bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postoperative Titration of Intravenous Morphine in the Elderly Patient
Authors: Aubrun Frédéric , Monsel Stéphanie , Langeron Olivier , Coriat Pierre , Riou Bruno 
Published: November 2003

Background
Intravenous morphine titration is used to obtain rapid and complete postoperative pain relief. Whether this titration can be safely administered in the elderly patients remains a matter for debate.

Methods
Intravenous morphine titration was administered as a bolus of 2 (body weight < or = 60 kg) or 3 (body weight > 60 kg) mg. The interval between each bolus was 5 min. There was no limitation in the number of boluses given until pain relief or severe adverse effect occurred. The visual analog scale threshold required to administer morphine was 30 mm, and pain relief was defined as a visual analog scale score of 30 mm or less. Patients were divided into two groups: young and elderly (age > or = 70 yr) patients. Data were expressed as mean +/- SD.

Results
Eight hundred seventy-five patients (83%) were young and 175 patients (17%) were elderly. At the end of morphine titration, the visual analog scale score and the number of patients with pain relief were not significantly different between groups. The total dose of morphine per kilograms of body weight administered was not significantly different between groups (0.15 +/- 0.10 vs. 0.14 +/- 0.09 mg/kg, not significant). No significant differences were observed in the incidence of morphine-related adverse effects (13 vs. 14%, not significant), the number of sedated patients (60 vs. 60%, not significant), and the number of patients whose titration had to be stopped (2 vs. 2%, not significant).

Conclusion
Intravenous morphine titration can be safely administered to elderly patients. Because titration is adapted to individual pain, the same protocol can be applied to young and elderly patients.
Early Decay of Pain-related Cerebral Activation in Functional Magnetic Resonance Imaging
Authors: Kurata Jiro , Thulborn Keith R. , Gyulai Ferenc E. , Firestone Leonard L. 
Published: November 2003

Background
Although pain-related activation was localized in multiple brain areas by functional imaging, the temporal profile of its signal has been poorly understood. The authors characterized the temporal evolution of such activation in comparison to that by conventional visual and motor tasks using functional magnetic resonance imaging.

Methods
Five right-handed volunteers underwent whole brain echo-planar imaging on a 3 T magnetic resonance imaging scanner while they received pain stimulus on the right and left forearm and performed visually guided saccade and finger tapping tasks. Pain stimulus on the right and left forearm consisted of four cycles of 15-s stimulus at 47.2-49.0 degrees C, interleaved with 30-s control at 32 degrees C, delivered by a Peltier-type thermode, and visually guided saccade and finger tapping of three cycles of 30-s active and 30-s rest conditions. Voxel-wise t statistical maps were standardized and averaged across subjects. Blood oxygenation level-dependent signal time courses were analyzed at local maxima of representative activation clusters (t > 3.5).

Results
Pain stimulus on the right forearm activated the secondary somatosensory (S2), superior temporal, anterior cingulate, insular, prefrontal cortices, premotor area, and lenticular nucleus. Pain stimulus on the left forearm activated similar but fewer areas at less signal intensity. The S2 activation was dominant on the contralateral hemisphere. Pain-related activation was statistically weaker and showed less consistent signal time courses than visually guided saccade- and finger tapping-related activation. Pain-related signals decayed earlier before the end of stimulus, in contrast to well-sustained signal plateaus induced by visually guided saccade and finger tapping.

Conclusions
The authors speculate that pain-related blood oxygenation level-dependent signals were attenuated by the pain-induced global cerebral blood flow decrease or activation of the descending pain inhibitory systems.
Artifact Robustness, Inter- and Intraindividual Baseline Stability, and Rational EEG Parameter Selection
Authors: Bruhn Jörgen , Bouillon Thomas W. , Hoeft Andreas , Shafer Steven L. 
Published: November 2003

Background
Artifact robustness (i.e., size of deviation of an electroencephalographic parameter value from baseline caused by artifacts) and baseline stability (i.e., consistency of median baseline values) of electroencephalographic parameters profoundly influence electroencephalography-based pharmacodynamic parameter estimation and the usefulness of the processed electroencephalogram as measure of the arousal state of the central nervous system (depth of anesthesia). In this study, the authors compared the artifact robustness and the interindividual and intraindividual baseline stability of several univariate descriptors of the electroencephalogram (Shannon entropy, approximate entropy, spectral edge frequency 95, delta ratio, and canonical univariate parameter).

