bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrograde Air Embolization during Routine Radial Artery Catheter Flushing in Adult Cardiac Surgical Patients
Authors: Murphy Glenn S. , Szokol Joseph W. , Marymont Jesse H. , Avram Michael J. , Vender Jeffery S. 
Published: August 2004

Background
Rapid flushing of radial artery catheters may result in retrograde embolization of air into the cerebral circulation. This study examined the incidence of central air embolization during and after flushing of an arterial pressure monitoring system.

Methods
One hundred adult patients undergoing cardiac surgical procedures were enrolled in this study. Ten ml of saline and blood were withdrawn into a syringe in the arterial flushing-sampling pressure system and then readministered to the patient through a 20-gauge radial artery catheter over 3-12 s. The right carotid artery, left carotid artery, and aortic arch were visualized using ultrasound imaging techniques during three manual flushes of the system. The left and right common carotid arteries were examined for the presence of macrobubbles or microbubbles using a linear array ultrasound transducer. The aortic arch was imaged using transesophageal echocardiography to detect retrograde air emboli. The severity of air embolization was quantified using a modification of an established grading system.

Results
A total of 298 ultrasound studies in 100 patients were recorded and analyzed after radial artery catheter flushing. Two aortic arch images were not obtained because of an inability to place the probe. Most clinicians (54%) returned flush solution to patients at near-maximal injection rates (2-3 ml per second). No air emboli (macrobubbles or microbubbles) were detected in the carotid arteries or aortic arch of any subject.

Conclusion
Retrograde air embolization is a rare event after routine radial artery catheter flushing in adult patients with stable hemodynamic conditions.
Recruitment Maneuvers after a Positive End-expiratory Pressure Trial Do Not Induce Sustained Effects in Early Adult Respiratory Distress Syndrome
Authors: Oczenski Wolfgang , Hörmann Christoph , Keller Christian , Lorenzl Norbert , Kepka Anton , Schwarz Sylvia , Fitzgerald Robert D. 
Published: August 2004

Background
Recruitment maneuvers performed in early adult respiratory distress syndrome remain a matter of dispute in patients ventilated with low tidal volumes and high levels of positive end-expiratory pressure (PEEP). In this prospective, randomized controlled study the authors evaluated the impact of recruitment maneuvers after a PEEP trial on oxygenation and venous admixture (Qs/Qt) in patients with early extrapulmonary adult respiratory distress syndrome.

Methods
After a PEEP trial 30 consecutive patients ventilated with low tidal volumes and high levels of PEEP were randomly assigned to either undergo a recruitment maneuver or not. Data were recorded at baseline, 3 min after the recruitment maneuver, and 30 min after baseline. Recruitment maneuvers were performed with a sustained inflation of 50 cm H2O maintained for 30 s.

Results
Compared with baseline the ratio of the arterial oxygen partial pressure to the fraction of inspired oxygen (Pao2/Fio2) and Qs/Qt improved significantly at 3 min after the recruitment maneuver (Pao2/Fio2, 139 +/- 46 mm Hg versus 246 +/- 111 mm Hg, P < 0.001; Qs/Qt, 30.8 +/- 5.8% versus 21.5 +/- 9.7%, P < 0.005), but baseline values were reached again within 30 min. No significant differences in Pao2/Fio2 and Qs/Qt were detected between the recruitment maneuver group and the control group at baseline and after 30 min (recruitment maneuver group [n = 15]: Pao2/Fio2, 139 +/- 46 mm Hg versus 138 +/- 39 mm Hg; Qs/Qt, 30.8 +/- 5.8% versus 29.2 +/- 7.4%; control group: [n = 15]: Pao2/Fio2, 145 +/- 33 mm Hg versus 155 +/- 52 mm Hg; Qs/Qt, 30.2 +/- 8.5% versus 28.1 +/- 5.4%).

Conclusion
In patients with early extrapulmonary adult respiratory distress syndrome who underwent a PEEP trial, recruitment maneuvers failed to induce a sustained improvement of oxygenation and venous admixture.
Remifentanil versus Morphine Analgesia and Sedation for Mechanically Ventilated Critically Ill Patients
Authors: Dahaba Ashraf A. , Grabner Tanja , Rehak Peter H. , List Werner F. , Metzler Helfried 
Published: August 2004

Background
The rapid onset and offset of action of remifentanil could make it quickly adjustable to the required level of sedation in critically ill patients. The authors hypothesized that the efficacy of a remifentanil-based regimen was greater than that of a morphine-based regimen.

