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2,332,700
Low-dose clonidine and neostigmine prolong the duration of intrathecal bupivacaine-fentanyl for labor analgesia.
Intrathecal (IT) opioid and local anesthetic combinations are popular for labor analgesia because of rapid, effective pain relief, but the duration of analgesia is limited. This study was undertaken to determine whether the addition of clonidine and neostigmine to IT bupivacaine-fentanyl would increase the duration of analgesia without increasing side effects for patients in labor.</AbstractText>Forty-five healthy parturients in active labor were randomized to receive a 2-ml IT dose of one of the following dextrose-containing solutions using the combined spinal-epidural technique: (1) bupivacaine 2.5 mg and fentanyl 25 microg (BF); (2) BF plus clonidine 30 microg (BFC); or (3) BFC plus neostigmine 10 microg (BFCN). Pain, sensory levels, motor block, side effects, maternal vital signs, and fetal heart rate were systematically assessed.</AbstractText>Patients administered BFCN had significantly longer analgesia (165+/-32 min) than those who received BF (90+/-21 min; P&lt;0.001) or BFC (123+/-21 min; P&lt;0.001). Pain scores, block characteristics, maternal vital signs, Apgar scores, maternal satisfaction, and side effects were similar among groups except for nausea, which was significantly greater in the BFCN group (P&lt;0.05 as compared with BFC).</AbstractText>The addition of clonidine and neostigmine significantly increased the duration of analgesia from IT bupivacaine-fentanyl during labor, but neostigmine caused more nausea. Although serious side effects were not observed in this study, safety must be further addressed before the routine use of multiple IT drugs is advocated.</AbstractText>
2,332,701
Block of human heart hH1 sodium channels by amitriptyline.
Amitriptyline is a tricyclic antidepressant used to treat major depression and various neuropathic pain syndromes. This drug also causes cardiac toxicity in patients with overdose. We characterized the tonic and use-dependent amitriptyline block of human cardiac (hH1) Na(+) channels expressed in human embryonic kidney cells under voltage-clamp conditions. Our results show that, near the therapeutic plasma concentration of 1 microM, amitriptyline is an effective use-dependent blocker of hH1 Na(+) channels during repetitive pulses (approximately 55% block at 5 Hz). The tonic block for resting and for inactivated hH1 channels by amitriptyline (0.1-100 microM) yielded IC(50) values (50% inhibitory concentration) of 24.8 +/- 2.0 (n = 9) and 0.58 +/- 0.03 microM (n = 7), respectively. Substitution of phenylalanine with lysine at the hH1-F1760 position, a putative binding site for local anesthetics, eliminates the use-dependent block by amitriptyline at 1 microM. The time constants of recovery from the inactivated-state amitriptyline block in hH1 wild-type and hH1-F1760K mutant channels are 8.0 +/- 0. 5 (n = 6) and 0.45 +/- 0.07 s (n = 6), respectively. A substitution at either hH1-F1760K or hH1-Y1767K significantly increases the IC(50) values for resting and inactivated states of amitriptyline, but the increase is much more pronounced with the hH1-F1760K mutation. Because these two residues were proposed to form a part of the local anesthetic binding site, we conclude that amitriptyline and local anesthetics interact with a common binding site. Furthermore, at therapeutic concentrations, the ability of amitriptyline to act as a potent use-dependent blocker of Na(+) channels may, in part, explain its analgesic actions.
2,332,702
Inflammation and infection imaging with a 99mTc-neutrophil elastase inhibitor in monkeys.
A radiolabeled human neutrophil elastase inhibitor (EPI-HNE-2) may represent an improved nuclear medicine imaging agent for inflammation and infection. This peptide displays rapid pharmacokinetics due to its low molecular weight and localizes specifically on neutrophil elastase released in inflammatory sites by activated neutrophils.</AbstractText>In this investigation, the peptide was radiolabeled with 99mTc using N-hydroxysuccinimidyl S-acetylmercaptoacetyltriglycline (NHS-MAG3) as a bifunctional chelator and was administered on 18 occasions to 5 rhesus monkeys with inflammation/infection.</AbstractText>Plasma clearance was rapid, with liver and kidneys representing the major organs of accumulation. No evidence of toxicity, dosage effects, or circulating antiMAG3-EPI-HNE-2 antibodies was observed. Specificity of localization was established using radiolabeled bovine pancreatic trypsin inhibitor (a non-hNE-binding peptide of similar size) as a nonspecific negative control peptide and by predosing with unlabeled EPI-HNE-2 to block receptor sites before the administration of radiolabeled EPI-HNE-2. The ability of radiolabeled EPI-HNE-2 to image inflammation/infection was evaluated in 12 studies in monkeys receiving only radiolabeled EPI-HNE-2 and with lesions in the arm, shoulder, or lower back. Positive images were obtained in all studies, uptake was apparent almost immediately, and images were still positive 24 h later. As a positive control, animals also received nonspecific IgG antibody radiolabeled with 99mTc either directly or by NHS-MAG3. Compared with labeled antibody, plasma clearance of 99mTc was faster with labeled EPI-HNE-2 and accumulation in liver and heart was lower. Uptake of radioactivity in the inflammation was higher during the first hour with EPI-HNE-2 versus antibody but lower thereafter.</AbstractText>When radiolabeled with 99mTc, EPI-HNE-2 localized specifically in inflammations in a monkey model and provided early images of diagnostic quality.</AbstractText>
2,332,703
Linkage of hereditary distal myopathy with desmin accumulation to 2q.
We are investigating the genetics of a large family with an autosomal dominant form of hereditary distal myopathy. This slowly progressive myopathy begins during early adulthood in the distal leg muscles, producing a gait disturbance. Cardiomyopathy is also present in most affected family members, manifesting itself as conduction block or congestive heart failure. Histologically, an accumulation of the protein, desmin, occurs in the subsarcolemmal spaces of myofibers. We have performed linkage analyses of this family, and have mapped the location of the gene causing the myopathy to human chromosome 2q33. The gene is within a 17-cM segment of chromosome 2q bounded by the DNA markers D2S2248 and D2S401. The best candidate gene for this myopathy is desmin.
2,332,704
Effect of vitamin E sources (RRR- or all-rac-alpha-tocopheryl acetate) and levels on sow reproductive performance, serum, tissue, and milk alpha-tocopherol contents over a five-parity period, and the effects on the progeny.
Two dietary sources of vitamin E (DL-alpha-tocopheryl acetate [DL-beta-TAc], or D-alpha-tocopheryl acetate [DL-alpha-TAc]) at two dietary supplemental levels (30 vs 60 IU/kg) were evaluated in reproducing sows over a five-parity period. The experiment was a 2 x 2 factorial arrangement of treatments conducted as a randomized complete block in two replicates. A total of 48 gilts were fed their treatment diets from 40 kg BW through five parities, reflecting a total of 171 farrowings. Reproductive measurements of litter size, sow weight, and back-fat thickness were collected. The incidence of mastitis-metritis-agalactia (MMA) and fluid discharge from the vagina were evaluated for each sow on each of the first 3 d postpartum. Sows were bled at periodic intervals during gestation and at weaning (21 d) and serum was frozen. After the fifth parity, two to four sows from each treatment group were killed and tissues collected. At birth, two to three neonatal pigs were killed from each sow treatment group within each parity and livers were collected and frozen. In addition, three pigs from each litter from three to four sows per treatment group within each parity were bled at weaning and serum was saved. Six pigs from each sow group at weaning of Parity 5 were also killed and livers were collected and frozen. Sow and pig sera and tissues were analyzed for a-tocopherol. There was no effect (P &gt; .15) of vitamin E source or level on the various sow reproductive measurements, litter size, or the incidences of MMA or fluid discharges from the vagina. Feeding D-alpha-TAc compared with DL-alpha-TAc or 60 IU compared with 30 IU vitamin E/kg diet resulted in higher (P &lt; .01) sow serum, colostrum, and milk alpha-tocopherol contents at each measurement period. Sow liver, adipose, lung, and heart alpha-tocopherol contents were also higher (P &lt; .01) when the 60 IU vitamin E level had been fed. Both serum and liver a-tocopherol contents in 21-d-old nursing pigs were higher (P &lt; .01) when the sow had been fed D-alpha-TAc compared with the DL-alpha-TAc source or when the 60 IU level had been fed. There were no vitamin E source x vitamin E level interactions (P &gt; .15) for the various alpha-tocopherol measurements. Although the supplemental vitamin E sources were provided on an equivalent IU basis, these results suggest that D-alpha-TAc has a higher equivalency than DL-alpha-TAc on an IU basis, but higher dietary levels also resulted in higher sow and pig alpha-tocopherol contents.
2,332,705
A critical residue for isoform difference in tetrodotoxin affinity is a molecular determinant of the external access path for local anesthetics in the cardiac sodium channel.
Membrane-impermeant quaternary derivatives of lidocaine (QX222 and QX314) block cardiac Na(+) channels when applied from either side of the membrane, but they block neuronal and skeletal muscle channels poorly from the outside. To find the molecular determinants of the cardiac external QX access path, mutations of adult rat skeletal muscle (micro1) and rat heart (rH1) Na(+) channels were studied by two-electrode voltage clamp in Xenopus oocytes. Mutating the micro1 domain I P-loop Y401, which is the critical residue for isoform differences in tetrodotoxin block, to the heart sequence (Y401C) allowed outside QX222 block, but its mutation to brain type (Y401F) showed little block. mu1-Y401C accelerated recovery from block by internal QX222. Block by external QX222 in mu1-Y401C was diminished by chemical modification with methanethiosulfonate ethylammonium (MTSEA) to the outer vestibule or by a double mutant (mu1-Y401C/F1579A), which altered the putative local anesthetic binding site. The reverse mutation in heart rH1-C374Y reduced outside QX314 block and slowed dissociation of internal QX222. Mutation of mu1-C1572 in IVS6 to Thr, the cardiac isoform residue (C1572T), allowed external QX222 block, and accelerated recovery from internal QX222 block, as reported. Blocking efficacy of outside QX222 in mu1-Y401C was more than that in mu1-C1572T, and the double mutant (mu1-Y401C/C1572T) accelerated internal QX recovery more than mu1-Y401C or mu1-C1572T alone. We conclude that the isoform-specific residue (Tyr/Phe/Cys) in the P-loop of domain I plays an important role in drug access as well as in tetrodotoxin binding. Isoform-specific residues in the IP-loop and IVS6 determine outside drug access to an internal binding site.
2,332,706
The effect of Portuguese Man-of-war (Physalia physalis) venom on calcium, sodium and potassium fluxes of cultured embryonic chick heart cells.
Portuguese Man-of-war venom markedly increases calcium (45Ca2+) influx into primary, cultured, embryonic chick heart cells. This action is dose-dependent, but is unaffected by organic calcium blockers (diltiazem, verapamil, nifedipine, nimodipine and mibefradil). On the other hand, certain trivalent (La3+, Gd3+) and divalent (Zn2+, Ni2+, Cu2+, Mn2+) metals inhibit venom-induced calcium influx. Sodium (22Na+) influx into chick heart cells is also significantly increased by Man-of-war venom. Flecainide does not block venom-induced sodium influx. The efflux of the potassium analogue, 86Rb+, from heart cells is also significantly increased by the venom. The venom, however, has little or no effect on rubidium (86Rb+) or 2-deoxy-D-[2-3H] glucose influx.
2,332,707
Presenilin-1 mutation increases neuronal vulnerability to focal ischemia in vivo and to hypoxia and glucose deprivation in cell culture: involvement of perturbed calcium homeostasis.
Many cases of early-onset inherited Alzheimer's disease (AD) are caused by mutations in the presenilin-1 (PS1) gene. Studies of cultured neural cells suggest that PS1 mutations result in perturbed cellular calcium homeostasis and may thereby render neurons vulnerable to apoptosis. In light of evidence that metabolic impairment plays a role in AD, that cerebral ischemia may be a risk factor for AD, and that individuals with AD have increased morbidity and mortality after stroke, we examined the impact of a PS1 mutation on neuronal vulnerability to ischemic injury. We report that the extent of brain injury after focal cerebral ischemia reperfusion is increased, and behavioral outcome is worsened, in PS1 mutant knock-in mice compared to wild-type mice. Cultured cortical neurons from PS1 mutant mice exhibit increased vulnerability to glucose deprivation and chemical hypoxia compared to their wild-type counterparts. Calcium imaging studies demonstrated enhanced elevation of intracellular calcium levels after glucose deprivation and chemical hypoxia in neurons from PS1 mutant mice. Agents that block calcium release from IP(3)- and ryanodine-sensitive stores (xestospongin and dantrolene, respectively) protected against the endangering action of the PS1 mutation. Our data suggest that presenilin mutations may promote neuronal degeneration in AD by increasing the sensitivity of neurons to age-related ischemia-like conditions. The data further suggest that drugs that stabilize endoplasmic reticulum calcium homeostasis may prove effective in suppressing the neurodegenerative process in AD patients.
2,332,708
Rectal cancer in pregnancy: a new management based on blended anesthesia and monitoring of fetal well being.
Colorectal carcinoma presenting during pregnancy is an extremely rare condition associated with a poor prognosis. In this report we studied a patient referred to our hospital at 26 weeks of gestation with the diagnosis of rectal adenocarcinoma. Tumor resection with a colostomy was planned in the attempt to preserve pregnancy until fetal viability could be reached. Blended anesthesia (general and epidural) was chosen to avoid surgical and anesthesiological risks; in fact this technique allows either an optimal block of neurohormonal response or a good control of surgical stress to be obtained. In order to monitor fetal well being during surgery, Doppler evaluations of fetal heart rate and umbilical artery flow velocity waveforms were performed. The patient was dismissed in good health and then rehospitalized at 32 weeks of gestation in order to perform an elective cesarean section. In conclusion we suggest that, with the choice of a good anesthesiological technique and monitoring of fetal well being, surgical treatment in case of rectal cancer could be performed without affecting the course of pregnancy.
2,332,709
[Effect of stellate ganglion block on human retinal blood flow].
The effect of stellate ganglion block (SGB) on human retinal blood flow was evaluated.</AbstractText>We measured the diameter of the retinal artery and vein, and retinal venous flow rate by laser speckle retinal blood flow meter simultaneously in 11 eyes of 11 normal volunteers.</AbstractText>The reliable data from 9 eyes of 9 person were used for analysis. SGB did not change the blood pressure, heart rate, retinal arterial diameter, or venous diameter. However SGB increased retinal blood velocity significantly from 9.9 +/- 1.6 (mean +/- standard deviation) mm/s to 11.1 +/- 1.5 mm/s (p &lt; 0.01). Intraocular pressure decreased from 12.3 +/- 2.1 (mean +/- standard deviation)mmHg to 9.4 +/- 2.2 mmHg after SGB (p &lt; 0.01). There was no relationship between the change of ocular perfusion pressure and that of retinal venous blood velocity.</AbstractText>SGB increased the retinal venous blood velocity without changing the retinal vessel diameter.</AbstractText>
2,332,710
Subdivision of the cardiac Nkx2.5 expression domain into myogenic and nonmyogenic compartments.
Nkx2.5 is expressed in the cardiogenic mesoderm of avian, mouse, and amphibian embryos. To understand how various cardiac fates within this domain are apportioned, we fate mapped the mesodermal XNkx2.5 domain of neural tube stage Xenopus embryos. The lateral portions of the XNkx2.5 expression domain in the neural tube stage embryo (stage 22) form the dorsal mesocardium and roof of the pericardial cavity while the intervening ventral region closes to form the myocardial tube. XNkx2.5 expression is maintained throughout the period of heart tube morphogenesis and differentiation of myocardial, mesocardial, and pericardial tissues. A series of microsurgical experiments showed that myocardial differentiation in the lateral portion of the field is suppressed during normal development by signals from the prospective myocardium and by tissues located more dorsally in the embryo, in particular the neural tube. These signals combine to block myogenesis downstream of XNkx2.5 and at or above the level of contractile protein gene expression. We propose that the entire XNkx2.5/heart field is transiently specified as cardiomyogenic. Suppression of this program redirects lateral cells to adopt dorsal mesocardial and dorsal pericardial fates and subdivides the field into distinct myogenic and nonmyogenic compartments.
2,332,711
Kearns-Sayre syndrome presenting as 2-oxoadipic aciduria.
A patient with 2-oxoadipic aciduria and 2-aminoadipic aciduria presented at 2 years of age with manifestations typical of organic acidemia, episodes of ketosis and acidosis, progressive to coma. This resolved and the key metabolites disappeared from the urine and blood. At 9 years of age she developed typical Kearns-Sayre syndrome with complete heart block, retinopathy, and ophthalmoplegia. Southern blot revealed a deletion in the mitochondrial genome.
2,332,712
Cytochrome c release from mitochondria of early postimplantation murine embryos exposed to 4-hydroperoxycyclophosphamide, heat shock, and staurosporine.
Cell death is an early and common event in the pathogenesis associated with the abnormal development induced by a variety of teratogens. Previously, we showed that the cell death induced in day 9 mouse embryos by three teratogens, hyperthermia (HS), 4-hydroperoxycyclophosphamide (4-CP), and sodium arsenite (As), is apoptotic in nature involving the activation of caspase-3, cleavage of poly(ADP-ribose) polymerase (PARP), and DNA fragmentation. We now show that HS, 4-CP, and staurosporine (ST) induce the release of cytochrome c from mitochondria with kinetics suggesting a causal relationship with the activation of caspase-3 and caspase-2. This causal relationship is supported by data showing that procaspase-3 and -2 can be activated in vitro by the addition of cytochrome c to a S-100 fraction prepared from control day 9 embryos. Together, these data support the notion that these three teratogens induce changes in embryonic mitochondria resulting in the release of cytochrome c and the subsequent activation of caspase-9, the upstream activator of caspase-3. Previously, we also showed that cells within the day 9 mouse embryo are differentially sensitive/resistant to the cell death-inducing potential of HS, 4-CP, and As. The most dramatic example of this differential sensitivity is the complete resistance of heart cells, characterized by the lack of caspase-3 activation, PARP cleavage, and DNA fragmentation. We now show that this block in the terminal phase of the apoptotic pathway in heart cells is associated with a lack of teratogen-induced release of cytochrome c. Together, our data indicate that mitochondria play a pivotal role in cell death during the early phases of teratogenesis.
2,332,713
Caspase activation and mitochondrial cytochrome C release during hypoxia-mediated apoptosis of adult ventricular myocytes.
Oxygen deprivation for prolonged periods leads to cardiac cell death and ventricular dysfunction. The ability to prevent myocardial cell death would be of significant therapeutic value in maintaining cardiac function after injury. While caspases have been suggested to play a critical role in apoptosis, their involvement during hypoxic injury has not been formally determined. In this report, we show that adult ventricular myocytes subjected to hypoxia for 1 h undergo a three-fold increase (P&lt;0.05) in the incidence of apoptosis as determined by TUNEL analysis and Hoechst 33258 nuclear staining. Western blot analysis of hypoxic myocytes revealed a 10-fold increase in the proteolytic processing of caspase 3 to p17 with a concomitant cleavage of the caspase 3 substrate PARP from 116 kd to p85 kd compared to normoxic controls. Defects in mitochondrial membrane integrity were also observed as evidenced by the translocation of cytochrome c from the mitochondrial to cytosolic compartment of hypoxic cells. Pretreatment of ventricular myocytes with the peptide-caspase inhibitor known to block caspases related to caspase 1 (Ac-YVAD-CHO) attenuated cytochrome c release, processing of caspase 3, and apoptosis. While the caspase inhibitor (Ac-DEVD-CHO) which blocks caspases related to caspase 3, suppressed the cleavage of PARP and apoptosis, it had no effect on cytochrome c release by mitochondria. The data provide direct evidence for the proteolytic activation of caspases during hypoxia-mediated apoptosis of adult ventricular myocytes. Furthermore, the data suggest a hierarchical scheme for caspase activation with mitochondrial cytochrome c release occurring proximally to DEVD-CHO-inhibitable caspases.
2,332,714
Catecholaminergic activity and 3',5'-cyclic adenosine monophosphate levels in heart right ventricle after naloxone induced withdrawal.
This study evaluated the adaptive changes in noradrenergic neurons and the concomitant production of cAMP during morphine dependence and withdrawal in the right ventricle of the rat. Rats were made dependent on morphine by morphine pellet implantation for 7 days. On the day of sacrifice animals received an acute injection of saline or naloxone (1 mg/kg s.c.) and were decapitated 30 min later. Pretreatment with propranolol 15 min prior to naloxone was conducted to evaluate the possible implication of beta-adrenoceptors. The contents of noradrenaline and dopamine and their metabolites were examined. After naloxone administration to morphine-dependent rats (withdrawal) there was a pronounced increase in the content of normetanephrine and 3,4-dihydroxyphenylacetic acid and increased noradrenaline and dopamine turnover. In addition cAMP levels were increased after naloxone administration to morphine-treated rats. Propranolol did not block the hyperactivity of catecholaminergic neurons or the enhancement of cAMP observed in the heart during withdrawal. The present results indicate that heart catecholaminergic neurons play a significant role in the alterations in heart functions during morphine abstinence syndrome and suggest that those alterations are mediated through cAMP.
2,332,715
Prevention of hypotension by a single 5-mg dose of ephedrine during small-dose spinal anesthesia in prehydrated cesarean delivery patients.
To evaluate the effectiveness of prophylactic ephedrine for the prevention of hypotension associated with spinal anesthesia, 50 parturients undergoing cesarean delivery received either ephedrine 5 mg or saline IV in a double-blinded fashion immediately after the induction of spinal anesthesia. Spinal anesthesia was performed with hyperbaric bupivacaine 6.6 mg combined with sufentanil 3.3 microg as part of a combined spinal-epidural technique. All patients received 1000 mL of lactated Ringer's solution and 500 mL of hydroxyethylstarch 6% before the spinal injection. Additional ephedrine boluses (5 mg) were administered IV when the systolic blood pressure or heart rate decreased by more than 30% from baseline values, when systolic blood pressure became &lt;100 mm Hg, or when patients complained of nausea or feeling faint. The height of the block was equal in the groups; however, more patients in the placebo group were found to develop hypotension (58% vs 25%, P &lt; 0. 05). Only 2 (8%) patients in the ephedrine group developed hypotension with systolic blood pressure values &lt;90 mm Hg, whereas 10 patients (42%) in the saline group experienced hypotension of this severity (P &lt; 0.05). In addition, there was a higher incidence of nausea in the placebo-treated patients. The total amount of ephedrine administered did not differ between groups. These findings suggest that the incidence and severity of hypotension are significantly reduced by the IV administration of a prophylactic dose of 5 mg ephedrine in patients receiving small-dose spinal anesthesia for cesarean delivery.</AbstractText>Ephedrine is the drug most often used to correct hypotension during spinal anesthesia for cesarean delivery in healthy patients. A single IV dose of 5 mg decreases the occurrence and limits the severity of hypotension in prehydrated subjects receiving a small-dose spinal local anesthetic-opioid combination.</AbstractText>
2,332,716
Short-term and long-term blood pressure and heart rate variability in the mouse.
