Objectives To report on the monitoring of diaphragm electrical activity (Edi) using neurally adjusted ventilator assist (NAVA) technology to investigate the mechanisms of ventilator dependence in children with neuromuscular and respiratory control disorders. Patients and methods Using NAVA technology, electrical activity of the diaphragm (Edi) was monitored at the lowest achievable level of respiratory support in six ventilator-dependent patients with neuromuscular and respiratory control disorders, aged 6?weeks to 12?years, admitted to a tertiary paediatric intensive care unit between 2009 and 2011. Results Edi monitoring identified markedly abnormal respiratory dynamic patterns that were not always apparent clinically. These were associated with disorders of central respiratory control, ...

Mechanisms linking obesity with upper airway dysfunction in obstructive sleep apnea are reviewed. Obstructive sleep apnea is due to alterations in upper airway anatomy and neuromuscular control. Upper airway structural alterations in obesity are related to adipose deposition around the pharynx, whic...

Administration of aminoglycoside antibiotics can precipitate sudden, profound bouts of weakness that have been attributed to block of presynaptic voltage-activated calcium channels (VACCs) and failure of neuromuscular transmission. This serious adverse drug reaction is more likely in neuromuscular diseases such as myasthenia gravis. The relatively low affinity of VACC for aminoglycosides prompted us to explore alternative mechanisms. We hypothesized that the presynaptic Ca2+-sensing receptor (CaSR) may contribute to aminoglycoside-induced weakness due to its role in modulating synaptic transmission and its sensitivity to aminoglycosides in heterologous expression systems. We have previously shown that presynaptic CaSR controls a non-selective cation channel (NSCC) that regulates nerve term...

We provide an overview of optimal control methods to nonlinear neuromuscular systems and discuss their limitations. Moreover we extend current optimal control methods to their application to neuromuscular models with realistically numerous musculotendons; as most prior work is limited to torque-driven systems. Recent work on computational motor control has explored the used of control theory and estimation as a conceptual tool to understand the underlying computational principles of neuromuscular systems. After all, successful biological systems regularly meet conditions for stability, robustness and performance for multiple classes of complex tasks. Among a variety of proposed control theory frameworks to explain this, stochastic optimal control has become a dominant framework to the point of being a standard computational technique to reproduce kinematic trajectories of reaching movements (see [12]) In particular, we demonstrate the application of optimal control to a neuromuscular model of the index finger with all seven musculotendons producing a tapping task. Our simulations include 1) a muscle model that includes force- length and force-velocity characteristics; 2) an anatomically plausible biomechanical model of the index finger that includes a tendinous network for the extensor mechanism and 3) a contact model that is based on a nonlinear spring-damper attached at the end effector of the index finger. We demonstrate that it is feasible to apply optimal control to systems with realistically large state vectors and conclude that, while optimal control is an adequate formalism to create computational models of neuro-musculoskeletal systems, there remain important challenges and limitations that need to be considered and overcome such as contact transitions, curse of dimensionality, and constraints on states and controls. PMID:21095783

AChR is concentrated at the postjunctional membrane at the neuromuscular junction. However, the underlying mechanism is unclear. We show that ?-actinin, a protein known to cross-link F-actin, interacts with rapsyn, a scaffold protein essential for neuromuscular junction formation. ?-Actinin, rapsyn,...

Neuromuscular blocking agents have generally been avoided during intraoperative neurophysiological monitoring (IOM) where muscle responses to nerve stimulation or transcranial stimulation are monitored. However, a variety of studies and clinical experience indicate partial neuromuscular blockade is compatible with monitoring in some patients. This review presents these experiences after reviewing the currently used agents and the methods used to assess the blockade. A review was conducted of the published literature regarding neuromuscular blockade during IOM. A variety of articles have been published that give insight into the use of partial pharmacological paralysis during monitoring. Responses have been recorded from facial muscles, vocalis muscles, and peripheral nerve muscles from transcranial or neural stimulation with neuromuscular blockade measured in the muscle tested or in the thenar muscles from ulnar nerve stimulation. Preconditioning of the nervous system with tetanic or sensory stimulation has been used. In patients without neuromuscular pathology intraoperative monitoring using peripheral muscle responses from neural stimulation is possible with partial neuromuscular blockade. Monitoring of muscle responses from cranial nerve stimulation may require a higher degree of stimulation and less neuromuscular blockade. The role of tetanic or sensory conditioning of the nervous system is not fully characterized. The impact of neuromuscular pathology or the effect of partial blockade on monitoring muscle responses from spontaneous neural activity or mechanical nerve stimulation has not been described. PMID:23015366

... X-Plain.com nr230105 Last reviewed: 6/8/2009 1 Certain muscles, such as the ones controlling ... X-Plain.com nr230105 Last reviewed: 6/8/2009 2 As messages arrive to the neuromuscular junction ...

To determine the mechanism of the beneficial effects of prednisolone on Duchenne muscular dystrophy (DMD), we examined the short-term effects of prednisolone on neuromuscular transmission by using conventional microelectrode methods in the mdx mice. High (56 ?mol/liter) and low (2.8 ?mol/liter) concentrations of prednisolone were applied to a bath containing phrenic nerve-diaphragm preparations from mdx mice, and several parameters related to neuromuscular transmission were recorded. The high dose of prednisolone significantly decreased parameter n on quantal release by nerve impulse and decay time-constant of end-plate potentials, which showed adverse effect on neuromuscular transmission. The low dose of prednisolone did not significantly increase quantal content, but could assist the compensatory reaction to maintain the safety margin of neuromuscular transmission in the mdx mice. Our results suggest that the latter effect represents one of the possible mechanisms of the therapeutic effects of prednisolone on DMD.   

We evaluated the neuromuscular reversal with edrophonium using peripheral nerve stimulator and recorder in a patient with malathion intoxication. Edrophonium 10 mg i.v. caused an increase in single twitch tension by 76% of the control during the recovery phase from an acute cholinergic crisis 16 days after ingestion of malathion solution. The present study indicated that edrophonium test seems to be a reliable monitoring in evaluating neuromuscular reversal in the patient with acute malathion insecticide poisoning.   

Neuromuscular blocking agents are among the most commonly used drugs during general anesthesia. They compete with acetylcholine and interfere with the transmission of nerve impulses resulting in skeletal muscle relaxation. Based on their mechanism of action, neuromuscular blocking agents are classified as either depolarizing or nondepolarizing. Succinylcholine is a short-acting depolarizing agent. Commonly used nondepolarizing agents are curare (long-acting), pancuronium (long-acting), atracurium (intermediate-acting), and vecuronium (intermediate-acting). Neuromuscular blocking agents are used clinically to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery. This article provides an overview of the physiology of the neuromuscular transmission and summarizes our current knowledge on the use of these agents during general anesthesia. PMID:1672571

