Search

Objectives: To determine whether administration of single dose prophylactic intravenous gentamicin prior to intravesical injection of botulinum toxin type A (BoNT-A) is associated with adverse extravesical neuromuscular effects in idiopathic overactive bladder syndrome. Patients and methods: A retrospective analysis of 220 consecutive idiopathic overactive bladder patients following sedation-free flexible cystoscopic injection of intravesical BoNT-A. All patients received a single dose of intravenous gentamicin (160 mg) followed by 100-200 IU of BoNT-A. They were followed up at intervals to determine whether they had experienced any adverse extravesical neuromuscular side effects. Results: None of our patients developed adverse extravesical neuromuscular side effects from intravesical botulinum injections with concomitant administration of intravenous gentamicin. Conclusion: Single dose intravenous gentamicin is safe to use as a prophylaxis for intravesical BoNT-A injections of 200 IU or below in idiopathic overactive bladder patients. Level of evidence: Not applicable.

Varespladib (LY315920) is a synthetic phospholipase A2 (PLA2) inhibitor that has been demonstrating antiophidic potential against snake venoms that present PLA2 neurotoxins. In this study, we evaluate the capacity of Varespladib to inhibit the neuromuscular effects of crotoxin (CTX), the main toxic component of Crotalus durissus terrificus snake venom, and its PLA2 subunit (CB). We performed a myographic study to compare the neuromuscular effects of CTX or CB and the mixture of these substances plus Varespladib in mice phrenic nerve-diaphragm muscle preparations. CTX (5 μg/mL), CB (20 μg/mL), or toxin-inhibitor mixtures pre-incubated with different concentration ratios of Varespladib (1:0.25; 1:0.5; 1:1; w/w) were added to the preparations and maintained throughout the experimentation period. Myotoxicity was assessed by light microscopic analysis of diaphragm muscle after myographic study. CTX and CB blocked the nerve-evoked twitches, and only CTX induced histological alterations in diaphragm muscle. Pre-incubation with Varespladib abolished the muscle-paralyzing activity of CTX and CB, and also the muscle-damaging activity of CTX. These findings emphasize the clinical potential of Varespladib in mitigating the toxic effects of C. d. terrificus snakebites and as a research tool to advance the knowledge of the mechanism of action of snake toxins.

Midfoot- (MFS) and forefoot-striking (FFS) runners usually switch to rearfoot-striking (RFS) during marathons. However, world-class runners might resist modifications during shorter races. The purpose of this study was to analyse footstrike patterns, ground contact times and running speeds in a World Championship men’s 10,000 m final. Footstrike patterns and contact times of the top 12 finishing men (24 ± 5 years) were recorded (150 Hz) during laps 1, 5, 11, 15, 20 and 25. Split times for each 100-m segment were obtained. No RFS patterns were observed; there was no difference between the number of FFS and MFS athletes at any distance (p ≥ 0.581) and no change in the proportions of FFS and MFS occurred (p = 0.383). No link between race performance and footstrike pattern appeared given the similar number who used FFS or MFS and their similar finishing times. Despite slower running speeds and longer contact times in the middle of the race (p ≤ 0.024), no effect on footstrike patterns occurred. The prevalence of anterior footstrike patterns in this world-class race reflects the capability of maintaining fast paces (>22 km/h). Changes in footstrike pattern might accompany the physiological and neuromuscular effects of fatigue over longer distances.

The 2015–2017 Zika Virus outbreak caused a high increase in patients with Guillain-Barré syndrome (GBS), a post infectious autoimmune disease of the peripheral nerves. The severity of GBS can range from mild impairment with fast recovery to complete paralysis including severe respiratory or autonomic failure. Recovery may take months and even years and may be incomplete despite disease modifying treatment with IVIG or plasma exchange. Therefore, optimal supportive care and effective rehabilitation remain crucial. Multidisciplinary rehabilitation is recommended but may be challenging in the acute phase because of limited patient participation due to profound muscle weakness and severe pain. Inactive denervated muscles will inevitably undergo rapid degeneration resulting in wasting, weakness, and contractures as major long-term complications in severely affected patients. In this chapter, the current evidence of rehabilitation on the short- and long-term motor function in GBS is reviewed, including newly obtained experiences with neuromuscular electrical stimulation (NMES). Rehabilitation remains an area lacking well designed and controlled clinical studies and thus a clear lack of evidence-based guidelines.

Background: It is generally believed that the anticholinesterase effect is induced by the organophosphate insecticide parathion only through its bioactive metabolite (i.e., paraoxon) that is created in the liver. Objectives: This study aimed to evaluate the intrinsic anticholinesterase effect of parathion, compared to its main metabolite. Methods: This study has been conducted to prepare the isolated chick biventer cervicis nerve-muscle using the twitch tension recording method. Results: According to the results, paraoxon (0.1 µM) induced a highly significant increase (more than 100%) in the twitch height, while higher concentrations (0.3 and 1 µM) induced partial or total contractures. Furthermore, parathion induced almost the same percentage of increase in the twitch height at 1 µM and partial or total contractures at 3 and 10 µM. It should be noted that pralidoxime (2-PAM), at 300 µM, reversed the effects of paraoxon and its parent (i.e., parathion). Conclusion: These results demonstrate that both parathion and its metabolite inhibit the acetylcholinesterase enzyme which can be reactivated by pralidoxime, whereas parathion is about 10 times less potent, compared to its metabolite. Therefore, the intrinsic toxic effects of parathion, regardless of its metabolite, should be considered in future studies.

The paper presents research on the electromagnetic hazards related to the flow of electric currents throughout the bodies of employees using portable radios. The values often exceed established limits, which may lead to potential dysfunctions of the body and affect the safety of performed professional duties. The measurements of the electric field (E-field) distribution of a typical commercial portable radio, the limb contact current calculations, and the computer simulations determining a specific absorption rate (SAR) were supplemented with pilot neurophysiological tests. The assessment indicated a large spatial variability of the E-field strength around the devices. The head of the operator and the hand holding the radio were often in the electromagnetic field (EMF), which exceeded the established limits. The calculated SAR values ranged within the permitted limits. The conducted neurophysiological tests showed no effects of EMF exposure in comparison to the control group. The assessment of exposure to the EMF using a portable radio is initially performed by analyzing external measures: both computer simulations and measurements of workers’ limb currents. The SAR values exclude thermal effects; however, they do not eliminate potential neuromuscular effects. More neurophysiological tests are needed to obtain a broader picture of possible health effects.

