bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opiate-induced Analgesia Is Increased and Prolonged in Mice Lacking P-glycoprotein
Authors: Thompson Susan J. , Koszdin Kari , Bernards Christopher M. 
Published: August 2004

Background
P-glycoprotein is a transmembrane protein expressed by multiple mammalian cell types, including the endothelial cells that comprise the blood-brain-barrier. P-glycoprotein functions to actively pump a diverse array of xenobiotics out of the cells in which it is expressed. The purpose of this study was to determine if P-glycoprotein alters the analgesic efficacy of clinically useful opioids.

Methods
Using a standard hot-plate method, the magnitude and duration of analgesia from morphine, morphine-6-glucuronide, methadone, meperidine, and fentanyl were assessed in wild-type Friends virus B (FVB) mice and in FVB mice lacking P-glycoprotein [mdr1a/b(-/-)]. Analgesia was expressed as the percent maximal possible effect (%MPE) over time, and these data were used to calculate the area under the analgesia versus time curves (AUC) for all opioids studied. In addition, the effect of a P-glycoprotein inhibitor (cyclosporine, 100 mg/kg) on morphine analgesia in both wild-type and mdr knockout mice was also determined.

Results
Morphine induced greater analgesia in knockout mice compared with wild-type mice (AUC 6,450 %MPE min vs. 1,610 %MPE min at 3 mg/kg), and morphine brain concentrations were greater in knockout mice. Analgesia was also greater in knockout mice treated with methadone and fentanyl but not meperidine or morphine-6-glucuronide. Cyclosporine pretreatment markedly increased morphine analgesia in wild-type mice but had no effect in knockout mice.

Conclusions
These results suggest that P-glycoprotein acts to limit the entry of some opiates into the brain and that acute administration of P-glycoprotein inhibitors can increase the sensitivity to these opiates.
Isoflurane Preconditions Myocardium Against Infarction via Activation of Inhibitory Guanine Nucleotide Binding Proteins
Authors: Toller Wolfgang G. , Kersten Judy R. , Gross Eric R. , Pagel Paul S. , Warltier David C. 
Published: August 2004

Background
Isoflurane-induced myocardial protection during ischemia is mediated by adenosine triphosphate-regulated potassium (KATP) channels; however, the intracellular signal transduction cascade responsible for this process has been incompletely evaluated. The authors tested the hypothesis that isoflurane reduces myocardial infarct size through a Gi protein-mediated process.

Methods
Forty-eight hours after pretreatment with vehicle (0.9% saline) or the Gi protein inhibitor pertussis toxin (10 microg/kg intravenously), barbiturate-anesthetized dogs (n = 43) were instrumented for measurement of aortic and left ventricular pressures and maximum rate of increase of left ventricular pressure. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3-h reperfusion. In four separate groups, vehicle- or pertussis toxin-pretreated dogs were studied with or without administration of 1 minimum alveolar concentration isoflurane. In two additional groups, dogs received the direct KATP channel agonist nicorandil (100 microg/kg bolus and 10 microg x kg-1 x min-1 intravenous infusion) in the presence or absence of pertussis toxin pretreatment. Myocardial perfusion and infarct size were measured with radioactive microspheres and triphenyltetrazolium staining, respectively.

Results
Isoflurane significantly (P < 0.05) decreased infarct size to 7 +/- 2% of the area at risk compared with control experiments (26 +/- 2%). Pertussis toxin pretreatment alone had no effects on myocardial infarct size (31 +/- 4%) but blocked the beneficial effects of isoflurane (21 +/- 3%). Nicorandil decreased infarct size (11 +/- 2%), but, in contrast to isoflurane, this effect was independent of pertussis toxin pretreatment (11 +/- 1%).

