bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tail Clamp Responses in Stomatin Knockout Mice Compared with Mobility Assays in Caenorhabditis elegans during Exposure to Diethyl Ether, Halothane, and Isoflurane
Authors: Sedensky Margaret M. , Pujazon Melissa A. , Morgan Phil G. 
Published: August 2006

Background
The gene unc-1 plays a central role in determining volatile anesthetic sensitivity in Caenorhabditis elegans. Because different unc-1 alleles cause strikingly different phenotypes in different volatile anesthetics, the UNC-1 protein is a candidate to directly interact with volatile anesthetics. UNC-1 is a close homologue of the mammalian protein stomatin, for which a mouse knockout was recently constructed. Because the stomatin gene is expressed in dorsal root ganglion cells, the authors hypothesized that the knockout would have an effect on anesthetic sensitivity in mice similar to that seen in nematodes.

Methods
Mice were placed in semiclosed chambers and exposed to continuous flows of diethyl ether, halothane, or isoflurane in air. Using lack of response to tail clamp as an endpoint, the authors determined the EC50s for the knockout strain compared with the nonmutated parental strain. They compared the differences seen in the mouse strains with the differences seen in the nematode strains.

Results
Stomatin-deficient mice had a 12% increase in sensitivity to diethyl ether but no significant change in sensitivity to halothane or isoflurane compared with wild type. No defect in locomotion was noted in the mutant mouse.

Conclusions
Nematodes and mice with deletions of the stomatin gene both have increased sensitivity to diethyl ether. Neither nematodes nor mice with stomatin deficiencies have significantly altered sensitivity to isoflurane or halothane. The effects of stomatin deficiency cross phylogenetic boundaries and support the importance of this protein in anesthetic response and the use of C. elegans as a model for anesthetic action in mammals.
Role of the β1-Adrenergic Pathway in Anesthetic and Ischemic Preconditioning against Myocardial Infarction in the Rabbit Heart In Vivo
Authors: Lange Markus , Smul Thorsten M. , Blomeyer Christoph A. , Redel Andreas , Klotz Karl-Norbert , Roewer Norbert , Kehl Franz 
Published: August 2006

Background
Anesthetic and ischemic preconditioning share similar signal transduction pathways. The authors tested the hypothesis that the beta1-adrenergic signal transduction pathway mediates anesthetic and ischemic preconditioning in vivo.

Methods
Pentobarbital-anesthetized (30 mg/kg) rabbits (n = 96) were instrumented for measurement of systemic hemodynamics and subjected to 30 min of coronary artery occlusion and 3 h of reperfusion. Sixty minutes before occlusion, vehicle (control), 1.0 minimum alveolar concentration desflurane, or sevoflurane, and esmolol (30.0 mg x kg(-1) x h(-1)) were administered for 30 min, respectively. Administration of a single 5-min cycle of ischemic preconditioning was instituted 35 min before coronary artery occlusion. In separate groups, the selective blocker esmolol or the protein kinase A inhibitor H-89 (250 microg/kg) was given alone and in combination with desflurane, sevoflurane, and ischemic preconditioning.

Results
Baseline hemodynamics and area at risk were not significantly different between groups. Myocardial infarct size (triphenyltetrazolium staining) as a percentage of area at risk was 61 +/- 4% in control. Desflurane, sevoflurane, and ischemic preconditioning reduced infarct size to 34 +/- 2, 36 +/- 5, and 23 +/- 3%, respectively. Esmolol did not alter myocardial infarct size (65 +/- 5%) but abolished the protective effects of desflurane and sevoflurane (57 +/- 4 and 52 +/- 4%, respectively) and attenuated ischemic preconditioning (40 +/- 4%). H-89 did not alter infarct size (60 +/- 4%) but abolished preconditioning by desflurane (57 +/- 5%) and sevoflurane (61 +/- 1%). Ischemic preconditioning (24 +/- 7%) was not affected by H-89.

Conclusions
The results demonstrate that anesthetic preconditioning is mediated by the beta1-adrenergic pathway, whereas this pathway is not essential for ischemic preconditioning. These results indicate important differences in the mechanisms of anesthetic and ischemic preconditioning.
Distinct Pharmacologic Properties of Neuromuscular Blocking Agents on Human Neuronal Nicotinic Acetylcholine Receptors
Authors: Jonsson Malin , Gurley David , Dabrowski Michael , Larsson Olof , Johnson Edwin C. , Eriksson Lars I. 
Published: August 2006

Background
Nondepolarizing neuromuscular blocking agents (NMBAs) are extensively used in the practice of anesthesia and intensive care medicine. Their primary site of action is at the postsynaptic nicotinic acetylcholine receptor (nAChR) in the neuromuscular junction, but their action on neuronal nAChRs have not been fully evaluated. Furthermore, observed adverse effects of nondepolarizing NMBAs might originate from an interaction with neuronal nAChRs. The aim of this study was to examine the effect of clinically used nondepolarizing NMBAs on muscle and neuronal nAChR subtypes.

