bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in Properties of Substantia Gelatinosa Neurons after Surgical Incision in the Rat
Authors: Kawamata Mikito , Furue Hidemasa , Kozuka Yuji , Narimatsu Eichi , Yoshimura Megumu , Namiki Akiyoshi 
Published: February 2006

Background
Noxious information through A delta and C afferent fibers is transmitted to substantia gelatinosa, a process that plays an important role in plastic changes of nociceptive processing in pathophysiological conditions. In this study, changes in properties of substantia gelatinosa neurons and their sensitivity to systemic administration of lidocaine after surgical incision were investigated using the in vivo patch-clamp technique.

Methods
Under urethane anesthesia, in the current clamp mode, spontaneous activities and responses of substantia gelatinosa neurons to nonnoxious air-puff stimuli and noxious pinch stimuli were recorded before and after 1-cm-long incisions had been made in hairy skin of the hindquarters of rats. Systemic administration of lidocaine (2 mg/kg) was applied at 30 min after the incision.

Results
Stable recordings for 30 min or more after the incision were obtained from 18 substantia gelatinosa neurons that were classified as multireceptive (n = 8), nociceptive (n = 5), and subthreshold (n = 5) neurons. Action potential firing disappeared immediately after completion of the wound closure in most multireceptive and nociceptive neurons, and sustained spontaneous action potential firing was observed in 23% of these substantia gelatinosa neurons. Responsiveness of these substantia gelatinosa neurons, but not that of subthreshold neurons, increased after the incision. Systemic administration of lidocaine suppressed spontaneous firings of action potentials of the substantia gelatinosa neurons and reversed the increased responsiveness of the neurons.

Conclusions
The results suggest that (1) changes in properties of substantia gelatinosa neurons after incision vary depending on the classification of substantia gelatinosa neurons and (2) systemic administration of lidocaine can reverse increased responsiveness of substantia gelatinosa neurons after incision injury.
Cortical Processing of Complex Auditory Stimuli during Alterations of Consciousness with the General Anesthetic Propofol
Authors: Plourde Gilles , Belin Pascal , Chartrand Daniel , Fiset Pierre , Backman Steven B. , Xie Guoming , Zatorre Robert J. 
Published: February 2006

Background
The extent to which complex auditory stimuli are processed and differentiated during general anesthesia is unknown. The authors used blood oxygenation level-dependent functional magnetic resonance imaging to examine the processing words (10 per period; compared with scrambled words) and nonspeech human vocal sounds (10 per period; compared with environmental sounds) during propofol anesthesia.

Methods
Seven healthy subjects were tested. Propofol was given by a computer-controlled pump to obtain stable plasma concentrations. Data were acquired during awake baseline, sedation (propofol concentration in arterial plasma: 0.64 +/- 0.13 microg/ml; mean +/- SD), general anesthesia (4.62 +/- 0.57 microg/ml), and recovery. Subjects were asked to memorize the words.

Results
During all periods including anesthesia, the sounds conditions combined elicited significantly greater activations than silence bilaterally in primary auditory cortices (Heschl gyrus) and adjacent regions within the planum temporale. During sedation and anesthesia, however, the magnitude of the activations was reduced by 40-50% (P < 0.05). Furthermore, anesthesia abolished voice-specific activations seen bilaterally in the superior temporal sulcus during the other periods as well as word-specific activations bilaterally in the Heschl gyrus, planum temporale, and superior temporal gyrus. However, scrambled words paradoxically elicited significantly more activation than normal words bilaterally in planum temporale during anesthesia. Recognition the next day occurred only for words presented during baseline plus recovery and was correlated (P < 0.01) with activity in right and left planum temporale.

Conclusions
The authors conclude that during anesthesia, the primary and association auditory cortices remain responsive to complex auditory stimuli, but in a nonspecific way such that the ability for higher-level analysis is lost.
Propofol Pharmacokinetics and Pharmacodynamics for Depth of Sedation in Nonventilated Infants after Major Craniofacial Surgery
Authors: Peeters Mariska Y. M. , Prins Sandra A. , Knibbe Catherijne A. J. , DeJongh Joost , van Schaik Ron H. N. , van Dijk Monique , van der Heiden Ilse P. , Tibboel Dick , Danhof Meindert 
Published: February 2006

Background
To support safe and effective use of propofol in nonventilated children after major surgery, a model for propofol pharmacokinetics and pharmacodynamics is described.

