bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensory Processing in the Deep Spinal Dorsal Horn of Neurokinin-1 Receptor Knockout Mice
Authors: Weng Han-Rong , Mansikka Heikki , Winchurch Ronald , Raja Srinivasa N. , Dougherty Patrick M. 
Published: November 2003

Background
The neurokinin-1 receptor and its primary ligand, substance P, are widely recognized as contributing to the spinal processing of nociceptive stimuli, yet the specific function of the neurokinin-1 receptor remains unclear.

Methods
To better clarify these functions, the authors examined the neurophysiologic responses of L4-L5 neurons in the deep dorsal horn to acute mechanical, thermal, and electrical stimuli in knockout and wild-type mice. In addition, the capacity of knockout and wild-type mice to show wind-up to repeated C-fiber stimuli and to show sensitization after cutaneous mustard oil was assessed.

Results
A total of 68 nociceptive neurons (35 in knockout, 33 in wild type) in laminae III-V were studied. No differences in the acute responses of neurons in knockout and wild-type mice to graded mechanical, thermal, or electrical stimuli or in the acute responses to mustard oil were observed. However, wind-up to repeated electrical stimulation at C-fiber intensity was significantly attenuated in the knockout mice compared with wild type controls. In addition, mustard oil-induced mechanical hypersensitivity was significantly reduced in the knockout mice.

Conclusions
These results indicate that neurokinin-1 receptors do not play a significant role in the responses of nociceptive neurons in the deep spinal dorsal horn to acute noxious mechanical, thermal, electrical, or chemical stimuli. On the other hand, neurokinin-1 receptors are critical for the central hyperexcitability that is observed in these neurons with repeated C-fiber inputs and to the central sensitization induced by topical mustard oil application.
Comparison of Five Experimental Pain Tests to Measure Analgesic Effects of Alfentanil
Authors: Luginbühl Martin , Schnider Thomas W. , Petersen-Felix Steen , Arendt-Nielsen Lars , Zbinden Alex M. 
Published: November 2003

Background
Several experimental pain models have been used to measure opioid effects in humans. The aim of the current study was to compare the qualities of five frequently used experimental pain tests to measure opioid effects.

Methods
The increase of electrical, heat, and pressure pain tolerance and the decrease of ice-water and ischemic pain perception was determined at baseline and at four different plasma concentrations of alfentanil (n = 7) administered as target controlled infusion or placebo (n = 7). A linear mixed-effects modeling (NONMEM) was performed to detect drug, placebo, and time effect as well as interindividual and intraindividual variation of effect.

Results
Only the electrical, ice-water, and pressure pain tests are sensitive to assess a concentration-response curve of alfentanil. At a plasma alfentanil concentration of 100 ng/ml, the increase in pain tolerance compared with baseline was 42.0% for electrical pain, 22.2% for pressure pain, and 21.7% for ice-water pain. The slope of the linear concentration-response curve had an interindividual coefficient of variation of 58.3% in electrical pain, 35.6% in pressure pain, and 60.0% in ice-water pain. The residual error including intraindividual variation at an alfentanil concentration of 100 ng/ml was 19.4% for electrical pain, 6.1% for pressure pain, and 13.0% for ice-water pain. Electrical pain was affected by a significant placebo effect, and pressure pain was affected by a significant time effect.

Conclusion
Electrical, pressure, and ice-water pain, but not ischemic and heat pain, provide significant concentration-response curves in the clinically relevant range of 200 ng/ml alfentanil or lower. The power to detect a clinically relevant shift of the curve is similar in the three tests. The appropriate test(s) for pharmacodynamic studies should be chosen according to the investigated drug(s) and the study design.
Shannon Entropy Applied to the Measurement of the Electroencephalographic Effects of Desflurane
Authors: Bruhn Jörgen , Lehmann Lutz E. , Röpcke Heiko , Bouillon Thomas W. , Hoeft Andreas 
Published: November 2003

Background
The Shannon entropy is a standard measure for the order state of sequences. It quantifies the degree of skew of the distribution of values. Increasing hypnotic drug concentrations increase electroencephalographic amplitude. The probability density function of the amplitude values broadens and flattens, thereby changing from a skew distribution towards equal distribution. We investigated the dose-response relation of the Shannon entropy of the electroencephalographic amplitude values during desflurane monoanesthesia in comparison with previously used electroencephalographic parameters.

