongation risk of mAbs and other types of biologicals. It is more appropriate to assess QTc risk by integrating cardiovascular endpoints into repeat-dose general toxicology studies performed in an appropriate non-rodent species. These recommendations should help shape future regulatory strategy and discussions for the cardiovascular safety pharmacology testing of mAbs as well as other biologicals and provide guidance for the preclinical cardiovascular evaluation of such agents. |
2,332,966 | The link between repolarisation alternans and ventricular arrhythmia: does the cellular phenomenon extend to the clinical problem? | T-wave alternans is considered a potentially useful clinical marker for the risk of ventricular arrhythmia in patients with heart disease. Cellular repolarisation alternans is thought to underlie T-wave alternans, and moreover, to cause re-entrant ventricular arrhythmia. This review examines the experimental and clinical evidence linking repolarisation alternans and T-wave alternans with the occurrence of ventricular arrhythmia. Repolarisation alternans, manifest as alternating changes in action potential duration, is observed in isolated ventricular cardiomyocytes and in multicellular preparations. Its underlying causes are discussed particularly with respect to the role of intracellular Ca(2+). The repolarisation alternans observed at the single cell level is compared to the alternating behaviour observed in isolated multicellular preparations including the perfused ventricular wedge and Langendorff perfused heart. The evidence concerning spatial differences in repolarisation alternans is considered, particularly the situation where adjacent regions of myocardium exhibit repolarisation alternans of different phases. This extreme behaviour, known as discordant alternans, is thought to produce marked gradients of repolarisation that can precipitate unidirectional block and re-entrant ventricular arrhythmias. Finally, the difficulties in extrapolating between experimental models of alternans and arrhythmias and the clinical manifestation are discussed. The areas where experimental evidence is weak are highlighted, and areas for future research are outlined. |
2,332,967 | Extremely low ventricular rate in a fetus with an isolated non-autoimmune complete congenital heart block. Case report. | Congenital complete heart block (CCHB) is an uncommon disorder with an incidence of about 1/20,000 in liveborn infants. It can occur in the setting of structurally normal heart or with structural disease; it is associated with high mortality and morbidity and requires a high index of suspicion for early diagnosis and therapy. Isolated CCHB in a fetus is usually associated with the presence of autoantibodies to SSA (Ro) and SSB (La) antigens in the maternal circulation. Such antibodies cross into the fetal circulation and cause inflammation of the conduction tissues; the causal mechanism is not known. Although the prognosis for the majority of fetuses is good, it is less favourable in fetuses with a ventricular rate <55 bpm in early pregnancy or with a decrease in the ventricular rate by >5 bpm during pregnancy. It is not known if the same prognostic criteria apply for fetuses with isolated non-autoimmune CCHB. This article reports authors' experience in managing a pregnancy with an extremely low fetal heart rate (47 bpm) in a single fetus with an isolated non-autoimmune CCHB in which the outcome was favorable. |
2,332,968 | Prospective assessment of cardiovascular events in patients with partial and advanced interatrial conduction delay: a preliminary observation. | Major adverse cardiovascular events (MACE) have been investigated with partial interatrial block (IAB; P wave > or = 110 ms) but not with advanced IAB.</AbstractText>Twenty-four advanced IAB and 34 partial IAB patients were followed for 24 months for MACE, change in renal function and death.</AbstractText>Three patients with advanced IAB had myocardial infarction compared to none with partial IAB (p = 0.03). However, overall MACE was not significantly different between groups with an overall low event rate. There was also no difference between change in mean blood urea nitrogen levels and calculated glomerular filtration rates over time.</AbstractText>In a preliminary 24-month period, when compared to patients with partial IAB, those with the uncommon, advanced form of IAB do not appear to be overly at increased risk for MACE. However, larger prospective studies are needed to confirm these results in order to appraise other cardiovascular risk factors.</AbstractText> |
2,332,969 | Efficacy of monensin and tylosin in finishing diets based on steam-flaked corn with and without corn wet distillers grains with solubles. | Three hundred seventy-one crossbred-yearling heifers (299 +/- 9 kg initial BW) were obtained from a common source and used in a randomized complete-block designed finishing study. A 2 x 3 factorial arrangement of treatments was used with one factor being diet: based on steam-flaked corn finishing diet (SFC) or SFC plus 25% (dry basis) corn wet distillers grains with solubles (WDGS). The second factor was feed additives: no added antibiotics (NONE), 300 mg of monensin daily (MONENSIN), or 300 mg of monensin + 90 mg of tylosin daily (MON+TYL). Main effect of diet resulted in no difference in DMI (P = 0.34). Heifers fed SFC gained 9% faster (P = 0.01) and were 7% more efficient (P = 0.01) than heifers fed WDGS. In addition, heifers fed SFC had 3% heavier (P = 0.01) HCW; 1% greater (P = 0.01) dress yield; and had 3% larger (P = 0.05) LM area. Marbling score and carcasses that graded USDA Choice or better were both greater (P </= 0.03) for heifers fed SFC. Heifers fed MONENSIN had a smaller (P = 0.01) LM area than heifers fed NONE and tended (P = 0.09) to have smaller LM area than heifers fed MON+TYL. Marbling score, USDA quality grade, and USDA yield grade were not different (P >/= 0.12) among feed additive treatments. Kidney, pelvic, and heart fat and s.c. fat thickness at the 12th rib were also not different (P >/= 0.55) for main effects of diet and feed additive. There was a tendency (P = 0.09) for a diet x feed additive interaction for the most severe (A+) liver abscesses. Heifers fed NONE yielded the greatest percentage (16%) of A+ livers in the SFC treatment, whereas heifers fed MON+TYL yielded the greatest percentage (10%) in the WDGS treatment. Including wet distillers grains with solubles in diets based on steam-flaked corn decreased finishing heifer performance, HCW, and marbling. Tylosin addition tended to decrease severity of liver abscesses in diets containing SFC, but not in diets containing WDGS. These data indicate that monensin and tylosin may not be as effective when used in steam-flaked corn diets with 25% WDGS. |