Conclusion
Isoflurane reduces myocardial infarct size by a Gi protein-mediated mechanism in vivo.
Differential Neurotoxic Effects of Propofol on Dissociated Cortical Cells and Organotypic Hippocampal Cultures
Authors: Spahr-Schopfer Isabelle , Vutskits Lazlo , Toni Nicholas , Buchs Pierre-Alain , Parisi Lorena , Muller Dominique 
Published: August 2004

Background
Propofol is a widely used anesthetic agent for adults and children. Although extensive clinical use has demonstrated its safety, neurologic dysfunctions have been described after the use of this agent. A recent study on a model of aggregating cell cultures reported that propofol might cause irreversible lesions of gamma-aminobutyric acid-mediated (GABAergic) neurons when administered at a critical phase of brain development. We investigated this issue by comparing the effects of long-term propofol treatment on two models of brain cultures: dissociated neonatal cortical cell cultures and organotypic slice cultures.

Methods
Survival of GABAergic neurons in dissociated cultures of newborn rat cortex (postnatal age, 1 day) treated for 3 days with different concentrations of propofol was assessed using histologic and cytochemical methods. For hippocampal organotypic slice cultures (postnatal age, 1 and 7 days), cell survival was assessed by measuring functional and morphologic parameters: extracellular and intracellular electrophysiology, propidium staining of dying cells, and light and electron microscopy.

Results
In dissociated neonatal cell cultures, propofol induced dose-dependent lesions of GABAergic neurons and of glial cells. In contrast, no evidence for neurotoxic effects of propofol were found after long-term treatment of organotypic slice cultures. Excitatory transmission was not affected by propofol, and inhibitory transmission was still functional. Histologic preparations showed no evidence for cell degeneration or death.

Conclusion
Although long-term applications of propofol to dissociated cortical cell cultures produced degeneration and death of GABAergic neurons and glial cells, no such lesions were found when using a model of postnatal organotypic slice cultures. This conclusion is based on both functional and morphologic tests.
The Action of Sevoflurane on Vascular Smooth Muscle of Isolated Mesenteric Resistance Arteries (Part 1)
Authors: Izumi Kaoru , Akata Takashi , Takahashi Shosuke 
Published: August 2004

Background
The direct action of sevoflurane on systemic resistance arteries is not fully understood.

Methods
Isometric force was recorded in isolated rat small mesenteric arteries.

Results
Sevoflurane (2-5%) enhanced contractile response to norepinephrine only in the presence of endothelium, but inhibited it in its absence. Sevoflurane still enhanced the norepinephrine response after inhibitions of the nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase and lipoxygenase pathways, or after blockade of either endothelin-1 ET-1), angiotensin-II, or sevotonin receptors. Sevoflurane (3-5%) inhibited contractile response to potassium chloride only in the absence of endothelium but did not influence it in its presence. In the endothelium-intact strips, inhibition of the norepinephrine response, which was enhanced during application of sevoflurane, was observed after washout of sevoflurane and persisted for approximately 15 min. In the endothelium-denuded strips, the inhibition of norepinephrine response was similarly prolonged after washout of sevoflurane. However, no significant inhibitions of potassium chloride response were observed after washout of sevoflurane in both the endothelium-intact and the endothelium-denuded strips.

Conclusions
The action of sevoflurane on norepinephrine contractile response consists of endothelium-dependent vasoconstricting and endothelium-independent vasodilating components. In the presence of endothelium, the former predominates over the latter, enhancing the norepinephrine response. The endothelium-independent component persisted after washout of sevoflurane, leading to prolonged inhibition of the norepinephrine response. The mechanisms behind the sevoflurane-induced inhibition of norepinephrine response are at least in part different from those behind its inhibition of potassium chloride response. Nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase products, lipoxygenase products, endothelin-1, angiotensin-II, and serotonin are not involved in the vasoconstricting action. (Key words: Halogenated volatile anesthetics; sympathetic nervous system; systemic hypotension; vascular endothelium.)
Surgeon and Type of Anesthesia Predict Variability in Surgical Procedure Times
Authors: Strum David P. , Sampson Allan R. , May Jerrold H. , Vargas Luis G. 
Published: August 2004

Background
Variability in surgical procedure times increases the cost of healthcare delivery by increasing both the underutilization and overutilization of expensive surgical resources. To reduce variability in surgical procedure times, we must identify and study its sources.

