bluuebunny/crossref_metadata_2025 huggingface dataset:
Parts of the Soul
Authors: Lorenz Hendrik
Published: September 2006

This chapter raises and explains two central questions about Plato’s theory of the tripartite soul. First, what is involved in Plato’s claim that the embodied human soul is a thing of parts? Secondly, does Plato have a reasonable basis for holding that the soul is composed of precisely three parts, reason, spirit, and appetite?
The Argument for Tripartition
Authors: Lorenz Hendrik
Published: September 2006

This chapter argues that Republic-style partition of the soul amounts to a position that can fairly be characterized in terms of two main claims. First, the proper subjects of desires and aversions are not whole souls, but in each case some part or other of the soul in question. Secondly, the parts of the soul that are the proper subjects of desires and aversions are unified in the strong sense that it is impossible for a given soul-part to desire something and at the same time to be averse to it.
Partition
Authors: Lorenz Hendrik
Published: September 2006

This chapter addresses the concern that for a Platonic soul to make sense, is not right to say that it has genuine parts. It also assesses the philosophical cost of soul-partition by considering its impact on the question of the soul’s immortality and by worrying, with Aristotle, about the soul’s unity.
Introduction
Authors: Lorenz Hendrik
Published: September 2006

In a much-discussed passage in Republic 10 (602c-603b), Plato appears to divide the rational soul-part into two distinct sub-parts. By considering the passage in its context, the chapter shows that appearance to be false. It closes by spelling out what can be learned about Plato’s psychological theory by reflecting on the passage, once it is properly interpreted.
Preliminaries
Authors: Lorenz Hendrik
Published: September 2006

In De Motu Animalium 8, Aristotle presents a picture of animal motivation in which a capacity he calls phantasia is given the role of ‘suitably preparing’ desire. The chapter offers some preliminary remarks on how Aristotle conceives of phantasia and its role in the production of animal movement.
The Workings of phantasia
Authors: Lorenz Hendrik
Published: September 2006

This chapter discusses Aristotle’s version of the association of ideas. It exposes a rich conception of sense, or the perceptual system, which can account not only for acts of sense-perception, but also for associating one thing with another, remembering things, and being reminded by something of something else. So conceived of, the perceptual system can also account for the occurrence of action-guiding representations that are indeterminately complex, and at the same time relevant and suitable to the perceiving subject’s current circumstances.
Phantasia and Practical Thought
Authors: Lorenz Hendrik
Published: September 2006

Given the richness of Aristotle’s conception of sense, the question arises of what he takes to be distinctive of the intellect and its functioning. The chapter therefore offers a detailed account of practical thought, as Aristotle conceives of it. For Aristotle, practical thought has a number of distinctive features that centre on the ability to apprehend ‘for the sake of’ relations, which include, but are not limited to, means-end relations. The chapter concludes that Aristotle has a well-grounded and defensible distinction between intellectual and non-intellectual cognition.
Reason and Non-rational Desire
Authors: Lorenz Hendrik
Published: September 2006

The chapter explores Aristotle’s moral psychology, arguing that it not only leaves room for, but in fact requires, a conception of non-rational or non-intellectual cognition along the lines set out in Chapters 8-11. Even though it is part of Aristotle’s moral psychology that all of a human being’s cognitive and motivating conditions are rational in a way, this leaves intact a clear sense in which appetite and spirit are non-rational forms of motivation, and also a clear sense in which at least some of the cognition involved in such motivation is non-rational.
On Images
Authors: Kulvicki John V.
Published: September 2006

This book argues that what it is to be a picture does not fundamentally concern how such representations can be perceived, but how they relate to one another syntactically and semantically. This kind of approach, first championed by Nelson Goodman in his Languages of Art, has not found many supporters in part because of weaknesses with Goodman’s account. It is shown that a properly crafted structural account of pictures has many advantages over the perceptual accounts that dominate the literature on this topic. Part I (Chapters 1-5) presents the account and draws out some of its immediate consequences. In particular, it explains the close relationship between pictures, diagrams, graphs, and other kinds of non-linguistic representation. Also, it undermines the claim that pictures are essentially visual by showing how many kinds of non-visual representations, including audio recordings and tactile line drawings, are genuinely pictorial. Part II (Chapters 6-10) shows that the structural account of depiction can help to explain why pictures seem so perceptually special. Part III (Chapters 11-12) provides a new account of pictorial realism and shows how accounting for realism relates to an account of depiction in general.
Introduction: Alberti's Window, Leonardo's Mirror, and van Gogh's Room
Authors: Kulvicki John V.
Published: September 2006

This chapter reviews Nelson Goodman’s proposals concerning depiction, identifies problems with them, and suggests how they can be overcome without appealing to a perceptual account of pictorial representation. Goodman’s proposal is that all pictorial systems are relatively replete, syntactically dense, and semantically dense. This is problematic because repleteness is not as well-defined as it should be, and density requires that pictures be analog representations, while many seem to be digital. These conditions were never meant to be sufficient for a system to be pictorial, but the problem is that they seem to be unnecessary as well.
Mimesis
Authors: Kulvicki John V.
Published: September 2006

