bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized, Single-blinded Trial of Laparoscopic Versus Open Appendectomy in Children
Authors: Lejus C. , Delile L. , Plattner V. , Baron M. , Guillou S. , Heloury Y. , Souron R. 
Published: November 2003

Background
The benefit of laparoscopy to patients has been clearly established in adults undergoing cholecystectomy. Results are less clear for appendectomy. The current study was undertaken to compare the respective 3-day postoperative periods after laparoscopic and open appendectomy in children.

Methods
Sixty-three children (aged 8-15 yr) scheduled for appendectomy were randomly assigned to two groups: open and laparoscopic. Postoperative evaluation included delay of postoperative recovery (walking and feeding), pain assessment by visual analog scale during the 3 subsequent days, amount of nalbuphine administered via a patient-controlled analgesia system during the first 48 h and responses by children, parents, and nurses on the overall quality of analgesia.

Results
There was no difference between groups for demographic data (particularly macroscopic aspect of appendix) analgesia, sedation, delay before eating and walking, incidence of urinary retention, nausea, vomiting. Operative time was long (P < or = to 0.05) in the laparoscopic group (54 +/- 17 min) than in the open group (39 +/- 18 min). Thirty five percent of the children had pain at the shoulder in the LAP group versus ten percent in the open group (P < or = 0.05).

Conclusions
Laparoscopy did not improve analgesia and postoperative recovery after appendectomy in children.
Pharmacokinetics and Pharmacodynamics of Remifentanil in Volunteer Subjects with Severe Liver Disease
Authors: Dershwitz Mark , Hoke J. Frank , Rosow Carl E. , Michalowski Piotr , Connors Patricia M. , Muir Keith T. , Dienstag Jules L. 
Published: November 2003

Background
Remifentanil, a new mu-opioid agonist with an extremely short duration of action, is metabolized by circulating and tissue esterases; therefore, its clearance should be relatively unaffected by changes in hepatic or renal function. This study was designed to determine whether severe hepatic disease affects the pharmacokinetics or pharmacodynamics of remifentanil.

Methods
Ten volunteers with chronic, stable, severe hepatic disease and awaiting liver transplantation and ten matched controls were enrolled. Each subject was given a 4-h infusion of remifentanil. The first five pairs received 0.0125 microgram x kg(-1) x min(-1) for 1 h followed by 0.025 microgram x kg(-1) x min(-1) for 3 h; the second five pairs received double these infusion rates. During and after the infusion, arterial blood was obtained for pharmacokinetic analyses, and the ventilatory response to a hypercarbic challenge was assessed. Simultaneous pharmacokinetic and pharmacodynamic analyses were performed. The pharmacokinetics were described using a one-compartment intravenous infusion model, and ventilatory depression was modelled using the inhibitory E(max) model. The pharmacokinetics of the metabolite GR90291 were determined using noncompartmental methods.

Results
There were no differences in any of the pharmacokinetic parameters for remifentanil or GR90291 between the two groups. The subjects with liver disease were more sensitive to the ventilatory depressant effects of remifentanil. The EC(50) values (the remifentanil concentrations determined from simultaneous pharmacokinetic/pharmacodynamic analyses to depress carbon dioxide-stimulated minute ventilation by 50%) in the control and hepatic disease groups were 2.52 ng/ml (95% confidence interval 2.07-2.97 ng/ml) and 1.56 ng/ml (95% confidence interval 1.37-1.76 ng/ml), respectively.

Conclusions
The pharmacokinetics of remifentanil and GR90291 are unchanged in persons with severe, chronic liver disease. Such patients may be more sensitive to the ventilatory depressant effects of remifentanil, a finding of uncertain clinical significance, considering the extremely short duration of action of the drug.
Pharmacokinetics and Analgesic Effect of Ropivacaine during Continuous Epidural Infusion for Postoperative Pain Relief
Authors: Erichsen Carl-Johan , Sjovall Jan , Kehlet Henrik , Hedlund Cecilia , Arvidsson Torbjorn 
Published: November 2003

Background
The pharmacokinetics and clinical efficacy of ropivacaine (2.5 mg/ml) during a 24-h continuous epidural infusion for postoperative pain relief in 20 patients scheduled for abdominal hysterectomy were characterized using an open-label, increasing-dose design.