Methods
Forty intent-to-treat patients were randomly allocated to receive a blinded infusion of either remifentanil 0.15 microg x kg(-1) x min(-1) or morphine 0.75 microg x kg(-1) x min(-1). The opioid infusion was titrated, in the first intent, to achieve optimal sedation defined as Sedation Agitation scale of 4. A midazolam open-label infusion was started if additional sedation was required.

Results
The mean percentage hours of optimal sedation was significantly longer in the remifentanil group (78.3 +/- 6.2) than in the morphine group (66.5 +/- 8.5). This was achieved with less frequent infusion rate adjustments (0.34 +/- 0.25 changes/h) than in the morphine group (0.42 +/- 0.22 changes/h). The mean duration of mechanical ventilation and extubation time were significantly longer in the morphine group (18.1 +/- 3.4 h, 73 +/- 7 min) than in the remifentanil group (14.1 +/- 2.8 h, 17 +/- 6 min), respectively. Remifentanil mean infusion rate was 0.13 +/- 0.03 microg x kg(-1) x min(-1), whereas morphine mean infusion rate was 0.68 +/- 0.28 microg x kg(-1) x min(-1). More subjects in the morphine group (9 of 20) than in the remifentanil group (6 of 20) required midazolam. The incidence of adverse events was low and comparable across the two treatment groups.

Conclusions
A remifentanil-based regimen was more effective in the provision of optimal analgesia-sedation than a standard morphine-based regimen. The remifentanil-based regimen allowed a more rapid emergence from sedation and facilitated earlier extubation.
Inhibitory Effect of Glucocorticoids on Human-cloned 5-hydroxytryptamine3AReceptor Expressed in Xenopus Oocytes
Authors: Suzuki Takahiro , Sugimoto Masahiro , Koyama Hideki , Mashimo Takashi , Uchida Ichiro 
Published: August 2004

Background
Methylprednisolone, dexamethasone, and other glucocorticoids have been found effective against nausea and vomiting induced by chemotherapy and surgery. Although the specific 5-hydroxytriptamine3 (5-HT3) receptor antagonists such as ondansetron and ramosetron are used as antiemetics, reports show that the use of 5-HT3 receptor antagonists with some glucocorticoids brings additional effects. Glucocorticoids are reported to be antiemetic. The effect of glucocorticoids on 5-HT3 receptor, however, has not been well characterized. This study was designed to examine whether dexamethasone and methylprednisolone had direct effects on human-cloned 5-HT3A receptor expressed in Xenopus oocytes.

Methods
Homomeric human-cloned 5-HT3A receptor was expressed in Xenopus oocytes. The authors used the two-electrode voltage-clamping technique to study the effect of methylprednisolone and dexamethasone on 5-HT-induced current.

Results
Both dexamethasone and methylprednisolone concentration-dependently attenuated 5-HT-induced current. Dexamethasone inhibited 2 microm 5-HT-induced current, which was equivalent to EC30 concentration for 5-HT3A receptor, with an inhibitory concentration 50% of 5.29 +/- 1.02 microm. Methylprednisolone inhibited 2 microm 5-HT-induced current with an inhibitory concentration 50% of 1.07 +/- 0.15 mm. The mode of inhibition with either dexamethasone or methylprednisolone was noncompetitive and voltage-independent. When administered together with the 5-HT3 receptor antagonists, ramosetron or metoclopramide, both glucocorticoids showed an additive effect on 5-HT3 receptor.

Conclusion
The glucocorticoids had a direct inhibitory effect on 5-HT3 receptors. The combined effect of glucocorticoids and the 5-HT3 receptor antagonists seems additive.
Effects of Isoflurane and Sevoflurane on Intracellular Calcium and Contractility in Pressure-overload Hypertrophy
Authors: Hannon James D. , Cody Mark J. , Sun David X. , Housmans Philippe R. 
Published: August 2004

Background
Depression of myocardial contractility as a result of isoflurane appears to be greater in myocardial hypertrophy, and the cellular basis for this difference in susceptibility is not clear. In this study we examined the effects of isoflurane and sevoflurane on contractility and intracellular calcium in an animal model of pressure-overload hypertrophy.

Methods
Pressure-overload hypertrophy was established in young male ferrets by banding the main pulmonary artery for 1 month and the effects of isoflurane and sevoflurane on contractility and intracellular calcium ([Ca]i) were examined in isolated right ventricular papillary muscles, trabeculae, and myocytes. Intracellular calcium was measured with the bioluminescent photoprotein aequorin in isolated papillary muscles, and also with the fluorescent indicator fluo-3 in isolated ventricular myocytes. In addition, Ca sensitivity was assessed in isolated trabeculae after disruption of the surface membrane with a nonionic detergent (skinned fibers).