Methods
After craniofacial surgery, 22 of the 44 evaluated infants (aged 3-17 months) in the pediatric intensive care unit received propofol (2-4 mg . kg-1 . h-1) during a median of 12.5 h, based on the COMFORT-Behavior score. COMFORT-Behavior scores and Bispectral Index values were recorded simultaneously. Population pharmacokinetic and pharmacodynamic modeling was performed using NONMEM V (GloboMax LLC, Hanover, MD).

Results
In the two-compartment model, body weight (median, 8.9 kg) was a significant covariate. Typical values were Cl = 0.70 . (BW/8.9)0.61 l/min, Vc = 18.8 l, Q = 0.35 l/min, and Vss = 146 l. In infants who received no sedative, depth of sedation was a function of baseline, postanesthesia effect (Emax model), and circadian night rhythm. In agitated infants, depth of sedation was best described by baseline, postanesthesia effect, and propofol effect (Emax model). The propofol concentration at half maximum effect was 1.76 mg/l (coefficient of variation = 47%) for the COMFORT-Behavior scale and 3.71 mg/l (coefficient of variation = 145%) for the Bispectral Index.

Conclusions
Propofol clearance is two times higher in nonventilated healthy children than reported in the literature for ventilated children and adults. Based on the model, the authors advise a propofol dose of 30 mg/h in a 10-kg infant to achieve values of 12-14 on the COMFORT-Behavior scale and 70-75 on the Bispectral Index during the night. Wide pharmacodynamic variability emphasizes the importance of dose titration.
Evaluation of Patient Simulator Performance as an Adjunct to the Oral Examination for Senior Anesthesia Residents
Authors: Savoldelli Georges L. , Naik Viren N. , Joo Hwan S. , Houston Patricia L. , Graham Marianne , Yee Bevan , Hamstra Stanley J. 
Published: February 2006

Background
Patient simulators possess features for performance assessment. However, the concurrent validity and the "added value" of simulator-based examinations over traditional examinations have not been adequately addressed. The current study compared a simulator-based examination with an oral examination for assessing the management skills of senior anesthesia residents.

Methods
Twenty senior anesthesia residents were assessed sequentially in resuscitation and trauma scenarios using two assessment modalities: an oral examination, followed by a simulator-based examination. Two independent examiners scored the performances with a previously validated global rating scale developed by the Anesthesia Oral Examination Board of the Royal College of Physicians and Surgeons of Canada. Different examiners were used to rate the oral and simulation performances.

Results
Interrater reliability was good to excellent across scenarios and modalities: intraclass correlation coefficients ranged from 0.77 to 0.87. The within-scenario between-modality score correlations (concurrent validity) were moderate: r = 0.52 (resuscitation) and r = 0.53 (trauma) (P < 0.05). Forty percent of the average score variance was accounted for by the participants, and 30% was accounted for by the participant-by-modality interaction.

Conclusions
Variance in participant scores suggests that the examination is able to perform as expected in terms of discriminating among test takers. The rather large participant-by-modality interaction, along with the pattern of correlations, suggests that an examinee's performance varies based on the testing modality and a trainee who "knows how" in an oral examination may not necessarily be able to "show how" in a simulation laboratory. Simulation may therefore be considered a useful adjunct to the oral examination.
Protective Effects of Isoflurane Pretreatment in Endotoxin-induced Lung Injury
Authors: Reutershan Jörg , Chang Daniel , Hayes John K. , Ley Klaus 
Published: February 2006

Background
The concept of antiinflammatory effects of volatile anesthetics is well established in vitro and in some organ systems. Their protective role in lung injury, however, remains to be elucidated. The authors hypothesized that in the lung, isoflurane pretreatment may attenuate neutrophil infiltration and reduce endotoxin-induced injury.