Methods
Xenopus laevis oocytes were injected with messenger RNA encoding for the subunits included in the human alpha1beta1epsilondelta, alpha3beta2, alpha3beta4, alpha4beta2, and alpha7 nAChR subtypes. The interactions between each of these nAChR subtypes and atracurium, cisatracurium, d-tubocurarine, mivacurium, pancuronium, rocuronium, and vecuronium were studied using an eight-channel two-electrode voltage clamp setup. Responses were measured as peak current and net charge.

Results
All nondepolarizing NMBAs inhibited both muscle and neuronal nAChRs. The neuronal nAChRs were reversibly and concentration-dependently inhibited in the low micromolar range. The mechanism (i.e., competitive vs. noncompetitive) of the block at the neuronal nAChRs was dependent both on subtype and the NMBA tested. The authors did not observe activation of the nAChR subtypes by any of the NMBAs tested.

Conclusions
The authors conclude that nondepolarizing NMBAs concentration-dependently inhibit human neuronal nAChRs. The inhibition of the presynaptic alpha3beta2 nAChR subtype expressed at the motor nerve ending provides a possible molecular explanation for the tetanic and train-of-four fade seen during a nondepolarizing neuromuscular block.
Mechanism of Cardiac Sarcolemmal Adenosine Triphosphate–sensitive Potassium Channel Activation by Isoflurane in a Heterologous Expression System
Authors: Bienengraeber Martin , Warltier David C. , Bosnjak Zeljko J. , Stadnicka Anna 
Published: August 2006

Background
Activation of the cardiac sarcolemmal adenosine triphosphate-sensitive potassium (KATP) channel during metabolic stress initiates cellular events that preserve cardiac performance. Previous studies showed that halogenated anesthetics prime KATP channels under whole cell voltage clamp and act in intracellular pH (pHi)-dependent manner on KATP channels in excised membrane patches. However, it is not known how halogenated anesthetics interact with these channels.

Methods
The authors evaluated the effect of pHi and isoflurane on the KATP channel subunits, the pore-forming inward rectifier Kir6.2, and the regulatory sulfonylurea receptor SUR2A, using HEK293 cells as a heterologous expression system. Single channel activity was recorded in the inside-out patch configuration.

Results
At pHi 7.4, isoflurane had negligible effect on activity of wild-type Kir6.2/SUR2A, but at pHi 6.8, the channel open probability was increased by isoflurane (0.177 +/- 0.077 to 0.364 +/- 0.164). By contrast, the open probability of truncated Kir6.2DeltaC26, which forms a functional channel without SUR2A, was attenuated by isoflurane at both pHi 7.4 and pHi 6.8. Coexpression of Kir6.2DeltaC26 with SUR2A restored pHi sensitivity of channel activation by isoflurane. Site-directed mutagenesis within the Walker motifs of SUR2A abolished isoflurane activation of KATP channel at pHi 6.8. In addition, the pancreatic-type channels expressing sulfonylurea receptor SUR1 could not be activated by isoflurane.

Conclusions
The nucleotide binding domains of SUR2A play a crucial role in isoflurane facilitation of the KATP channel activity at moderately acidic pHi as would occur during early ischemia. These findings support direct and differential interaction of isoflurane with the subunits of the cardiac sarcolemmal KATP channel.
κ-Opioid Receptors Mediate Cardioprotection by Remote Preconditioning
Authors: Zhang Shi-zhong , Wang Ning-fu , Xu Jian , Gao Qin , Lin Guo-hua , Bruce Iain C. , Xia Qiang 
Published: August 2006

Background
Remote preconditioning is known to be cardioprotective, but the exact mechanism has not been fully elucidated. The objective of the current study was to investigate the role of kappa-opioid receptors in cardioprotection by remote preconditioning and reveal possible underlying mechanisms.

Methods
Remote preconditioning was induced in anesthetized male Sprague-Dawley rats by three cycles of 5 min of right femoral artery occlusion followed by 5 min of reperfusion. Myocardial ischemia-reperfusion was achieved by ligation of the left anterior descending coronary artery for 30 min and then reperfusion for 120 min. Infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining. Levels of lactate dehydrogenase, dynorphin, and met-enkephalin in plasma were measured. The opening of the mitochondrial permeability transition pore was monitored with fluorescent calcein in isolated ventricular myocytes.