Methods
Through an epidural catheter inserted at T10-T12, a test dose of 7.5 mg ropivacaine was given 3 min before a bolus dose of 42.5 mg and immediately followed by a 24-h continuous epidural infusion with either 10 or 20 mg/h. Peripheral venous plasma samples were collected up to 48 h after infusion, and urinary excretion was followed up to the end of infusion. Postoperative pain at rest, on coughing, and at mobilization was assessed by means of a visual analog scale 2,4,6,8,12, and 24 h after the end of surgery. Sensory (pinprick) and motor block (modified Bromage scale) were assessed at the same intervals.

Results
The total plasma concentrations of ropivacaine increased markedly and consistently during the 24-h epidural infusion, in contrast to stable unbound concentrations. Both total and unbound plasma concentrations at the end of infusion were proportional to the total dose, although only the latter was proportional to the infusion rate. The total and unbound plasma clearance was independent of dose. Total mean clearance decreased on average by 21% (P < 0.001) during the last 12 h of epidural infusion, i.e., from 539 +/- 191 ml/min to 418 +/- 138 ml/min, indicating time-dependent kinetics. The unbound clearance also varied between estimates after 8 h of infusion and the end of treatment, i.e., a 5.3% decrease from 10.4 +/- 5.3 l/min to 9.5 +/- 3.9 l/min (P < 0.05). The unbound fraction of ropivacaine in plasma decreased during treatment, and this was related to the increase in alpha1-acid glycoprotein concentration. Pain was generally well controlled, and median visual analog scale scores during mobilization were less than 30 mm in patients receiving ropivacaine at 20 mg/h.

Conclusions
The pharmacokinetics of ropivacaine were independent of dose, but total clearance decreased with time over 24 h. The consistent increase in total plasma concentration during the postoperative epidural infusion contrasted to much less variation in the unbound plasma concentrations of ropivacaine.
Location and Characteristics of Nitric Oxide Synthase in Sheep Spinal Cord and Its Interaction with α2-Adrenergic and Cholinergic Antinociception
Authors: Xu Zemin , Li Ping , Tong Chuanyao , Figueroa Jorge , Tobin Joseph R. , Eisenach James C. 
Published: November 2003

Background
Nitric oxide synthase is located in the spinal cord dorsal horn and intermediolateral cell column, where it may modulate sensory and sympathetic neuronal activity. However, the biochemical characteristics of this enzyme have not been examined in these different areas in the spinal cord. Although alpha(2)-adrenergic agonists, muscarinic agonists, and nitric oxide may interact in the spinal cord to produce antinociception, these interactions have not been characterized.

Methods
Sheep spinal cord tissue was homogenized ad centrifuged at high sped to separate soluble and membrane-bound fractions. Nitric oxide synthase activity was determined by conversion of [(14)C]-L-arginine to [(14)C]-L-citrulline and its kinetic characteristics, dependency on cofactors, and sensitivity to inhibitors determined. Sheep spinal cord was stained for nicotinamide adenine dinucleotide phosphate diaphorase as a marker for nitric oxide synthase. Antinociception to a mechanical stimulus from intrathecal clonidine alone and with neostigmine was determined and the effects of L-arginine and n-methyl-L-arginine were determined.

Results
More than 85% of nitric oxide synthase activity was present in the soluble form and its kinetic, cofactor, and antagonist properties were similar to those of the neuronal isoform of nitric oxide synthase. Biochemical and histochemical studies localized nitric oxide synthase to the superficial dorsal horn and the intermediolateral cell column. Clonidine antinociception was enhanced by L-arginine and neostigmine, but not by D-arginine. Neostigmine's enhancement of clonidine antinociception was blocked by n-methyl-L-arginine.

Conclusions
These results confirm those of previous studies demonstrating localization of nitric oxide synthase to superficial dorsal horn and intermediolateral cell column of mammalian spinal cord, and suggesting its identity as the neuronal isoform. Spinal alpha(2)-adrenergic agonist antinociception may be partly dependent on cholinergic and nitric oxide mechanisms.
Continuous Intrathecal Administration of Short-lasting micro Opioids Remifentanil and Alfentanil in the Rat
Authors: Buerkle Hartmut , Yaksh Tony L. 
Published: November 2003

Background
Lipid soluble mu opioids given intrathecally produce a potent, dose-dependent analgesic response, which because of rapid clearance, is of short duration. Such agents delivered by continuous infusion can result in systemic accumulation and significant extraspinally mediated side effects. The effects of intrathecal infusions of two lipid-soluble mu opioids were investigated: remifentanil, an esterase metabolized agent with an inactive metabolite, and alfentanil.