Abstract in portuguese O objetivo do presente trabalho foi investigar o tráfego de vesículas sinápticas quando estas apresentam alterações no armazenamento de neurotransmissores e acidificação em duas distintas sinapses: a junção neuromuscular colinérgica de rãs versus o terminal nervoso glutamatérgico do tipo ribbon em céulas bipolares da retina. Essas sinapses exibem notáveis diferenças estruturais e funcionais e os mecanismos de regulação de ciclo das vesículas sinápticas (more) podem ser diferentes entre eles. Para monitorar o tráfego de vesícula, foi utilizado o marcador lipofílico FM1-43. Ambas as preparações foram expostas a agentes farmacológicos que provocam o colapso de ?pH (NH4Cl e metilamina) ou de todo ?µH+ (bafilomicina), gradientes necessários para o acúmulo de neurotransmissores em vesículas sinápticas. Nossos resultados demonstram que a marcação e desmarcação de FM1-43 nas junções neuromusculares não foi estatisticamente diferente entre as diversas condições experimentais (P > 0,05). Além disso, a marcação de FM1-43 em terminais sinápticos de células bipolares foram bastante semelhantes em todas as condições testadas. Apesar das diferenças marcantes em ambos os modelos experimentais, nossos achados demonstram que a acidificação e o preenchimento de vesículas sinápticas não são necessários para o tráfico normal da vesícula nas sinapses estudadas. Abstract in english The purpose of the present work was to investigate synaptic vesicle trafficking when vesicles exhibit alterations in filling and acidification in two different synapses: a cholinergic frog neuromuscular junction and a glutamatergic ribbon-type nerve terminal in the retina. These synapses display remarkable structural and functional differences, and the mechanisms regulating synaptic vesicle cycling might also differ between them. The lipophilic styryl dye FM1-43 was used (more) to monitor vesicle trafficking. Both preparations were exposed to pharmacological agents that collapse ?pH (NH4Cl and methylamine) or the whole ?µH+ (bafilomycin), a necessary situation to provide the driving force for neurotransmitter accumulation into synaptic vesicles. The results showed that FM1-43 loading and unloading in neuromuscular junctions did not differ statistically between control and experimental conditions (P > 0.05). Also, FM1-43 labeling in bipolar cell terminals proved highly similar under all conditions tested. Despite remarkable differences in both experimental models, the present findings show that acidification and filling are not required for normal vesicle trafficking in either synapse.

Administration of aminoglycoside antibiotics can precipitate sudden, profound bouts of weakness that have been attributed to block of presynaptic voltage-activated calcium channels (VACCs) and failure of neuromuscular transmission. This serious adverse drug reaction is more likely in neuromuscular diseases such as myasthenia gravis. The relatively low affinity of VACC for aminoglycosides prompted us to explore alternative mechanisms. We hypothesized that the presynaptic Ca(2+)-sensing receptor (CaSR) may contribute to aminoglycoside-induced weakness due to its role in modulating synaptic transmission and its sensitivity to aminoglycosides in heterologous expression systems. We have previously shown that presynaptic CaSR controls a non-selective cation channel (NSCC) that regulates nerve terminal excitability and transmitter release. Using direct, electrophysiological recording, we report that neuronal VACCs are inhibited by neomycin (IC(50) 830 +/- 110 microM) at a much lower affinity than CaSR-modulated NSCC currents recorded from acutely isolated presynaptic terminals (synaptosomes; IC(50) 20 +/- 1 microM). Thus, at clinically relevant concentrations, aminoglycoside-induced weakness is likely precipitated by enhanced CaSR activation and subsequent decrease in terminal excitability rather than through direct inhibition of VACCs themselves. PMID:19646457

Background: A functionally induced, transient low back pain model consisting of exposure to prolonged standing has been used to elucidate baseline neuromuscular differences between previously asymptomatic individuals classified as pain developers and non-pain developers based on their pain response during a standing exposure. Previous findings have included differences in frontal plane lumbopelvic control and altered movement strategies that are present prior to pain development. Control strategies during sagittal plane movement have not been previously investigated in this sample. The purpose of this research was to investigate neuromuscular control differences during the extension phase from trunk flexion between pain developers and non-pain developers. Methods: Continuous electromyograp...

The type I receptor-like protein tyrosine kinase MuSK is essential for the neuromuscular junction formation. MuSK expression is tightly regulated during development, but the underlying mechanisms were unclear. Here we identified a novel mechanism by which MuSK expression may be regulated. A cyclic A...

Spontaneous contractions of the intestine are thought to play an important role in the gastrointestinal motility, including peristalsis. In the present study, we investigated mechanisms for regulation of the frequency of spontaneous contractions, using longitudinal muscle strips in rat distal colon. Atropine significantly decreased the frequency of spontaneous contractions, indicating that neuromuscular transmission via muscarinic receptors increases the frequency of spontaneous contractions. SB-204070, 5-HT4 receptor antagonist also significantly decreased the frequency of spontaneous contractions, indicating that the activation of 5-HT4 receptors also increases the frequency of spontaneous contractions. In conclusion, it is suggested that muscarinic and 5-HT4 receptors participate in the regulation of the frequency of spontaneous contractions in the longitudinal muscle in rat distal colon, and that the frequency of spontaneous contraction is controlled by the enteric neurons.   

Chronic ankle instability represents a typical sports injury. After an acute ankle sprain 20-40% of the injured develop chronic ankle instability. From an orthopaedic point of view chronic ankle instability can be subdivided into lateral and medial instability or a combination of both, the so-called rotational ankle instability. From a pathophysiological point of view, chronic ankle instability can be either mechanical with a structural ligament lesion or functional with loss of neuromuscular control. For the physician chronic ankle instability is a difficult entity as the diagnosis is usually complex and the therapy often surgical. This review on chronic ankle instability deals with the pathomechanisms, diagnostics, indications for conservative and surgical treatments, and possible long-term sequelae, such as ligamentous osteoarthritis. PMID:17684717

Amyotrophic lateral sclerosis (ALS) is a progressive, neuromuscular disease without any curative therapy at the moment. Non-invasive BIPAP-ventilation has proven to be helpful to cope with the increasing hypoventilation due to weakness in ventilatory muscles in ALS. If BIPAP-ventilation is well tolerated by the patient, it can be very helpful for symptom control in palliative homecare. In this case presentation we discuss how non-invasive ventilation can influence perception of dying at home and thereby quality of life of patients, caregivers and members of palliative teams. We will see that especially during this sensible terminal phase various questions and fears concerning the mechanically assisted ventilation may arise. These issues should be addressed in advance with careful attention and information. Members of palliative teams should therefore be provided with good training and regular supervision. PMID:20151350

This study describes the effects of Bothrops marajoensis venom (Marajó lancehead) on isolated neuromuscular preparations of chick biventer cervicis (CBC) and mouse phrenic nerve-diaphragm (PND). At low concentrations (1µg/ml for CBC and 5µg/ml for PND), the venom exhibited a neuromuscular blocking without any damaging effect on the muscle integrity. At higher concentration (20?g/ml for PND), together with the neuromuscular blockade, there was a moderate myonecrosis. The results show differences between mammalian and avian preparations in response to venom concentration; the avian preparation was more sensitive to venom neurotoxic effect than the mammalian preparation. The possible presynaptic mechanism underlying the neuromuscular blocking effect was reinforced by the observed increase in MEPPs at the same time (at 15min) when the facilitation of twitch tension occurred. These results indicate that the B. marajoensis venom produced neuromuscular blockade, which appeared to be presynaptic at low concentrations with a postsynaptic component at high concentrations, leading to muscle oedema. These observations demand the fractionation of the crude venom and characterization of its active components for a better understanding of its biological dynamics. PMID:17178238