2,332,970 | Comparison of midazolam sedation with or without fentanyl in cataract surgery. | We compared the effect of midazolam sedation with or without fentanyl on the hemodynamic parameters, sedation, and pain and satisfaction profile in cataract surgery. Two hundred and ten patients were randomly allocated to receive either midazolam 1 mg i.v. (Group M, n = 101) alone or with fentanyl 25 microg (Group MF, n = 100) before retrobulbar injection. Hemodynamic parameters, observer's assessment of alertness/sedation (OAA/S) scores, pain during block and surgery, satisfaction of patient and surgeons were assessed. Heart rate and diastolic arterial pressure decreased after retrobulbar injection in comparison to baseline whereas systolic arterial pressure values increased in both groups. The majority of patients in both groups experienced mild pain during retrobulbar injection but no pain during surgery. There was a significant decrease in OAA/S scores in both groups (p = 0.001) and this decline was more significant in Group MF (p = 0.038). We suggest that midazolam alone may produce optimal block conditions for the patient and it is satisfactory during the procedure while the addition of fentanyl has not improved the effect on the examined parameters. |
2,332,971 | Post-mastectomy radiotherapy in Denmark: from 2D to 3D treatment planning guidelines of The Danish Breast Cancer Cooperative Group. | This paper describes the procedure of changing from 2D to 3D treatment planning guidelines for post-mastectomy radiotherapy in Denmark. The aim of introducing 3D planning for post-mastectomy radiotherapy was to optimize the target coverage and minimize the dose to the normal tissues. Initially, it was investigated whether it was possible to find a treatment technique alternative to the one recommended by the Danish Breast Cancer Cooperative Group (DBCG). A dosimetric comparison of a combined photon/electron 3-field technique (3F) and a partial wide tangent technique (PWT) was carried out on individual planning CT-scans from seven patients selected to represent a wide range of sizes and shapes of chest walls. The heart dose was lower for PWT than for 3F, however, for both techniques the dose was within the accepted constraints. The lung dose was higher but acceptable for six of the seven patients with PWT. The dose to the internal mammary nodes (IMN) was not satisfactory for five of the seven patients for 3F, whereas only two of the seven patients had a minimum dose lower than 95% of the prescribed dose with PWT. Finally, the dose to the contralateral breast was increased when using PWT compared to 3F. It was concluded that PWT was an appropriate choice of technique for future radiation treatment of post-mastectomy patients. A working group was formed and guidelines for 3D planning were developed during a series of workshops where radiation oncologists and physicists from all radiotherapy centres participated. This work also included a definition of the tissue structures needed to be outlined on the planning CT-scan. The work was initiated in 2003 and the guidelines were approved by the DBCG Radiotherapy Committee in 2006. The first of January 2007 the 3D guidelines had been fully implemented in five of the seven radiotherapy centres. |
2,332,972 | Inhibition of MCP-1/CCR2 signaling does not inhibit intimal proliferation in a mouse aortic transplant model. | Transplant arteriopathy is the leading cause of long term morbidity and mortality following heart transplantation. Animal models have demonstrated that monocyte chemoattractant protein (MCP)-1 is induced early after transplant in cardiac and aortic allografts. We have previously reported that deficiency of MCP-1 or its receptor, CC chemokine receptor 2 (CCR2), is associated with a reduction in intimal proliferation in a mouse femoral artery injury model. Using knockout mice, we have now examined the role of MCP-1 and CCR2 in the development of the intimal proliferation of transplant arteriopathy.</AbstractText>C57Bl/6 CCR2 and MCP-1 wild-type and knockout mice were used in the studies and aortic transplants were performed between Balb/c mice and C57Bl/6 mice. Aortas from recipient animals were harvested 8 weeks after transplant.</AbstractText>Unlike arterial injury, in an aortic transplant model inhibition of MCP-1/CCR2 signaling did not result in reduced intimal proliferation.</AbstractText>Despite a pathology that appears similar, the inflammatory mediators that regulate transplant arteriopathy differ from those regulating intimal proliferation secondary to wire injury. Our results suggest that targeting MCP-1/CCR2 signaling is not sufficient to block transplant arteriopathy across a complete MHC-mismatch barrier.</AbstractText>Copyright 2008 S. Karger AG, Basel.</CopyrightInformation> |
2,332,973 | Frontrunners in novel pharmacotherapy of COPD. | The mainstay of current drug therapy is long-acting bronchodilators; several longer acting inhaled beta(2)-agonists and muscarinic antagonists (and combinations) are now in development. No treatments reduce the progression or suppress the inflammation of COPD. With better understanding of the inflammatory and destructive process, several new targets have been identified. Several mediator antagonists tested in COPD have been disappointing, but of CXCR2 antagonists that block pulmonary neutrophil and monocyte recruitment may be more promising. Broad spectrum anti-inflammatory drugs may be more effective, and include inhibitors of PDE4, p38 MAPK and NF-kappaB, but side effects will be a major limitation so that inhaled delivery will be necessary. Perhaps the most promising approach is reversal corticosteroid resistance through increasing HDAC2 activity. This may be achieved by theophylline-like drugs, more effective antioxidants and non-antibiotic macrolides. |