Methods
Rats with chronic lumbar intrathecal catheters received intrathecal infusions (in flow rates of 1.0 microliters/min and 0.1 microliters/min) of remifentanil or alfentanil and were tested for hind paw thermal withdrawal latency, supraspinal side effects (sedation, block of pinna, and corneal responses) and motor impairment. Remifentanil was delivered either in a glycine formulation (R(g)) or in a saline vehicle (R(s)). Separate studies with the glycine vehicle also were undertaken.

Results
At an infusion rate of 0.1 microliters/min, remifentanil and alfentanil produced naloxone-reversible, dose-dependent analgesia and supraspinal side effects with the intrathecal ED(50) (micrograms/min; 95% confidence interval) for analgesia: R(s) = 1.5 (1.2-1.8), R(g) = 1.2 (0.7-2.3); alfentanil = 1.5 (1.4-1.6) and for supraspinal side effects: R(s) = 1.7 (1.4-1.9); R(g) = 1.9 (1.6-2.4); alfentanil = 1.5 (1.4-1.7). There was no difference in potency or time until onset for analgesia at either delivery rate (12-20 min), whereas for supraspinal side effects, 1.0 microliters/min resulted in a faster onset for R(g). Recovery of normal thresholds after equianalgesic doses was faster in R(s) than alfentanil and for the supraspinal index faster in R(s) and R(g) groups. R(g), but not R(s), or alfentanil, produced a dose-dependent motor impairment after 90 min of intrathecal infusion at a flow rate of 0.1 microliters/min. Both glycine in R(g) and glycine (matching glycine dose) alone showed parallel time courses for motor impairment and similar intrathecal ED(50) (6.6 vs. 6.4 micrograms/min over 90 min) for this nonnaloxone reversible effect. Intrathecal bolus administration of the same total dose of glycine showed no significant motor effects.

Conclusions
Remifentanil has a rapid onset like alfentanil but shows a faster recovery of action after intrathecal infusion. Despite its rapid clearance, remifentanil induces supraspinal side effects at analgesic effective doses. Moreover, in the current formulation, with glycine, a reversible motor impairment can occur after intrathecal delivery.
Isoform-dependent Effects of Halothane in Human Skinned Striated Fibers
Authors: Tavernier Benoit M. , Haddad Elie , Adnet Pascal J. , Etchrivi Toussaint S. , Lacroix Dominique , Reyford Hugo 
Published: November 2003

Background
Reports of the effects of halothane on isoform contractile proteins of striated muscles are conflicting. To determine whether halothane affects cardiac and skeletal contractile proteins differently, the authors examined the effects of two doses of halothane (0.44 and 1.26 mM, equivalent to 0.75 and 2.25 vol%, respectively) on the Ca++ sensitivity and maximal force in human skinned cardiac, type I (slow twitch), and type II (fast twitch) skeletal muscle fibers.

Methods
Left ventricular muscle strips and skeletal muscle biopsy specimens were obtained from eight and ten patients undergoing cardiac and orthopedic surgery, respectively. Sarcolemma and sarcoplasmic reticulum were destroyed with ethylene glycol bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid plus Brij 58. Ca++ sensitivity was studied by observing the isometric tension developed by skinned fibers challenged with increasing concentrations of Ca++. Muscle fiber type was determined in each skeletal fiber by the difference in strontium-induced tension measurements.

Results
Halothane shifted the Ca++ tension curves toward higher Ca++ concentrations and increased the Ca++ concentrations for half-maximal activation in both cardiac and type I skeletal muscle fibers (from 1.96 microM and 1.06 microM under control conditions to 2.92 microM and 1.71 microM in presence of 0.75 vol% halothane, respectively) without changing the slope of this relationship (Hill coefficient). In contrast, no significant effect was observed in type II fibers. Halothane also decreased the maximal activated tension in the three groups of fibers with a lesser effect in type II fibers.