Results
In the presence of isoflurane and sevoflurane, papillary muscles from banded animals exhibited a greater depression of contractility and isolated ventricular myocytes showed a greater decrease in peak [Ca]i. Furthermore, baseline calcium sensitivity was decreased and the slope of the relationship between [Ca] and force was increased in skinned trabeculae from banded animals. Isoflurane decreased calcium sensitivity in trabeculae from both normal and banded animals.

Conclusions
These results suggest that changes in [Ca]i and altered calcium sensitivity are both responsible for the exaggerated effects of some volatile anesthetics on contractility in pressure-overload hypertrophy.
Inhibitory Effects of the Anesthetics Propofol and Sevoflurane on Spontaneous Lymphatic Vessel Activity in Rats
Authors: Hattori Jun-Ichi , Yamakage Michiaki , Seki Sumihiko , Okazaki Kayoko , Namiki Akiyoshi 
Published: August 2004

Background
The effects of propofol and sevoflurane on lymphatic vessel activity are unknown. This study aimed to clarify the effects of these anesthetics on lymphatic vessel activity in rats by the use of a technique for mechanical removal of the endothelium.

Methods
The authors first examined the effects of propofol (8 mg/kg) and sevoflurane (2.0%) on in vivo lymphatic flow by injection of dye into the femoral regions of rats. In the in vitro study, the ends of the vessel segments of rat thoracic duct were connected to a syringe and stopcock, respectively. Spontaneous changes in diameter of each segment were monitored, and the extraluminal side of each segment was exposed to propofol (1 x 10(-6) approximately 3 x 10(-5) M) or sevoflurane (0.5 approximately 2.0%). Endothelial function was eliminated by perfusion of air into the lumen.

Results
In the dye uptake study, 80% of iliac lymphatic nodes were positively stained in a control group, whereas only 10% and 20% were positively stained in propofol and sevoflurane groups, respectively. In the in vitro study, both of the anesthetics significantly decreased the amplitude of spontaneous activity of lymphatic vessels with or without endothelial function. Sevoflurane inhibited the frequency of lymphatic vessel activity but propofol had no effect on it. When the endothelial function was eliminated, both anesthetics decreased the frequency of spontaneous activity of lymphatic vessels.

Conclusions
Propofol and sevoflurane seem to have some different effects on endothelial function, which regulates the pacemaking of spontaneous contraction of lymphatic vessels.
Isoflurane Preconditioning Induces Neuroprotection That Is Inducible Nitric Oxide Synthase–dependent in Neonatal Rats
Authors: Zhao Ping , Zuo Zhiyi 
Published: August 2004

Background
Perinatal stroke is a common human disease. Neonatal brains are immature and engaged in active synaptogenesis. Preconditioning adult rats with the volatile anesthetic isoflurane induces neuroprotection. Whether isoflurane preconditioning induces neuroprotection in neonates is not known.

Methods
Seven-day-old Sprague-Dawley rats had left common carotid arterial ligation followed by hypoxia with 8% oxygen for 1, 2, or 2.5 h at 37 degrees C. Isoflurane preconditioning with 1 or 1.5% isoflurane for 30 min was performed at 24 h before the brain hypoxia/ischemia. The inducible nitric oxide synthase inhibitor aminoguanidine (200 mg/kg, intraperitoneally) was administered 30 min before the isoflurane pretreatment. The weight ratio of left to right cerebral hemispheres at 7 days after the brain hypoxia/ischemia was calculated. The mortality during the period from cerebral hypoxia/ischemia to 7 days afterwards was monitored. In another experiment, 6-day-old rats were exposed to 1.5% isoflurane for 30 min. The cerebral hemispheres were removed at various time points for Western analysis of inducible nitric oxide synthase.

Results
The mortality was about 40% in neonates with brain hypoxia/ischemia for 2 h or 2.5 h and was not altered by isoflurane preconditioning. The weight ratio of left/right cerebral hemispheres in the survivors was 0.99 +/- 0.02, 0.65 +/- 0.19, and 0.86 +/- 0.15 (n = 7-18) for the rats in control, brain hypoxia/ischemia for 2.5 h, and isoflurane preconditioning plus brain hypoxia/ischemia for 2.5 h groups, respectively (P < 0.05 for the comparisons between control versus brain hypoxia/ischemia and brain hypoxia/ischemia versus isoflurane preconditioning plus brain hypoxia/ischemia). This isoflurane preconditioning-induced neuroprotection was abolished by aminoguanidine (the weight ratio was 0.61 +/- 0.18, n = 12). Isoflurane induced a time-dependent increase in the inducible nitric oxide synthase proteins.