The aim of this study was to evaluate the effect of indirect vibratory stimulation on different magnitudes of displacement on acute and residual neuromuscular responses. Fifteen healthy volunteers were randomly submitted to 3 experimental sessions, with intervals of 5 to 7 days (5 maximal voluntary contractions - MVC, 12 s of duration each and 5 min of recovery) between sessions. To determine the residual responses, the volunteers performed a MVC before and after each treatment for 12 s, with a 5-minute recovery. The experimental sessions were composed of isometric actions without vibrations (CONTROL) and two sessions of isometric actions with the addition of vibrations at 20 Hz and 3 mm (Sinusoidal Vibration A) and 5 mm (Sinusoidal Vibration B). Before and after each of the experimental sessions, an isometric evaluation without vibrations was performed. For the acute effect, it was verified that the addition of vibrations induced a facilitatory effect on the explosive strength variables (p .05), independent of the type of studied displacement in relation to the control treatment. In short, it was verified that the addition of vibration induced an acute facilitating effect on the explosive strength. However, the induced effect was not persistent (residual effect) for the explosive strength.

Purpose: Rhinella schneideri is a toad found in many regions of the South America. The poison of the glands has cardiotoxic effect in animals and neuromuscular effects in mice and avian preparation. The purpose of this work was to identify the toxin responsible for the neuromuscular effect in avian and mice neuromuscular preparation. Methods: The methanolic extract from R. schneideri poison was fractioned by reversed phase HPLC. The purity and molecular mass were determined by LC/MS mass spectrometry. Chick biventer cervicis and mouse phrenic-nerve diaphragm were used as neuromuscular preparations to identify the toxin. Results: The purification resulted in 32 fractions, which 4 of them were active in neuromuscular preparation. The toxin of fraction 20 were chosen for better reproducibility of the whole extract activity and its molecular mass was 730.6 Da. The toxin produced facilitation of the muscle contraction followed by a complete neuromuscular blockade in chick biventer cervicis preparation in 90 min without interfering with the exogenous response to ACh and KCl. The quantal content was increased from 128 ± 13 (control) to 216 ± 44 (after 5 min and sustained until 60 min) in the presence of the toxin. Conclusion: In conclusion, our results demonstrated that the neuromuscular action of the poison of Rhinella schneideri is a multitoxin effect. More, the present work first isolated a 730.6 Da toxin that better represent the whole poison neuromuscular effect, to which is attributed a presynaptic action in avian and mouse neuromuscular preparation.

The time-course of the neuromuscular effects of vecuronium (n = 25) and atracurium (n = 25) has been compared at three different levels of maintenance dose in anaesthetized patients. Following intubation with vecuronium 0.1 mg kg-1 or atracurium 0.5 mg kg-1, surgical muscle relaxation was maintained by using increments of equipotent maintenance doses equivalent to 0.5, 1.0 and 1.5 x ED95 for each drug. Repeat doses were administered each time the twitch height, depressed by the previous dose, returned to 25% of its control value. The apparent increase in the duration of action, i.e. the difference between the duration of the last and the first maintenance dose, did not reach statistical significance and approximated 3 +/- 2, 6 +/- 4, 11 +/- 5 and 3 +/- 2, 8 +/- 13, 5 +/- 7 min following the low, medium and high maintenance doses of vecuronium and atracurium, respectively.

189 p. Objetivo El objetivo principal de este proyecto de tesis, es analizar las respuestas del sistema neuromuscular ante la aplicación de vibraciones efectuadas con diferentes modos y medios vibratorios. Metodología Se desarrollaron cinco fases experimentales de carácter agudo con sujetos sanos, analizando diferentes variables neuromusculares. En el primer estudio, los sujetos experimentaron tres condiciones diferentes de estímulo vibratorio en apoyo monopodal; tras las cuales, se analizó la potencia de prensa de pierna y la actividad eléctrica muscular de la pierna contralateral. En el segundo estudio, se comparó la fuerza máxima isométrica de presión manual con la actividad muscular durante tres condiciones distintas de estímulo vibratorio, cuerpo completo (WBV), vibración del brazo contralateral (AV), y combinación de las dos anteriores (WBV+AV). En el tercer estudio, se aplicaron diferentes estímulos vibratorios (50 Hz y 30 Hz) durante el ejercicio de battling rope simultáneo y alterno, y se estudiaron los efectos neuromusculares. En el cuarto estudio, se analizó la potencia y actividad muscular del press de banca declinado con tres diferentes porcentajes respecto a una repetición máxima (30%, 50% y 70% 1RM) durante la aplicación de WBV. Finalmente, en el quinto estudio, se comparó la movilidad dorsal de tobillo de ambas piernas tras la aplicación de un masaje con foam roller con y sin vibración. Resultados En el primer estudio, se observó un efecto condición x pierna x tiempo (p=0.001) para la potencia de prensa de pierna en la pierna no estimulada, sin encontrase cambios significativos en la actividad muscular. En el segundo estudio, se encontró una menor coactivación de los músculos extensores digitales en la condición WBV+AV, que en las demás condiciones (p

Accurate prediction of deformation and collapse of the upper airway during breathing is required for effective and personalised treatment of obstructive sleep apnoea (OSA). While numerical modelling techniques such as fluid-structure interaction (FSI) are promising, an outstanding challenge is to accurately predict the deformation of the airway during breathing and thus the occurrence of OSA. These difficulties arise because the effective stiffness of the soft tissue in the human upper airway varies due to neuromuscular effects on the stiffness of the underlying muscles. In addition, both the elasticity and anisotropy of the soft tissues along the upper airway are poorly characterised. Finally, gravitational effects on anatomic features are yet to be considered. In this study, a validated FSI technique is introduced that allows prediction of the extent and position of the major deformation in the upper airway. This technique is used to analyse the behaviour of the upper airway in the two most common sleeping positions and for a range of effective tissue stiffnesses. The results demonstrate that sleeping position, gravity and soft tissue stiffness (used here as a proxy for neuromuscular effects) are the main factors that affect upper airway collapse. Therefore, this study provides new insights into the mechanisms of OSA and a new methodology that significantly advances the patient-specific treatment of OSA.

