bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism by Which a Sustained Inflation Can Worsen Oxygenation in Acute Lung Injury
Authors: Musch Guido , Harris R. Scott , Vidal Melo Marcos F. , O’Neill Kevin R. , Layfield J. Dominick H. , Winkler Tilo , Venegas Jose G. 
Published: January 2004

Background
Sustained lung inflations (recruitment maneuvers [RMs]) are occasionally used during mechanical ventilation of patients with acute lung injury to restore aeration to atelectatic alveoli. However, RMs do not improve, and may even worsen, gas exchange in a fraction of these patients. In this study, the authors sought to determine the mechanism by which an RM can impair gas exchange in acute lung injury.

Methods
The authors selected a model of acute lung injury that was unlikely to exhibit sustained recruitment in response to a lung inflation. In five sheep, lung injury was induced by lavage with 0.2% polysorbate 80 in saline. Positron emission tomography and [13N]nitrogen were used to assess regional lung function in dependent, middle, and nondependent lung regions. Physiologic data and positron emission scans were collected before and 5 min after a sustained inflation (continuous positive airway pressure of 50 cm H2O for 30 s).

Results
All animals showed greater loss of aeration and higher perfusion and shunting blood flow in the dependent region. After the RM, Pao2 decreased in all animals by 35 +/- 22 mmHg (P < 0.05). This decrease in Pao2 was associated with redistribution of pulmonary blood flow from the middle, more aerated region to the dependent, less aerated region (P < 0.05) and with an increase in the fraction of pulmonary blood flow that was shunted in the dependent region (P < 0.05). Neither respiratory compliance nor aeration of the dependent region improved after the RM.

Conclusions
When a sustained inflation does not restore aeration to atelectatic regions, it can worsen oxygenation by increasing the fraction of pulmonary blood flow that is shunted in nonaerated regions.
Molecular Mechanisms of the Inhibitory Effects of Propofol and Thiamylal on Sarcolemmal Adenosine Triphosphate–sensitive Potassium Channels
Authors: Kawano Takashi , Oshita Shuzo , Takahashi Akira , Tsutsumi Yasuo , Tomiyama Yoshinobu , Kitahata Hiroshi , Kuroda Yasuhiro , Nakaya Yutaka 
Published: January 2004

Background
Both propofol and thiamylal inhibit adenosine triphosphate-sensitive potassium (KATP) channels. In the current study, the authors investigated the effects of these anesthetics on the activity of recombinant sarcolemmal KATP channels encoded by inwardly rectifying potassium channel (Kir6.1 or Kir6.2) genes and sulfonylurea receptor (SUR1, SUR2A, or SUR2B) genes.

Methods
The authors used inside-out patch clamp configurations to investigate the effects of propofol and thiamylal on the activity of recombinant KATP channels using COS-7 cells transfected with various types of KATP channel subunits.

Results
Propofol inhibited the activities of the SUR1/Kir6.2 (EC50 = 77 microm), SUR2A/Kir6.2 (EC50 = 72 microm), and SUR2B/Kir6.2 (EC50 = 71 microm) channels but had no significant effects on the SUR2B/Kir6.1 channels. Propofol inhibited the truncated isoform of Kir6.2 (Kir6.2DeltaC36) channels (EC50 = 78 microm) that can form functional KATP channels in the absence of SUR molecules. Furthermore, the authors identified two distinct mutations R31E (arginine residue at position 31 to glutamic acid) and K185Q (lysine residue at position 185 to glutamine) of the Kir6.2DeltaC36 channel that significantly reduce the inhibition of propofol. In contrast, thiamylal inhibited the SUR1/Kir6.2 (EC50 = 541 microm), SUR2A/Kir6.2 (EC50 = 248 microm), SUR2B/Kir6.2 (EC50 = 183 microm), SUR2B/Kir6.1 (EC50 = 170 microm), and Kir6.2DeltaC36 channels (EC50 = 719 microm). None of the mutants significantly affects the sensitivity of thiamylal.