This chapter explores the range of pictorial representation. It considers many kinds of projective systems and shows how they all manage to satisfy the conditions set forth in Chapters 2 and 3 for being pictures. In addition, common systems of auditory representation turn out to be pictorial according to this view; this is surprising but not terribly counterintuitive. Tactile line drawings sometimes used by the blind also turn out to be pictorial on the account offered herein, and the discussion of bare-bones content suggests some new avenues of research on tactile pictures. The chapter closes by considering how well the structural account fares with respect to a list of explananda offered by Robert Hopkins as the gold standard for a theory of depiction.
Other Visibilia and Other Media
Authors: Kulvicki John V.
Published: September 2006

This chapter considers John Haugeland’s original proposal for how bare-bones content should figure in an account of depiction. It argues that his account fails and identifies where the account fails, transparency, and the other conditions set forth in Chapters 2 and 3 step in to fill the gaps and explain Haugeland’s mistakes. The upshot is that Haugeland introduced an important (and neglected) tool for understanding pictures, but he did not use it to its fullest potential.
Bare Bones Content
Authors: Kulvicki John V.
Published: September 2006

Dominic Lopes proposed that pictures differ from other kinds of representations in that only pictures explicitly non-commit to properties. That is to say, with pictures, the price of representing something — say someone standing in front of someone else — is not being able to represent other things, such as the features of things behind the person represented. It is argued that this is not essential or unique to depiction, even though it is common only in pictures. Moreover, explicit non-commitment is only a feature of pictures’ fleshed-out contents: it does not appear in their bare-bones contents.
Understanding Commitments
Authors: Kulvicki John V.
Published: September 2006

Chapters 6 and 7 describe the features of pictures’ bare-bones and fleshed-out contents, and raise important questions about how the two relate to one another. This chapter suggests that the relation between them is analogous to the relation that was supposed to exist between sense data and the objects we take ourselves to perceive. Sense data were a bad idea in the philosophy of perception, but they are a useful tool for understanding pictorial content.
Perceiving Pictures
Authors: Kulvicki John V.
Published: September 2006

This chapter shows that the account of picture perception and pictorial content sheds light on the debate between the two most popular theories of picture perception: the recognition theory due to Flint Schier and Dominic Lopes, and the experienced resemblance view due to Robert Hopkins. Though the present account sides with Lopes overall, Hopkins has captured something important about how we come to know pictures’ contents.
1 Deliberative democracy and legitimacy
Authors: Parkinson John
Published: September 2006

This chapter outlines the theory of deliberative democracy and deliberative institutions, highlighting the legitimacy problems — to do with the scale of the deliberations and the motivation to participate — as experienced by the organizers of a citizens’ jury in Leicester, England, in 2000. It explains the approach and methods, outlines the argument, and summarizes five cases of deliberation in the UK’s National Health Service.
5 Deliberation as drama: publicity and accountability
Authors: Parkinson John
Published: September 2006

This chapter discusses the second broad solution to the legitimacy problems: sharing arguments through the media. It sets out the structural features of the news media and shows how they filter out certain kinds of arguments and issues, using the example of a deliberative poll. It argues that successful argument sharing (or publicity) depends on the salience of the issue, but in such cases, small-scale deliberative processes can provide a useful focal point for coverage of all the arguments. ‘Manufacturing’ salience can lead to distortion of the issue and arguments.
6 Reason and Persuasion
Authors: Parkinson John
Published: September 2006

This chapter argues that the definition of rationality is a major source of disagreement over the legitimacy of decision making processes. It draws attention to battles over competing problem definitions and agendas as a means of controlling debate, and the failure of micro-deliberative processes to handle such battles. It identifies the rhetorical devices used by deliberators to persuade their external audiences, and the impact these have on the rationality of the process. It argues that the more decisive a process is, the more it will attract publicity and the more inclusive it will be, but also the greater the incentives are to act strategically.
National and global structural macroeconometric modelling
Authors: Garratt Anthony , Lee Kevin , Pesaran M. Hashem , Shin Yongcheol
Published: September 2006

This chapter describes a framework for macroeconometric modelling, which draws out the links with economic theory relating to the long run and with theory relating to the short run. It elaborates a modelling strategy that can be employed to accommodate directly the theory of the long run, and notes the ways in which short-run theory can also be accommodated in national and global models. Recent literature on modelling short-run dynamics is reviewed, highlighting the difficulties in obtaining consensus on appropriate short-run restrictions and commenting on the approaches taken in the literature in examining policy shocks in general, and monetary policy in particular.
An economic theory of the short run
Authors: Garratt Anthony , Lee Kevin , Pesaran M. Hashem , Shin Yongcheol
Published: September 2006

This chapter explores a set of identifying restrictions on the short-run dynamics that might be used to supplement the long-run restrictions if the model is to be used to investigate the effect of economically-meaningful shocks. Particular attention is paid to modelling monetary policy decisions, inflation targeting, the derivation of a base rate reaction function, and the identification of monetary policy shocks.
The UK macroeconomy
Authors: Garratt Anthony , Lee Kevin , Pesaran M. Hashem , Shin Yongcheol
Published: September 2006

