bluuebunny/crossref_metadata_2025 huggingface dataset:
New Composite Index Based on Midlatency Auditory Evoked Potential and Electroencephalographic Parameters to Optimize Correlation with Propofol Effect Site Concentration
Authors: Vereecke Hugo E. M. , Vasquez Pablo Martinez , Jensen Erik Weber , Thas Olivier , Vandenbroecke Rudy , Mortier Eric P. , Struys Michel M. R. F.
Published: August 2005

Background

This study investigates the accuracy of a composite index, the A-Line(R) auditory evoked potentials index version 1.6 (AAI1.6; Danmeter A/S, Odense, Denmark), as a measure of cerebral anesthetic drug effect in a model for predicting a calculated effect site concentration of propofol (CePROP). The AAI1.6 algorithm extracts information from the midlatency auditory evoked potentials, the spontaneous electroencephalographic activity, and the detection of burst suppression. The former version of this monitor, the A-Line auditory evoked potential index version 1.5, is only based on fast extracted midlatency auditory evoked potential information.

Methods

After institutional ethics committee approval (University Hospital, Ghent, Belgium), informed consent was obtained from 13 patients (10 women, 3 men) with an American Society of Anesthesiologists physical status of I, aged 18-65 yr, who were scheduled to undergo ambulatory gynecologic or urologic surgery. The authors evaluated for Bispectral Index, A-Line auditory evoked potential index, version 1.5, AAI1.6 scaled from 0 to 100 and AAI1.6 scaled from 0 to 60, the interpatient stability at baseline, the detection of burst suppression, prediction probability, and correlation with CePROP, during a constant infusion of 1% propofol at 300 ml/h. The authors developed pharmacodynamic models relating the predicted CePROP to each measure of cerebral anesthetic drug effect.

Results

Bispectral Index had the lowest interindividual baseline variability. No significant difference was found with prediction probability analysis for all measures. Comparisons for correlation were performed for all indices. The AAI1.6 scaled to 60 had a significantly higher correlation with CePROP compared with all other measures. The AAI1.6 scaled to 100 had a significant higher correlation with CePROP compared with the A-Line auditory evoked potential index version 1.5 (P < 0.05)

Conclusions

The authors found that the application of AAI1.6 has a better correlation with a calculated CePROP compared with a solitary fast extracting midlatency auditory evoked potential measure. Whether this improvement in pharmacodynamic tracing is accompanied by an improved clinical performance should be investigated using clinical endpoints.
Cardiac and Renal Effects of Levosimendan, Arginine Vasopressin, and Norepinephrine in Lipopolysaccharide-treated Rabbits
Authors: Faivre Valérie , Kaskos Husam , Callebert Jacques , Losser Marie-Reine , Milliez Paul , Bonnin Philippe , Payen Didier , Mebazaa Alexandre
Published: August 2005

Background

Because sepsis-induced myocardial dysfunction related to sepsis is at least partially related to a decrease in cardiac myofilament response to calcium, the use of the new myofilament-calcium sensitizer, levosimendan, has been proposed. In addition, arginine vasopressin is increasingly proposed as a vasopressor in septic patients, although data on its effects on cardiac function are still scarce. The aim of the current study was to assess, invasively and noninvasively, whether levosimendan, arginine vasopressin, and norepinephrine, either alone or combined, may modify sepsis-induced myocardial dysfunction and renal hemodynamics.

Methods

Thirty-six hours after lipopolysaccharide or saline administration, rabbits were studied either after slight sedation for echocardiography or after general anesthesia with sodium pentobarbital for the following measurements: aortic flow velocity and maximum acceleration of blood flow in the ascending aorta and renal macrocirculation and microcirculation.

Results

Levosimendan improved, within 30 min of administration, both maximum acceleration of blood flow by 20 +/- 12% (n = 8; P < 0.05) and left ventricular shortening fraction by a similar extent. Furthermore, low doses of arginine vasopressin markedly deteriorated cardiac function via an afterload-independent mechanism, even when animals were pretreated with levosimendan, whereas norepinephrine showed no detrimental effects on cardiac function. The study also showed that norepinephrine often improved renal medullary blood flow, whereas arginine vasopressin consistently decreased it.

Conclusion

Levosimendan and norepinephrine both exert beneficial effects in endotoxemic animals and should be further explored in human sepsis trials.
Oxygen Attenuates Atelectasis-induced Injury in the In Vivo Rat Lung
Authors: Duggan Michelle , McNamara Patrick J. , Engelberts Doreen , Pace-Asciak Cecil , Babyn Paul , Post Martin , Kavanagh Brian P.
Published: August 2005

Background

Atelectasis results in impaired compliance and gas exchange and, in extreme cases, increased microvascular permeability, pulmonary hypertension, and right ventricular dysfunction. It is not known whether such atelectasis-induced lung injury is due to the direct mechanical effects of lung volume reduction and alveolar collapse or due to the associated regional lung hypoxia. The authors hypothesized that addition of supplemental oxygen to an atelectasis-prone ventilation strategy would attenuate the pulmonary vascular effects and reduce the local levels of vasoconstrictor eicosanoids.

Methods

In series 1, anesthetized, atelectasis-prone mechanically ventilated rats were randomly assigned to one of six groups based on the inspired oxygen concentration and ventilated without recruitment. Series 2 was performed to determine the cardiac and pulmonary vascular effects of 21% versus 100% inspired oxygen. In series 3, computed tomography scans were performed after ventilation with a recruitment strategy (21% O2) or no recruitment strategy (21% O2 or 100% O2). In series 4, functional residual capacity was measured in animals where the gas was 21% or 100% O2.

