bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orally Administered Paracetamol Does Not Act Locally in the Rat Formalin Test
Authors: Bonnefont Jérôme , Alloui Abdelkrim , Chapuy Eric , Clottes Eric , Eschalier Alain 
Published: November 2003

Background
The mechanism of action of paracetamol (acetaminophen) remains elusive because it is still under discussion as to whether it acts locally and/or centrally. The primary aim of this study was to clarify its site(s) of action (central and/or local) using the rat formalin test.

Methods
Spontaneous biting and licking of the injected paw following intraplantar injection of formalin 2.5% was monitored during the two phases of nociceptive behavior (0-5 and 20-40 min after injection), and the authors examined the antinociceptive activity of paracetamol following oral, intravenous, intraplantar, and intrathecal administrations as well as the reversion of this effect by an intrathecal injection of WAY 100,635, a selective 5-HT1A receptor antagonist.

Results
The oral administration of paracetamol (300, 400 mg/kg) reduced nociceptive behavior in both phases (400 mg/kg: 36.9 +/- 4.6% and 61.5 +/- 5.2% of inhibition in phases I and II, respectively, P <0.05), whereas lower doses reduced primarily the score of the second phase of the test. Only high doses of 10 to 20 mg/kg intraplantarly administered paracetamol, which were ineffective when administered subcutaneously, produced a significant but limited reduction in the early phase of the test and had no effect on the second phase or any antiinflammatory activity. Thus, this local effect did not seem to participate in the antinociceptive action of 400 mg/kg orally given paracetamol, which was totally blocked in both phases by an intrathecal injection of 40 microg WAY 100,635 per rat. Such an inhibition was not observed when paracetamol (200 microg per rat) was intrathecally coinjected with WAY 100,635, whereas the antinociceptive action of 5-HT (50 microg per rat, intrathecally) during both phases of pain was inhibited by WAY 100,635 (intrathecally).

Conclusions
Orally administered paracetamol does not seem to exert any relevant local action in the formalin model of tonic pain in rats, but it might activate the serotonergic bulbospinal pathways via a supraspinal site of action that remains to be elucidated.
Optimal Dose of Succinylcholine Revisited
Authors: Naguib Mohamed , Samarkandi Abdulhamid , Riad Waleed , Alharby Saleh W. 
Published: November 2003

Background
The authors reappraised the conventional wisdom that the intubating dose of succinylcholine must be 1.0 mg/kg and attempted to define the lower range of succinylcholine doses that provide acceptable intubation conditions in 95% of patients within 60 s.

Methods
This prospective, randomized, double-blind study involved 200 patients. Anesthesia was induced with 2 mug/kg fentanyl and 2 mg/kg propofol. After loss of consciousness, patients were randomly allocated to receive 0.3, 0.5, or 1.0 mg/kg succinylcholine or saline (control group). Tracheal intubation was performed 60 s later. A blinded investigator performed all laryngoscopies and also graded intubating conditions.

Results
Intubating conditions were acceptable (excellent plus good grade combined) in 30%, 92%, 94%, and 98% of patients after 0.0, 0.3, 0.5, and 1.0 mg/kg succinylcholine, respectively. The incidence of acceptable intubating conditions was significantly greater (P < 0.05) in patients receiving succinylcholine compared with those in the control group but was not different among the different succinylcholine dose groups. The calculated doses of succinylcholine (and their 95% confidence intervals) that were required to achieve acceptable intubating conditions in 90% and 95% of patients at 60 s were 0.24 (0.19-0.31) mg/kg and 0.56 (0.43-0.73) mg/kg, respectively.

Conclusions
The use of 1.0 mg/kg of succinylcholine may be excessive if the goal is to achieve acceptable intubating conditions within 60 s. Comparable intubating conditions were achieved after 0.3, 0.5, or 1.0 mg/kg succinylcholine. In a rapid-sequence induction, 95% of patients with normal airway anatomy anesthetized with 2 mug/kg fentanyl and 2 mg/kg propofol should have acceptable intubating conditions at 60 s after 0.56 mg/kg succinylcholine. Reducing the dose of succinylcholine should allow a more rapid return of spontaneous respiration and airway reflexes.
Influence of Nitrous Oxide on Minimum Alveolar Concentration of Sevoflurane for Laryngeal Mask Insertion in Children
Authors: Kihara Shinichi , Yaguchi Yuichi , Inomata Shinichi , Watanabe Seiji , Brimacombe Joseph R. , Taguchi Noriko , Komatsuzaki Tetsuya 
Published: November 2003

Background
Inhalational induction with sevoflurane and nitrous oxide is frequently used for Laryngeal Mask Airway (LMA; Laryngeal Mask Company, Henley-on-Thames, United Kingdom) insertion in children. The authors determined the influence of nitrous oxide on the minimum alveolar concentration (MAC) of sevoflurane for LMA insertion.

