bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local Anesthetic Inhibition of m1 Muscarinic Acetylcholine Signaling
Authors: Hollmann Markus W. , Fischer Lars G. , Byford Anne M. , Durieux Marcel E. 
Published: November 2003

Background
Local anesthetics inhibit lipid mediator signaling (lysophosphatidate, thromboxane) by acting on intracellular domains of the receptor or on the G protein. On receptors for polar agonists, the ligand-binding pocket could form an additional site of interaction, possibly resulting in superadditive inhibition. The authors therefore investigated the effects of local anesthetics on m1 muscarinic receptor functioning.

Methods
The authors expressed receptors in isolation using Xenopus oocytes. Using a two-electrode voltage clamp, the authors measured the effects of lidocaine, QX314 (permanently charged), and benzocaine (permanently uncharged) on Ca2+-activated Cl- currents elicited by methylcholine. The authors also characterized the interaction of lidocaine with [3H] quinuclydinyl benzylate ([3H]QNB) binding to m1 receptors.

Results
Lidocaine inhibited muscarinic signaling with a half-maximal inhibitory concentration (IC50 18 nm) 140-fold less than that of extracellularly administered QX314 (IC50 2.4 microm). Intracellularly injected QX314 (IC50 0.96 mm) and extracellularly applied benzocaine (IC50 1.2 mm) inhibited at high concentrations only. Inhibition of muscarinic signaling by extracellularly applied QX314 and lidocaine was the result of noncompetitive antagonism. Intracellularly injected QX314 and benzocaine inhibited muscarinic and lysophosphatidate signaling at similar concentrations, suggesting an action on the common G-protein pathway. Combined administration of intracellularly injected (IC50 19 microm) and extracellularly applied QX314 (IC50 49 nm) exerted superadditive inhibition. Lidocaine did not displace specific [3H]QNB binding to m1 receptors.

Conclusions
m1 Muscarinic signaling is inhibited by clinically relevant concentrations of lidocaine and by extracellularly administered QX314, suggesting that the major site of action is a extracellular domain of the muscarinic receptor. An additional less potent but superadditive inhibitory effect on the G-protein is suggested.
Process Analysis in Outpatient Knee Surgery
Authors: Williams Brian A. , Kentor Michael L. , Williams John P. , Figallo Chiara M. , Sigl Jeffrey C. , Anders Joel W. , Bear Taylor C. , Tullock William C. , Bennett Craig H. , Harner Christopher D. , Fu Freddie H. 
Published: November 2003

Background
The performance of anesthetic procedures before operating room entry (e.g., with either general or regional anesthesia [RA] induction rooms) should decrease anesthesia-controlled time in the operating room. The authors retrospectively studied the associations between anesthesia techniques and anesthesia-controlled time, evaluating one surgeon performing a single procedure over a 3-yr period. The authors hypothesized that, using the anesthesia care team model, RA would be associated with reduced anesthesia-controlled time compared with general anesthesia (GA) alone or combined general-regional anesthesia (GA-RA).

Methods
The authors queried an institutional database for 369 consecutive patients undergoing the same procedure (anterior cruciate ligament reconstruction) performed by one surgeon over a 3-yr period (July 1995 through June 1998). Throughout the period of study, anesthesia staffing consisted of an attending anesthesiologist medically directing two nurse anesthetists in two operating rooms. Anesthesia-controlled time values were compared based on anesthesia techniques (GA, RA, or GA-RA) using one-way analysis of variance, general linear modeling using time-series and seasonal adjustments, and chi-square tests when appropriate. P < 0. 05 was considered significant.

Results
RA was associated with the lowest anesthesia-controlled time (11.4 +/- 1.3 min, mean +/- 2 SEM). GA-RA (15.7 +/- 1.0 min) was associated with lower anesthesia-controlled time than GA used alone (20.3 +/- 1.2 min).

Conclusions
When compared with GA without an induction room for outpatients undergoing anterior cruciate ligament reconstruction, RA with an induction room was associated with the lowest anesthesia- controlled time. Managers must weigh the costs and time required for anesthesiologists and additional personnel to place nerve blocks or induce GA preoperatively in such a staffing model.
Age Is Not an Impediment to Effective Use of Patient-controlled Analgesia by Surgical Patients
Authors: Gagliese Lucia , Jackson Marla , Ritvo Paul , Wowk Adarose , Katz Joel 
Published: November 2003

Background
Obstacles to the use of patient-controlled analgesia (PCA) by elderly surgical patients have not been well-documented. Age differences in preoperative psychological factors, postoperative pain and analgesic consumption, treatment satisfaction, and concerns regarding PCA were measured to identify factors important to effective PCA use.