Results

The partial pressure of arterial oxygen increased with increasing inspired oxygen, but the alveolar-arterial oxygenation gradient was also greater with higher inspired oxygen. Ventilation with 21% O2 (but not with 100% O2) was associated with progressive pulmonary vascular impedance and increased pulmonary vascular permeability. Prostaglandin F2alpha was increased by mechanical ventilation, especially without supplemental oxygen. Computed tomography scans demonstrated no atelectasis in recruited lungs, and atelectasis in nonrecruited lungs that was greater with supplemental oxygen. Increased atelectasis with 100% O2 (vs. 21% O2) was demonstrated by measurement of functional residual capacity.

Conclusions

Although supplemental oxygen worsened atelectasis in this model, it prevented the pathologic effects of atelectasis, including microvascular leak and pulmonary hypertension. Atelectasis-induced lung injury seems to be mediated by hypoxia rather than by the direct mechanical effects of atelectasis.
Isoflurane Preconditions Hippocampal Neurons against Oxygen–Glucose Deprivation
Authors: Bickler Philip E. , Zhan Xinhua , Fahlman Christian S.
Published: August 2005

Background

Isoflurane preconditions neurons to improve tolerance of subsequent ischemia in both intact animal models and in in vitro preparations. The mechanisms for this protection remain largely undefined. Because isoflurane increases intracellular Ca2+ concentrations and Ca2+ is involved in many processes related to preconditioning, the authors hypothesized that isoflurane preconditions neurons via Ca2+-dependent processes involving the Ca2+- binding protein calmodulin and the mitogen-activated protein kinase-ERK pathway.

Methods

The authors used a preconditioning model in which organotypic cultures of rat hippocampus were exposed to 0.5-1.5% isoflurane for a 2-h period 24 h before an ischemia-like injury of oxygen-glucose deprivation. Survival of CA1, CA3, and dentate neurons was assessed 48 later, along with interval measurements of intracellular Ca2+ concentration (fura-2 fluorescence microscopy in CA1 neurons), mitogen-activated protein kinase p42/44, and the survival associated proteins Akt and GSK-3beta (in situ immunostaining and Western blots).

Results

Preconditioning with 0.5-1.5% isoflurane decreased neuron death in CA1 and CA3 regions of hippocampal slice cultures after oxygen-glucose deprivation. The preconditioning period was associated with an increase in basal intracellular Ca2+ concentration of 7-15%, which involved Ca2+ release from inositol triphosphate-sensitive stores in the endoplasmic reticulum, and transient phosphorylation of mitogen-activated protein kinase p42/44 and the survival-associated proteins Akt and GSK-3beta. Preconditioning protection was eliminated by the mitogen-activated extracellular kinase inhibitor U0126, which prevented phosphorylation of p44 during preconditioning, and by calmidazolium, which antagonizes the effects of Ca2+-bound calmodulin.

Conclusions

Isoflurane, at clinical concentrations, preconditions neurons in hippocampal slice cultures by mechanisms that apparently involve release of Ca2+ from the endoplasmic reticulum, transient increases in intracellular Ca2+ concentration, the Ca2+ binding protein calmodulin, and phosphorylation of the mitogen-activated protein kinase p42/44.
Preconditioning by Isoflurane Induces Lasting Sensitization of the Cardiac Sarcolemmal Adenosine Triphosphate–sensitive Potassium Channel by a Protein Kinase C-δ–mediated Mechanism
Authors: Marinovic Jasna , Bosnjak Zeljko J. , Stadnicka Anna
Published: August 2005

Background

Cardioprotective effects of volatile anesthetics in anesthetic-induced preconditioning involve activation of the cardiac sarcolemmal adenosine triphosphate-sensitive potassium (sarcKATP) channels. This study addressed the memory phase of anesthetic preconditioning by investigating whether brief exposure to isoflurane produces lasting sensitization of the sarcKATP channel and whether protein kinase C mediates this effect.

Methods

Whole cell sarcKATP channel current (IKATP) was monitored from single isolated rat ventricular cardiomyocytes. Pinacidil was used to open the channel, and the magnitude of activated IKATP was an indicator of channel's ability to open. Involvement of protein kinase C was investigated using chelerythrine and isoform-specific peptide inhibitors and activators of protein kinase C-delta and protein kinase C-epsilon.

Results

The mean density of IKATP elicited by pinacidil (5 microm) in anesthetic-free conditions was 3.8 +/- 3.7 pA/pF (n = 11). After 10 min of exposure to isoflurane (0.56 mm) and 10 or 30 min of anesthetic washout, pinacidil-elicited IKATP was increased to 15.6 +/- 11.3 pA/pF (n = 12; P < 0.05) and 11.8 +/- 3.9 pA/pF (n = 6; P < 0.05), respectively. In the presence of chelerythrine (5 microm), isoflurane did not potentiate channel opening, and IKATP was 6.6 +/- 4.6 pA/pF (n = 11). Application of protein kinase C-delta peptide inhibitor also abolished isoflurane-induced sensitization of sarcKATP channel, and IKATP was 7.7 +/- 5.4 pA/pF (n = 12). In contrast, protein kinase C-epsilon peptide inhibitor did not affect channel sensitization, and pinacidil-elicited current was 14.8 +/- 9.6 pA/pF (n = 12). Interestingly, when both protein kinase C-delta and protein kinase C-epsilon activators were applied instead of isoflurane, they sensitized the channel to the same extent as isoflurane (18.9 +/- 7.2 pA/pF, n = 11, and 18.6 +/- 11.1 pA/pF, n = 10, respectively).