This chapter introduces the part of the book concerned with the practicalities involved in constructing a model of the UK economy. It describes the time series of the UK’s key macroeconomic variables over the last 30 to 40 years to provide an overview and commentary on the UK’s recent macroeconomic experiences.
Probability event forecasting with the UK model
Authors: Garratt Anthony , Lee Kevin , Pesaran M. Hashem , Shin Yongcheol
Published: September 2006

This chapter is concerned with forecasting and prediction based on the UK model. It elaborates on the notion of probability forecasting, which provides a useful means of conveying the uncertainties surrounding forecasts obtained from the model. It illustrates the usefulness of probability forecasts with reference to the Bank of England’s inflation targets and the UK’s growth prospects.
Political Economy and Natural Resource Use
Authors: Ramón López , Toman Michael A.
Published: September 2006

This chapter examines evidence on the four ways in which a nation’s political system and its natural resource use are linked. First, when property rights to resources are weak, competition to acquire resources can be wasteful and characterized by rent-seeking and violent conflict. Weak ownership claims are most likely in countries where the rule of law is not well-established. Second, when a country’s political system is unstable or non-representative, the individual’s claim to a resource stock’s future return can be rendered insecure, reducing the payoff to natural resource conservation. Third, when a country’s natural resources are capable of generating significant rents but institutions of democratic governance and the rule of law are not well-established, corruption by government officials responsible for resource management can encourage rent-seeking, dissipating the benefits those resources would otherwise confer. Fourth, the mix of private vs. public good outputs produced by a nation’s natural resources (e.g., forests) can be affected by its political system. When a country’s government does not represent the interests of the entire population, the use of resource stocks to provide public good amenities, as opposed to salable products, may be under-emphasized.
Trade and the Environment in Developing Economies
Authors: Ramón López , Toman Michael A.
Published: September 2006

This chapter studies the relationship between international trade, capital mobility, and environmental quality in developing countries. Although the ‘pollution haven hypothesis’ has dominated much of the discussion of the composition effects of trade between rich and poor countries, this paper argues that it is not supported by empirical evidence. Regardless of environmental policy, trade liberalization may still shift the development path towards environmentally-intensive activity in countries with a comparative advantage in this area. This paper also considers the fundamental differences between environmental problems associated industrial pollution emissions, and those that affect stocks of natural capital, such as fisheries and forests. In addition, it examines the effects of linkage between trade policies and environmental concerns in developing countries. Section 1 discusses the role of the environmental policy process and institutions, and how they interact with the trade regime. Section 2 reviews the empirical evidence on the effects of environmental policy on trade patterns, and the evidence on the effect of trade on environmental quality. Section 3 considers policy issues.
Environmental Policy Instruments and Institutions in Developing Countries
Authors: Ramón López , Toman Michael A.
Published: September 2006

The failure of public good provision in developing countries implies that many environmental and natural resource allocation problems that have been solved in developed countries, such as water pollution from sewage and indoor air pollution from cooking fires, continue to loom large. Decentralization and transparency in decision making, due process, and stakeholder participation in reform are needed to address these shortfalls. Because of poverty, efficiency is crucial to minimize overall costs. This, together with the wide dispersion in the distribution of pollution between polluters, speaks in favor of the use of flexible instruments such as information and market based mechanisms. At the same time, risk aversion, poverty, and unequal distribution imply that considerable attention must be paid to the distribution of costs and to a participatory approach in policy design.
Energy, Equity, and Economic Development
Authors: Ramón López , Toman Michael A.
Published: September 2006

There exists the misconception that the percentage of energy used by households declines with development. However, the reverse is true: the use of modern energy by households increases both absolutely and as a percentage of energy use with development. As a result, there are several reasons to focus on energy, namely, that the increased provision of energy services has a demonstrated high marginal value in the context of broader economic growth; that energy services remain physically scarce and costly in many parts of the developing world; that production and provision of energy services give rise to thorny issues of economic sector regulation; and that there are important and challenging energy-environment links throughout the chain of production and consumption. This chapter considers the first three of these four aspects of energy and development, and concludes with a summary of lessons learned from previous energy-related development activities and implications for future activities in this area.
Water Quality Issues in Developing Countries
Authors: Ramón López , Toman Michael A.
Published: September 2006

Of all the environmental concerns that developing countries face, the lack of adequate and good quality water is probably the most serious. This chapter examines two issues arising from poor water quality: (i) the impact it has on households through their use of such water for drinking and other domestic purposes, and through the facilities they employ for the disposal of household waste; and (ii) the consequence of poor water quality in inland rivers and lakes on other water uses (recreation, abstraction for domestic use, etc.). The overall implication of the analysis is that water supply targets under the Millennium Development Goals need careful cost benefit appraisal before they are implemented. Such targets also need a careful analysis of financial sustainability and in this regard, affordability is a critical element. The same remarks apply to sanitation programs, but the cost and benefit comparison is less clearly in favor of the program as a whole.
Recurrent Hypoxemia in Children Is Associated with Increased Analgesic Sensitivity to Opiates
Authors: Brown Karen A. , Laferrière André , Lakheeram Indrani , Moss Immanuela Ravé
Published: September 2006

Background

Postsurgical administration of opiates in patients with obstructive sleep apnea (OSA) has recently been linked to an increased risk for respiratory complications. The authors have attributed this association to an effect of recurrent oxygen desaturation accompanying OSA on endogenous opioid mechanisms that, in turn, alter responsiveness to subsequent administration of exogenous opiates. In a retrospective study, the authors have shown that oxygen desaturation and young age in children with OSA are correlated with a reduced opiate requirement for postoperative analgesia.