Abstract in spanish En la práctica clínica un común efecto adverso del litio es la aparición de temblor en reposo. Actualmente no existe una explicación satisfactoria de este fenómeno, por lo que se dificulta su manejo. El objetivo del presente estudio fue determinar el efecto del litio sobre la excitabilidad de la unión neuromuscular en una preparación in vitro, con el fin de dilucidar un mecanismo periférico que contribuya al entendimiento de la etiología del temblor inducido por (more) litio. Para ello se expuso la preparación frénico diafragma de rata a concentraciones ascendentes de litio (0,25 mmol/l a 8 mmol/l). La preparación se sometió a estimulo directo e indirecto y se midieron, como indicadores de excitabilidad, la frecuencia de estímulo mínima necesaria para desencadenar un tétanos perfecto, el voltaje mínimo necesario para generar una respuesta regular y la presencia de actividad espontánea de la preparación. El grupo control se sometió al mismo tiempo y protocolo de estimulación en ausencia de litio. Se utilizaron pruebas no paramétricas para evidenciar diferencias significativas. Se observó un aumento en la frecuencia de estímulo mínima necesaria para desencadenar un tétanos perfecto, comparada con el control, tanto con estimulación directa (p=0) como indirecta (p=0,014); no se observó un cambio significativo en el voltaje mínimo necesario para generar una respuesta regular, ni se observó actividad espontánea en la preparación. Los resultados nos permitieron concluir que el litio no aumenta la excitabilidad de la preparación neuromuscular in vitro y, por lo tanto, no predispone a la aparición de temblor, lo cual sugiere que el temblor no se explica por un mecanismo periférico. Abstract in english One of the most common adverse effects detected with the use of lithium in clinical practice is tremor. Currently the explanation for this phenomenon is incomplete; therefore, its treatment is difficult. This study evaluated the lithium's effect on neuromuscular junction excitability using an in vitro preparation. In order to investigate a peripheral mechanism that could explain lithium induced tremor. The in vitro rat phrenic nerve-diaphragm preparation was exposed to in (more) creasing concentrations of Lithium (0,25 - 8 mmol/l). The preparation excitability was assessed under direct and indirect stimulation by measuring both the minimal stimulating frequency necessary to achieve a completely fused tetanus and the minimal stimulating voltage necessary to achieve a regular contractile response. We also looked for spontaneous contractile activity. Finally, nonparametric tests were used to detect differences between control and lithium groups. An increase on the minimal frequency necessary to achieve a completely fused tetanus compared with control was detected under direct stimulation (p=0,000) and under indirect stimulation (p=0,014). We did not detect a significant change on the minimal voltage necessary to achieve a regular contractile response nor a spontaneous activity in the preparation. In our experimental model Lithium does not increase the excitability of the neuromuscular phrenic nerve-diaphragm preparation; therefore, it does not predispose to tremor development. In view of our finding, our study suggests that lithium tremor is not caused by a peripheral mechanism of action of the drug.

More than a century ago the fruit fly Drosophila melanogaster was established as a genetic model system. The Drosophila neuromuscular junction (NMJ) has proven as an adequate model system to study molecular mechanisms of development of glutamatergic synapses. Discoveries first made in flies had a br...

Myasthenia gravis is a prototype anti-receptor autoimmune disease. Antibodies against proteins at the neuromuscular junction cause a defect in the signal transmission from nerve terminal to the damaged postsynaptic membrane. This issue of Autoimmunity reviews the mechanisms that lead to the destruct...

In providing the cell with ATP generated by oxidative phosphorylation, the mitochondrial ADP/ATP carrier plays a central role in aerobic eukaryotic cells. Combining biochemical, genetic, and structural approaches contributes to understanding the molecular mechanism of this essential transport system, the dysfunction of which is implicated in neuromuscular diseases.

The capacity of pre-habilitative conditioning - exercise performed a priori - to mitigate neuromuscular maladaptations to disuse is unclear. This study evaluated pre-habilitation by examining neuromuscular junctions (NMJs) and the myofibers they innervate in young adult and aged muscles. Within each age category, 40 rats were divided into four treatment groups: 1) control, 2) hindlimb suspended (unloaded), 3) prehabilitative conditioning preceding hindlimb suspension, and 4) pre-habilitative conditioning alone. Cytofluorescent staining was used to visualize NMJs, and histochemical staining to assess myofiber profiles (size and type). Statistical analysis featured 2-way ANOVA with main effects for age and treatment, along with interaction. NMJs consistently revealed significant (P 0.05) mai...

The aim of this study was to identify differences in knee range of motion (ROM), movement speed, ground reaction forces (GRF) profile, neuromuscular activity, and muscle coactivation during the transition between stair descent and level walking in meniscectomized patients at high risk of knee osteoarthritis (OA) compared with the nonoperated leg and with healthy controls.

The objective of this study was to investigate premotor modulation of motor cortical excitability between rhythmic unimanual finger contractions. Applying TMS at rest prior to an anticipated contraction provides a measure of cortical excitability that reflects premotor modulatory drive and is uncontaminated by the alterations in spinal and cortical excitability that occur during muscle activation. We hypothesized that premotor structures contribute to unimanual movement through the modulation of intracortical and interhemispheric inhibitory circuits within the primary motor cortex and that this premotor modulation would be evident at rest between contractions. Thus, we used transcranial magnetic stimulation (TMS) to assess short interval intracortical inhibition (SICI) and interhemispheric inhibition (IHI) in a 500-ms epoch prior to a planned contraction of the right FDI in 10 participants (21.4±1.9 years). These measures of inhibition were made in three different states: (1) at complete rest (with no plan to contract), (2) at rest between rhythmic contractions, and (3) during low level contractions. Cortical excitability was enhanced prior to a contraction and during a contraction compared to at rest (F?,??=758.3, pIHI was also increased prior to a contraction compared to at rest and during a contraction while SICI was only reduced during a contraction (F?,??=30.3, p<0.001).We used this pre-contraction protocol to investigate the cortical mechanisms of unimanual control. However, this protocol would be a useful tool to investigate any neuromuscular adaptation that may occur as a result of altered premotor modulation of cortical excitability, such as neuromuscular fatigue, training and movement disorders. PMID:22850557

Background? Motility and functional gastrointestinal disorders have high prevalence in the community, cause significant morbidity, and represent a major health care burden. Despite major advances in our understanding of the cellular and molecular basis of gastrointestinal neuromuscular functions, many of these diseases still defy mechanistic explanations. The biopsychosocial model underlying the current classification of functional gastrointestinal disorders recognizes and integrates the pathogenetic role of genetic, environmental, and psychosocial factors but has not been associated with specific molecular mechanisms. Purpose? Here, we propose that this integrative function is encoded in the chromatin, composed of the DNA and associated histone and non-histone proteins and non-coding RNA. By establishing epigenetically heritable 'molecular memories' of past stimuli including environmental challenges, the chromatin determines an individual's responses to future insults and translates them into high-order outputs such as symptoms and illness behavior. Thus, surveying epigenetic signatures throughout the genome of affected cells in individual patients may make it possible to better understand and ultimately control the phenomena described by the biopsychosocial model. In this review, we provide a high-level but comprehensive description of the concepts and mechanisms underlying epigenetics and chromatin dynamics, describe the mechanisms whereby the environment can alter the epigenome and identify aspects of functional gastrointestinal and motility disorders where epigenetic mechanisms are most likely to play important roles. PMID:23095056