Methods
Electroencephalographic records previously obtained in 12 female patients during gynecologic laparotomies were reanalyzed. Between opening and closure of the peritoneum, desflurane vapor settings were varied between 0.5 and 1.6 minimum alveolar concentration. Electroencephalographic Shannon entropy, approximate entropy, median electroencephalographic frequency, SEF 95, total power, log total power, and Bispectral Index were determined, and their correlations with the desflurane effect compartment concentration, obtained by simultaneous pharmacokinetic-pharmacodynamic modeling, were compared.

Results
The electroencephalographic Shannon entropy increased continuously over the observed concentration range of desflurane. The correlation of the Shannon entropy (R2 = 0.84+/-0.08, mean +/- SD) with the desflurane effect compartment concentrations is similar to approximate entropy (R2 = 0.85+/-0.12), SEF 95 (R2 = 0.85+/-0.10), and Bispectral Index (R2 = 0.82+/-0.13) and is more statistically significant than median frequency (R2 = 0.72+/-0.17), total power (R2 = 0.67+/-0.18), and log total power (R2 = 0.80+/-0.09).

Conclusions
The Shannon entropy seems to be a useful electroencephalographic measure of anesthetic drug effect.
The Validity of Performance Assessments Using Simulation
Authors: Devitt J. Hugh , Kurrek Matt M. , Cohen Marsha M. , Cleave-Hogg Doreen 
Published: November 2003

Background
The authors wished to determine whether a simulator-based evaluation technique assessing clinical performance could demonstrate construct validity and determine the subjects' perception of realism of the evaluation process.

Methods
Research ethics board approval and informed consent were obtained. Subjects were 33 university-based anesthesiologists, 46 community-based anesthesiologists, 23 final-year anesthesiology residents, and 37 final-year medical students. The simulation involved patient evaluation, induction, and maintenance of anesthesia. Each problem was scored as follows: no response to the problem, score = 0; compensating intervention, score = 1; and corrective treatment, score = 2. Examples of problems included atelectasis, coronary ischemia, and hypothermia. After the simulation, participants rated the realism of their experience on a 10-point visual analog scale (VAS).

Results
After testing for internal consistency, a seven-item scenario remained. The mean proportion scoring correct answers (out of 7) for each group was as follows: university-based anesthesiologists = 0.53, community-based anesthesiologists = 0.38, residents = 0.54, and medical students = 0.15. The overall group differences were significant (P < 0.0001). The overall realism VAS score was 7.8. There was no relation between the simulator score and the realism VAS (R = -0.07, P = 0.41).

Conclusions
The simulation-based evaluation method was able to discriminate between practice categories, demonstrating construct validity. Subjects rated the realism of the test scenario highly, suggesting that familiarity or comfort with the simulation environment had little or no effect on performance.
A Randomized, Controlled Trial of Advance Care Planning Discussions during Preoperative Evaluations
Authors: Grimaldo Denise A. , Wiener-Kronish Jeanine P. , Jurson Tamara , Shaughnessy Thomas E. , Curtis J. Randall , Liu Linda L. 
Published: November 2003

Background
Although many patients and physicians support the concept of advance care planning, only a small percentage of patients actually have the necessary discussion with health care providers. Hospital-based physicians other than primary care providers often are needed to increase physician, patient, and proxy communication about advanced directives. This study evaluated the effectiveness of a 5-10-min discussion designed to foster dialogue between patients and their proxies in a preoperative evaluation clinic. The discussions were lead by anesthesiologists.

Methods
A randomized controlled trial was conducted from September 1998 through May 1999 in a preoperative evaluation clinic at University of California, San Francisco, a tertiary care center. English-speaking patients aged 65 yr or older who were scheduled for elective surgery were randomized to receive a short information session stressing the importance of communication about end-of-life care between the patients and their proxies. Patients randomized to the control group received the standard preoperative anesthesia screening. An admitting counselor questioned all patients (control and intervention) about whether they have an advanced directive as part of the registration process before their arrival in clinic.