Knowledge on murine blood pressure and heart rate control mechanisms is limited. With the use of a tethering system, mean arterial pressure (MAP) and pulse interval (PI) were continuously recorded for periods up to 3 wk in Swiss mice. The day-to-day variation of MAP and PI was stable from 5 days after surgery. Within each mouse (n = 9), MAP and PI varied by 21+/-6 mm Hg and 17+/-4 ms around their respective 24-h averages (97+/-3 mm Hg and 89+/-3 ms). Over 24-h periods, MAP and PI were bimodally distributed and clustered around two preferential states. Short-term variability of MAP and PI was compared between the resting (control) and active states using spectral analysis. In resting conditions, variability of MAP was mainly confined to frequencies &lt;1 Hz, whereas variability of PI was predominantly linked to the respiration cycle (3-6 Hz). In the active state, MAP power increased in the 0.08- to 3-Hz range, whereas PI power fell in the 0.08- to 0.4-Hz range. In both conditions, coherence between MAP and PI was high at 0.4 Hz with MAP leading the PI fluctuations by 0.3-0.4 s, suggesting that reflex coupling between MAP and PI occurred at the same frequency range as in rats. Short-term variability of MAP and PI was studied after intravenous injection of autonomic blockers. Compared with the resting control state, MAP fell and PI increased after ganglionic blockade with hexamethonium. Comparable responses of MAP were obtained with the alpha-blocker prazosin, whereas the beta-blocker metoprolol increased PI similarly. Muscarinic blockade with atropine did not significantly alter steady-state levels of MAP and PI. Both hexamethonium and prazosin decreased MAP variability in the 0.08- to 1-Hz range. In contrast, after hexamethonium and metoprolol, PI variability increased in the 0.4- to 3-Hz range. Atropine had no effect on MAP fluctuations but decreased those of PI in the 0.08- to 1-Hz range. These data indicate that, in mice, blood pressure and its variability are predominantly under sympathetic control, whereas both vagal and sympathetic nerves control PI variability. Blockade of endogenous nitric oxide formation by N(G)-nitro-L-arginine methyl ester increased MAP variability specifically in the 0.08- to 0.4-Hz range, suggesting a role of nitric oxide in buffering blood pressure fluctuations.
2,332,717
Roles of mitochondrial ATP-sensitive K channels and PKC in anti-infarct tolerance afforded by adenosine A1 receptor activation.
This study intended to assess the role of mitochondrial ATP-sensitive potassium (mitoK ATP) channels and the sequence of signal transduction with protein kinase C (PKC) and adenosine A1 receptors in rabbits.</AbstractText>To our knowledge, the link between trigger receptors of preconditioning, PKC and mitoK ATP channels has not been examined in a whole heart model of infarction.</AbstractText>In the first series of experiments, myocardial infarction was induced in isolated buffer-perfused rabbit hearts by 30-min global ischemia and 2-h reperfusion. Infarct size in the left ventricle was determined by tetrazolium staining and expressed as a percentage of area at risk (i.e., the whole left ventricle) (%IS/AR). In the second series of experiments, mitochondria were isolated from the heart, and their respiratory function was examined using glutamate as a substrate.</AbstractText>Pretreatment with R-phenylisopropyladenosine (R-PIA, 1 micromol/liter), an A1-receptor agonist, reduced %IS/AR from 49.8 +/- 6.5% to 13.4 +/- 2.9%. This protection was abolished by calphostin C, a PKC inhibitor, and by 5-hydroxydecanoate (5-HD), a selective inhibitor of mitoK ATP channels. A selective mitoK ATP channel opener, diazoxide (100 micromol/liter), mimicked the effect of R-PIA on infarct size (%IS/AR = 11.6 +/- 4.0%), and this protective effect was also abolished by 5-HD. However, calphostin C failed to block the infarct size-limiting effect of diazoxide. Neither calphostin C nor 5-HD alone modified %IS/AR. State III respiration (QO2) and respiratory control index (RCI) were reduced after 30 min of ischemia (QO2 = 147.3 +/- 5.3 vs. 108.5 +/- 12.3, RCI = 22.3 +/- 1.1 vs. 12.1 +/- 1.8, p &lt; 0.05). This mitochondrial dysfunction was persistent after 10 min of reperfusion (QO2 = 96.1 +/- 15.5, RCI = 9.5 +/- 1.9). Diazoxide significantly attenuated the respiratory dysfunction after 30 min of ischemia (QO2 = 142.8 +/- 9.7, RCI = 16.2 +/- 0.8) and subsequent 10-min reperfusion (QO2 = 135.3 +/- 7.2, RCI = 19.1 +/- 0.8).</AbstractText>These results suggest that mitoK ATP channels are downstream of PKC in the mechanism of infarct-size limitation by A1-receptor activation and that the anti-infarct tolerance afforded by opening of mitoK ATP channels is associated with preservation of mitochondrial function during ischemia/reperfusion.</AbstractText>
2,332,718
Anesthetic efficacy and heart rate effects of the intraosseous injection of 3% mepivacaine after an inferior alveolar nerve block.
The purpose of this study was to determine the anesthetic efficacy and heart rate effects of an intraosseous injection of 3% mepivacaine after an inferior alveolar nerve block.</AbstractText>Through use of a repeated-measures design, each of 48 subjects randomly received 2 combinations of injections at 2 separate appointments. The combinations were (1) an inferior alveolar nerve block (with 1.8 mL of 3% mepivacaine) + intraosseous injection with 1.8 mL of 3% mepivacaine and (2) an inferior alveolar nerve (with 1. 8 mL of 3% mepivacaine) + mock intraosseous injection. The first molar was blindly pulp tested at 2-minute cycles for 60 minutes postinjection. Anesthesia was considered successful with 2 consecutive 80 readings. Heart rate (pulse rate) was measured with a pulse oximeter.</AbstractText>All subjects had lip numbness with both of the inferior alveolar nerve + intraosseous techniques. Anesthetic success for the first molar was significantly increased for 30 minutes with intraosseous injection of mepivacaine in comparison with the inferior alveolar nerve block alone (mock intraosseous injection). Subjects receiving the intraosseous injection of mepivacaine experienced minimal increases in heart rate.</AbstractText>The intraosseous injection of 1.8 mL of 3% mepivacaine, when used to augment an inferior alveolar nerve block, significantly increased anesthetic success for 30 minutes in the first molar. The 3% mepivacaine had a minimal effect on heart rate and would be useful in patients with contraindications to epinephrine use.</AbstractText>
2,332,719
Effects of a selective inhibitor of Na+/Ca2+ exchange, KB-R7943, on reoxygenation-induced injuries in guinea pig papillary muscles.
The effects of a novel agent that is reported to selectively block Ca2+ influx by Na+/Ca2+ exchange (NCX), KB-R7943, on the reoxygenation-induced arrhythmias and the recovery of developed tension after reoxygenation, were investigated in guinea pig papillary muscles. KB-R7943 dose-dependently suppressed the contracture tension during low-sodium (21.9 mM) perfusion (23+/-8% of steady-state developed tension at 10 microM vs. 56+/-11% in control; n = 6, p&lt;0.05), but did not change action potential and contractile parameters. During the reoxygenation period after 60-min substrate-free hypoxia, KB-R7943 (10 microM) significantly decreased the incidence of arrhythmias (44 vs. 100% in control; n = 9, p &lt;0.05) and shortened the duration of arrhythmias (16+/-11 vs. 72+/-14 s; p&lt;0.01). KB-R7943 (10 microM) significantly enhanced the recovery of developed tension after reoxygenation (83+/-4 vs. 69+/-3% in control; p&lt;0.05). We conclude that KB-R7943 (10 microM) selectively inhibits the reverse mode of NCX, and that it attenuates reoxygenation-induced arrhythmic activity and prevents contractile dysfunction in guinea pig papillary muscles. These results suggest that Ca2+ influx by NCX may play a key role in reoxygenation injury.
2,332,720
Potentiation of fractional sarcoplasmic reticulum calcium release by total and free intra-sarcoplasmic reticulum calcium concentration.
Our aim was to measure the influence of sarcoplasmic reticulum (SR) calcium content ([Ca](SRT)) and free SR [Ca] ([Ca](SR)) on the fraction of SR calcium released during voltage clamp steps in isolated rabbit ventricular myocytes. [Ca](SRT), as measured by caffeine application, was progressively increased by conditioning pulses. Sodium was absent in both the intracellular and in the extracellular solutions to block sodium/calcium exchange. Total cytosolic calcium flux during the transient was inferred from I(Ca), [Ca](SRT), [Ca](i), and cellular buffering characteristics. Fluxes via the calcium current (I(Ca)), the SR calcium pump, and passive leak from the SR were evaluated to determine SR calcium release flux (J(rel)). Excitation-contraction (EC) coupling was characterized with respect to both gain (integral J(rel)/integral I(Ca)) and fractional SR calcium release. Both parameters were virtually zero for a small, but measurable [Ca](SRT). Gain and fractional SR calcium release increased steeply and nonlinearly with both [Ca](SRT) and [Ca](SR). We conclude that potentiation of EC coupling can be correlated with both [Ca](SRT) and [Ca](SR). While fractional SR calcium release was not linearly dependent upon [Ca](SR), intra-SR calcium may play a crucial role in regulating the SR calcium release process.
2,332,721
Gating and flickery block differentially affected by rubidium in homomeric KCNQ1 and heteromeric KCNQ1/KCNE1 potassium channels.
The voltage-gated potassium channel KCNQ1 associates with the small KCNE1 subunit to form the cardiac IKs delayed rectifier potassium current and mutations in both genes can lead to the long QT syndrome. KCNQ1 can form functional homotetrameric channels, however with drastically different biophysical properties compared to heteromeric KCNQ1/KCNE1 channels. We analyzed gating and conductance of these channels expressed in Xenopus oocytes using the two-electrode voltage-clamp and the patch-clamp technique and high extracellular potassium (K) and rubidium (Rb) solutions. Inward tail currents of homomeric KCNQ1 channels are increased about threefold upon substitution of 100 mM potassium with 100 mM rubidium despite a smaller rubidium permeability, suggesting an effect of rubidium on gating. However, the kinetics of tail currents and the steady-state activation curve are only slightly changed in rubidium. Single-channel amplitude at negative voltages was estimated by nonstationary noise analysis, and it was found that rubidium has only a small effect on homomeric channels (1.2-fold increase) when measured at a 5-kHz bandwidth. The apparent single-channel conductance was decreased after filtering the data at lower cutoff frequencies indicative of a relatively fast "flickery/block" process. The relative conductance in rubidium compared to potassium increased at lower cutoff frequencies (about twofold at 10 Hz), suggesting that the main effect of rubidium is to decrease the probability of channel blockage leading to an increase of inward currents without large changes in gating properties. Macroscopic inward tail currents of heteromeric KCNQ1/KCNE1 channels in rubidium are reduced by about twofold and show a pronounced sigmoidal time course that develops with a delay similar to the inactivation process of homomeric KCNQ1, and is indicative of the presence of several open states. The single channel amplitude of heteromers is about twofold smaller in rubidium than in potassium at a bandwidth of 5 kHz. Filtering at lower cutoff frequencies reduces the apparent single-channel conductance, the ratio of the conductance in rubidium versus potassium is, however, independent of the cutoff frequency. Our results suggest the presence of a relatively rapid process (flicker) that can occur almost independently of the gating state. Occupancy by rubidium at negative voltages favors the flicker-open state and slows the flickering rate in homomeric channels, whereas rubidium does not affect the flickering in heteromeric channels. The effects of KCNE1 on the conduction properties are consistent with an interaction of KCNE1 in the outer vestibule of the channel.
2,332,722
Isoform-specific lidocaine block of sodium channels explained by differences in gating.
When depolarized from typical resting membrane potentials (V(rest) approximately -90 mV), cardiac sodium (Na) currents are more sensitive to local anesthetics than brain or skeletal muscle Na currents. When expressed in Xenopus oocytes, lidocaine block of hH1 (human cardiac) Na current greatly exceeded that of mu1 (rat skeletal muscle) at membrane potentials near V(rest), whereas hyperpolarization to -140 mV equalized block of the two isoforms. Because the isoform-specific tonic block roughly parallels the drug-free voltage dependence of channel availability, isoform differences in the voltage dependence of fast inactivation could underlie the differences in block. However, after a brief (50 ms) depolarizing pulse, recovery from lidocaine block is similar for the two isoforms despite marked kinetic differences in drug-free recovery, suggesting that differences in fast inactivation cannot entirely explain the isoform difference in lidocaine action. Given the strong coupling between fast inactivation and other gating processes linked to depolarization (activation, slow inactivation), we considered the possibility that isoform differences in lidocaine block are explained by differences in these other gating processes. In whole-cell recordings from HEK-293 cells, the voltage dependence of hH1 current activation was approximately 20 mV more negative than that of mu1. Because activation and closed-state inactivation are positively coupled, these differences in activation were sufficient to shift hH1 availability to more negative membrane potentials. A mutant channel with enhanced closed-state inactivation gating (mu1-R1441C) exhibited increased lidocaine sensitivity, emphasizing the importance of closed-state inactivation in lidocaine action. Moreover, when the depolarization was prolonged to 1 s, recovery from a "slow" inactivated state with intermediate kinetics (I(M)) was fourfold longer in hH1 than in mu1, and recovery from lidocaine block in hH1 was similarly delayed relative to mu1. We propose that gating processes coupled to fast inactivation (activation and slow inactivation) are the key determinants of isoform-specific local anesthetic action.
2,332,723
Targeting of the chemokine receptor CCR1 suppresses development of acute and chronic cardiac allograft rejection.
Although mononuclear cell infiltration is a hallmark of cellular rejection of a vascularized allograft, efforts to inhibit rejection by blocking leukocyte-endothelial cell adhesion have proved largely unsuccessful, perhaps in part because of persistent generation of chemokines within rejecting grafts. We now provide, to our knowledge, the first evidence that in vivo blockade of specific chemokine receptors is of therapeutic significance in organ transplantation. Inbred mice with a targeted deletion of the chemokine receptor CCR1 showed significant prolongation of allograft survival in 4 models. First, cardiac allografts across a class II mismatch were rejected by CCR1(+/+) recipients but were accepted permanently by CCR1(-/-) recipients. Second, CCR1(-/-) mice rejected completely class I- and class II-mismatched BALB/c cardiac allografts more slowly than control mice. Third, levels of cyclosporin A that had marginal effects in CCR1(+/+) mice resulted in permanent allograft acceptance in CCR1(-/-) recipients. These latter allografts showed no sign of chronic rejection 50-200 days after transplantation, and transfer of CD4(+) splenic T cells from these mice to naive allograft recipients significantly prolonged allograft survival, whereas cells from CCR1(+/+) mice conferred no such benefit. Finally, both CCR1(+/+) and CCR1(-/-) allograft recipients, when treated with a mAb to CD4, showed permanent engraftment, but these allografts showed florid chronic rejection in the former strain and were normal in CCR1(-/-) mice. We conclude that therapies to block CCR1/ligand interactions may prove useful in preventing acute and chronic rejection clinically.
2,332,724
Comparative analgesic and cardiopulmonary effects of bupivacaine and ropivacaine in the epidural space of the conscious dog.
To compare the cardiopulmonary effects and sensory blockade of epidural bupivacaine and ropivacaine.</AbstractText>Prospective randomized study.</AbstractText>Six young adult medium-sized crossbred dogs weighing 25.7 &#xb1; 7.1 kg.</AbstractText>Dogs were chronically implanted with a lumbosacral epidural catheter. Acepromazine sedated dogs received all treatments: 0.5% bupivacaine at 0.14 mL kg-1</sup> (LB5) or 0.22 mL kg-1</sup> (HB5); 0.5% ropivacaine at 0.14 mL kg-1</sup> (LR5) or 0.22 mL kg-1</sup> (HR5); 0.75% bupivacaine at 0.22 mL kg-1</sup> (HB7.5) or 0.75% ropivacaine at 0.22 mL kg-1</sup> (HR7.5). Loss of sensation was tested at the level of the perineum, hind toe webs, flank, and caudodorsal rib areas before injection, and post-injection (PI) up to 150 minutes PI. Systemic arterial blood pressure and heart rate were recorded before injection, and every 10 minutes PI until 150 minutes PI. Arterial blood gas analyses were performed prior to injection, and at 30, 60 and 150 minutes PI.</AbstractText>No statistical differences existed between groups for the cardiopulmonary data or time to onset of block. Group HR7.5 had lower systolic (10-70 minutes PI) and diastolic (10-70 minutes PI) blood pressures and group HR5 had lower mean (10-90 minutes PI) and diastolic (10-90 minutes PI) blood pressures compared to baseline. Heart rate was lower compared to baseline in groups LR5 and HB7.5. A significant, but mild metabolic acidosis developed in groups LR5 and HB7.5 (150 minutes PI). No differences were present for the duration of block between groups, but duration of block in the dorsocaudal rib area was shorter in group HR5 compared to HR7.5.</AbstractText>Epidural ropivacaine and bupivacaine at the doses used have mild effects on the cardiopulmonary system, and extent of block are similar.</AbstractText>The 0.75% concentration of bupivacaine and ropivacaine at 0.22 mL kg-1</sup> appeared to contribute to greater success of block (&gt;80%) at dermatomes L5</sub>-L7</sub>.</AbstractText>Copyright &#xa9; 2000 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.</CopyrightInformation>
2,332,725
Cellular and in vivo electrophysiological effects of dronedarone in normal and postmyocardial infarcted rats.
We studied the effects of dronedarone (SR 33589) on the action potentials, membrane ionic currents, and arrhythmic activity in control rats and in rats after myocardial infarction, a model known to develop anomalous electrical activity. Dronedarone increased action potential duration in normal hearts. It had little effect on the action potentials that were already prolonged in the postmyocardial infarcted (PMI) rats. Particularly, dronedarone reduced the late sustained K(+) current, I(K) (or Isus) by 69%. Dronedarone induced only a tonic block of I(K). Similar relative inhibitions of I(K) by dronedarone were obtained in young, sham, and PMI rats, even if I(K) was less in sham than in young and further reduced in PMI rats. The EC(50) values were 0.78 and 0.85 microM in sham and PMI rats. Dronedarone induced a weak increase in the fast transient outward current, I(to). Time-to-peak and inactivation time constant of I(to) were decreased by dronedarone that also induced a marked slowing of I(to) recovery from inactivation. Similar effects were observed on the reduced I(to) recorded in PMI rats. Holter monitoring study in control, unthetered animals showed that dronedarone had no proarrhythmic effect. On rats, which after myocardial infarction exhibited ventricular premature beats, dronedarone significantly decreased beat occurrence during the 7-day treatment; this effect was sustained for two more weeks. Thus, dronedarone exerts antiarrhythmic effects on PMI rat heart. Its effects are attributable for the most part to the inhibition of outward K(+) currents and the increase in effective refractory period.
2,332,726
Caudal bupivacaine vs bupivacaine plus tramadol in post-operative analgesia in children.
Caudal analgesia with bupivacaine is used commonly for pain relief in children and extradural administration of tramadol seemed to be a safe method of analgesia. The aim of the study is to compare the analgesic efficacy of caudal bupivacaine and bupivacaine and tramadol mixture for postoperative analgesia and to observe for side effects.</AbstractText>Forty children, aged between 1- 6 years undergoing infra umbilical surgeries were selected for this randomized, control trial. They were randomly divided into two groups. Group A (n = 20) received 0.5 ml/kg of 0.25 % bupivacaine and Group B (n = 20) received 0.5 ml/kg of 0.25 % bupivacaine with 1 mg/kg of tramadol as a single shot caudal block. In the postoperative period heart rate, respiratory rate, pain score, recovery to first analgesic time, total number of analgesics required in 24 hours and side effects were noted and analyzed.</AbstractText>It was observed that the mean duration of pain relief was significantly longer in Group B (8.8 hrs Vs 7 hrs). Nausea and vomiting was observed in 25% of the patients in group B and 20 % of the patients in group A. None of the patients in both the groups had complication like motor weakness, urinary retention in the postoperative period.</AbstractText>The addition of tramadol to bupivacaine in the caudal analgesic technique provides longer analgesia and lesser need for rescue analgesic in the postoperative period compared to bupivacaine.</AbstractText>
2,332,727
Acute cardiac toxicity of nerium oleander/indicum poisoning (kaner) poisoning.
We present a case of oleander leaf extract poisoning manifested by vomiting, lightheadedness, and heart block. Practicing physicians should understand the potential lethal properties of oleander and its availability throughout the world.
2,332,728
Sex, drugs, and cognition: effects of marijuana.
Despite the knowledge that many drugs affect men and women differently, few studies exploring the effects of marijuana use on cognition have included women. Findings from both animal and human studies suggest marijuana may have more marked effects in women. This study examined sex differences in the acute effects of marijuana on cognition in 70 (n=35 male, 35 female) occasional users of marijuana. Tasks were chosen to tap a wide variety of cognitive domains affected by sex and/or marijuana including attention, cognitive flexibility, time estimation, and visuospatial processing. As expected, acute marijuana use impaired performance on selective and divided attention, time estimation, and cognitive flexibility. While there did not appear to be sex differences in marijuana's effects on cognition, women requested to discontinue the smoking session more often than men, likely leading to an underestimation of differences. Further study of psychological differences in marijuana's effects on men and women following both acute and residual effects of marijuana is warranted.