Conclusions
Isoflurane preconditioning induces neuroprotection in neonatal rats. This neuroprotection is inducible nitric oxide synthase-dependent.
Inhaled Anesthetic Enhancement of Amyloid-β Oligomerization and Cytotoxicity
Authors: Eckenhoff Roderic G. , Johansson Jonas S. , Wei Huafeng , Carnini Anna , Kang Baobin , Wei Wenlin , Pidikiti Ravindernath , Keller Jason M. , Eckenhoff Maryellen F. 
Published: August 2004

Background
The majority of surgical patients receive inhaled anesthetics, principally small haloalkanes and haloethers. Long-term cognitive problems occur in the elderly subsequent to anesthesia and surgery, and previous surgery might also be a risk factor for neurodegenerative disorders like Alzheimer and Parkinson disease. The authors hypothesize that inhaled anesthetics contribute to these effects through a durable enhancement of peptide oligomerization.

Methods
Light scattering, filtration assays, electron microscopy, fluorescence spectroscopy and size-exclusion chromatography was used to characterize the concentration-dependent effects of halothane, isoflurane, propofol, and ethanol on amyloid beta peptide oligomerization. Pheochromocytoma cells were used to characterize cytotoxicity of amyloid oligomers with and without the above anesthetics.

Results
Halothane and isoflurane enhanced amyloid beta oligomerization rates and pheochromocytoma cytotoxicity in vitro through a preference for binding small oligomeric species. Ethanol and propofol inhibited oligomerization at low concentration but enhanced modestly at very high concentration. Neither ethanol nor propofol enhanced amyloid beta toxicity in pheochromocytoma cells.

Conclusions
Inhaled anesthetics enhance oligomerization and cytotoxicity of Alzheimer disease-associated peptides. In addition to the possibility of a general mechanism for anesthetic neurotoxicity, these results call for further evaluation of the interaction between neurodegenerative disorders, dementia, and inhalational anesthesia.
Sevoflurane Inhibits Phorbol-Myristate-Acetate-induced Activator Protein-1 Activation in Human T Lymphocytes in Vitro : Potential Role of the p38-Stress Kinase Pathway
Authors: Loop Torsten , Scheiermann Patrick , Doviakue David , Musshoff Frank , Humar Matjaz , Roesslein Martin , Hoetzel Alexander , Schmidt Rene , Madea Burkhard , Geiger Klaus K. , Pahl Heike L. , Pannen Benedikt H. J. 
Published: August 2004

Background
Modulation of immune defense mechanisms by volatile anesthetics during general anesthesia may compromise postoperative immune competence and healing reactions and affect the infection rate and the rate of tumor metastases disseminated during surgery. Several mechanisms have been suggested to account for these effects. The current study was undertaken to examine the molecular mechanisms underlying these observations.

Methods
Effects of sevoflurane, isoflurane, and desflurane were studied in vitro in primary human CD3 T-lymphocytes. DNA-binding activity of the transcription factor activator protein-1 (AP-1) was assessed using an electrophoretic mobility shift assay. Phorbol-myristate-acetate-dependent effects of sevoflurane on the phosphorylation of the mitogen-activated protein kinases were studied using Western blots, the trans-activating potency of AP-1 was determined using reporter gene assays, and the cytokine release was measured using enzyme-linked immunosorbent assays.

Results
Sevoflurane inhibited activation of the transcription factor AP-1. This effect was specific, as the activity of nuclear factor kappabeta, nuclear factor of activated T cells, and specific protein-1 was not altered and several other volatile anesthetics studied did not affect AP-1 activation. Sevoflurane-mediated suppression of AP-1 could be observed in primary CD3 lymphocytes from healthy volunteers, was time-dependent and concentration-dependent, and occurred at concentrations that are clinically achieved. It resulted in an inhibition of AP-1-driven reporter gene activity and of the expression of the AP-1 target gene interleukin-3. Suppression of AP-1 was associated with altered phosphorylation of p38 mitogen-activated protein kinases.