Methods
Electroencephalographic data of 16 healthy volunteers before and after administration of an intravenous bolus of propofol (2 mg/kg body weight) were analyzed. Each volunteer was studied twice. The baseline electroencephalogram was recorded for a median of 18 min before drug administration. For each electroencephalographic descriptor, the authors calculated the following: (1) baseline variability (= (median baseline - median effect) [i.e., signal]/SD baseline [i.e., noise]) without artifact rejection; (2) baseline variability with artifact rejection; and (3) baseline stability within and between individuals (= (median baseline - median effect) averaged over all volunteers/SD of all median baselines).

Results
Without artifact rejection, Shannon entropy and canonical univariate parameter displayed the highest signal-to-noise ratio. After artifact rejection, approximate entropy, Shannon entropy, and the canonical univariate parameter displayed the highest signal-to-noise ratio. Baseline stability within and between individuals was highest for approximate entropy.

Conclusions
With regard to robustness against artifacts, the electroencephalographic entropy parameters and the canonical univariate parameter were superior to spectral edge frequency 95 and delta ratio. Electroencephalographic approximate entropy displayed the best interindividual and intraindividual baseline stability.
Intrathecal Adenosine following Spinal Nerve Ligation in Rat
Authors: Bantel Carsten , Tobin Joseph R. , Li Xinhui , Childers Steven R. , Chen Shao Rui , Eisenach James C. 
Published: November 2003

Background
Intrathecal adenosine produces a remarkably prolonged effect to relieve mechanical hypersensitivity after peripheral nerve injury in animals. The purpose of the current study was to investigate whether this reflected an alteration in kinetics of adenosine in cerebrospinal fluid or in the number of spinal A1 adenosine receptors after nerve injury.

Methods
Male rats were anesthetized, and the left L5 and L6 spinal nerves were ligated. Two weeks later, a lumbar intrathecal catheter and intrathecal space microdialysis catheter were inserted. Adenosine, 20 microg, was injected intrathecally in these and in normal rats, and microdialysates of the intrathecal space were obtained. Radioligand binding studies of adenosine A1 receptors were determined in spinal cord tissue from other normal and spinal nerve-ligated rats.

Results
Adenosine disappeared from rat cerebrospinal fluid within 30 min after intrathecal injection, with no difference between normal and spinal nerve-ligated animals. A1 adenosine receptor binding sites in the spinal cord were increased after spinal nerve ligation. This increase disappeared when adenosine deaminase was added to the membrane homogenates, suggestive of decreased endogenous adenosine in the membranes of nerve-ligated animals.

Conclusion
These data show that prolonged alleviation of hypersensitivity observed with intrathecal adenosine in this animal model of neuropathic pain is not due to prolonged residence in cerebrospinal fluid, although pharmacokinetics in tissues are unknown. Similarly, there is no evidence for up-regulation in spinal A1 adenosine receptors after spinal nerve ligation, and the adenosine deaminase experiment is consistent with a depletion of adenosine in spinal cord tissue after spinal nerve ligation.
Effect of Halothane and Isoflurane on Binding of ADP- and TRAP-6- activated Platelets to Leukocytes in Whole Blood
Authors: de Rossi Lothar W. , Horn Nicola A. , Hecker Klaus E. , Robitzsch Tilo , Hutschenreuter Gabriele , Rossaint Rolf 
Published: November 2003

Background
Adhesion of activated platelets to neutrophils and monocytes has an important role in the regulation of inflammatory processes. This study investigates whether halothane and isoflurane affect binding of activated platelets to leukocytes in human whole blood.

Methods
Citrated whole blood was incubated for 60 min with either 1 or 2 minimum alveolar concentration (MAC) halothane or isoflurane. After stimulation with adenosine-5-diphosphate (ADP) or the thrombin receptor agonist protein TRAP-6, platelet-leukocyte adhesion and surface expression of CD62P on platelets were evaluated by flow cytometry.

Results
Halothane led to an inhibition of agonist-induced adhesion of activated platelets to neutrophils and monocytes. One MAC halothane reduced the formation of TRAP-6-induced platelet-monocyte conjugates. After exposure to 2 MAC halothane, agonist-induced platelet-monocyte and platelet-neutrophil adhesion were inhibited. Surface expression of CD62P on ADP- and TRAP-6-stimulated platelets were significantly reduced after 1 and 2 MAC halothane. After 2 MAC isoflurane, the authors observed an increase of the percentage of lymphocytes with bound platelets after activation with ADP. The percentage of neutrophils with bound platelets after activation with ADP or TRAP-6 was also increased in this group. Two MAC isoflurane led to an increase of the percentage of platelets expressing CD62P in the unstimulated and TRAP-6 stimulated samples, and of the amount of CD62P epitopes on the surface of platelets in the ADP-stimulated samples.