2,332,974 | Expression profile and characterisation of a truncated KCNQ5 splice variant. | Ion channels encoded by KCNQ genes (1-5) are key regulators of membrane properties in many cell types. The KCNQ5 gene was the last to be identified and has three splice variants that are expressed in human brain and skeletal muscle. The KCNQ5 encoded channel possesses M-current properties and so far no channelopathy has been associated with any of the three variants. We now show that only the shortest KCNQ5 variant, which has exon 9 deleted, was expressed in a variety of murine vascular smooth muscle. In Xenopus oocytes, this variant generated currents with amplitudes, activation kinetics and biophysical properties similar to the full-length variant normally expressed in neuronal tissue. Furthermore sensitivity to block by XE991 and activation by retigabine were also similar between both variants. These data represent an exhaustive characterisation of a truncated KCNQ5 splice variant that may contribute to the native XE991-sensitive channel in murine vasculature. |
2,332,975 | Computational analysis of the effects of the hERG channel opener NS1643 in a human ventricular cell model. | Dysfunction or pharmacologic inhibition of repolarizing cardiac ionic currents can lead to fatal arrhythmias. The hERG potassium channel underlies the repolarizing current I(Kr), and mutations therein can produce both long and short QT syndromes (LQT2 and SQT1). We previously reported on the diphenylurea compound NS1643, which acts on hERG channels in two distinct ways: by increasing overall conductance and by shifting the inactivation curve in the depolarized direction.</AbstractText>The purpose of this study was to determine which of the two components contributes more to the antiarrhythmic effects of NS1643 under normokalemic and hypokalemic conditions.</AbstractText>The study consisted of mathematical simulation of action potentials in a human ventricular ionic cell model in single cell and string of 100 cells.</AbstractText>Regardless of external potassium concentration or diastolic interval used, NS1643 decreases action potential duration and triangulation. For single cells, NS1643 increases the postrepolarization refractory time but shortens the absolute refractory period. In one dimensional simulations, NS1643 increases the vulnerable window for unidirectional block but suppresses the emergence of premature action potentials and unidirectional blocks around APD(90). During normokalemia, shifting the inactivation curve has greater impact than increasing conductance, whereas the opposite occurs during hypokalemia.</AbstractText>Increased hERG conductance and the depolarizing shift of the inactivation curve both contribute to the antiarrhythmic actions of NS1643, with relative effects dependent on external K(+) concentration.</AbstractText> |
2,332,976 | Peripheral heart blocks associated with myocardial infarcts: clinical diagnosis based on experimental findings. | Septal necrosis + peripheral left blocks. Because of an extensive septal necrosis, the manifestation of the initial ventricular activation forces decreases in the precordial leads. With left bifascicular block (LASB + LPSB), the first ventricular activation forces become more evident and the electrical signs of septal necrosis can be concealed. In the presence of a trifascicular block, manifestation of the first ventricular electromotive forces diminishes again and the electrical signs of septal necrosis become evident once more. Small Q waves are present in leads V(1 )to V(4).Extensive anterior necrosis + peripheral blocks. This necrosis is manifested by QS complexes from V(2) to V(6). An associated left bifascicular block reduces the electrical manifestation of dead tissue: QS complexes persist only in V(3) and V(4). In turn, a coexisting trifascicular block causes the presence of QS complexes from V(2) to V(5). Posteroinferior necrosis + peripheral blocks. Electromotive forces of the ventricular activation shift upward, due to a posteroinferior necrosis and QS or QR complexes are recorded in leads aVF, II and III. An associated left bifascicular block displaces the main electromotive forces downward, posteriorly and to the left, due to a delay of the posteroinferior activation fronts. The ventricular complexes become positive and wider in all leads, reflecting the potential variations of the inferior portions of the left ventricle: aVF, II, III, sometimes V(5) and V(6). Consequently, the electrical signs of necrosis are reduced or abolished. Due to a trifascicular block, wide and slurred QS complexes are recorded in aVF, II, III and sometimes in V(5) and V(6). |
2,332,977 | Enhanced calreticulin expression promotes calcium-dependent apoptosis in postnatal cardiomyocytes. | Calreticulin (CRT) is one of the major Ca2+ binding chaperone proteins of the endoplasmic reticulum (ER) and an unusual luminal ER protein. Postnatally elevated expression of CRT leads to impaired development of the cardiac conductive system and may be responsible for the pathology of complete heart block. In this study, the molecular mechanisms that affect Ca2+-dependent signal cascades were investigated using CRT-overexpressing cardiomyocytes. In particular, we asked whether calreticulin plays a critical role in the activation of Ca2+-dependent apoptosis. In the cells overexpressing CRT, the intracellular calcium concentration was significantly increased and the activity of PKC and level of SECAR2a mRNA were reduced. Phosphorylation of Akt and ERKs decreased compared to control. In addition the activity of the anti-apoptotic factor, Bcl-2, was decreased and the activities of pro-apoptotic factor, Bax, p53 and caspase 8 were increased, leading to a dramatic augmentation of caspase 3 activity. Our results suggest that enhanced CRT expression in mature cardiomyocytes disrupts intracellular calcium regulation, leading to calcium-dependent apoptosis. |
