bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perfluorohexane Attenuates Proinflammatory and Procoagulatory Response of Activated Monocytes and Alveolar Macrophages
Authors: Koch Thea , Ragaller Maximilian , Haufe Dirk , Hofer Andreas , Grosser Marianne , Albrecht Detlev M. , Kotzsch Matthias , Luther Thomas 
Published: November 2003

Background
A number of studies have demonstrated the effectiveness of liquid ventilation with perfluorocarbons in improving pulmonary function in acute respiratory distress syndrome. Although it is known that perfluorocarbon-associated gas exchange facilitates lung mechanics and oxygenation, the complete mechanism by which perfluorocarbons exert their beneficial effects in acute lung injury still remains unclear. Possibly, an influence of perfluorocarbons on proinflammatory and procoagulant features of monocytic cells present in the alveolar space, such as alveolar macrophages (AMs), may be involved. Therefore, we examined in an in vitro model the effects of perfluorocarbon on both activated mononuclear blood cells (MBCs) and AMs by monitoring the expression of interleukin (IL)-1 beta, tumor necrosis factor (TNF)alpha, and tissue factor (TF).

Methods
Mononuclear blood cells, obtained from peripheral blood of healthy volunteers, or AMs from diagnostic bronchoalveolar lavage were stimulated by incubation with lipopolysaccharide in the presence of different amounts of perfluorohexane, which was devoid of cytotoxicity.

Results
Using both video-enhanced contrast and electron microscopy, the authors observed that perfluorohexane droplets were phagocytosed by activated monocytes as well as by in vitro--cultured AMs within 1--3 h. After lipopolysaccharide stimulation of monocytes or AMs, we observed a down-regulation of TF mRNA and a significant inhibition (P < 0.05) of cellular TF antigen by perfluorohexane. In addition, the concentration of both IL-1 beta and TNF alpha in the supernatant of lipopolysaccharide-stimulated MBC was significantly decreased (P < 0.01) by perfluorohexane compared with controls without perfluorohexane. By preincubation of lipopolysaccharide-containing medium with perfluorohexane, the authors could exclude that the inhibitory effect of perfluorohexane was caused by binding or sequestering limited amounts of lipopolysaccharide.

Conclusion
Taken together, our results demonstrate an interference of perfluorohexane with the expression of the procoagulant protein TF on monocytes and AMs as well as with the release of proinflammatory cytokines by MBCs. These effects may contribute to the protective role of liquid ventilation with perfluorocarbons in injuries associated with local activation of inflammatory processes.
Anesthetic-like Interaction of the Sleep-inducing Lipid Oleamide with Voltage-gated Sodium Channels in Mammalian Brain
Authors: Nicholson Russell A. , Zheng Jian , Robin Ganellin C. , Verdon Bernard , Lees George 
Published: November 2003

Background
cis-9,10-Octadecenoamide (cOA) accumulates in cerebrospinal fluid during sleep deprivation and induces sleep in animals, but its cellular actions are poorly characterized. In earlier studies, like a variety of anesthetics, cOA modulated gamma-aminobutyric acidA receptors and inhibited transmitter release/burst firing in cultured neurones or synaptoneurosomes.

Methods
Here, radioligand binding ([3H]batrachotoxinin A 20-alpha-benzoate and mouse central nervous system synaptoneurosomes) and voltage clamp (whole cell recording from cultured NIE115 murine neuroblastoma) confirmed an interaction with neuronal voltage-gated sodium channels (VGSC).

Results
cOA stereoselectively inhibited specific binding of toxin to VGSC (inhibitor concentration that displaces 50% of specifically bound radioligand, 39.5 microm). cOA increased (4x) the Kd of toxin binding without affecting its binding maximum. Rate of dissociation of radioligand was increased without altering association kinetics, suggesting an allosteric effect (indirect competition at site 2 on VGSC). cOA blocked tetrodotoxin-sensitive sodium currents (maximal effect and affinity were significantly greater at depolarized potentials; P < 0.01). Between 3.2 and 64 microm, the block was concentration-dependent and saturable, but cOA did not alter the V50 for activation curves or the measured reversal potential (P > 0.05). Inactivation curves were significantly shifted in the hyperpolarizing direction by cOA (maximum, -15.4 +/- 0.9 mV at 32 microm). cOA (10 microm) slowed recovery from inactivation, with tau increasing from 3.7 +/- 0.4 ms to 6.4 +/- 0.5 ms (P < 0.001). cOA did not produce frequency-dependent facilitation of block (up to 10 Hz).