Background: This study aimed to investigate the neuromuscular effects of 0.6 mg/kg rocuronium under desflurane anesthesia in patients with and without renal failure. Methods: The neuromuscular effects of rocuronium 0.6 mg/kg under desflurane anesthesia were investigated in 20 patients with renal failure undergoing renal transplantation surgery and in 20 patients with normal renal function. Neuromuscular transmission was monitored using acceleromyography with single stimuli at 0.1 Hz . The onset and 25%, 75%, and 95% twitch recovery times, the recovery of the train-of-four ratio to 70% (TOF70), and the recovery index (25−75%) were recorded. Results: Block onset was similar in the groups. The 25%, 75% and 95% twitch recovery times, the TOF70 time, and the recovery index were found to be prolonged in patients with renal failure compared to those with normal renal function (e.g. TOF70: 123.1 ± 49.1 vs. 68.7 ± 15.5 min) (P ＜ 0.001). A very strong association between the time to TOF70 and the diagnostic duration of renal failure was found (R 2 = 0.79, P ＜ 0.001). Conclusions: The duration of action of a bolus dose of 0.6 mg/kg rocuronium under desflurane anesthesia was increased significantly in patients with end-stage renal failure compared to that of healthy controls and was prolonged according to the duration of renal failure. (Korean J Anesthesiol 2009; 57: 566∼71)

This study investigated physiological, cognitive and neuromuscular performances in firefighters after a structural live-fire scenario. Changes in vital signs, environmental parameters and cognitive and neuromuscular performance were measured before and after a live-fire training session in a closed environment, in conditions similar to those one could encounter in a structural fire. Very high ambient temperature peaks were reached during the 30-min sessions. After the session, the forehead temperature was increased by 0.5 °C, mean water body loss was 639 ml and the mean heart rate increase was 7.5 bpm. Mental calculation speed did not vary significantly, however we observed a reduction in reaction time. These findings demonstrated that after 30 min of exposure, heat stress had little impact on firemen. Stress activation seems beneficial after firefighting operations. Normal vital parameters should allow re-engagement for a second firefighting task. This result must be compared with longer exposures.

Objective: To examine the biomechanical and neuromuscular effects of a longitudinal multi-muscle electrical stimulation (submaximal intensities) training of the lower limbs combined with/without activity-based stand training, on the recovery of stability and function for one individual with spinal cord injury (SCI). Design: Single-subject, longitudinal study. Setting: Neuroplasticity laboratory. Participant: A 34-year-old male, with sensory- and motor-complete SCI (C5/C6). Interventions: Two consecutive interventions: 61 hours of supine, lower-limb ES (ES-alone) and 51 hours of ES combined with stand training using an overhead body-weight support system (ST + ES). Outcome Measures: Clinical measures, trunk stability, and muscle activity were assessed and compared across time points. Trunk Stability Limit (TSL) determined improvements in trunk independence. Results: Functional clinical values increased after both interventions, with further increases post ST + ES. Post ES-alone, trunk stability was maintained at 81% body-weight (BW) loading before failure; post ST + ES, BW loading increased to 95%. TSL values decreased post ST + ES (TSL(A/P)=54.0 kg.cm, TSL(M/L)=14.5 kg.cm), compared to ES-alone (TSL(A/P)=8.5 kg.cm, TSL(M/L)=3.9 kg.cm). Trunk muscle activity decreased post ST + ES training, compared to ES-alone. Conclusion: Neuromuscular and postural trunk control dramatically improved following the multi-muscle ES of the lower limbs with stand training. Multi-muscle ES training paradigm of the lower limb, using traditional parameters, may contribute to the functional recovery of the trunk.

BACKGROUND Myopathies are generally considered to increase the risk for succinylcholine-induced hyperkalaemia and may affect the duration of action of neuromuscular blockers. Centronuclear (myotubular) myopathy (CNM) is congenital and produces various degrees of muscular weakness and associated complications such as respiratory failure. The effects of succinylcholine and the potentially lethal consequences of hyperkalaemia on patients with CNM are unknown due to its rarity. One source of information is the dog, as CNM occurs naturally in dogs. Because of its remarkable similarity with the disease in man, canine CNM can serve as a model to further our knowledge of the effects of succinylcholine. OBJECTIVES We examined the kalaemic and neuromuscular effects of succinylcholine in dogs with and without autosomal-recessive CNM. DESIGN A prospective, experimental study. SETTING Anaesthesiology laboratory, College of Veterinary Medicine, Cornell University, New York, USA. PATIENTS Six dogs with autosomal-recessive CNM and six control dogs. INTERVENTIONS Dogs received succinylcholine 0.3 mg kg during isoflurane anaesthesia. MAIN OUTCOME MEASURES Whole blood potassium concentration was measured 5 min before and after succinylcholine administration. Neuromuscular function was measured with acceleromyography and single twitch stimulation. RESULTS All dogs recovered uneventfully from anaesthesia. The increase in potassium concentration [mean (SD)] following succinylcholine was similar between groups: CNM 0.5 (0.4) mmol l and control 0.7 (0.4) mmol l (P = 0.47). Recovery of the single twitch to 25, 75 and 90% was longer in the CNM group (all P

This study compared the effects of a variable vs. a constant lower limb resistance training program on muscle strength, muscle activation, and ballistic muscle performance at different knee angles. Thirty-two females were randomized to a constant resistance training free-weight group (FWG) or a variable resistance training group using free weights in combination with elastic bands (EBG). Two variations of the squat exercise (back squat and split) were performed 2 days per week for 10 weeks. Knee extensor maximal voluntary isometric contraction (MVC) and countermovement jump were assessed at knee angles of 60, 90, and 120° before and after the intervention. During the MVCs, muscle activation of the superficial knee extensor muscles was measured using surface electromyography. The FWG increased their MVCs at 60 and 90° (24 and 15%, respectively), whereas the EBG only increased significantly at 60° (15%). The FWG increased their jump height significantly at all angles (12-16%), whereas the EBG only improved significantly at 60 and 90° (15 and 10%, respectively). Both groups improved their 6-repetition maximum free-weight squat performance (EBG: 25% and FWG: 23%). There were no significant changes in muscle activation. In conclusion, constant and variable resistance training provided similar increases in dynamic and isometric strength, and ballistic muscle performance, albeit most consistently for the group training only with free weights.