2,332,978 | Validation of the MEDFICTS dietary assessment questionnaire in a diverse population. | The National Cholesterol Education Program (NCEP) recommends MEDFICTS, a rapid screening instrument for dietary fat, to assess adherence to the Adult Treatment Panel (ATP) III Therapeutic Lifestyle Changes (TLC) diet (score <40 points indicates intake of <7% of energy from saturated fat, <30% of energy from total fat, and <200 mg dietary cholesterol/day). MEDFICTS has only been validated in small, select populations and its utility in diverse clinical settings is unknown.</AbstractText>To evaluate the ability of MEDFICTS to identify individuals who are nonadherent to a TLC diet in an ethnically diverse population that includes both English- and Spanish-speakers.</AbstractText>MEDFICTS was administered concurrently with the Gladys Block Food Frequency Questionnaire to participants (n=501; mean age 48+/-13.5 years; 36% nonwhite; 66% female) in the National Heart, Lung, and Blood Institute Family Intervention Trial for Heart Health (FIT Heart) at the baseline screening visit. Reliability and validity analyses were conducted overall and by sex, age, and race/ethnicity.</AbstractText>MEDFICTS score correlated significantly with percentage of energy from saturated fat (r=0.52, P<0.0001), percentage of energy from total fat (r=0.31, P<0.0001), and milligrams per day of dietary cholesterol (r=0.54, P<0.0001). Sensitivity of MEDFICTS to correctly identify TLC diet adherence was 85.7% and did not differ significantly by sex, age, or race/ethnicity. Specificity of MEDFICTS to correctly identify nonadherence to the TLC diet was low (56.9%) and significantly worse for women than men (48.4% vs 72.9%; P<0.0001), but did not differ significantly in older vs younger participants or among white, black, or Hispanic participants.</AbstractText>Our data suggest that sex-specific recalibration of MEDFICTS may improve specificity and clinical utility.</AbstractText> |
2,332,979 | The platelet activating factor triggers preconditioning-like cardioprotective effect via mitochondrial K-ATP channels and redox-sensible signaling. | Endogenous platelet activating factor (PAF) is involved in heart ischemic preconditioning. PAF can also afford pharmacological preconditioning. We studied whether mitochondrial-ATP-sensitive K(+) (mK(ATP)) channels and reactive oxygen species (ROS) are involved in PAF-induced cardioprotection. In Group 1 control hearts, Langendorff-perfused rat hearts underwent 30 min ischemia and 2 hours of reperfusion. Group 2 hearts, before ischemia, were perfused for 19 min with PAF (2x10(-11) M); Groups 3 and 4 hearts were co-infused with PAF and N-acetyl-L-cysteine or 5-hydroxydecanoate to scavenge ROS or to block mK(ATP) channels, respectively. Left ventricular pressure and infarct size were determined. PAF-pretreatment reduced infarct size (33 +/- 4% vs 64 +/- 4.6 % of the area at risk of control hearts) and improved pressure recovery. Infarct-sparing effect of PAF was abolished by N-acetyl-L-cysteine and 5-hydroxydecanoate. Thus, the cardioprotective effect exerted by PAF-pretreatment involves activation of mK(ATP) channels and redox signaling in pre-ischemic phase. |
2,332,980 | Cyclooxygenase inhibition attenuates sympathetic responses to muscle stretch in humans. | Passive muscle stretch performed during a period of post-exercise muscle ischemia (PEMI) increases muscle sympathetic nerve activity (MSNA), and this suggests that the muscle metabolites may sensitize mechanoreceptors in healthy humans. However, the responsible substance(s) has not been studied thoroughly in humans. Human and animal studies suggest that cyclooxygenase products sensitize muscle mechanoreceptors. Thus we hypothesized that local cyclooxygenase inhibition in exercising muscles could attenuate MSNA responses to passive muscle stretch during PEMI. Blood pressure (Finapres), heart rate, and MSNA (microneurography) responses to passive muscle stretch were assessed in 13 young healthy subjects during PEMI before and after cyclooxygenase inhibition, which was accomplished by a local infusion of 6 mg ketorolac tromethamine in saline via Bier block. In the second experiment, the same amount of saline was infused via the Bier block. Ketorolac Bier block decreased prostaglandin synthesis to approximately 34% of the baseline. Before ketorolac Bier block, passive muscle stretch evoked significant increases in MSNA (P < 0.005) and mean arterial blood pressure (P < 0.02). After ketorolac Bier block, passive muscle stretch did not evoke significant responses in MSNA (P = 0.11) or mean arterial blood pressure (P = 0.83). Saline Bier block had no effect on the MSNA or blood pressure response to ischemic stretch. These observations indicate that cyclooxygenase inhibition attenuates MSNA responses seen during PEMI and suggest that cyclooxygenase products sensitize the muscle mechanoreceptors. |
2,332,981 | Regulation of apoptosis by the redox state of cytochrome c. | Cytochrome c, released from mitochondria into the cytosol, triggers formation of the apoptosome resulting in activation of caspases. This paper reviews the evidence for and against the redox state of cytochrome c regulating apoptosis, and possible mechanisms of this. Three research groups have found that the oxidized form of cytochrome c (Fe(3+)) can induce caspase activation via the apoptosome, while the reduced form (Fe(2+)) cannot. It is unclear whether this is due to the oxidized and reduced forms of cytochrome c having: (i) different affinities for Apaf-1, (ii) different abilities to activate Apaf-1 once bound, or (iii) different affinities for other components of the cell. Experiments replacing the Fe of cytochrome c with redox-inactive metals indicate that cytochrome c does not have to change redox states to activate caspases. In healthy cells, cytosolic cytochrome c is rapidly reduced by various enzymes and/or reductants, which may function to block apoptosis. However, in apoptotic cells, cytosolic cytochrome c is rapidly oxidized by mitochondrial cytochrome oxidase, to which it has access due to permeabilization of the outer membrane. Regulation of the redox state of cytochrome c potentially enables regulation of the intrinsic pathway of apoptosis at a relatively late stage. |