Conclusions
Halothane decreases Ca++ sensitivity and maximal force in human skinned cardiac and type I fibers at 20 degrees C. It is concluded that the negative inotropic effects of halothane depend on contractile proteins isoforms.
Halothane and Isoflurane Inhibit Vasodilation Due to Constitutive but Not Inducible Nitric Oxide Synthase
Authors: Zuo Zhiyi , Tichotsky Alexandra , Johns Roger A. 
Published: November 2003

Background
Inhalational anesthetics inhibit the nitric oxide-guanylyl cyclase signaling pathway, but the site of this inhibition is not yet clear. This study was designed to test the hypothesis that receptor activation or downstream signaling events leading to nitric oxide synthase activation are important sites for this inhibition by comparing the effect of anesthetics on vasodilation caused by the calcium-dependent constitutive endothelial nitric oxide synthase versus the calcium-independent inducible nitric oxide synthase.

Methods
Endothelium-intact or -denuded rat thoracic aorta rings preincubated with or without lipopolysaccharide were mounted for isometric tension measurement, constricted with phenylephrine, then relaxed with methacholine in the presence or absence of halothane (1-3%) or isoflurane (1-3%). The cyclic guanosine 3,5-monophosphate content in the endothelium-denuded rings preincubated with or without lipopolysaccharide in the presence or absence of 3% halothane or 3% isoflurane was quantified by radioimmunoassay. The activity of partially purified inducible nitric oxide synthase from activated mouse macrophage was assayed in the presence or absence of halothane (1-4%) or isoflurane (1-5%) by the conversion of 3H-L-arginine to 3H-L-citrulline.

Results
Halothane and isoflurane inhibited methacholine-stimulated, nitric oxide-mediated vasorelaxation in endothelium-intact aortic rings. Neither halothane nor isoflurane affected the vasorelaxation caused by basal endothelial nitric oxide synthase or inducible nitric oxide synthase activity. Neither anesthetic altered the cyclic guanosine 3,5-monophosphate increase caused by inducible nitric oxide synthase in the lipopolysaccharide-treated rings.

Conclusions
The results demonstrated that halothane and isoflurane inhibit only receptor/calcium-activated nitric oxide synthase action and that direct inhibition of nitric oxide synthase, soluble guanylyl cyclase, or an interaction with nitric oxide are not responsible for anesthetic inhibition of endothelium-dependent vasorelaxation.
Involvement of Glutamate Receptors in Strychnine- and Bicuculline-induced Allodynia in Conscious Mice
Authors: Onaka Masahiko , Minami Toshiaki , Nishihara Isao , Ito Seiji 
Published: November 2003

Background
Glycine and gamma-aminobutyric acid (GABA) are inhibitory neurotransmitters that appear to be important in sensory processing in the spinal dorsal horn. Intrathecal administration of strychnine (strychnine-sensitive glycine receptor antagonist) or bicuculline (GABAA antagonist) was reported to induce allodynia. Although the strychnine-induced allodynia was shown to be mediated through the N-methyl-D-aspartate (NMDA)-type glutamate receptor, it is not clear whether the bicuculline-evoked-allodynia is mediated through the glutamate receptor system or how different the allodynia induced by strychnine and bicuculline are.

Methods
Male ddY mice weighing 20 +/- 2 g were used in this study. A 27-G stainless-steel needle attached to a microsyringe was inserted between the L5 and L6 vertebrae by a slight modification of the method of Hylden and Wilcox. Drugs in vehicle were injected slowly into the subarachnoid space to conscious mice at 22 +/- 2 degrees C. The volume of the intrathecal injection was 5 microliters. Studies on allodynia were carried out essentially according to the method of Yaksh and Harty.

Results
The intrathecal administration of strychnine or bicuculline in conscious mice resulted in allodynia elicited by nonnoxious brushing of the flanks. The maximum allodynia induced by strychnine was observed 5 min after intrathecal injection, but that induced by bicuculline was observed 10 min after intrathecal injection. Both responses gradually decreased over the experimental period of 50 min. The allodynia induced by strychnine was dose-dependently relieved by NMDA receptor antagonists (D-AP5, ketamine, and 7-C1-KYNA) and non-NMDA receptor antagonists (GAMS and CNQX) but not by metabotropic receptor antagonists (L-AP3 and L-AP4). On the other hand, allodynia induced by bicuculline was dose-dependently relieved by GAMS, L-AP3, and L-AP4, but not by D-AP5, ketamine, 7-C1-KYNA, and CNQX. Whereas the strychnine-evoked allodynia was dose-dependently relieved by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) and the soluble guanylate cyclase inhibitor methylene blue, the bicuculline-induced one was dose-dependently relieved by methylene blue but not by L-NAME.