Results
The intervention significantly increased discussions about end-of-life care between patients and their proxies. Eighty seven percent of patients reported having discussions with their proxies as compared with only 66% of control patients (P = 0.001). The intervention also increased durable power of attorney completion rate to 27% as compared with 10% completion rate by controls.

Conclusions
The preoperative evaluation period can be an opportunity to encourage patient and proxy communication about end-of-life care.
Distribution of the Probability of Survival Is a Strategic Issue for Randomized Trials in Critically Ill Patients
Authors: Riou Bruno , Landais Paul , Vivien Benoît , Stell Philippe , Labbene Iheb , Carli Pierre 
Published: November 2003

Background
Many randomized clinical trials in trauma have failed to demonstrate a significant improvement in survival rate. Using a trauma patient database, we simulated what could happen in a trial designed to improve survival rate in this setting.

Methods
The predicted probability of survival was assessed using the TRISS methodology in 350 severely injured trauma patients. Using this probability of survival, the authors simulated the effects of a drug that may increase the probability of survival by 10-50% and calculated the number of patients to be included in a triad, assuming alpha = 0.05 and beta = 0.10 by using the percentage of survivors or the individual probability of survival. Other distributions (Gaussian, J shape, uniform) of the probability of survival were also simulated and tested.

Results
The distribution of the probability of survival was bimodal with two peaks (< 0.10 and > 0.90). There were major discrepancies between the number of patients to be included when considering the percentage of survivors or the individual value of the probability of survival: 63,202 versus 2,848 if the drug increases the probability of survival by 20%. This discrepancy also occurred in other types of distribution (uniform, J shape) but to a lesser degree, whereas it was very limited in a Gaussian distribution.

Conclusions
The bimodal distribution of the probability of survival in trauma patients has major consequences on hypothesis testing, leading to overestimation of the power. This statistical pitfall may also occur in other critically ill patients.
Anaphylactic Reactions to Aprotinin Reexposure in Cardiac Surgery
Authors: Dietrich Wulf , Späth Paul , Zühlsdorf Michael , Dalichau Harald , Kirchhoff Paul G. , Kuppe Hermann , Preiss Dieter U. , Mayer Gabriele 
Published: November 2003

Background
Aprotinin, a serine proteinase inhibitor, reduces bleeding during cardiac surgery. As aprotinin is derived from bovine lung, it has antigenic properties. This investigation examined the incidence of anaphylactic reactions in patients reexposed to aprotinin and the relation to preformed antiaprotinin immunoglobulin (Ig)G and IgE antibodies.

Methods
This prospective observational study conducted at five centers in Germany evaluated patients undergoing repeat cardiac surgery reexposed to aprotinin between 1995 and 1996. Antiaprotinin IgG and IgE antibody measurements, using a noncommercial enzyme-linked immunosorbent assay and an immunofluorescence assay, respectively, were performed preoperatively and postoperatively. An anaphylactic reaction was defined as major changes from baseline within 10 min of aprotinin administration of systolic pressure 20% or greater, heart rate 20% or greater, inspiratory pressure greater than 5 cm H2O, or a skin reaction.

Results
In 121 cases (71 adults, 46 children), a mean aprotinin reexposure interval of 1,654 days (range, 16-7,136 days) was observed. Preoperative antiaprotinin IgG (optical density ratio > 3) and IgE antibodies (radioallergosorbent test [RAST] score < 3) were detected in 18 and 9 patients, respectively. High concentrations of each (IgG, optical density ratio > 10; IgE, RAST score > or = 3) were detected in five patients. Three patients (2.5%; 95% confidence interval, 0.51-7.1%) experienced an anaphylactic reaction after aprotinin exposure, followed by full recovery; these patients had reexposure intervals less than 6 months (22, 25, and 25 days) and the highest preoperative IgG concentrations of all patients (P < 0.05). Assay sensitivity was 100%, as no anaphylactic reactions occurred in IgG-negative patients (95% confidence interval, 0.0-3.1%); assay specificity was 98%. Preoperative IgE measurements were quantifiable in two of three reactive patients and in three nonreacting patients.