A myographic study was performed to compare the neuromuscular effects of venoms and crotoxin-like proteins from Crotalus durissus ruruima and Crotalus durissus cumanensis in mice phrenic-diaphragm preparation. It was concluded that both venoms present neurotoxic activity as a consequence of their crotoxin content. Furthermore, crotoxin from C.d. cumanensis is more potent than that from C.d. ruruima venom. At the concentration range in which both venoms express neurotoxic activity, only C.d. cumanensis venom also manifest a direct myotoxic effect that probably involves the synergic participation of other components than crotoxin.

A 47 year-old male presented with unilateral, non-painful, near-total, non-erythematous left eyelid swelling with anesthesia that developed overnight, approximately 24 hours after a wasp sting within the left eyebrow. The left eye itself remained unaffected. The acute findings completely resolved within four days of the event, mainly with supportive therapy. Hymenoptera venom can have marked neuromuscular effects on the superior eyelid, and clinicians are particularly alerted to the possibility of insect stings involving the supraorbital nerve within the differential diagnosis of non-painful, unilateral eyelid edema.

Zusammenfassung In dieser Studie wurde untersucht, ob durch die Anwendung von Sprunggelenkorthesen bei Sportlern in Risikosportarten in Spiel und Training neuromuskulare Effekte nachweisbar sind. In einer kontrollierten Langsschnittuntersuchung wurden 58 Sportler aus verschiedenen Mannschaften in eine Kontrollgruppe und eine Orthesengruppe aufgeteilt. Vor und nach einer halben Spielsaison wurde die Aktivierung der Sprunggelenkmuskulatur mit einem komplexen biomechanischen Untersuchungsverfahren in verschiedenen Messbedingungen getestet. Fur den Beobachtungszeitraum von ca. sechs Monaten konnten zwischen Eingangs- und Abschluss-Untersuchung keine signifikanten Unterschiede zwischen den Gruppen festgestellt werden. Hauptproblem der Untersuchung waren Probleme bei der Probandenakquise und die hohe Fluktuationsrate (ca. 50%) in beiden Gruppen.

Objective We aimed to investigate neurophysiological and clinical effects of common krait envenoming, including the time course and treatment response. Methodology Patients with definite common krait (Bungarus caeruleus) bites were recruited from a Sri Lankan hospital. All patients had serial neurological examinations and stimulated concentric needle single-fibre electromyography (sfEMG) of orbicularis oculi in hospital at 6wk and 6–9mth post-bite. Principal Findings There were 33 patients enrolled (median age 35y; 24 males). Eight did not develop neurotoxicity and had normal sfEMG. Eight had mild neurotoxicity with ptosis, normal sfEMG; six received antivenom and all recovered within 20–32h. Seventeen patients developed severe neurotoxicity with rapidly descending paralysis, from ptosis to complete ophthalmoplegia, facial, bulbar and neck weakness. All 17 received Indian polyvalent antivenom a median 3.5h post-bite (2.8–7.2h), which cleared unbound venom from blood. Despite this, the paralysis worsened requiring intubation and ventilation within 7h post-bite. sfEMG showed markedly increased jitter and neuromuscular blocks within 12h. sfEMG abnormalities gradually improved over 24h, corresponding with clinical recovery. Muscle recovery occurred in ascending order. Myotoxicity was not evident, clinically or biochemically, in any of the patients. Patients were extubated a median 96h post-bite (54–216h). On discharge, median 8 days (4–12days) post-bite, patients were clinically normal but had mild sfEMG abnormalities which persisted at 6wk post-bite. There were no clinical or neurophysiological abnormalities at 6–9mth. Conclusions Common krait envenoming causes rapid onset severe neuromuscular paralysis which takes days to recover clinically consistent with sfEMG. Subclinical neuromuscular dysfunction lasts weeks but was not permanent. Antivenom effectively cleared venom but did not prevent worsening or reverse neuromuscular paralysis., Author Summary Common krait bites cause muscular paralysis due to the venom disrupting communication between the nerves and muscles. This becomes life-threatening for the patient if there is paralysis of the muscles used for breathing. We studied the severity of paralysis, long term effects and the value of antivenom treatment in authenticated Indian krait bite patients from Sri Lanka. In addition to standard treatment with antivenom, the patients had single-fibre electromyography done, a sensitive neurophysiological test that detects the abnormalities of communication between the nerves and muscles. Half of the patients had severe paralysis and required mechanical ventilation, and the remainder had mild or no effects. Antivenom was given to all patients with severe paralysis and most with mild effects. However, despite antivenom binding all free venom after it was administered, it did not prevent or reverse already developed paralysis. Clinically evident paralysis resolved after a few days, but the neurophysiological abnormalities lasted for weeks. No permanent neurological damages were noted at 6 to 9 months after the snake bite.

Ankle foot orthoses (AFOs) provide immediate changes to gait kinematics and alter EMG-recorded muscle activity during gait; yet our understanding of neuromuscular adaptations while using AFOs remains incomplete. To address this, we have developed a tunable AFO model to predict torque from ankle angle and velocity and to identify plausible changes in muscle excitation and function in a walking simulation. Using a dynamometer in passive mode, we isolated flexion/extension torque of three polypropylene spring leaf AFOs at 5 degrees/s, 30 degrees/s and 120 degrees/s, from which a model of AFO torque as a function of deformation angle, velocity and size was derived with predictive ability of R20.9. The model coefficients did not vary linearly with size, illustrating the need to test AFO deformation response individually. We applied the tuned models to simulations of normal healthy gait to isolate AFO-induced neuromuscular changes. Compared to the No-AFO condition, AFO results show decreased net tibialis anterior excitation. Our results also show that net soleus excitation is not diminished with an AFO although soleus-induced ankle accelerations were reduced. With a tunable AFO model applied to walking simulations, we can quantify the contributions of muscle and orthosis to net joint torque and predict changes in neuromuscular control during walking.