Methods
One hundred twenty unpremedicated children (age, 1-9 yr; American Society of Anesthesiologists physical status I) were randomly assigned to receive 1 of 15 end-tidal concentrations of nitrous oxide and sevoflurane for inhalational induction via a facemask: 0% nitrous oxide with 1.2, 1.4, 1.6, 1.8, or 2.0% sevoflurane; 33% nitrous oxide with 0.8, 1.0, 1.2, 1.4, or 1.6% sevoflurane; or 67% nitrous oxide with 0.4, 0.6, 0.8, 1.0, or 1.2% sevoflurane. The LMA was inserted after steady state end-tidal anesthetic concentrations had been maintained for 15 min. The response to insertion was recorded by three independent blinded observers. The interaction between nitrous oxide and sevoflurane was determined using logistic regression analysis.

Results
The MAC of sevoflurane for LMA insertion (95% confidence limit) was 1.57% (1.42-1.72%), and the concentration of sevoflurane required to prevent movement in 95% of children was 1.99% (1.81-2.57%). The addition of 33% and 67% nitrous oxide linearly decreased the MAC of sevoflurane for LMA insertion by 22% and 49%, respectively (P < 0.001). The interaction coefficient between nitrous oxide and sevoflurane did not differ from zero (P = 0.7843), indicating that the relation was additive.

Conclusions
Nitrous oxide and sevoflurane suppress the responses to LMA insertion in a linear and additive fashion in children.
Women Appear to Have the Same Minimum Alveolar Concentration as Men
Authors: Eger Edmond I , Laster Michael J. , Gregory George A. , Katoh Takasumi , Sonner James M. 
Published: November 2003

Background
A recent report finds that elderly Japanese women given xenon have a significantly smaller (26% less) MAC (minimum alveolar concentration required to eliminate movement in response to surgical incision in 50% of patients) than Japanese men of the same age. The authors assessed whether this finding applied to other/all anesthetics.

Methods
The authors reviewed data obtained previously for 258 patients (127 women and 131 men) anesthetized with desflurane, diethyl ether, halothane, methoxyflurane, sevoflurane, or xenon. Data were normalized to the MAC for the anesthetic as determined by logistic regression (i.e., MAC would equal a value of 1.000).

Results
The MAC for the normalized combined (all) data for women (1.013 +/- 0.017; mean +/- SEM) did not differ significantly from the normalized combined data for men (1.005 +/- 0.009), and neither differed significantly from 1.000. However, a significantly smaller MAC value was found for women in two studies of sevoflurane (subsets of the above studies) given to Japanese patients: 12% in one study and 16% in the other.

Conclusions
Overall, no difference in MAC was found for women versus men. Whether women (particularly older Japanese women) have a smaller MAC than men remains to be confirmed by prospective studies.
Narcotrend® and Bispectral Index® Monitor Are Superior to Classic Electroencephalographic Parameters for the Assessment of Anesthetic States during Propofol-Remifentanil Anesthesia
Authors: Schmidt Gunter N. , Bischoff Petra , Standl Thomas , Jensen Kai , Voigt Moritz , Schulte am Esch Jochen 
Published: November 2003

Background
A new electroencephalogram monitor, the Narcotrend, was developed to measure anesthetic depth. The authors compared the Narcotrend, the Bispectral Index, and classic electroencephalographic and hemodynamic parameters during anesthesia with propofol and remifentanil.

Methods
The authors investigated 25 patients undergoing laminectomy at different anesthetic states: awake, steady state anesthesia, first reaction during emergence, and extubation. Narcotrend value; BIS; relative power (percent) in delta, theta, alpha, and beta; median frequency; spectral edge frequency; and hemodynamic parameters were recorded simultaneously. The ability of the classic and processed electroencephalographic and hemodynamic parameters to predict the clinically relevant anesthetic states of awake, steady state anesthesia, first reaction, and extubation was tested using prediction probability.

Results
Only the Narcotrend was able to differentiate between awake versus steady state anesthesia and steady state anesthesia versus first reaction/extubation with a prediction probability value of more than 0.90.