Conclusions
Quantitative detection of antiaprotinin IgE and IgG lacks specificity for predictive purposes; however, quantitation of antiaprotinin IgG may identify patients at risk for developing an anaphylactic reaction to aprotinin reexposure.
Local Anesthetic Effects on Priming and Activation of Human Neutrophils
Authors: Hollmann Markus W. , Gross Ariane , Jelacin Niko , Durieux Marcel E. 
Published: November 2003

Background
Local anesthetics (LAs) have been shown to inhibit human polymorphonuclear neutrophil (hPMN) functions in vitro, but mechanisms are poorly understood. In this study the authors determined how LAs affect superoxide anion production of hPMNs primed with platelet-activating factor (PAF). The authors studied which pharmacologic properties of LAs are important for this action and assessed the LA site of action within the PAF signaling pathway.

Methods
Metabolic activity of primed and/or activated hPMNs were measured using the cytochrome-c assay. hPMNs were incubated with several LAs for 1 h to assess interference with PAF signaling. Using protein kinase C (PKC) inhibitors, the PKC activator phorbol myristate acetate (PMA), and the phospholipase C (PLC) antagonist U-73122, we studied involvement of PKC and PLC in the priming process. Pertussis toxin (PTX) was used to characterize the G proteins mediating this pathway. Combined administration of lidocaine with PMA or PTX was used to determine the LA site of action within the priming pathway.

Results
Platelet-activating factor effectively primed hPMNs. Ester LAs (tetracaine and benzocaine) exerted the most profound inhibitory effect on PAF-primed hPMNs, whereas inhibitory potency of amide LAs increased with decreased charged fraction. The major PAF-induced priming pathway is PLC- and PKC-dependent and mainly Gq-mediated. The main target site for LA in this pathway is located upstream of PKC.

Conclusions
Local anesthetics in clinically relevant concentrations inhibit superoxide anion production of PAF-primed hPMNs. Effects on priming by these compounds might explain, at least in part, the previously unexplained difference between concentrations of LAs required for their antiinflammatory action in vitro and in vivo. This study suggests a target site for LAs within a Gq-coupled signaling pathway.
Intravenous Anesthetics Inhibit Nonadrenergic Noncholinergic Lower Esophageal Sphincter Relaxation via Nitric Oxide–Cyclic Guanosine Monophosphate Pathway Modulation in Rabbits
Authors: Kohjitani Atsushi , Miyawaki Takuya , Funahashi Makoto , Mitoh Yoshihiro , Matsuo Ryuji , Shimada Masahiko 
Published: November 2003

Background
Nonadrenergic noncholinergic (NANC) nerves have important roles in the regulation of the lower esophageal sphincter (LES) motility and function. The effects of thiopental, ketamine, and midazolam on NANC LES relaxation were investigated.

Methods
The isometric tension of circular muscle strips from Japanese White rabbits was examined. The NANC relaxation was induced by KCl (30 mM) in the presence of atropine (3 x 10(-6) M) and guanethidine (3 x 10(-6) M). The modifications of the NANC and sodium nitroprusside (SNP; 10(-5) M)-induced relaxation by the anesthetics were examined. The content of 3',5'-cyclic guanosine monophosphate (cGMP) was measured by radioimmunoassay.

Results
The KCl-induced relaxation was abolished by pretreating with tetrodotoxin (10(-6) M). The NANC relaxation was inhibited in the presence of N(G)-nitro-L-arginine (L-NNA; 3 x 10(-5) M), methylene blue (10(-6) M), apamin (10(-7) M), and glibenclamide (10(-5) M). The SNP-induced relaxation was inhibited by methylene blue but was not affected by tetrodotoxin, L-NNA, apamin, or glibenclamide. Ketamine (EC50 = 8.8 x 10(-5) M) and midazolam (EC50 = 4.8 x 10(-6) M) suppressed the NANC response in a concentration-dependent manner, leaving SNP-induced response unchanged. Thiopental altered neither of the relaxations. cGMP content was decreased in the presence of ketamine and midazolam.