Conclusions
These results demonstrate that both strychnine- and bicuculline-evoked allodynia were mediated through pathways that include the glutamate receptor and nitric oxide systems but in a different manner. the current study suggests that GABA and glycine may modulate responses to an innocuous tactile stimulus as inhibitory neurotransmitters at presynaptic and postsynaptic sites in the spinal cord, respectively.
Central Nervous System Sodium Channels Are Significantly Suppressed at Clinical Concentrations of Volatile Anesthetics
Authors: Rehberg Benno , Xiao Yong-Hong , Duch Daniel S. 
Published: November 2003

Background
Although voltage-dependent sodium channels have been proposed as possible molecular sites of anesthetic action, they generally are considered too insensitive to be likely molecular targets. However, most previous molecular studies have used peripheral sodium channels as models. To examine the interactions of volatile anesthetics with mammalian central nervous system voltage-gated sodium channels, rat brain IIA sodium channels were expressed in a stably transfected Chinese hamster ovary cell line, and their modification by volatile anesthetics was examined.

Methods
Sodium currents were measured using whole cell patch clamp recordings. Test solutions were equilibrated with the test anesthetics and perfused externally on the cells. Anesthetic concentrations in the perfusion solution were determined by gas chromatography.

Results
All anesthetics significantly suppressed sodium currents at clinical concentrations. This suppression occurred through at least two mechanisms: (1) a potential-independent suppression of resting or open sodium channels, and (2) a hyperpolarizing shift in the voltage-dependence of channel inactivation resulting in a potential-dependent suppression of sodium currents. The voltage-dependent interaction results in IC50 values for anesthetic suppression of sodium channels that are close to clinical concentrations at potentials near the resting membrane potential.
Preemptive Analgesia: Intraperitoneal Local Anesthetic in Laparoscopic Cholecystectomy
Authors: Pasqualucci Alberto , De Angelis Verena , Contardo Riccardo , Colo Francesca , Terrosu Giovanni , Donini Annibale , Pasetto Alberto , Bresadola Fabrizio 
Published: November 2003

Background
A controversy exists over the effectiveness and clinical value of preemptive analgesia. Additional studies are needed to define the optimum intensity, duration, and timing of analgesia relative to incision and surgery.

Methods
One hundred twenty patients undergoing laparoscopic cholecystectomy under general anesthesia plus topical peritoneal local anesthetic or saline were studied. Local anesthetic (0.5% bupivacaine with epinephrine) or placebo solutions were given as follows: immediately after the creation of a pneumoperitoneum (blocking before surgery), and at the end of the operation (blocking after surgery). Patients were randomly assigned to one of four groups of 30 patients each. Group A (placebo) received 20 ml 0.9% saline both before and after surgery, group B received 20 ml 0.9% saline before surgery and 20 ml local anesthetic after surgery, group C received 20 ml local anesthetic both before and after surgery, group P received 20 ml local anesthetic before and 20 ml 0.9% saline after surgery. Pain was assessed using a visual analog scale and a verbal rating scale at 0, 4, 8, 12, and 24 h after surgery. Metabolic endocrine responses (blood glucose and cortisol concentrations) and analgesic requirements also were investigated.

Results
Pain intensity (visual analog and verbal rating scales) and analgesic requirements were significantly less in the group receiving bupivacaine after surgery compared to placebo. However, in the groups receiving bupivacaine before surgery, both pain intensity and analgesic consumption were less than in the group receiving bupivacaine only after surgery. Blood glucose and cortisol concentrations 3 h after surgery were significantly less in groups receiving bupivacaine before surgery.

Conclusions
The results indicate that intraperitoneal local anesthetic blockade administered before or after surgery preempts postoperative pain relative to an untreated placebo-control condition. However, the timing of administration is also important in that postoperative pain intensity and analgesic consumption are both lower among patients treated with local anesthetic before versus after surgery.