Conclusions
Modern electroencephalographic parameters, especially Narcotrend, are more reliable indicators for the clinical assessment of anesthetic states than classic parameters.
Lidocaine Enhances GαiProtein Function
Authors: Benkwitz Claudia , Garrison James C. , Linden Joel , Durieux Marcel E. , Hollmann Markus W. 
Published: November 2003

Background
Local anesthetics inhibit several G protein-coupled receptors by interaction with the Galphaq protein subunit. It is not known whether this effect on G protein function can be extrapolated to other classes of G proteins. The authors investigated interactions of lidocaine with the human adenosine 1 receptor (hA1R)-coupled signaling pathway. Activated A1Rs couple to adenylate cyclase via the pertussis toxin sensitive Galphai protein, thereby decreasing cyclic adenosine monophosphate formation. A1Rs are widely expressed and abundant in the spinal cord, brain, and heart. Interactions of LAs with the hA1R-coupled transduction cascade therefore might produce a broad range of clinically relevant effects.

Methods
The function of hA1Rs stably expressed in Chinese hamster ovary cells was determined with assays of cyclic adenosine monophosphate, receptor binding, and guanosine diphosphate/guanosine triphosphate gamma35S exchange by using reconstituted defined G protein subunits. Involvement of phosphodiesterase and Galphai was characterized by using the phosphodiesterase inhibitor rolipram and pertussis toxin, respectively.

Results
Lidocaine (10-9-10-1 M) had no significant effects on agonist or antagonist binding to the hA1R or on receptor-G protein interactions. However, cyclic adenosine monophosphate levels were reduced significantly to 50% by the LAs, even in the absence of an A1R agonist or presence of an A1R antagonist. This effect was unaffected by rolipram (10 mum), but abolished completely by pretreatment with pertussis toxin, which inactivates the Galphai protein. Therefore, the main target site for LAs in this pathway is located upstream from adenylate cyclase.

Conclusions
Lidocaine potentiates Galphai-coupled A1R signaling by reducing cyclic adenosine monophosphate production. The study suggests an interaction site for LAs in a Galphai-coupled signaling pathway, with the Galphai protein representing the prime candidate. Taken together with previous results showing inhibitory LA interactions on the Galphaq protein subunit, the data in the current study support the hypothesis that specific G protein subunits represent alternative sites of LA action.
Induction of Malignant Hyperthermia in Susceptible Swine by 3,4-Methylenedioxymethamphetamine (“Ecstasy”)
Authors: Fiege Marko , Wappler Frank , Weisshorn Ralf , Gerbershagen Mark U. , Menge Melanie , Schulte am Esch Jochen 
Published: November 2003

Background
3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") can mediate acute toxic effects such as muscle rigidity, metabolic acidosis, and hyperthermia. Because of close clinical similarities, an association between MDMA intoxication and malignant hyperthermia (MH) was suggested. The aim of this study was to investigate whether MDMA is a trigger of MH in susceptible swine.

Methods
MH-nontriggering general anesthesia was performed in six MH-susceptible (MHS) and six MH-normal swine. The animals were exposed to MDMA in cumulative doses of 0.5, 1, 2, 4, 8, and 12 mg/kg. The clinical occurrence of MH was defined by achievement of two of three conditions: central venous Pco2 >/=75 mmHg, central venous pH </= 7.20, and increase of body core temperature >/= 2.0 degrees C. Once MH occurred, a standardized therapy with dantrolene, sodium bicarbonate, and hyperventilation with 100% oxygen was initialized.

Results
Administration of 8 mg/kg MDMA triggered MH in all MHS swine. The MH-normal swine also developed clinical signs of hypermetabolism, but even after administration of 12 mg/kg MDMA, changes were moderate compared with the MHS swine. Dantrolene therapy of MDMA-induced MH crisis in the MHS swine partially counteracted the clinical signs of MH immediately.

Conclusions
MDMA induces MH in genetically susceptible swine in relevant doses. Therefore, MHS patients should avoid use of MDMA or related drugs. Patients with a personal or family history of MDMA-induced hyperthermia should be tested for a diagnosis of MH susceptibility. Dantrolene is effective in therapy of MDMA-induced porcine MH.
Quality of Recovery from Anesthesia in Neurosurgical Patients
Authors: Leslie Kate , Troedel Sally , Irwin Kimberley , Pearce Frances , Ugoni Antony , Gillies Robyn , Pemberton Elizabeth , Dharmage Shyamali 
Published: November 2003

Background
Factors influencing quality of recovery in cranial and spinal neurosurgical patients are not known, possibly because of lack of a suitable instrument. Therefore, the authors measured quality of recovery using the QoR-40 score (a 40-item questionnaire on quality of recovery from anesthesia).

Methods
With informed consent, 200 patients undergoing elective neurosurgery were recruited. The QoR-40 score, visual analog scores for pain and quality of recovery, and data on complications were collected over 90 days. The psychometrics of the QoR-40 were tested and regression models were developed to determine predictors of quality of recovery and postoperative pain.