2,332,729
[Computer simulations of pacemaker shift in the sinoatrial node].<Pagination><StartPage>1132</StartPage><EndPage>1137</EndPage><MedlinePgn>1132-7</MedlinePgn></Pagination><Abstract><AbstractText>The initiation and propagation of electrical pulses in the sinoatrial node under normal conditions and after the application of acetylcholine have been simulated. It has been found that normally a single or a few leading centers are formed in the tissue. When acetylcholine is applied, a temporary functional block of conduction may appear; the leading center migrates under these conditions.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Siuniaev</LastName><ForeName>R A</ForeName><Initials>RA</Initials></Author><Author ValidYN="Y"><LastName>Aliev</LastName><ForeName>R R</ForeName><Initials>RR</Initials></Author></AuthorList><Language>rus</Language><PublicationTypeList><PublicationType UI="D004740">English Abstract</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Russia (Federation)</Country><MedlineTA>Biofizika</MedlineTA><NlmUniqueID>0372666</NlmUniqueID><ISSNLinking>0006-3029</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>N9YNS0M02X</RegistryNumber><NameOfSubstance UI="D000109">Acetylcholine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000109" MajorTopicYN="N">Acetylcholine</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003198" MajorTopicYN="N">Computer Simulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006329" MajorTopicYN="Y">Heart Conduction System</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="Y">Heart Rate</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008955" MajorTopicYN="Y">Models, Cardiovascular</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012849" MajorTopicYN="N">Sinoatrial Node</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2011</Year><Month>1</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2011</Year><Month>1</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2011</Year><Month>3</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">21268360</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">21254643</PMID><DateCompleted><Year>2011</Year><Month>02</Month><Day>17</Day></DateCompleted><DateRevised><Year>2011</Year><Month>01</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">1728-2985</ISSN><JournalIssue CitedMedium="Print"><Issue>5</Issue><PubDate><Year>2010</Year><Season>Sep-Oct</Season></PubDate></JournalIssue><Title>Urologiia (Moscow, Russia : 1999)</Title><ISOAbbreviation>Urologiia</ISOAbbreviation></Journal>[Sympathic hyperactivity and reservoir function of the bladder in men].
The initiation and propagation of electrical pulses in the sinoatrial node under normal conditions and after the application of acetylcholine have been simulated. It has been found that normally a single or a few leading centers are formed in the tissue. When acetylcholine is applied, a temporary functional block of conduction may appear; the leading center migrates under these conditions.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Siuniaev</LastName><ForeName>R A</ForeName><Initials>RA</Initials></Author><Author ValidYN="Y"><LastName>Aliev</LastName><ForeName>R R</ForeName><Initials>RR</Initials></Author></AuthorList><Language>rus</Language><PublicationTypeList><PublicationType UI="D004740">English Abstract</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Russia (Federation)</Country><MedlineTA>Biofizika</MedlineTA><NlmUniqueID>0372666</NlmUniqueID><ISSNLinking>0006-3029</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>N9YNS0M02X</RegistryNumber><NameOfSubstance UI="D000109">Acetylcholine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000109" MajorTopicYN="N">Acetylcholine</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003198" MajorTopicYN="N">Computer Simulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006329" MajorTopicYN="Y">Heart Conduction System</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="Y">Heart Rate</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008955" MajorTopicYN="Y">Models, Cardiovascular</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012849" MajorTopicYN="N">Sinoatrial Node</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2011</Year><Month>1</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2011</Year><Month>1</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2011</Year><Month>3</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">21268360</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">21254643</PMID><DateCompleted><Year>2011</Year><Month>02</Month><Day>17</Day></DateCompleted><DateRevised><Year>2011</Year><Month>01</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">1728-2985</ISSN><JournalIssue CitedMedium="Print"><Issue>5</Issue><PubDate><Year>2010</Year><Season>Sep-Oct</Season></PubDate></JournalIssue><Title>Urologiia (Moscow, Russia : 1999)</Title><ISOAbbreviation>Urologiia</ISOAbbreviation></Journal><ArticleTitle>[Sympathic hyperactivity and reservoir function of the bladder in men].</ArticleTitle><Pagination><StartPage>57</StartPage><EndPage>61</EndPage><MedlinePgn>57-61</MedlinePgn></Pagination><Abstract>Effects of the sympathetic nervous system (SNS) on detrusor function in the collection phase were studied in 57 men over 50 years of age. Heart rate (HR) was a clinical marker of SNS activity, effective volume of the bladder marked detrusor activity in 34 patients of group 1. The value HR/volume were registered in all voidings for 1-3 days. It was found that enhancement of SNS activity was accompanied by a decline of the reservoir function of the bladder. In HR &lt; 80 and &gt; 100 b/min the differences were significant and reached 56%. Group 2 patients (n = 23) with prostatic adenoma have undergone uroflowmetric monitoring before and after treatment with doxasozine (640 uroflowgrams). The reservoir function of the bladder increased from 111.0 to 151.4 ml (by 36.3%) in response to block of alphal-adrenoreceptors. Thus, SNS plays an essential role in management of detrusor function in the collection phase. Its hyperactivity leads to this phase decifiency. It may be a humoral process mediated by vasoconstriction and disorder of vesical blood flow. The proportion HR/volume shows "sympathetic background" in patients before administration of alpha1-adrenoblockers.
2,332,730
Rami Communicans Nerve Block for the Treatment of Symptomatic Schmorl's Nodes -A Case Report-.
Histologically, Schmorl's nodes are defined as the loss of nuclear material through the cartilage plate, growth plate, and end plate into the vertebral body. Most Schmorl's nodes are asymptomatic, although there are some reports of symptomatic Schmorl's nodes, which should be treated similarly to vertebral compression fractures, with conservative treatment as the first choice. We report the case that we reduced the pain by blocking the ramus communicans nerve in a patient with Schmorl's node.
2,332,731
[A clinical research about the effect of vagus nerve block in cervical part to prevent Oculocardiac Reflex].
To investigate the preventive effect of vagus nerve block in cervical part on Oculocardiac Reflex (OCR).</AbstractText>Case control study. 40 patients undergoing prosthesis of right orbital wall bone fracture were randomly divided into two groups: experiment group (group I) and control group (group II). Both of the group adopted vagus nerve block in cervical part before anesthesia. Group I accepted 1% lidocaine and group II received 0.9% Sodium Chloride. The same anesthesia method was applied on both groups. We recorded the index change of mean arterial pressure (MAP), heart rate (HR) and pulse oxygen saturation (SpO2) before (T(0)) and after vagus nerve block in cervical part 3 min (T(1)), 5 min (T(2)), 10 min (T(3)) and 120 min (T(4)); the changes of MAP and HR when we oppressed the eyeball or drag muscular apparatus; the times of using atropine; adverse reactions and the alteration of Acetylcholine (ACh). Numerical data was carried on statistical analysis processing using the SPSS 13.0. Data among groups were compared by t test and numeration data were compared by chi-square criterion. P-value &lt; 0.05 was considered to be statistically significant.</AbstractText>In group I, we found that heart rate significantly increased after block 3 min to 120 min compared with before block (F = 15.46, P = 0.000); The incidence of OCR was lower, and the incidence of adverse effects in PACU such as nausea and vomiting had statistically significant (&#x3c7;(2) = 8.28, P = 0.004); Content of ACh in group I changed significantly, it was lower after block than before block (t = 2.935, P = 0.003).</AbstractText>Vagus nerve block in cervical part significantly decreased the incidence of OCR and brought into preventive effect.</AbstractText>
2,332,732
The oxime pro-2-PAM provides minimal protection against the CNS effects of the nerve agents sarin, cyclosarin, and VX in guinea pigs.
This study examined whether pro-2-PAM, a pro-drug dihydropyridine derivative of the oxime 2-pralidoxime (2-PAM) that can penetrate the brain, could prevent or reverse the central toxic effects of three nerve agents; sarin, cyclosarin, and VX. The first experiment tested whether pro-2-PAM could reactivate guinea pig cholinesterase (ChE) in vivo in central and peripheral tissues inhibited by these nerve agents. Pro-2-PAM produced a dose-dependent reactivation of sarin- or VX-inhibited ChE in both peripheral and brain tissues, but with substantially greater reactivation in peripheral tissues compared to brain. Pro-2-PAM produced 9-25% reactivation of cyclosarin-inhibited ChE in blood, heart, and spinal cord, but no reactivation in brain or muscle tissues. In a second experiment, the ability of pro-2-PAM to block or terminate nerve agent-induced electroencephalographic seizure activity was evaluated. Pro-2-PAM was able to block sarin- or VX-induced seizures (16-33%) over a dose range of 24-32 mg/kg, but was ineffective against cyclosarin-induced seizures. Animals that were protected from seizures showed significantly less weight loss and greater behavioral function 24 h after exposure than those animals that were not protected. Additionally, brains were free from neuropathology when pro-2-PAM prevented seizures. In summary, pro-2-PAM provided modest reactivation of sarin- and VX-inhibited ChE in the brain and periphery, which was reflected by a limited ability to block or terminate seizures elicited by these agents. Pro-2-PAM was able to reactivate blood, heart, and spinal cord ChE inhibited by cyclosarin, but was not effective against cyclosarin-induced seizures.
2,332,733
Genetic parameters for direct and maternal effects on post-weaning body measurements of Muzaffarnagari sheep in India.
Variance components and genetic parameters were estimated for post-weaning (i.e., at 6, 9, and 12 months of age) body measurements in Muzaffarnagari sheep maintained at the Central Institute for Research on Goats, Makhdoom, Mathura, India over a period of 29 years (1976 through 2004). Records of 2,965 lambs descended from 162 rams and 1,213 ewes were used in the study. Analyses were carried out by REML fitting an animal model and ignoring or including maternal genetic or permanent environmental effects. Six different animal models were fitted for all traits. The best model was chosen after testing the improvement of the log-likelihood values. Direct heritability estimates were inflated substantially for all traits when maternal effects were ignored. Moderate estimates of direct heritability for body length (0.11-0.15), height at withers (0.14-0.19), and heart girth (0.14-0.24) of lambs were observed at post-weaning stages of growth. Results suggest that only direct additive genetic effects were important for body measurements at post-weaning stages of growth, and hence, modest rates of genetic progress were possible for post-weaning body measurements.
2,332,734
Endoscopic left sympathetic blockade in the treatment for dilated cardiomyopathy.<Pagination><StartPage>685</StartPage><EndPage>690</EndPage><MedlinePgn>685-90</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0066-782X2010005000152</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">The level of sympathetic nervous activity is a major determinant of prognosis in patients with heart failure.</AbstractText><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">The purpose of this investigation was to perform a proof-of-principle trial of therapeutic endoscopic left thoracic sympathetic blockade in heart failure patients to assess safety and immediate effects.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">Fifteen patients with dilated cardiomyopathy and left ventricular ejection fraction (LVEF) &lt; 40%, New York Heart Association functional class II or III, and heart rate &gt; 65 bpm, despite either adequate betablocker use or intolerant to it, were enrolled. Ten patients underwent left infra-stellate ganglion plus T3-T4 interspinal space clipping through videothoracoscopy, while the other five patients were randomized to a control group.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">None of the treated patients had any procedure-related adverse cardiovascular events at the perioperative period. Two patients from the surgical group died due to pulmonary thromboembolism or myocardial infarction within 6 months of the initial follow-up, while three patients from the control group had heart failure progression and died or developed cardiogenic shock during the same period. Treated patients presented improvement in quality of life, level of physical activity and LVEF (from 25 &#xb1; 9% to 32 &#xb1; 8%, p=0.024) at 6 months of follow-up, whereas these parameters did not change in control patients.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Endoscopic left thoracic sympathetic blockade is feasible and appears to be safe in severe heart failure patients. This initial study suggests that this procedure might be an effective alternative approach to sympathetic blockade in the treatment of dilated cardiomyopathies.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>P&#xea;go-Fernandes</LastName><ForeName>Paulo M</ForeName><Initials>PM</Initials><AffiliationInfo><Affiliation>Instituto do Cora&#xe7;&#xe3;o do Hospital das Cl&#xed;nicas da Faculdade de Medicina da Universidade de S&#xe3;o Paulo, S&#xe3;o Paulo, SP - Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moreira</LastName><ForeName>Luiz Felipe P</ForeName><Initials>LF</Initials></Author><Author ValidYN="Y"><LastName>Souza</LastName><ForeName>Germano Em&#xed;lio C</ForeName><Initials>GE</Initials></Author><Author ValidYN="Y"><LastName>Bacal</LastName><ForeName>Fernando</ForeName><Initials>F</Initials></Author><Author ValidYN="Y"><LastName>Bocchi</LastName><ForeName>Edimar Alcides</ForeName><Initials>EA</Initials></Author><Author ValidYN="Y"><LastName>Stolf</LastName><ForeName>Noedir Ant&#xf4;nio G</ForeName><Initials>NA</Initials></Author><Author ValidYN="Y"><LastName>Jatene</LastName><ForeName>F&#xe1;bio Biscegli</ForeName><Initials>FB</Initials></Author></AuthorList><Language>eng</Language><Language>por</Language><Language>spa</Language><PublicationTypeList><PublicationType UI="D017426">Clinical Trial, Phase I</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016449">Randomized Controlled Trial</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2010</Year><Month>11</Month><Day>19</Day></ArticleDate></Article><MedlineJournalInfo><Country>Brazil</Country><MedlineTA>Arq Bras Cardiol</MedlineTA><NlmUniqueID>0421031</NlmUniqueID><ISSNLinking>0066-782X</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D001340" MajorTopicYN="N">Autonomic Nerve Block</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002311" MajorTopicYN="N">Cardiomyopathy, Dilated</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013233" MajorTopicYN="N">Stellate Ganglion</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013318" MajorTopicYN="N">Stroke Volume</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013562" MajorTopicYN="N">Sympathectomy</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName><QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013564" MajorTopicYN="N">Sympathetic Nervous System</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020775" MajorTopicYN="N">Thoracic Surgery, Video-Assisted</DescriptorName><QualifierName UI="Q000295" MajorTopicYN="N">instrumentation</QualifierName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016277" MajorTopicYN="N">Ventricular Function, Left</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2010</Year><Month>4</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2010</Year><Month>8</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2010</Year><Month>11</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2010</Year><Month>11</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2011</Year><Month>8</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">21085758</ArticleId><ArticleId IdType="doi">10.1590/s0066-782x2010005000152</ArticleId><ArticleId IdType="pii">S0066-782X2010005000152</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">21085098</PMID><DateCompleted><Year>2010</Year><Month>12</Month><Day>17</Day></DateCompleted><DateRevised><Year>2021</Year><Month>10</Month><Day>20</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1940-087X</ISSN><JournalIssue CitedMedium="Internet"><Issue>44</Issue><PubDate><Year>2010</Year><Month>Oct</Month><Day>30</Day></PubDate></JournalIssue><Title>Journal of visualized experiments : JoVE</Title><ISOAbbreviation>J Vis Exp</ISOAbbreviation></Journal>Performing and processing FNA of anterior fat pad for amyloid.
Historically, heart, liver, and kidney biopsies were performed to demonstrate amyloid deposits in amyloidosis. Since the clinical presentation of this disease is so variable and non-specific, the associated risks of these biopsies are too great for the diagnostic yield. Other sites that have a lower biopsy risk, such as skin or gingival, are also relatively invasive and expensive. In addition, these biopsies may not always have sufficient amyloid deposits to establish a diagnosis. Fat pad aspiration has demonstrated good clinical correlation with low cost and minimal morbidity. However, there are no standardized protocols for performing this procedure or processing the aspirated specimen, which leads to variable and nonreproducible results. The most frequently utilized modality for detecting amyloid in tissue is an apple-green birefringence on Congo red stained sections using a polarizing microscope. This technique requires cell block preparation of aspirated material. Unfortunately, patients presenting in early stage of amyloidosis have minimal amounts of amyloid which greatly reduces the sensitivity of Congo red stained cell block sections of fat pad aspirates. Therefore, ultrastructural evaluation of fat pad aspirates by electron microscopy should be utilized, given its increased sensitivity for amyloid detection. This article demonstrates a simple and reproducible procedure for performing anterior fat pad aspiration for the detection of amyloid utilizing both Congo red staining of cell block sections and electron microscopy for ultrastructural identification.
2,332,735
[Comparison of the influences of continuous femoral nerve block and patient controlled intravenous analgesia on total knee arthroplasty].
To assess the influences of continuous femoral nerve block (CFNB) and patient-controlled intravenous analgesia (PCIA) on postoperative pain scores,knee rehabilitation,and stress response after total knee arthroplasty (TKA).</AbstractText>Totally 32 adult patients scheduled for elective total knee arthroplasty were equally randomized into CFNB group or PCIA group. Intraoperative hemodynamics and fentanyl dose were recorded. Pain was assessed at rest and during continuous passive motion (CPM) using a visual analog scale at post-anesthesia care unit (PACU) and 4, 8, 12, 24, and 48 hours postoperatively. Morphine consumption was also recorded. As indicators of stress and inflammatory response,the leukocyte count, serum lactic acid, blood glucose, serum C-reactive protein (CRP), and serum cortisol were determined on admission, to operation room, immediately after skin incision, before extubation,on post-operation day 1 (POD1), and on POD2.</AbstractText>CFNB group showed significantly lower heart rate compared with PCIA group 60 minutes and 90 minutes intraoperatively (P&#xfc;0.05). Intraoperative consumption of fentanyl was significantly lower in CFNB group (137.5&#x2213;44.4) &#x3bc;g than in PCIA group (264.1&#x2213;67.1) &#x3bc;g (P&#xfc;0.01). The CFNB group showed significantly lower VAS scores both at rest and during CPM compared with PCIA group at all time points (P&#xfc;0.05). Morphine consumption was significantly lower in CFNB group than in PCIA group at different time points (P&#xfc;0.05 or P&#xfc;0.01). The maximal continuous passive motion amplitude of CFNB group were significantly larger than that of PCIA group on POD1 [(55.0&#x2213;9.4) vs.(44.6&#x2213;9.9), P[(76.3&#x2213;11.0) vs. (67.5&#x2213;10.3), P&lt;0.05]. The incidences of somnolence and nausea/vomiting in CFNB group were 37.5% and 37.5%, respectively,which were significantly lower than those of PCIA group (75.0% and 81.3%) (P&#xfc;0.05). Patient satisfaction scores on anesthesia and post-operative analgesia was significantly higher in CFNB group than in PCIA group (93.1&#x2213;7.9 vs. 79.1&#x2213;11.9, respectively) (P&#xfc;0.05).</AbstractText>After TKA,CFNB technique provides more stable intraoperative hemodynamics than PCIA, with better pain relief,faster postoperative knee rehabilitation,less side effects,and higher patient satisfaction.</AbstractText>
2,332,736
[Anesthesia in a patient with Ellis-van Creveld syndrome].
Ellis-van Creveld syndrome is a rare type of developmental chondroectodermal dysplasia. We report the case of a 32-year-old woman with this syndrome who was scheduled for cesarean section. She had no related heart defect. A spinal block was attempted but after confirming that no sensory blockade had been achieved, general anesthesia was administered. Both the operation and the anesthetic procedure were without complications. The clinical manifestations of Ellis-van Creveld syndrome are short-limbed dwarfism, postaxial polydactyly, fingernail dysplasia, cleft palate and lips, and heart defects. Diagnosis is based on clinical manifestations and radiography. Treatment involves correction of heart defects and orthopedic problems. Perioperative airway management problems may develop. A preoperative echocardiogram should be done to assess heart function and ascertain anatomical abnormalities. Thoracic deformities may make mechanical ventilation difficult and there is risk of barotrauma. Intraoperative management requires rapid control of the airway and prevention of bronchial aspiration. Vigilance in preventing hemodynamic instability and myocardial depression is essential. Postoperative analgesia must be managed carefully and adverse cardiorespiratory events avoided.
2,332,737
Scavenger receptors and their potential as therapeutic targets in the treatment of cardiovascular disease.
Scavenger receptors act as membrane-bound and soluble proteins that bind to macromolecular complexes and pathogens. This diverse supergroup of proteins mediates binding to modified lipoprotein particles which regulate the initiation and progression of atherosclerotic plaques. In vascular tissues, scavenger receptors are implicated in regulating intracellular signaling, lipid accumulation, foam cell development, and cellular apoptosis or necrosis linked to the pathophysiology of atherosclerosis. One approach is using gene therapy to modulate scavenger receptor function in atherosclerosis. Ectopic expression of membrane-bound scavenger receptors using viral vectors can modify lipid profiles and reduce the incidence of atherosclerosis. Alternatively, expression of soluble scavenger receptors can also block plaque initiation and progression. Inhibition of scavenger receptor expression using a combined gene therapy and RNA interference strategy also holds promise for long-term therapy. Here we review our current understanding of the gene delivery by viral vectors to cells and tissues in gene therapy strategies and its application to the modulation of scavenger receptor function in atherosclerosis.
2,332,738
Differences in posture-movement changes induced by repetitive arm motion in healthy and shoulder-injured individuals.
Neck/Shoulder pain is linked to movement repetition, awkward postures, prolonged maintenance of static postures, and muscular fatigue. Studies have examined the influence of pain and fatigue on movement characteristics, but few reported multi-dimensional adaptations to movement repetition. We compared the adaptations measured in three-dimensions during a repetitive reaching task in persons with chronic neck/shoulder pain and healthy subjects.</AbstractText>A shoulder-injured group (intensity &gt;3/10, duration &gt;3 consecutive months) and an age-sex-matched control group (n=16 in each) performed a repetitive reaching task to voluntary termination. Kinematics, kinetics, heart rate and muscle activity were recorded throughout. Power output on a 10-s pushing/pulling task was assessed pre- and post-reaching. Group comparisons were made in absolute time and at task end.</AbstractText>Control subjects performed the task 55% longer than the pain group; yet, both groups demonstrated task-related increased heart rate (6 beats per minute) and decreased power output (6 W). Throughout the task, the pain group demonstrated: higher supraspinatus activity, and less elbow flexion and endpoint movement. The control group increased movement amplitude of the endpoint, elbow, and shoulder, while the pain group moved the shoulder less and increased center of mass excursion to maintain the task.</AbstractText>Both groups adapted to the task in unique ways. The control group continually increased elbow and endpoint range of motion, bringing the arm closer to the targets, possibly to prolong task performance. The pain group used a fixed, en block arm strategy, likely to reduce the load on the injured structures; however, this may place other structures at risk for pain and injury.</AbstractText>Copyright &#xa9; 2010 Elsevier Ltd. All rights reserved.</CopyrightInformation>
2,332,739
Thoracic epidural anesthesia and analgesia during the perioperative period of thoracic surgery: levobupivacaine versus bupivacaine.