Since normative surface EMG (SEMG) values for muscles acting at the knee joint are available for people with haemophilia, increasing interest is noticeable for other joints affected by haemophilic arthropathy. Adequate activity of shank muscles is an important key for appropriate postural control. The aim of this study was to determine differences in muscle activation patterns of lower leg muscles between people with and without haemophilia during upright standing. SEMG of tibialis anterior (TA), fibularis longus (FL), lateral (LG) and medial (MG) heads of gastrocnemius, and soleus (SO) muscles of both sides were recorded in 25 haemophilic patients (H) and 25 non-haemophilic control subjects (C) while standing on even ground. The Gilbert-Score was used to assign sides to major (H-MA) and minor (H-MI) affected ankle joints in H. To normalize the SEMG amplitudes, amplitude ratios (percentage of cumulated activity) were calculated. Compared to controls, TA ratios showed higher and MG reduced levels in both H groups (P < 0.01). In the H-MA subgroup of H, FL also joined the TA behaviour whereas SO had similar activation direction as MG. Although possible descending influences from the knee joints cannot be excluded, this can be interpreted as a compensational mechanism due to the severity of the orthopaedic status of the ankle, which with increasing heaviness is accompanied by reduced plantar flexion capability. However, ankle joint integrity appears to be reduced in H, with TA and MG seeming to play key roles for neuromuscular control of upright posture. PMID:22642532

Wing damage is common in flying insects and has been studied using a variety of approaches to assess its biomechanical and fitness consequences. Results of these studies range from strong to nil effect among the variety of species, fitness measurements and damage modes studied, suggesting that not all damage modes are equal and that insects may be well adapted to compensate for some types of damage. Here, we examine the biomechanical and neuromuscular means by which flying insects compensate for asymmetric wing damage, which is expected to produce asymmetric flight forces and torques and thus destabilize the animal in addition to reducing its total wing size. We measured the kinematic and neuromuscular responses of hawkmoths (Manduca sexta) hovering in free flight with asymmetrically damaged wings via high-speed videography and extracellular neuromuscular activity recordings. The animals responded to asymmetric wing damage with asymmetric changes to wing stroke amplitude sufficient to restore symmetry in lift production. These asymmetries in stroke amplitude were significantly correlated with bilateral asymmetries in the timing of activation of the dorsal ventral muscle among and within trials. Correspondingly, the magnitude of wing asymmetry was significantly, although non-linearly, correlated with the magnitude of the neuromuscular response among individuals. The strongly non-linear nature of the relationship suggests that active neural compensation for asymmetric wing damage may only be necessary above a threshold (>12% asymmetry in wing second moment of area in this case) below which passive mechanisms may be adequate to maintain flight stability. PMID:22771747

The dynamic behavior of a neuromusculoskeletal system results from the complex mechanical interaction between muscle visco-elasticity resulting from (co-)contraction and afferent feedback from muscle spindles and Golgi tendon organs. As a result of the multiple interactions the individual effect of each of the structures to the overall dynamics is hard to recognize, if not impossible. Here a neuromuscular control (NMC) model is developed to analyze the functional contribution of the various physiological structures on the mechanical behavior of a limb. The dynamics of a joint are presented in admittances, i.e. the dynamic relation between input force (or torque) and the output displacement, which can be represented by either frequency or impulse response functions. With the model it can be shown that afferent feedback reduces, while muscle visco-elasticity increases, the stability margins. This implicates that there is a delicate balance between muscle co-contraction and afferent feedback, which depends on the joint specific physiological properties. The main application of the model is educational; it is implemented in a graphical user interface allowing users to explore the role of the various physiological structures on joint dynamics. Other applications of the model are more experimental, e.g. to elucidate experimentally measured admittances and to compare the quantified parameter values with the theoretically optimal ones. It is concluded that the NMC model is a useful and intuitive tool to investigate human motor control, in a theoretical as well as an experimental way. PMID:18457842

Abstract in portuguese JUSTIFICATIVA E OBJETIVOS: Uma das mais importantes propriedades dos bloqueadores neuromusculares é o rápido início de ação, possibilitando intubação traqueal precoce. A administração de pequena dose de bloqueador não-despolarizante antes da dose plena é sabidamente redutora da latência da maioria dos bloqueadores neuromusculares utilizados. O brometo de pipecurônio é um agente aminoesteróide de longa duração com grande estabilidade cardiovascular, porém (more) , com início de ação tardio. O objetivo desse estudo foi avaliar o efeito do priming do pipecurônio em pacientes adultos submetidos a cirurgias eletivas sob anestesia geral. MÉTODO: Foram estudados 33 pacientes adultos de ambos os sexos, com idade entre 20 e 65 anos, estado físico ASA I ou II, submetidos a cirurgias eletivas sob anestesia geral. Foram excluídos do estudo pacientes com insuficiência renal ou hepática, neuromiopatia, uso concomitante de drogas que influenciem a sua farmacocinética ou pacientes com histórico familiar de hipertermia maligna. Foram divididos em dois grupos: Grupo 1 onde foi utilizado o priming com 0,01 mg.kg-1 e três minutos depois completada a dose de 0,08 mg.kg-1 e o Grupo 2, sem dose priming (Grupo Controle). O relaxamento neuromuscular foi controlado pela aceleromiografia (Aparelho TOF-Guard) e no momento em que T1 Abstract in spanish JUSTIFICATIVA Y OBJETIVOS: Una de las más importantes propiedades de los bloqueadores neuromusculares es el rápido inicio de acción, posibilitando intubación orotraqueal precoz. La administración de pequeña dosis del bloqueador no despolarizante antes de la dosis completa es consabidamente reductora de la latencia de la mayoría de los bloqueadores neuromusculares utilizados. El bromuro de pipecuronio es un agente aminoesteroide de larga duración con grande estabil (more) idad cardiovascular, sin embargo, con inicio de acción tardía. El objetivo de ese estudio es evaluar el efecto del priming del pipecuronio en pacientes adultos sometidos a cirugías electivas bajo anestesia general. MÉTODO: Fueron estudiados 32 pacientes adultos de ambos sexos, con edad entre 20 y 65 años, estado físico ASA I ó II, a ser sometidos a cirugías electivas bajo anestesia general. Fueron excluidos del estudio pacientes con insuficiencia renal o hepática, neuromiopatia, uso concomitante de drogas que influencien la farmacocinética de la droga o pacientes con histórico familiar de hipertermia maligna. Fueron divididos en dos grupos: Grupo 1 donde fue utilizada el priming con 0,01 mg.kg-1 3 minutos después de completada la dosis de 0,08 mg.kg-1 y el Grupo 2, sin dosis priming (Grupo Control). El relajamiento neuromuscular fue controlado por la aceleromiografía (Aparato TOF-Guard) y en el momento en que T1 Abstract in english BACKGROUND AND OBJECTIVES: One of the most important neuromuscular blockers property is short onset, allowing early tracheal intubation. Low nondepolarizing blocker dose before the full dose is known to decrease the onset of most neuromuscular blockers. Pipecuronium bromide is a long-lasting aminosteroid with major cardiovascular stability, however, with late onset. This study aimed at evaluating pipecuronium priming effect in adult patients submitted to elective surgerie (more) s under general anesthesia. METHODS: Participated in this study 33 adult patients of both genders, aged 20 to 65 years, physical status ASA I or II, to be submitted to elective surgeries under general anesthesia. Exclusion criteria were patients with kidney or liver failure, neuromuscular diseases, in concurrent use of drugs influencing pipecuronium pharmacokinetics, and patients with family history of malignant hyperthermia. Patients were divided in 2 groups: Group 1 = priming with 0.01 mg.kg-1 and 3 minutes later the remaining 0.07 mg.kg-1 (total 0.08 mg.kg-1); Group 2 = no priming dose (group control). Neuromuscular relaxation was controlled by acceleromyography (TOF-Guard device) and laryngoscopy was accomplished when T1