Methods
Our data set consisted of all surgeries performed over a 7-yr period at a large teaching hospital, resulting in 46,322 surgical cases. To study factors associated with variability in surgical procedure times, data mining techniques were used to segment and focus the data so that the analyses would be both technically and intellectually feasible. The data were subdivided into 40 representative segments of manageable size and variability based on headers adopted from the common procedural terminology classification. Each data segment was then analyzed using a main-effects linear model to identify and quantify specific sources of variability in surgical procedure times.

Results
The single most important source of variability in surgical procedure times was surgeon effect. Type of anesthesia, age, gender, and American Society of Anesthesiologists risk class were additional sources of variability. Intrinsic case-specific variability, unexplained by any of the preceding factors, was found to be highest for shorter surgeries relative to longer procedures. Variability in procedure times among surgeons was a multiplicative function (proportionate to time) of surgical time and total procedure time, such that as procedure times increased, variability in surgeons' surgical time increased proportionately.

Conclusions
Surgeon-specific variability should be considered when building scheduling heuristics for longer surgeries. Results concerning variability in surgical procedure times due to factors such as type of anesthesia, age, gender, and American Society of Anesthesiologists risk class may be extrapolated to scheduling in other institutions, although specifics on individual surgeons may not. This research identifies factors associated with variability in surgical procedure times, knowledge of which may ultimately be used to improve surgical scheduling and operating room utilization.
Validation of the Non-communicating Children's Pain Checklist–Postoperative Version
Authors: Breau Lynn M. , Finley G. Allen , McGrath Patrick J. , Camfield Carol S. 
Published: August 2004

Background
This study evaluated the psychometric properties of the Non-communicating Children's Pain Checklist-Postoperative Version (NCCPC-PV) when used with children with severe intellectual disabilities.

Methods
The caregivers of 24 children with severe intellectual disabilities (aged 3-19 yr) took part. Each child was observed by one of their caregivers and one of the researchers for 10 min before and after surgery. They independently completed the NCCPC-PV and made a visual analog scale rating of the child's pain intensity for those times. A nurse also completed a visual analog scale for the same observations.

Results
The NCCPC-PV was internally reliable (Cronbach alpha = 0.91) and showed good interrater reliability. A repeated-measures analysis of variance indicated NCCPC-PV total and subscale scores were significantly higher after surgery and did not differ by observer. Postoperative NCCPC-PV scores correlated with visual analog scale ratings provided by caregivers and researchers, but not with those of nurses. A score of 11 on the NCCPC-PV, by caregivers, provided 0.88 sensitivity and 0.81 specificity for classifying children with moderate to severe pain.

Conclusions
The NCCPC-PV displayed good psychometric properties when used for the postoperative pain of children with severe intellectual disabilities and has the potential to be useful in a clinical setting. The results suggest familiarity with an individual child with intellectual disabilities is not necessary for pain assessment.
Chronobiology of Epidural Ropivacaine
Authors: Debon Richard , Chassard Dominique , Duflo Frédéric , Boselli Emmanuel , Bryssine Boris , Allaouchiche Bernard 
Published: August 2004

Background
A temporal pattern of the kinetics of local anesthetics is demonstrated in dental and skin anesthesia, with an important variation in the duration of action related to the hour of administration. The aim of this study is to determine whether the hour of injection influences the duration of epidurally administered ropivacaine during labor.

Methods
One hundred ninety-four women in the first stage of labor were assigned to one of four groups throughout the day period: group 1 (night: from 1:01 to 7:00 am), group 2 (morning: from 7:01 am to 1:00 pm), group 3 (afternoon: from 1:01 to 7:00 pm), and group 4 (evening: from 7:01 pm to 1:00 am). Each patient received 14 ml ropivacaine, 0.17%, epidurally, and analgesia duration was measured.

Results
Pain assessed by a visual analog score was not differ-ent among groups before the first injection of local anesthetic. Analgesia duration was greater in the diurnal period (group 2: 110 +/- 25 min and group 3: 117 +/- 23 min) compared with the nocturnal period (group 1: 94 +/- 23 min and group 4: 91 +/- 23 min) (P < 0.01). The largest intraday variation of analgesia duration among groups reached 28%.