Results
Both remote preconditioning and U-50,488H (10 mg/kg intravenous), a kappa-opioid receptor agonist, significantly decreased the infarct size and plasma lactate dehydrogenase level induced by ischemia-reperfusion, and these effects were attenuated by nor-binaltorphimine (10 mg/kg intravenous), a kappa-opioid receptor antagonist, and atractyloside (5 mg/kg intravenous), a mitochondrial permeability transition pore activator. However, administration of naltrindole (5 mg/kg), a delta-opioid receptor antagonist, had no effect on the cardioprotection by remote preconditioning. The dynorphin plasma level was increased after remote preconditioning treatment, but the met-enkephalin level did not change. In isolated ventricular myocytes loaded with calcein, U-50,488H (300 microM) decreased the mitochondrial permeability transition pore opening induced by calcium (200 microM), and this effect was attenuated by cotreatment with nor-binaltorphimine (5 microM) or atractyloside (20 microM).

Conclusion
Activation of cardiac kappa-opioid receptors is involved in the cardioprotection induced by remote preconditioning, and the mitochondrial permeability transition pore may participate in the postreceptor pathway.
Postoperative Left Prefrontal Repetitive Transcranial Magnetic Stimulation Reduces Patient-controlled Analgesia Use
Authors: Borckardt Jeffrey J. , Weinstein Mitchel , Reeves Scott T. , Kozel F Andrew , Nahas Ziad , Smith Arthur R. , Byrne T Karl , Morgan Katherine , George Mark S. 
Published: August 2006

Background
Several recent studies suggest that repetitive transcranial magnetic stimulation can temporarily reduce pain perception in neuropathic pain patients and in healthy adults using laboratory pain models. No studies have investigated the effects of prefrontal cortex stimulation using transcranial magnetic stimulation on postoperative pain.

Methods
Twenty gastric bypass surgery patients were randomly assigned to receive 20 min of either active or sham left prefrontal repetitive transcranial magnetic stimulation immediately after surgery. Patient-controlled analgesia pump use was tracked, and patients also rated pain and mood twice per day using visual analog scales.

Results
Groups were similar at baseline in terms of body mass index, age, mood ratings, pain ratings, surgery duration, time under anesthesia, and surgical anesthesia methods. Significant effects were observed for surgery type (open vs. laparoscopic) and condition (active vs. sham transcranial magnetic stimulation) on the cumulative amount of patient-delivered morphine during the 44 h after surgery. Active prefrontal repetitive transcranial magnetic stimulation was associated with a 40% reduction in total morphine use compared with sham during the 44 h after surgery. The effect seemed to be most prominent during the first 24 h after cortical stimulation delivery. No effects were observed for repetitive transcranial magnetic stimulation on mood ratings.

Conclusions
A single session of postoperative prefrontal repetitive transcranial magnetic stimulation was associated with a reduction in patient-controlled analgesia pump use in gastric bypass surgery patients. This is important because the risks associated with postoperative morphine use are high, especially among obese patients who frequently have obstructive sleep apnea, right ventricular dysfunction, and pulmonary hypertension. These preliminary findings suggest a potential new noninvasive method for managing postoperative morphine use.
The Sheath of the Brachial Plexus
Authors: Cornish Philip B. , Leaper Christopher 
Published: August 2006

Background
The concept of the axillary "sheath" has been a central tenet of brachial plexus regional anesthesia for many years. Recent investigations have cast doubt on its nature and existence. This study further examines the issue.

Methods
Computerized axial tomographic dye studies were performed using continuous catheter systems for the sciatic nerve and the brachial plexus. The resultant images were compared and contrasted.

Results
The images of the two catheter systems were the same, with the exception that one was of the upper extremity and the other was of the lower extremity.

Conclusions
The sciatic nerve is not surrounded or enveloped by a "sheath"--it lies in the tissue plane between rigid anatomical structures. Similarly, the brachial plexus lies in the tissue plane between the rigid anatomy of the chest wall, scapula, humerus, and pectoral fascia. This finding is inconsistent with the concept of the axillary sheath.
Effect of Patient-controlled Perineural Analgesia on Rehabilitation and Pain after Ambulatory Orthopedic Surgery
Authors: Capdevila Xavier , Dadure Christophe , Bringuier Sophie , Bernard Nathalie , Biboulet Philippe , Gaertner Elisabeth , Macaire Philippe 
Published: August 2006

Background
Efficacy of continuous perineural and patient-controlled ropivacaine infusion at home after orthopedic surgery was compared with patient-controlled intravenous morphine for functional recovery and postoperative analgesia in a multicenter randomized trial.