Conclusions
These results suggest that the major effects of both propofol and thiamylal on KATP channel activity are mediated via the Kir6.2 subunit. Site-directed mutagenesis study suggests that propofol and thiamylal may influence Kir6.2 activity by different molecular mechanisms; in thiamylal, the SUR subunit seems to modulate anesthetic sensitivity.
Effects of the α2-Adrenoceptor Agonist Dexmedetomidine on Bronchoconstriction in Dogs
Authors: Groeben Harald , Mitzner Wayne , Brown Robert H. 
Published: January 2004

Background
Tracheal intubation can elicit reflex bronchoconstriction in patients with asthma or chronic obstructive pulmonary disease, complicating mechanical ventilation and weaning from mechanical support. In vitro studies of human and animal bronchial tissue indicate that alpha2-adrenoceptor stimulation can lead to smooth muscle relaxation and prevention of bronchoconstriction. Dexmedetomidine is a selective alpha2-adrenoceptor agonist approved for sedation in the intensive care unit. Whether dexmedetomidine can affect reflex bronchoconstriction is unknown.

Methods
After the approval of the institutional animal care and use committee, five mongrel dogs were anesthetized with thiopental, endotracheally intubated, and ventilated, and their airways were challenged with histamine. High-resolution computed tomography was used to measure airway luminal areas at baseline and after nebulized histamine. After recovery to baseline, on separate days, dexmedetomidine (0.5 microg/kg) was administered either intravenously or as an aerosol, and the histamine challenge was repeated.

Results
At baseline, histamine constricted the airways to 66 +/- 27% (mean +/- SD) (P < 0.0001) and 59 +/- 30% (P < 0.0001) of maximum on the days dexmedetomidine was administered by intravenous and inhalational means, respectively. After recovery, intravenous administration of dexmedetomidine blocked the histamine-induced bronchoconstriction (87 +/- 30.4% of maximum, compared with histamine alone (P < 0.0001), whereas dexmedetomidine administered by inhalation showed no protective effect (45 +/- 30% of maximum; P < 0.0001 compared with histamine alone).

Conclusion
alpha2-Adrenoceptor stimulation with intravenous dexmedetomidine completely blocked histamine-induced bronchoconstriction in dogs. Therefore, dexmedetomidine might be beneficial to decrease airway reactivity in patients with chronic obstructive pulmonary disease or asthma, particularly during weaning from mechanical ventilation, when neurally mediated airway reflexes may be elicited.
Upregulation of Spinal Cyclooxygenase-2 in Rats after Surgical Incision
Authors: Kroin Jeffrey S. , Ling Zao D. , Buvanendran Asokumar , Tuman Kenneth J. 
Published: January 2004

Background
Although upregulation of cyclooxygenase (COX)-2 in spinal cord after peripheral inflammation has been well documented, the effect of surgery on spinal COX-2 has not been examined in detail. The present study uses a bilateral foot incision in rats to examine the magnitude and duration of surgically induced changes in spinal COX-2 protein.

Methods
A longitudinal incision was made in both plantar hind paws of isoflurane-anesthetized rats. Spinal cords were removed at various postoperative times (1-48 h), and spinal COX-2 protein levels were compared with the results of Western blot analysis. Ropivacaine-induced blockade of sciatic nerve function was used to determine the importance of afferent nerve activity on spinal COX-2 after incision. Dexamethasone and the COX-2-selective inhibitor L-745,337 were administered intrathecally to modulate spinal COX-2 after incision.

Results
COX-2 protein levels increased in the lumbar spinal cord at 3 (1.32-fold) and 6 (1.26-fold) h after bilateral foot incision. At later times, lumbar COX-2 levels were no different than in control animals not undergoing surgery. Cervical COX-2 protein levels remained unchanged. Sciatic nerve blockade with ropivacaine did not prevent the increase in lumbar spinal COX-2 protein levels after incision. Intrathecal dexamethasone decreased lumbar spinal COX-2 levels after incision, and an intrathecal COX-2-selective inhibitor did not reduce the COX-2 upregulation.

Conclusions
After bilateral foot incision in rats, lumbar spinal COX-2 protein levels increase, although the magnitude and duration are less than reported in models of peripheral inflammation. This COX-2 upregulation does not seem to be mediated by afferent nerve activity.
Ophthalmic Regional Anesthesia
Authors: Nouvellon Emmanuel , L’Hermite Joel , Chaumeron Arnaud , Mahamat Aba , Mainemer Martine , Charavel Pierre , Mahiou Philippe , Dupeyron Gérard , Bassoul Bruno , Dareau Stephane , Eledjam Jean-Jacques , Ripart Jacques 
Published: January 2004

Background
The purpose of this study was to evaluate the efficacy and safety of episcleral single-injection anesthesia in a large number of patients.