2,332,982 | Essential role of cyclin-G-associated kinase (Auxilin-2) in developing and mature mice. | Hsc70 with its cochaperone, either auxilin or GAK, not only uncoats clathrin-coated vesicles but also acts as a chaperone during clathrin-mediated endocytosis. However, because synaptojanin is also involved in uncoating, it is not clear whether GAK is an essential gene. To answer this question, GAK conditional knockout mice were generated and then mated to mice expressing Cre recombinase under the control of the nestin, albumin, or keratin-14 promoters, all of which turn on during embryonic development. Deletion of GAK from brain, liver, or skin dramatically altered the histology of these tissues, causing the mice to die shortly after birth. Furthermore, by expressing a tamoxifen-inducible promoter to express Cre recombinase we showed that deletion of GAK caused lethality in adult mice. Mouse embryonic fibroblasts in which the GAK was disrupted showed a lack of clathrin-coated pits and a complete block in clathrin-mediated endocytosis. We conclude that GAK deletion blocks development and causes lethality in adult animals by disrupting clathrin-mediated endocytosis. |
2,332,983 | Sevoflurane concentrations required to block autonomic hyperreflexia during transurethral litholapaxy in patients with complete spinal cord injury. | Autonomic hyperreflexia (AHR) is a potentially life-threatening hypertensive condition that occurs in patients with high spinal cord injury (SCI). The current study was aimed to determine sevoflurane concentrations that block AHR in SCI patients.</AbstractText>The study involved 28 patients with chronic, complete SCI scheduled to undergo transurethral litholapaxy during general anesthesia. Nine patients without SCI served as controls post hoc. Anesthesia was induced with thiopental, and sevoflurane concentrations in 50% nitrous oxide were adjusted to maintain a Bispectral Index of 40-50. When a patient developed AHR during bladder distension, the target sevoflurane concentration was maintained for at least 10 min, and then the procedure was resumed. Systolic blood pressure, heart rate, and Bispectral Index as well as plasma concentrations of catecholamines and arginine vasopressin were measured before and during the bladder distension. Each target concentration was determined by the up-and-down method based on changes (15% increase or more) of systolic blood pressure in response to bladder distension.</AbstractText>In SCI, systolic pressure increased by 67 +/- 33 mmHg, whereas heart rate decreased by 13 +/- 8 beats/min during the first trial (P < 0.01). The hypertensive event was associated with increases of norepinephrine concentrations, but not of epinephrine or vasopressin concentrations. Systolic pressure, heart rate, and norepinephrine concentrations did not change significantly in the control patients. The end-tidal concentrations of sevoflurane to prevent AHR were EC50 of 3.12% and EC95 of 3.83%.</AbstractText>The EC95 for sevoflurane in 50% nitrous oxide to block AHR during transurethral litholapaxy in patients with SCI was 3.83%.</AbstractText> |
2,332,984 | Relapsing polychondritis presenting with complete heart block. | Relapsing polychondritis (RP) is a rare autoimmune disease characterized by recurrent inflammation of cartilagenous structures, including the ears, nose, trachea, and joints. Cardiovascular involvement is relatively common, but involvement of the conduction system leading to various degrees of heart block is a rare and late manifestation of the disease usually requiring a pacemaker. We report here a patient with RP who presented with complete heart block that resolved promptly after treatment with prednisone. To our knowledge, this is the first reported case of RP with abnormal cardiac conduction on initial presentation and a rapid response to anti-inflammatory treatment. Heart block during the phase of active inflammation may respond to corticosteroid treatment as in our patient without the need for cardiac pacing. |
2,332,985 | [Neuroprotection in perinatal hypoxic-ischemic encephalopathy. Effective treatment and future perspectives]. | The aim of this paper is to review the results of recent clinical studies of some therapies that have demonstrated a neuroprotective effect in perinatal hypoxic-ischemic encephalopathy (HIE) and to present the future perspectives of other clinical and basic research investigations. THERAPIES WITH DEMONSTRATED CLINICAL EFFICACY: ALLOPURINOL: It blocks the production of free radicals following hypoxia-ischemia. In a recent study, infants with hypoplastic left heart syndrome treated with allopurinol, but not those with other congenital cardiopathies, had significantly less number of complications than controls, including death, seizures, coma or cardiac events.</AbstractText>In another recent study, newborns with HIE treated with morphine or phentanyl, had less severe brain damage on MRI and a better neurological outcome. HYPOTHERMIA: Both local (head cooling) or systemic (whole body) hypothermia have a neuroprotective effect in selected newborns with HIE.</AbstractText>ANTIEPILEPTIC DRUGS: They have multiple mechanisms of action that can block the biochemical cascade of neuronal damage in HIE. OTHER THERAPEUTIC MODALITIES: Among them the following should be emphasized: combined neuroprotective treatments, growth factors, genetic therapies, stem cell transplant, and neuroprotective immunization. In conclusion, a better knowledge of the molecular mechanisms of HIE pathogenesis and better clinical studies of neuroprotective therapies will open new possibilities aplicable to clinical practice. These advances will undoubtedly improve the prognosis of newborns with HIE.</AbstractText> |
2,332,986 | Intravenous lipid infusion in the successful resuscitation of local anesthetic-induced cardiovascular collapse after supraclavicular brachial plexus block. | We describe a case of successful resuscitation with an i.v. lipid infusion of local anesthetic-induced cardiovascular toxicity after supraclavicular brachial plexus block with mepivacaine and bupivacaine. Lipid therapy was initiated after 10 min of unsuccessful resuscitation and resulted in restoration of cardiovascular activity and hemodynamic stability. This case illustrates the utility of i.v. lipid therapy in the treatment of local anesthetic toxicity. |