Methods
Preoperatively, young (mean age +/- SD, 39 +/- 9 yr; n = 45) and older (mean age +/- SD, 67 +/- 8 yr; n = 44) general surgery patients completed measures of attitudes toward and expectations of postoperative pain and PCA, psychological distress, health opinions, self-efficacy, and optimism. On the first 2 postoperative days, pain at rest and with movement and satisfaction with pain control were assessed using visual analog scales. Daily opioid intake was recorded. When PCA was discontinued, satisfaction and concerns about it were assessed.

Results
The older patients expected less intense pain (P </= 0.003) and preferred less information about (P </= 0.02) and involvement in (P </= 0.002) health care than young patients. There were no age differences with regard to pain at rest (P </= 0.22) or with movement (P </= 0.68). The older group self-administered less opioid than the young group (P </= 0.0001) and received PCA for more days than the young group (P </= 0.004). The groups did not differ in concerns about pain relief, adverse drug effects, including opioid addiction, and equipment use or malfunction. Satisfaction with PCA was high and did not differ between the groups.

Conclusions
Patient-controlled analgesia use was not hindered by age differences in beliefs about postoperative pain and opioids. Younger and older patients attained comparable levels of analgesia and were equally satisfied with their pain control.
Cerebral Hyperthermia in Children after Cardiopulmonary Bypass
Authors: Bissonnette Bruno , Holtby Helen M. , Davis Annette J. , Pua Hweeleng , Gilder Fay J. , Black Michael 
Published: November 2003

Background
Cerebral hyperthermia after hypothermic cardiopulmonary bypass has been poorly documented for adults and never in children. This study was designed to monitor brain temperature during and up to 6 h after cardiopulmonary bypass in infants and children.

Methods
Fifteen infants and children, between 3 months and 6 yr of age, were studied. A right retrograde jugular bulb catheter was used to measure the jugular venous bulb temperature (JVBT) during the procedure and the first 6 h in the critical care unit. The temperature of the blood from the bypass machine was measured at the aorta through the cannula using an indwelling temperature probe. All data were acquired every minute.

Results
The age of the patients ranged from 3 to 71 months (median, 15 months). The mean weight was 11.5 +/- 8.4 kg. The mean JVBT recorded at the end of cardiopulmonary bypass was 36.9 +/- 1.4 degrees C but reached 39.6 +/- 0.8 degrees C after six h (P < 0.01). The kinetics of brain rewarming was determined by the slope of the mean JVBT and corresponded to y +/- 0.006x + 37.21 (r2 = 0.97). The JVBT differed from the tympanic temperature after 200 min (P < 0.01) and the lower esophageal (P < 0.05) and rectal (P < 0.001) temperatures after 300 min. After 6 h, the tympanic, rectal, and lower esophageal temperatures were 37.8 +/- 0.9, 37.7 +/- 0.6, and 38.4 +/- 0.7 degrees C, respectively, whereas the JVBT was 39.6 +/- 0.8 degrees C (P < 0.001). However, the correlation coefficients between the JVBT and the tympanic, rectal, and esophageal temperatures were 0.98, 0. 85, and 0.97, respectively. No complications were recorded with placement of the jugular bulb catheter.

Conclusions
Mean JVBT was significantly increased over the mean core temperature at all times from rewarming by cardiopulmonary bypass onward. Although the lower esophageal, rectal, and tympanic temperatures correlated well with JVBT, all three failed to reflect JVBT during recovery. This observation might help to elucidate factors involved in the functional and structural neurologic injury known to occur in pediatric patients.
Temporal Relation between Acoustic and Force Responses at the Adductor Pollicis during Nondepolarizing Neuromuscular Block
Authors: Bellemare François , Couture Jacques , Donati François , Plaud Benoît 
Published: November 2003

Background
Contracting muscle emits sounds. The purpose of this study was to compare the time course of muscular paralysis at the adductor pollicis muscle (AP) with use of acoustic myography and mechanomyography.

Methods
Thirteen elective surgery patients, American Society of Anesthesiologists physical status I, received rocuronium (0.6 mg/kg intravenously) as a bolus dose during general anesthesia. Force of AP was measured with use of a strain gauge, and sounds were recorded simultaneously with use of a small condenser microphone fixed on the palmar surface of the hand over the AP. Supramaximal stimulation was applied to the ulnar nerve at 0.1 Hz for 45-60 min. In seven patients, the response to train-of-four stimulation was also recorded during recovery.

