bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Effect of Halothane and Forskolin on Platelet Cytosolic Ca (2+) Mobilization and Aggregation
Authors: Corbin Francois , Blaise Gilbert , Sauve Remy 
Published: November 2003

Background
Previous works have suggested that the impairment of platelet aggregation by halothane was partly related to a stimulation of cyclic adenosine monophosphate (cAMP) production, to an inhibitory effect on Ca2+ signaling, or both. Intracellular Ca2+ measurements therefore were undertaken, first to determine the critical steps in the platelet CaZ+ signaling cascade most likely to be affected by halothane or by an increase in cAMP production, and second to establish if the effect of halothane involves aggregation-related biochemical pathways triggered by an increase in internal Ca2+.

Methods
Human washed platelets were treated with halothane or forskolin for 5 min before application of either platelet-activating factor, thrombin, U46619, or thapsigargin. The cytosolic Ca2+ concentration ([Ca2+]i) was measured with the fluorescent Ca2+ indicator fura-2. Nephelometric measurements were also performed to assay the aggregation process.

Results
Our results indicate that pretreating platelets with halothane leads to a partial impairment of the [Ca2+]i increase induced either by U46619, thrombin, or platelet-activating factor, but this had no significant effect on the [Ca2+]i response triggered by thapsigargin. In addition, our results show that halothane inhibits platelet aggregation triggered by U46619, but not by thapsigargin. Conversely, forskolin completely inhibited the [Ca2+]i response to U46619 and thapsigargin and prevented platelet aggregation induced by both agonists.

Conclusions
These results suggest that halothane and cAMP exert their effects on platelet aggregation and Ca2+ signaling through different mechanisms, and that halothane cannot impair platelet aggregation independently of phospholipase C stimulation.
Epigastric Antinociception by Cervical Dorsal Column Lesions in Rats
Authors: Feng Yi , Cui Minglei , Al-Chaer Elie D. , Willis William D. 
Published: November 2003

Background
Previous clinical evidence and electrophysiologic studies in the authors' laboratory have implicated the dorsal column (DC) as an important pathway for the transmission of visceral colorectal pain. This study examined, behaviorally and electrophysiologically, the role of the DC in mediating epigastric nociception using a visceral pain model involving duodenal distension in rats.

Methods
For behavioral testing, the writhing-like responses produced in awake rats by graded intraduodenal balloon distension (0.1 to 0.7 ml) were tested. A DC mechanical lesion at the C2 level or a sham operation (SH, same spinal cord segment exposed but no DC lesion) was performed. The writhing-like responses to duodenal distension were tested again and the rats were compared with other rats with no lesions and with SH rats. For electrophysiologic testing, the extracellular activity of single neurons was recorded in the ventrobasal nucleus of the thalamus in anesthetized rats. The ventrobasal cells that responded to duodenal distension were tested further with this visceral stimulus before and after a lesion of the DC.

Results
The mechanical DC lesion significantly reduced the intensity of the writhing-like responses and increased the threshold volume that would elicit writhing-like responses compared with rats with no lesions and SH rats without any observable neurologic deficit. A lesion of the DC also significantly reduced the responses of ventrobasal cells to duodenal distension.

Conclusions
The DC plays an important role in signaling epigastric nociception in this experimental model. A mechanical DC lesion can produce significant visceral antinociception in rats.
Exogenous Surfactant Preserves Lung Function and Reduces Alveolar Evans Blue Dye Influx in a Rat Model of Ventilation-induced Lung Injury
Authors: Verbrugge Serge J. C. , Vazguez de Anda Gilberto , Gommers Diederik , Neggers Sabastian J. C. M. M. , Sorm Vera MSc , Bohm Stephan H. , Lachmann Burkhard 
Published: November 2003

Background
Changes in pulmonary edema infiltration and surfactant after intermittent positive pressure ventilation with high peak inspiratory lung volumes have been well described. To further elucidate the role of surfactant changes, the authors tested the effect of different doses of exogenous surfactant preceding high peak inspiratory lung volumes on lung function and lung permeability.

