Intoxication with the organophosphorus compound paraoxon (POX), an inhibitor of serine hydrolases, is frequent. Although oximes are the only enzyme reactivators presently available, clinical experience with their use was rather disappointing. Recent work has shown that under certain conditions l-lactate is also able to reduce in vitro the POX inhibition of butyrylcholine- and acetylcholineesterase (BChE and AChE). To assess the practical relevance, if any, of these findings, the protective effects of pralidoxime (PRX) and those of lactate had to be compared in the same in vitro model. Effects of PRX on the inhibition of AChE by POX were assessed in vitro in plasma of 12 (six male and six female) healthy human volunteers. The determinations were repeated using different oxime and different POX concentrations. The AChE activity determinations were performed using the following sampler: sample BL-baseline (or untreated plasma); sample a-after addition of POX to plasma (pl + POX); sample b-after POX and plasma were incubated and then oxime was added (pl + POX/PRX); sample c-after addition of oxime to plasma (pl + PRX); sample d-after oxime and plasma were incubated and then POX was added (pl + PRX/POX); sample e-after oxime and POX were incubated and then added to plasma (PRX + POX/pl). Results were corrected for spurious enzyme 'pseudo-activity' due to interaction between PRX and substrate (acetylthiocholine) in the absence of enzyme. In the micro- and millimolar ranges, PRX is able to protect in vitro AChE from inhibition by POX when added to human plasma prior to POX or when incubated with POX prior to addition to plasma. Adding PRX to plasma after POX has no protective effect. The PRX results were compared statistically with historical lactate data (obtained under identical conditions) using the Wilcoxon matched pairs test, with significance assumed for p = 0.01. No difference between PRX and lactate's protective effect on the AChE inhibition by POX was found in the in vitro model used. We therefore conclude that in vivo testing of lactate as a POX protective agent is warranted.

Acetylcholinesterase↗

PubMedDate not supplied

Present as prologue? Psychiatry in the 1980s.

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Forecasting↗

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Mechanical circulatory assistance with the intraaortic balloon pump and other counterpulsation devices.

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Arrhythmias, Cardiac↗

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Precipitated cannabinoid withdrawal is reversed by Delta(9)-tetrahydrocannabinol or clonidine.

The availability of the cannabinoid antagonist, SR 141716A, to precipitate withdrawal following repeated cannabinoid administration provides a model to investigate the mechanisms underlying cannabinoid dependence as well as potential treatments to alleviate withdrawal symptoms. The goal of the present study was to determine whether SR 141716A-precipitated withdrawal symptoms in Delta(9)-tetrahydrocannabinol (Delta(9)-THC)-tolerant mice could be alleviated by either readministration of Delta(9)-THC or clonidine, an alpha(2)-receptor agonist. SR 141716A elicited paw tremors in Delta(9)-THC-tolerant mice, but produced a significant increase in head shakes independently of repeated Delta(9)-THC treatment. Readministration of Delta(9)-THC, following SR 141716A-precipitated withdrawal, reversed paw tremors (ED(50)=9.9 mg/kg), but failed to reduce head shaking behavior. Clonidine reversed SR 141716A-precipitated paw tremors (ED(50)=0.18 mg/kg) and blocked head shakes at all doses tested. The reversal effects did not appear to be the result of motor impairment because neither decreases in spontaneous locomotor activity nor motor incoordination, as assessed in the inverted screen test, could account for the effects. These findings suggest that SR 141716A precipitates paw tremors in mice by competing with Delta(9)-THC at the CB(1) receptor, though it also produced head shaking in nondependent animals. Finally, the observation that clonidine alleviated SR 141716A-precipitated paw tremors suggests its potential as a treatment for cannabinoid dependence.

Adrenergic alpha-Agonists↗

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Does crew resource management training work?

INTRODUCTION: Effective crew resource management (CRM) may play a major role in decreasing the number of accidents and increasing overall safety of air medical programs. The purpose of the study was to compare the responses of crew members, in a variety of situations, who received CRM training and those who did not. The numerical results of the responses were used to evaluate the effectiveness of CRM in increasing crew awareness and promoting team concepts. METHOD: During a 12-month period, crew members of randomly selected air medical programs (fixed- and rotor-wing) were surveyed by questionnaire. Participants were asked if they had received CRM, effective communication, and team-building training. The next 15 questions pertained to crew interaction/communication in everyday and emergent situations and were scored on a Likert scale (1 = strongly agree and 5 = strongly disagree). A lower total score indicated a greater understanding of team awareness and effective communication. RESULTS: The mean score of crew members who received the three identified areas of training (initial CRM, team-building, effective communications) (37.96, SD +/- 7.67) was found to be significantly lower than the mean score of those who had received none of the training (44.13, SD +/- 5.0) and P < .05. CONCLUSION: Based on the results, CRM training increases crew awareness and promotes team concepts in both everyday and emergent situations.