Methods

The current study was designed to test that conclusion prospectively in 22 children with OSA scheduled to undergo adenotonsillectomy. The children were stratified to those having displayed < 85% or > or = 85% oxygen saturation nadir during sleep preoperatively. Using a blinded design, the children were given morphine postoperatively to achieve an identical behavioral pain score.

Results

As compared with children in the > or = 85% group, the < 85% oxygen saturation nadir group required one half the total analgesic morphine dose postoperatively, indicating heightened analgesic sensitivity to morphine after recurrent hypoxemia.

Conclusions

Previous recurrent hypoxemia in OSA is associated with increased analgesic sensitivity to subsequent morphine administration. Therefore, opiate dosing in children with OSA must take into account a history of recurrent hypoxemia.
Mechanical Ventilation with Lower Tidal Volumes and Positive End-expiratory Pressure Prevents Alveolar Coagulation in Patients without Lung Injury
Authors: Choi Goda , Wolthuis Esther K. , Bresser Paul , Levi Marcel , van der Poll Tom , Dzoljic Misa , Vroom Margreeth B. , Schultz Marcus J.
Published: September 2006

Background

Alveolar fibrin deposition is a hallmark of acute lung injury, resulting from activation of coagulation and inhibition of fibrinolysis. Previous studies have shown that mechanical ventilation with high tidal volumes may aggravate lung injury in patients with sepsis and acute lung injury. The authors sought to determine the effects of mechanical ventilation on the alveolar hemostatic balance in patients without preexistent lung injury.

Methods

Patients scheduled for an elective surgical procedure (lasting > or = 5 h) were randomly assigned to mechanical ventilation with either higher tidal volumes of 12 ml/kg ideal body weight and no positive end-expiratory pressure (PEEP) or lower tidal volumes of 6 ml/kg and 10 cm H2O PEEP. After induction of anesthesia and 5 h later bronchoalveolar lavage fluid and blood samples were obtained, and markers of coagulation and fibrinolysis were measured.

Results

In contrast to mechanical ventilation with lower tidal volumes and PEEP (n = 21), the use of higher tidal volumes without PEEP (n = 19) caused activation of bronchoalveolar coagulation, as reflected by a marked increase in thrombin-antithrombin complexes, soluble tissue factor, and factor VIIa after 5 h of mechanical ventilation. Mechanical ventilation with higher tidal volumes without PEEP caused an increase in soluble thrombomodulin in lavage fluids and lower levels of bronchoalveolar activated protein C in comparison with lower tidal volumes and PEEP. Bronchoalveolar fibrinolytic activity did not change by either ventilation strategy.

Conclusions

Mechanical ventilation with higher tidal volumes and no PEEP promotes procoagulant changes, which are largely prevented by the use of lower tidal volumes and PEEP.
Short-term Cardiorespiratory Effects of Proportional Assist and Pressure-support Ventilation in Patients with Acute Lung Injury/Acute Respiratory Distress Syndrome
Authors: Kondili Eumorfia , Xirouchaki Nectaria , Vaporidi Katerina , Klimathianaki Maria , Georgopoulos Dimitris
Published: September 2006

Background

Recent data indicate that assisted modes of mechanical ventilation improve pulmonary gas exchange in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Proportional assist ventilation (PAV) is a new mode of support that amplifies the ventilatory output of the patient effort and improves patient-ventilator synchrony. It is not known whether this mode may be used in patients with ALI/ARDS. The aim of this study was to compare the effects of PAV and pressure-support ventilation on breathing pattern, hemodynamics, and gas exchange in a homogenous group of patients with ALI/ARDS due to sepsis.

Methods

Twelve mechanically ventilated patients with ALI/ARDS (mean ratio of partial pressure of arterial oxygen to fractional concentration of oxygen 190 +/- 49 mmHg) were prospectively studied. Patients received pressure-support ventilation and PAV in random order for 30 min while maintaining mean airway pressure constant. With both modes, the level of applied positive end-expiratory pressure (7.1 +/- 2.1 cm H2O) was kept unchanged throughout. At the end of each study period, cardiorespiratory data were obtained, and dead space to tidal volume ratio was measured.

Results

With both modes, none of the patients exhibited clinical signs of distress. With PAV, breathing frequency and cardiac index were slightly but significantly higher than the corresponding values with pressure-support ventilation (24.5 +/- 6.9 vs. 21.4 +/- 6.9 breaths/min and 4.4 +/- 1.6 vs. 4.1 +/- 1.3 l . min . m, respectively). None of the other parameters differ significantly between modes.