Methods
Over a period of 5 yr, in four institutions, anesthesiologists involved in this prospective study completed a standardized form to evaluate single-injection medial canthus high-volume episcleral anesthesia. The success rate of the block was rated according to an akinesia score. The study parameters included demographic data, surgical procedure, and anesthetic management. All patients were followed up at least until postoperative day 1, and all complications, pain, and discomfort were noted. Statistical analysis was done to assess the risk factors for complications.

Results
A total of 2,031 patients were included in the study. The most frequent surgical procedures performed were phacoemulsification and posterior chamber artificial lens implantation (91.0%). A total of 66 complications (3.3%) occurred in 60 patients. One patient had a retrobulbar hemorrhage, and 59 had one or two more minor incidents or pain/discomfort with the procedure. The complications consisted of subconjunctival hematoma (1.3%), ocular hypertonia (0.4%), and chemosis (0.30%). Statistical analysis revealed that inexperience in the technique represented a risk factor for complications.

Conclusions
This is the first survey of a large experience in episcleral single-injection anesthesia, a form of anesthesia that does not preclude sharp-needle complications and does require training. Only one complication occurred among 2,031 patients; however, a larger number of patients is needed to definitively evaluate the safety of episcleral single-injection anesthesia.
Epidural Neostigmine Produces Analgesia but Also Sedation in Women after Cesarean Delivery
Authors: Kaya F. Nur , Sahin Sukran , Owen Medge D. , Eisenach James C. 
Published: January 2004

Background
Intrathecal neostigmine produces analgesia but also nausea, limiting its utility. In contrast, epidural administration of neostigmine has been suggested to produce postoperative analgesia without nausea in nonpregnant patients. The purpose of this study was to examine the dose range for efficacy and side effects of epidural neostigmine in women at cesarean delivery receiving combined spinal-epidural anesthesia.

Methods
After institutional approval and informed consent, 80 patients for elective cesarean delivery were given combined spinal-epidural anesthesia with 8 mg hyperbaric bupivacaine plus 10 microg fentanyl. Patients were randomized to receive either saline or 75, 150, or 300 microg neostigmine (n = 20 per group) in 10 ml saline after cord clamping. Pain, morphine consumption, and side effects were monitored for 24 h.

Results
Global pain assessment for the first 24 h was reduced from 5.4 +/- 0.2 in the saline group to 3.0-3.5 +/- 0.3 in the neostigmine groups, dose independently. Correspondingly, global satisfaction with neostigmine was also improved (P < 0.05). Nausea and morphine consumption were similar among groups. Intraoperative shivering and sedation were increased in the 300-microg neostigmine group only (P < 0.05), and postoperative sedation was increased by neostigmine in a dose-independent fashion (P < 0.05).

Conclusions
Epidural neostigmine produced modest analgesia in women after cesarean delivery. In contrast with previous reports, which focused primarily on nausea, these data suggest that epidural neostigmine can also produce mild sedation for several hours. These data suggest a limited role for single bolus-administration epidural neostigmine for analgesia after cesarean delivery. They also support future study of epidural neostigmine for obstetric analgesia.
Dose-dependent Effects of Propofol on the Central Processing of Thermal Pain
Authors: Hofbauer Robert K. , Fiset Pierre , Plourde Gilles , Backman Steven B. , Bushnell M. Catherine 
Published: January 2004

Background
Anatomic and physiologic data show that multiple regions of the forebrain are activated by pain. However, the effect of anesthetic level on nociceptive input to these regions is not well understood.

Methods
The authors used positron emission tomography to measure the effect of various concentrations of propofol on pain-evoked changes in regional cerebral blood flow. Fifteen volunteers were scanned while warm and painful heat stimuli were presented to the volar forearm using a contact thermode during administration of target propofol concentrations of 0.0 microg/ml (alert control), 0.5 microg/ml (mild sedation), 1.5 microg/ml (moderate sedation), and 3.5 microg/ml (unconsciousness).