Conclusions
These effects (and the capacity of oleamide to modulate gamma-aminobutyric acidA receptors in earlier studies) are strikingly similar to those of a variety of anesthetics. Oleamide may represent an endogenous ligand for depressant drug sites in mammalian brain.
Halothane Increases Smooth Muscle Protein Phosphatase in Airway Smooth Muscle
Authors: Hanazaki Motohiko , Jones Keith A. , Perkins William J. , Warner David O. 
Published: November 2003

Background
Halothane relaxes airway smooth muscle, in part, by decreasing the force produced for a given intracellular [Ca(2+)] (i.e., Ca(2+) sensitivity) during muscarinic stimulation, an effect produced by a decrease in regulatory myosin light-chain (rMLC) phosphorylation. The authors tested the hypothesis that halothane reduces rMLC phosphorylation during muscarinic stimulation at constant intracellular [Ca(2+)] by increasing smooth muscle protein phosphatase (SMPP) activity, without changing myosin light-chain kinase (MLCK) activity.

Methods
Enzyme activities were assayed in beta-escin permeabilized strips of canine tracheal smooth muscle. Under conditions of constant intracellular [Ca(2+)], the rate of rMLC phosphorylation was measured by Western blotting during inhibition of SMPP with microcystin-LR (to assay MLCK activity) or during inhibition of MLCK by wortmannin and adenosine triphosphate depletion (to assay SMPP activity). The effect of halothane (0.8 mm) on enzyme activities and isometric force during stimulation with 0.6 microm Ca(2+) and 10 microm acetylcholine was determined.

Results
Halothane produced a 14 +/- 8% (mean +/- SD) decrease in isometric force by significantly reducing rMLC phosphorylation (from 32 +/- 9% to 28 +/- 9%). Halothane had no significant effect on any parameter of a monoexponential relation fit to the data for the MLCK activity assay. In contrast, halothane significantly decreased the half-time for rMLC dephosphorylation in the SMPP activity assay (from 0.74 +/- 0.28 min to 0.44 +/- 0.10 min), indicating that it increased SMPP activity.

Conclusions
Halothane decreases Ca(2+) sensitivity and rMLC phosphorylation in airway smooth muscle during muscarinic receptor stimulation by increasing SMPP activity, without affecting MLCK, probably by disrupting receptor G-protein signaling pathways that inhibit SMPP.
Relation between Initial Blood Distribution Volume and Propofol Induction Dose Requirement
Authors: Kazama Tomiei , Ikeda Kazuyuki , Morita Koji , Ikeda Takehiko , Kikura Mutsuhito , Sato Shigehito 
Published: November 2003

Background
Propofol induction dose is variable and depends on many factors, including initial volume of distribution and early disposition. The authors hypothesized that preadministration blood distribution volumes, cardiac output (CO), and hepatic blood flow (HBF) could be examined to establish a propofol induction dose.

Methods
Propofol dose required to reach loss of consciousness, when infused at infusion rate per lean body mass (LBM) of 40 mg x kg(-1) x h(-1), was determined in 75 patients aged 11-85 yr. CO, blood volume (BV), central blood volume (CBV), and HBF were measured with indocyanine green pulse spectrophotometry. Univariate least squares linear regression analysis was used to individually analyze the relation between propofol induction dose and patient characteristics, including LBM, baseline distribution volumes, CO, and HBF. Stepwise multiple linear regression models were used to select important predictors of induction dose.

Results
Although there was a significant correlation between the induction dose and each of the eight variables of age, sex, LBM, hemoglobin, CO, BV, CBV, and HBF, only factors of age (partial r = -0.655), LBM (partial r = 0.325), CBV (partial r = 0.540), and HBF (partial r = 0.357) were independently associated with the induction dose (R2 = 0.85) when all variables were included in a multivariate model.