Conclusion

Isoflurane induces prolonged sensitization of the sarcKATP channel to opening that persists even after anesthetic withdrawal. Our results indicate that protein kinase C-delta, rather than protein kinase C-epsilon, is a likely mediator of isoflurane effects, although both protein kinase C-delta and protein kinase C-epsilon can modulate the channel function.
Involvement of Ca2+Sensitization in Ropivacaine-induced Contraction of Rat Aortic Smooth Muscle
Authors: Yu Jingui , Tokinaga Yasuyuki , Kuriyama Toshiyuki , Uematsu Nobuhiko , Mizumoto Kazuhiro , Hatano Yoshio
Published: August 2005

Background

The mechanisms of amino-amide local anesthetic agent-induced vasoconstriction remain unclear. The current study was designed to examine the roles of the protein kinase C (PKC), Rho kinase, and p44/42 mitogen-activated protein kinase (p44/42 MAPK) signaling pathways in calcium (Ca2+)-sensitization mechanisms in ropivacaine-induced vascular contraction.

Methods

Endothelium-denuded rat aortic rings, segments, and strips were prepared. The cumulative dose-response relations of contraction and intracellular Ca2+ concentration to ropivacaine were tested, using isometric force transducers and a fluorometer, respectively. The dose-dependent ropivacaine-induced phosphorylation of PKC and p44/42 MAPK and the membrane translocation of Rho kinase were also detected using Western blotting.

Results

Ropivacaine induced a dose-dependent biphasic contractile response and an increase in intracellular Ca2+ concentration of rat aortic rings, increasing at concentrations of 3 x 10 m to 3 x 10 m and decreasing from 10 m to 3 x 10 m, with a greater tension/intracellular Ca2+ concentration ratio than that induced with potassium chloride. The contraction was attenuated in a dose-dependent manner, by the PKC inhibitors bisindolylmaleimide I and calphostin C, the Rho-kinase inhibitor Y 27632, and the p44/42 MAPK inhibitor PD 098059. Ropivacaine also induced an increase in phosphorylation of PKC and p44/42 MAPK, and membrane translocation of Rho kinase in accordance with the contractile responses, which were also significantly inhibited by bisindolylmaleimide I and calphostin C, Y 27632, and PD 098059, correspondingly.

Conclusion

These findings demonstrated that PKC-, Rho kinase-, and p44/42 MAPK-mediated Ca2+-sensitization mechanisms are involved in the ropivacaine-induced biphasic contraction of rat aortic smooth muscle.
Isoflurane Disrupts Central Pattern Generator Activity and Coordination in the Lamprey Isolated Spinal Cord
Authors: Jinks Steven L. , Atherley Richard J. , Dominguez Carmen L. , Sigvardt Karen A. , Antognini Joseph F.
Published: August 2005

Background

Although volatile anesthetics such as isoflurane can depress sensory and motor neurons in the spinal cord, movement occurring during anesthesia can be coordinated, involving multiple limbs as well as the head and trunk. However, it is unclear whether volatile anesthetics depress locomotor interneurons comprising central pattern generators or disrupt intersegmental central pattern generator coordination.

Methods

Lamprey spinal cords were excised during anesthesia and placed in a bath containing artificial cerebrospinal fluid and D-glutamate to induce fictive swimming. The rostral, middle, and caudal regions were bath-separated using acrylic partitions and petroleum jelly, and in each compartment, the authors recorded ventral root activity. The authors selectively delivered isoflurane (0.5, 1, and 1.5%) only to the middle segments of the spinal cord. Spectral analyses were then used to assess isoflurane effects on central pattern generator activity and coordination.

Results

Isoflurane dose-dependently reduced fictive locomotor activity in all three compartments, with 1.5% isoflurane nearly eliminating activity in the middle compartment and reducing spectral amplitudes in the anesthetic-free rostral and caudal compartments to 23% and 31% of baseline, respectively. Isoflurane decreased burst frequency in the caudal compartment only, to 53% of baseline. Coordination of central pattern generator activity between the rostral and caudal compartments was also dose-dependently decreased, to 42% of control at 1.5% isoflurane.

Conclusion

Isoflurane disrupts motor output by reducing interneuronal central pattern generator activity in the spinal cord. The effects of isoflurane on motor output outside the site of isoflurane application were presumably independent of effects on sensory or motor neurons.
Effects of Perfluorohexan Vapor on Gas Exchange, Respiratory Mechanics, and Lung Histology in Pigs with Lung Injury after Endotoxin Infusion
Authors: Kemming Gregor I. , Flondor Michael , Hanser Anja , Pallivathukal Sabine , Holtmannspötter Markus , Kneisel Florian F. , Reuter Daniel A. , Kisch-Wedel Hille , Zwissler Bernhard
Published: August 2005

Background

Inhaled perfluorohexan vapor has been shown to improve gas exchange and pulmonary mechanics in oleic acid- and ventilator-induced lung injury. However, in the clinical setting, lung injury frequently occurs in the context of systemic inflammation and consecutive lung injury, which may be induced experimentally by intravenous administration of endotoxin. The authors studied whether vaporized perfluorohexan is efficacious during endotoxin-induced lung injury in domestic pigs.

Methods

Twenty-two pigs (29 [23, 31] kg body weight [first, third interquartile]; tracheostomy) were anesthetized and mechanically ventilated. In the endotoxin (n = 8) and perfluorohexan groups (n = 7), we administered endotoxin of Escherichia coli 111:B4, 1 mg.kg . h for 1 h and 10 microg.kg.h for 5 h in consecutive order. In the perfluorohexan group, inhalation of the test drug was started 2 h 30 min after the start of the intravenous endotoxin and terminated after 30 min. In a control group (n=7), animals were instrumented and observed over time without further intervention. Oxygenation function was assessed from oxygen partial pressures (Po2, blood gases) and calculated shunt fraction. Respiratory compliance was calculated from airway pressure and tidal volume. Measurements were performed before and every hour during endotoxin infusion.