Methods
Five groups of Sprague-Dawley rats (n = 6 per group) were subjected to 20 min of high peak inspiratory lung volumes. Before high peak inspiratory lung volumes, four of these groups received intratracheal administration of saline or 50, 100, or 200 mg/kg body weight surfactant; one group received no intratracheal administration. Gas exchange was measured during mechanical ventilation. A sixth group served as nontreated, nonventilated controls. After death, all lungs were excised, and static pressure-volume curves and total lung volume at a transpulmonary pressure of 5 cm H2O were recorded. The Gruenwald index and the steepest part of the compliance curve (Cmax) were calculated. A bronchoalveolar lavage was performed; surfactant small and large aggregate total phosphorus and minimal surface tension were measured. In a second experiment in five groups of rats (n = 6 per group), lung permeability for Evans blue dye was measured. Before 20 min of high peak inspiratory lung volumes, three groups received intratracheal administration of 100, 200, or 400 mg/ kg body weight surfactant; one group received no intratracheal administration. A fifth group served as nontreated, nonventilated controls.

Results
Exogenous surfactant at a dose of 200 mg/kg preserved total lung volume at a pressure of 5 cm H2O, maximum compliance, the Gruenwald Index, and oxygenation after 20 min of mechanical ventilation. The most active surfactant was recovered in the group that received 200 mg/kg surfactant, and this dose reduced minimal surface tension of bronchoalveolar lavage to control values. Alveolar influx of Evans blue dye was reduced in the groups that received 200 and 400 mg/kg exogenous surfactant.

Conclusions
Exogenous surfactant preceding high peak inspiratory lung volumes prevents impairment of oxygenation, lung mechanics, and minimal surface tension of bronchoalveolar lavage fluid and reduces alveolar influx of Evans blue dye. These data indicate that surfactant has a beneficial effect on ventilation-induced lung injury.
Tryptase Levels Are Not Increased during Vancomycin-induced Anaphylactoid Reactions
Authors: Renz Cheryl L. , Laroche Dominique , Thurn John D. , Finn Henry A. , Lynch James P. , Thisted Ronald , Moss Jonathan 
Published: November 2003

Background
Anaphylaxis, mediated by immunoglobulin E, may be clinically indistinguishable but is mechanistically different than chemically mediated anaphylactoid reactions induced by drugs such as morphine, curare, and vancomycin. A test to distinguish anaphylactic from anaphylactoid reactions would clarify therapeutic and medicolegal issues. Tryptase levels identify anaphylactic reactions but have not been evaluated in vivo during anaphylactoid reactions. A prospective, randomized, double-blinded, placebo-controlled trial of antihistamine chemoprophylaxis for rapid vancomycin infusion was performed, and plasma tryptase was measured using a new immunoassay. Histamine release was established by measurement of plasma histamine and the ability of prophylactic H1 and H2 antagonists to prevent common histamine-associated side effects. Tryptase levels were compared with histamine levels and clinical symptoms.

Methods
Before elective arthroplasty, 40 patients received vancomycin infusion (1 g over 10 min) and pretreatment with either antihistamines (1 mg/kg diphenhydramine and 4 mg/kg cimetidine) or placebo. Changes in tryptase (at peak histamine and 10 min after vancomycin infusion), histamine levels, and histamine-mediated symptoms were assessed using Fisher's exact test, the Student's t test, or the paired t test, as appropriate. Logistic regression models were used to quantify the association of clinical symptoms with antihistamine treatment and serum levels.

Results
Plasma tryptase levels were unchanged (99% CI, -0.5 to 1.6) independent of increased histamine levels, antihistamine pretreatment, clinical symptoms, or all of these. Histamine levels >1 ng/ml were significantly associated with hypotension, moderate-to-severe rash, and stopped infusion. Antihistamine pretreatment significantly decreased the incidence and severity of the reactions.

Conclusion
Plasma tryptase levels were not significantly elevated in confirmed anaphylactoid reactions, so they can be used to distinguish chemical from immunologic reactions.
Effect of Isoflurane on the Auditory Steady-state Response and on Consciousness in Human Volunteers
Authors: Plourde Gilles , Villemure Chantal , Fiset Pierre , Bonhomme Vincent , Backman Steven B. 
Published: November 2003

Background
The auditory steady state response (ASSR) is a sustained electrical response of the brain to auditory stimuli delivered at fast rates (30-50 responses/s). The aim of this study was to evaluate the effect of 0.26-0.50% isoflurane on the ASSR and on consciousness, defined as responsiveness to verbal commands.

Methods
Ten volunteers (21-31 yr) participated. Isoflurane was administered at three stable, end-tidal concentrations: 0.26%, 0.38%, and 0.50%. The ASSR in response to 18,000 stimuli (500-Hz tonebursts, 10 ms, 82-dB, the right ear, 35-45 bursts/s) was recorded from the vertex with reference to the right mastoid. Recordings were made during baseline, at each isoflurane concentration, and during recovery.