Conclusion
This study indicates that halothane inhibits, whereas isoflurane enhances, adhesion of agonist-activated platelets to leukocytes. Interaction of both anesthetics with the expression of CD62P on platelets contribute to theses effects.
Functional Cerebral Hyperemia Is Unaffected by Isovolemic Hemodilution
Authors: Shen Hui , Greene Andrew S. , Stein Elliot A. , Hudetz Anthony G. 
Published: November 2003

Background
The cerebral hyperemic effect of hemodilution is well known; however, its mechanism and potential modifying effect on the functional hyperemic response to neuronal activation are unclear. The authors investigated the effects of isovolemic hemodilution on vibrissal stimulation-induced changes in cerebrocortical laser Doppler flow and tissue oxygen tension in the rat.

Methods
The hyperemic response to whisker stimulation was assessed in the whisker barrel cortex of 12 rats anesthetized with chloralose-urethane before and after hemodilution. Graded, isovolemic hemodilution was performed by three repeated withdrawals of 3 ml blood with replacement of equal volume of 5% serum albumin. Measured systemic hematocrit values were 39.3 +/- 1.3% (control), 29.5 +/- 1.0%, 22.3 +/- 1.5%, and 17.0 +/- 1.6% (after the three hemodilution steps). Arterial blood pressure was maintained at control levels with an infusion of methoxamine. Unilateral whisker stimulation was performed with a mechanical actuator at 8 Hz, and 10 cycles of 10 s on-30 s off periods. In six control animals, shed blood was immediately reinfused, resulting in no change in hematocrit, and whisker stimulation was performed using the same timeline as in the other animals. In six additional experiments, resting cerebral cortical oxygen tension was measured using the phosphorescence quenching technique following the same hemodilution protocol.

Results
Graded hemodilution increased baseline laser Doppler flow by 5.5 +/- 0.9%, 13 +/- 1.6%, and 23.7 +/- 2.2%. Vibrissal stimulation transiently increased laser Doppler flow by 17.0 +/- 2.0%. The hyperemic response was unchanged after hemodilution and was identical to that seen in the control group in all conditions. Tissue oxygen tension increased slightly but significantly with hemodilution at a rate of 1.4 mmHg per 10% hematocrit change (r = 0.83). Mean arterial pressure, arterial oxygen tension, carbon dioxide tension, and pH were within normal limits in each experimental group and were not different from control during hemodilution.

Conclusions
The results suggest that an increase in baseline flow during hemodilution maintains cortical oxygen supply and consequently preserves the normal functional hyperemic response.
Role of PKC in Isoflurane-induced Biphasic Contraction in Skinned Pulmonary Arterial Strips
Authors: Su Judy Y. , Vo Anhkiet C. 
Published: November 2003

Background
Activation or inhibition of protein kinase C (PKC) has been implicated in the anesthetic-induced contraction or relaxation of different types of arteries. In skinned pulmonary arterial strips, the initial halothane-induced contraction has been attributed to PKC activation, but the subsequent relaxation has not. Whether isoflurane has a similar biphasic effect is not known. This study examined the role of PKC and its isoforms in the effect of isoflurane on pulmonary artery.

Methods
Rabbit pulmonary arterial strips were mounted on force transducers and treated with saponin to make the sarcolemma permeable ("skinned" strips). Skinned strips were activated by low Ca(2+) (pCa 6.5 or pCa 6.3 buffered with 7 mm EGTA) or the PKC activator phorbol-12,13-dibutyrate (1 microm) until force reached a steady state (control). Various concentrations of isoflurane (test) were administered, and force was observed at time intervals up to 60 min. The PKC inhibitors (bisindolylmaleimide and Go6976 from 0.1 to 10 microm) were preincubated in a relaxing solution and the subsequent contracting solutions. The results were expressed as a percentage of control, with P < 0.05 considered significant for statistical comparison between the tests and time controls.

Results
In a dose-dependent fashion, isoflurane (1-5%) initially increased (5-40%) and then decreased (3-70%) the Ca(2+)- or phorbol-12,13-dibutyrate (pCa 6.7 buffer)-activated force. The increased in force caused by isoflurane was partially reduced by 3 and 10 microm bisindolylmaleimide, but not by Go6976. Isoflurane-induced relaxation was partially prevented by both inhibitors at 0.1 and 0.3 microm.