To compare the effects of thoracic epidural anesthesia with levobupivacaine or bupivacaine on block features, intraoperative hemodynamics, and postoperative analgesia for thoracic surgery.</AbstractText>A prospective, randomized, and double-blind study.</AbstractText>A university hospital.</AbstractText>Fifty patients undergoing thoracic surgery.</AbstractText>Patients received thoracic epidural catheterization either with levobupivacaine or bupivacaine. A bolus of 0.1 mL/kg of 0.25% levobupivacaine or 0.25% bupivacaine was administered, and infusion of the same drug with 0.25% concentration was started at 0.1 mL/kg/h. General anesthesia was induced after assessing the sensory block and maintained with 0.3% to 0.8% isoflurane and 50% O(2) in air. Epidural patient-controlled analgesia with the same agent was started at the end of the operation for 48 hours postoperatively.</AbstractText>Sensory block features such as onset time and spread were assessed for the next 20 minutes after the bolus dose. Heart rate and systolic, diastolic, and mean arterial blood pressures were recorded intraoperatively and postoperatively. Pain at rest and activity was evaluated by the visual analog scale (VAS) for 48 hours after the operation. All patients were comparable with respect to the demographic data. Onset time of the block and the number of blocked dermatomes and hemodynamic parameters were similar in both groups. All VAS assessments were comparable between groups except VAS at the 36th hour postoperative, which was higher in the levobupivacaine group (p = 0.039).</AbstractText>Thoracic epidural anesthesia with either levobupivacaine or bupivacaine provided comparable sensory block features, intraoperative hemodynamics, and postoperative analgesia for thoracic surgery.</AbstractText>Copyright &#xa9; 2011 Elsevier Inc. All rights reserved.</CopyrightInformation>
2,332,740
Quantification and identification of mitochondrial proteins containing vicinal dithiols.
Vicinal dithiols may play a role in mitochondrial antioxidant defences and in redox signalling. We quantified protein vicinal dithiols within mammalian mitochondria using the vicinal dithiol-specific reagent phenylarsine oxide (PAO). We found 5-15% of thiols exposed on mitochondrial proteins were vicinal dithiols and that these thiols were particularly sensitive to oxidation by hydrogen peroxide. To visualise these proteins we used PAO to block vicinal dithiols, followed by alkylation of other thiols with N-ethylmaleimide (NEM). The PAO was then removed with 2,3-dimercapto-1-propanesulfonic acid (DMPS) and the exposed vicinal dithiols were labelled with iodoacetamide-biotin. To identify these proteins, we developed a selective proteomic methodology, based on Redox difference in gel electrophoresis (Redox-DIGE). Vicinal dithiol proteins were selectively labelled with a red fluorescent thiol-reactive Cy5 maleimide and mixed with Cy3 maleimide labelled protein in which vicinal dithiols remained untagged. Individual proteins were resolved by 2D gel electrophoresis and fluorescent scanning revealed vicinal dithiol proteins by the increase in Cy5 red fluorescence. These proteins were identified by peptide mass fingerprinting and mass spectrometry. These findings are consistent with roles for mitochondrial vicinal dithiol proteins in antioxidant defence and redox signalling and these methodologies will enable these roles to be explored.
2,332,741
Role of surface protein SasG in biofilm formation by Staphylococcus aureus.
The SasG surface protein of Staphylococcus aureus has been shown to promote the formation of biofilm. SasG comprises an N-terminal A domain and repeated B domains. Here we demonstrate that SasG is involved in the accumulation phase of biofilm, a process that requires a physiological concentration of Zn(2+). The B domains, but not the A domain, are required. Purified recombinant B domain protein can form dimers in vitro in a Zn(2+)-dependent fashion. Furthermore, the protein can bind to cells that have B domains anchored to their surface and block biofilm formation. The full-length SasG protein exposed on the cell surface is processed within the B domains to a limited degree, resulting in cleaved proteins of various lengths being released into the supernatant. Some of the released molecules associate with the surface-exposed B domains that remain attached to the cell. Studies using inhibitors and mutants failed to identify any protease that could cause the observed cleavage within the B domains. Extensively purified recombinant B domain protein is very labile, and we propose that cleavage occurs spontaneously at labile peptide bonds and that this is necessary for biofilm formation.
2,332,742
Addition of low-dose morphine to intrathecal bupivacaine/sufentanil labour analgesia: A randomised controlled study.
Single-shot spinal analgesia with bupivacaine and a short-acting opioid for labour pain is popular due to its simplicity, rapid onset, and profound analgesia without significant motor block. Its limitation is the short duration of action. Supplementation with intrathecal morphine has been shown to prolong analgesia. We compared the addition of placebo or morphine 50 or 100 &#x3bc;g to intrathecal bupivacaine and sufentanil to evaluate the impact on duration of labour analgesia.</AbstractText>Following ethics committee approval and verbal and written patient consent, 90 healthy nulliparous women were included in the study. As part of a combined spinal-epidural technique, women were randomised to receive intrathecal bupivacaine 1.25mg and sufentanil 5 &#x3bc;g with morphine 50 &#x3bc;g, 100 &#x3bc;g or saline placebo in a double-blind fashion. Onset of analgesia was measured as the time from intrathecal injection to a visual analogue scale pain score &lt; or =4 (scale 0-10) and the duration of analgesia as the time from intrathecal injection to the return of pain &gt;4.</AbstractText>No significant differences between the groups were seen in onset or duration of analgesia, side effects or obstetric and neonatal outcome.</AbstractText>The addition of 50 or 100 &#x3bc;g morphine to 1.25mg bupivacaine and 5 &#x3bc;g sufentanil during established labour did not significantly increase the duration of analgesia.</AbstractText>Copyright &#xa9; 2010 Elsevier Ltd. All rights reserved.</CopyrightInformation>
2,332,743
How different two almost identical action potentials can be: a model study on cardiac repolarization.
Spatial heterogeneity in the properties of ion channels generates spatial dispersion of ventricular repolarization, which is modulated by gap junctional coupling. However, it is possible to simulate conditions in which local differences in excitation properties are electrophysiologically silent and only play a role in pathological states. We use a numerical procedure on the Luo-Rudy phase 1 model of the ventricular action potential (AP1) in order to find a modified set of model parameters which generates an action potential profile (AP2) almost identical to AP1. We show that, although the two waveforms elicited from resting conditions as a single AP are very similar and belong to membranes sharing similar passive electrical properties, the modified membrane generating AP2 is a weaker current source than the one generating AP1, has different sensitivity to up/down-regulation of ion channels and to extracellular potassium, and a different electrical restitution profile. We study electrotonic interaction of AP1- and AP2- type membranes in cell pairs and in cable conduction, and find differences in source-sink properties which are masked in physiological conditions and become manifest during intercellular uncoupling or partial block of ion channels, leading to unidirectional block and spatial repolarization gradients. We provide contour plot representations that summarize differences and similarities. The present report characterizes an inverse problem in cardiac cells, and strengthen the recently emergent notion that a comprehensive characterization and validation of cell models and their components are necessary in order to correctly understand simulation results at higher levels of complexity.
2,332,744
HIV protease inhibitors elicit volume-sensitive Cl- current in cardiac myocytes via mitochondrial ROS.
HIV protease inhibitors (HIV PI) reduce morbidity and mortality of HIV infection but cause multiple untoward effects. Because certain HIV PI evoke production of reactive oxygen species (ROS) and volume-sensitive Cl(-) current (I(Cl,swell)) is activated by ROS, we tested whether HIV PI stimulate I(Cl,swell) in ventricular myocytes. Ritonavir and lopinavir elicited outwardly rectifying Cl(-) currents under isosmotic conditions that were abolished by the selective I(Cl,swell)-blocker DCPIB. In contrast, amprenavir, nelfinavir, and raltegravir, an integrase inhibitor, did not modulate I(Cl,swell) acutely. Ritonavir also reduced action potential duration, but amprenavir did not. I(Cl,swell) activation was attributed to ROS because ebselen, an H(2)O(2) scavenger, suppressed ritonavir- and lopinavir-induced I(Cl,swell). Major ROS sources in cardiomyocytes are sarcolemmal NADPH oxidase and mitochondria. The specific NADPH oxidase inhibitor apocynin failed to block ritonavir- or lopinavir-induced currents, although it blocks I(Cl,swell) elicited by osmotic swelling or stretch. In contrast, rotenone, a mitochondrial e(-) transport inhibitor, suppressed both ritonavir- and lopinavir-induced I(Cl,swell). ROS production was measured in HL-1 cardiomyocytes with C-H(2)DCFDA-AM and mitochondrial membrane potential (&#x394;&#x3a8;(m)) with JC-1. Flow cytometry confirmed that ritonavir and lopinavir but not amprenavir, nelfinavir, or raltegravir augmented ROS production, and HIV PI-induced ROS production was suppressed by rotenone but not NADPH oxidase blockade. Moreover, ritonavir, but not amprenavir, depolarized &#x394;&#x3a8;(m). These data suggest ritonavir and lopinavir activated I(Cl,swell) via mitochondrial ROS production that was independent of NADPH oxidase. ROS-dependent modulation of I(Cl,swell) and other ion channels by HIV PI may contribute to some of their actions in heart and perhaps other tissues.
2,332,745
Efficacy of bupivacaine-neostigmine and bupivacaine-tramadol in caudal block in pediatric inguinal herniorrhaphy.
Limited duration of analgesia is among the limitations of single caudal injection with local anesthetics. Therefore, the purpose of this study was to evaluate the effectiveness and safety of bupivacaine in combination with either neostigmine or tramadol for caudal block in children undergoing inguinal herniorrhaphy.</AbstractText>In a double-blinded randomized trial, sixty children undergoing inguinal herniorrhaphy were enrolled to receive a caudal block with either 0.25% bupivacaine (1 ml x kg(-1)) with neostigmine (2 microg x kg(-1)) (group BN) or tramadol (1 mg x kg(-1)) (group BT). Hemodynamic variables, pain and sedation scores, additional analgesic requirements, and side effects were compared between two groups.</AbstractText>Duration of analgesia was longer in group BT (17.30 +/- 8.24 h) compared with group BN (13.98 +/- 10.03 h) (P = 0.03). Total consumption of rescue analgesic was significantly lower in group BT compared with group BN (P = 0.04). There were no significant differences in heart rate, mean arterial pressure, and oxygen saturation between groups. Adverse effects excluding the vomiting were not observed in any patients.</AbstractText>In conclusion, tramadol (1 mg x kg(-1)) compared with neostigmine (2 microg x kg(-1)) might provide both prolonged duration of analgesia and extended time to first analgesic in caudal block.</AbstractText>
2,332,746
Post-operative analgesia following total knee arthroplasty: comparison of low-dose intrathecal morphine and single-shot ultrasound-guided femoral nerve block: a randomized, single blinded, controlled study.
Total knee arthroplasty often results in marked postoperative pain. A recent meta-analysis supports the use of femoral nerve block or alternatively spinal injection of morphine plus local anaesthetic for post-operative analgesia. On the other hand, the use of intrathecal morphine may be associated with a large number of distressing side effects (itching, urinary retention, nausea and vomiting, delayed respiratory depression). The aim of this study was to compare the effectiveness of femoral nerve block and low dose intrathecal morphine in post-operative analgesia after primary unilateral total knee arthroplasty.</AbstractText>Fifty-two consecutive patients scheduled for primary unilateral total knee arthroplasty were allocated to the intrathecal morphine group (ITM group) or to the femoral nerve block group (FNB group). In ITM group a subarachnoid puncture was performed at the L3-L4 inter-vertebral space with hyperbaric bupivacaine 15 mg plus 100 mcg of preservative-free morphine. Patients allocated to the FNB group received a single-injection ultrasound-assisted femoral nerve block with ropivacaine 0.75% 25 ml before the spinal injection of hyperbaric bupivacaine 15 mg. All patients received postoperative patient-controlled-analgesia (PCA) morphine, using a 1-mg bolus and a 5-minute lockout period. Data were analyzed using Student t test or two-way analysis of variance (ANOVA) for repeated measures with time and treatment as the 2 factors. Post hoc comparisons were performed by Bonferroni test. Statistical significance for all test was a p value &lt; 0.05.</AbstractText>Patient characteristics were similar between the 2 groups. We found a statistically significant differences in postoperative pain between the two groups: ITM group had the lower visual analogic pain score (VAS) values. Morphine consumption was lower in the ITM group: average consumption within the first 6 hours was 0.9 mg in IT group compared to 3.1 mg in FNB group; at 12 h 4.2 mg vs 6.3 mg; at 24 h 6.9 mg vs 10.3 mg; at 48 h 9.7 mg vs 13.6 mg. However, the difference in the opiate consumption was not statistically different (p value = 0.06). Thirteen patients in ITM group experienced itching, only 5 in FNB group. We did not find any difference in the two treatment groups in the use of antiemetic and antipruritic medication. No cases of respiratory depression was recorded.</AbstractText>Our results show that low dose of intrathecal morphine may be safe and more efficient than single-shot femoral nerve block for post-operative analgesia after total knee arthroplasty.</AbstractText>
2,332,747
Transplantation in Hungary--preface on the occasion of Transplantation Proceedings becoming the official journal of the Hungarian Transplantation Society.
The first, long-term successful kidney transplantation happened 37 years ago in Hungary. At the same time an organized renal program was initiated followed by transplantations of other solid organs. The authors remember previous milestone operations and the preceding events. In 1982, Hungary was the first country in the Eastern block to introduce cyclosporine. After the Iron Curtain fell new circumstances and possibilities opened for the transplant community also. Young transplant surgeons were sent to Western countries returning with new experiences. In 1992 the heart transplantation program started in Budapest. The Universities of Debrecen and P&#xe9;cs joined Budapest and Szeged with renal transplant programs. In 1994, a new Department was initiated at Semmelweis University with an immediate increase of 50%. The next year a liver transplantation program was launched. Pancreas transplants were performed in 1998 in P&#xe9;cs, followed by Budapest. In 2003, a collaboration was initiated between Geneva and Budapest for islet transplantation and another with Vienna for lung transplantation. This article provides an overview of Hungarian transplant activities.
2,332,748
[Effect of yiqi huoxue recipe containing drug-serum on the Toll-Iike receptor-4 and its downstream signaling components MyD88 as well as the tumor necrosis factor receptor related factor-6 in human vein endothelial cells].
To investigate the influence of Yiqi Huoxue Recipe (YHR) containing drug-serum on the expression of Toll-like receptor-4 (TLR4) and its downstream signaling components MyD88, as well as the tumor necrosis factor receptor related factor-6 (TRAF-6) in human vein endothelial cells (HUVECs) induced by lipopolysaccharide (LPS), and to study its possible anti-atherosclerotic mechanism from the gene and protein levels.</AbstractText>Twenty New Zealand male rabbits were equally divided into four groups in random: the normal control group and the three YHR groups, 5 in each group. They were gastric perfused daily with normal saline and YHR in low, moderate and high concentration respectively. Blood drawn from rabbits' heart 2 h after ending perfusion on the 7th day, and the serum separated (that is the drug-serum) was taken for testing. HUVECs were cultured in vitro and equally divided into six groups in random: the normal control group, the model group, the Western medicine group and the three YHR groups. HUVECs were stimulated with LPS, then treated separately with the drug-serum containing different concentrations of YHR for 24 h. Then the mRNA expressions of TLR4, MyD88 and TRAF-6 were measured with Real-time PCR, and their protein expressions were analyzed using Western blotting.</AbstractText>Protein and mRNA expressions of TLR4, MyD88 and TRAF-6 increased significantly after LPS stimulation (P &lt; 0.01), but the changes in the drug-serum treated groups were significantly lower than those in the saline control group respectively (P &lt; 0.01 or P &lt; 0.05).</AbstractText>YHR can block the high expression of TLR4, and also influence the MyD88-dependent signaling pathway of TLR4, suppress the downstream expression of NF-kappaB and various related gene expressions, which may be one of its mechanisms of action for anti-atherosclerosis.</AbstractText>
2,332,749
Activation of reverse Na+-Ca2+ exchange by the Na+ current augments the cardiac Ca2+ transient: evidence from NCX knockout mice.
The hypothesis that Na(+) influx during the action potential (AP) activates reverse Na(+)-Ca(2+) exchange (NCX) and subsequent entry of trigger Ca(2+) is controversial. We tested this hypothesis by monitoring intracellular Ca(2+) before and after selective inactivation of I(Na) prior to a simulated action potential in patch-clamped ventricular myocytes isolated from adult wild-type (WT) and NCX knockout (KO) mice. First, we inactivated I(Na) using a ramp prepulse to 45 mV. In WT cells, inactivation of I(Na) decreased the Ca(2+) transient amplitude by 51.1 +/- 4.6% (P &lt; 0.001, n = 14) and reduced its maximum release flux by 53.0 +/- 4.6% (P &lt; 0.001, n = 14). There was no effect on diastolic Ca(2+). In striking contrast, Ca(2+) transients in NCX KO cardiomyocytes were unaffected by the presence or absence of I(Na) (n = 8). We obtained similar results when measuring trigger Ca(2+) influx in myocytes with depleted sarcoplasmic reticulum. In WT cells, inactivation of I(Na) decreased trigger Ca(2+) influx by 37.8 +/- 6% and maximum rate of flux by 30.6 +/- 7.7% at 2.5 mm external Ca(2+) (P &lt; 0.001 and P &lt; 0.05, n = 9). This effect was again absent in the KO cells (n = 8). Second, exposure to 10 mum tetrodotoxin to block I(Na) also reduced the Ca(2+) transients in WT myocytes but not in NCX KO myocytes. We conclude that I(Na) and reverse NCX modulate Ca(2+) release in murine WT cardiomyocytes by augmenting the pool of Ca(2+) that triggers ryanodine receptors. This is an important mechanism for regulation of Ca(2+) release and contractility in murine heart.
2,332,750
Caudal epidural block in children: comparison of needle insertion parallel with caudal canal versus conventional two-step technique.
This study compared the technique of inserting the needle for caudal epidural blockade in a single pass parallel to the caudal canal versus the conventional technique of approaching the caudal canal with the needle at a steeper angle. Seventy-five patients, aged 0 to 72 months, scheduled for urological surgery were prospectively enrolled in this study. Patients were randomly divided into two groups: a conventional method group (caudal block performed with conventional needle insertion, n=40) and a new method group (needle inserted into the skin at an angle of 200 and into the caudal space without redirection, n=35). Two anaesthetists (A, B) performed the caudal blocks. For anaesthetist A, the mean time required (standard deviation) to perform needle insertion in the conventional method group was 2.2 (0.8) minutes and in the new method group 1.1 (0.7) minutes (P = 0.03). For anaesthetist B the mean time (standard deviation) to perform needle insertion in the conventional method group was 2.1 (1.1) minutes and in the new method group 1.3 (0.8) minutes (P = 0.04). Successful block was considered as first pass placement of the needle in the caudal canal confirmed (after placement) by ultrasound imaging, and the absence of a bloody tap. Subcutaneous placement of the needle after the first attempt occurred in two cases in the conventional method group and three cases in the new method group. Bloody tap occurred in four cases, all in the conventional method group and none in the new method group. When required, the second pass was successful in all cases.
2,332,751
The changes of heart rate variability after unilateral stellate ganglion block.
The effect of the unilateral stellate ganglion block (SGB) on cardiovascular regulation remains controversial. We wished to evaluate the changes in heart rate variability (HRV) after a unilateral stellate ganglion block in patients with head and neck pain in the present study.</AbstractText>Patients with head and neck pain (n = 89) were studied. HRV was determined before and after a C6 unilateral stellate ganglion block (right-sided SGB, 40; left-sided SGB, 49) using a paratracheal technique with 1% mepivacaine (6 ml).</AbstractText>There were no significant differences in HRV indices before and after right-sided SGB. The log scale of power in the high frequency range (lnHF) was increased and ratio of power in the low frequency range (LF) to power in the high frequency range (HF) ratio was decreased after left-sided SGB.</AbstractText>These results demonstrated that left-sided SGB increased parasympathetic activities in patients with head and neck pain.</AbstractText>
2,332,752
Effect of ramosetron on shivering during spinal anesthesia.
Shivering associated with spinal anesthesia is uncomfortable and may interfere with monitoring. The aim of this study is to evaluate the effect of ramosetron, a serotonin-3 receptor antagonist, on the prevention of shivering during spinal anesthesia.</AbstractText>We enrolled 52 patients who were ASA I or II and who had undergone knee arthroscopy under spinal anesthesia. Warmed (37 degrees ) lactated Ringer's solution was infused over 15 minutes before spinal anesthesia. Patients were randomly allocated to a control group (group S, N = 26) or study group (group R, N = 26). Spinal anesthesia was performed with a 25-G Quincke-type spinal needle between the lumbar 3-4 interspace with 2.2 ml 0.5% hyperbaric bupivacaine. For patients allocated in groups S and R, 2 ml 0.9% saline and 0.3 mg ramosetron, respectively, was intravenously injected immediately before intrathecal injection at identical times. Shivering and spinal block levels were assessed immediately after the completion of subarachnoid injection, as well as 5, 10, 15, 20, 25, 30, 60, and 120 minutes after spinal anesthesia. Systolic and diastolic blood pressures, heart rate, and peripheral oxygen saturation were also recorded. Core temperatures were measured by tympanic thermometer and recorded before and during spinal anesthesia at 30-minute intervals.</AbstractText>Shivering was observed in 2 patients in group R and 9 patients in group S (P = 0.038, odds ratio = 6.14, 95% C.I. = 1.08-65.5). The difference in core temperature between the groups was not significant.</AbstractText>Compared to control, ramosetron is an effective way to prevent shivering during spinal anesthesia.</AbstractText>
2,332,753
BAFF mediates splenic B cell response and antibody production in experimental Chagas disease.