General anesthesia has been in use for ophthalmic surgery since 1847. The subsequent predominance of local anesthetic techniques made ophthalmic anesthesia the "Cinderella of anesthesia services" until its clinical and scientific rehabilitation in the second half of this century. Precise control of intraocular tension is an accepted advantage of general anesthesia. The exercise of such control requires understanding of intraocular physiology and the effects exerted by anesthetic techniques. Hence, the impact of anesthetic drugs on intraocular pressure (IOP) must be considered when ophthalmic surgery is to be carried out under general anesthesia. Intravenous anesthetics and volatile agents reduce IOP, with the possible exception of ketamine. Underlying mechanisms include a direct effect on cerebral IOP control centers and indirect effects mediated through the balance between production and drainage of aqueous humor, general circulation and ocular muscle tone. IOP is likely to be elevated during induction and recovery. Currently suggested measures to prevent the increase in IOP associated with laryngoscopic tracheal intubation facilitated by succinylcholine include oral premedication with clonidine, intravenous administration of lidocaine 3 min prior to laryngoscopy, and anesthetic induction with propofol or narcotics. Non depolarizing neuromuscular blocking drugs either do not affect IOP or produce a slight decrease; depolarizing muscle relaxants increase IOP. It remains controversial whether this effect, which is pronounced with succinylcholine, may be reliably abolished by any concomitant medication. The new competitive relaxants atracurium and vecuronium provide stable conditions with respect to IOP and systemic circulation, combined with a rapid onset and intermediate duration of action. PMID:3052165

Dp116 is a non-muscle isoform of dystrophin that assembles the dystrophin-glycoprotein complex (DGC), but lacks actin-binding domains. To examine the functional role of the DGC, we expressed the Dp116 transgene in mice lacking both dystrophin and utrophin (mdx:utrn(-/-)). Unexpectedly, expression of Dp116 prevented the most severe aspects of the mdx:utrn(-/-) phenotype. Dp116:mdx:utrn(-/-) transgenic mice had dramatic improvements in growth, mobility and lifespan compared with controls. This was associated with increased muscle mass and force generating capacity of limb muscles, although myofiber size and specific force were unchanged. Conversely, Dp116 had no effect on dystrophic injury as determined by muscle histopathology and serum creatine kinase levels. Dp116 also failed to restore normal fiber-type distribution or the post-synaptic architecture of the neuromuscular junction. These data demonstrate that the DGC is critical for growth and maintenance of muscle mass, a function that is independent of the ability to prevent dystrophic pathophysiology. Likewise, this is the first demonstration in skeletal muscle of a positive functional role for a dystrophin protein that lacks actin-binding domains. We conclude that both mechanical and non-mechanical functions of dystrophin are important for its role in skeletal muscle. PMID:21949353

Since previous numbers-needed-to-treat (NNT) and relative risk reduction (RRR) report, a few studies were published to evaluate prophylactic effectiveness of neuromuscular training for anterior cruciate ligament (ACL) injury in female athletes. The purpose of the current analyses was to determine the effectiveness of neuromuscular training interventions in reducing both non-contact and overall ACL injury risk in female athletes through RRR and NNT. The keywords 'knee', 'anterior cruciate ligament', 'ACL', 'prospective', 'neuromuscular', 'training', 'female' and 'prevention' were searched to find studies published from 1995 to 2011 in PubMed and EBSCO (CINAHL, Health source, MEDLINE and SPORT Discus). Inclusion criteria required that relevant studies: recruited physically active young girls as subjects, documented the number of ACL injuries, employed a neuromuscular training intervention, and used a prospective controlled study design. The numbers of non-contact and overall ACL injuries, subjects and observation time period were used to calculate RRR and NNT for each study. A total of 12 studies met the inclusion criteria. There was a 73.4% (95% CI 62.5% to 81.1%) and 43.8% (95% CI 28.9% to 55.5%) of RRR for non-contact and overall ACL injuries. From the NNT analysis, it was determined that, respectively, 108 (95% CI 86 to 150) and 120 (95% CI 74 to 316) individuals would need to be trained to prevent one non-contact or one overall ACL injury over the course of one competitive season. Although the RRR analysis indicated prophylactic benefits of neuromuscular training, the relatively large NNT indicated that many athletes are needed to prevent one ACL injury. A future direction to reduce NNT and improve the efficiency of ACL injury-prevention strategies is to develop a screening system for identifying at-risk athletes. PMID:22745221

Management of the patient who refuses blood products based on religious grounds poses ethical and clinical challenges, especially when the degree of anemia becomes life-threatening. In this report, we present the case of a 52-year-old Jehovah's Witness with sickle cell disease in whom he and his family refused blood products for the treatment of severe anemia associated with profound and progressive acidosis, acute oliguric renal failure, and hemodynamic instability. Attempts carried out during the first 3 hospital days to stabilize the patient using standard therapies to support oxygen delivery as well as the use of sedation, pain control, temperature control, neuromuscular blockade, and mechanical ventilation to reduce oxygen demand were not successful. Thus, because oxygen consumption by the brain represents approximately 20 per cent of the body's oxygen needs, and pentobarbital's primary action is as a central nervous system depressant, the induction of pentobarbital coma was instituted to reduce cerebral oxygen consumption. The institution of pentobarbital on hospital Day 3 was sufficient to acutely stabilize the patient's deteriorating metabolic state and ultimately was associated with survival. Thus, we conclude that there is a potential role for barbiturate coma in Jehovah's Witness patients who refuse blood transfusions and dying of anemia when other modalities of support are not sufficient. PMID:19999907

CT-documentation of skeletal muscular lesions caused by neuromuscular diseases implies an essential contribution to conventional techniques in the macroscopic field. Size, distribution and degree of lesions as well as compensatory mechanisms are proved thereby. We report about the different effects on muscle appearance referring to 106 patients of our own experience in amyotrophic lateral sclerosis, spinal muscular atrophy, poliomyelitis, polyradiculitis, polyneuropathy as well as peripheral traumatic nerve lesions.