Summary Mivacurium chloride has been assessed in respect of intubating conditions and neuromuscular effects. The influence of suxamethonium on the onset and duration of subsequently administered mivacurium was also studied. A dose of 0.15 mg.kg−1 of mivacurium was found to provide unacceptable intubating conditions at 2 min in 9/9 patients and further studies were conducted using 0.2 mg.kg−1. Intubating conditions with this dose were acceptable in 65% and 80% of patients at 2 min and 2.5 min respectively. In comparison, intubating conditions were acceptable in 100% of patients at 1 min following 1 mg.kg−1 of suxamethonium. The onset of block occurred in 96 s and 97 s after 0.15 mg.kg−1 and 0.2 mg.kg−1 respectively, and the durations of block in terms of recovery of the first twitch (T1) to 25% and 90% of control, and to recovery of train-of-four ratio to 0.7, were 16.1 and 17.9; 24.1 and 25.8; and 24.2 and 27.0 min respectively with the two doses. The time for the onset of complete block with suxamethonium 1.0 mg.kg−1 was 50 s and the times to 25% and 90% recovery were 9.8 min and 13.3 min. The differences between suxamethonium and both doses of mivacurium were significant (p < 0.05) but there were no significant differences between the two doses of mivacurium in any of the neuromuscular measurements. Prior administration of suxamethonium had no influence on the effects of mivacurium. Cutaneous flushing was observed in 30 out of 75 patients but this was associated with transient hypotension in only two patients. Our results show mivacurium to have a duration of action approximately half that of comparable doses of the intermediate acting relaxants atracurium and vecuronium.

We confirmed the ability of the triterpenoid betulin to protect against neurotoxicity caused byBothrops jararacussusnake venomin vitroin mouse isolated phrenic nerve-diaphragm (PND) preparations and examined its capability ofin vivoprotection using the rat external popliteal/sciatic nerve-tibialis anterior (EPSTA) preparation. Venom caused complete, irreversible blockade in PND (40 μg/mL), but only partial blockade (~30%) in EPSTA (3.6 mg/kg, i.m.) after 120 min. In PND, preincubation of venom with commercial bothropic antivenom (CBA) attenuated the venom-induced blockade, and, in EPSTA, CBA given i.v. 15 min after venom also attenuated the blockade (by ~70% in both preparations). Preincubation of venom with betulin (200 μg/mL) markedly attenuated the venom-induced blockade in PND; similarly, a single dose of betulin (20 mg, i.p., 15 min after venom) virtually abolished the venom-induced decrease in contractility. Plasma creatine kinase activity was significantly elevated 120 min after venom injection in the EPSTA but was attenuated by CBA and betulin. These results indicate that betulin given i.p. has a similar efficacy as CBA given i.v. in attenuating the neuromuscular effects ofB. jararacussuvenomin vivoand could be a useful complementary measure to antivenom therapy for treating snakebite.

Considerable concentrations of the explosive, 2,4,6-trinitrotoluene (TNT) have been found in the soil at many installations where explosives have been used, manufactured, assembled, or destroyed. To evaluate risk to avian receptors, measures of exposure are compared with a threshold level of sublethal toxicity. To date, a single feeding study has evaluated the responses of oral TNT exposure to birds with equivocal results regarding sublethal effects. The present study followed a controlled dosing regime comprising four dose groups and a control (200, 120, 70, 20, and 0 mg TNT/kg body weight [bw]-day) in the common pigeon ( Columba livia) for 60 days. Overt signs of toxicity occurred with both sexes between 2 and 3 weeks of exposure. Signs included weight loss, neuromuscular effects (e.g., ataxia, tremors, etc.), and scant red feces (chromaturia). Emetic events following dosing were common and proportional to dose; however, attempts to quantify vomitus compound concentration suggests that birds were marginally successful at removing TNT following administration. Eight of 12 and 2 of 12 males and females died or were moribund in the 200 and 120 mg/kg-day groups, respectively. Changes in hematological parameters, liver, kidney, and ovary weights were related to treatment. Dose-related changes in plasma albumin and sodium concentrations were also observed. These results suggest that subchronic exposure to TNT can adversely affect the central nervous system and hematological parameters in birds. Chemical analysis of blood detected concentrations of the two primary reduction metabolites, but not parent compound, suggesting that toxicity may be due to the bioaccumulation of a toxic intermediate.

Medicinal plants are being widely used, either as a single drug or in combination in health care delivery system. Medicinal plants can be important source of previously unknown chemical substances with potential therapeutic effects. Abrus precatorius L. is commonly known as Gunja or Jequirity and abundantly found all throughout the plains of India, from Himalaya down to Southern India and Ceylon. This plant is having medicinal potential to cure various diseases. The roots, leaves and seeds of this plant are used for different medicinal purpose. It principally contains flavonoids, triterpene glycosides, abrin and alkaloids. The plant have been reported for neuromuscular effects, neuro-protective, abortifacient, antiepileptic, anti-viral, anti-malarial, antifertility, nephroprotective, immunomodulator, immunostimulatory properties, anti-inflammatory activity, antidiabetic effect, etc. As this is a potential medicinal plant, present review reveals chemical constituents of leaf, root and seeds of Abrus precatorius. The plant is considered as a valuable source of unique natural products for development of medicines against various diseases and also for the development of industrial products.