Conclusions
Isoflurane causes biphasic effects in skinned pulmonary arterial strips that may be in part mediated by different isoforms of PKC.
Comparison of Amsorb®, Sodalime, and Baralyme®Degradation of Volatile Anesthetics and Formation of Carbon Monoxide and Compound A in Swine In Vivo
Authors: Kharasch Evan D. , Powers Karen M. , Artru Alan A. 
Published: November 2003

Background
Consequences of volatile anesthetic degradation by carbon dioxide absorbents that contain strong base include formation of compound A from sevoflurane, formation of carbon monoxide (CO) and CO toxicity from desflurane, enflurane and isoflurane, delayed inhalation induction, and increased anesthetic costs. Amsorb (Armstrong Ltd., Coleraine, Northern Ireland) is a new absorbent that does not contain strong base and does not form CO or compound A in vitro. This investigation compared Amsorb, Baralyme (Chemetron Medical Division, Allied Healthcare Products, St. Louis, MO), and sodalime effects on CO (from desflurane and isoflurane) and compound A formation, carboxyhemoglobin (COHb) concentrations, and anesthetic degradation in a clinically relevant porcine in vivo model.

Methods
Pigs were anesthetized with desflurane, isoflurane, or sevoflurane, using fresh or partially dehydrated Amsorb, Baralyme, and new and old formulations of sodalime. Anesthetic concentrations in the fresh (preabsorber), inspired (postabsorber), and end-tidal gas were measured, as were inspired CO and compound A concentrations and blood oxyhemoglobin and COHb concentrations.

Results
For desflurane and isoflurane, the order of inspired CO and COHb formation was dehydrated Baralyme > soda-lime > Amsorb. For desflurane and Baralyme, peak CO was 9,700 +/- 5,100 parts per million (ppm), and the increase in COHb was 37 +/- 14%. CO and COHb increases were undetectable with Amsorb. Oxyhemoglobin desaturation occurred with desflurane and Baralyme but not Amsorb or sodalime. The gap between inspired and end-tidal desflurane and isoflurane did not differ between the various dehydrated absorbents. Neither fresh nor dehydrated Amsorb caused compound A formation from sevoflurane. In contrast, Baralyme and sodalime caused 20-40 ppm compound A. The gap between inspired and end-tidal sevoflurane did not differ between fresh absorbents, but was Amsorb < sodalime < Baralyme with dehydrated absorbents.

Conclusion
Amsorb caused minimal if any CO formation, minimal compound A formation regardless of absorbent hydration, and the least amount of sevoflurane degradation. An absorbent like Amsorb, which does not contain strong base or cause anesthetic degradation and formation of toxic products, may have benefit with respect to patient safety, inhalation induction, and anesthetic consumption (cost).
Hyperglycemia Prevents Isoflurane-induced Preconditioning against Myocardial Infarction
Authors: Kehl Franz , Krolikowski John G. , Mraovic Boris , Pagel Paul S. , Warltier David C. , Kersten Judy R. 
Published: November 2003

Background
Volatile anesthetics stimulate but hyperglycemia attenuates activity of mitochondrial adenosine triphosphate-regulated potassium channels. The authors tested the hypothesis that acute hyperglycemia interferes with isoflurane-induced preconditioning in vivo.

Methods
Barbiturate-anesthetized dogs (n = 79) were instrumented for measurement of hemodynamics. Myocardial infarct size and collateral blood flow were assessed with triphenyltetrazolium chloride staining and radioactive microspheres, respectively. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Dogs were randomly assigned to receive an infusion of normal saline (normoglycemic controls) or 15% dextrose in water to increase blood glucose concentrations to 300 or 600 mg/dl in the absence or presence of isoflurane (0.5 or 1.0 minimum alveolar concentration [MAC]) in separate experimental groups. Isoflurane was discontinued, and blood glucose concentrations were allowed to return to baseline values before left anterior descending coronary artery occlusion.

Results
Myocardial infarct size was 26 +/- 1% of the left ventricular area at risk in control experiments. Isoflurane reduced infarct size (15 +/- 2 and 13 +/- 1% during 0.5 and 1.0 MAC, respectively). Hyperglycemia alone did not alter infarct size (26 +/- 2 and 33 +/- 4% during 300 and 600 mg/dl, respectively). Moderate hyperglycemia blocked the protective effects of 0.5 MAC (25 +/- 2%) but not 1.0 MAC isoflurane (13 +/- 2%). In contrast, severe hyperglycemia prevented reductions of infarct size during both 0.5 MAC (29 +/- 3%) and 1.0 MAC isoflurane (28 +/- 4%).