Abstract in portuguese JUSTIFICATIVA E OBJETIVOS: Freqüentemente em cirurgias abdominais, na fase de fechamento da parede, há necessidade de doses adicionais de bloqueador neuromuscular. O objetivo deste estudo foi analisar, na vigência de recuperação parcial do bloqueio neuromuscular induzido pelo pancurônio, o efeito da administração de dose complementar de atracúrio sobre a recuperação espontânea do bloqueio neuromuscular. MÉTODO: Foram estudados 30 pacientes, divididos em dois (more) grupos, 14 pacientes formaram o grupo pancurônio e 16 pacientes, o grupo atracúrio. A função neuromuscular foi monitorizada de forma contínua por acelerometria do músculo adutor do polegar, utilizando a seqüência de quatro estímulos (SQE), através da estimulação supramáxima do nervo ulnar. A indução da anestesia foi feita com propofol, fentanil, pancurônio 0,08 mg.kg-1 e a manutenção com N2O 60% em oxigênio e isoflurano na concentração expirada de 0,5%. Quando a primeira contração da seqüência de quatro estímulos (T1) recuperou 25%, o grupo pancurônio recebeu pancurônio 0,025 mg.kg-1 e o grupo atracúrio, 0,20 mg.kg-1 de atracúrio. Após a dose complementar foram anotados os tempos para recuperação espontânea de T1 igual a 10%, 25%, 75%, do índice de recuperação (IR25-75%) e da relação T4/T1 igual a 0,8. RESULTADOS: Os tempos de recuperação espontânea após dose complementar de pancurônio ou atracúrio não diferiram quando avaliados pela recuperação de T1 em 10% (45,00 ± 15,50 vs 49,69 ± 9,41), 25% (61,64 ± 18,58 vs 64,25 ± 12,51) e 75% (94,00 ± 28,52 vs 84,69 ± 16,50). O IR25-75% (32,36 ± 13,76 vs 20,44 ± 9,24) e o tempo de recuperação da relação T4/T1 = 0,8 (176,86 ± 29,57 vs 141,50 ± 29,57) foram menores no grupo do atracúrio. CONCLUSÕES: Nas condições deste estudo, a complementação com atracúrio não promoveu alteração na recuperação espontânea inicial do bloqueio neuromuscular induzido pelo pancurônio e promoveu diminuição de 20% no tempo de recuperação total. Abstract in spanish JUSTIFICATIVA Y OBJETIVOS: Frecuentemente en cirugías abdominales, en la fase de cerramiento de la pared, hay necesidad de dosis adicionales de bloqueador neuromuscular. El objetivo de este estudio fue analizar, en la vigencia de recuperación parcial del bloqueo neuromuscular inducido por el pancuronio, el efecto de la administración de dosis complementares de atracúrio sobre la recuperación espontanea del bloqueo neuromuscular. MÉTODO: Fueron estudiados 30 paciente (more) s, divididos en dos grupos, 14 pacientes formaron el grupo pancuronio y 16 pacientes, el grupo atracúrio. La función neuromuscular fue monitorizada de forma continua por acelerometria del músculo aductor del pulgar, utilizando la secuencia de cuatro estímulos (SQE), a través de la estimulación supramáxima del nervio ulnar. La inducción de la anestesia fue hecha con propofol, fentanil, pancuronio 0,08 mg.kg-1 y la manutención con N2O 60% en oxígeno e isoflurano en la concentración expirada de 0,5%. Cuando la primera contracción de la secuencia de cuatro estímulos (T1) recuperó 25%, el grupo pancuronio recibió pancuronio 0,025 mg.kg-1 y el grupo atracúrio, 0,20 mg.kg-1 de atracúrio. Después de la dosis complementar fueron anotados los tiempos para recuperación espontanea de T1 igual a 10%, 25%, 75%, del índice de recuperación (IR25-75%) y de la relación T4/T1 igual a 0,8. RESULTADOS: Los tiempos de recuperación espontanea después de la dosis complementar de pancuronio o atracúrio no divergieron cuando evaluados por la recuperación de T1 en 10% (45,00 ± 15,50 vs 49,69 ± 9,41), 25% (61,64 ± 18,58 vs 64,25 ± 12,51) y 75% (94,00 ± 28,52 vs 84,69 ± 16,50). El IR25-75% (32,36 ± 13,76 vs 20,44 ± 9,24) y el tiempo de recuperación de la relación T4/T1 = 0,8 (176,86 ± 29,57 vs 141,50 ± 29,57) fueron mayores en el grupo en que la complementación fue realizada con pancuronio. CONCLUSIONES: En las condiciones de este estudio, la complementación con atracúrio no promovió alteración en la recuperación espontanea inicial del bloqueo neuromuscular inducido por el pancuronio y promovió diminución de 20% en el tiempo de recuperación total. Abstract in english BACKGROUND AND OBJECTIVES: Additional neuromuscular blocker doses are in general needed during wall closing after abdominal surgeries. This study aimed at determining during partial pancuronium-induced neuromuscular block recovery, the effect of additional atracurium dose on spontaneous neuromuscular block recovery. METHODS: Participated in this study 30 patients divided in two groups: pancuronium group (n = 14) and atracurium group (n = 16). Neuromuscular function was co (more) ntinuously monitored by accelerometry of abductor pollicis muscle using TOF to supramaximally stimulate ulnar nerve. Anesthesia was induced with propofol, fentanyl and 0.08 mg.kg-1 pancuronium, and was maintained with 60% N2O in oxygen and 0.5% isoflurane expired concentration. When T1 returned to 25% of control, 0.025 mg.kg-1 pancuronium or 0.20 mg.kg-1 atracurium were administered to pancuronium or atracurium group, respectively. Time for spontaneous T1 recovery = 10%, 25%, 75% of recovery index (RI 25-75%) and time to T4/T1 equal 0.8 after complementary dose, were recorded. RESULTS: There were no differences between groups on T1 spontaneous recovery to 10% (45.00 ± 15.50 vs. 49.69 ± 9.41), 25% (61.64 ± 18.58 vs. 64.25 ± 12.51) and 75% (94.00 ± 28.52 vs. 84.69 ± 16.50). Recovery index (RI 25-75%) and time to T4/T1= 0.8 were shorter in the atracurium group. CONCLUSIONS: In this study, atracurium complementation has made no difference in initial spontaneous recovery of pancuronium-induced neuromuscular block, but has decreased total recovery time in 20%.

Background Gowers? sign is a screening test for muscle weakness, typically seen in Duchenne muscular dystrophy but also seen in numerous other conditions. The mildest presentations and the variations of Gowers? sign are poorly described in the literature but are important to recognize to help with early diagnosis of a neuromuscular problem. Questions/purposes We therefore (1) defined the characteristics of the mildest forms and the compensatory mechanism used, (2) categorized the spectrum of this sign as seen in various neuromuscular diseases, and (3) provide educational videos for clinicians. Methods We videotaped 33 patients with Gowers? sign and three healthy children. Weakness was categorized as: mild?=?prolonged or rise using single-hand action; moderate?=?forming prone crawl position...

It is well established that female athletes are at increased risk for sustaining ACL injuries in sports, where sudden changes of direction are a frequent movement pattern. The underlying neuromuscular mechanisms related to the elevated ACL injury rate in female athletes has yet to be fully investigated. This cross-sectional study aimed to examine gender differences in neuromuscular pre-activity during a maneuver that mimics a movement associated with the incidence of ACL injuries. Twenty-four team handball players (12 male and 12 female) with no history of ACL injury were tested for EMG pre-activity of vastus lateralis, vastus medialis, semitendinosus, and biceps femoris during a side-cutting maneuver. Mean EMG amplitude 50 ms prior to toe down was normalized to maximal EMG obtained during...