Conclusion
The NANC relaxation was mediated by nitric oxide and by low-conductance calcium- and adenosine triphosphate-sensitive potassium channels of smooth muscle. The modulation of the nitric oxide-cGMP pathway was related, at least in part, to the inhibitory actions of ketamine and midazolam on the NANC LES relaxation.
Sedative but Not Analgesic α2Agonist Tolerance Is Blocked by NMDA Receptor and Nitric Oxide Synthase Inhibitors
Authors: Davies M. Frances , Reid Kristina , Guo Tian-Zhi , Agashe Geeta S. , Amin Yogen K. , Maze Mervyn 
Published: November 2003

Background
Studies show that the sedative and analgesic effects of alpha2 adrenergic agonists decrease over time, which is a form of synaptic plasticity referred to as tolerance. Because both the N-methyl-D-aspartate (NMDA) receptor complex and nitric oxide synthase are pivotal for some forms of synaptic plasticity, their role in tolerance to the hypnotic and analgesic effects of alpha2 agonists was investigated.

Methods
After institutional approval, rats were made tolerant to the hypnotic or analgesic action of an alpha2 agonist, dexmedetomidine. The hypnotic response to dexmedetomidine was assessed by the duration of loss of righting reflex, and the analgesic response to dexmedetomidine was assessed by the tail-flick assay. In separate cohorts, either the NMDA receptors or nitric oxide synthase was antagonized by coadministration of MK-801, ketamine, or NO2-arginine, respectively, during induction of tolerance. In a separate series of experiments, after tolerance was induced, the hypnotic and analgesic responses to dexmedetomidine were assessed in the presence of acutely administered MK-801 or NO2-arginine.

Results
Induction of tolerance to the hypnotic effect of dexmedetomidine is blocked by coadministration of MK-801, ketamine, and NO2-arginine. However, after tolerance developed, acute administration of MK-801, ketamine, or NO2-arginine did not prevent the expression of tolerance. Coadministration of MK-801 or NO2-arginine neither prevents the development nor reverses the expression of tolerance to the analgesic action of dexmedetomidine.

Conclusion
The underlying processes responsible for the development of tolerance to the hypnotic and analgesic actions of systemically administered alpha2 agonists were different, with only the sedative tolerance involving the NMDA receptor and nitric oxide synthase system.
Venous Air Embolism during Endoscopic Strip Craniectomy for Repair of Craniosynostosis in Infants
Authors: Tobias Joseph D. , Johnson Joel O. , Jimenez David F. , Barone Constance M. , McBride D. Scott 
Published: November 2003

Background
Various studies have reported an incidence of venous air embolism (VAE) as high as 82.6% during surgical procedures for craniosynostosis. There has been an increase in the use of minimally invasive, endoseopie surgical procedures, including applications for endoscopic strip craniectomy. The current study prospectively evaluated the incidence of VAF during endoscopic strip craniectomy.

Methods
Continuous, intraoperative monitoring for VAE was performed using precordial Doppler monitoring. A recording was made of the Doppler tones and later reviewed to verify its accuracy.

Results
The cohort for the study included 50 consecutive neonates and infants ranging in age from 3.5 to 36 weeks and ranging in weight from 3 to 9 kg. Surgical time varied from 31 to 95 min for a total of 2,701 mm of operating time, during which precordial Doppler tones were auscultated. In 46 patients, there was no evidence of VAE. In four patients, there was a single episode of VAE. Two of the episodes of VAE were grade I (change in Doppler tones), and two were grade H (change in Doppler tones and decrease in end-tidal carbon dioxide). No grade III (decrease in systolic blood pressure by 20% from baseline) VAF was noted.

Conclusion
In addition to previously reported benefits of decreased blood loss, decreased surgical time, and improved postoperative recovery time, the authors noted a low incidence of VAF during endoscopic strip craniectomy in neonates and infants.