Background The time-course of the effect of rocuronium during isoflurane anesthesia in children has rarely been evaluated. Forty-five children, aged 2–14 years, ASA 1, undergoing elective surgery and receiving isoflurane anesthesia, were studied. Methods Patients randomly received a dose of 400, 600, or 800 μg/kg of rocuronium. The first response to the control height (T1:T0) was fitted to time in order to obtain times to onset of action (TOA) including time to 90 (B 90 ) and 99.9% (B 100 ) of relaxation and to spontaneous recovery of 10 (T 10 ), 25 (T 25 ), 50 (T 50 ), 75 (T 75 ), and 90% (T 90 ) of neuromuscular function (NMF). Each time was compared among groups. Linear regression analysis between the TOA or the times to spontaneous recovery of NMF (TSRNMF) and age or weight were also performed. Results The TOA were similar among the three groups while TSRNF in children receiving 600 or 800 μg/kg were longer ( p 10 and T 25 were related to age ( p = 0.05), whereas T 10 , T 50 , T 75, and T 90 were related to weight ( p Conclusions Maximal relaxation was reached in all children receiving 600 or 800 μg/kg of rocuronium. The TSRNMF were mainly related to the weight of the children, and gender affected each relationship. Widely variable responses were observed with all three doses.

Background: The pharmacodynamic profile of muscle relaxants is usually changed by volatile anaesthetics. These changes seem to be time-dependent, even though few data are available to substantiate this. Methods: We studied neuromuscular effects of a single dose of mivacurium (0.2 mg kg -1 ) during short and intermediate duration of isoflurane anaesthesia. Forty-five children 1-10 years of age were randomized to receive 1.5% end-tidal concentration of isoflurane in N 2 O/O 2 for 10 or 30 min (groups Iso-10 and Iso-30, respectively) or to receive nitrous oxide in oxygen for 10 min (Group N 2 O) before 0.2 mg. kg -1 of mivacurium was given. Neuromuscular response was recorded by adductor pollicis electromyogram. Results: The onset time of mivacurium was shorter in Group Iso-30, 1.7 (1.0-2.3) min than in Group Iso-10, 2.3 (1.7-3.3) min or Group N 2 O, 2.3 (1.7-3.3) min (median with 10-90% percen-tiles) (P

The effects of 1 MAC of desflurane and isoflurane (in 66% nitrous oxide) on the potency and duration of action of mivacurium were studied in 80 patients. The ED95 of mivacurium was 86 micrograms.kg-1 (74-100) and 88 micrograms.kg-1 (76-103) (mean and 95% confidence intervals) during anaesthesia with desflurane and isoflurane respectively. The onset and duration of recovery to 25, 75 and 90% of T1 (first response in the TOF) of 200 micrograms.kg-1 of mivacurium were 1.4 (0.3) and 1.5 (0.3) min (mean and SD), 22 (4.9) and 19 (4.0), 29 (6.6) and 26 (5.8), and 32 (7.3) and 29 (6.6) min respectively. There was no significant difference in any of the variables between desflurane and isoflurane. It is concluded that the neuromuscular effects of mivacurium are similar during anaesthesia with 1 MAC of desflurane and isoflurane.

重症筋無力症であるが,抗アセチルコリンレセプター抗体が陰性の胸腺摘出術予定患者5例を対象とした.マイオグラフ2000TMを用いて栂指内転筋の単収縮高(T1)および四連反応比を記録し,2.5%セボフルランで調節呼吸下,T1が対照値の10%以下になるまで,ベクロニウム0.01mg/kgを繰り返し静注した.全身型(Osserman分類のIIA)の3例では,初回投与だけでT1がほぼ対照値の5%以下に低下した.また,全身型で四連反応比が初めから25%と著しく低い例があった.一方,眼筋型の2例は,ベクロニウムの追加投与を必要とした.抗体陰性であっても全身型の患者は,ベクロニウムに対して感受性が高いと考えられる.

We compared both the time course of neuromuscular blockade and the cardiovascular side-effects of suxamethonium and mivacurium during halothane and nitrous oxide anaesthesia in infants 2-12 months and children 1-12 years of age. Equipotent doses of mivacurium and suxamethonium were studied; 2.2 x ED95 was used in four groups of infants and children, while 3.4 x ED95 was used in two groups of children. Onset of neuromuscular block in infants was not significantly faster with suxamethonium than with mivacurium (P = 0.2). In all infants given suxamethonium, intubating conditions were excellent, while, in 6/10 infants given mivacurium, intubating conditions were excellent. Onset of complete neuromuscular block in children was significantly faster with suxamethonium, 0.9 min compared with mivacurium, 1.4 min (P < or = 0.05). Increasing the dose of suxamethonium or mivacurium in children to 3.4 x ED95 did not change the onset of neuromuscular block. Recovery of neuromuscular transmission to 25% of initial twitch height (T25) in infants and children was significantly faster after suxamethonium than after mivacurium, at 2.5 and 6 min, respectively (P < or = 0.05). In children given 3.4 x ED95 of suxamethonium or mivacurium, recovery from neuromuscular block was almost identical with the dose of 2.2 x ED95, with spontaneous recovery to T25 prolonged by only 0.5 min. No infant or child had hypotension after the mivacurium bolus dose.

Metabolic and neurological responses to 4 bouts of lower-body or upper-body resistance exercise preceded by cycle ergometry or rest were assessed. Nine resistance-trained men (26.7 ± 6.6 years) underwent bouts of (a) cycle ergometry then bench press, (b) bench press only, (c) cycle ergometry then back squat, and (d) back squat only. Cycle ergometry was performed at 75% maximum heart rate for 45 minutes. Bench press and back squat protocols required 6 sets to volitional fatigue at 80% 1RM with 2 minutes rest between sets. Significantly more repetitions were performed during set 1 for back squat without preceding aerobic exercise (12.6 ± 4.5 vs. 10.0 ± 3.5, p = 0.000) and cumulatively at set 3 (27.1 ± 10.6 vs. 23.1 ± 9.2, p = 0.014), and no differences were noted for bench press repetitions. Inclusion of cycle ergometry results in impaired back squat, but not bench press, performance likely because of a combination of local metabolic stress and various neuromuscular effects.