Air Ambulances↗

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Long-term wear of HIPed alumina on alumina bearings for THR under microseparation conditions.

The long term wear and wear debris generated in HIPed alumina on alumina bearings for hip prostheses with microseparation in vitro is compared to standard simulator conditions and ex vivo specimens. Microseparation studies were completed to five million cycles at two severity levels in attempts to rigorously evaluate the long-term tribological performance of the bearings. During the first million cycles (bedding-in) of the microseparation tests characteristic stripe wear was observed on all of the femoral heads with a matching area on the rim of the acetabular inserts. Under mild microseparation conditions an average wear rate of 0.55 mm3/million cycles was observed during the initial million cycles which reduced to a steady state level of 0.1 mm3/million cycles. Under more severe conditions an average wear rate of 4.0 mm3/million cycles was observed during bedding-in which reduced to a steady state level of 1.3 mm3/million cycles. These compare to a bedding-in wear rate of 0.11 mm3/million cycles and steady-state wear rate of 0.05 mm3/million cycles for the same material under normal simulation with no microseparation. Furthermore, under microseparation the wear mechanisms and wear debris were similar to those observed in previous alumina retrieval studies with debris ranging from 10 nm to 1 microm in size.

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Wear of fixed bearing and rotating platform mobile bearing knees subjected to high levels of internal and external tibial rotation.

In order to extend the lifetime of total knee replacements (TKR) in vivo, reduction of the volumetric wear rate of ultra high molecular weight polyethylene (UHMWPE) bearings remains an important goal. The volume of wear debris generated in fixed bearing total knee devices increases significantly when subjected to higher levels of internal-external rotation and anterior-posterior displacement. Six PFC Sigma fixed bearing TKR were compared with six LCS rotating platform mobile bearing knees using a physiological knee simulator with high rotation kinematic inputs. The rotating platform polyethylene inserts exhibited a mean wear rate which was one-third of that of the fixed bearing inserts despite having increased femoral contact areas and additional tibial wear surfaces. The rotating platform design decouples knee motions, by allowing unidirectional motion at the tray-insert articulation, which reduces rotation at the femoral-insert counterface. This translation of complex knee motions into more unidirectional motions results in molecular orientation of the UHMWPE and reduced volumetric wear.

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Comparison of wear in a total knee replacement under different kinematic conditions.

A six station ProSim (Manchester, UK) knee simulator was used to assess the wear of six PFC (DePuy) fixed bearing total knee replacements under two different kinematic conditions defined as low and high kinematic inputs. The high kinematics displacement and rotation inputs were based on the kinematics of the natural knee with ISO standards used for the axial load and flexion. Low kinematics were defined as approximately half the magnitude. The six specimens were run for three million cycles under low kinematics and three million cycles under high kinematics. The mean wear rate found during the low kinematics phase was 7.7 +/- 2 mm3 per million cycles. This then increased significantly to an average wear rate of 41 +/- 14 mm3 during the high kinematics input phase. The wear areas were characterized by a predominant damage mode of burnishing with some abrasive wear occurring during the high kinematics phase. This study supports the findings that introduction of cross-shearing of the polyethylene by introducing both rotational and anterior/posterior displacement increases the wear rate. This has implications for younger patients with higher levels of activity that need knee replacements.

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The effect of accelerated aging on the wear of UHMWPE.

Oxidative degradation of UHMWPE has been found to be a cause of elevated wear rate of the polymer in total joint replacement leading to failure of these devices. In order to evaluate long term stability of polymers, various accelerated aging methods have been developed. In this study, wear rates of shelf aged UHMWPE and "accelerated aged" UHMWPE were compared using a multi-directional pin-on-plate wear test machine in order to evaluate the effect of the accelerated aging on wear. Wear factors of the aged materials were found to depend on their density, which is a measure of oxidation level. Finally, accelerated aging was calibrated against shelf aging in terms of wear rate.

Journal Article↗