Duchenne muscular dystrophy (DMD) is an incurable, rapidly-worsening neuromuscular degenerative disease caused by the absence of dystrophin. In skeletal muscle, lack of dystrophin disrupts the recruitment of neuronal nitric oxide synthase (nNOS) to the sarcolemma thus affecting nitric oxide (NO) production. Utrophin is a dystrophin homolog whose expression is greatly upregulated in the sarcolemma of dystrophin-negative fibers from mdx mice, a mouse model of DMD. Although cardiomyopathy is an important cause of death, little is known about the NO signaling pathway in cardiac muscle of DMD patients. Thus, we used cardiomyocytes and hearts from two month-old mdx and mdx:utrophin (-/-) double knockout mice (mdx:utr) to study key steps in NO signaling: L-arginine transporters, NOS, and soluble guanylyl cyclase (sGC). nNOS did not co-localize with dystrophin or utrophin to the cardiomyocyte membrane. Despite this, nNOS activity was markedly decreased in both mdx and mdx:utr mice while nNOS expression was only decreased in mdx:utr hearts, suggesting that utrophin upregulation in cardiomyocytes maintains nNOS levels but not function. sGC protein levels and activity remained at control levels. Unexpectedly, L-arginine transporter expression and function were significantly increased, suggesting a novel biochemical compensatory mechanism of the NO pathway and a potential entry site for therapeutics. PMID:23009292

Interventions for strengthening intrinsic foot muscles may be beneficial for rehabilitation from overuse injuries. In this study the acute effects of high-frequency, low-intensity wide-pulse electrical stimulation (WPS) over an intrinsic muscle on subsequent foot function during walking was assessed in healthy participants. WPS was delivered to the m. abductor hallucis (m.AH) of the non-dominant foot during relaxed standing. 3-dimensional forefoot (FF) - rearfoot (RF) coordination was quantified with a vector coding technique within separate periods of the stance phase to study WPS functional effects on foot motion. 4 types of coordinative strategies between the FF and RF were interpreted and compared PRE-to-POST-WPS for both the experimental and control feet. Bilateral electromyography (EMG) from m.AH was analysed during the intervention period for evidence of acute neuromuscular adaptation. The results showed that WPS significantly modulated FF-RF coordination during mid-stance, indicative of a more stable foot. Specifically, a statistically significant increase in FF eversion with concomitant RF inversion in the frontal plane and RF-dominated adduction in the transverse plane was observed. Subject-specific increases in post-stimulus m.AH EMG activation were observed but this was not reflected in an overall group effect. It is concluded that the structural integrity of the foot during walking is enhanced following an acute session of WPS and that this mechanical effect is most likely due to stimulation induced post-tetanic potentiation of synaptic transmission. PMID:23059559

Altered RNA processing is an underlying mechanism of amyotrophic lateral sclerosis (ALS). Missense mutations in a number of genes involved in RNA function and metabolisms are associated with ALS. Among these genes is angiogenin (ANG), the fifth member of the vertebrate-specific, secreted ribonuclease superfamily. ANG is an angiogenic ribonuclease, and both its angiogenic and ribonucleolytic activities are important for motor neuron health. Ribonuclease 4 (RNASE4), the fourth member of this superfamily, shares the same promoters with ANG and is co-expressed with ANG. However, the biological role of RNASE4 is unknown. To determine whether RNASE4 is involved in ALS pathogenesis, we sequenced the coding region of RNASE4 in ALS and control subjects and characterized the angiogenic, neurogenic, and neuroprotective activities of RNASE4 protein. We identified an allelic association of SNP rs3748338 with ALS and demonstrated that RNASE4 protein is able to induce angiogenesis in in vitro, ex vivo, and in vivo assays. RNASE4 also induces neural differentiation of P19 mouse embryonal carcinoma cells and mouse embryonic stem cells. Moreover, RNASE4 not only stimulates the formation of neurofilaments from mouse embryonic cortical neurons, but also protects hypothermia-induced degeneration. Importantly, systemic treatment with RNASE4 protein slowed weight loss and enhanced neuromuscular function of SOD1 ( G93A ) mice. PMID:23143660

This study measures standing stability of four individuals with paraplegia using knee-ankle-foot orthoses (KAFOs) with a center-of-force monitoring platform as compared with similar data from 10 neurologically healthy subjects. Both groups were compared under conditions of quiet standing with eyes open and closed and with hands on and off parallel bars. Individuals with paraplegia were also tested under similar conditions with the ankles of their KAFOs mechanically unlocked and with bilateral functional neuromuscular stimulation of the quadriceps muscles. Sway path, mean amplitude, and mean frequency were measured for each subject. We found that postural stability in paraplegic individuals using KAFOs compared favorably with the control group under conditions of eyes open and closed with hands on parallel bars; however, visual information was much more important for paraplegic individuals during quiet stance. Unlocking the ankles of the KAFOs resulted in an increase in swap path and mean frequency. Functional muscular stimulation of the quadriceps muscles resulted in standing stability slightly less than with KAFOs. Although KAFOs may not be the ideal assistive device for various reasons, postural stability appears reasonable, and other proposed orthoses must be comparable in order to be considered as an alternative. PMID:3754129

Understanding the biological activity profile of the snake venom components is fundamental for improving the treatment of snakebite envenomings and may also contribute for the development of new potential therapeutic agents. In this work, we tested the effects of BthTX-I, a Lys49 PLA(2) homolog from the Bothrops jararacussu snake venom. While this toxin induces conspicuous myonecrosis by a catalytically independent mechanism, a series of in vitro studies support the hypothesis that BthTX-I might also exert a neuromuscular blocking activity due to its ability to alter the integrity of muscle cell membranes. To gain insight into the mechanisms of this inhibitory neuromuscular effect, for the first time, the influence of BthTX-I on nerve-evoked ACh release was directly quantified by radiochemical and real-time video-microscopy methods. Our results show that the neuromuscular blockade produced by in vitro exposure to BthTX-I (1 ?M) results from the summation of both pre- and postsynaptic effects. Modifications affecting the presynaptic apparatus were revealed by the significant reduction of nerve-evoked [(3)H]-ACh release; real-time measurements of transmitter exocytosis using the FM4-64 fluorescent dye fully supported radiochemical data. The postsynaptic effect of BthTX-I was characterized by typical histological alterations in the architecture of skeletal muscle fibers, increase in the outflow of the intracellular lactate dehydrogenase enzyme and progressive depolarization of the muscle resting membrane potential. In conclusion, these findings suggest that the neuromuscular blockade produced by BthTX-I results from transient depolarization of skeletal muscle fibers, consequent to its general membrane-destabilizing effect, and subsequent decrease of evoked ACh release from motor nerve terminals. PMID:23142504

Amidated neuropeptides of the FMRFamide class regulate numerous physiological processes including synaptic efficacy at the Drosophila neuromuscular junction (NMJ). We demonstrate here that mutations in wishful thinking (wit) a gene encoding a Drosophila Bmp type 2 receptor that is required for proper neurotransmitter release at the neuromuscular junction, also eliminates expression of FMRFa in that subset of neuroendocrine cells (Tv neurons) which provide the systemic supply of FMRFa peptides. We show that Gbb, a Bmp ligand expressed in the neurohemal organ provides a retrograde signal that helps specify the peptidergic phenotype of the Tv neurons. Finally, we show that supplying FMRFa in neurosecretory cells partially rescues the wit lethal phenotype without rescuing the primary morphological or electrophysiological defects of wit mutants. We propose that Wit and Gbb globally regulate NMJ function by controlling both the growth and transmitter release properties of the synapse as well as the expression of systemic modulators of NMJ synaptic activity. PMID:14507784

The ontogenetic cycle of the barnacle Balanus amphitrite (=Amphibalanus amphitrite) (Darwin, 1854) includes a cyprid that binds submerged surfaces, metamorphosing into a sessile adult. g-Aminobutyric acid (GABA) and GABA receptors have recently been located in its cyprid with a similar pattern to other crustaceans. Since NMDA R1 ionotropic glutamatergic receptors have been identified in crustacean neuromuscular junctions, we have investigated their presence in the B. amphitrite cyprid. The presence of NMDA R1 receptors might indicate a role for glutamate in neuromuscular control in B. amphitrite cyprids, therefore we studied the presence and distribution of the NMDA R1 by immunohistochemistry. Its distribution was observed in the peripheral nervous system and in non-neuronal elements. Actu...