Although the effects of attention on movement execution are well documented behaviorally, much less research has been done on the neurophysiological changes that underlie attentional focus effects. This study presents two experiments exploring effects of attention during an isometric plantar-flexion task using surface electromyography (sEMG). Participants' attention was directed either externally (towards the force plate they were pushing against) or internally (towards their own leg, specifically the agonist muscle). Experiment 1 tested the effects of attention on accuracy and efficiency of force produced at three target forces (30, 60, and 100% of the maximum voluntary contraction; MVC). An internal focus of attention reduced the accuracy of force being produced and increased cocontraction of the antagonist muscle. Error on a given trial was positively correlated with the magnitude of cocontraction on that trial. Experiment 2 tested the effects of attention on muscular fatigue at 30, 60 and 100%MVC. An internal focus of attention led to less efficient intermuscular coordination, especially early in the contraction. These results suggest that an internal focus of attention disrupts efficient motor control in force production resulting in increased cocontraction, which potentially explains other neuromechanical findings (e.g. reduced functional variability with an internal focus).

BACKGROUND Rocuronium is a new nondepolarizing neuromuscular blocking agent with a rapid onset but with intermediate duration of action. Mivacurium, on the other hand, is a new short-acting nondepolarizing neuromuscular relaxant, but of slower onset of action. The current study was undertaken to characterize the interaction between rocuronium and mivacurium. METHODS In the first study, the dose-response relations of rocuronium, mivacurium, and their combination were studied in ASA physical status 1 or 2 patients during thiopental-fentanyl-N2O anesthesia. One hundred ten patients, randomly assigned to 1 of 11 groups of 10 patients each, received mivacurium 30, 50, or 70 micrograms.kg-1; rocuronium 100, 200, 250, or 300 micrograms.kg-1; or an equieffective combination of both drugs (1 ED50 rocuronium + 1 ED50 mivacurium; 1/2 ED50 rocuronium + 1/2 ED50 mivacurium; 1/4 ED50 rocuronium + 1/4 ED50 mivacurium; or 1/8 ED50 rocuronium + 1/8 ED50 mivacurium, where ED50 is the dose producing 50% depression of the first twitch height). In the second study, 50 patients, ASA physical status 1 or 2, anesthetized with thiopental-fentanyl-N2O, were randomly allocated to 5 groups of 10 patients each to receive one of the following neuromuscular blocking drugs or drug combination: rocuronium 600 micrograms.kg-1 (group 1), mivacurium 150 micrograms.kg-1 (group 2) rocuronium 150 micrograms.kg-1 + mivacurium 37.5 micrograms.kg-1 (group 3), rocuronium 300 micrograms.kg-1 + mivacurium 75 micrograms.kg-1 ((group 4), or rocuronium 600 micrograms.kg-1 + mivacurium 150 micrograms.kg-1 (group 5). RESULTS The calculated ED50 values and their 95% confidence intervals were 125 (122-129) and 37 (36-38) micrograms.kg-1 for the rocuronium and mivacurium groups, respectively. The interaction between rocuronium and mivacurium was found to be synergistic. The measured ED50 of the mixture was only 62% of the predicted value assuming a purely additive interaction. In the second study, rocuronium 600 micrograms.kg-1 group and group 3 had similar onset times (99 [74-123] and 114 [100-128] s, respectively), which were significantly shorter than that observed in the mivacurium 150 micrograms.kg-1 group (178 [149-206] s). Onset times in groups 4 and 5 were significantly shorter than that in each of the other study groups (69 [63-76] and 73 [65-80] s, respectively). Clinical duration of action (recovery of T1 to 25% of baseline twitch height) was significantly greater in group 5 (55 [51-60] min) than with all other doses and agents, and briefest (P < 0.01) with mivacurium 150 micrograms.kg-1 (14.5 [12.6-16.5] min) and group 3 (14.7 [13.4-16] min). CONCLUSIONS The interaction between rocuronium and mivacurium was found to be synergistic.

重症筋無力症(MG)患者と対照患者に,エンフルラン終末呼気濃度2.5%麻酔下で手術を行ない,神経筋伝達反応を経時的に比較検討した。MG患者8例中6例では吸入開始直後から単収縮反応,四連反応比(TR)の低下がともに著明に進行し,シナプス後抑制のみならず,シナプス前抑制効果も初期から強力に発現する可能性が示唆された。しかしうち1例はTR低下の反応までの時間に遅れがみられ,1例は変化しなかった。対照患者7例の筋弛緩はすべてごくわずかであった。神経筋伝達抑制効果と抗アセチルコリン受容体抗体価,OssermanとGenkinsの臨床分類,大島の重症度評価基準,病悩期間,術前プレドニゾロン投与量などとの間に相関はなく,胸腺組織型とも特に関連はなかった。

Mivacurium is metabolized by plasma pseudocholinesterase (PChE) enzyme, which is decreased in burns. We tested whether the decreased metabolism of mivacurium due to decreased PChE activity can overcome the pharmacodynamic resistance to non-depolarizing relaxants previously seen in major burns.Thirty adults with 35 (13)% [mean (sd)] burn were studied at 5-91 post-burn days and 31 non-burns matched controls. Mivacurium 0.2 mg kg(-1) was administered as a single bolus. Neuromuscular block was monitored with single-twitch response using TOF-Watch™. Onset time (drug administration to maximal twitch suppression) and spontaneous recovery were measured.Onset time was significantly prolonged in burns when compared with non-burns (115 vs 90 s; P0.001). The PChE levels were lower in burns [1432 (916) vs 2866 (731) IU litre(-1); P0.001] and the neuromuscular recovery to 50% of baseline twitch height was prolonged in burns (41 vs 26 min; P0.001). There was a significant correlation between PChE and time to 50% recovery for the whole group together (r=-0.6; P0.001). The dibucaine numbers were not different.The prolonged onset time suggests resistance to neuromuscular effects, whereas the prolonged recovery suggests increased sensitivity. This divergent response can be explained by qualitative and quantitative changes in acetylcholine receptor expression causing resistance and decreased PChE activity causing sensitivity. Despite using a relatively large dose of mivacurium (0.2 mg kg(-1)) in the presence of decreased PChE levels, this did not overcome the resistance resulting from up-regulated receptors.