2,332,987 | Acute inhibition of superoxide formation and Rac1 activation by nitric oxide and iloprost in human vascular smooth muscle cells in response to the thromboxane A2 analogue, U46619. | The over-production of superoxide (O(2)(-)) derived from NADPH oxidase (NOX) plays a central role in cardiovascular diseases. By contrast, nitric oxide (NO) and prostacyclin (PGI(2)) are vasculoprotective. The effect of the NO donor, NONOate and iloprost on O(2)(-) formation, p47(phox) and Rac(1) activation in human vascular smooth muscle cells (hVSMCs) was investigated.</AbstractText>hVSMCs were incubated with 10nM thromboxane A(2) analogue, U46619 for 16h, and then with apocynin (a NOX inhibitor), NONOate or iloprost for 1h and O(2)(-) measured spectrophometrically. The role of cyclic AMP and cyclic GMP was examined by co-incubation of drugs with protein kinase (PK) A and G inhibitors listed above. Rac(1) was studied using pull-down assays.</AbstractText>NONOate and iloprost inhibited O(2)(-) formation, acutely, effects blocked by inhibition of PKG and PKA, respectively. Rac(1) and p47(phox) activation and translocation to the plasma membrane was completely inhibited by NONOate and iloprost, effects again reversed by co-incubation with PKG or PKA inhibitors.</AbstractText>NO and PGI(2) block the acute activity of NOX in hVSMCs via the cGMP-PKG axis (for NO) and by the cAMP-PKA axis (for iloprost) through inhibition of Rac(1) and p47(phox) translocation. These findings have implications in the pathophysiology and treatment of CVD.</AbstractText> |
2,332,988 | [Real time intracardiac electrograms for the diagnosis of pacemaker malfunction]. | Chronic ventricular lead dislodgement is an infrequent complication of pacemaker implantation. Occasionally, the dislodged lead may sense and capture a chamber in which the lead was not originally positioned. Intracardiac real time electrograms and channel markers are useful tools for the diagnosis of pacemaker malfunction. We present the case of a patient with a ventricular lead dislodgement into the atrium. The ventricular lead was able to sense and capture the atrium. Initial diagnosis was performed based on the deductive analysis of intracardiac real time electrograms and channel markers and confirmed by chest X-ray. |
2,332,989 | [Peculiarities of Ca2+ regulation of functional activity of myocardium of frog Rana temporaria]. | To elucidate role of intra- and extracellular Ca2+ in regulation of rhythm and strength of frog heart contractions, there were studied ECC and isometric contraction of myocardium preparations in response to verapamil, adrenaline, and blockers of alpha- and beta-adrenoreceptors. It has been shown that after an intramuscular injection of verapamil (6 mg/kg), bradycardia develops, the heart rate (HR) decreasing by 50-70 %. Further, the cardiac arrest occurred; however, administration to the animals of adrenaline (100 mg/kg) restored the cardiac rhythm for a short while. After an intramuscular injection of adrenaline at doses of 0.1-10 mg/kg, no essential changes were observed in the potential action amplitude and HR; an increase of the administered adrenalin concentration to 100 mg/kg was not accompanied by the cardiac rhythm stimulation, as this takes place in homoiothermal animals and human; on the contrary, an essential HR deceleration was revealed. Phentolamine (5 mg/kg) gradually decelerated HR rhythm by 32-45 %. The potential amplitude changed insignificantly. A subsequent intracardiac injection of adrenaline (100 mg/kg) on the background of block of alpha-adrenoreceptors produced acceleration of the rhythm (by 13-21%) and fall of the electrogram amplitude. These results can indicate that in the frog heart, phentolamine interacts predominanty with alpha-adrenoreceptors. An intracardiac administration of propranolol (1 mg/kg) to frogs promoted inhibition of beta-adrenergic receptors and produced a gradual cardiac rhythm deceleration. In experiments on assessment of verapamil effect on the character of contractions this preparation at a concentration of 150 microM was established to produce a significant dosedependent decrease of the contraction strength. A rise of verapamil concentration in the sample to 200 microM led to a decrease of the amplitude, on average, by 68-70 % and in individual preparations -- by 80-85 %; however, administration into the sample of adrenaline (10 microM) restored the cardiac contraction strength. Adrenaline (1 nM--100 microM) increased markedly the contraction amplitude. Phentolamine (10 microM) did not inhibit transmission of contractile signal to cardiomyocytes; this was manifested in that the contraction amplitude after addition of adrenaline (10 microM) into the sample was approximately the same as in the sample containing no phentolamine. Propranolol (10 microM) eliminated the stimulatory action of adrenaline (10 microM). The results of these experiments indicate that in the frog ventricular cardiomyocytes the main adrenaline acceptors are beta-adrenoreceptors. |
2,332,990 | Enflurane requirement for blocking adrenergic responses to incision in infants and children. | Enflurane is one of the most commonly used inhaled anesthetics in China, but its requirement to block adrenergic responses after skin incision in pediatric patients is still unknown. This study was to determine the minimum alveolar anesthetic concentration (MAC) of potent inhaled anesthetics required to blunt the adrenergic response to skin incision of enflurane (MACBAR) in infants and children.</AbstractText>Twenty-eight patients, 10 infants (6-12 months) and 18 young children (1-6 years), were studied. The 18 children were randomly assigned into two groups, with or without fentanyl. Anesthesia was induced with 3 mg/kg propofol and 0.15 mg/kg vecuronium, and maintained with enflurane in 100% oxygen. Fentanyl (3 microg/kg) was given intravenously 5 minutes before incision for the patients of fentanyl group. The "up and down" method (with 0.3 MAC as a step size and 1 MAC as the start dose) was applied to determine MACBAR. The response was considered positive if the mean arterial pressure (MAP) or heart rate (HR) increased > or =15% after incision. The MACBAR was calculated as the mean of four independent cross-over responses in each group.</AbstractText>MACBAR of enflurane in children of 1-6 years old was 3.2% (95% CI, 2.8%-3.6%) and was reduced to 2.2% (95% CI, 1.8%-2.5%) by 3 microg/kg fentanyl. In infants of 6-12 months old, the MACBAR of enflurane was 3.4% (95% CI, 3.0%-3.8%).</AbstractText>MACBAR of enflurane in infants older than 6 months is similar to that in young children. The MACBAR of enflurane decreases with co-administration of fentanyl in the pediatric population.</AbstractText> |
