Anesthetic potencies of n-alkanols: results of additivity and solubility studies suggest a mechanism of action similar to that for conventional inhaled anesthetics

The mechanism by which n-alkanols produce anesthesia and the characteristics relevant to those mechanisms (e.g., lipid solubilities versus potencies) remain unknown. Accordingly, we determined potencies (minimum alveolar anesthetic concentration [MAC]) and solubilities of normal methanol, ethanol, butanol, hexanol, and octanol. We also determined the additivity of these alkanols with a conventional anesthetic (desflurane) and the additivity of methanol with butanol. Finally, we determined whether alkanol metabolism influences alkanol potencies. MAC for methanol, ethanol, butanol, hexanol, and octanol (0.00200, 0.000989, 0.000133, 0.0000214, and 0.00000117 atm, respectively) increased with an increasing solubility in olive oil (olive oil/gas partition coefficients 48.6, 108, 1,650, 11,600, and 93,500, respectively) and octanol (octanol/gas partition coefficients 163, 1,150, 22,900, 135,000, and 4,140,000) to give a product of MAC x solubility for olive oil approximately 10 times less (values of 0.10-0.25) than that expected from the Meyer-Overton hypothesis (compared with conventional inhaled anesthetics). There was less deviation for octanol, but the results were more variable. Inhibition of methanol and butanol metabolism by 4-methylpyrazole did not alter MAC. Methanol, ethanol, butanol, hexanol, and octanol had approximately additive anesthetic effects with desflurane, with some small but statistically significant deviations both above and below additivity. In the presence of 0.5 MAC of desflurane, we needed to add 0.4-0.6 MAC of each alkanol to inhibit the movement of 50% of the rats in response to noxious stimulation. Similarly, the effects of methanol and butanol were additive (with each other). The saline/gas partition coefficient for each alkanol was high (3700, 2650, 1400, 900, and 709 for methanol through octanol), which indicates high polarity. We conclude that the potent anesthetic effects of normal alkanols may result from an affinity to both polar and nonpolar phases. Our finding of additivity of alkanols with each other is consistent with a common mechanism of action. Similarly, the finding of additivity or slight deviations from additivity for alkanols with desflurane is consistent with mechanisms of action that have much in common.     

Meta-analysis of the sensitivity decrement in vigilance.

Observers' perceptual sensitivity to critical target events can deteriorate when they must remain alert for prolonged periods. The dominant characterization of this sensitivity decrement has been the R. Parasuraman and D. R. Davies (1977) taxonomy of vigilance, which attributes the decline in perceptual ability to the type of discrimination (successive-absolute vs simultaneous-comparative judgment) and the event rate (rate of stimulus presentation) required for task completion. According to the model, sensitivity decrements occur chiefly in tasks that couple successive discrimination with a high event rate. This meta-analysis of 42 vigilance studies attempted to refine the taxonomy by identifying other task characteristics related to the sensitivity decrement. The analysis confirmed that the magnitude of this sensitivity decrement is substantial and that it is a function of the type of discrimination and the event rate, but it also revealed that the current taxonomy should be revised to incorporate a new dimension: the sensory–cognitive distinction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Transient weakness and compound muscle action potential decrement in myotonia congenita

Twenty-five Turkish patients with recessive myotonia congenita (RMC), 16 of whom had genetic confirmation, were studied. Nineteen had transient weakness. In the upper extremities, onset age of transient weakness was usually in the early teens. All untreated RMC patients had a compound muscle action potential decrement of > or =25%, usually above 50%, with repetitive nerve stimulation at 10/s for 5 s. Patients with other nondystrophic diseases with myotonia, except 1 patient with dominant myotonia congenita, had no transient weakness and a CMAP decrement below 25%.     

Clinical comparison of isoflurance and halothane anesthetics

Isoflurane and halothane were compared in two similar groups of 100 patients each. Isoflurane compared favorably with halothane in producing adequate anesthesia in all our patients. Induction period was a little stormy when there was direct induction with isoflurane. Maintenance was excellent and recovery was good. Mean concentration necessary to induce anesthesia was 3.07% with isoflurane and 2.56% with halothane. Mean maintenance with isoflurane was 1.39%, compared to 1.40% with halothane. Less curare was required for relaxation when used with isoflurane than with halothane. This difference was not seen with pancuronium (Pavulon). Patient recovery was faster with isoflurane than with halothane. Incidence of delirium and shivering in the recovery period was similar for both agents. Incidence of nausea and vomiting was greater with isoflurane. Other clinical and biochemical postoperative comparisons did not show any significant differences between the two agents.     

The pharmacology of local anesthetics

As practitioners of dentistry we are truly fortunate to have these wonder agents which we tend to use like water everyday. It is estimated that over 11,000,000 cartridges of local anesthetics are administered every year in Ontario. The incredible safety record speaks for itself. However, we must caution ourselves that a local anesthetic is a drug and as such demands our ongoing skill, care and judgment for each individual case.     

Review of Other times, other realities: Toward a theory of psychoanalytic treatment.