Conclusions
Acute hyperglycemia attenuates reductions in myocardial infarct size produced by isoflurane in dogs.
Effects of the Selective H1and H2Histamine Receptor Antagonists Loratadine and Ranitidine on Autonomic Control of the Heart
Authors: Nault Michael A. , Milne Brian , Parlow Joel L. 
Published: November 2003

Background
H1 and H2 histamine receptor subtypes are present throughout the heart and may be involved in disturbances of cardiac rhythm that occur during anaphylaxis. Although H1 and H2 receptor antagonists are used in the treatment of anaphylaxis, there have been reports implicating these drugs in the genesis of dysrhythmias. This study was designed to investigate the effects of the selective H1 and H2 receptor antagonists loratadine and ranitidine on physiologic autonomic control of the healthy cardiovascular system.

Methods
Using a double-blind, crossover design, 14 healthy volunteers completed the protocol and were randomized to receive one dose of loratadine (20 mg), ranitidine (300 mg), or placebo on each of three separate testing sessions. Continuous electrocardiogram and BP recordings were obtained before and 3 h after administration of study drug. Effects on cardiac autonomic control were quantified using power spectral analysis of heart rate variability and calculation of spontaneous baroreflex sensitivity.

Results
Neither placebo nor loratadine significantly altered indices of autonomic cardiovascular control. Conversely, H2 antagonism with ranitidine resulted in a 23.3% decrease in baroreflex sensitivity (P < 0.05) and a corresponding 25.0% decrease in the ratio of high frequency to total power of heart rate variability, both indices of parasympathetic modulation (P < 0.01). Furthermore, ranitidine evoked a concomitant 103.8% increase in the ratio of low to high frequency power of heart rate variability, an index of sympathetic control (P < 0.01).

Conclusions
H1 receptor antagonism with loratadine does not influence physiologic cardiovascular control in young healthy subjects. However, the altered cardiac sympathovagal balance after oral administration of the H2 receptor antagonist ranitidine indicates a shift toward sympathetic predominance in heart rate control. The authors postulate that this could have implications regarding susceptibility to arrhythmias in conditions of heightened sympathetic stimulation.
Cognitive Impairment after Small-dose Ketamine Isomers in Comparison to Equianalgesic Racemic Ketamine in Human Volunteers
Authors: Pfenninger Ernst G. , Durieux Marcel E. , Himmelseher Sabine 
Published: November 2003

Background
Ketamine is increasingly used in pain therapy but may impair brain functions. Mood and cognitive capacities were compared after equianalgesic small-dose S(+)-, R(-)-, and racemic ketamine in healthy volunteers.

Methods
Twenty-four subjects received intravenous 0.5 mg/kg racemic, 0.25 mg/kg S(+)-, and 1.0 mg/kg R(-)-ketamine in a prospective, randomized, double-blind, crossover study. Hemodynamic variables, mood, and cognitive capacities were assessed for 60 min.

Results
Transient increases in blood pressure, heart rate, and catecholamines were similar after administration of all drugs. At 20 min after injection, subjects felt less decline in concentration and were more brave after S(+)- than racemic ketamine. They reported being less lethargic but more out-of-control after R(-)- than racemic ketamine. Ketamine isomers induced less drowsiness, less lethargy, and less impairment in clustered subjective cognitive capacity than racemic ketamine for the 60-min study. Objective concentration capacity [test time, S(+): 25.4 +/- 15.2 s, R(-): 34.8 +/- 18.4 s, racemic ketamine: 40.8 +/- 20.8 s, mean +/- SD] and retention in primary memory [test time, S(+): 4.6 +/- 1.2 s, R(-): 4.2 +/- 1.4 s, racemic ketamine: 4.0 +/- 1.4 s, mean +/- SD] declined less after S(+)- than either R(-)- or racemic ketamine at 1 min. At 5 min, immediate recall, anterograde amnesia, retention in primary memory, short-term storage capacity, and intelligence quotient were less reduced after the isomers than racemic ketamine. Speed reading and central information flow decreased less after S(+)- than racemic ketamine.

Conclusions
Early after injection, ketamine isomers induce less tiredness and cognitive impairment than equianalgesic small-dose racemic ketamine. In addition, S(+)-ketamine causes less decline in concentration capacity and primary memory. The differences in drug effects cannot be explained by stereoselective action on one given receptor.