Results
Force and sounds both were equally sensitive in measuring maximum block. The relation between sound and force was curvilinear, with good agreement near 0 and 100% and acoustic response exceeding mechanical response at intermediate levels of block. The acoustic signal had a slower onset and a faster recovery than the force response. The fade response of sound to train-of-four stimulation also recovered faster than that of force.

Conclusion
Acoustic myography is an alternative method to monitor muscular paralysis that is easy to set up and applicable to most superficial muscles. However, the time course of relaxation at AP using acoustic myography differs from the time course of force relaxation. Therefore, these two methods are not equivalent when applied to AP.
Optimal Propofol Plasma Concentration during Upper Gastrointestinal Endoscopy in Young, Middle-aged, and Elderly Patients
Authors: Kazama Tomiei , Takeuchi Ken , Ikeda Kazuyuki , Ikeda Takehiko , Kikura Mutsuhito , Iida Takayuki , Suzuki Shuji , Hanai Hiroyuki , Sato Shigehito 
Published: November 2003

Background
Suitable propofol plasma concentrations during gastroscopy have not been determined for suppressing somatic and hemodynamic responses in different age groups.

Methods
Propofol sedation at target plasma concentrations from 0.5 to 4.0 microgram/ml were performed randomly in three groups of patients (23 per group) who were undergoing elective outpatient gastroscopy: ages 17-49 yr (group 1), 50-69 yr (group 2), and 70-89 yr (group 3). Plasma propofol concentration in which 50% of patients do not respond to these different stimuli were determined by logistic regression: verbal command (Cp50ls), somatic response to gastroscopy (Cp50endo), and gag response to gastroscopy (Cp50gag). Hemodynamic responses were also investigated in the different age groups.

Results
Cp50ls concentrations were 2.23 microgram/ml (group 1), 1.75 microgram/ml (group 2), and 1.40 microgram/ml (group 3). The Cp50endo values in groups 1 and 2 were 2.87 and 2.34 microgram/ml, respectively, which were significantly higher than their respective Cp50ls values. Cp50endo value in group 3 was 1.64 microgram/ml, which was close to its Cp50ls value. Because of a high degree of interpatient variability, Cp50gag could not be defined. Systolic blood pressure response decreased with increasing propofol concentrations.

Conclusions
The authors determined the propofol concentration necessary for gastroscopy and showed that increasing age reduces it. Propofol concentration that suppresses somatic response induces loss of consciousness in almost all young patients.
Gender Affects Report of Pain and Function after Arthroscopic Anterior Cruciate Ligament Reconstruction
Authors: Taenzer Andreas H. , Clark Cantwell , Curry Craig S. 
Published: November 2003

Background
Gender-related differences in pain have been clearly shown in experimental settings. Clinical studies of such differences have produced conflicting findings. No studies have shown a significant difference in pain experience associated with differences in functional outcomes. Arthroscopic anterior cruciate ligament reconstruction (AACLR) produces pain of moderate intensity and provides a useful setting for examining gender-related differences in pain and function.

Methods
This study was a retrospective review of prospectively gathered data collected for a continuous quality improvement program and involved all patients who underwent AACLR at a single outpatient facility since June 1992. Anesthetic, surgical, and perioperative management techniques were standardized. Using a questionnaire, all patients were routinely asked to record pain scores, narcotic consumption, and whether they were able to perform a standardized straight leg-raising maneuver on each of the first 5 postoperative days.

Results
A total of 736 patients were enrolled for surgery, 58% of whom completed the entire 5-day questionnaire. Women reported higher pain scores at rest as well as with activity on postoperative day 1 compared with men (P < 0.005). In addition, fewer women were able to perform the straight leg-raising maneuver on postoperative day 1 (P = 0.002) and postoperative day 2 (P = 0.004). There was no difference in the amount of narcotics consumed at any time during the study period.

Conclusions
Women seem to experience greater intensity of pain after AACLR that is associated with a decrease in an intermediate measure of functional outcome. These differences may result from differences in either response to analgesics or neuroprocessing.
Changes in Regional Myocardial Function after Coronary Artery Bypass Graft Surgery Are Predicted by Intraoperative Low-dose Dobutamine Echocardiography
Authors: Aronson Solomon , Dupont Frank , Savage Robert , Drum Melinda , Gunnar William , Jeevanandam Valluvan 
Published: November 2003

Background
Left ventricular dysfunction is often reversed after coronary artery bypass graft (CABG) surgery; however, this change is not easily predicted. The authors hypothesized that functional changes after a low dose of dobutamine (5 microgram. kg-1. min-1) intraoperatively would predict functional changes when complete revascularization was achieved.