B cells and antibodies are involved not only in controlling the spread of blood circulating Trypanosoma cruzi, but also in the autoreactive manifestations observed in Chagas disease. Acute infection results in polyclonal B cell activation associated with hypergammaglobulinemia, delayed specific humoral immunity and high levels of non-parasite specific antibodies. Since TNF superfamily B lymphocyte Stimulator (BAFF) mediates polyclonal B cell response in vitro triggered by T. cruzi antigens, and BAFF-Tg mice show similar signs to T. cruzi infected mice, we hypothesized that BAFF can mediate polyclonal B cell response in experimental Chagas disease.</AbstractText><AbstractText Label="METHODOLOGY/PRINCIPAL FINDINGS" NlmCategory="RESULTS">BAFF is produced early and persists throughout the infection. To analyze BAFF role in experimental Chagas disease, Balb/c infected mice were injected with BR3:Fc, a soluble receptor of BAFF, to block BAFF activity. By BAFF blockade we observed that this cytokine mediates the mature B cell response and the production of non-parasite specific IgM and IgG. BAFF also influences the development of antinuclear IgG and parasite-specific IgM response, not affecting T. cruzi-specific IgG and parasitemia. Interestingly, BAFF inhibition favors the parasitism in heart.</AbstractText><AbstractText Label="CONCLUSIONS/SIGNIFICANCE" NlmCategory="CONCLUSIONS">Our results demonstrate, for the first time, an active role for BAFF in shaping the mature B cell repertoire in a parasite infection.</AbstractText>
2,332,754
First analysis of a bacterial collagen-binding protein with collagen Toolkits: promiscuous binding of YadA to collagens may explain how YadA interferes with host processes.
The Yersinia adhesin YadA mediates the adhesion of the human enteropathogen Yersinia enterocolitica to collagens and other components of the extracellular matrix. Though YadA has been proposed to bind to a specific site in collagens, the exact binding determinants for YadA in native collagen have not previously been elucidated. We investigated the binding of YadA to collagen Toolkits, which are libraries of triple-helical peptides spanning the sequences of type II and III human collagens. YadA bound to many of them, in particular to peptides rich in hydroxyproline but with few charged residues. We were able to block the binding of YadA to collagen type IV with the triple-helical peptide (Pro-Hyp-Gly)(10), suggesting that the same site in YadA binds to triple-helical regions in network-forming collagens as well. We showed that a single Gly-Pro-Hyp triplet in a triple-helical peptide was sufficient to support YadA binding, but more than six triplets were required to form a tight YadA binding site. This is significantly longer than the case for eukaryotic collagen-binding proteins. YadA-expressing bacteria bound promiscuously to Toolkit peptides. Promiscuous binding could be advantageous for pathogenicity in Y. enterocolitica and, indeed, for other pathogenic bacteria. Many of the tightly binding peptides are also targets for eukaryotic collagen-binding proteins, and YadA was able to inhibit the interaction between selected Toolkit peptides and platelets. This leads to the intriguing possibility that YadA may interfere in vivo with host processes mediated by endogenous collagen-binding proteins.
2,332,755
Comparison of spinal, low-dose spinal and epidural anesthesia with ropivacaine plus fentanyl for transurethral surgical procedures.
The aim of This study was to compare spinal, low-dose spinal, and epidural anesthesia using ropivacaine and fentanyl combinations for transurethral surgical procedures. Sixty patients with American Society of Anesthesiologists scores of I-III were allocated into three groups. After pre- loading with 5 mL/kg normal saline, patients in the spinal anesthesia group (Group S) received 15 mg of hyperbaric ropivacaine plus 25 microg of fentanyl intrathecally; patients in the epidural anesthesia group (Group E) received 112.5 mg of ropivacaine plus 25 microg of fentanyl epidurally via an epidural catheter; and patients in the low-dose spinal anesthesia group (Group L) received 10 mg of hyperbaric ropivacaine plus 25 microg of fentanyl intrathecally. Blood pressure, heart rate, peripheral oxygen saturation, time to onset of thoracic (T)-10 dermatome, two-segment sensorial block regression time, full recovery of sensorial block, maximum motor blockade levels, motor blockade regression time, additional analgesic administration, patient comfort, and complications were recorded. The time to the onset of T10 dermatome level was shortest in Group S and longest in Group E (p &lt; 0.001). The sensorial blockade time and motor blockade regression time were shorted in Group L (p &lt; 0.001). The two-segment sensorial block regression time in Group E exceeded that in the other groups. Additional analgesic administration was not needed in any group. No complications or adverse effects were observed in any patient. We conclude that all three anesthetic techniques may be used safely and are appropriate for transurethral surgical procedures. However, low-dose spinal anesthesia with ropivacaine plus fentanyl may be preferable in transurethral surgery because we reach an adequate sensorial level with less motor blockade.
2,332,756
Levobupivacaine-tramadol combination for caudal block in children: a randomized, double-blinded, prospective study.
The aim of this prospective study was to compare the postoperative analgesic efficacy and duration of analgesia after caudal levobupivacaine 0.125% or caudal tramadol 1.5 mg.kg(-1) and mixture of both in children undergoing day-case surgery.</AbstractText>Sixty-three American Society of Anesthesiologists (ASA) I or II children between 1 and 7 years old scheduled for inguinal hernia repair under sevoflurane anesthesia were randomized to receive caudal levobupivacaine 0.125% (group L), caudal tramadol 1.5 mg.kg(-1) (group T) or mixture of both (group LT) (total volume of caudal solution was 1 ml.kg(-1)). Duration of analgesia and requirement for additional analgesics were noted. Postoperative pain was evaluated using the Children's and Infants' Postoperative Pain Scale (CHIPPS) every 15 min for the first hour, and after 2, 3, 4, 6, 12, and 24 h. Analgesia was supplemented whenever pain score was &gt; or =4.</AbstractText>No patient experienced significant intraoperative hemodynamic response to surgical incision. Duration of analgesia was significantly longer in group LT than in group L and group T (545 +/- 160 min vs 322 +/- 183 min and 248 +/- 188 min, respectively) (P &lt; 0.01). There were no significant differences between the group L and group T for duration of analgesia (P &gt; 0.05). There were no significant differences among the groups in the number of patients requiring analgesia after operation (P = 0.7). No signs of motor block were observed after the first postoperative hour in any of the patients.</AbstractText>Addition of tramadol increased the duration of analgesia produced by caudal levobupivacaine in children.</AbstractText>
2,332,757
MicroRNAs and the regulation of fibrosis.
MicroRNAs (miRNAs) are small, noncoding RNAs of 18-25 nucleotides that are generally believed to either block the translation or induce the degradation of target mRNA. miRNAs have been shown to play fundamental roles in diverse biological and pathological processes, including cell proliferation, differentiation, apoptosis and carcinogenesis. Fibrosis results from an imbalance in the turnover of extracellular matrix molecules and is a highly debilitating process that can eventually lead to organ dysfunction. A growing body of evidence suggests that miRNAs participate in the fibrotic process in a number of organs including the heart, kidney, liver and lung. In this review, we summarize our current understanding of the role of miRNAs in the development of tissue fibrosis and their potential as novel drug targets.
2,332,758
Local adenosine receptor blockade accentuates the sympathetic responses to fatiguing exercise.
The role adenosine plays in evoking the exercise pressor reflex in humans remains controversial. We hypothesized that localized forearm adenosine receptor blockade would attenuate muscle sympathetic nerve activity (MSNA) responses to fatiguing handgrip exercise in humans. Blood pressure (Finometer), heart rate, and MSNA from the peroneal nerve were assessed in 11 healthy young volunteers during fatiguing isometric handgrip, postexercise circulatory occlusion (PECO), and passive muscle stretch during PECO. The protocol was performed before and after adenosine receptor blockade by local infusion of 40 mg aminophylline in saline via forearm Bier block (regional intravenous anesthesia). In the second experiment, the same amount of saline was infused via the Bier block. After aminophylline, the MSNA and blood pressure responses to fatiguing handgrip, PECO, and passive stretch (all P &lt; 0.05) were significantly greater than during the control condition. Saline Bier block had no similar effects on the MSNA and blood pressure responses. These data suggest that adenosine receptor antagonism in the exercising muscles may accentuate sympathetic activation during fatiguing exercise.
2,332,759
Usurping the mitochondrial supremacy: extramitochondrial sources of reactive oxygen intermediates and their role in beta cell metabolism and insulin secretion.
Insulin secretion from pancreatic beta cells is a process dependent on metabolism. While oxidative stress is a well-known inducer of beta cell toxicity and impairs insulin secretion, recent studies suggest that low levels of metabolically-derived reactive oxygen intermediates (ROI) also play a positive role in insulin secretion. Glucose metabolism is directly correlated with ROI production, particularly in beta cells in which glucose uptake is proportional to the extracellular concentration of glucose. Low levels of exogenously added ROI or quinones, which stimulate ROI production, positively affect insulin secretion, while antioxidants block insulin secretion, suggesting that ROI activate unidentified redox-sensitive signal transduction components within these cells. The mitochondria are one source of ROI: increased metabolic flux increases mitochondrial membrane potential resulting in electron leakage and adventitious ROI production. A second source of ROI are cytosolic and plasma membrane oxidoreductases which oxidize NAD(P)H and directly produce ROI through the reduction of molecular oxygen. The mechanism of ROI-mediated potentiation of insulin secretion remains an important topic for future study.
2,332,760
Peripheral blockade as treatment of arm ischaemia at birth.
Limbs ischaemia represents a rare event during the neonatal period. The present paper reports an unusual case of precocious arm ischemia that occurred immediately after birth and successfully treated with a peripheral nerve blockade.</AbstractText>Peripheral nerve blockade resulted in an effective and safe therapeutic approach able to allow the salvaging of the limbs.</AbstractText>
2,332,761
Ganglionic transmission in a vasomotor pathway studied in vivo.
Intracellular recordings were made in vivo from 40 spontaneously active cells in the third lumbar sympathetic ganglion of urethane-anaesthetized rats. In 38/40 cells ongoing action potentials showed strong cardiac rhythmicity (93.4 +/- 1.9% modulation) indicating high barosensitivity and probable muscle vasoconstrictor (MVC) function. Subthreshold excitatory postsynaptic potentials (EPSPs) showed the same pattern. The 38 barosensitive neurons fired action potentials at 2.9 +/- 0.3 Hz. All action potentials were triggered by EPSPs, most of which were unitary events. Calculations indicated that &lt;5% of action potentials were triggered by summation of otherwise subthreshold EPSPs. 'Dominant' synaptic inputs with a high safety factor were identified, confirming previous work. These were active in 24/38 cells and accounted for 32% of all action potentials; other ('secondary') inputs drove the remainder. Inputs (21 dominant, 19 secondary) attributed to single preganglionic neurons fired at 1.38 +/- 0.16 Hz. An average of two to three preganglionic neurons were estimated to drive each ganglion cell's action potentials. When cells were held hyperpolarized to block spiking, a range of spontaneous EPSP amplitudes was revealed. Threshold equivalent was defined as the membrane potential value that was exceeded by spontaneous EPSPs at the same frequency as the cell's original firing rate. In 10/12 cells examined, a continuum of EPSP amplitudes overlapped threshold equivalent. Small changes in cell excitability could therefore raise or lower the percentage of preganglionic inputs triggering action potentials. The results indicate that vasoconstrictor ganglion cells in vivo mostly behave not as 1:1 relays, but as continuously variable gates.
2,332,762
Prolonged pharmacodynamic effects of S-0139, an intravenously administered endothelin A (ET) antagonist, in the human forearm blood flow model.
To estimate the pharmacologically active dose range of a new investigational compound S-0139, a selective endothelin A (ET(A)) receptor antagonist, in man, and to examine the duration of its pharmacodynamic effect.</AbstractText>Venous occlusion plethysmography was performed to assess changes in forearm blood flow following intra-brachial administration of endothelin-1 (ET-1). ET(A) antagonists have been shown to block ET-1-induced vasoconstriction in this model. The study was conducted in three parts: (1) a pilot study to explore dose-response (dose range 0.08-13.33 microg kg(-1) min(-1)), (2) a randomized study to confirm dose-response (placebo, 2.5, 6.67 and 15 microg kg(-1) min(-1)), and (3) a delayed administration study (15.7 microg kg(-1) min(-1)) to explore the duration of the pharmacodynamic effect. In all studies a 3-h infusion of S-0139 was given and during the last 90 min of the infusion, ET-1 was infused concurrently for 90 min. In study (3) a second ET-1 infusion was given starting 3 h after completion of the first.</AbstractText>Intravenously administered S-0139 resulted in significant inhibition of ET-1-induced vasoconstriction in the forearm (plasma concentration 800-2000 ng ml(-1)). In the delayed administration study, the same extent of inhibition was still present when ET-1 was administered 3 h after the end of infusion of S-0139, even though the S-0139 plasma concentrations (mean 17 ng ml(-1)) were well below pharmacologically active concentrations as determined in studies 1 and 2.</AbstractText>S-0139 dose-dependently blocks ET-1-mediated vasoconstriction in the forearm and has a prolonged duration of effect beyond that expected from its pharmacokinetic profile.</AbstractText>
2,332,763
Comparison of combined spinal and general anesthesia block and combined epidural and general anesthesia block in laparoscopic cholecystectomy.
Combined spinal and general anesthesia block (CSGAB) and combined epidural and general anesthesia block (CEGAB) in laparoscopic cholecystectomy were compared.</AbstractText>Forty patients were randomly selected (ASA physical status I-II) to receive sevoflurane plus 10 to 15 mg of bupivacaine weighed at 0.5% and 20 microg of fentanyl (CSGAB) or sevoflurane plus 150 mg of ropivacaine and 1 microg/kg of fentanyl (CEGAB). Blood pressure, heart rate, oxygen and carbon dioxide saturation, drug doses and sevoflurane MAC (minimum alveolar concentration) were evaluated during surgery. Anesthesia recovery time and pain intensity and duration were evaluated during the first two postoperative hours. Frequency of incisional or referred pain, dyspnea, headache, cramping, nausea and vomiting were evaluated 24 hours after surgery. Statistical analysis was carried out using the Chi-square test and Student t test. Relative risk, absolute risk reduction and number needed to treat (NNT) for adverse reactions were determined.</AbstractText>Systolic and diastolic arterial pressures posterior to semi-Fowler's position were lower in the CSGAB group than in the CEGAB group. (94 +/- 16 vs. 110 +/- 18 mmHg; p &lt; 0.01 and 59 +/- 8 vs. 69 +/- 12, mmHg; p &lt; 0.01, respectively). Anesthesia recovery time (32 +/- 17 vs. 61 +/- 29 minutes; p &lt; 0.01) and pain duration (26 +/- 42 vs. 83 +/- 46 minutes; p &lt; 0.01) were shorter in the CSGAB group. NNT was 8 for postoperative pain, 8 for nausea, and 95 for vomiting.</AbstractText>CSGAB was more efficacious for rapid anesthesia recovery and had a shorter post-operative pain duration than CEGAB.</AbstractText>
2,332,764
A novel surgical approach to impacted mandibular third molars to reduce the risk of paresthesia: a case series.
Extraction of impacted mandibular third molars (M3s) may cause temporary or permanent neurosensorial disturbances of the inferior alveolar nerve (IAN). Although the incidence of this complication is low, a great range of variability has been reported in the literature. Several methods to reduce or eliminate this complication have been proposed, such as orthodontic-assisted extraction, extraction of the second molar, or intentional odontoectomy. The purpose of this series of cases is to present a novel approach for a riskless extraction of impacted mandibular M3s in contact with the IAN.</AbstractText>Nine consecutive patients (4 male and 5 female; mean age 24.9 years, range 18-43 years) required the extraction of 10 horizontally or mesioangular impacted mandibular M3s. In all cases the M3 was in contact with the IAN with a high risk of nerve injury. A staged approached was proposed and accepted by the patients. This approach consisted in the surgical removal of the mesial portion of the anatomic crown to create adequate space for mesial M3 migration. After the migration of the M3 had taken place, the extraction could then be accomplished in a second surgical session minimizing neurological risks.</AbstractText>All M3s moved mesially within 6 months (mean 174.1 days, range 92-354 days) and could be successfully removed without any neurological consequences.</AbstractText>This technique may be considered as an alternative approach to the extraction of horizontally or mesioangular impacted M3s in proximity to the IAN.</AbstractText>Copyright 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
2,332,765
Clinical comparison of 12 mg ropivacaine and 8 mg bupivacaine, both with 20 microg fentanyl, in spinal anaesthesia for major orthopaedic surgery in geriatric patients.
The aim of this study was to compare the haemodynamic and anaesthetic effects of 12 mg ropivacaine and 8 mg bupivacaine, both with 20 microg fentanyl, in spinal anaesthesia for major orthopaedic surgery in geriatric patients.</AbstractText>Sixty American Society of Anesthesiologists (ASA) II-III patients scheduled for hip arthroplasty were randomly assigned to receive an intrathecal injection of either 12 mg ropivacaine with 20 microg fentanyl (group R, aged 70 +/- 7 years, range 67-89) or 8 mg hyperbaric bupivacaine with 20 microg fentanyl (group B, aged 69 +/- 6 years, range 66-92). Motor and sensory block, haemodynamics and side effects were recorded.</AbstractText>Mean levels of sensory block were similar, but the onset time of sensory block in group B (2.52 +/- 0.69 min) was shorter than that in group R (3.17-0.72 min); the difference was statistically significant (p &lt; 0.01), and the number of patients who had motor Bromage scale 3 in group B (24) was greater than in group R (16). The difference was also statistically significant (p &lt; 0.05). Systolic and diastolic arterial pressures (SAP, DAP) and heart rate (HR) decreased after the block in both groups. SAP (after the 60th and 120th min of block), DAP (all measurement times), and HR (after the 20th, 25th and 30th min of block) were lower in group B than in group R.</AbstractText>The data showed that 12 mg of ropivacaine and 8 mg of bupivacaine with 20 microg fentanyl in spinal anaesthesia can provide sufficient motor and sensory block for major orthopaedic surgery in geriatric patients. However, ropivacaine caused less motor block and haemodynamic side effects than bupivacaine during the procedure.</AbstractText>Copyright 2010 S. Karger AG, Basel.</CopyrightInformation>
2,332,766
Increased interstitial loading reduces the effect of microstructural variations in cardiac tissue.
Electrical propagation in diseased and aging hearts is strongly influenced by structural changes that occur in both the intracellular and interstitial spaces of cardiac tissue; however, very few studies have investigated how interactions between the two spaces affect propagation at the microscale. In this study, we used one-dimensional microstructural computer models of interconnected ventricular myocytes to systematically investigate how increasing the effective interstitial resistivity (rho(oeff)) influences action potential propagation in fibers with variations in intracellular properties such as cell coupling and cell length. Changes in rho(oeff) were incorporated into a monodomain model using a correction to the intracellular properties that was based on bidomain simulations. The results showed that increasing rho(oeff) in poorly coupled one-dimensional fibers alters the distribution of electrical load at the microscale and causes propagation to become more continuous. In the poorly coupled fiber, this continuous state is characterized by decreased gap junction delay, sustained conduction velocity, increased sodium current, reduced maximum upstroke velocity, and increased safety factor. Long, poorly coupled cells experience greater loading effects than short cells and show the greatest initial response to changes in rho(oeff). In inhomogeneous fibers with adjacent well-coupled and poorly coupled regions, increasing rho(oeff) in the poorly coupled region also reduces source-load mismatch, which delays the onset of conduction block and reduces the dispersion of repolarization at the transition between the two regions. Increasing the rho(oeff) minimizes the effect of cell-to-cell variations and may influence the pattern of activation in critical regimes characterized by low intercellular coupling, microstructural heterogeneity, and reduced or abnormal membrane excitability.
2,332,767
Association of JAG1 with bone mineral density and osteoporotic fractures: a genome-wide association study and follow-up replication studies.
Bone mineral density (BMD), a diagnostic parameter for osteoporosis and a clinical predictor of fracture, is a polygenic trait with high heritability. To identify genetic variants that influence BMD in different ethnic groups, we performed a genome-wide association study (GWAS) on 800 unrelated Southern Chinese women with extreme BMD and carried out follow-up replication studies in six independent study populations of European descent and Asian populations including 18,098 subjects. In the meta-analysis, rs2273061 of the Jagged1 (JAG1) gene was associated with high BMD (p = 5.27 x 10(-8) for lumbar spine [LS] and p = 4.15 x 10(-5) for femoral neck [FN], n = 18,898). This SNP was further found to be associated with the low risk of osteoporotic fracture (p = 0.009, OR = 0.7, 95% CI 0.57-0.93, n = 1881). Region-wide and haplotype analysis showed that the strongest association evidence was from the linkage disequilibrium block 5, which included rs2273061 of the JAG1 gene (p = 8.52 x 10(-9) for LS and 3.47 x 10(-5) at FN). To assess the function of identified variants, an electrophoretic mobility shift assay demonstrated the binding of c-Myc to the "G" but not "A" allele of rs2273061. A mRNA expression study in both human bone-derived cells and peripheral blood mononuclear cells confirmed association of the high BMD-related allele G of rs2273061 with higher JAG1 expression. Our results identify the JAG1 gene as a candidate for BMD regulation in different ethnic groups, and it is a potential key factor for fracture pathogenesis.