Conclusions

In patients with ALI/ARDS due to sepsis, PAV and pressure-support ventilation both have clinically comparable short-term effects on gas exchange and hemodynamics.
Desflurane-induced Preconditioning against Myocardial Infarction Is Mediated by Nitric Oxide
Authors: Smul Thorsten M. , Lange Markus , Redel Andreas , Burkhard Natalie , Roewer Norbert , Kehl Franz
Published: September 2006

Background

Volatile anesthetics induce myocardial preconditioning through a signal transduction pathway that is remarkably similar to that observed during ischemic preconditioning. Nitric oxide-dependent signaling plays an important role in anesthetic and ischemic preconditioning. Therefore, the authors tested the hypothesis that desflurane-induced preconditioning is mediated by nitric oxide.

Methods

Barbiturate-anesthetized rabbits were instrumented for measurement of hemodynamics. All rabbits were subjected to 30-min coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size was assessed with triphenyltetrazolium chloride staining. Myocardial nitric oxide synthase activity was assessed with a [H]L-arginine-conversion assay. Rabbits were randomized to five separate experimental groups. They received 0.0 or 1.0 minimum alveolar concentration desflurane for 30 min, which was discontinued 30 min before ischemia in the absence or presence of the nitric oxide synthase inhibitor N-nitro-L-arginine (L-NA). L-NA was given either 20 min before or 10 min after desflurane administration, respectively. Data are mean +/- SEM.

Results

Infarct size was 56 +/- 8% in control experiments. Desflurane significantly (P < 0.05) reduced infarct size to 35 +/- 4%. Preconditioning by desflurane was totally blocked by administration of L-NA either during or after desflurane inhalation (58 +/- 4 and 59 +/- 9%, respectively). L-NA alone had no effect on infarct size (56 +/- 7%). Nitric oxide synthase activity was significantly (P < 0.05) increased by desflurane.

Conclusion

The results demonstrate that desflurane-induced preconditioning markedly reduced myocardial infarct size. This beneficial effect was blocked by the nitric oxide synthase inhibitor L-NA either during or after desflurane-administration. These data suggest that early desflurane-induced preconditioning is mediated by nitric oxide.
New Insights into the Mechanism of Methoxyflurane Nephrotoxicity and Implications for Anesthetic Development (Part 1)
Authors: Kharasch Evan D. , Schroeder Jesara L. , Liggitt H Denny , Park Sang B. , Whittington Dale , Sheffels Pamela
Published: September 2006

Background

Methoxyflurane nephrotoxicity results from biotransformation; inorganic fluoride is a toxic metabolite. Concern exists about potential renal toxicity from volatile anesthetic defluorination, but many anesthetics increase fluoride concentrations without consequence. Methoxyflurane is metabolized by both dechlorination to methoxydifluoroacetic acid (MDFA, which may degrade to fluoride) and O-demethylation to fluoride and dichloroacetatic acid. The metabolic pathway responsible for methoxyflurane nephrotoxicity has not, however, been identified, which was the aim of this investigation.

Methods

Experiments evaluated methoxyflurane metabolite formation and effects of enzyme induction or inhibition on methoxyflurane metabolism and toxicity. Rats pretreated with phenobarbital, barium sulfate, or nothing were anesthetized with methoxyflurane, and renal function and urine methoxyflurane metabolite excretion were assessed. Phenobarbital effects on MDFA metabolism and toxicity in vivo were also assessed. Metabolism of methoxyflurane and MDFA in microsomes from livers of pretreated rats was determined in vitro.

Results

Phenobarbital pretreatment increased methoxyflurane nephrotoxicity in vivo (increased diuresis and blood urea nitrogen and decreased urine osmolality) and induced in vitro hepatic microsomal methoxyflurane metabolism to inorganic fluoride (2-fold), dichloroacetatic acid (1.5-fold), and MDFA (5-fold). In contrast, phenobarbital had no influence on MDFA renal effects in vivo or MDFA metabolism in vitro or in vivo. MDFA was neither metabolized to fluoride nor nephrotoxic. Barium sulfate diminished methoxyflurane metabolism and nephrotoxicity in vivo.

Conclusions

Fluoride from methoxyflurane anesthesia derives from O-demethylation. Phenobarbital increases in methoxyflurane toxicity do not seem attributable to methoxyflurane dechlorination, MDFA toxicity, or MDFA metabolism to another toxic metabolite, suggesting that nephrotoxicity is attributable to methoxyflurane O-demethylation. Fluoride, one of many metabolites from O-demethylation, may be toxic and/or reflect formation of a different toxic metabolite. These results may have implications for interpreting anesthetic defluorination, volatile anesthetic use, and methods to evaluate anesthetic toxicity.
New Insights into the Mechanism of Methoxyflurane Nephrotoxicity and Implications for Anesthetic Development (Part 2)
Authors: Kharasch Evan D. , Schroeder Jesara L. , Liggitt H Denny , Ensign Dustin , Whittington Dale
Published: September 2006

Background

Methoxyflurane nephrotoxicity results from its metabolism, which occurs by both dechlorination (to methoxydifluoroacetic acid [MDFA]) and O-demethylation (to fluoride and dichloroacetic acid [DCAA]). Inorganic fluoride can be toxic, but it remains unknown why other anesthetics, commensurately increasing systemic fluoride concentrations, are not toxic. Fluoride is one of many methoxyflurane metabolites and may itself cause toxicity and/or reflect formation of other toxic metabolite(s). This investigation evaluated the disposition and renal effects of known methoxyflurane metabolites.