Conclusions
At a constant propofol infusion rate of 40 mg x kg(-1) x h(-1) as a function of LBM in patients with American Society of Anesthesiologists physical status I or II, the induction dose can be determined from four variables: age, LBM, CBV, and HBF.
Opioids Inhibit Febrile Responses in Humans, Whereas Epidural Analgesia Does Not
Authors: Negishi Chiharu , Lenhardt Rainer , Ozaki Makoto , Ettinger Katharine , Bastanmehr Hiva , Bjorksten Andrew R. , Sessler Daniel I. 
Published: November 2003

Background
Epidural analgesia is frequently associated with hyperthermia during labor and in the postoperative period. The conventional assumption is that hyperthermia is caused by the technique, although no convincing mechanism has been proposed. However, pain in the "control" patients is inevitably treated with opioids, which themselves attenuate fever. Fever associated with infection or tissue injury may then be suppressed by opioids in the "control" patients while being expressed normally in patients given epidural analgesia. The authors therefore tested the hypothesis that fever in humans is manifested normally during epidural analgesia, but is suppressed by low-dose intravenous opioid.

Methods
The authors studied eight volunteers, each on four study days. Fever was induced each day by 150 IU/g intravenous interleukin 2. Volunteers were randomly assigned to: (1) a control day when no opioid or epidural analgesia was given; (2) epidural analgesia using ropivacaine alone; (3) epidural analgesia using ropivacaine in combination with 2 microg/ml fentanyl; or (4) intravenous fentanyl at a target plasma concentration of 2.5 ng/ml.

Results
Fentanyl halved the febrile response to pyrogen, decreasing integrated core temperature from 7.0 +/- 3.2 degrees C. h on the control day, to 3.8 +/- 3.0 degrees C. h on the intravenous fentanyl day. In contrast, epidural ropivacaine and epidural ropivacaine-fentanyl did not inhibit fever. The fraction of core-temperature measurements that exceeded 38 degrees C was halved by intravenous fentanyl, and the fraction exceeding 38.5 degrees C was reduced more than fivefold.

Conclusions
These data support the authors' proposed mechanism for hyperthermia during epidural analgesia. Fever during epidural analgesia should thus not be considered a complication of the anesthetic technique per se.
Subarachnoid Sufentanil for Early Postoperative Pain Management in Orthopedic Patients
Authors: Standl Thomas G. , Horn Ernst-Peter , Luckmann Michael , Burmeister Marc-Alexander , Wilhelm Stefan , Schulte am Esch Jochen 
Published: November 2003

Background
Continuous spinal anesthesia is frequently used for intraoperative anesthesia but rarely for postoperative pain management. Because even small doses of local anesthetics can be associated with motor deficits, subarachnoid opioid injection may be an alternative.

Methods
Eighty patients randomly received a subarachnoid injection of 10 microg sufentanil, 5 mg bupivacaine, 2.5 microg sufentanil plus 2.5 mg bupivacaine, or saline through 28-gauge spinal microcatheters for early postoperative pain relief after major lower-limb surgery (n = 20 in each group). Hemodynamic and respiratory parameters, pain scores, and motor function were monitored, and sufentanil concentrations in plasma and cerebrospinal fluid were measured. Ten additional patients received up to three repetitive injections of 10 microg sufentanil over 24 h.

Results
All drugs provided excellent pain relief within 15 min after injection, lasting 128 +/- 61 min with sufentanil, 146 +/- 74 min with bupivacaine, and 167 +/- 78 min with the mixture. Patients receiving bupivacaine showed the highest cephalad extension of sensory block (median, T6) and the most intense motor block, whereas patients given only sufentanil had no motor deficit. The duration of analgesia was shorter after subsequent sufentanil injection (100-115 min) than after the first injection (198 +/- 70 min). Six of 50 patients with sufentanil experienced a short episode of respiratory depression within 30 min after the first injection. Cerebrospinal fluid concentrations of sufentanil peaked at 5 min after injection (183 +/- 167 ng/ml) but were at the level of detection in the plasma.

Conclusions
Sufentanil injected through microspinal catheters provided profound pain relief without impairing motor function when compared with bupivacaine. However, close monitoring remains mandatory in this setting.
Chlorhexidine versus Povidone Iodine in Preventing Colonization of Continuous Epidural Catheters in Children
Authors: Kinirons Brian , Mimoz Olivier , Lafendi Leila , Naas Thierry , Meunier Jean-François , Nordmann Patrice 
Published: November 2003

Background
Chlorhexidine is better than povidone iodine for skin preparation before intravascular device insertion or blood culture collection, but it is not known whether chlorhexidine is superior in reducing colonization of continuous epidural catheters.