Results
During the 0.5-microg/ml target propofol concentration (mild sedation), the subjects' pain ratings increased relative to the alert control condition; correspondingly, pain-evoked regional cerebral blood flow increased in the thalamus and the anterior cingulate cortex. In contrast, when subjects lost consciousness (3.5 microg/ml), pain-evoked responses in the thalamus and the anterior cingulate cortex were no longer observed, whereas significant pain-evoked activation remained in the insular cortex.

Conclusion
These data show that propofol has a dose-dependent effect on thalamocortical transfer of nociceptive information but that some pain-evoked cortical activity remains after loss of consciousness.
Infraclavicular Perineural Local Anesthetic Infusion
Authors: Ilfeld Brian M. , Morey Timothy E. , Enneking F. Kayser 
Published: January 2004

Background
In this randomized, double-blind study, the authors investigated the efficacy of continuous and patient-controlled ropivacaine infusions via an infraclavicular perineural catheter in ambulatory patients undergoing moderately painful orthopedic surgery at or distal to the elbow.

Methods
Preoperatively, patients (n = 30) received an infraclavicular perineural catheter and nerve block. Postoperatively, patients were discharged home with both oral analgesics and a portable infusion pump delivering 0.2% ropivacaine (500-ml reservoir) in one of three dosing regimens: the basal group (12 ml/h basal, 0.05-ml patient-controlled bolus dose), the basal-bolus group (8 ml/h basal, 4 ml bolus), or the bolus group (0.3 ml/h basal, 9.9 ml bolus). Investigators and patients were blinded to random group assignment.

Results
The basal group (n = 10) required more oral analgesics than the basal-bolus group (P = 0.002) and had a shorter median infusion duration than the other two groups (P < 0.001 for both). The bolus group had the longest median infusion duration (P < 0.001 for both) but experienced an increase in breakthrough pain incidence (P = 0.004) and intensity (P = 0.04 vs. basal-bolus group) as well as sleep disturbances (P < 0.001 for both) compared with the other groups. Overall satisfaction was greatest in the basal-bolus group (9.7 +/- 0.5 vs. 7.9 +/- 1.7 and 8.1 +/- 1.5; P < 0.05 for both).

Conclusions
After moderately painful orthopedic surgery at or distal to the elbow, 0.2% ropivacaine delivered as a continuous infusion combined with patient-controlled bolus doses via an infraclavicular perineural catheter optimizes analgesia while minimizing oral analgesic use compared with basal- or bolus-only dosing regimens.
Is Risk for Alcoholism Mediated by Individual Differences in Drinking Motivations?
Authors: Prescott Carol A. , Cross Rebecca J. , Kuhn Jonathan W. , Horn John L. , Kendler Kenneth S. 
Published: January 2004

Abstract: Background: Individual differences in motivations to drink have been proposed as a mechanism that mediates risk for alcoholism. We investigated the genetic and environmental sources of variation in motivations for drinking, as assessed by four scales of the Alcohol Use Inventory (AUI), and then examined the extent to which genetic and environmental variations in risk for alcoholism are mediated by individual differences in drinking motives.Methods: Data on four AUI scales (assessing drinking to manage mood states, to relieve social anxiety, in social situations, and to improve mental functioning) and lifetime DSM‐IV alcohol abuse and/or dependence (AAD) were obtained from 2529 female and 3709 male adult twins, including 2229 complete twin pairs, from the population‐based Virginia Twin Registry.Results: Logistic regression analyses indicated that higher scores on each of the four AUI variables were significantly associated with AAD, with increases in risk for diagnosis of 40% to 141% per standard deviation increase in AUI score. Structural modeling analyses conducted using Mplus indicated that individual differences in AUI scores were in part due to genetic variation, particularly among women. Among males, genetic factors were substantial for drinking to alter mood but small for other measures. A substantial portion of the genetic variation in AAD overlapped with drinking to manage mood states. Results from bivariate twin models of AAD and the AUI scales were consistent with the mediation hypothesis for the social anxiety and social interaction scales but not drinking to manage mood or to enhance mental functioning.Conclusions: Genetic contributions to variation in risk for alcoholism may be mediated in part by individual differences in motivations related to drinking in social settings. Drinking to manage mood indexes genetic risk for alcoholism but does not appear to act as a direct cause of alcoholism.
Ethanol Selectively Inhibits Enhanced Vesicular Release at Excitatory Synapses: Real‐Time Visualization in Intact Hippocampal Slices
Authors: Maldve Regina E. , Chen Xiaochun , Zhang Tao A. , Morrisett Richard A. 
Published: January 2004