Results
The QoR-40 score demonstrated significant responsiveness, validity, and reliability. In cranial surgery patients, QoR-40 scores were lower on days 1 and 2 than either preoperatively or on days 3, 30, and 90. In spinal surgery patients, QoR-40 scores were lower preoperatively and on days 1 and 2 than on days 3, 30, and 90. Longer duration of surgery, more complications, and higher visual analog scores for pain were predictors of poor quality of recovery on day 3. Cranial surgery patients had moderately severe pain on days 1 and 2, whereas spinal surgery patients reported moderate pain for the whole study period. Neurologic deficits were negatively correlated with QoR-40 scores in cranial and spinal surgery patients.

Conclusions
The QoR-40 score is a useful instrument with which to assess quality of recovery in cranial and spinal surgery patients. Postoperative pain and neurologic deficits correlate with poor quality of recovery in these patients.
Inhibition of Spinal Prostaglandin Synthesis Early after L5/L6 Nerve Ligation Prevents the Development of Prostaglandin-dependent and Prostaglandin-independent Allodynia in the Rat
Authors: Hefferan Michael P. , O'Rielly Darren D. , Loomis Christopher W. 
Published: November 2003

Background
Prostaglandins, synthesized in the spinal cord in response to noxious stimuli, are known to facilitate nociceptive transmission, raising questions about their role in neuropathic pain. The current study tested the hypothesis that spinal nerve ligation-induced allodynia is composed of an early prostaglandin-dependent phase, the disruption of which prevents allodynia.

Methods
Male Sprague-Dawley rats, fitted with intrathecal drug delivery or microdialysis catheters, underwent left L5-L6 spinal nerve ligation or sham surgery. Paw withdrawal threshold, brush-evoked behavior, and the concentration of prostaglandin E2 (PGE2) in spinal cerebrospinal fluid ([PGE2]dialysate) were determined for up to 24 days. PGE2-evoked glutamate release from spinal slices was also determined.

Results
Paw withdrawal threshold decreased from at least 15 g (control) to less than 4 g, beginning 1 day after ligation. Brushing the affected hind paw evoked nociceptive-like behavior and increased [PGE2]dialysate (up to 257 +/- 62% of baseline). There was no detectable change in basal [PGE2]dialysate from preligation values. The EC50 of PGE2-evoked glutamate release (2.4 x 10-11 M, control) was significantly decreased in affected spinal segments of allodynic rats (8.9 x 10-15 M). Treatment with intrathecal S(+)-ibuprofen or SC-560, beginning 2 h after ligation, prevented the decrease in paw withdrawal threshold, the brush-evoked increase in [PGE2]dialysate, and the change in EC50 of PGE2-evoked glutamate release. R(-)-ibuprofen or SC-236 had no effect.

Conclusions
The results of this study provide solid evidence that spinal prostaglandins, synthesized by cyclooxygenase-1 in the first 4-8 h after ligation, are critical in the pathogenesis of prostaglandin-dependent and prostaglandin-independent allodynia and that their early pharmacologic disruption affords protection against this neuropathic state in the rat.
Salsolinol Produces Reinforcing Effects in the Nucleus Accumbens Shell of Alcohol‐Preferring (P) Rats
Authors: Rodd Zachary A. , Bell Richard L. , Zhang Ying , Goldstein Avram , Zaffaroni Alejandro , McBride William J. , Li Ting‐Kai 
Published: November 2003