Conclusion
The data demonstrate that sevoflurane is a specific inhibitor of AP-1 and may thus provide a molecular mechanism for the antiinflammatory effects associated with sevoflurane administration.
Influence of Hepatic and Intestinal Cytochrome P4503A Activity on the Acute Disposition and Effects of Oral Transmucosal Fentanyl Citrate
Authors: Kharasch Evan D. , Whittington Dale , Hoffer Christine 
Published: August 2004

Background
Oral transmucosal fentanyl citrate (OTF) was developed to provide rapid analgesia and is specifically approved for treating breakthrough cancer pain. Fentanyl in OTF is absorbed across the oral mucosa, but a considerable portion is swallowed and absorbed enterally. Fentanyl metabolism is catalyzed by cytochrome P4503A4 (CYP3A). The role of intestinal or hepatic first-pass metabolism and CYP3A activity in OTF disposition is unknown. This investigation examined the influence of hepatic and intestinal CYP3A activity on the disposition and clinical effects of OTF.

Methods
Healthy volunteers (n = 12) were studied in an Institutional Review Board-approved, randomized, balanced, four-way crossover. They received OTF (10 microg/kg) after hepatic/intestinal CYP3A induction by rifampin, hepatic/intestinal CYP3A inhibition by troleandomycin, selective intestinal CYP3A inhibition by grapefruit juice, or nothing (control). Plasma fentanyl and norfentanyl concentrations were determined by mass spectrometry. Fentanyl effects were measured by dark-adapted pupil diameter and subjective self-assessments using visual analog scales.

Results
: Peak plasma fentanyl concentrations, time to peak, and maximum pupil diameter change from baseline were unchanged after rifampin, troleandomycin, and grapefruit juice. Fentanyl elimination, however, was significantly affected by CYP3A alterations. After control, rifampin, troleandomycin and grapefruit juice, respectively, area under the curve of plasma fentanyl versus time was 5.9 +/- 3.7, 2.2 +/- 0.8,* 10.4 +/- 8.9,* and 5.8 +/- 3.3 h x ng/ml; norfentanyl/fentanyl plasma area under the curve ratios were 0.92 +/- 0.63, 3.2 +/- 1.8,* 0.08 +/- 0.14,* and 0.67 +/- 0.33 (*P < 0.05 versus control).

Discussion
Peak fentanyl concentrations and clinical effects after OTF were minimally affected by altering both intestinal and hepatic CYP3A activity, whereas fentanyl metabolism, elimination, and duration of effects were significantly affected; selective intestinal CYP3A inhibition had minimal effects. This suggests that first-pass metabolism minimally influences OTF bioavailability. When treating breakthrough pain, with careful attention to maximal mucosal absorption and minimal swallowing, CYP3A variability and drug interactions are unlikely to affect the onset or magnitude of OTF analgesia; however, duration may be affected.
Influence of Age on the Pharmacokinetics and Pharmacodynamics of Oral Transmucosal Fentanyl Citrate
Authors: Kharasch Evan D. , Hoffer Christine , Whittington Dale 
Published: August 2004

Background
Cancer pain is primarily a problem of older persons. Oral transmucosal fentanyl citrate (OTF) was developed to provide rapid analgesia and is the first drug specifically approved for treating breakthrough cancer pain. Fentanyl in OTF is absorbed across the oral mucosa but a considerable portion is swallowed and absorbed enterally. The effects of age on OTF pharmacokinetics and pharmacodynamics are unknown. This investigation evaluated OTF disposition and clinical effects in older (60-75 yr) compared with younger (18-40 yr) volunteers.

Methods
Healthy young (26 +/- 6 yr) and older (67 +/- 6 yr) volunteers (n = 12 each) were studied in an Institutional Review Board approved protocol. They received OTF (10 microg/kg). Plasma fentanyl and norfentanyl concentrations were determined by mass spectrometry. Fentanyl effects were measured by dark-adapted pupil diameter and by subjective self-assessments using visual analog scales.

Results
Plasma fentanyl and norfentanyl concentrations and pharmacokinetic parameters did not differ between younger and older subjects. Maximum pupil diameter change from baseline was significantly less in older (3.1 +/- 0.7 mm) compared with younger (4.5 +/- 1.1 mm) subjects (P < 0.05). OTF-dependent subjective assessments of alertness/sedation, energy level, confusion, clumsiness, anxiety, and nausea did not differ in the older subjects.

Discussion
The pharmacokinetics of OTF were not altered in older volunteers. In contrast, there was a somewhat diminished response to the miotic effects of fentanyl in older subjects. No change in OTF dosing in the elderly would appear necessary because of altered pharmacokinetics. If the response to OTF in older patients is similar to that in older volunteers and miosis is representative of analgesia and respiratory depression, then changes in OTF dosing with age alone do not appear indicated.