Abstract: Background: Conflicting information exists concerning the actions of ethanol on vesicular release at excitatory synapses. Because long‐term alterations in synaptic transmission are thought to underlie neuroadaptive responses to ethanol, we have directly measured the actions of ethanol on release dynamics at an intact central synapse.Methods: Here we investigated the effects of ethanol on release dynamics in hippocampal slices using confocal microscopy with the lipophilic dye, FM1‐43, complemented by a patch clamp analysis of AMPA miniature excitatory postsynaptic currents (mEPSCs). After a pretreatment/loading paradigm with sulforhodamine (S‐Rhd) and FM1‐43, stable, dense punctate FM1‐43 staining in the CA1 stratum radiatum was evident.Results: FM1‐43 fluorescence destaining was dose‐dependently induced by perfusion with elevated K+ (20–60 mM). Cadmium inhibited K+‐induced destaining, whereas nifedipine had no significant effect. Ethanol (25–75 mM) inhibited K+‐induced destaining with high efficacy and had no effect on basal destaining. Both ω‐Conotoxin GVIA and ω‐Agatoxin IVA inhibited K+‐induced destaining with high efficacy. The combination of ω‐Conotoxin GVIA and ω‐Agatoxin IVA occluded the inhibitory effect of ethanol, indicating that ethanol inhibition of release was dependent on inhibition of N/P/Q‐voltage‐gated calcium channels (VGCCs). Patch clamp studies of AMPA mEPSCs revealed similar findings in that vesicular release was enhanced with K+ depolarization in an ethanol‐sensitive manner.Conclusions: These findings indicate that the FM1‐43/S‐Rhd method is a stable and powerful approach for direct real‐time measurement of vesicular release kinetics in intact brain slice preparations and that ethanol inhibits vesicular release induced by depolarization via inhibition of N/P/Q‐VGCCs.
Ethanol Interferes With the Measurement of Extracellular Ionized Calcium
Authors: Keiver Kathy 
Published: January 2004

Abstract: Background: Maintenance of extracellular calcium (Ca) concentration within narrow limits is critical for normal cell function and optimization of bone health. Ionized Ca (iCa), the form of Ca that is regulated, has been reported to vary inversely with blood alcohol concentration (BAC). The mechanism by which ethanol decreases blood iCa levels is unknown. However, one possible explanation is that it is, at least partially, a methodological artifact due to an effect of ethanol on the function of the ion selective electrode used to measure iCa. The purpose of this study was to determine if ethanol interferes with the measurement of iCa and if this interference can account for the typically observed in vivo effects of ethanol consumption on blood iCa levels.Methods: Ethanol (0–5 μl/ml) was added to blood or iCa standards and the iCa concentration measured using the ICA2 iCa analyzer (Radiometer) or the I‐Stat Clinical Analyzer (Abbott Laboratories). Both instruments use an ion selective electrode to measure iCa. The relationship between iCa and BAC determined from the ex vivo addition of ethanol to blood was compared with relationships obtained in vivo during chronic ethanol consumption.Results: Addition of ethanol to blood or iCa standards resulted in a dose‐dependent decrease in iCa concentration when iCa was measured using the ICA2 analyzer but had no effect on iCa concentration when measured with the I‐Stat Clinical Analyzer. Ethanol's effect on iCa with the ICA2 analyzer did not differ between blood and standards, and ethanol had no effect on pH, suggesting that the ethanol‐induced decrease in iCa was due to a methodological artifact. However, the magnitude of ethanol's effect was small and does not account entirely for the relationship between iCa and BAC observed in vivo with chronic ethanol consumption.Conclusion:: Ethanol can interfere with the measurement of iCa using ion selective electrodes, but this interference depends on the analyzer used. This is a significant methodological issue that has largely been unrecognized in the field of alcohol research. Although this interference does not explain entirely the relationship between iCa and BAC observed in vivo in studies on chronic ethanol consumption, it complicates investigations designed to assess the effect of ethanol on Ca homeostasis.