Background: The formation of salsolinol (SAL) has been hypothesized to be a factor contributing to alcoholism and alcohol abuse. If SAL is formed under chronic alcohol‐drinking conditions, then it may contribute to alcohol addiction by being rewarding itself. Because SAL can be formed by the nonenzymatic condensation of acetaldehyde with dopamine, the reinforcing effects of SAL were tested in the nucleus accumbens shell, a dopamine‐rich site considered to be involved in regulating alcohol‐drinking behavior.Methods: The intracranial self‐administration technique was used to test the reinforcing properties of SAL. Adult, female alcohol‐preferring (P) rats were stereotaxically implanted with guide cannulae aimed at the nucleus accumbens shell. After 7 to 10 days to allow recovery from surgery, P rats were attached to the electrolytic microinfusion transducer system, placed in two‐lever experimental chambers, and allowed to respond for the self‐infusion of 100 nl of modified artificial cerebrospinal fluid (aCSF) or 0.03, 0.3, 3.0, or 12.5 μM SAL (3–1250 fmol/100 nl). Sessions were 4 hr in duration and were conducted in the dark cycle every 48 hr. The effects of coinfusing 10 to 400 μM sulpiride (given in sessions 5 and 6 after four acquisition sessions) on the intracranial self‐administration of 3.0 μM SAL were tested in a separate experiment.Results: P rats given 0.3 to 12.5 μM SAL received significantly more infusions per session than did the group given aCSF alone (e.g., 50 infusions for 3.0 μM SAL versus 10 or fewer infusions for the aCSF group) and responded significantly more on the active than inactive lever. Coinfusion of 100 or 400 μM sulpiride reduced the responding on the active lever (80–100 responses/session without sulpiride) to levels observed for the inactive lever (fewer than 10 responses/session with sulpiride). This effect was reversible because giving SAL alone in session 7 reinstated responding on the active lever.Conclusions: SAL is reinforcing in the nucleus accumbens shell of P rats at concentrations that are pharmacologically possible, and these reinforcing actions are mediated in part by D2/D3‐like receptors.
Effect of Chronic Alcohol Consumption on the Activity of the Hypothalamic‐Pituitary‐Adrenal Axis and Pituitary β‐Endorphin as a Function of Alcohol Intake, Age, and Gender
Authors: Gianoulakis Christina , Dai Xing , Brown Thomas 
Published: November 2003

Background: Experimental evidence indicates that components of the hypothalamic‐pituitary‐adrenal (HPA) axis and of the endogenous opioid system, such as β‐endorphin (β‐END), influence alcohol consumption, whereas chronic alcohol abuse alters the activity of both systems. Furthermore, gender and age differences have been reported in the activity of the HPA axis under basal conditions, in response to stress and acute alcohol challenge. The objective of the present studies was to investigate the hypothesis that chronic alcohol consumption alters the activity of the HPA axis and pituitary β‐END as a function of severity of alcohol abuse, gender, and age.Methods: Three age groups of each gender (18–29, 30–44, and 45–60 years old) were recruited. Each age and gender group included four subgroups: (a) nondrinkers, (b) light drinkers, (c) heavy drinkers, and (d) alcoholics in treatment. Demographic characteristics, alcohol consumption, and presence of alcohol dependence were recorded by using a structured interview. Blood samples were taken on the day of the interview. The levels of plasma adrenal corticotropic hormone (ACTH), cortisol, and β‐END were estimated as an index of the activity of the HPA‐axis and pituitary β‐END.Results: Plasma ACTH and β‐END levels were significantly lower in females than males of all age and drinking category groups. Plasma cortisol levels were higher in 18‐ to 29‐year‐old female subjects compared with the 18‐ to 29‐year‐old male subjects. The plasma ACTH and β‐END levels were lower whereas plasma cortisol levels were higher in heavy drinkers than nondrinkers. This decrease in plasma ACTH and β‐END levels with heavy drinking was more pronounced in female than male subjects of the 30–44 and 45–60 age groups.Conclusions: Chronic drinking, gender, and age influence the activity of the HPA‐axis and pituitary β‐END, which in turn may influence drinking behavior.
ADH Genotype Does Not Modify the Effects of Alcohol on High‐Density Lipoprotein
Authors: Whitfield John B. , O'Brien Martin E. , Nightingale Brian N. , Zhu Gu , Heath Andrew C. , Martin Nicholas G. 
Published: November 2003

Background: Alcohol consumption has beneficial effects on mortality which are mainly due to reduction in cardiovascular disease. These are believed to be due, at least in part, to the increase in plasma high‐density lipoprotein (HDL) which is associated with alcohol consumption. It has been proposed that ADH3 genotype modifies the relationships between alcohol intake and cardiovascular disease by altering the HDL response to alcohol. The aim of this paper was to test for effects of ADH2 and ADH3 genotypes on the response of HDL components to habitual alcohol consumption.Methods: Adult male and female subjects were genotyped for ADH2 and ADH3; and plasma HDL cholesterol, apolipoprotein A‐I, and apolipoprotein A‐II were measured. Nine hundred one subjects had both ADH2 and ADH3 genotypes and HDL cholesterol results, while 753 had both genotypes and all three lipid results. The effect of alcohol intake on the three measured HDL components, and a factor score derived from them, was estimated for each of the ADH2 and ADH3 genotype groups.Results: All the measured components of HDL increased with increasing alcohol consumption over the range of intakes studied, 0–4 drinks per day. There were no significant interactions between alcohol consumption and ADH2 or ADH3 genotypes.Conclusions: The concept that alcohol dehydrogenase genotype and alcohol metabolic rate modify the effects of alcohol on plasma HDL concentration is not supported by our results.