Reviews the book, Other times, other realities: Toward a theory of psychoanalytic treatment by Arnold H. Modell (see record 1990-97902-000). This book is addressed to the psychoanalytically sophisticated reader. Its introduction and 10 chapters take the reader through a history of ideas that have been postulated to explain why psychoanalysis works. Interspersed are valuable comments by Modell that include his own original contributions to the discussion. Chapter 1 revolves around Freud and Nachtr?glichkeit. Chapter 2 illuminates the paradoxical relation between reality and illusions that is manifested in the analytic setting. The concept of reality and its various levels are examined in chapter 3. Chapter 4 discusses the neurobiological theories of Edelman, who postulates that memory is not isomorphic with past experience but a recategorization. Modell sees different levels of reality as corresponding to different forms of transference. He relabels transference neurosis as iconic/projective transference and the transference derived from the setting as dependent/containing transference. Chapter 5 amplifies his remarks on linear and cyclic time. Chapter 6 discusses interpretation and chapter 7 examines the concept of resistance. Other chapters deal with the patient's use of the therapist, with paradox and therapeutic dilemmas, and with various theories of psychoanalytic treatment. Modell tries to classify contemporary theories of psychoanalytic treatment but recognizes such attempts as little more than convenient fictions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of inhaled corticosteroids

OBJECTIVE: To review the comparative studies evaluating both efficacy and safety of inhaled corticosteroids in the management of asthma. Specifically, comparative clinical trials are evaluated that allow clinicians to determine relative potencies of the various inhaled corticosteroids. METHODS: A critical review was performed of the published clinical trials, either as articles or abstracts, comparing the clinical efficacy or systemic activity of inhaled corticosteroids. No a priori criteria were applied, as this was not a meta-analysis. FINDINGS: In vitro measures of antiinflammatory activity of corticosteroids consistently demonstrate potency differences among the various corticosteroids. Traditionally, these in vitro measures have been used to develop new corticosteroids with greater topical activity. While no accepted direct measure of antiasthmatic antiinflammatory activity exists, clinical trials using surrogate measures (e.g., forced expiratory volume in 1 second, peak expiratory flow, bronchial hyperresponsiveness, symptom control) indicate that in vitro measures provide a relatively accurate assessment of antiasthmatic potency. The relative antiinflammatory potency of the inhaled corticosteroids is in the following rank order. flunisolide = triamcinolone acetonide < beclomethasone dipropionate = budesonide < fluticasone. Studies of systemic activity appear to confirm this relative order of potency. Currently, no evidence exists for greater efficacy for any of the inhaled corticosteroids when administered in their relative equipotent dosages. The preponderance of current data suggests that when administered in equipotent antiinflammatory doses as a metered-dose inhaler plus spacer or as their respective dry-powder inhaler, the existing inhaled corticosteroids have similar risks of producing systemic effects. CONCLUSIONS: Delivery systems can significantly affect both topical and systemic activity of inhaled corticosteroids. More direct comparative studies between agents are required to firmly establish comparative topical to systemic activity ratios. The preponderance of evidence suggests that the agents are not equipotent on a microgram basis.     

Toxicity and complications of inhaled nitric oxide

The extent of toxicity and adverse effects resulting from inhaled NO is poorly understood. Presumably, toxicity is low and adverse effects are rare at the doses commonly used to treat acute respiratory failure. Much remains to be learned about this important topic, however.     

Interaction of alcohols and anesthetics with protein kinase Calpha

The key signal transduction enzyme protein kinase C (PKC) contains a hydrophobic binding site for alcohols and anesthetics (Slater, S. J., Cox, K. J. A., Lombardi, J. V., Ho, C., Kelly, M. B., Rubin, E., and Stubbs, C. D. (1993) Nature 364, 82-84). In this study, we show that interaction of n-alkanols and general anesthetics with PKCalpha results in dramatically different effects on membrane-associated compared with lipid-independent enzyme activity. Furthermore, the effects on membrane-associated PKCalpha differ markedly depending on whether activity is induced by diacylglycerol or phorbol ester and also on n-alkanol chain length. PKCalpha contains two distinct phorbol ester binding regions of low and high affinity for the activator, respectively (Slater, S. J., Ho, C., Kelly, M. B., Larkin, J. D., Taddeo, F. J., Yeager, M. D., and Stubbs, C. D. (1996) J. Biol. Chem. 271, 4627-4631). Short chain n-alkanols competed for low affinity phorbol ester binding to the enzyme, resulting in reduced enzyme activity, whereas high affinity phorbol ester binding was unaffected. Long chain n-alkanols not only competed for low affinity phorbol ester binding but also enhanced high affinity phorbol ester binding. Furthermore, long chain n-alkanols enhanced phorbol ester induced PKCalpha activity. This effect of long chain n-alkanols was similar to that of diacylglycerol, although the n-alkanols alone were weak activators of the enzyme. The cellular effects of n-alkanols and general anesthetics on PKC-mediated processes will therefore depend in a complex manner on the locality of the enzyme (e.g. cytoskeletal or membrane-associated) and activator type, apart from any isoform-specific differences. Furthermore, effects mediated by interaction with the region on the enzyme possessing low affinity for phorbol esters represent a novel mechanism for the regulation of PKC activity.     

"In situ" anesthetics and experimental cryotumorectomy

The results obtained by testing 3127 mink sera as well as the analysis of families completely confirmed that the Lpm allotype system of very high density proteins is under genetic control, as postulated earlier. The polymorphism of the first five allotypes is due to the genetic units Lpm1, Lpm4, Lpm1,2, Lpm3,4 and Lpm2,4,5, which behave as Mendelian alleles. The data obtained suggest the existence of an additional gene, LpmX, which, in the homozygous state, determines a very rare phenotype, negative for the first five markers.     

The second facet of forgetting: A review of warm-up decrement.

Interference theory, though generally accepted as an adequate explanation of forgetting, may not be sufficient to account for all the data. An alternative position hypothesizes that warm-up is a 2nd part of forgetting independent of direct interference with the goal responses. Experimental studies of this 2-factor view are not sufficiently strong to warrant acceptance or rejection at this time. (79 ref.) From Psyc Abstracts 36:01:3CL57A. (PsycINFO Database Record (c) 2010 APA, all rights reserved)