Methods
Male C57Bl/6 mice were exposed to aerosolized lipopolysaccharide. Neutrophil recruitment into the pulmonary vasculature and migration into the different lung compartments (interstitium and alveolar air space) were determined by flow cytometry. Capillary protein leakage, formation of lung edema, and concentration of the chemokines keratinocyte-derived chemokine (CXCL1) and macrophage inflammatory protein 2 (CXCL2/3) in bronchoalveolar lavage were compared in mice with or without isoflurane treatment (1.4% inspired for 30 min) at different times before and after endotoxin exposure.

Results
Endotoxin inhalation induced significant neutrophil migration into all lung compartments. Isoflurane pretreatment attenuated both neutrophil recruitment into lung interstitium and alveolar space when given 1 or 12 h before or 1 h after lipopolysaccharide but not at 4, 6, or 24 h before endotoxin exposure. Isoflurane pretreatment 1 or 12 h before lipopolysaccharide also reduced protein leakage and pulmonary edema. Production of CXCL1 and CXCL2/3 in the bronchoalveolar lavage was reduced when isoflurane was given 1 h but not 12 h before lipopolysaccharide, suggesting different mechanisms for early and late protection.

Conclusion
Isoflurane pretreatment reduces acute lung injury when given 1 or 12 h before an endotoxin challenge or within the first hour of an already established inflammation.
Differential Effect of Ketamine and Lidocaine on Spontaneous and Mechanical Evoked Pain in Patients with Nerve Injury Pain
Authors: Gottrup Hanne , Bach Flemming W. , Juhl Gitte , Jensen Troels S. 
Published: February 2006

Background
The mechanisms underlying neuropathic pain are incompletely understood. Targeting specific molecular mechanisms in the pain signaling system may assist in understanding key features in neuropathic pains such as allodynia. This study examined the effect of systemically administered ketamine, an N-methyl-D-aspartate receptor antagonist and lidocaine, a sodium channel blocker, on spontaneous pain, brush-evoked pain, and pinprick-evoked pain in patients with nerve injury pain.

Methods
Twenty patients participated in two randomized, double-blinded, placebo-controlled, crossover experiments in which they, on four different days, received a 30-minute intravenous infusion of ketamine (0.24 mg/kg), lidocaine (5 mg/kg), or saline. Ongoing pain, pain evoked by brush and repetitive pinprick stimuli, and acetone was measured before, during, and after infusion.

Results
Ketamine significantly reduced ongoing pain and evoked pain to brush and pinprick, whereas lidocaine only reduced evoked pain to repetitive pinprick stimuli. In individual patients, there was no correlation between the pain-relieving effect of lidocaine and ketamine on ongoing or mechanically evoked pains.

Conclusions
N-methyl-D-aspartate receptor-linked systems and sodium channels are involved in generation and maintenance of pain in patients with peripheral nerve injury. It is likely that ongoing pain as well as mechanical hyperalgesia in individual patients is dependent on several separate molecular mechanisms.
Heart Rate Variability Predicts Severe Hypotension after Spinal Anesthesia
Authors: Hanss Robert , Bein Berthold , Weseloh Hendrik , Bauer Martin , Cavus Erol , Steinfath Markus , Scholz Jens , Tonner Peter H. 
Published: February 2006

Background
Hypotension due to vasodilatation after spinal anesthesia (SA) may be harmful. Heart rate variability, an indirect measure of autonomic control, may predict hypotension.

Methods
One hundred patients were studied. Retrospectively, heart rate variability was analyzed in 30 patients, classified depending on the lowest systolic blood pressure (SBP) after SA. Seventy patients were studied prospectively, assigned to one of two groups by their low to high frequency ratio (LF/HF) before SA. Sensitivity and specificity of LF/HF for prediction of decrease of SBP greater 20% of baseline were tested.

Results
Retrospective analysis showed differences of LF/HF depending on the degree of hypotension after SA. Prospective analysis demonstrated significant differences of SBP after SA depending on baseline LF/HF (mean +/- SD): low LF/HF (1.3 +/- 0.7) = > SBP: 91 +/- 8% of baseline versus high LF/HF (5.5 +/- 2.4) = > SBP: 66 +/- 10% of baseline (P < 0.05). Baseline LF/HF as well as high frequency and proportional decrease of SBP after SA correlated significantly, in contrast to baseline hemodynamic parameters heart rate and SBP. A receiver operator curve characteristic analysis showed a sensitivity and specificity of LF/HF > 2.5 of 85% to predict SBP decrease of greater than 20% of baseline after SA.