Methods
Eighty-three patients scheduled to undergo acromioplasty or hallux valgus surgery received an interscalene (n = 40) or popliteal (n = 43) peripheral nerve block with 30 ml ropivacaine, 0.5%. After randomization, patients were discharged home 24 h after surgery with a disposable infusion pump delivering either patient-controlled intravenous morphine (n = 23) or perineural 0.2% ropivacaine infusion, either continuous infusion without bolus (n = 30) or basal infusion plus bolus (n = 30). The patients recorded pain scores on movement and/or walking and were directed to take paracetamol and rescue analgesics if necessary. The time necessary to be able to walk for 10 min; daily activities on days 1, 2, and 3; adverse events; and overall satisfaction scores were noted and graded by the patient.

Results
Basal-bolus ropivacaine decreased the time to 10 minutes' walk, optimized daily activities (P < 0.01), and decreased the amount of ropivacaine used. The morphine group had greater pain scores and consumption of morphine and ketoprofen compared with both ropivacaine groups (P < 0.05). The incidence of nausea/vomiting, sleep disturbance, and dizziness increased, and the patient satisfaction score decreased in the morphine group (P < 0.05).

Conclusions
After ambulatory orthopedic surgery, 0.2% ropivacaine delivered as a perineural infusion using a disposable elastomeric pump with patient-controlled anesthesia bolus doses optimizes functional recovery and pain relief while decreasing the consumption of rescue analgesics and ropivacaine, and the number of adverse events.
Enhancement of Morphine Analgesic Effect with Induction of μ-Opioid Receptor Endocytosis in Rats
Authors: Hashimoto Tatsuya , Saito Yoji , Yamada Kazuo , Hara Nobumasa , Kirihara Yumiko , Tsuchiya Mikako 
Published: August 2006

Background
Morphine can desensitize mu-opioid receptor (MOR), but it does not cause internalization of the receptor after binding. Acute desensitization of MOR impairs the efficiency of signaling, whereas the receptor internalization restores the cell responsiveness to the agonists. Thereby, the property of morphine may limit the analgesic effects of this opiate drug. It has been shown that [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO), a potent MOR agonist inducing the internalization, facilitates morphine to internalize MOR, suggesting that MOR agonists with low relative activity versus endocytosis (RAVE) values such as DAMGO can potentiate analgesic effects of morphine through stimulating MOR internalization. The authors examined whether the acute analgesic effect of morphine can be potentiated by low relative activity versus endocytosis agonists DAMGO and fentanyl.

Methods
Rats injected intrathecally with opioids were subjected to a hot plate test for antinociceptive effect. Immunostained spinal dorsal horn was analyzed by confocal microscopy.

Results
Fentanyl induced MOR internalization to a lesser extent than DAMGO at equianalgesic doses. Coadministration of fentanyl promoted morphine-induced MOR internalization. The analgesic effect of morphine was greatly potentiated together with decrease in the relative activity versus endocytosis value when MOR internalization was induced by coadministration of a subanalgesic dose of DAMGO or fentanyl. In contrast, the combination of DAMGO and fentanyl increased neither the analgesic effect nor the internalization of MOR.

Conclusions
The results suggest that the coadministration of morphine with MOR-internalizing agonist is clinically applicable to develop successful pain-management regimens to achieve satisfactory analgesia using less morphine.
Time Course and Role of Morphine Dose and Concentration in Intrathecal Granuloma Formation in Dogs
Authors: Allen Jeffrey W. , Horais Kjersti A. , Tozier Nicolle A. , Wegner Kirsten , Corbeil Jacqueline A. , Mattrey Robert F. , Rossi Steven S. , Yaksh Tony L. 
Published: August 2006

Background
Intrathecal morphine infusion leads to intrathecal granulomas. In dogs, the authors examined time course of granuloma formation and the role of concentration in granuloma development.

Methods
Dogs were prepared with lumbar intrathecal catheters and vest-mounted pumps. To define the time course of granuloma formation, serial magnetic resonance imaging was performed in animals receiving 10 or 31 days of morphine infusion (12.5 mg/ml at 40 microl/h). At these times, morphine was removed from the infusate, and further magnetic resonance images were acquired over 14-35 additional days. To assess dose versus concentration, dogs received 28-day infusions of vehicle, 12 mg morphine/day as 12.5 mg/ml at 40 microl/h, or 1.5 mg/ml at 334 microl/h (12 mg/day) for 28 days. Additional dogs received 3 mg/day as 12.5 mg/ml at 10 mul/h.