We have studied the neuromuscular effects of pipecuronium, vecuronium and their combination in 130 ASA group I or II patients. Patients were anaesthetized with 0.8% halothane and 60% nitrous oxide in oxygen. Neuromuscular block was recorded as the evoked thenar mechanomyographic response to train-of-four stimulation of the ulnar nerve (2Hz at 10-s intervals). The dose-response curves were determined by probit analysis. The calculated doses producing 50% depression of the first twitch height were 15.6, 16.9 and 15.0 μg kg−1 for the pipecuronium, vecuronium and pipecuronium-vecuronium combination groups, respectively. Isobolo graphic and algebraic (fractional) analyses were used to assess quantitatively the combined neuromuscular effect of pipecuronium and vecuronium and to define the type of interaction between these drugs. The interaction between pipecuronium and vecuronium was found to be additive. (Br. J. Anaesth. 1993; 71: 556–560)

Sevoflurane was compared to isoflurane anesthesia alone and in combination with atracurium or vecuronium in 84 rats using the sciatic nerve-anterior tibialis muscle preparation. Both bolus injection and infusion rate techniques were used to evaluate these drug interactions. The ED(50) (dose which produced a 50% depression of twitch tension) of atracurium was 311 +/- 31 and 360 +/- 32 microg.kg(-1) during 1.25 MAC sevoflurane and isoflurane anesthesia respectively. The ED(50) of vecuronium was 190 +/- 27 and 149 +/- 14 microg.kg(-1) during 1.25 MAC sevoflurane and isoflurane anesthesia respectively. The mean infusion rates of atracurium and vecuronium required to maintain a 50% depression of twitch tension were 5.04 +/- 0.7 and 2.02 +/- 0.3 mg.kg(-1).hr(-1). These infusion rates were 5.04 +/- 0.7 and 2.02 +/- 0.3 mg.kg(-1).hr(-1) during 1.25 MAC sevoflurane and 3.73 +/- 0.3 and 1.81 +/- 0.4 mg.kg(-1).hr(-1) during 1.25 MAC isoflurane anesthesia respectively. With both atracurium and vecuronium, the infusion rate required to maintain a 50% depression twitch of tension was inversely related to the concentrations of isoflurane and sevoflurane. The authors conclude that sevoflurane is similar in potency to that of isoflurane in augmenting a vecuronium or atracurium induced neuromuscular blockade in a dose-dependent manner.

In searching for a nondepolarizing muscle relaxant with intermediate duration but more rapid onset of action than the presently available compounds, the neuromuscular and circulatory effects of ORG9426 were investigated in two studies in humans receiving fentanyl, droperidol, thiopental, and nitrous oxide-oxygen anesthesia. Eighty patients, randomly assigned to one of four groups of 20 each, received 0.12, 0.16, 0.20, or 0.24 mg/kg ORG9426. In the first study, the doses (in milligrams per kilogram) of ORG9426 that caused 50% (ED50), 90% (ED90), or 95% (ED95) neuromuscular block were determined by the individual dose-response method; they were 0.170, 0.268, and 0.305 mg/kg, respectively. In the second study, after induction of anesthesia, patients received 0.6 mg/kg (about 2 x ED95) of ORG9426, either in a single bolus (group 1) or in two unequal (0.1 and 0.5 mg/kg) increments 4 min apart (group 2). After the administration of 0.6 mg/kg ORG9426, maximal neuromuscular block developed in 1.5 +/- 0.12 min in group 1 and in 1.2 +/- 0.14 min in group 2. Patients tracheas were intubated after development of the maximal neuromuscular effect of the intubating dose and after the recording of heart rate and systolic and diastolic blood pressure. There was no difference in the clinical duration of the intubating doses, which were 40.0 +/- 3.2 (15-73) min in group 1 and 39.3 +/- 2.4 (19-57) min in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND AND OBJECTIVES The elderly represent a wide and increasing patient population and significant numbers of elderly patients have chronic renal disease. This study aimed to investigate the neuromuscular effects of 0.6 mg kg(-1) rocuronium under propofol anaesthesia in young adults and elderly patients with or without renal failure. METHODS The neuromuscular effects of rocuronium 0.6 mg kg(-1) under propofol anaesthesia were investigated in 40 patients with renal failure undergoing arteriovenous shunt surgery, of whom 20 were young adults (18-50 yr) and 20 were elderly (>65 yr) and in 40 patients with normal renal function undergoing peripheral venous surgery, of whom 20 were young adults and 20 were elderly. Neuromuscular transmission was monitored using acceleromyography. The times to recovery of the twitch (T1) to 25%, 50%, 75% and 90% and of the train-of-four ratio to 70%, and the recovery index were recorded. RESULTS The times to recovery of the first twitch to 25%, 50%, 75% and 90% and train-of-four to 70% and recovery index were found to be prolonged in both young and elderly patients with renal failure compared to those with normal renal function (e.g. T1 25%: 58.4 +/- 20.2 and 80.1 +/- 23.7 min vs. 32.8 +/- 5.6 and 46.3 +/- 9.0 min, respectively) (P < 0.05). These parameters were also prolonged in the elderly when compared with young adults in both the renal failure and the non-renal failure groups. CONCLUSIONS The neuromuscular effects of 0.6 mg kg(-1) rocuronium under propofol anaesthesia were markedly prolonged in young and elderly renal failure patients compared to patients with normal renal function, and also in elderly patients with normal renal function compared with young adults.

Seventeen myasthenia gravis and seven control patients were studied mechano (MMG)- and electromyographically (EMG) during isoflurane/oxygen/air anaesthesia. In myasthenic patients the mean train-of-four ratio and neuromuscular block (by MMG) during 1.9 MAC isoflurane anaesthesia were 55 +/- 9% and 46 +/- 12%, respectively. The correlation between simultaneous MMG and EMG measurements was excellent (r2 = 0.933, P less than 0.001). The occurrence of HLA-B8 together with acetylcholine receptor antibodies seems to predispose myasthenic patients to a neuromuscular depression produced by isoflurane. Our current and prior results show that isoflurane possesses approximately twice as strong a neuromuscular blocking effect as halothane in myasthenic patients.