Conclusions
Heart rate variability analysis before SA may predict hypotension after SA with high sensitivity and specificity. LF/HF may be a tool to detect patients at high risk of hypotension due to SA. This indicates that the predictive value of LF/HF is superior to established predictors.
Basic concepts in plasma accelerators
Authors: Bingham Robert 
Published: February 2006

In this article, we present the underlying physics and the present status of high gradient and high-energy plasma accelerators. With the development of compact short pulse high-brightness lasers and electron and positron beams, new areas of studies for laser/particle beam–matter interactions is opening up. A number of methods are being pursued vigorously to achieve ultra-high-acceleration gradients. These include the plasma beat wave accelerator (PBWA) mechanism which uses conventional long pulse (∼100 ps) modest intensity lasers (
I
∼10
14
–10
16
W cm
−2
), the laser wakefield accelerator (LWFA) which uses the new breed of compact high-brightness lasers (<1 ps) and intensities >10
18
W cm
−2
, self-modulated laser wakefield accelerator (SMLWFA) concept which combines elements of stimulated Raman forward scattering (SRFS) and electron acceleration by nonlinear plasma waves excited by relativistic electron and positron bunches the plasma wakefield accelerator.

In the ultra-high intensity regime, laser/particle beam–plasma interactions are highly nonlinear and relativistic, leading to new phenomenon such as the plasma wakefield excitation for particle acceleration, relativistic self-focusing and guiding of laser beams, high-harmonic generation, acceleration of electrons, positrons, protons and photons. Fields greater than 1 GV cm
−1
have been generated with monoenergetic particle beams accelerated to about 100 MeV in millimetre distances recorded. Plasma wakefields driven by both electron and positron beams at the Stanford linear accelerator centre (SLAC) facility have accelerated the tail of the beams.
How much can treatment reduce national drug problems?
Authors: Reuter Peter , Pollack Harold 
Published: February 2006

ABSTRACTAims  Treatment of drug addiction has been the subject of substantial research and, in contrast to several other methods of reducing drug use, has been found to be both effective and cost‐effective. This review considers what is known about how much a nation can reduce its drug problems through treatment alone and what is known at the aggregate level about the effectiveness of prevention and enforcement.Methods  The literature on the effectiveness of treatment, prevention and enforcement are reviewed, and set in a policy analytical framework. Findings  Many studies have found treatment to have large effects on individuals’ consumption and harms. However, there is an absence of evidence that even relatively well‐funded treatment systems have much reduced the number of people in a nation who engage in problematic drug use. For prevention, the scientific literature shows useful and modest effects at the individual level but there is little support for substantial aggregate effects. For enforcement, research has failed almost uniformly to show that intensified policing or sanctions have reduced either drug prevalence or drug‐related harm. Nor—outside the UK—is there more than a modest effort to improve the evidence base for making decisions about the appropriate level of enforcement of drug prohibitions.Conclusions  Treatment can justify itself in terms of reductions in harms to individuals and communities. However, even treatment systems that offer generous access to good quality services will leave a nation with substantial drug problem. Finding effective complementary programs remains a major challenge.
What drug policies cost. Estimating drug policy expenditures in Sweden, 2002: work in progress
Authors: Ramstedt Mats 
Published: February 2006

ABSTRACTAim  To estimate drug policy expenditures in Sweden for 2002.Data and method  The various governmental agencies with drug policy responsibilities were identified and then requested to provide information on their actual spending on these activities. For most agencies additional information was obtained from special studies or expert opinion.Findings  Drug policy expenditures are not easily identified in Swedish official statistics. The results have a very wide range between 500 and 1400 million Euros during 2002, with 950 million Euros as a baseline estimate. Two items each account for almost 60% of the total—police (including customs and courts) and corrections—whereas treatment expenditures and income support represent about one‐fifth, respectively. Comparison with the most recent previous estimate (1991) shows a substantial higher level in 2002.Conclusions  The findings suggest that a great deal of money is invested in drug policy measures in Sweden today and that it has most probably increased since the early 1990s. This development probably reflects the increase in number of problematic drug users in Sweden as well as increasing attention paid to the drug problem, foremost in the criminal justice system. More work is needed in developing a drug budget that is more easily available and in producing more reliable estimates both across sectors and across time. The need to develop the conceptualization of drug policy measures is also discussed.
The three year course of alcohol use disorders in the general population: DSM‐IV, ICD‐10 and the Craving Withdrawal Model
Authors: De Bruijn Carla , Van Den Brink Wim , De Graaf Ron , Vollebergh Wilma A. M. 
Published: February 2006