2,332,768
[Minimally invasive surgical treatment with per-pancreat region for sever acute pancreatitis.].<Pagination><StartPage>1464</StartPage><EndPage>1467</EndPage><MedlinePgn>1464-7</MedlinePgn></Pagination><Abstract><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">To investigate the clinical effect of the minimally invasive surgical treatment with per-pancreat region for sever acute pancreatitis (SAP).</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">Fify-four cases of SAP were divided into two groups, patients of group A (n = 28) were given minimally invasive surgical treatments (step 1: under local anesthesia, patients were put the home-made double cannula in the abdominal around the region of pancreas.step 2:patients with biliary stone were performed by laparoscopical operations). Patients of group B (n = 26) were treatment by open operations including biliary decompression, gastrostomy, jejunostomy, removing necrotic pancreatic organizations and puting the double cannula around the region of pancreas. Through double cannula around the pancreas area, all patient's cavity were persistently douched using 0.5% 5-FU saline solution.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Washed after one week, two groups patient's drainage fluid amylase concentration were decreased significantly (t = 2.68, P = 0.013; t = 2.41, P = 0.028), patient's white cell count, body temperature, heart rate of Groups A were also decreased significantly (t = 2.32, P = 0.035; t = 2.39, P = 0.021; t = 2.38, P = 0.023). Compared with group B, the mortality, the incidence of complications, hospitalization time and total cost of treatment of group A patients were significantly lower than that of group B (chi(2) = 8.62, P = 0.001; chi(2) = 6.35, P = 0.014; t = 2.22, P = 0.034; t = 2.67, P = 0.010), but the cure rate was significantly higher than that of group B (chi(2) = 3.89, P = 0.045).</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Minimally invasive surgical treatment of per-pancreatic region for SAP can not only remove the causes, but also fully drainage and timely block the pathological vicious cycle of SAP. What is more, it is simple, minimally invasive and have few complications and significant effect.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Fan</LastName><ForeName>Ying-Fang</ForeName><Initials>YF</Initials><AffiliationInfo><Affiliation>Department of Hepatobiliary Surgery I, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fang</LastName><ForeName>Chi-Hua</ForeName><Initials>CH</Initials></Author><Author ValidYN="Y"><LastName>Deng</LastName><ForeName>Ming-Fu</ForeName><Initials>MF</Initials></Author><Author ValidYN="Y"><LastName>Xiang</LastName><ForeName>Nan</ForeName><Initials>N</Initials></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Jian</ForeName><Initials>J</Initials></Author></AuthorList><Language>chi</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>China</Country><MedlineTA>Zhonghua Wai Ke Za Zhi</MedlineTA><NlmUniqueID>0153611</NlmUniqueID><ISSNLinking>0529-5815</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D004322" MajorTopicYN="N">Drainage</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010535" MajorTopicYN="N">Laparoscopy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019060" MajorTopicYN="Y">Minimally Invasive Surgical Procedures</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010179" MajorTopicYN="N">Pancreas</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010195" MajorTopicYN="Y">Pancreatitis</DescriptorName><QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2010</Year><Month>1</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2010</Year><Month>1</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>4</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">20092759</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">20091662</PMID><DateCompleted><Year>2010</Year><Month>04</Month><Day>16</Day></DateCompleted><DateRevised><Year>2018</Year><Month>12</Month><Day>21</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1469-493X</ISSN><JournalIssue CitedMedium="Internet"><Issue>1</Issue><PubDate><Year>2010</Year><Month>Jan</Month><Day>20</Day></PubDate></JournalIssue><Title>The Cochrane database of systematic reviews</Title><ISOAbbreviation>Cochrane Database Syst Rev</ISOAbbreviation></Journal>Blood pressure lowering efficacy of potassium-sparing diuretics (that block the epithelial sodium channel) for primary hypertension.
To investigate the clinical effect of the minimally invasive surgical treatment with per-pancreat region for sever acute pancreatitis (SAP).</AbstractText>Fify-four cases of SAP were divided into two groups, patients of group A (n = 28) were given minimally invasive surgical treatments (step 1: under local anesthesia, patients were put the home-made double cannula in the abdominal around the region of pancreas.step 2:patients with biliary stone were performed by laparoscopical operations). Patients of group B (n = 26) were treatment by open operations including biliary decompression, gastrostomy, jejunostomy, removing necrotic pancreatic organizations and puting the double cannula around the region of pancreas. Through double cannula around the pancreas area, all patient's cavity were persistently douched using 0.5% 5-FU saline solution.</AbstractText>Washed after one week, two groups patient's drainage fluid amylase concentration were decreased significantly (t = 2.68, P = 0.013; t = 2.41, P = 0.028), patient's white cell count, body temperature, heart rate of Groups A were also decreased significantly (t = 2.32, P = 0.035; t = 2.39, P = 0.021; t = 2.38, P = 0.023). Compared with group B, the mortality, the incidence of complications, hospitalization time and total cost of treatment of group A patients were significantly lower than that of group B (chi(2) = 8.62, P = 0.001; chi(2) = 6.35, P = 0.014; t = 2.22, P = 0.034; t = 2.67, P = 0.010), but the cure rate was significantly higher than that of group B (chi(2) = 3.89, P = 0.045).</AbstractText>Minimally invasive surgical treatment of per-pancreatic region for SAP can not only remove the causes, but also fully drainage and timely block the pathological vicious cycle of SAP. What is more, it is simple, minimally invasive and have few complications and significant effect.</AbstractText>
2,332,769
TNFalpha and its receptors in psoriatic skin, before and after treatment with etanercept.
Psoriasis is a chronic inflammatory skin condition characterized by inflammatory dermal infiltrate and hyperproliferative keratinocytes. The pathogenesis of this disease is mediated by a dysregulation of the innate immunity and cytokine production. Tumor necrosis factor alpha (TNFalpha) is considered the most important cytokine involved in the pathological mechanism of psoriasis. Recently, several therapies have been introduced for the treatment of psoriasis that try to block TNF alpha activity. Among these treatments etanercept is a fusion protein that specifically targets TNF alpha. We performed a study on twelve psoriatic patients aimed at evaluating the effect of etanercept treatment on the production and expression of TNFalpha and its receptors, in lesional and uninvolved psoriatic skin. We demonstrated that after three month of etanercept treatment at 50 mg/wk, TNF, TNF-RI and TNF-RII immunostaining in lesional and non-lesional skin samples of patients was greatly reduced, suggesting that this treatment not only acts on stable lesional plaques, but also at a very early stage of the disease.
2,332,770
Training characteristics of paralympic swimmers.
The ability to monitor training is critical to the process of quantifying training periodization plans, yet weekly patterns of volume and intensity for Paralympic swimmers before competition have not been reported. Sixteen swimmers were monitored prospectively over a 16-week training block constituting 4 training phases (early, mid, late, and taper), before a World Championship. Training volume (total and main set distance) and intensity (percentage of peak heart rate [HR], swimming velocity, and rate of perceived exertion [RPE]) were quantified using an online training diary, and changes in training load were examined over the 4 training phases. For a subgroup of swimmers (n = 12), with similarities in underlying disability, change in performance between Selection Trials and World Championships was also quantified. Substantial increases in total training volume (29.6%) were observed late phase, and main set volume was reduced substantially (24.1%) during the taper phase. Small to moderate increases in training intensity (HR 2.4%, velocity 4.5%, and RPE 6.7%) were observed late phase and maintained through the taper. There were no clear associations between discrete training measures and competition performance. Swimmers competing at the Paralympic level seem to follow traditional periodized patterns of training, similar to those of swimmers at the Olympic level, before competition. Coaches of elite swimmers with a disability should review their prescribed patterns of training before major competition: A more substantial taper (larger reduction in volume) could elicit a greater improvement in performance. Training prescription should account for different disabilities and classes and individual circumstances of elite swimmers with a disability.
2,332,771
Mitochondrial matrix K+ flux independent of large-conductance Ca2+-activated K+ channel opening.
Large-conductance Ca(2+)-activated K(+) channels (BK(Ca)) in the inner mitochondrial membrane may play a role in protecting against cardiac ischemia-reperfusion injury. NS1619 (30 microM), an activator of BK(Ca) channels, was shown to increase respiration and to stimulate reactive oxygen species generation in isolated cardiac mitochondria energized with succinate. Here, we tested effects of NS1619 to alter matrix K(+), H(+), and swelling in mitochondria isolated from guinea pig hearts. We found that 30 microM NS1619 did not change matrix K(+), H(+), and swelling, but that 50 and 100 microM NS1619 caused a concentration-dependent increase in matrix K(+) influx (PBFI fluorescence) only when quinine was present to block K(+)/H(+) exchange (KHE); this was accompanied by increased mitochondrial matrix volume (light scattering). Matrix pH (BCECF fluorescence) was decreased slightly by 50 and 100 microM NS1619 but markedly more so when quinine was present. NS1619 (100 microM) caused a significant leak in lipid bilayers, and this was enhanced in the presence of quinine. The K(+) ionophore valinomycin (0.25 nM), which like NS1619 increased matrix volume and increased K(+) influx in the presence of quinine, caused matrix alkalinization followed by acidification when quinine was absent, and only alkalinization when quinine was present. If K(+) is exchanged instantly by H(+) through activated KHE, then matrix K(+) influx should stimulate H(+) influx through KHE and cause matrix acidification. Our results indicate that KHE is not activated immediately by NS1619-induced K(+) influx, that NS1619 induces matrix K(+) and H(+) influx through a nonspecific transport mechanism, and that enhancement with quinine is not due to the blocking of KHE, but to a nonspecific effect of quinine to enhance current leak by NS1619.
2,332,772
Therapy-related myelodysplastic syndrome presenting as fulminant heart failure secondary to myeloid sarcoma.<Pagination><StartPage>41</StartPage><EndPage>46</EndPage><MedlinePgn>41-6</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s12308-010-0058-4</ELocationID><Abstract><AbstractText>Rapidly progressive heart failure is commonly caused by an extensive myocardial infarction, a mechanical complication of infarction, myocarditis, or acute valvular insufficiency. We present an unusual case that was caused by a diffuse infiltration of the myocardium with leukemic cells (myeloid sarcoma). The patient presented with episodic shortness of breath, he was anemic and thrombocytopenic, and his bone marrow biopsy revealed myelodysplastic syndrome from treatment for oligodendroglioma. His clinical course was characterized by a chronic leak of cardiac enzymes, a new right bundle branch block, and a large pericardial effusion causing tamponade and death from fulminant heart failure and ventricular arrhythmias within 2&#xa0;weeks. At autopsy, the heart was massively infiltrated with myeloblasts and other immature myeloid cells. There was no evidence of acute leukemia in the bone marrow or peripheral blood. Cardiac infiltration in a patient with myelodysplastic syndrome is extremely rare, especially in the absence of bone marrow involvement by blasts. The recognition of this entity is becoming increasingly important as the incidence of cardiac myeloid sarcoma may be on the rise as the number of patients receiving chemotherapy increases.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Matkowskyj</LastName><ForeName>Kristina A</ForeName><Initials>KA</Initials></Author><Author ValidYN="Y"><LastName>Wiseman</LastName><ForeName>William R</ForeName><Initials>WR</Initials></Author><Author ValidYN="Y"><LastName>Robin</LastName><ForeName>Jason C</ForeName><Initials>JC</Initials></Author><Author ValidYN="Y"><LastName>Norvell</LastName><ForeName>John P</ForeName><Initials>JP</Initials></Author><Author ValidYN="Y"><LastName>Puthumana</LastName><ForeName>Jyothy</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Nelson</LastName><ForeName>Beverly</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Peterson</LastName><ForeName>Loann</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>McGarry</LastName><ForeName>Thomas J</ForeName><Initials>TJ</Initials></Author><Author ValidYN="Y"><LastName>Tourtellotte</LastName><ForeName>Warren G</ForeName><Initials>WG</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>K02 NS046468</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>K26 OD010945</GrantID><Acronym>OD</Acronym><Agency>NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>K26 RR026099</GrantID><Acronym>RR</Acronym><Agency>NCRR NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2010</Year><Month>05</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>Germany</Country><MedlineTA>J Hematop</MedlineTA><NlmUniqueID>101491976</NlmUniqueID><ISSNLinking>1865-5785</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Leukemia cordis</Keyword><Keyword MajorTopicYN="N">Myeloid sarcoma</Keyword><Keyword MajorTopicYN="N">Rapidly progressive heart failure</Keyword><Keyword MajorTopicYN="N">Therapy-related myelodysplastic syndrome</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2009</Year><Month>7</Month><Day>9</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2010</Year><Month>4</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2011</Year><Month>5</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2010</Year><Month>1</Month><Day>1</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>1</Month><Day>1</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">21544187</ArticleId><ArticleId IdType="pmc">PMC2883902</ArticleId><ArticleId IdType="doi">10.1007/s12308-010-0058-4</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Traweek ST, Arber DA, Rappaport H, Brynes RK. 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Rapidly progressive heart failure is commonly caused by an extensive myocardial infarction, a mechanical complication of infarction, myocarditis, or acute valvular insufficiency. We present an unusual case that was caused by a diffuse infiltration of the myocardium with leukemic cells (myeloid sarcoma). The patient presented with episodic shortness of breath, he was anemic and thrombocytopenic, and his bone marrow biopsy revealed myelodysplastic syndrome from treatment for oligodendroglioma. His clinical course was characterized by a chronic leak of cardiac enzymes, a new right bundle branch block, and a large pericardial effusion causing tamponade and death from fulminant heart failure and ventricular arrhythmias within 2&#xa0;weeks. At autopsy, the heart was massively infiltrated with myeloblasts and other immature myeloid cells. There was no evidence of acute leukemia in the bone marrow or peripheral blood. Cardiac infiltration in a patient with myelodysplastic syndrome is extremely rare, especially in the absence of bone marrow involvement by blasts. The recognition of this entity is becoming increasingly important as the incidence of cardiac myeloid sarcoma may be on the rise as the number of patients receiving chemotherapy increases.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Matkowskyj</LastName><ForeName>Kristina A</ForeName><Initials>KA</Initials></Author><Author ValidYN="Y"><LastName>Wiseman</LastName><ForeName>William R</ForeName><Initials>WR</Initials></Author><Author ValidYN="Y"><LastName>Robin</LastName><ForeName>Jason C</ForeName><Initials>JC</Initials></Author><Author ValidYN="Y"><LastName>Norvell</LastName><ForeName>John P</ForeName><Initials>JP</Initials></Author><Author ValidYN="Y"><LastName>Puthumana</LastName><ForeName>Jyothy</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Nelson</LastName><ForeName>Beverly</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Peterson</LastName><ForeName>Loann</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>McGarry</LastName><ForeName>Thomas J</ForeName><Initials>TJ</Initials></Author><Author ValidYN="Y"><LastName>Tourtellotte</LastName><ForeName>Warren G</ForeName><Initials>WG</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>K02 NS046468</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>K26 OD010945</GrantID><Acronym>OD</Acronym><Agency>NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>K26 RR026099</GrantID><Acronym>RR</Acronym><Agency>NCRR NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2010</Year><Month>05</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>Germany</Country><MedlineTA>J Hematop</MedlineTA><NlmUniqueID>101491976</NlmUniqueID><ISSNLinking>1865-5785</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Leukemia cordis</Keyword><Keyword MajorTopicYN="N">Myeloid sarcoma</Keyword><Keyword MajorTopicYN="N">Rapidly progressive heart failure</Keyword><Keyword MajorTopicYN="N">Therapy-related myelodysplastic syndrome</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2009</Year><Month>7</Month><Day>9</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2010</Year><Month>4</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2011</Year><Month>5</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2010</Year><Month>1</Month><Day>1</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>1</Month><Day>1</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">21544187</ArticleId><ArticleId IdType="pmc">PMC2883902</ArticleId><ArticleId IdType="doi">10.1007/s12308-010-0058-4</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Traweek ST, Arber DA, Rappaport H, Brynes RK. Extramedullary myeloid cell tumors. An immunohistochemical and morphologic study of 28 cases. Am J Surg Pathol. 1993;17:1011&#x2013;1019. doi: 10.1097/00000478-199310000-00006.</Citation><ArticleIdList><ArticleId IdType="doi">10.1097/00000478-199310000-00006</ArticleId><ArticleId IdType="pubmed">8372941</ArticleId></ArticleIdList></Reference><Reference><Citation>Quintanilla-Martinez L, Zukerberg LR, Ferry JA, Harris NL. Extramedullary tumors of lymphoid or myeloid blasts. The role of immunohistology in diagnosis and classification. Am J Clin Pathol. 1995;104:431&#x2013;443.</Citation><ArticleIdList><ArticleId IdType="pubmed">7572794</ArticleId></ArticleIdList></Reference><Reference><Citation>Comings DE, Fayen AW, Carter P. Myeloblastoma preceeding blood and marrow evidence of acute leukemia. 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BMC Blood Disord. 2006;6:4. doi: 10.1186/1471-2326-6-4.</Citation><ArticleIdList><ArticleId IdType="doi">10.1186/1471-2326-6-4</ArticleId><ArticleId IdType="pmc">PMC1569821</ArticleId><ArticleId IdType="pubmed">16953890</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedBookArticle><BookDocument><PMID Version="1">21452479</PMID><ArticleIdList><ArticleId IdType="bookaccession">NBK53553</ArticleId></ArticleIdList><Book><Publisher><PublisherName>CRC Press/Taylor &amp; Francis</PublisherName><PublisherLocation>Boca Raton (FL)</PublisherLocation></Publisher><BookTitle book="frfatdet">Fat Detection: Taste, Texture, and Post Ingestive Effects</BookTitle><PubDate><Year>2010</Year></PubDate><AuthorList Type="editors" CompleteYN="Y"><Author ValidYN="Y"><LastName>Montmayeur</LastName><ForeName>Jean-Pierre</ForeName><Initials>JP</Initials><AffiliationInfo><Affiliation>Centre National de la Recherche Scientifique, Dijon, France</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>le Coutre</LastName><ForeName>Johannes</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Nestl&#xe9; Research Center, Lausanne, Switzerland</Affiliation></AffiliationInfo></Author></AuthorList><CollectionTitle book="frontcollect">Frontiers in Neuroscience</CollectionTitle><Isbn>9781420067750</Isbn></Book><LocationLabel Type="chapter">Chapter 5</LocationLabel><ArticleTitle book="frfatdet" part="ch5">Peripheral Gustatory Processing of Free Fatty Acids</ArticleTitle><Language>eng</Language><AuthorList Type="authors" CompleteYN="Y"><Author ValidYN="Y"><LastName>Stratford</LastName><ForeName>Jennifer M.</ForeName><Initials>JM</Initials></Author><Author ValidYN="Y"><LastName>Contreras</LastName><ForeName>Robert J.</ForeName><Initials>RJ</Initials></Author></AuthorList><PublicationType UI="D016454">Review</PublicationType><Abstract>It is well known that obesity is a major health problem, with approximately 66% of adults in the United States considered overweight and more than 1 billion overweight adults worldwide (Ogden et al., 2006) (World Health Organization). In addition to the impact on the joints and bones caused by increased body mass, obesity can also lead to heart disease, hypertension, diabetes, and stroke (Wong and Marwick, 2007). Given the severity and consequences of these conditions, it is not surprising that there is a large body of research exploring factors that contribute to the development of obesity, including diet and, more specifically, the proportion of certain foods in the diet. Vilified in the media as &#x201c;Public Enemy Number One in the Battle of the Bulge,&#x201d; dietary fat, and in particular the over consumption of fat, is considered by many to be the greatest contributing factor to obesity. Yet, is fat the enemy? Clearly, high fat ingestion, along with lack of exercise, has the potential to negatively impact a healthy lifestyle. At the same time, however, fats are critical for many biological processes. As the lipid bilayer of cells, fat is a building block for life and, in the form of myelin, enables fast electrical communication between neurons. Fat provides insulation that helps conserve body heat in cold climates and also can protect organs, like those necessary for reproduction, from damage. Fats and the main component of fats, free fatty acids, are essential for the growth and development of vital organs, including the brain (Spector, 2001). Clearly, fat is crucial for life, yet the body cannot synthesize certain kinds of fats. Rather, these fats are obtained from ingested food. Thus, the ability to detect certain kinds of fat in food sources is necessary for survival. Fortunately, there is strong motivation to find and subsequently consume fat because fat is preferred by many animals, including humans. What is it about fat that is so alluring? In the past, the palatability of fat was thought to be the result of smell and/or texture. For example, impairment of the ability to smell (either by bilateral transection of the olfactory nerve or by destruction of the olfactory mucosa with ZnSO<sub>4</sub>) eliminates the preference for high-fat foods in mice (Mela, 1988; Kinney and Antill, 1996). Moreover, increasing the texture of low-fat dairy products also increases the perceived fat content. Interestingly, sensitivity to the texture of fat seems to be related to the number of functional taste buds on the tongue, as people with the greatest number of taste buds (i.e., so-called &#x201c;super tasters&#x201d;) are the best at discriminating between solutions with varying fat contents (Bartoshuk et al., 1994). Moreover, there are even cells in a specialized primate brain area called the orbitofrontal cortex that respond only to the texture of fats (Verhagen et al., 2003). Clearly, smell and texture are important for fat perception. However, rats can discriminate between different kinds of oils that, presumably, have a similar texture and continue to prefer fat solutions when texture and smell are minimized in behavioral tests (Larue, 1978; Fukuwatari et al., 2003). Furthermore, ingested fats are rapidly (within 1&#x2013;5 s) broken down into free fatty acids in the oral cavity by lingual lipase (Kawai and Fushiki, 2003). In fact, rats have a robust preference for free fatty acids; however, prevention of the breakdown of fats into free fatty acids by the addition of a lingual lipase inhibitor greatly reduces rats&#x2019; preference for fat solutions. Thus, fat and in particular the building blocks of fats&#x2014;free fatty acids&#x2014;have a taste component that plays a strong role in our fat preference.
2,332,773
Pain treatment in post-traumatic hip fracture in the elderly: regional block vs. systemic non-steroidal analgesics.
The renin-angiotensin system is a complex biologic system between the heart, brain, blood vessels, and kidneys that leads to the production of biologically active agents, including angiotensin I and II and aldosterone, which act together to impact a variety of bodily functions including blood vessel tone, sodium balance, and glomerular filtration pressure. The multiple and varied effects of these agents allows the renin-angiotensin system to play a wide role in the pathology of hypertension, cardiovascular health, and renal function. Our ability to begin to intervene upon the complex cycle of hormone and other biochemical agent production within the renin-angiotensin system began with the advent of the first orally active ACE-I (angiotensin converting enzyme inhibitor), captopril, in 1981. AIIRAs (angiotensin II receptor blockers) were developed as an alternative to ACE-I, and block the interaction between angiotensin II and the angiotensin receptor. Losartan, the first commercially available AIIRA, was approved for clinical use in 1995. The goal of this report is to compare the effectiveness and harms between aliskiren and placebo and between AIIRAs and ACEIs in the treatment of diagnosed coronary heart disease, hypertension, left ventricular dysfunction, heart failure, nondiabetic chronic kidney disease, or diabetic nephropathy.
2,332,774
[Experiment research of Jiajian Yunvjian granules on hyperthyroidism graves].