Results

After 6 h of endotoxin, gas exchange and pulmonary compliance were deteriorated in the endotoxin group (Pao2: 184 [114, 289] vs. 638 [615, 658] mmHg, pulmonary shunt fraction: 30 [23, 38] vs. 4 [3, 6]%, respiratory compliance: 12 [11, 14] vs. 22 [19, 23] ml/mbar; P < 0.05, endotoxin vs. control). Inhalation of vaporized perfluorohexan did not improve Pao 2 (107 [60, 221] mmHg), pulmonary shunt fraction (32 [26, 58]%), or respiratory compliance (14 [10, 17] ml/mbar) when compared with intravenous endotoxin (not significant, perfluorohexan vs. endotoxin).

Conclusions

Inhalation of vaporized perfluorohexan does not improve pulmonary gas exchange or respiratory compliance in endotoxin-induced porcine lung injury.
The ED50and ED95of Intrathecal Isobaric Bupivacaine with Opioids for Cesarean Delivery
Authors: Carvalho Brendan , Durbin Marie , Drover David R. , Cohen Sheila E. , Ginosar Yehuda , Riley Edward T.
Published: August 2005

Background

The ideal intrathecal isobaric bupivacaine dose for cesarean delivery anesthesia is uncertain. While small doses (5-9 mg) of bupivacaine may reduce side effects such as hypotension, they potentially increase spinal anesthetic failures. This study determined the ED50 and ED95 of intrathecal isobaric bupivacaine (with adjuvant opioids) for cesarean delivery.

Methods

After institutional review board approval and written informed consent were obtained, 48 parturients undergoing elective cesarean delivery under combined spinal-epidural anesthesia were enrolled in this double-blind, randomized, dose-ranging study. Patients received a 5-, 6-, 7-, 8-, 9-, 10-, 11-, or 12-mg intrathecal isobaric bupivacaine dose with 10 microg fentanyl and 200 microg morphine. Overall anesthetic success was recorded when no intraoperative epidural supplement was required during the cesarean delivery. ED50 and ED95 values for overall anesthetic success were determined using a logistic regression model.

Results

ED50 and ED95 values for overall anesthetic success were 7.25 and 13.0 mg, respectively. No advantages for low doses could be demonstrated with regard to hypotension, nausea, vomiting, pruritus, or maternal satisfaction, although this study was underpowered to detect significant differences in secondary outcome variables.

Conclusions

The ED50 and ED95 values (7.25 and 13.0 mg, respectively) for intrathecal isobaric bupivacaine in this circumstance are similar to values the authors determined recently for hyperbaric bupivacaine using similar methodology. These ED50 and ED95 values are significantly higher than those advocated in previous reports in which success was claimed using lower intrathecal bupivacaine doses. The current study used stricter criteria to define "successful" anesthesia and support the use of larger bupivacaine doses to ensure adequate patient comfort.
Predicting Postoperative Pain by Preoperative Pressure Pain Assessment
Authors: Hsu Yung-Wei , Somma Jacques , Hung Yu-Chun , Tsai Pei-Shan , Yang Chen-Hsien , Chen Chien-Chuan
Published: August 2005

Background

The goal of this study was to evaluate whether preoperative pressure pain sensitivity testing is predictive of postoperative surgical pain.

Methods

Female subjects undergoing lower abdominal gynecologic surgery were studied. A pressure algometer was used preoperatively to determine the pressure pain threshold and tolerance. A visual analog scale (VAS) was used to assess postoperative pain. A State-Trait Anxiety Inventory was used to assess patients' anxiety. Subjects received intravenous patient-controlled analgesia for postoperative pain control. The preoperative pain threshold and tolerance were compared with the postoperative VAS pain score and morphine consumption.

Results

Forty women were enrolled. Their preoperative pressure pain threshold and tolerance were 141 +/- 65 kPa and 223 +/- 62 kPa, respectively. The VAS pain score in the postanesthesia care unit and at 24 h postoperatively were 81 +/- 24 and 31 +/- 10, respectively. Highly anxious patients had higher VAS pain scores in the postanesthesia care unit (P < 0.05). Pressure pain tolerance was significantly correlated with the VAS at 24 h postoperatively (P < 0.001, r = -0.52). Pressure pain tolerance after fentanyl administration (mean, 272 +/- 68 kPa) correlated significantly with morphine consumption in the first 24 h postoperatively (P < 0.002, r = -0.48).

Conclusions

Assessment of preoperative pressure pain tolerance is significantly correlated with the level of postoperative pain. Pain tolerance assessment after fentanyl was administered and fentanyl sensitivity predicted the dose of analgesics used in the first 24 h after surgery. The algometer is thus a simple, useful tool for predicting postoperative pain and analgesic consumption.
Postamputation Pain and Sensory Changes in Treatment-naive Patients
Authors: Wilder-Smith Clive H. , Hill Lauren T. , Laurent Sophie
Published: August 2005

Background

Pain after amputation is common but difficult to treat, and few controlled treatment studies exist.

Methods

In the current study, 94 treatment-naive posttraumatic limb amputees with phantom pain (intensity: mean visual analog scale score [0-100], 40 [95% confidence interval, 38-41]) were randomly assigned to receive individually titrated doses of tramadol, placebo (double-blind comparison), or amitriptyline (open comparison) for 1 month. Nonresponders were crossed over to the alternative active treatment.