2,332,991 | Clinical comparison of cardiorespiratory effects during unilateral and conventional spinal anaesthesia. | Spinal anaesthesia is widely employed in clinical practice but has the main drawback of post-spinal block hypotension. Efforts must therefore continue to be made to obviate this setback</AbstractText>To evaluate the cardiovascular and respiratory changes during unilateral and conventional spinal anaesthesia.</AbstractText>With ethical approval, we studied 74 American Society of Anesthesiologists (ASA), physical status class 1 and 2 patients scheduled for elective unilateral lower limb surgery. Patients were randomly allocated into one of two groups: lateral and conventional spinal anaesthesia groups. In the lateral position with operative side down, patients recived 10 mg (2mls) of 0.5% hyperbaric bupivacaine through a 25-gauge spinal needle. Patients in the unilateral group were maintained in the lateral position for 15 minutes following spinal injection while those in the conventional group were turned supine immediately after injection. Blood pressure, heart rate, respiratory rate and oxygen saturation were monitored over 1 hour.</AbstractText>Three patients (8.1%) in the unilateral group and 5 (13.5%) in the conventional group developed hypotension, P= 0.71. Four (10.8%) patients in the conventional group and 1 (2.7%) in the unilateral group, P= 0.17 required epinephrine infusion to treat hypotension. Patients in the conventional group had statistically significant greater fall in the systolic blood pressures at 15, 30 and 45 minutes when compared to the baseline (P= 0.003, 0.001 and 0.004). The mean respiratory rate and oxygen saturations in the two groups were similar.</AbstractText>Compared to conventional spinal anaesthesia, unilateral spinal anaesthesia was associated with fewer cardiovascular perturbations. Also, the type of spinal block instituted affected neither the respiratory rate nor the arterial oxygen saturation.</AbstractText> |
2,332,992 | Life-threatening pacemaker dysfunction associated with therapeutic radiation: a case report. | Reports about pacemaker (PM) dysfunction during irradiation (IR) are very rare, which is because of the extensive protective mechanisms that exist in these devices against electromagnetic interference (EMI). We report a case in which one of the most clinically relevant type of PM malfunctions, a runaway PM, occurred during radiation in a 76-year-old woman who was treated for inoperable esophageal cancer with a course of photon IR. The estimated IR dose of 0.11 Gy was the lowest in vivo dose ever reported. So a direct radiation effect as cause for this malfunction appears to be improbable. It could be concluded that the PM dysfunction was most likely induced by EMI during radiotherapy. The real reason of the device's software failure remains unclear. |
2,332,993 | Signs of myocardial ischaemia after injection of oxytocin: a randomized double-blind comparison of oxytocin and methylergometrine during Caesarean section. | ECG changes, similar to those seen during myocardial ischaemia, together with symptoms of chest pain, are common during Caesarean section (CS). We hypothesized that oxytocin administration has cardiovascular effects leading to these symptoms and ECG changes.</AbstractText>Forty women undergoing elective CS under spinal anaesthesia were given an i.v. bolus of either 10 IU of oxytocin (Group OXY-CS, n=20) or 0.2 mg of methylergometrine (Group MET-CS, n=20), in a double-blind, randomized fashion after delivery. Ten healthy, non-pregnant, non-anaesthetized women were used as normal controls (Group OXY-NC, n=10) and were given 10 IU of oxytocin i.v. Twelve-lead ECG, on-line, computerized vectorcardiography (VCG), and invasive arterial pressure were recorded.</AbstractText>Oxytocin produced a significant increase in heart rate, +28 (SD 4) and +52 (3) beats min(-1) [mean (SEM); P<0.001], decreases in mean arterial pressure, -33 (2) and -30 (3) mm Hg (P<0.001), and increases in the spatial ST-change vector magnitude (STC-VM), +77 (12) and +114 (8) microV (P<0.001), in CS patients and controls, respectively. Symptoms of chest pain and subjective discomfort were simultaneously present. Methylergometrine produced mild hypertension and no significant ECG changes.</AbstractText>Oxytocin administered as an i.v. bolus of 10 IU induces chest pain, transient profound tachycardia, hypotension, and concomitant signs of myocardial ischaemia according to marked ECG and STC-VM changes. The effects are related to oxytocin administration and not to pregnancy, surgical procedure, delivery, or sympathetic block from spinal anaesthesia.</AbstractText> |
2,332,994 | Remifentanil versus fentanyl in combination with midazolam for retrobulbar block in cataract surgery. | To compare the effects of fentanyl or remifentanil in combination with midazolam on hemodynamic parameters, pain, and satisfaction profile in cataract surgery.</AbstractText>This randomized, double blind, prospective study was conducted between 10 and 20th July 2005 at Kudret Eye Hospital, Ankara, Turkey. Patients scheduled for cataract surgery by the phacoemulsification technique were randomly enrolled to receive sedation with midazolam 1 mg intravenous iv either with fentanyl 25 microgram group 1, n=54 or remifentanil 0.3 microgram/kg group 2, n= 46. Heart rate, systolic and diastolic arterial pressure values were recorded as baseline, after retrobulbar injection, and during the operation. We evaluated recall of retrobulbar block, pain during injection and operation, satisfaction of patient and surgeon, and the adverse effects.</AbstractText>There were statistically significant alterations in systolic and diastolic arterial pressure measurements within and between groups, whereas all kept in the clinically normal range. Twenty-four percent of patients in group 1 and 15.2% in group 2 did not even remember the retrobulbar injection. The pain scores during retrobulbar injection and operation were similar in both groups. Also, satisfaction of patients and surgeon was high and comparable between groups.</AbstractText>Remifentanil and fentanyl are both efficient and comparable opioid adjuncts to midazolam providing low injection pain and high satisfaction level with hemodynamic stability in cataract surgery under retrobulbar injection.</AbstractText> |