Methods
The authors analyzed 560 segments in 40 patients scheduled for elective CABG surgery for regional wall motion (1-5 scoring system) at four stages: baseline (after induction and intubation), with administration of low-dose dobutamine before cardiopulmonary bypass, after separation from cardiopulmonary bypass (early), and after administration of protamine (late). Two independent observers scored the myocardial regions according to a 16-segment model in multiple imaging planes. For each segment, the response to dobutamine was dichotomized as improved or not improved from baseline and analyzed with logistic regression. The influence of covariates (ejection fraction, myocardial infarction, diabetes mellitus, and beta blockers) was also determined with logistic regression models. P < 0.05 was considered significant.

Results
Changes in myocardial function after low-dose dobutamine were highly predictive for early (P < 0.0001) and late (P < 0.0001) changes in myocardial function from baseline regional scores. The overall odds ratio for early and late improvement increased by 20.7 and 34.6, respectively, when improvement was observed after low-dose dobutamine was administered. The overall positive predictive value of improved regional wall motion after CABG did not vary with left ventricular ejection fraction, a history of myocardial infarction, or beta blocker use, and it varied little with diabetic status (range, 0.86-0.96) if regional wall motion improved with low-dose dobutamine before CABG. The overall negative predictive value was 0.70; however, the range varied with diabetic status (i.e., lowest in diabetic patients and highest in nondiabetic patients).

Conclusion
Intraoperative low-dose dobutamine is a reliable method to predict myocardial functional reserve and to determine functional recovery expected after coronary revascularization.
Intracarotid Infusion of the Nitric Oxide Synthase Inhibitor, l-NMMA, Modestly Decreases Cerebral Blood Flow in Human Subjects
Authors: Joshi Shailendra , Young William L. , Duong D. Hoang , Ostapkovich Noeleen D. , Aagaard Beverly D. , Hashimoto Tomoki , Pile-Spellman John 
Published: November 2003

Background
The authors hypothesized that if nitric oxide (NO) was a determinant of background cerebrovascular tone, intracarotid infusion of NG-monomethyl-L-arginine (L-NMMA), a NO synthase (NOS) inhibitor, would decrease cerebral blood flow (CBF) and intracarotid L-arginine would reverse its effect.

Methods
In angiographically normal cerebral hemispheres, after the initial dose-escalation studies (protocol 1), the authors determined the effect of intracarotid L-NMMA (50 mg/min for 5 min) on CBF and mean arterial pressure (MAP) over time (protocol 2). Changes in CBF and MAP were then determined at baseline, during L-NMMA infusion, and after L-NMMA during L-arginine infusion (protocol 3). To investigate effects of higher arterial blood concentrations of L-NMMA, changes in CBF and MAP were assessed at baseline and after a bolus dose of L-NMMA (250 mg/1 min), and vascular reactivity was tested by intracarotid verapamil (1 mg/min, protocol 4). CBF changes were also assessed during induced hypertension with intravenous phenylephrine (protocol 5).

Results
Infusion of L-NMMA (50 mg/min for 5 min, n = 7, protocol 2) increased MAP by 17% (86 +/- 8 to 100 +/- 11 mmHg; P < 0.0001) and decreased CBF by 20% (45 +/- 8 to 36 +/- 6 ml. 100 g-1. min-1; P < 0.005) for 10 min. Intracarotid l-arginine infusion after L-NMMA (protocol 3) reversed the effect of L-NMMA. Bolus L-NMMA (protocol 4) increased MAP by 20% (80 +/- 11 to 96+/-13 mmHg; P< 0.005), but there was no significant decrease in CBF. Intracarotid verapamil increased CBF by 41% (44+/- 8 to 62 +/- 9 ml. 100 g-1. min-1; P< 0.005). Phenylephrine-induced hypertension increased MAP by 20% (79 +/- 9 to 95 +/- 6 mmHg; P = 0.001) but did not affect CBF.