ABSTRACTAims  To determine the course of alcohol use disorders (AUD) in a prospective general population study using three different classification systems: Diagnostic and Statistical Manual version IV (DSM‐IV), International Classification of Diseases version 10 (ICD‐10) and the craving withdrawal model (CWM). The latter is an alternative classification, which requires craving and withdrawal for alcohol dependence and raises the alcohol abuse threshold to two criteria.Design, setting and participants  Data were derived from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), a large (n = 7076) representative general population study with a baseline and 1‐ and 3‐year follow‐up assessments.Measurements  Diagnostic status according to DSM‐IV, ICD‐10 and CWM at baseline and at follow‐up was established using a structured interview (Composite International Diagnostic Interview: CIDI).Findings  DSM‐IV abuse, ICD‐10 harmful use and CWM abuse all showed a favourable course with remission rates of 81, 89 and 71%, respectively, at 1‐year follow‐up and 85, 92 and 79% at 3‐year follow‐up. Dependence according to DSM‐IV, ICD‐10 and CWM had a somewhat less favourable course, with remission rates (no dependence) of 67, 67 and 57% at 1‐year follow‐up and 74, 69 and 73% at 3‐year follow‐up, respectively. Subjects who were remitted at 1‐year follow‐up showed relapse‐rates of 0–14% for dependence and 4–12% for abuse at 3‐year follow‐up. Although CWM diagnoses tended towards greater diagnostic stability than DSM‐IV and ICD‐10, most differences were not significant.Conclusion  The conviction that addiction is a chronic relapsing disease may apply to treatment‐seeking alcoholics, but our data show a far more favourable course of alcohol use disorders in the general population.
An injection depot formulation of buprenorphine: extended biodelivery and effects
Authors: Sigmon Stacey C. , Moody David E. , Nuwayser Elie S. , Bigelow George E. 
Published: February 2006

ABSTRACTAim  Buprenorphine is an effective medication for treatment of opioid dependence. An injectable depot formulation of buprenorphine has been developed using biodegradable polymer microcapsule technology. This formulation may offer effective treatment of opioid dependence and enhance treatment delivery while minimizing risks of patient non‐adherence or illicit diversion of the medication. This report provides a characterization of the biodelivery of this injectable depot in humans and of the relationship of drug blood levels to pharmacodynamic indices. Method and participants  The data are from two studies in which 11 opioid‐dependent volunteers each received a single depot injection containing 58 mg of buprenorphine, and include previously unreported detailed plasma concentration data over a 6‐week time‐course following depot administration and examination of their relationship to pharmacodynamic indices.Findings  Mean plasma buprenorphine increased gradually following depot administration, peaked at 2–3 days with a mean concentration of 1.25 ng/ml and then decreased gradually, approaching undetectable levels (< 0.10 ng/mL) by 6 weeks. There was substantial between‐subject consistency in several aspects of buprenorphine biodelivery, including time to first detectable blood level (4 hours), peak blood level (2 days) and undetectable blood level (6–6.5 weeks). In contrast, there was marked between‐subject variability in the magnitude of peak buprenorphine concentrations, ranging from 0.17 to 3.47 ng/ml. Extent of opioid blockade was tested by weekly opioid challenges with 3 mg subcutaneous hydromorphone; subjective response and pupillary constriction were related inversely to both buprenorphine and norbuprenorphine plasma concentrations (r = 0.84–0.95).Conclusion  The data document that this depot formulation provides effective buprenorphine delivery for several weeks and that effects persist even at fairly low buprenorphine plasma concentrations. Suggestions are offered for further research needed to develop this formulation for clinical use as a detoxification and/or maintenance pharmacotherapy for opioid dependence.