2,332,995 | Is sitaxsentan a good therapeutic option for pulmonary arterial hypertension associated with connective tissue disease? | Agents that indiscriminately block endothelin receptors have been shown to cause moderate improvements in the outcomes of patients who have pulmonary arterial hypertension (PAH) as a complication of connective tissue disease (CTD). Girgis et al. investigated the effects of sitaxsentan, a selective endothelin receptor type A antagonist, in patients with CTD and comcomitant PAH. After 12 weeks of treatment, patients who received sitaxsentan showed more improvement from baseline compared with those receiving placebo in terms of exercise capacity, hemodynamics and physical-health-related quality of life. At the end of the extension study (median total follow-up 26 weeks), 16 of the 41 patients with CTD had an improvement of at least one New York Heart Association functional class compared with at the start of sitaxsentan therapy. The effects of sitaxsentan observed in the CTD group were comparable to those seen in the idiopathic PAH group. The authors concluded that treatment with sitaxsentan might be beneficial in patients with PAH associated with CTD. |
2,332,996 | Physiological heart activation by adrenaline involves parallel activation of ATP usage and supply. | During low-to-high work transition in adult mammalian heart in vivo the concentrations of free ADP, ATP, PCr (phosphocreatine), P(i) and NADH are essentially constant, in striking contrast with skeletal muscle. The direct activation by calcium ions of ATP usage and feedback activation of ATP production by ADP (and P(i)) alone cannot explain this perfect homoeostasis. A comparison of the response to adrenaline (increase in rate-pressure product and [PCr]) of the intact beating perfused rat heart with the elasticities of the PCr producer and consumer to PCr concentration demonstrated that both the ATP/PCr-producing block and ATP/PCr-consuming block are directly activated to a similar extent during physiological heart activation. Our finding constitutes a direct evidence for the parallel-activation mechanism of the regulation of oxidative phosphorylation in heart postulated previously in a theoretical way. |
2,332,997 | Bending of z-lines by mechanical stimuli: an input signal for integrin dependent modulation of ion channels? | We studied which components of mechanical cell deformation are involved in "stretch modulated ion currents" (SMIC). Murine ventricular myocytes were attached to glass coverslips and deformed in x, y and z with a 16 microm thin glass stylus (S) of calibrated stiffness. Three-dimensional confocal microscopy characterized cell deformation (T-tubular membranes, mitochondria) and bending of S (indicative of the applied force). Axial (x-) displacement of S sheared the upper cell part versus the attached bottom, close to S, it changed sarcomere length and bent z-lines ("z-line displacement"). Vertical (z-press) or transversal (y-shear) displacement of S bulged cytoplasm and mitochondria transversally without detectable z-line displacement. Axial stiffness increased with the extent of stress ("stress stiffening"). Depolymerization of F-actin or block of integrin receptors reduced stiffness. SMIC served as a proxy readout of deformation-induced signaling. Axial deformation activated a non-selective cation conductance (Gns) and deactivated an inwardly rectifying K+ conductance (GK1), z-press or y-shear did not induce SMIC. Depolymerization of F-actin or block of integrin receptors reduced SMIC. SMIC did not depend on changes in sarcomere length but correlated with the extent of z-line bending. We discuss that both shear stress at the attached cell bottom and z-line bending could activate mechanosensors. Since SMIC was absent during deformations without z-line bending we postulate that z-line bending is a necessary component for SMIC signaling. |
2,332,998 | Lipid emulsion as rescue for local anesthetic-related cardiotoxicity. | Regional anesthesia techniques use local anesthetics to provide sensory and motor block for surgical intervention. Intravascular absorption of the local anesthetics may induce toxic effects, such as seizure activity or cardiac depression, leading to cardiac arrest. Standard, prolonged resuscitation efforts are not always successful in the event of local anesthetic cardiotoxicity. Research in animals, however, has shown that, with the administration of intravenous lipid emulsion, hemodynamic stability can be restored after local anesthetic-induced cardiac arrest. Recent case reports have detailed successful resuscitation from cardiac arrest in several patients with local anesthetic-induced cardiotoxicity. |
2,332,999 | Factors that affect pulse wave time transmission in the monitoring of cardiovascular system. | Vascular transit time (VTT) can be defined as the first heart sound of the phonocardiography (PCG) signal to its arrival at the photoplethysmography (PPG). Studies have shown that monitoring VTT can be useful as an early prognosis of cardiac diseases. However, there is limited study conducted to understand the physiologic factors that affect VTT at the upper limb. In this study, the effect associated with difference in subject height, weight, heart rate, mean arterial pressure, systolic and diastolic blood pressure was assessed.</AbstractText>A study population of 31 healthy Chinese young adults (21 male; age range 20-33 yr) were recruited. PCG and PPG were recorded non-invasively from the fourth costal cartilage at the midclavicular line and right index finger, respectively. A single sample Kolmogorov-Smirnov (K-S) goodness-of-fit hypothesis test, a univariate linear regression analysis, and a multiple linear regression modelling were performed on the VTT measurements and the associated physiologic parameters.</AbstractText>The results from the K-S test showed that the physiologic parameters and VTT measurements had a normal cumulative distribution function. Furthermore, all physiologic parameters were significantly and independently related to VTT (P < 0.05). Based on these physiological parameters, a VTT regression model was also derived (r (2) = 0.79).</AbstractText>The findings herein suggest that the observed physiologic parameters have significant contributions to the nominal VTT value of a subject. Unlike pulse transit time, the VTT technique has the added advantage that the left ventricular isometric contraction time is not included in the timing derivation.</AbstractText> |
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