To investigate the effects and the related mechanisms of Jiajian Yunujian (JJYNJ) granules, which were made from traditional Chinese medicinal prescription, on hyperthyroidism graves.</AbstractText>Except that in the normal group, all mice were injected 350 mcirog x kg x d(-1) L-Thyroxin sodium to establish the hyperthyroidism graves model. The model mice were divided randomly into model control group, 3 different groups of JJYNJ granules at oral dosage of 2.17, 4.33, 8.66 g x kg(-1), every day and thiamazole group at oral dosage of 10 mg x kg(-1) every day, respectively. The body weight, heart/body weight index, heart rate (HR), spontaneous activity and oxygen consumption of all the mice were measured. The serum T3, T4 levels were evaluated with the method of RIA. Meanwhile, the effect of JJYNJ granules and thiamazole on iodine uptake by thyroid was determined by radio-assay.</AbstractText>JJYNJ granules could improve the symptoms caused by thyroxin, increase body weight (P &lt; 0.05), reduce heart/body weight index, spontaneous activity and oxygen consumption (P &lt; 0.05). The HR of model group was (794.5 +/- 47.8) beats x min(-1), significantly faster than that of normal group (682.5 +/- 116.4) beats x min(-1). Those of low, middle and high JJYNJ granule group were (736.9 +/- 66.6), (742.1 +/- 62.3), (715.8 +/- 102.8) beats x min(-1) respectively, obviously slower than that of model group (P &lt; 0.05). The serum T3, T4 levels of model group were (3.85 +/- 0.960), (234.46 +/- 58.11) microg x L(-1), significantly higher than those of normal group (0.99 +/- 0.30), (65.94 +/- 13.94) microg x L(-1), P &lt; 0.01). Those of middle, high of JJYNJ granule group were (2.57 +/- 0.81), (164.27 +/- 72.63) microg x L(-1) and (2.70 +/- 0.55), (157.26 +/- 35.03) microg x L(-1). Those of thiamazole group were (2.88 +/- 0.59), (172.65 +/- 39.73) miicrog x L(-1). These values were significantly lower than those of model group. Thiamazole could significantly inhibit the iodine uptake in thyroid (P &lt; 0.01), but JJYNJ granules did not block that obviously.</AbstractText>JJYNJ granules could significantly improve the symptoms of experimental hyperthyroidism graves. Its mechanisms may be different from that of thiamazole, which is related to inhibiting the synthesis of thyroxin in thyroid.</AbstractText>
2,332,775
Gold-coated pacemaker implantation after allergic reactions to pacemaker compounds.<Pagination><StartPage>749</StartPage><EndPage>750</EndPage><MedlinePgn>749-50</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1093/europace/eup411</ELocationID><Abstract><AbstractText>An 86-year-old man underwent pacemaker implantation for symptomatic atrio-ventricular block grade 2 Mobitz II. The patient suffered repeated admissions for iterative sterile wound necrosis, leading to two generator re-implantations. No bacterial infection was detected in the microbiological screening tests. The skin patch testing to titanium was negative. Nevertheless, we decided to remove the pacemaker system and to implant a gold-plated generator with polyurethane leads. Since then, there has been no recurrence of wound complications. Gold-plated generator and polyurethane leads are effective in treating allergic reactions to pacemaker system components in selected cases. Negative skin patch testing to titanium does not exclude allergic reaction to this pacemaker component.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Syburra</LastName><ForeName>Thomas</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Cardiac Surgery Division, City Hospital Triemli Zurich, Birmensdorferstrasse 497, CH-8063 Zurich, Switzerland. thomas.syburra@triemli.stzh.ch</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schurr</LastName><ForeName>Ulrich</ForeName><Initials>U</Initials></Author><Author ValidYN="Y"><LastName>Rahn</LastName><ForeName>Mariette</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Graves</LastName><ForeName>Kirk</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Genoni</LastName><ForeName>Michele</ForeName><Initials>M</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2009</Year><Month>12</Month><Day>17</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Europace</MedlineTA><NlmUniqueID>100883649</NlmUniqueID><ISSNLinking>1099-5129</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>7440-57-5</RegistryNumber><NameOfSubstance UI="D006046">Gold</NameOfSubstance></Chemical><Chemical><RegistryNumber>D1JT611TNE</RegistryNumber><NameOfSubstance UI="D014025">Titanium</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000369" MajorTopicYN="N">Aged, 80 and over</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D054537" MajorTopicYN="N">Atrioventricular Block</DescriptorName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006046" MajorTopicYN="Y">Gold</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006967" MajorTopicYN="N">Hypersensitivity</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010138" MajorTopicYN="N">Pacemaker, Artificial</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012882" MajorTopicYN="N">Skin Tests</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014025" MajorTopicYN="N">Titanium</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2009</Year><Month>12</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2009</Year><Month>12</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>9</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">20022879</ArticleId><ArticleId IdType="doi">10.1093/europace/eup411</ArticleId><ArticleId IdType="pii">eup411</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">20020260</PMID><DateCompleted><Year>2010</Year><Month>03</Month><Day>11</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0171-2004</ISSN><JournalIssue CitedMedium="Print"><Issue>196</Issue><PubDate><Year>2010</Year></PubDate></JournalIssue><Title>Handbook of experimental pharmacology</Title><ISOAbbreviation>Handb Exp Pharmacol</ISOAbbreviation></Journal>Molecular mechanisms of adverse drug reactions in cardiac tissue.
An 86-year-old man underwent pacemaker implantation for symptomatic atrio-ventricular block grade 2 Mobitz II. The patient suffered repeated admissions for iterative sterile wound necrosis, leading to two generator re-implantations. No bacterial infection was detected in the microbiological screening tests. The skin patch testing to titanium was negative. Nevertheless, we decided to remove the pacemaker system and to implant a gold-plated generator with polyurethane leads. Since then, there has been no recurrence of wound complications. Gold-plated generator and polyurethane leads are effective in treating allergic reactions to pacemaker system components in selected cases. Negative skin patch testing to titanium does not exclude allergic reaction to this pacemaker component.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Syburra</LastName><ForeName>Thomas</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Cardiac Surgery Division, City Hospital Triemli Zurich, Birmensdorferstrasse 497, CH-8063 Zurich, Switzerland. thomas.syburra@triemli.stzh.ch</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schurr</LastName><ForeName>Ulrich</ForeName><Initials>U</Initials></Author><Author ValidYN="Y"><LastName>Rahn</LastName><ForeName>Mariette</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Graves</LastName><ForeName>Kirk</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Genoni</LastName><ForeName>Michele</ForeName><Initials>M</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2009</Year><Month>12</Month><Day>17</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Europace</MedlineTA><NlmUniqueID>100883649</NlmUniqueID><ISSNLinking>1099-5129</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>7440-57-5</RegistryNumber><NameOfSubstance UI="D006046">Gold</NameOfSubstance></Chemical><Chemical><RegistryNumber>D1JT611TNE</RegistryNumber><NameOfSubstance UI="D014025">Titanium</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000369" MajorTopicYN="N">Aged, 80 and over</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D054537" MajorTopicYN="N">Atrioventricular Block</DescriptorName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006046" MajorTopicYN="Y">Gold</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006967" MajorTopicYN="N">Hypersensitivity</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010138" MajorTopicYN="N">Pacemaker, Artificial</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012882" MajorTopicYN="N">Skin Tests</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014025" MajorTopicYN="N">Titanium</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2009</Year><Month>12</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2009</Year><Month>12</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>9</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">20022879</ArticleId><ArticleId IdType="doi">10.1093/europace/eup411</ArticleId><ArticleId IdType="pii">eup411</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">20020260</PMID><DateCompleted><Year>2010</Year><Month>03</Month><Day>11</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0171-2004</ISSN><JournalIssue CitedMedium="Print"><Issue>196</Issue><PubDate><Year>2010</Year></PubDate></JournalIssue><Title>Handbook of experimental pharmacology</Title><ISOAbbreviation>Handb Exp Pharmacol</ISOAbbreviation></Journal><ArticleTitle>Molecular mechanisms of adverse drug reactions in cardiac tissue.</ArticleTitle><Pagination><StartPage>77</StartPage><EndPage>109</EndPage><MedlinePgn>77-109</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/978-3-642-00663-0_4</ELocationID><Abstract>The myocardium is the target of toxicity for a number of drugs. Based on pharmacological evidence, cellular targets for drugs that produce adverse reactions can be categorized into a number of sites that include the cell membrane-bound receptors, the second messenger system, ionic channels, ionic pumps, and intracellular organelles. Additionally, interference with the neuronal input to the heart can also present a global site where adverse drug effects can manifest themselves. Simply, a drug can interfere with the normal cardiac action by modifying an ion channel function at the plasma membrane level leading to abnormal repolarization and/or depolarization of the heart cells thus precipitating a disruption in the rhythm and causing dysfunction in contractions and/or relaxations of myocytes. It is now recognized that toxic actions of drugs against the myocardium are not exclusive to the antitumor or the so-called cardiac drugs, and many other drugs with diverse chemical structures, such as antimicrobial, antimalarial, antihistamines, psychiatric, and gastrointestinal medications, seem to be capable of severely compromising myocardium function. At present, great emphasis in terms of drug safety is being placed on the interaction of many classes of drugs with the hERG potassium channel in cardiac tissue. The interest in the latter channel stems from the simplified view that drugs that block the hERG potassium channel cause prolongation of the QT interval, and this can cause life-threatening cardiac arrhythmias. Based on the evidence in the current literature, this concept does not seem to always hold true.
2,332,776
Disparate effects on renal and oxidative parameters following RAGE deletion, AGE accumulation inhibition, or dietary AGE control in experimental diabetic nephropathy.
Advanced glycation end products (AGEs) and the receptor for AGEs (RAGE) generate ROS, and therefore this study evaluated the effects of RAGE deletion, decreasing AGE accumulation, or lowering dietary AGE content on oxidative parameters in diabetic nephropathy (DN). Control and diabetic male wild-type and RAGE-deficient (RAGE-/-) mice were fed high- or low-AGE diets, with two groups given the inhibitor of AGE accumulation, alagebrium chloride, and followed for 24 wk. Diabetic RAGE-/- mice were protected against albuminuria, hyperfiltration, glomerulosclerosis, decreased renal mitochondrial ATP production, and excess generation of both mitochondrial and cytosolic superoxide. Whereas glomerulosclerosis, tubulointerstitial expansion, and hyperfiltration were improved in diabetic mice treated with alagebrium, there was no effect on urinary albumin excretion. Both diabetic RAGE-/- and alagebrium-treated mice had an attenuation of renal RAGE expression and decreased renal and urinary AGE (carboxymethyllysine) levels. Low-AGE diets did not confer renoprotection, lower the AGE burden or renal RAGE expression, or improve cytosolic or mitochondrial superoxide generation. Renal uncoupling protein-2 gene expression and mitochondrial membrane potential were attenuated by all therapeutic interventions in diabetic mice. In the present study, diverse approaches to block the AGE-RAGE axis had disparate effects on DN, which has potential clinical implications for the way this axis should be targeted in humans.
2,332,777
Spread of subarachnoid sensory block with hyperbaric bupivacaine in second trimester of pregnancy.
To compare the spread of subarachnoid sensory block with hyperbaric bupivacaine in second trimester pregnant and non-pregnant women.</AbstractText>Prospective study.</AbstractText>University teaching hospital.</AbstractText>44 ASA physical status I and II women patients, 22 of whom were in their second trimester of pregnancy undergoing cervical cerclage, and 22 non-pregnant women scheduled for perianal surgery.</AbstractText>The extent of sensory block and hemodynamic changes were assessed.</AbstractText>Number of dermatomes blocked was determined by testing for pinprick; systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were measured at 3, 5, 10, 15, 30 and 60 minutes.</AbstractText>Maximal sensory block was higher in the second trimester of the pregnant group by three dermatomes than the non-pregnant group. There were no statistically significant differences in SBP, DBP, or HR changes between the groups.</AbstractText>Pregnant women in the second trimester exhibit enhanced spread of spinal analgesia with hyperbaric bupivacaine more so than non-pregnant women.</AbstractText>
2,332,778
Low-dose spinal hyperbaric bupivacaine for adult anorectal surgery: a double-blinded, randomized, controlled study.
To produce selective spinal anesthesia for adult anorectal surgery.</AbstractText>Double-blinded, randomized, controlled trial.</AbstractText>Operating room and postoperative recovery area.</AbstractText>152 adult, consecutive ASA physical status I, II, and III patients.</AbstractText>After patients underwent dural puncture in the sitting position at L3-L4 or L4-L5, 0.5% hyperbaric bupivacaine was injected over two minutes: Group S7.5 received 1.5 mL, Group S5 received 1.0 mL, and Group S4 0.8 mL. After sitting for 10 minutes, patients were positioned for surgery.</AbstractText>Rate of success, level and duration of sensory and motor block, time to voiding and ambulation, complications, and quality of anesthesia according to the patient and medical staff, were recorded.</AbstractText>Spinal block had a 98% rate of success. Mean level of sensory block was 10.4 +/- 1.7, 7.4 +/- 2.2, and 7.0 +/- 1.8 dermatomes in Groups S7.5, S5, and S4 (P &lt; 0.01 S7.5 vs S5, and S7.5 vs S4). Mean duration of sensory block was 310.5 +/- 42.6, 255.9 +/- 43.7, and 228.8 +/- 34.8 min in Groups S7.5, S5, and S4 (P &lt; 0.01 S7.5 vs S5, S7.5 vs S4, and S5 vs S4). Motor block was Bromage score 2-3 in 70.5% of Group S7.5 patients versus Bromage score 0-1 in 97.3% of Group S5 and 92.1% of Group S4 patients (P &lt; 0.05).</AbstractText>A dose of 4 mg of hyperbaric bupivacaine produces a similar level of sensory and motor block as a 5 mg dose but with shorter duration and faster recovery.</AbstractText>
2,332,779
[Neuromuscular block monitoring for optimisation of conditions for endotracheal intubation].
The choice of an appropriate moment for endotracheal intubation is essential to avoid serious motor and cardiovascular reactions during laryngoscopy and tube insertion.The purpose of the study was to compare the effects of intubation on laryngoscopy conditions and cardiovascular response, when choice of the moment for intubation was directed by either clinical or train-of-four assessment.</AbstractText>Adult ASA I patients, scheduled for lumbar disc hernia surgery, who received 0.15 mg kg(-1) of cis-atracurium for muscle relaxation, were divided in two groups. Patients in group I were intubated when the attending anaesthesiologist assessed muscle relaxation to be adequate. Patients in group II were intubated when there was no visual response to train-of-four stimulation of the ulnar nerve.</AbstractText>Forty-five patients were enrolled in the study. The mean time for intubation was 162.3+/-35 sec in group I and 339.3+/-73.7 sec in group II. Adequate and excellent conditions for intubation were achieved in all patients of group II, compared to only 53% of patients in group I. Heart rate and arterial blood pressure immediately after intubation were significantly lower (p&lt;0.001) in group II.</AbstractText>The objective assessment of neuromuscular relaxation priorto endotracheal intubation provides better conditions and minimization of cardiovascular reaction.</AbstractText>
2,332,780
Blood pressure, but not cerebrospinal fluid fentanyl concentration, predicts duration of labor analgesia from spinal fentanyl.
There is a wide variability in dilution of drugs in cerebrospinal fluid after spinal injection, as measured near the site of injection. With local anesthetics, there is a wide variability in speed of onset, which correlates with block duration. The authors tested whether local cerebrospinal fluid drug concentrations and onset time would predict duration of analgesia from spinal fentanyl in laboring women.</AbstractText>After written informed consent, fentanyl (50 microg) was injected using the combined spinal epidural method in 56 women requesting analgesia for labor. The stylet was reinserted in the spinal needle, and 60 s later, the cerebrospinal fluid was aspirated for fentanyl assay. Time to analgesia and duration of analgesia were recorded, and data were analyzed by linear regression.</AbstractText>Fifty-two women were included for data analysis. The cerebrospinal fluid fentanyl concentrations were 3.1 +/- 5.9 microg/ml, with a 7-fold range (0.9-5.9 microg/ml). Fentanyl concentration did not correlate with onset, initial sensory level at 5 and 10 min, or duration of analgesia. Decreased diastolic and increased systolic blood pressure and lower parity, but not fentanyl concentrations, correlated with longer labor analgesia. The resultant model was predictive when applied to data from four previous studies of spinal opioid analgesia duration.</AbstractText>Contrary to our hypothesis, the local concentration of fentanyl in the cerebrospinal fluid 1 min after injection was not correlated with onset or duration of labor analgesia. The unexpected but consistent relationship between blood pressure and combined spinal epidural analgesia duration suggests that resting hemodynamic state affects the distribution and/or clearance of intrathecally administered opioids.</AbstractText>
2,332,781
Anaesthesia for total knee arthroplasty: efficacy of single-injection or continuous lumbar plexus associated with sciatic nerve blocks--a randomized controlled study.
Total knee arthroplasty (TKA) often results in marked postoperative pain. We compared in a randomized controlled study tramadol consumption, postoperative pain and patient satisfaction after primary TKA in patients who received a single injection lumbar plexus and sciatic nerve blocks or a continuous lumbar plexus and sciatic nerve blocks. Forty-four patients scheduled for unilateral total knee arthroplasty were allocated to the single shot group (group A) or to the catheter group (group B). All patients (in both groups) reported being satisfied with their anaesthetic management. Although pain scores and tramadol consumption appeared lower in the active infusion group, the differences did not reach statistical significance. This study confirms that either single injection or continuous infusion of Ropivacaine in lumbar plexus provides reliable and long-acting anaesthesia and analgesia.
2,332,782
[Effects of combined intercostal nerves block-sevoflurane used inhalation anesthesia with laryngeal mask ventilation on the stress response in patients suffered from breast neoplasms undergoing modified radical mastectomy].
To investigate the influence of combined intercostal nerves block-sevoflurane used inhalation anesthesia with laryngeal mask ventilation on the stress response to modified radical mastectomy.</AbstractText>60 patients with ASA physical status I-II, aged 33-53 years and scheduled for modified radical mastectomy were randomly divided into group I and group II. 30 cases each group. Patients in both groups received modified radical mastectomy under sevoflurane used inhalation anesthesia with laryngeal mask ventilation, and group II received intercostal nerves block before anesthesia induction. Blood samples were taken before anesthesia,at incision, one hour after incision and 5 minutes after the end of surgery for determination of serum concentration of cortisol and angiotension. Blood pressure and heart rate of patients was also recorded during the operation.</AbstractText>Compared with the baseline value before anesthesia, serum cortisol and angiotension increased 5 minutes after the end of surgery in both groups, but the concentration in group I were higher than that in group II. At incision the concentration of cortisol in group I were higher than the baseline value and the same time in group II.</AbstractText>Combined intercostal nerves block-sevoflurane used inhalation anesthesia with laryngeal mask ventilation can reduce the stress response in patients undergoing modified radical mastectomy.</AbstractText>
2,332,783
The effects of adding various doses of clonidine to ropivacaine in spinal anesthesia.
In this study, we compared the clinical effects of combined doses of ropivacaine and clonidine.</AbstractText>Seventy-five patients between ages 18 and 75, in ASA I-III groups who were to undergo elective lower extremity surgery, were included in the study with informed consent. Subjects were randomly assigned to 3 groups. Group I: % 1 ropivacaine 12 mg, group II: % 1 ropivacaine 12 mg + clonidine 15 &#xb5;g, group III: % 1 ropivacaine 12 mg + clonidine 30 &#xb5;g. Mean arterial pressure, breathing, heart rate and peripheral oxygen saturation, total amount of ephedrine and atropine used, sensory and motor block levels, level of sedation, pain level and complications were monitored.</AbstractText>The mean arterial pressure recorded in group III decreased significantly at 75, 105 and 120 min compared to groups I and II. In group I, time to two segment regression and time to sensory block to S2 was shorter when compared to the other groups (P&lt;0.0001). The time to voiding and the duration of motor blockade was significantly longer in group I in comparison to the other groups. The need for atropine in group III was significantly higher (P&lt;0.001). The incidence of hypotension and the requirement for ephedrine were significantly higher in groups II and III as compared to group I (P&lt;0.01). Similarly, sedation in group III was significantly higher compared to the other groups (P&lt;0.05).</AbstractText>In summary, our study revealed that clonidine can be added to ropivacaine for spinal anesthesia in surgical interventions to obtain deeper and longer sensory and motor block. However, hypotension, bradycardia and sedation should be monitored closely.</AbstractText>
2,332,784
Out-of-hospital cardiac arrest frequency and survival: evidence for temporal variability.
Some cardiac phenomena demonstrate temporal variability. We evaluated temporal variability in out-of-hospital cardiac arrest (OHCA) frequency and outcome.</AbstractText>Prospective cohort study (the Resuscitation Outcomes Consortium) of all OHCA of presumed cardiac cause who were treated by emergency medical services within 9 US and Canadian sites between 12/1/2005 and 02/28/2007. In each site, Emergency Medical System records were collected and analyzed. Outcomes were individually verified by trained data abstractors.</AbstractText>There were 9667 included patients. Median age was 68 (IQR 24) years, 66.7% were male and 8.3% survived to hospital discharge. The frequency of cardiac arrest varied significantly across time blocks (p&lt;0.001). Compared to the 0001-0600 hourly time block, the odds ratios and 95% CIs for the occurrence of OHCA were 2.02 (1.90, 2.15) in the 0601-1200 block, 2.01 (1.89, 2.15) in the 1201-1800 block, and 1.73 (1.62, 1.85) in the 1801-2400 block. The frequency of all OHCA varied significantly by day of week (p=0.03) and month of year (p&lt;0.001) with the highest frequencies on Saturday and during December. Survival to hospital discharge was lowest when the OHCA occurred during the 0001-0600 time block (7.3%) and highest during the 1201-1800 time block (9.6%). Survival was highest for OHCAs occurring on Mondays (10.0%) and lowest for those on Wednesdays (6.8%) (p=0.02).</AbstractText>There is temporal variability in OHCA frequency and outcome. Underlying patient, EMS system and environmental factors need to be explored to offer further insight into these observed patterns.</AbstractText>Copyright 2009 Elsevier Ireland Ltd. All rights reserved.</CopyrightInformation>
2,332,785
Addition of dexmedetomidine to bupivacaine for greater palatine nerve block prolongs postoperative analgesia after cleft palate repair.