Results

After 1 month, phantom pain intensity was 1 (0-2) in the 48 tramadol responders (mean dose, 448 mg [95% confidence interval, 391-505 mg]), 0 (0-0) in the 40 amitriptyline responders (55 [50-59] mg), and 0 (0-0) in the 2 placebo responders, with similar effects on stump pain. Cytochrome P-450 2D6 slow metabolizers derived greater analgesia from tramadol and less from amitriptyline compared with fast metabolizers in the first treatment week (P < 0.01). Electrical pain thresholds increased and pain during suprathreshold stimulation decreased markedly on the stump and, to a lesser extent, on the contralateral limb after 1 month of treatment with amitriptyline or tramadol. Adverse effects were minor in all groups, but more common with tramadol.

Conclusions

In treatment-naive patients, both amitriptyline and tramadol provided excellent and stable phantom limb and stump pain control with no major adverse events. Both drugs demonstrated consistent and large antinociceptive effects on both the stump and the intact limbs.
Abdominal Surgery Decreases Food-reinforced Operant Responding in Rats
Authors: Martin Thomas J. , Kahn William R. , Eisenach James C.
Published: August 2005

Background

Establishment of early oral nutrition after surgery is associated with a decrease in morbidity and mortality. The following studies were undertaken to determine how surgery influences food-reinforced behavior in rats and to determine the relevance of afferent input from the incision site on this behavior.

Methods

Rats were trained to press a lever for food pellets to assess the effects of various abdominal surgical manipulations. Operant requirements and food availability were also manipulated. The effects of wound infiltration with bupivacaine and denervation of the abdominal musculature in the area of the incision were similarly examined.

Results

Incision of the skin and abdominal musculature produced significant behavioral effects. Food pellets earned were significantly decreased, with gut manipulation producing effects of greater magnitude and duration than incision alone. Operant requirements or different schedules of food availability did not influence the effect of surgery on behavior. Infiltration of the wound with bupivacaine produced a reversal of the effects of surgery on behavior after skin and muscle incision but had minimal effects when the viscera were manipulated. Similarly, denervation of the abdominal musculature reversed the effects of abdominal incision on behavior.

Conclusions

Food maintained behavior is disrupted after laparotomy in rats. The time course and magnitude of this disruption, as well as its reversal by bupivacaine or denervation, are consistent with postoperative incisional pain. Manipulation of the viscera produces a greater effect than laparotomy alone, and additional mechanisms unrelated to incisional pain affect food reinforcement and feeding after surgery.
Postpolio Syndrome and Anesthesia
Authors: Lambert David A. , Giannouli Eleni , Schmidt Brian J. , Warltier David C.
Published: August 2005

The development of polio vaccines 50 yr ago essentially halted childhood polio epidemics in the industrialized world. During the past quarter century, a constellation of delayed neuromuscular symptoms, called postpolio syndrome, became recognized among the aging polio survivors. The prevalence of postpolio syndrome in the U.S. population is estimated to be in the hundreds of thousands. The most common symptoms are fatigue, pain, and new onset weakness thought to be related to delayed deterioration of motor neuron function. When a patient with postpolio syndrome presents for surgery, special precautions are warranted, because these patients may have respiratory impairment, sleep apnea, swallowing difficulties, and cold intolerance. This article first reviews clinical features and some pathoetiologic theories of postpolio syndrome and then focuses on anesthetic considerations including the use of common anesthetics, neuromuscular blockade, regional anesthesia, and general anesthetic management strategies.
Possible Mechanism of the Vasodepressor Effect of Endokinin A/B in Anesthetized Rats
Authors: Abdelrahman Aly Mohamed , Syyong Harley , Tjahjadi Anindita , Pang Catherine Cheuk Ying
Published: August 2005

We investigated the mechanism of the vasodepressor effect of endokinin A/B. An intravenous (IV) bolus of endokinin A/B (0.05-0.3 nmol/kg) dose-dependently decreased mean arterial pressure in thiobutabarbital-anesthetized rats. The magnitude of the response was unaffected by IV pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, inhibitor of nitric oxide synthase), methylene blue (inhibitor of soluble guanylyl cyclase), indomethacin (cyclooxygenase inhibitor), or tetraethylammonium (TEA, nonspecific K+ channel blocker). L-NAME reduced the half-recovery time of the vasodepressor effect of endokinin A/B relative to responses in rats pretreated with either saline or norepinephrine, which caused a similar pressor effect as did L-NAME. Methylene blue, but not TEA or indomethacin, reduced the recovery time of the vasodepressor effect of endokinin A/B. Therefore, the vasodepressor effect of endokinin A/B is mediated via the nitric oxide/L-arginine pathway and activation of soluble guanylyl cyclase but not by production of prostanoids or opening of TEA-sensitive K+ channels.
Negative Inotropic Effect of Low-Dose Ethanol in Mouse Ventricular Myocytes is Mediated by Activation of Endothelial Nitric Oxide Synthase
Authors: Zhang Shengjun , Grover Gary J , Stokes Henry , Scholz Peter M , Weiss Harvey R
Published: August 2005