Conclusions
Epidural analgesia duration exhibits a temporal pattern with important differences among diurnal and nocturnal phases. The authors emphasize that the lack of consideration of the chronobiologic conditions in epidural analgesia studies may create significant statistical bias. Future studies dealing with epidural local anesthetics should consider the time of drug administration.
Cesarean Delivery
Authors: Sharma Shiv K. , Alexander James M. , Messick Gary , Bloom Steven L. , McIntire Donald D. , Wiley Jackie , Leveno Kenneth J. 
Published: August 2004

Background
Controversy concerning increased cesarean births as a result of epidural analgesia for relief of labor pain has been attributed, in large part, to difficulties interpreting published studies because of design flaws. In this study, the authors compared epidural analgesia to intravenous meperidine analgesia using patient-controlled devices during labor to evaluate the effects of labor epidural analgesia, primarily on the rate of cesarean deliveries while minimizing limitations attributable to study design.

Methods
Four hundred fifty-nine nulliparous women in spontaneous labor at term were randomly assigned to receive either epidural analgesia or intravenous meperidine analgesia. Epidural analgesia was initiated with 0.25% bupivacaine and was maintained with 0.0625% bupivacaine and fentanyl 2 microg/ml at 6 ml/h with 5-ml bolus doses every 15 min as needed using a patient-controlled pump. Women in the intravenous analgesia group received 50 mg meperidine with 25 mg promethazine hydrochloride as an initial bolus, followed by 15 mg meperidine every 10 min as needed, using a patient-controlled pump. A written procedural manual that prescribed the intrapartum obstetric management was followed for each woman randomized in the study.

Results
A total of 226 women were randomized to receive epidural analgesia, and 233 women were randomized to receive intravenous meperidine analgesia. Protocol violations occurred in 8% (38 of 459) of women. There was no difference in the rate of cesarean deliveries between the two analgesia groups (epidural analgesia, 7% [16 of 226; 95% confidence interval, 4-11%] vs. intravenous meperidine analgesia, 9% [20 of 233; 95% confidence interval, 5-13%]; P = 0.61). Significantly more women randomized to epidural analgesia had forceps deliveries compared with those randomized to meperidine analgesia (12% [26 of 226] vs. 3% [7 of 233]; P < 0.001). Women who received epidural analgesia reported lower pain scores during labor and delivery compared with women who received intravenous meperidine analgesia.

Conclusions
Epidural analgesia compared with intravenous meperidine analgesia during labor does not increase cesarean deliveries in nulliparous women.
Inability to Consistently Elicit a Motor Response following Sensory Paresthesia during Interscalene Block Administration
Authors: Urmey William F. , Stanton Jennifer 
Published: August 2004

Background
Two methods of nerve block based on eliciting neural feedback with the block needle currently exist. The paresthesia technique uses sensory feedback to ascertain that the needle tip is close to the nerve. By contrast, a peripheral nerve stimulator makes use of motor responses to electrical stimulation. The relation of motor responses to an electrical peripheral nerve stimulator and sensory nerve contact (paresthesia) had not been studied.

Methods
Thirty consecutive unpremedicated patients who presented for shoulder surgery with interscalene block anesthesia were prospectively studied. Interscalene block was performed by the single paresthesia method of Winnie, using an insulated or non-insulated needle connected to a peripheral nerve stimulator with the power off. At the precise point of paresthesia, the peripheral nerve stimulator was turned on, and the current was slowly increased to 1.0 mA with a pulse width of 0.2 ms. Presence and location of any motor responses were observed and recorded.

Results
All patients had easily elicited paresthesias. The site of first paresthesia was to the shoulder in 73% of patients. Only 30% of patients exhibited any motor response to electrical stimulation up to 1.0 mA. There was no relation between site of paresthesia and associated motor nerve response.

Conclusion
Elicitation of paresthesia does not translate to an ability to elicit a motor response to a peripheral nerve stimulator in the majority of patients.
The Influence of Remifentanil on the Dynamic Relationship between Sevoflurane and Surrogate Anesthetic Effect Measures Derived from the EEG
Authors: Olofsen Erik , Sleigh James W. , Dahan Albert 
Published: August 2004

Background
The authors modeled the influence of remifentanil on the dynamics of sevoflurane using three parameters derived from the electroencephalogram: 95% spectral edge frequency (SEF), canonical univariate parameter (CUP), and Bispectral Index (BIS).