Results
Serial magnetic resonance images in dogs receiving morphine (12.5 mg/ml at 40 microl/h) revealed pericatheter-enhancing tissues as early as 3 days with a prominent signal by 10 days. Removal of morphine reduced the mass volume within 7 days. At a fixed infusion rate, the incidence of granuloma formation with the continuous intrathecal infusion of morphine ranged from 0 in vehicle-treated dogs to 100% in dogs treated with 12.5 mg/ml at 40 microl/h (12 mg/day). Infusion of 12 mg/day at 1.5 mg/ml (334 microl/h) resulted in granuloma in one of four animals. The authors found that infusion of morphine in different concentrations at a fixed rate resulted in a dose-dependent increase in concentration, with the granuloma-producing, dose-yielding lumbar cerebrospinal fluid morphine concentrations around 40 microg/ml.

Conclusions
Serial magnetic resonance imaging showed a rapid formation and regression of the masses initiated by intrathecal morphine infusion. These masses are dependent on local concentration.
Opiate Pharmacology of Intrathecal Granulomas
Authors: Allen Jeffrey W. , Horais Kjersti A. , Tozier Nicolle A. , Yaksh Tony L. 
Published: August 2006

Background
Chronic intrathecal morphine infusion produces intradural granulomas. The authors examined a variety of opioids infused intrathecal for analgesic activity and toxicity.

Methods
Two sets of experiments were undertaken in dogs with chronic intrathecal catheters: (1) Six-hour intrathecal infusions were used to determine the full analgesic dose and the maximum tolerated dose. (2) To establish toxicity, the maximum tolerated dose was given for up to 28 days by continuous intrathecal infusion. Drugs examined were morphine sulfate, hydromorphone, D/L-methadone, L-methadone, D-methadone, fentanyl, [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO), naloxone, or saline. RESULTS ANALGESIA AND TOLERABILITY: Six-hour intrathecal infusion of agonists resulted in a time-dependent increase in thermal escape latency. At higher concentrations, dose-limiting motor dysfunction and sedation occurred, and hypersensitivity occurred. The concentrations, in mg/ml, for full analgesic dose/maximum tolerated dose were as follows: morphine, 0.9/12.0; hydromorphone, 1.0/3.0; D/L-methadone, 2.8/3; L-methadone, 1.0/> 1.0; fentanyl, 0.3/2.0; DAMGO, 0.1/> 2.0; D-methadone, > 1/> 1; naloxone, > 10/> 10. SPINAL PATHOLOGY: Chronic intrathecal infusion of the maximum tolerated dose revealed 100% intradural granuloma formation after morphine, hydromorphone, L-methadone, and naloxone. DAMGO induced a mass in only a single animal (one of three). D/L- and D-methadone produced intradural granulomas but were also associated with parenchymal necrosis. Saline and fentanyl animals displayed no granulomas.

Conclusions
Intrathecal opiate-induced granulomas are not strictly dependent on opioid receptor activation. Therefore, opiates at equianalgesic doses present different risks for granuloma formation. Importantly, D/L- and D-methadone also resulted in parenchymal necrosis, an affect associated with the N-methyl-D-aspartate antagonist action of the D-isomer.
Concussion history is not a predictor of computerised neurocognitive performance
Authors: Broglio S P , Ferrara M S , Piland S G , Anderson R B 
Published: August 2006

Background:The long term effects of self reported concussion on neurocognitive functioning have been found to be variable.Objectives:To evaluate cognitive performance on the Headminder concussion resolution index (CRI) and ImPACT assessment tests of subjects with and without a history of self reported concussion.Methods:A retrospective analysis was completed on 235 Headminder CRI baseline assessments and 264 ImPACT baseline assessments. Participants were divided into four groups on the basis of reported number of concussions (zero, one, two, or three). Multivariate analysis of variance was used to evaluate differences between the concussion history groups on the two computer based concussion assessment programs.Results:Multivariate analysis of variance indicated no significant difference between those with and without a history of concussion on the CRI (Λ  =  0.963,F(15, 627.05) =  0.57, p  =  0.898). It also revealed no significant differences between groups on the ImPACT test (Λ  =  0.951,F(12, 672.31) =  1.07, p  =  0.381).Conclusions:The results suggest that either long term cognitive decrements may not be associated with a history of concussion or the decrements may be subtle and undetectable by these computer programs.