Low doses of ethanol can produce negative functional effects in ventricular myocytes. This may be related to the nitric oxide-cyclic GMP signal transduction system. We tested the hypothesis that ethanol stimulated endothelial nitric oxide synthase and this caused the negative functional effects in cardiac myocytes. This hypothesis was tested in ventricular myocytes isolated from endothelial nitric oxide synthase-knockout (eNOS−/−) and wild-type (WT) control mice. Cell function was determined with a video edge detector at 37°C. Myocytes were administered 5 or 10 mM ethanol alone or after 10−6 M L-nitro-arginine-methyl ester (L-NAME, nitric oxide synthase inhibitor) or 10−6 M 1H[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ, soluble guanylyl cyclase inhibitor). There were no differences in basal perecentage shortening (2.6 ± 0.2% WT versus 2.4 ± 0.2% eNOS) or maximal rate of shortening (44 ± 6 WT versus 47 ± 6 μms eNOS) between groups. In the WT mice, 10 mM ethanol significantly decreased percentage shortening (1.8 ± 0.1) and maximal rate of shortening (35 ± 4). These effects were blocked by L-NAME and ODQ. In the eNOS−/− mice, these values were not affected by ethanol. Similar data were seen for both maximal rate of shortening and relaxation. These data provide both pharmacological and direct genetic proof that these low doses of ethanol act as a stimulator of endothelial nitric oxide synthase, and this leads to the negative functional effects in ventricular myocytes.
Triple ACE-ECE-NEP Inhibition in Heart Failure: A Comparison With ACE and Dual ECE-NEP Inhibition
Authors: Mellin Virginie , Jeng Arco Y , Monteil Christelle , Renet Sylvanie , Henry Jean Paul , Thuillez Christian , Mulder Paul
Published: August 2005

Mortality remains high in chronic heart failure (CHF) because under ACE inhibitor treatment other neurohumoral systems remain/become (de)activated, such as the endothelin and atrial natriuretic peptide pathways. Dual endothelin-converting enzyme-neutral endopeptidase (ECE-NEP) inhibition exerts beneficial effects in experimental CHF, but whether “triple” ACE-ECE-NEP inhibition is superior to ACE or ECE-NEP inhibition is unknown. We compared, in rats with CHF, ACE-ECE-NEP to ACE or ECE-NEP inhibition in terms of left ventricular (LV) hemodynamics and remodeling. Benazepril (2 mg/kg/d) or the ECE-NEP inhibitor CGS26303 (10 mg/kg/d) were administered alone or in combination (subcutaneously for 28 days starting 7 days after coronary ligation). ACE-ECE-NEP inhibition reduced blood pressure more markedly than ACE or ECE-NEP inhibition. All treatments increased cardiac output to the same extent, but ACE-ECE-NEP inhibition reduced LV diameter and LV end-diastolic pressure more markedly than ACE or ECE-NEP inhibition. The reduction of LV weight and collagen accumulation in the “viable” myocardium was most pronounced after ACE-ECE-NEP inhibition. These results, obtained in experimental CHF, illustrate a further improvement of LV hemodynamics and structure after ACE-ECE-NEP inhibition compared with either ACE or ECE-NEP inhibition, but whether this is associated with a further improvement of exercise tolerance and/or survival remains to be determined.
Monitoring the European standard series in 10 centres 1996–2000
Authors: Bruynzeel D. P. , Diepgen T. L. , Andersen K. E. , Brandão F. M. , Bruze M. , Frosch P. J. , Goossens A. , Lahti A. , Mahler V. , Maibach H. I , Menné T. , Wilkinson J. D.
Published: August 2005

A 5‐year retrospective study of the frequency of sensitization to the 25 allergens of the European standard series (ESS) was conducted in 10 centres in 8 European countries. Included were the results of 26 210 patients. The range in sensitivities differed moderately between the centres. Combining results of different centres and drawing conclusions on incidences can be done only with great care. The information on the ranking of the allergens and their sensitization incidence in the clinics are useful for decisions on the future composition of the standard series. The ESS is still a valid screening tool, and no substances should be deleted.
A multicentre review of the hairdressing allergens tested in the UK
Authors: Katugampola Ruwani P. , Statham Barry N. , English John S. C. , Wilkinson Mark M. , Foulds Iain S. , Green Cathy M. , Ormerod Anthony D. , Stone Natalie M. , Horne Helen L. , Chowdhury Mahbub M. U.
Published: August 2005

Allergens used for patch testing in the hairdressing series vary between dermatology centres in the UK. The aim of our study is to ascertain the hairdressing allergens currently in use and their test results in several dermatology centres in the UK. Data were obtained from databases in 9 dermatology departments. The allergens with positive results and current/past relevance were included in a new hairdressing series based on collective experience, for wider use and further evaluation.
A multicentre review of the footwear allergens tested in the UK
Authors: Katugampola Ruwani P. , Statham Barry N. , English John S. C. , Wilkinson Mark M. , Foulds Iain S. , Green Cathy M. , Ormerod Anthony D. , Stone Natalie M. , Horne Helen L. , Chowdhury Mahbub M. U.
Published: August 2005

Footwear allergens used for patch testing vary between dermatology centres in the UK. The aim of our study is to ascertain the footwear allergens currently in use and their test results in several dermatology centres in the UK. Data were obtained from databases in 9 dermatology departments. A new footwear series consisting of 19 allergens including those with positive results and current/past relevance in this study based on collective experience is proposed for wider use and further evaluation.
Allergic contact dermatitis associated with reactive dyes in a dark garment: a case report
Authors: Moreau Linda , Goossens An
Published: August 2005

In this study, we present a case of a patient who has not been occupationally exposed to reactive dyes, but did present with a dermatitis from wearing a dark cotton garment. The patient experienced reactivation of his dermatitis when rewearing a new unwashed dark T‐shirt made of 100% cotton (in fact, the patient reported that it had to be washed at least 3 times before the skin reaction disappeared). He presented positive patch tests to 6 reactive dyes from Chemotechnique® textile series. The clothing could not be proved as the true cause of the dermatitis, but resolution occurred upon removal of the suspected garment. This suggests that contact allergy to the reactive dyes (he did not react to any other dyes and his garment was a natural fabric) was likely responsible. With this report, we would like to emphasize that reactive dyes, as a class, should be considered as potential allergens, both occupationally and from non‐occupational exposure such as garments. If garments containing reactive dyes are not properly rinsed in the manufacturing process, we believe that excess of dye can be retained that may cause allergic contact dermatitis (ACD). As the reactive dyes and their hydrolysis products are very water‐soluble, they can be easily washed off to prevent ACD.
DNA damage and TNFα cytokine production in hairdressers with contact dermatitis
Authors: Cavallo Delia , Ursini Cinzia Lucia , Setini Andrea , Chianese Concetta , Cristaudo Antonio , Iavicoli Sergio
Published: August 2005