Results
The mean (SD) ASSR amplitudes were 0.32 (0.23) microV during baseline, 0.24 (0.17) microV during 0.26% isoflurane, 0.09 (0.05) microV during 0.38% isoflurane, 0.04 (0.03) microV during 0.50% isoflurane, and 0.29 (0.33) microV during recovery. The amplitude during baseline and recovery was larger than during 0.38% and 0.50% isoflurane (P < 0.001). The amplitude at 0.26% was larger than at the other concentrations (P < 0.025). The logarithm of the ASSR amplitude was related linearly to the concentration of isoflurane (r = 0.85; P < 0.0001). The prediction probability (Pk) for loss of consciousness was 0.95 for both ASSR and measured isoflurane concentration. An ASSR amplitude < 0.07 microV was always associated with unconsciousness.

Conclusions
The ASSR is attenuated in a concentration-dependent manner by isoflurane. Suppression of consciousness and maximal attenuation of ASSR occur in the same isoflurane concentration range. Profound attenuation of ASSR appears to reflect unconsciousness, defined as unresponsiveness to verbal commands.
Population Pharmacodynamics and Pharmacokinetics of Remifentanil as a Supplement to Nitrous Oxide Anesthesia for Elective Abdominal Surgery
Authors: Drover David R. , Lemmens Harry J. M. 
Published: November 2003

Background
Remifentanil blood concentrations necessary for adequate intraoperative anesthesia have not been defined. The goal of this study was to determine the blood concentrations of remifentanil needed for anesthesia with 66% nitrous oxide during intraabdominal surgery. In addition, the pharmacokinetics of remifentanil and the effects of covariates on both the pharmacodynamics and the pharmacokinetics were determined.

Methods
Anesthesia was induced and maintained with 66% nitrous oxide in oxygen and remifentanil. Remifentanil was administered by a computer-controlled infusion pump that rapidly attained, and then maintained, constant remifentanil blood concentrations. If the patient showed signs of inadequate anesthesia (autonomic or somatic response), the target concentration was increased by 1 or 2 ng/ml. If no response occurred during a 15-min period, the concentration was decreased by 1 or 2 ng/ml. Remifentanil pharmacodynamics and pharmacokinetics were estimated using NONMEM.

Results
The remifentanil blood concentration for which there is a 50% probability of adequate anesthesia during abdominal surgery (Cb50) with 66% nitrous oxide was 4.1 ng/ml in men and 7.5 ng/ml in women. The Cb50 values for prostatectomy, nephrectomy, and other abdominal procedures were 3.8, 5.6, and 7.5 ng/ml, respectively. Remifentanil pharmacokinetics were best described by a two-compartment model with lean body mass as a significant covariate, where V1 = 0.129(lean body mass-50) + 3.79 l, V2 = 6.87 l, CL1 = 0.0389(lean body mass-50) + 2.34 l/min and CL2 = 1.14 l/min.

Conclusions
The Cb50 differed according to patient gender. However, because surgery type was not specified for each man or woman, this may reflect a difference in surgical procedure.
A Multi-center Study of Intrathecal Neostigmine for Analgesia following Vaginal Hysterectomy
Authors: Lauretti Gabriela R. , Hood David D. , Eisenach James C. , Pfeifer Ben L. 
Published: November 2003

Background
Intrathecal neostigmine injection produces analgesia in volunteers and reduces hypotension from intrathecal bupivacaine in animals. Initial clinical trials with neostigmine studied doses of more than 100 microg, but animal studies suggest that smaller doses may be effective. In addition, all controlled clinical trials of neostigmine have come from one Brazilian university. This multicenter, placebo-controlled trial investigated the effects of 25-75 microg intrathecal neostigmine on analgesia and blood pressure in women undergoing vaginal hysterectomy.

Methods
After institutional review board approval was obtained at the three university centers, and after patients gave informed consent, 92 women scheduled for vaginal hysterectomy were randomized to receive an intrathecal injection of 2 ml bupivacaine, 0.75%, in dextrose plus either 1 ml saline or 25, 50, or 75 microg neostigmine. Blood pressure, heart rate, pain and nausea (both assessed by visual analog scale), and intravenous morphine use were recorded during surgery and at specified intervals afterward.