Methods
Children requiring an epidural catheter for postoperative analgesia longer than 24 h were randomly assigned to receive skin preparation with an alcoholic solution of 0.5% chlorhexidine or an aqueous solution of 10% povidone iodine before catheter insertion. Using surgical aseptic techniques, catheters were inserted into either the lumbar or the thoracic epidural space based on the preferences of the anesthesia team, on clinical indication, or both. Immediately before epidural catheter removal, their insertion site and hub were qualitatively cultures. After their removal, the catheter tips were quantitatively cultured. Catheters were classified as colonized when their tips yielded 1,000 or more colony-forming units/ml in cultures.

Results
Of 100 randomly assigned patients, 96 were evaluable. The clinical characteristics of the patients and the risk factors for infection were similar in the two groups. Catheters were kept in place for a median (range) duration of 50 (range, 21-100) h. Catheters inserted after skin preparation with chlorhexidine were one sixth as likely and less quickly to be colonized as catheters inserted after skin preparation with povidone iodine (1 of 52 catheters [0.9 per 100 catheter days] vs. 5 of 44 catheters [5.6 per 100 catheter days]; relative risk, 0.2 [95% confidence interval, 0.1-1.0]; P = 0.02). Coagulase-negative staphylococci were the only colonizing microorganisms recovered, and the skin surrounding the catheter insertion site was the origin of all the colonizing microorganisms.

Conclusions
Compared with aqueous povidone iodine, the use of alcoholic chlorhexidine for cutaneous antisepsis before epidural catheter insertion reduces the risk of catheter colonization in children.
Effect of Cricoid Pressure on the Success of Endotracheal Intubation with a Lightwand
Authors: Hodgson R. Eric , Gopalan P. Dean , Burrows Richard C. , Zuma Khangelani 
Published: November 2003

Background
The lightwand may be useful as an alternative for tracheal intubation during a rapid-sequence induction of anesthesia in the presence of a full stomach. This study was undertaken to assess the effect of application of cricoid pressure on the success of lightwand intubation.

Methods
Sixty adult female patients presenting for abdominal hysterectomy were randomly allocated to lightwand intubation with and without cricoid pressure. The time to successful intubation and number of attempts were recorded.

Results
All 30 patients allocated to intubation without cricoid pressure were intubated successfully at the first attempt within a median time of 28 s (95% confidence interval, 18-77 s). Lightwand intubation with cricoid pressure was successful in 26 of 30 patients at the first attempt, but the median time to successful intubation was significantly longer at 48.5 s (95% confidence interval, 36-78 s; P = 0.001). Three patients required two attempts for successful intubation, and one could not be intubated with the lightwand while cricoid pressure was being applied.

Conclusions
The lightwand cannot be recommended for the first attempt at intubation where cricoid pressure is being applied because the time to successful intubation is significantly prolonged, and the failure rate for the first attempt at lightwand intubation is 13%.
Anesthetic Concentrations of Propofol Protect against Oxidative Stress in Primary Astrocyte Cultures
Authors: Peters Caralei E. , Korcok Jasminka , Gelb Adrian W. , Wilson John X. 
Published: November 2003

Background
The extracellular concentration of glutamate in the brain increases after oxidative damage. This increase may be caused, in part, by changes in glutamate transport by astrocytes. The authors hypothesized that propofol and hypothermia mitigate the effects on astrocytes of oxidative stress.

Methods
Primary cultures of rat cerebral astrocytes were subjected to oxidative stress by incubation with tert-butyl hydroperoxide for 30 min, followed by a 30-90-min washout period. The effects of prophylactic (simultaneous with tert-butyl hydroperoxide application) and delayed (administered 30 min after the oxidant) propofol or hypothermia were determined by measuring the uptake of glutamate as well as the release of preloaded d-aspartate (a nonmetabolizable analog of glutamate) and endogenous lactate dehydrogenase (a cytosolic marker).