Methods
Thirty-six patients with American Society of Anesthesiologists physical status class I or II were recruited, of which 12 received a target remifentanil concentration of 0 ng/ml, eight 2 ng/ml, eight 4 ng/ml, and another eight 8 ng/ml. Next (before surgery), several step-wise changes in the end-tidal sevoflurane concentration (F(ET,sevo)) were performed. A data acquisition system simultaneously recorded F(ET,sevo), the raw electroencephalogram, BIS, and SEF. The authors used a combination of an effect compartment and an inhibitory sigmoid E(MAX) model to describe the relation between F(ET,sevo) and BIS, SEF, and CUP. Model parameters (t(1/2)k(e0), E(MAX), E(MIN), C(50), gamma, CUP weight factors) were estimated using the population data analysis program NONMEM. Significant remifentanil model parameter dependencies (P < 0.01) were determined.

Results
Determined from SEF, remifentanil had no effect on t(1/2)k(e0) (1.91 +/- 0.26 min [mean +/- standard error]) but caused an increase in C(50) (baseline = 1.48 +/- 0.12%; 80% increase at 8 ng/ml) and decrease in E(MIN) (baseline = 10.8 +/- 0.6 Hz; 80% reduction at 8 ng/ml). Determined from CUP, remifentanil caused a dose-dependent decrease in t(1/2)k(e0) (baseline = 4.31 +/- 1.00 min; 60% decrease at 8 ng/ml), with no effect on C(50) (baseline = 0.88 +/- 0.13%). Determined from BIS, remifentanil caused a dose-dependent decrease in t(1/2)k(e0) (baseline value = 3.11 +/- 0.32 min; 40% decrease at 8 ng/ml), without affecting C(50) (baseline = 1.12 +/- 0.05%). Median R(2) values of the pooled data set were 0.815 for SEF, 0.933 for CUP (P < 0.01 vs. SEF), and 0.952 for BIS (P < 0.01 vs. SEF and CUP). Addition of remifentanil increased the R(2) values for CUP only.

Conclusions
Remifentanil accelerates sevoflurane blood-brain equilibration without affecting its hypnotic potency as determined from BIS and CUP. In terms of R(2), the authors' pharmacodynamic model describes the anesthetic-BIS relation best.
Development and Evaluation of a Graphical Anesthesia Drug Display
Authors: Syroid Noah D. , Agutter James , Drews Frank A. , Westenskow Dwayne R. , Albert Robert W. , Bermudez Julio C. , Strayer David L. , Prenzel Hauke , Loeb Robert G. , Weinger Matthew B. 
Published: August 2004

Background
Usable real-time displays of intravenous anesthetic concentrations and effects could significantly enhance intraoperative clinical decision-making. Pharmacokinetic models are available to estimate past, present, and future drug effect-site concentrations, and pharmacodynamic models are available to predict the drug's associated physiologic effects.

Methods
An interdisciplinary research team (bioengineering, architecture, anesthesiology, computer engineering, and cognitive psychology) developed a graphic display that presents the real-time effect-site concentrations, normalized to the drugs' EC(95), of intravenous drugs. Graphical metaphors were created to show the drugs' pharmacodynamics. To evaluate the effect of the display on the management of total intravenous anesthesia, 15 anesthesiologists participated in a computer-based simulation study. The participants cared for patients during two experimental conditions: with and without the drug display.

Results
With the drug display, clinicians administered more bolus doses of remifentanil during anesthesia maintenance. There was a significantly lower variation in the predicted effect-site concentrations for remifentanil and propofol, and effect-site concentrations were maintained closer to the drugs' EC(95). There was no significant difference in the simulated patient heart rate and blood pressure with respect to experimental condition. The perceived performance for the participants was increased with the drug display, whereas mental demand, effort, and frustration level were reduced. In a post-simulation questionnaire, participants rated the display to be a useful addition to anesthesia monitoring.

Conclusions
The drug display altered simulated clinical practice. These results, which will inform the next iteration of designs and evaluations, suggest promise for this approach to drug data visualization.