Results
Morphine use was reduced similarly by all doses of neostigmine. Only the 75-microg dose of neostigmine increased the nausea score in the recovery room. The incidence of treatment for nausea was greater in patients receiving neostigmine (61%) than in those receiving saline placebo (29%) and was unaffected by neostigmine dose. Neostigmine did not reduce the incidence of hypotension from bupivacaine.

Conclusion
These data in patients after vaginal hysterectomy suggest that analgesia from intrathecal neostigmine may occur at doses less than 50 microg. In these doses, neostigmine does not reduce spinal bupivacaine-induced hypotension but may increase the need for treatment of nausea.
γ-Adrenergic Blockade Accelerates Conversion of Postoperative Supraventricular Tachyarrhythmias
Authors: Balser Jeffrey R. , Martinez Elizabeth A. , Winters Bradford D. , Perdue Philip W. , Clarke Ann Wray , Huang Wenzheng , Tomaselli Gordon F. , Dorman Todd , Campbell Kurt , Lipsett Pamela , Breslow Michael J. , Rosenfeld Brian A. 
Published: November 2003

Background
Postoperative supraventricular tachyarrhythmia is a common complication of surgery. Because chemical cardioversion is often ineffective, ventricular rate control remains a principal goal of therapy. The authors hypothesized that patients with supraventricular tachyarrhythmia after major noncardiac surgery who receive intravenous beta-adrenergic blockade for ventricular rate control would experience conversion to sinus rhythm at a rate that differs from those receiving intravenous calcium channel blockade.

Methods
The rate of conversion to sinus rhythm at 2 and 12 h after treatment was examined in 64 cases of postoperative supraventricular tachyarrhythmia. After adenosine administration, patients who remained in supraventricular tachyarrhythmia were prospectively randomized to receive either intravenous diltiazem or intravenous esmolol for ventricular rate control (unblinded). Loading and infusion rates were adjusted to achieve equivalent degrees of ventricular rate control.

Results
Patients were similar with regard to age and Apache III score. Most patients in both groups had atrial fibrillation (esmolol, 79%; diltiazem, 81%), and none experienced stable conversion with adenosine. Patients randomized to receive esmolol experienced a 59% rate of conversion to sinus rhythm within 2 h of treatment, compared with only 33% for patients randomized to receive diltiazem (intention to treat, P = 0.049; odds ratio, 2.9; 95% confidence interval, 1.046 to 7.8). After 12 h of therapy, the number of patients converting to sinus rhythm increased in both groups (esmolol, 85%; diltiazem, 62%), and the rates of conversion no longer differed significantly. Ventricular rates when supraventricular tachyarrhythmia began and after 2 and 12 h of rate control therapy were similar in the two treatment groups. The in-hospital mortality rate and length of stay in the intensive care unit were not significantly influenced by treatment group.

Conclusions
Among adenosine-resistant patients in the intensive care unit with atrial fibrillation after noncardiac surgery, intravenous esmolol produced a more rapid (2-h) conversion to sinus rhythm than did intravenous diltiazem.
AMPA/Kainate Antagonist LY293558 Reduces Capsaicin-evoked Hyperalgesia but Not Pain in Normal Skin in Humans
Authors: Sang Christine N. , Hostetter Meredith P. , Gracely Richard H. , Chappell Amy S. , Schoepp Darryle D. , Lee Gloria , Whitcup Scott , Caruso Rafael , Max Mitchell B. 
Published: November 2003

Background
Animal studies suggest that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-kainate (AMPA-KA) receptors are involved in pain processing. The effects of the competitive AMPA-KA antagonist LY293558 in two types of experimental pain in human volunteers, brief pain sensations in normal skin, and mechanical allodynia-pinprick hyperalgesia were studied after the injection of intradermal capsaicin.

Methods
Brief intravenous infusions of the competitive AMPA-KA antagonist LY293558 were given to 25 healthy volunteers to examine acute toxicity and analgesic effects. Fifteen volunteers then entered a double-blinded, three-period crossover study. In a Phase II study, LY293558 infusions (100% maximally tolerated dose vs. 33% maximally tolerated dose vs. placebo) began 10 min after intradermal injection of 250 microg capsaicin in volar forearm. Spontaneous pain, areas of mechanical allodynia and pinprick hyperalgesia, and side effects were determined every 5 min for 60 min.