The present work was undertaken to study in hairdressers exposed to several irritants and allergens (prevalently hair‐dyeing) and affected by hand contact dermatitis the possible correlation between exposure and direct‐oxidative DNA damage, production of tumour necrosis factor alpha (TNFα) and allergic inflammatory disease. We evaluated in 19 hairdressers with hand contact dermatitis, 14 allergic contact dermatitis (ACD) and 5 irritant contact dermatitis (ICD) and in a selected control group TNFα serum levels by ELISA and direct‐oxidative DNA damage by Fpg (formamido‐pyrimidine‐glycosylase)‐modified Comet test on blood. Hairdressers were divided on the basis of number of hair‐dyeing carried out weekly into 2 groups: low‐exposure (<60 hair‐dyeing/week) and high‐exposure hairdressers (≥60 hair‐dyeing/week) that reflect also the exposure to other allergens and irritants and 2 different tasks (hairdressers and apprentice hairdressers, respectively). Serum levels of TNFα in hairdressers with ACD were significantly higher than controls with a correlation to exposure level. Significant DNA damage in ICD hairdressers with higher exposure as compared to controls was found. These findings suggest that occupational exposure can induce in hairdressers, particularly ICD, DNA damage, increase the TNFa levels particularly in ACD and induce allergic sensitization, suggesting a relationship between direct‐oxidative DNA damage, TNFα production and allergic inflammatory disease.
Implementation of an occupational skin disease prevention programme in Danish cheese dairies
Authors: Sell Lea , Flyvholm Mari‐Ann , Lindhard Gitte , Mygind Karen
Published: August 2005

The purpose of this study was to implement an evidence‐based prevention programme to reduce occupational skin diseases in a wet work occupation by educational activities and elements from an occupational health‐management system. The effects were studied by telephone interviews using a standardized questionnaire (NOSQ‐2002) with trade‐modified questions on work and exposure. The study population consisted of all employees at 5 cheese dairies. At baseline, October 2002, a total of 557 answered (83.8%). At follow up 1 year later, a total of 650 current and former employees answered (81.8%). At 4 of the 5 dairies, the eczema frequency at baseline was relatively low (11.8% and 5.9% at intervention dairies; 7.0%, 10.4% and 33.3% at comparison dairies). On all the studied dairies, about one‐third of the workers reported having 2 or more skin symptoms at baseline. At follow up, skin symptoms were reduced significantly on all dairies. Effects restricted to the intervention dairies included significant increases in the use of gloves and moisturizers. The comparison dairy with high eczema frequency at baseline introduced skin‐care products, changed hand soap and mowed employees with skin problems, away from adverse working areas during the intervention period, and the frequency of eczema was significantly reduced at follow up.
Common contact sensitizers in the Czech Republic. Patch test results in 12,058 patients with suspected contact dermatitis*
Authors: Machovcova A. , Dastychova E. , Kostalova D. , Vojtechovska A. , Reslova J. , Smejkalova D. , Vaneckova J. , Vocilkova A.
Published: August 2005

The patch test results of 12 058 patients (4416 male and 7642 female) referred to 9 clinics in the Czech Republic between January 1997 and December 2001 were evaluated. Patients were tested with the same series of allergens by using the standardized patch testing method. The current standard tool for diagnosing allergic contact dermatitis (ACD) in the Czech Republic is the Trolab®test panel (Hermal, Reinbeck, Germany) which consists of 23 allergens. Only a few data exists on ACD in the Czech Republic. All patients were tested with the 23 allergen European standard series. Of these patients, 7661 (63.5%) had 1 or more positive reactions. On average, there were 2.8 positive reactions per patient. ACD, according to clinical relevance, was diagnosed in 5339 (69.7%) of these patients. The most frequent allergens were metals (22.9%), especially nickel sulfate (13.8%), and followed by Myroxylon pereirae resin (balsam of Peru) (7.3%), fragrance mix (5.8%), formaldehyde (4.2%) and lanolin alcohol (3.0%). Our results were compared with results from other countries. We conclude that the European standard series is suitable for detection of ACD in the Czech Republic.
Gene Expression of Placental Glutathione S‐Transferase in Hereditary Hepatitis and Spontaneous Hepatocarcinogenesis of LEC Strain Rats
Authors: Masuda Ryuichi , Yoshida Michihiro C. , Sasaki Motomichi
Published: August 2005

Liver tissues of LEG rats, which develop fulminant hepatitis and hepatocellular carcinoma (hepatoma), were examined by Northern blot analysis using a cDNA probe of rat placental glutathione S‐transferase (GST‐P). GST‐P gene expression was observed not only during hepatocarcinogenesis but also in fulminant hepatitis before development of chronic hepatitis and hepatoma in LEC rats. Cholangiofibrosis in LEC rats also showed high GST‐P expression. A transplantable cell line derived from spontaneous LEC hepatoma exhibited a remarkably high expression. By contrast, very weak expression was observed in the livers of young LEC rats before development of hepatitis and control strain rats. Thus, spontaneous hepatic lesions in LEC rats may provide a new clue to elucidate the mechanism of GST‐P gene expression.
Synergism between Sodium Chloride and Sodium Taurocholate and Development of Pepsinogen‐altered Pyloric Glands: Relevance to a Medium‐term Bioassay System for Gastric Carcinogens and Promoters in Rats
Authors: Tatematsu Masae , Mutai Mamoru , Inoue Kaoru , Ozaki Keisuke , Furihata Chie , Ito Nobuyuki
Published: August 2005