Conclusions
The results suggest that intracarotid L-NMMA modestly decreases CBF, and the background tone of cerebral resistance vessels may be relatively insensitive to NOS inhibition by the intraarterial route.
Potency of Bupivacaine Stereoisomers Tested In Vitro and In Vivo
Authors: Vladimirov Marina , Nau Carla , Mok Wai Man , Strichartz Gary 
Published: November 2003

Background
Chiral local anesthetics, such as ropivacaine and levobupivacaine, have the potential advantage over racemic mixtures in showing reduced toxic side effects. However, these S-(levo, or "-")isomers also have reportedly lower potency than their optical antipode, possibly resulting in no advantage in therapeutic index. Potency for local anesthetics inhibiting Na+ channels or action potentials depends on the pattern of membrane potential and so also does the stereopotency ratio. Here the authors have quantitated the stereopotencies of R-, S-, and racemic bupivacaine, comparing several in vitro assays of neuronal Na+ channels with those from in vivo functional nerve block, to establish relative potencies and to understand better the role of different modes of channel inhibition in overall functional anesthesia.

Methods
The binding of bupivacaine to Na+ channels was assessed indirectly by its antagonism of [3H]-batrachotoxin binding to rat brain synaptosomes. Inhibition of Na+ currents by bupivacaine was directly assayed in voltage-clamped GH-3 neuroendocrine cells. Neurobehavioral functions were disrupted by bupivacaine percutaneously injected (0.1 ml; 0.0625-1.0%) at the rat sciatic nerve and semiquantitatively assayed. Concentration-dependent actions of R-, S-, and racemic bupivacaine were compared for their magnitude and duration of action.

Results
Competitive batrachotoxin displacement has a stereopotency ratio of R:S = 3:1. Inhibition of Na+ currents with different prepulse potentials shows that S > R potency when the membrane is hyperpolarized, and R > S potency when it is depolarized from normal resting values. Functional deficits assayed in vivo usually demonstrate no consistent enantioselectivity and only a modest stereopotency (R:S = 1.2-1.3) for peak analgesia achieved at the lowest doses. Other functions display no significant stereopotency in either the degree, the duration, or their product (area under the curve) at any dose.

Conclusion
Although the in vitro actions of bupivacaine showed stereoselectivity ratios of 1.3-3:1 (R:S), in vivo nerve block at clinically used concentrations showed much smaller ratios for peak effect and no significant enantioselectivity for duration. A primary role for the blockade of resting rather than open or inactivated Na+ channels may explain the modest stereoselectivity in vivo, although stereoselective factors controlling local disposition cannot be ruled out. Levo-(S-)bupivacaine is effectively equipotent to R- or racemic bupivacaine in vivo for rat sciatic nerve block.
Effects of Thiopental and Its Optical Isomers on Nicotinic Acetylcholine Receptors
Authors: Downie David L. , Franks Nicholas P. , Lieb William R. 
Published: November 2003

Background
With the exception of gamma-aminobutyric acidA (GABAA) receptors, the major molecular targets underlying the anesthetizing actions of thiopental have yet to be established. Neuronal nicotinic acetylcholine receptors (nAChRs) are closely related to GABAA receptors and hence might also be major targets. If so, they might be expected to be substantially inhibited by surgical concentrations (EC50 = 25 micrometer) of thiopental and to display the same stereoselectivity as does general anesthesia.

Methods
Neuronal alpha4beta2, neuronal alpha7 and muscle alphabetagammadelta nAChRs were expressed in Xenopus oocytes. Peak acetylcholine-activated currents were measured at -70 mV using the two-electrode voltage clamp technique. Racemic thiopental and its two optical isomers were applied with and without preincubation and at high and low concentrations of acetylcholine.

Results
Inhibition of all three nAChRs was enhanced by preincubation with thiopental, a protocol that mimics the pharmacologic situation in vivo. Using this protocol, inhibition was further enhanced by high concentrations of acetylcholine, with IC50 = 18 +/- 2, 34 +/- 4, and 20 +/- 2 micrometer (mean +/- SEM) thiopental for the neuronal alpha4beta2, neuronal alpha7 and muscle alphabetagammadelta nAChRs, respectively, with Hill coefficients near unity. Neither the neuronal alpha7 nor the muscle alphabetagammadelta nAChR differentiated between the optical isomers of thiopental. However, R(+)-thiopental was significantly more effective than the S(-) isomer at inhibiting the neuronal alpha4beta2 nAChR; interestingly, this is diametrically opposite to their stereoselectivity for general anesthesia.

Conclusions
Both central neuronal and peripheral muscle nAChRs can be substantially inhibited by thiopental at surgical EC50 concentrations but with either no stereoselectivity or one opposite to that for general anesthesia. Thus, nAChRs are probably not crucial targets for producing thiopental anesthesia, although nAChRs may play a part in the side effects produced by this agent.