Results
The median maximally tolerated dose was 1.3 +/- 0.4 (range, 0.9-2.0) mg/kg. Tests of cognitive and neurological function were unchanged. Dose-limiting side effects were hazy vision in 95% of volunteers and sedation in 40%. There were no significant changes in electrical or warm-cool detection and pain thresholds or heat pain thresholds. LY293558 had little effect on brief pain sensations in normal skin. Both high and low doses of LY293558 significantly reduced pain intensity, pain unpleasantness, and the area in which light brush evoked pain after intradermal capsaicin. There was a trend toward a dose-response effect of LY293558 on the area in which pinprick evoked pain after intradermal capsaicin, which did not reach statistical significance.

Conclusions
The authors infer that AMPA-KA receptor blockade reduces the spinal neuron sensitization that mediates capsaicin-evoked pain and allodynia. The low incidence of side effects at effective doses of LY293558 suggests that this class of drugs may prove to be useful in clinical pain states.
Cerebrospinal Fluid Pharmacokinetics and Pharmacodynamics of Intrathecal Neostigmine Methylsulfate in Humans
Authors: Shafer Steven L. , Eisenach James C. , Hood David D. , Tong Chuanyao 
Published: November 2003

Background
This study defines the cerebrospinal fluid (CSF) pharmacokinetics of neostigmine after intrathecal injection in humans and its effect on CSF acetylcholine, and it correlates physiologic effects with neostigmine dose and CSF acetylcholine concentrations.

Methods
The CSF was sampled via an indwelling spinal catheter in 12 volunteers receiving intrathecal neostigmine (50-750 microg) and analyzed for neostigmine and acetylcholine. Pharmacokinetic and pharmacodynamic analyses were performed with NONMEM. Effect-site models linked the time course of the neostigmine concentration with the time course of analgesia.

Results
Acetylcholine concentrations increased from <20 pmol/ml at baseline to >100 pmol/ml within 15 min of neostigmine injection. The pharmacokinetics of intrathecal neostigmine were best described by a triexponential function with an absorption phase. Individual predicted concentrations varied 100-fold. Post hoc Bayesian estimates described the observed neostigmine concentrations with a median error of 22% and did not show systematic model misspecification. Individual estimates of effect site concentration producing a 50% maximal effect for foot visual analog scale analgesia correlated with the magnitude of individual CSF neostigmine concentrations.

Conclusions
Intrathecal neostigmine concentrations can be well described by a triexponential disposition function, but the intersubject variability is large. The correlation between intersubject variability in concentration and intersubject variability in 50% maximal effect for foot analgesia suggests that both are offset by a common scalar, possibly the distance from the site of injection to the sampling and effect sites. These data provide the basis for the hypothesis of "observation at a distance" to describe the pharmacodynamics of intrathecally administered drugs.
Does Norepinephrine Modify the Effects of Inhaled Nitric Oxide in Septic Patients with Acute Respiratory Distress Syndrome?
Authors: Papazian Laurent , Bregeon Fabienne , Gaillat Francoise , Kaphan Elsa , Thirion Xavier , Saux Pierre , Badier Monique , Gregoire Regine , Gouin Francois , Jammes Yves , Auffray Jean-Pierre 
Published: November 2003

Unlabelled
Hypoxia-related pulmonary vasoconstriction enhanced by norepinephrine could be deleterious in patients with the acute respiratory distress syndrome (ARDS) and sepsis. A prospective study compared the effects of nitric oxide on cardiorespiratory parameters, including the evaluation of right ventricular function in patients with ARDS and sepsis who were receiving or not receiving norepinephrine.

Methods
During a 15-month period, 27 patients with ARDS and sepsis were prospectively investigated (group 1: 15 patients not receiving norepinephrine; group 2: 12 patients receiving norepinephrine). Right ventricular ejection fraction was measured by thermodilution. After baseline measurements, nitric oxide was administered at increasing inspiratory concentrations.

Results
The ratio of oxygen tension in arterial blood to the fractional concentration of oxygen in inspired gas increased in the two groups. After logarithmic transformation of the data, an analysis of variance was performed that did not show any difference between the two groups. A dose-dependent decrease in mean pulmonary arterial pressure was observed in the two groups. This decrease and the increase in right ventricular ejection fraction induced by inhaled nitric oxide were more marked when patients received norepinephrine (P < 0.0001).

Conclusion
Norepinephrine did not influence the beneficial effects of inhaled nitric oxide administered to patients with ARDS and sepsis on oxygenation.