In an approach to early detection of gastric carcinogens and promoters in an in vivo test system, promotion by sodium chloride (NaCl) and the synergistic effects of NaCl and sodium taurocholate (Na‐TC) on development of pepsinogen‐altered pyloric glands (PAPG) in rat glandular stomach after initiation with N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG) were investigated. A total of 205 male WKY/NCrj rats were divided into 8 groups. Group 1 was given a single dose of MNNG of 160 mg/ kg body weight by gastric intubation, and starting 2 weeks later basal diet containing Na‐TC for 18 weeks. In addition, 1 ml doses of saturated NaCl solution were given by gastric intubation at weeks 4, 6, 8 and 10. Similarly, group 2 was treated with MNNG and Na‐TC, while group 3 animals received MNNG and NaCl. Group 4 was given MNNG alone. Groups 5–8 served as equivalent controls without MNNG initiation. The results revealed significantly enhanced induction of immunohisto‐chemically defined PAPG in the Na‐TC + NaCl (P< 0.001), Na‐TC (P<0.01) and NaCl (P<0.01) treated animals initiated with MNNG. Sodium chloride demonstrated a clear synergistic effect with Na‐TC in promoting the development of PAPG, suggesting possible advantage for its use in medium‐term in vivo assays for detection of gastric carcinogens and promoters.
Strain Differences in Susceptibility to 2‐Acetylaminofluorene and Phenobarbital Promotion of Hepatocarcinogenesis: Immunohistocliemical Analysis of Cytochrome P‐450 Isozyme Induction by 2‐Acetylaminofluorene and Phenobarbital
Authors: Asamoto Makoto , Tsuda Hiroyuki , Kato Toshio , Ito Nobuyuki , Masuko Takashi , Hashimoto Yoshiyuki , Nagase Sumi
Published: August 2005

Strain differences in the expression of cytochrome P‐450 isoenzymes (P‐450s) during enhancement of hepatocarcinogenesis by 2‐acetylaminofluorene (2‐AAF) and phenobarbital (PB) were investigated immunohistochemically using monoclonal antibodies against phenobarbital (PB) (APF3) or 3‐methylcholanthrene (3‐MC) (APH8) inducible P‐450s. LEW, SD, WBN, F344, SHR, NAR, Wistar and ODS rats were studied, the first five strains proving to be less susceptible to 2‐AAF induction of APH8 while responding strongly to the promoting influence of this chemical, as reported previously. The other three strains, NAR, Wistar and ODS, demonstrated greater inducibility, this correlating with an observed resistance to promotion by 2‐AAF. PB administration was not associated with any strain difference in APF3 cytochrome P‐4SO inducibility except in the ODS rat, in which its effects were minimal. The results provide direct evidence that differential expression of cytochrome P‐450 species plays a major role in determining responsiveness to hepatocarcinogenesis‐promoting agents such as 2‐AAF.
Inductions of Ornithine Decarboxylase and Replicative DNA Synthesis but not DNA Single Strand Scission or Unscheduled DNA Synthesis in the Pyloric Mucosa of Rat Stomach by Catechol
Authors: Furihata Chie , Hatta Akiko , Matsushima Taijiro
Published: August 2005

The possible tumor‐promoting and genotoxic activities of catechol were examined. Administration of catechol by gastric intubation at doses of 10 to 90 mg/kg body weight to male F344 rats induced up to 19‐fold increase in ornithine decarboxylase activity with a maximum after 8 h and up to 8‐fold increase in replicative DNA synthesis with a maximum after 24 h in the pyloric mucosa of the stomach. These results suggest that catechol has tumor‐promoting activity in the pyloric mucosa of rat stomach. However, its administration at doses of 37.5 to 90 mg/kg body weight did not induce DNA single strand scission in the pyloric mucosa as determined by the alkaline elution method after 2 and 6 h or unscheduled DNA synthesis examined after 2 and 12 h.
Life‐span Studies on Spontaneous Tumor Development in the Medaka (Oryzias latipes)
Authors: Masahito Prince , Aoki Kazuko , Egami Nobuo , Ishikawa Takatoshi , Sugano Haruo
Published: August 2005

A total of 961 medaka, separated chronologically from the first to the fifth year of life, were examined for spontaneous tumor development. While no liver tumors were found in either male or female medaka under the age of 1 year and the incidence in 2‐year‐old fish was relatively low (males 1.9% and females 1.7%), they became more common with advancing age. The incidence was higher in females than in males from 3 to 5 years of age, reaching 7.1% in 5‐year‐old female stock. These liver tumors included a total of 12 adenomas and 9 hepatocellular carcinomas. The hepatocellular carcinomas were histologically well differentiated and were all observed in female medaka. Spontaneous tumors occurring in organs other than the liver were rare and sporadic. Four squamous cell carcinomas, 5 melanomas and 4 lymphosarcomas were observed with no sexual or pronounced age bias being evident. The squamous cell carcinomas developed in the surface epithelium with local invasion into the dermis. Melanomas occurred in the abdominal cavity and demonstrated systemic invasion into various parts of the body. Three out of the 4 lymphosarcomas arose from the inner part of the operculum suggesting that these tumors were of thymic origin. They also showed extensive invasion. The data indicate a particular susceptibility of older female medaka to liver but not other tumor development.