Results
Delayed administration of an anesthetic concentration of propofol (1-3 microm) prevented the inhibition of high-affinity glutamate uptake, stimulation of d-aspartate release, and increase in lactate dehydrogenase release caused by tert-butyl hydroperoxide (1 mm, 37 degrees C). The protective effect of propofol (EC50 = 2 microm) on glutamate uptake was 20-fold more potent than that of alpha-tocopherol (EC50 = 40 microm). Prophylactic hypothermia (28 and 33 degrees C) also protected astrocytes from tert-butyl hydroperoxide. Delayed hypothermia was not protective but did not compromise rescue by propofol.

Conclusions
Clinical levels of propofol and hypothermia mitigate the effects of oxidative stress on astrocytic uptake and retention of glutamate, with propofol having a relatively larger therapeutic window. The ability of these treatments to normalize cell transport systems may attenuate the pathologic increase in extracellular glutamate at synapses and thus prevent excitotoxic neuronal death.
Electrophysiologic Evidence for Increased Endogenous GABAergic but Not Glycinergic Inhibitory Tone in the Rat Spinal Nerve Ligation Model of Neuropathy
Authors: Kontinen Vesa K. , Stanfa Louise C. , Basu Amlan , Dickenson Anthony H. 
Published: November 2003

Background
Changes in the inhibitory activity mediated by gamma-aminobutyric acid (GABA) and glycine, acting at spinal GABAA receptors and strychnine-sensitive glycine receptors, are of interest in the development of neuropathic pain. There is anatomic evidence for changes in these transmitter systems after nerve injuries, and blocking either GABAA or glycine receptors has been shown to produce allodynia-like behavior in awake normal animals.

Methods
In this study, the possible changes in GABAergic and glycinergic inhibitory activity in the spinal nerve ligation model of neuropathic pain were studied by comparing the effects of the GABAA-receptor antagonist bicuculline and the glycine-receptor antagonist strychnine in neuropathic rats to their effects in sham-operated and nonoperated control rats.

Results
Bicuculline produced a dose-related facilitation of the Adelta-fiber-evoked activity in all study groups and increased C-fiber-mediated activity in the spinal nerve ligation group but not in either of the control groups. There were no differences in the effect of bicuculline on low threshold responses between the study groups. The glycine receptor antagonist strychnine did not have a statistically significant effect on any of the parameters studied in any of the control groups.

Conclusions
These results support the idea of an increased GABAergic inhibitory tone in the spinal cord of neuropathic rats, possibly as compensation for increased excitability after nerve injury.
Initial and Subsequent Dosing of Rectal Acetaminophen in Children
Authors: Birmingham, AF1-0567 Patrick K. , Tobin Michael J. , Fisher Dennis M. , Henthorn Thomas K. , Hall Steven C. , Coté Charles J. 
Published: November 2003

Background
Recent studies have determined that an initial rectal acetaminophen dose of approximately 40 mg/kg is needed in children to achieve target antipyretic serum concentrations. The timing and amount of subsequent doses after a 40-mg/kg dose has not been clarified for this route of administration. Based on the authors' previous pharmacokinetic data, they examined whether a 40-mg/kg loading dose followed by 20-mg/kg doses at 6-h intervals maintain serum concentrations within the target range of 10-20 microg/ml, without evidence of accumulation.

Methods
Children (n = 16) received rectal acetaminophen (40 mg/kg) and up to three additional doses of 20 mg/kg at 6-h intervals. Venous blood samples were taken every 30 min for 4 h, then every 60 min for 4 h, and every 4 h for 16 h. The authors assessed whether their published pharmacokinetic parameters predicted the acetaminophen concentrations in the present study. They also assessed their dosing regimen by determining the fraction of time each individual maintained the target concentration.

Results
All patients received the initial loading dose; 10 of 16 patients received three subsequent doses. Serum concentrations with the initial dose were in the target range 38 +/- 25% of the time. With subsequent dosing, the target range was maintained 60 +/- 29% of the time. The highest serum concentration with initial or subsequent dosing was 38.6 microg/ml. Pharmacokinetic parameters from the earlier study predicted the serum concentrations observed for both initial and subsequent doses.

Conclusions
A rectal acetaminophen loading dose of 40 mg/kg followed by 20-mg/kg doses every 6 h results in serum concentrations centered at the target range of 10-20 microg/ml. There was large interindividual variability in pharmacokinetic characteristics. There was no evidence of accumulation during the 24-h sampling period.