Methods

Rats were given by intraperitoneal injection the methoxyflurane metabolites MDFA, DCAA, or sodium fluoride (0.22, 0.45, 0.9, or 1.8 mmol/kg followed by 0.11, 0.22, 0.45, or 0.9 mmol/kg on the next 3 days) at doses relevant to metabolite exposure after methoxyflurane anesthesia, or DCAA and fluoride in combination. Renal histology and function (blood urea nitrogen, urine volume, urine osmolality) and metabolite excretion in urine were assessed.

Results

Methoxyflurane metabolite excretion in urine after injection approximated that after methoxyflurane anesthesia, confirming the appropriateness of metabolite doses. Neither MDFA nor DCAA alone had any effects on renal function parameters or necrosis. Fluoride at low doses (0.22, then 0.11 mmol/kg) decreased osmolality, whereas higher doses (0.45, then 0.22 mmol/kg) also caused diuresis but not significant necrosis. Fluoride and DCAA together caused significantly greater tubular cell necrosis than fluoride alone.

Conclusions

Methoxyflurane nephrotoxicity seems to result from O-demethylation, which forms both fluoride and DCAA. Because their co-formation is unique to methoxyflurane compared with other volatile anesthetics and they are more toxic than fluoride alone, this suggests a new hypothesis of methoxyflurane nephrotoxicity. This may explain why increased fluoride formation from methoxyflurane, but not other anesthetics, is associated with toxicity. These results may have implications for the interpretation of clinical anesthetic defluorination, use of volatile anesthetics, and the laboratory methods used to evaluate potential anesthetic toxicity.
Adding Bupivacaine to High-potassium Cardioplegia Improves Function and Reduces Cellular Damage of Rat Isolated Hearts after Prolonged, Cold Storage
Authors: Ross James D. , Ripper Richard , Law William R. , Massad Malek , Murphy Patricia , Edelman Lucas , Conlon Beth , Feinstein Douglas L. , Palmer June W. , DiGregorio Guido , Weinberg Guy L.
Published: September 2006

Background

Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone.

Methods

After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 microm bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4 degrees C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured.

Results

All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline.

Conclusions

Adding bupivacaine to a depolarizing cardioplegia solution reduces cell damage and improves cardiac function after prolonged storage. Metabolic inhibition may contribute to this phenomenon, which is not entirely explained by sodium channel blockade.
Supraspinal Anesthesia
Authors: Jugovac Izabela , Imas Olga , Hudetz Anthony G.
Published: September 2006

Background

Anesthetic endpoints of unconsciousness and immobility result from agent effects on both brain and spinal cord that are difficult to separate during systemic administration. To investigate cerebral mechanism of anesthetic-induced unconsciousness, the authors studied behavioral and electrophysiologic effects of four anesthetics infused intracerebroventricularly to conscious rats. The authors aimed to produce progressively increasing anesthetic depths, indicated by electro-encephalographic synchronization and behavioral change.

Methods

During anesthesia, rats were equipped with intracerebroventricular infusion catheters, hind-paw stimulation, and epidural electrodes to record the electroencephalogram from the somatosensory cortex. Silicone bolus was injected into the fourth ventricle to minimize drug distribution to the spinal cord. 60 min later, 50-min infusion of pentobarbital (6.0 mg/h), fentanyl (0.75 microg/h), propofol (3.0 mg/h), or midazolam (0.24 mg/h) was initiated. Vibrissal, olfactory, corneal, and tail-pinch responses were tested every 10 min.

Results

All agents depressed vibrissal, olfactory, and corneal responses; propofol and pentobarbital produced the strongest effect. All agents except propofol depressed tail-pinch response; fentanyl and pentobarbital produced the strongest effect. All agents except midazolam increased delta power. Pentobarbital enhanced theta power. All agents except fentanyl enhanced alpha and beta power. Pentobarbital and midazolam slightly increased, whereas fentanyl decreased, gamma power. Pentobarbital increased and midazolam decreased somatosensory evoked potential; these changes were small and apparently unrelated to behavior.

Conclusions

Alpha and beta power increase may reflect sedative component of anesthesia. Simultaneous delta, alpha, and beta power increase may correlate with loss of consciousness. Theta and delta power increase may reflect surgical anesthesia. Opioid-induced gamma power decrease may reflect suppression of pain perception. Pentobarbital-, fentanyl-, and midazolam-induced immobility to noxious stimulation may be mediated supraspinally.
Pain after Cardiac Surgery
Authors: Lahtinen Pasi , Kokki Hannu , Hynynen Markku
Published: September 2006

Background

Persistent chest pain may originate from cardiac surgery. Conflicting results have been reported on the incidence of persistent poststernotomy pain with considerable discrepancies between the retrospective reports and the one prospective study conducted to assess this pain. Therefore, the authors conducted a follow-up survey for the first 12 months after cardiac surgery in 213 patients who had a sternotomy.