The effect of dexmedetomidine on the duration of sensory blockade has not been studied in humans. We evaluated the effect of adding dexmedetomidine to bupivacaine on the duration of postoperative analgesia in children who underwent repair of a cleft palate.</AbstractText>Thirty children who were scheduled for repair of a complete cleft palate using a combination of general anaesthesia and greater palatine nerve block were allocated randomly into one of two equal groups (n = 15). In both groups, the greater palatine nerve block was performed bilaterally using 0.5 ml of solution on each side. The B group received bupivacaine 0.25%, whereas the BD group received bupivacaine 0.25% with 1 microg kg(-1) dexmedetomidine. Heart rate, systolic blood pressure, pain score, the time to the first request for analgesia, and the degree of sedation were recorded.</AbstractText>There was no difference in haemodynamic variables between the two groups. The pain score was significantly higher in the B group as compared with the BD group. The time to the first request for analgesia was significantly longer in children in the BD group (mean 22 h, range 20.6-23.7 h) as compared with those who received bupivacaine alone (14.2 h, 13-15 h). Sedation scores in the postoperative period did not differ between the study groups.</AbstractText>Greater palatine nerve block with a combination of dexmedetomidine and bupivacaine increased the duration of analgesia after repair of a cleft palate by 50% with no clinically relevant side effects.</AbstractText>
2,332,786
Hepatic effects of thoracic epidural analgesia in experimental severe acute pancreatitis.
Thoracic epidural anesthesia (TEA) protects the intestinal microcirculation and improves perioperative outcomes. TEA also reduces mortality in acute experimental pancreatitis. Its impact on hepatic microcirculation, however, in health and critical illness is unknown. Therefore, the authors studied the effect of TEA on the liver in healthy rats and in experimental severe acute pancreatitis.</AbstractText>TEA was induced by 15 microl/h bupivacaine, 0.5%. Necrotizing pancreatitis was induced by intraductal infusion of 2 ml/kg taurocholic acid, 5%. Twenty-eight rats were assigned to either Sham operation, Sham + TEA, Pancreatitis, or Pancreatitis + TEA. After 15 h, mean arterial pressure, heart rate, and respiratory function were recorded. Sinusoidal width and perfusion rate and the intrahepatic leukocyte adhesion were assessed by intravital microscopy. In an additional 22 rats randomly assigned to Sham, Pancreatitis, and Pancreatitis + TEA, hepatic apoptosis was evaluated by staining for single-stranded DNA and Fas ligand-positive cells.</AbstractText>TEA did not affect hepatic microcirculation and leukocyte adhesion in healthy rats. Blood pressure remained unchanged in the Sham + TEA group. In Pancreatitis, mean arterial pressure decreased from 141 + or - 6 mmHg to 127 + or - 13 mmHg but remained stable in Pancreatitis + TEA. The sinusoidal diameter decreased from 5.4 + or - 0.1 microm to 5.0 + or - 0.2 microm in Pancreatitis. This was restored in Pancreatitis + TEA. Intrahepatic leukocyte adhesion was not affected by TEA. The increased hepatocyte apoptosis in Pancreatitis was abolished in Pancreatitis + TEA. This might be mediated by inhibition of the Fas ligand pathway.</AbstractText>TEA reduces liver injury in necrotizing acute pancreatitis. This could be related to a regional sympathetic block. TEA could thus preserve liver function in systemic inflammatory disorders such as acute pancreatitis.</AbstractText>
2,332,787
Ketamine, but not priming, improves intubating conditions during a propofol-rocuronium induction.
Both ketamine and priming may shorten the onset time of rocuronium. This study investigates the effects of ketamine and priming as components of a propofol induction on intubating conditions and onset of neuromuscular block.</AbstractText>This prospective randomized double-blind study was performed in 120 American Society of Anesthesiologists (ASA) I-II patients who were assigned to one of four groups of 30 patients each: control, priming, ketamine, and ketamine-priming. Ketamine 0.5 mg x kg(-1) or saline was given before priming and induction. Rocuronium 0.06 mg x kg(-1) or saline was injected 2 min before propofol 2.5 mg x kg(-1). This was followed by rocuronium 0.6 mg x kg(-1) or by rocuronium 0.54 mg x kg(-1) if priming was given. Intubation was performed one minute later. Intubating conditions were graded as excellent, good, or poor. Heart rate, noninvasive blood pressure, and train-of-four (TOF) response were monitored.</AbstractText>Intubating conditions were graded excellent in 20% of the control group, 30% of the priming group, 47% of the ketamine group, and 57% of the ketamine-priming group. Analysis using forward stepwise regression indicated that ketamine improved intubating conditions (P = 0.001) but priming did not (P = 0.35). Time to reach a TOF count of zero was shortened by ketamine (P = 0.001) but not by priming (P = 0.94): 216 +/- 20 s in the control group, 212 +/- 27 s in the priming group, 162 +/- 18 s in the ketamine group, and 168 +/- 22 s in the ketamine-priming group.</AbstractText>A low-dose ketamine used with a propofol-rocuronium induction improved intubating conditions and shortened onset time. Priming did not influence intubating conditions or onset time.</AbstractText>
2,332,788
The cardiovascular response to an acute 1800-microT, 60-Hz magnetic field exposure in humans.
Previously published literature has suggested an effect of extremely low-frequency (ELF) magnetic fields (MF) on human heart rate (HR) and heart rate variability (HRV). The combined response of the microcirculation and macrocirculation to ELF MF exposure has not previously been studied in humans. This study investigated the effects of 1-h exposure to an 1800-muT, 60-Hz MF on human microcirculation (represented in this study as skin blood perfusion), HR, low-frequency HRV, and high-frequency HRV.</AbstractText>Fifty-eight volunteers were recruited to partake in a double-blinded, counterbalanced study consisting of two testing sessions (real and sham) administered on separate days. Each session included four consecutive blocks of measurements, separated by 15-min rest periods, allowing measurement of cumulative and residual MF effects. Within subjects, ANOVA were conducted on each of the measured parameters.</AbstractText>A decrease of skin blood perfusion and HR, and an increase of HRV were observed over blocks (p &lt; 0.05). No session by block interactions were found for any of the cardiovascular parameters which would have suggested a MF effect (p &gt; 0.05). A session by block interaction (p &lt; 0.001) and a MF order effect (sham or real exposure first, p &lt; 0.05) were observed for skin surface temperature.</AbstractText>The MF used in this experiment did not affect cardiovascular parameters. Although an alternative explanation for why skin surface temperatures decreased in the sham and not in the real exposure condition is presented, the possibility of a MF effect cannot be excluded.</AbstractText>
2,332,789
Removal of real-time reverse transcription polymerase chain reaction (RT-PCR) inhibitors associated with cloacal swab samples and tissues for improved diagnosis of Avian influenza virus by RT-PCR.
Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) is routinely used for the rapid detection of Avian influenza virus (AIV) in clinical samples, but inhibitory substances present in some clinical specimens can reduce or block PCR amplification. Most commercial RNA extraction kits have limited capacity to remove inhibitors from clinical samples, but using a modified commercial protocol (Ambion MagMAX, Applied Biosystems, Foster City, CA) with an added high-salt wash of 2 M NaCl and 2 mM ethylenediamine tetra-acetic acid was shown to improve the ability of the kit to remove inhibitors from cloacal swabs and some tissues. Real-time RT-PCR was carried out in the presence of an internal positive control to detect inhibitors present in the purified RNA. Cloacal swabs from wild birds were analyzed by real-time RT-PCR comparing RNA extracted with the standard (MagMAX-S) and modified (MagMAX-M) protocols. Using the standard protocol on 2,668 samples, 18.4% of the samples had evidence of inhibitor(s) in the samples, but the modified protocol removed inhibitors from all but 21 (4.8%) of the problem samples. The modified protocol was also tested for RNA extraction from tissues using a TRIzol-MagMAX-M hybrid protocol. Tissues from chickens and ducks experimentally infected with high-pathogenicity Asian H5N1 AIV were analyzed by real-time RT-PCR, and the limit of detection of the virus was improved by 0.5-3.0 threshold cycle units with the RNA extracted by the MagMAX-M protocol. The MagMAX-M protocol reported in the present study can be useful in extracting high-quality RNA for accurate detection of AIV from cloacal swabs and tissues by real-time RT-PCR.
2,332,790
I-TAC is a dominant chemokine in controlling skin intragraft inflammation via recruiting CXCR3+ cells into the graft.
Chemokines play a critical role in the acute transplant rejection. In order to provide an overview of the chemokine expression during the course of acute allograft rejection, the intragraft expression profile of 11 chemokines representative of all four chemokine subfamilies was analyzed in a murine skin transplantation model of acute rejection. It was found that RANTES/CCL5, TARC/CCL17 and FKN/CX(3)CL1 were expressed at equivalent levels in iso- and allografts. However, the other eight chemokines expression was up-regulated to some extent in allograft compared with that in isograft. The levels of MIP-1alpha/CCL3, MIP-3alpha/CCL20 and CTACK/CCL27 were progressively increased from early stage (day 3 post-transplantation) to late stage (day 11). Mig/CXCL9, IP-10/CXCL10, I-TAC/CXCL11, CXCL16 and LTN/XCL1 expression was elevated at middle stage (day 7), and peaked at late stage. Among the up-regulated chemokines, I-TAC was the most obviously elevated chemokine. Therefore, the effect of I-TAC on the skin acute allograft rejection was evaluated. Block of I-TAC by the intradermal injection of anti-I-TAC monoclonal antibody (mAb) reduced the number of CXCR3(+) cells in skin allograft and significantly prolonged the skin allograft survival. The mAb treatment did not influence the proliferation of the intragraft infiltrating cells in response to the allogeneic antigens, but significantly decreased the number of the infiltrating cells and consequently lowered the secretion of IFN-gamma and TNF-alpha. These data indicate I-TAC might be a dominant chemokine involved in the intradermal infiltration and I-TAC-targeted intervening strategies would have potential application for the alleviation of acute transplant rejection.
2,332,791
The neurofibromatosis type I pre-mRNA is a novel target of CELF protein-mediated splicing regulation.
The CUG-BP and ETR-3 like factors (CELF) are a family of six highly conserved RNA-binding proteins that preferentially bind to UG-rich sequences. One of the key functions of these proteins is to mediate alternative splicing in a number of tissues, including brain, heart and muscle. To fully understand the function of CELF proteins, it is important to identify downstream targets of CELF proteins. In this communication, we report that neurofibromatosis type I (NF1) exon 23a is a novel target of CELF protein-mediated splicing regulation in neuron-like cells. NF1 regulates Ras signaling, and the isoform that excludes exon 23a shows 10 times greater ability to down-regulate Ras signaling than the isoform that includes exon 23a. Five of the six CELF proteins strongly suppress the inclusion of NF1 exon 23a. Over-expression or siRNA knockdown of these proteins in cell transfection experiments altered the levels of NF1 exon 23a inclusion. In vitro binding and splicing analyses demonstrate that CELF proteins block splicing through interfering with binding of U2AF(65). These studies, combined with our previous investigations demonstrating a role for Hu proteins and TIA-1/TIAR in controlling NF1 exon 23a inclusion, highlight the complex nature of regulation of this important alternative splicing event.
2,332,792
Spread of spinal anesthesia in patients having perianal surgery in the jackknife position: effects of baricity of 0.5% bupivacaine and positioning during and after induction of spinal anesthesia.
To compare the influence of baricity and patient positioning during onset of subarachnoid block in patients placed in the prone, jackknife position with head-down tilt of 15 degrees .</AbstractText>Randomized study.</AbstractText>Operating room of Tonami General Hospital.</AbstractText>180 ASA physical I and II patients (134 men and 46 women), aged 18 to 54 years, scheduled for elective perianal surgery.</AbstractText>Patients were randomly divided into 6 groups (n = 30 each) based on baricity (hyperbaric or isobaric) of 0.5% bupivacaine (5 mg) and duration of the sitting position (two, 5, or 10 min) after injection.</AbstractText>Sensory block levels were examined by pinprick at 0, 5, 10, 20, and 60 minutes after jackknife positioning. Systolic blood pressure and heart rate were also recorded.</AbstractText>After jackknife positioning, sensory block levels progressively increased until 15 or 20 minutes in all groups. Regardless of baricity of bupivacaine, sensory block levels were higher at 10 through 60 minutes in the two-minute sitting groups than in the 5-minute or 10-minute sitting groups (P &lt; 0.01 and P &lt; 0.01, respectively), and in the 5-minute sitting groups than in the 10-minute sitting groups (P &lt; 0.05). The mean highest sensory block levels were T5, T9, and T11 in the two-minute, 5-minute, and 10-minute sitting groups, respectively.</AbstractText>Patient positioning, not baricity of bupivacaine, significantly affected the cephalad spread of spinal anesthesia, and a 10-minute period in the sitting position limits the maximum cephalad spread to T11.</AbstractText>
2,332,793
Three concentrations of levobupivacaine for ilioinguinal/iliohypogastric nerve block in ambulatory pediatric surgery.
To compare the postoperative analgesia of three different concentrations of levobupivacaine for ilioinguinal/iliohypogastric (II/IH) block in children undergoing inguinal hernia repair.</AbstractText>Double-blind, prospective, randomized, controlled trial.</AbstractText>Operating room and postoperative recovery area of a university hospital.</AbstractText>73 ASA physical status I and II children, aged one to 6 years, scheduled for outpatient inguinal hernia repair.</AbstractText>Patients were randomized to receive one of three levobupivacaine concentrations: 0.125% (L0.125), 0.25% (L0.25), or 0.375% (L0.375). All patients received standard anesthesia with sevoflurane and II/IH nerve block.</AbstractText>Heart rate (HR), non invasive blood pressure (NIBP), respiratory rate, end-tidal carbon dioxide concentration (ETCO(2)), and oxygen saturation via pulse oximetry (SpO(2)) were monitored during surgery. Postoperative pain scores with CHEOPS (Children's Hospital of Eastern Ontario Pain Scale) and need for rescue analgesia postoperatively were measured and recorded.</AbstractText>60 patients entered the postoperative observational period. The number of patients who received rescue analgesia was comparable in the three groups. In Group L0.125, mean CHEOPS score was significantly higher, and time to first administration of rescue analgesia was shorter, than in the other two groups (P &lt; 0.05). Pain scores and time to first administration of rescue analgesia were comparable between Groups L0.25 and L0.375.</AbstractText>II/IH nerve block using 0.4 mL kg(-1) of 0.25% levobupivacaine provided satisfactory postoperative pain relief after inguinal herniorraphy.</AbstractText>
2,332,794
Socioeconomic position and graft failure in pediatric heart transplant recipients.
Socioeconomic (SE) position may affect availability of resources, health-related behavior, and outcomes. We assessed whether patient SE position, determined for the block group of patient residence (average population 1000, smallest census unit with SE data), is associated with graft failure in pediatric heart transplant recipients.</AbstractText>We used the US Census 2000 database to derive a composite SE score for the block group of residence for all patients who underwent their first heart transplant at Children's Hospital Boston between 1991 and 2005 (n=135). Cox proportional hazards models were used to determine the risk of graft failure (death or retransplant) in the lowest tertile SE group (low SE group) compared with the remaining 2 of 3 patients (controls). The 2 groups were similar with respect to age, gender, diagnosis, and year of transplant. White race was less frequent in low SE group (64% versus 90%, P=0.001). Graft failure occurred in 46 transplant recipients (40 deaths, 6 retransplant). Low SE group (hazard ratio 2.4, 95% CI 1.3 to 4.3) and nonwhite race (hazard ratio 2.7, 95% CI 1.4 to 5.2) were both associated with higher risk of graft failure. In a multivariable model controlling for diagnosis and pretransplant support, race, and low SE position (hazard ratio 2.0, 95% CI 1.0 to 3.7, P=0.04) remained associated with graft failure. Low SE position group had a higher incidence rate of graft rejection and was at a higher risk of late rejection.</AbstractText>Low SE position may be an independent risk factor for graft failure in pediatric heart transplant recipients.</AbstractText>
2,332,795
Some variations in lymphatic drainage of selected bronchopulmonary segments in human lungs.
Interest in the role of the pulmonary lymphatic system in the pathophysiology of pulmonary and systemic diseases induced us to carry out anatomical research on the lung lymphatic system in the Polish population. The aim of the study was to evaluate whether lymphatic vessels respect bronchopulmonary segment borders and to determine how often lymphatic vessels run to nodes of another lymphatic region. A block of organs comprising the lungs with the trachea, larynx and tongue, the heart and esophagus was removed from the cadavers at autopsy. The research involved 96 lungs (48 left and 48 right), which were taken from 31 male and 17 female cadavers. The lymphatic vessels were visualized at the mediastinal and interlobar surface of the lung by visual inspection. These vessels were then cannulated and injected with drawing ink. Next, the course of a lymphatic vessel was checked to see whether it was compatible with the bronchopulmonary segments or lobar borders. The first lymph node to become ink-colored via injection was dissected and histologically examined. A total of 135 images of lymphatic vessels (63 in the left lungs and 72 in the right lung) running on the mediastinal or interlobar surface of the lung were evaluated. In all, 12 out of 135 vessels (8.9%) were observed to cross the border of the segment (6/12 vessels) or the border of the lobe (6/12 vessels). We found 10/135 vessels (7.4%) running to the lymph nodes of another lymphatic region.
2,332,796
The effects of intravenous ephedrine during spinal anesthesia for cesarean delivery: a randomized controlled trial.
We designed a randomized, double-blinded study to determine the efficacy and safety of 0.5 mg/kg intravenous ephedrine for the prevention of hypotension during spinal anesthesia for cesarean delivery. Patients were randomly allocated into two groups: ephedrine group (n=21) and control group (n=21). Intravenous preload of 15 mL/kg lactated Ringer's solution was given. Shortly after the spinal injection, ephedrine 0.5 mg/kg or saline was injected intravenous for 60 sec. The mean of highest and lowest heart rate in the ephedrine group was higher than those of control group (P&lt;0.05). There were significant lower incidences of hypotension and nausea and vomiting in the ephedrine group compared with the control group (8 [38.1%] vs. 18 [85.7%]); (4 [19%] vs. 12 [57.1%], respectively) (P&lt;0.05). The first rescue ephedrine time in the ephedrine group was significantly longer (14.9+/-7.1 min vs. 7.9+/-5.4 min) than that of the control group (P&lt;0.05). Neonatal outcome were similar between the study groups. These findings suggest, the prophylactic bolus dose of 0.5 mg/kg intravenous ephedrine given at the time of intrathecal block after a crystalloid fluid preload, plus rescue boluses reduce the incidence of hypotension.
2,332,797
[Intraosseous anesthesia X-tip system in tooth extraction].
The purpose of this study was to determine the anesthetic efficacy of a intraosseous anesthesia (IOA) as an alternative to the infra alveolar nerve block (IANB) or the maxillary anesthesia. 55 subjects who underwent a tooth extraction received a primary X-tip intraosseous injection (LLC Lakewood, New Jersey, U.S.A.) of Ubistesin forte (articaini hydrochloridum 40 mg, adrenalinum 10 pg ut adrenalini hydrochloridum 1:100000, median 1.5 ml). A pulse oximeter measured the heart rate and the oxygen saturation. The results demonstrated, that the maximum heart rate was higher with the intraosseous injection (average 14.6 beats/min increase) during 1.5-2 minutes, but there was no depression of the oxygen saturation. The wound healing was uneventful. We registered five non-responders which were treated additionally with 1.3 ml of Ubistesin forte terminal anesthesia. For all patients the IOA was unpleasant similar to a "normal" anesthesia. Success of the intraosseous injection was 91%, comparable to the study of Turner et al. (2002) (or the clinical experience after an IANB). For non-responders to an IANB the IOA seems to be a good alternative method.
2,332,798
Modafinil does not serve as a reinforcer in cocaine abusers.
The purpose of this double-blind, randomized, outpatient study was to evaluate the reinforcing and subjective effects of modafinil (200, 400, or 600 mg) in cocaine abusers. Twelve participants (2 female, 10 male) completed this study, consisting of 3 blocks of 7 sessions; each block tested a difference dose of modafinil. During the first 2 sessions of each block, participants "sampled" 1 of the doses of modafinil, and placebo. These doses of modafinil and placebo were available for the subsequent five choice sessions of the block. In each choice session, participants had an opportunity to administer active or placebo capsules. Modafinil administration did not differ from placebo administration, and subjective-effects ratings were not systematically altered as a function of modafinil dose. Results suggest that modafinil does not have abuse liability in cocaine abusers.
2,332,799
Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial.
In the post-intervention period of the Women's Health Initiative (WHI) trial, women assigned to treatment with oestrogen plus progestin had a higher risk of cancer than did those assigned to placebo. Results also suggested that the combined hormone therapy might increase mortality from lung cancer. To assess whether such an association exists, we undertook a post-hoc analysis of lung cancers diagnosed in the trial over the entire follow-up period.</AbstractText>The WHI study was a randomised, double-blind, placebo-controlled trial undertaken in 40 centres in the USA. 16 608 postmenopausal women aged 50-79 years with an intact uterus were randomly assigned by a computerised, stratified, permuted block algorithm to receive a once-daily tablet of 0.625 mg conjugated equine oestrogen plus 2.5 mg medroxyprogesterone acetate (n=8506) or matching placebo (n=8102). We assessed incidence and mortality rates for all lung cancer, small-cell lung cancer, and non-small-cell lung cancer by use of data from treatment and post-intervention follow-up periods. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00000611.</AbstractText>After a mean of 5.6 years (SD 1.3) of treatment and 2.4 years (0.4) of additional follow-up, 109 women in the combined hormone therapy group had been diagnosed with lung cancer compared with 85 in the placebo group (incidence per year 0.16%vs 0.13%; hazard ratio [HR] 1.23, 95% CI 0.92-1.63, p=0.16). 96 women assigned to combined therapy had non-small-cell lung cancer compared with 72 assigned to placebo (0.14%vs 0.11%; HR 1.28, 0.94-1.73, p=0.12). More women died from lung cancer in the combined hormone therapy group than in the placebo group (73 vs 40 deaths; 0.11%vs 0.06%; HR 1.71, 1.16-2.52, p=0.01), mainly as a result of a higher number of deaths from non-small-cell lung cancer in the combined therapy group (62 vs 31 deaths; 0.09%vs 0.05%; HR 1.87, 1.22-2.88, p=0.004). Incidence and mortality rates of small-cell lung cancer were similar between groups.</AbstractText>Although treatment with oestrogen plus progestin in postmenopausal women did not increase incidence of lung cancer, it increased the number of deaths from lung cancer, in particular deaths from non-small-cell lung cancer. These findings should be incorporated into risk-benefit discussions with women considering combined hormone therapy, especially those with a high risk of lung cancer.</AbstractText>National Heart, Lung and Blood Institute, National Institutes of Health.</AbstractText>