Methods

The authors performed a prospective inquiry of acute and chronic poststernotomy pain both before and after cardiac surgery. Two hundred thirteen coronary artery bypass patients received a questionnaire preoperatively, 4 days postoperatively, and 1, 3, 6, and 12 months postoperatively. All patients were asked about their expectations, their preferences, and the location and intensity of postoperative pain.

Results

The return rates for the postal questionnaires were 203 (95%) and 186 (87%) after 1 and 12 months, respectively. Patients experienced more pain postoperatively at rest than they had expected to preoperatively. At rest, the worst actual postoperative pain was 6 (0-10), and the worst expected pain as assessed preoperatively was 5 (0-10) (P = 0.013). The worst reported postoperative pain was severe (numeric rating scale score 7-10) in 49% at rest, in 78% during coughing, and in 62% of patients on movement. One year after the operation, 26 patients (14%) reported mild chronic poststernotomy pain at rest, 1 patient (1%) had moderate pain, and 3 patients (2%) had severe pain. Upon movement, persistent pain was even more common: 45 patients (24%) had mild, 5 patients (3%) had moderate, and 7 patients (4%) had severe pain. Patients who experienced moderate to severe acute postoperative pain also reported any chronic poststernotomy pain (numeric rating scale score 1-10) more frequently.

Conclusions

Although common, the incidence of persistent pain after sternotomy was lower than previously reported. Also, reassuringly, 1 year after surgery this pain was mostly mild in nature both at rest and on movement.
Antinociception by Spinal and Systemic Oxycodone: Why Does the Route Make a Difference?
Authors: Lemberg Kim K. , Kontinen Vesa K. , Siiskonen Antti O. , Viljakka Kaarin M. , Yli-Kauhaluoma Jari T. , Korpi Esa R. , Kalso Eija A.
Published: September 2006

Background

The pharmacology of oxycodone is poorly understood despite its growing clinical use. The discrepancy between its good clinical effectiveness after systemic administration and the loss of potency after spinal administration led the authors to study the pharmacodynamic effects of oxycodone and its metabolites using in vivo and in vitro models in rats.

Methods

Male Sprague-Dawley rats were used in hot-plate, tail-flick, and paw-pressure tests to study the antinociceptive properties of morphine, oxycodone, and its metabolites oxymorphone and noroxycodone. Mu-opioid receptor agonist-stimulated GTPgamma[S] autoradiography was used to study G-protein activation induced by morphine, oxycodone, and oxymorphone in the rat brain and spinal cord. Spontaneous locomotor activity was measured to assess possible sedation or motor dysfunction. Naloxone and the selective kappa-opioid receptor antagonist nor-binaltorphimine were used to study the opioid receptor selectivity of the drugs.

Results

Oxycodone showed lower efficacy and potency to stimulate GTPgamma[S] binding in the spinal cord and periaqueductal gray compared with morphine and oxymorphone. This could relate to the fact that oxycodone produced only weak naloxone-reversible antinociception after intrathecal administration. It also suggests that the metabolites may have a role in oxycodone-induced analgesia in rats. Intrathecal oxymorphone produced strong long-lasting antinociception, whereas noroxycodone produced antinociception with very high doses only. Subcutaneous administration of oxycodone and oxymorphone produced thermal and mechanical antinociception that was reversed by naloxone but not by nor-binaltorphimine. Oxymorphone was more potent than oxycodone, particularly in the hot-plate and paw-pressure tests.

Conclusions

The low intrathecal potency of oxycodone in rats seems be related to its low efficacy and potency to stimulate mu-opioid receptor activation in the spinal cord.
Severe Toxic Damage to the Rabbit Spinal Cord after Intrathecal Administration of Preservative-free S (+)-Ketamine
Authors: Vranken Jan H. , Troost Dirk , de Haan Peter , Pennings Fritz A. , van der Vegt Marinus H. , Dijkgraaf Marcel G. W. , Hollmann Markus W.
Published: September 2006

Background

Ketamine and S(+)-ketamine have been advocated for neuraxial use in the management of postoperative pain and severe intractable pain syndromes unresponsive to opioid escalation. Although clinical experience has accumulated with S(+)-ketamine, safety data on toxicity in the central nervous system after neuraxial administration of S(+)-ketamine are conflicting. In this study, neurologic and toxicologic effects on the spinal cord from repeated daily intrathecal administration of commercially available, preservative-free S(+)-ketamine were evaluated against placebo in a randomized, blinded design.

Methods

Eighteen white New Zealand rabbits were assigned to two groups receiving either 0.5 ml intrathecal S(+)-ketamine, 0.5% solution (12 rabbits), or 0.5 ml saline (6 rabbits) once a day for 7 consecutive days. During general anesthesia, an intrathecal catheter was placed between the fifth and sixth spinous processes (lumbar). Neurologic (according to Tarlov criteria) and histopathologic assessments were performed after 7 days of treatment.

Results

Postmortem investigation of the spinal cord and nerve roots revealed histopathologic lesions suggestive of toxic damage in 11 rabbits, from the group of 12 animals receiving S(+)-ketamine. These results were significantly different compared with 5 control animals (no histologic changes observed). There was no significant difference in neurologic status between the two groups after 7 days of intrathecal treatment.

Conclusions

The authors conclude that repeated intrathecal administration of preservative-free S(+)-ketamine in a clinically relevant concentration and dosage has, considering the extent and severity of the lesions, a toxic effect on the central nervous system of rabbits.
Methoxyflurane Revisited
Authors: Mazze Richard I. , Raja Srinivasa N.
Published: September 2006

Methoxyflurane metabolism and renal dysfunction: clinical correlation in man. By Richard I. Mazze, James R. Trudell, and Michael J. Cousins. Anesthesiology 1971; 35:247-52. Reprinted with permission. Serum inorganic fluoride concentration and urinary inorganic fluoride excretion were found to be markedly elevated in ten patients previously shown to have methoxyflurane induced renal dysfunction. Five patients with clinically evident renal dysfunction had a mean peak serum inorganic fluoride level (190 +/- 21 microm) significantly higher (P < 0.02) than that of those with abnormalities in laboratory tests only (106 +/- 17 microm). Similarly, patients with clinically evident renal dysfunction had a mean peak oxalic acid excretion (286 +/- 39 mg/24 h) significantly greater (P < 0.05) than that of those with laboratory abnormalities only (130 +/- 51 mg/24 h). That patients anesthetized with halothane had insignificant changes in serum inorganic fluoride concentration and oxalic acid excretion indicates that these substances are products of methoxyflurane metabolism. A proposed metabolic pathway to support this hypothesis is presented, as well as evidence to suggest that inorganic fluoride is the substance responsible for methoxyflurane renal dysfunction.
Silent night: adaptive disappearance of a sexual signal in a parasitized population of field crickets
Authors: Zuk Marlene , Rotenberry John T , Tinghitella Robin M
Published: September 2006

Sexual signals are often critical for mate attraction and reproduction, although their conspicuousness exposes them to parasites and predators. We document the near-disappearance of song, the sexual signal of crickets, and its replacement with a novel silent morph, in a population subject to strong natural selection by a deadly acoustically orienting parasitoid fly. On the Hawaiian Island of Kauai, more than 90% of male field crickets (
Teleogryllus oceanicus
) shifted in less than 20 generations from a normal-wing morphology to a mutated wing that renders males unable to call (flatwing). Flatwing morphology protects male crickets from the parasitoid, which uses song to find hosts, but poses obstacles for mate attraction, since females also use the males' song to locate mates. Field experiments support the hypothesis that flatwings overcome the difficulty of attracting females without song by acting as ‘satellites’ to the few remaining callers, showing enhanced phonotaxis to the calling song that increases female encounter rate. Thus, variation in behaviour facilitated establishment of an otherwise maladaptive morphological mutation.
Nonlinear mechanics of soft fibrous networks
Authors: Kabla A , Mahadevan L
Published: September 2006

Mechanical networks of fibres arise on a range of scales in nature and technology, from the cytoskeleton of a cell to blood clots, from textiles and felts to skin and collageneous tissues. Their collective response is dependent on the individual response of the constituent filaments as well as density, topology and order in the network. Here, we use the example of a low-density synthetic felt of athermal filaments to study the generic features of the mechanical response of such networks including strain stiffening and large effective Poisson ratios. A simple microscopic model allows us to explain these features of our observations, and provides us with a baseline framework to understand active biomechanical networks.
On the response of non-dissipative solids
Authors: Rajagopal K.R , Srinivasa A.R
Published: September 2006

In addition to being incapable of dissipation, in any process that it is subject to, there are other tacit requirements that a classical elastic body has to meet. The class of solids that are incapable of dissipation is far richer than the class of bodies that is usually understood as being elastic. We show that, unlike the case of a classical elastic body, the stress in non-dissipative bodies is not necessarily derivable from a stored energy that depends only on the deformation gradient.
Observations and models of deuterated in proto-planetary disks
Authors: Ceccarelli Cecilia , Dominik Carsten
Published: September 2006

Young, gas-rich proto-planetary disks orbiting around solar-type young stars represent a crucial phase in disk evolution and planetary formation. Of particular relevance is to observationally track the evolution of the gas, which governs the overall evolution of the disk and is eventually dispersed. However, the bulk of the mass resides in the plane, which is so cold and dense that virtually all heavy-element-bearing molecules freeze out onto the dust grains and disappear from the gas phase. In this paper, we show that the ground-state
ortho
-H
2
D
+
transition is the best, if not the only, tracer of the disk-plane gas. We report the theoretical models of the chemical structure of the plane of the disk, where the deuterated forms of

, including H
2
D
+
, play a major role. We also compare the theoretical predictions with the observations obtained towards the disk of the young star DM Tau and show that the ionization rate is probably enhanced there, perhaps owing to the penetration of X-rays from the central object through the disk plane. We conclude by remarking that the ground-state
ortho
-H
2
D
+
transition is such a powerful diagnostic that it may also reveal the matter in the dark halos of external galaxies, if it is hidden in cold, dense and small clouds, as several theories predict.