Purpose Many patients with respiratory failure related to neuromuscular disease receive chronic invasive ventilation through a tracheostomy. Improving quality of life, of which speech is an important component, is a major goal in these patients. We compared the effects on breathing and speech of low-level positive end-expiratory pressure (PEEP, 5?cmH2O) and of a Passy-Muir speaking valve (PMV) during assist-control ventilation. Methods We studied ten patients with neuromuscular disorders, between December 2008 and April 2009. Flow was measured using a pneumotachograph. Microphone speech recordings were subjected to both quantitative measurements and qualitative assessments; the latter consisted of both an intelligibility score (using a French adaptation of the Frenchay Dysarthria Assessmen...

The study design is retrospective. The aim is to describe our experience about the treatment of patients with neuromuscular scoliosis (NMS) using Cotrel???Dubousset instrumentation. Neuromuscular scoliosis are difficult deformities to treat. A careful assessment and an understanding of the primary disease and its prognosis are essential for planning treatment which is aimed at maximizing function. These patients may have pelvic obliquity, dislocation of the hip, limited balance or ability to sit, back pain, and, in some cases, a serious decrease in pulmonary function. Spinal deformity is difficult to control with a brace, and it may progress even after skeletal maturity has been reached. Surgery is the main stay of treatment for selected patients. The goals of surgery are to correct the de...

Purpose: The purpose of this study was to investigate the alteration of pain-induced neuromuscular trunk responses by expectations in healthy volunteers. Methods: Twenty-three asymptomatic participants performed series of flexion-extension movements in 3 different experimental conditions: innocuous heat stimulation (control) and noxious heat stimulation associated with expectations of low or high pain intensity. These stimuli were administered by a contact thermode placed over the lumbar region (L4 and L5) to assess the modulation of neuromuscular responses and kinematics during the flexion-extension task. Surface electromyography (EMG) of lumbar erector spinae at L2 and L3 and L4 and L5 as well as lumbopelvic kinematic variables were compared across conditions. Results: Noxious stimulatio...

The ontogenetic cycle of the barnacle Balanus amphitrite (=Amphibalanus amphitrite) (Darwin, 1854) includes a cyprid that binds submerged surfaces, metamorphosing into a sessile adult. ?-Aminobutyric acid (GABA) and GABA receptors have recently been located in its cyprid with a similar pattern to other crustaceans. Since NMDA R1 ionotropic glutamatergic receptors have been identified in crustacean neuromuscular junctions, we have investigated their presence in the B. amphitrite cyprid. The presence of NMDA R1 receptors might indicate a role for glutamate in neuromuscular control in B. amphitrite cyprids, therefore we studied the presence and distribution of the NMDA R1 by immunohistochemistry. Its distribution was observed in the peripheral nervous system and in non-neuronal elements. Actually, NMDA R1 immunoreactivity was detected in thoracic appendages, at the level of neuromuscular junctions, thus suggesting an involvement in motor control functions, as already demonstrated in other crustaceans. Immunoreactivity was also detected in ommatidia cells of the eye, in antennules, and in epidermal cells. The distribution pattern comparable to that of GABAergic molecules could indicate an interrelated agonistic/antagonistic role for these two systems, which could be considered as potential targets of combined antifouling strategies. PMID:20851741

Abstract in portuguese OBJETIVO: O objetivo desse estudo foi verificar o potencial da eletromiografia (EMG) de superfície para a avaliação da eficiência neuromuscular e da fadiga muscular localizada dos extensores lombares em indivíduos com escoliose. MÉTODOS: Participaram deste estudo 20 indivíduos divididos igualmente em dois grupos, (1) Grupo com Escoliose e (2) Grupo Controle, que foram submetidos a um teste de indução dos músculos extensores lombares a fadiga, o qual constituiu d (more) a realização de uma contração voluntária máxima isométrica (CVM), e realização de um teste com esforço a 80% da CVM. Foram coletados simultaneamente sinais de força e eletromiográficos (sinal EMG). O sinal EMG foi processado no domínio da freqüência, utilizando-se a transformada rápida de Fourier (FFT), por meio da mediana da freqüência (MF), e no domínio do tempo, pelo cálculo do valor root mean square (RMS). Os dados foram submetidos a uma análise de variância one-way para verificar as diferenças entre os dois grupos. Para verificar a simetria entre os lados direito e esquerdo, foi realizado o teste t pareado. O nível de significância adotado foi 0,05. RESULTADOS: os resultados demonstraram que indivíduos com escoliose apresentaram: (1) simetria de ativação neuromuscular entre os lados; (2) menor eficiência neuromuscular; (3) maior capacidade de resistir a fadiga; e (4) valores de força 42,6% menores que os indivíduos do GC. CONCLUSÕES: Os resultados sugerem que a EMG de superfície corresponde a um efetivo instrumento de avaliação funcional da escoliose, embora o protocolo estabelecido tenha limitado a participação dos indivíduos com escoliose, do ponto de vista da eficiência neuromuscular. Abstract in english OBJECTIVE: The aim of this study was to investigate the potential of surface electromyography (EMG) for assessing neuromuscular efficiency and localized muscle fatigue in the lumbar extensors, in individuals with scoliosis. METHODS: Twenty individuals participated in this study, divided equally into two groups: (1) Scoliosis Group and (2) Control Group. These subjects underwent a fatigue induction test on their lumbar extensor muscles, consisting of one maximum voluntary (more) isometric contraction (MVIC) followed by a test at 80% of the MVIC effort. Force and EMG signals were collected simultaneously. The EMG signal was processed in the frequency domain by means of fast Fourier transforms using the median frequency; and in the time domain by calculating the root mean square value. The data were analyzed by means of one-way analysis of variance to investigate the differences between the two groups. Paired t test was used to investigate the symmetry between the right and left sides. The significance level adopted was 0.05. RESULTS: The results showed that the individuals with scoliosis presented: (1) symmetrical neuromuscular activation between the sides; (2) lower neuromuscular efficiency; (3) greater capacity to resist fatigue; and (4) force values 42.6% lower than those of the individuals in the Control Group. CONCLUSIONS: The results suggest that surface EMG is an effective tool for functional assessments of scoliosis, although the protocol established limited the participation of individuals with scoliosis, from the perspective of neuromuscular efficiency.

Abstract in portuguese JUSTIFICATIVA E OBJETIVOS: Existem poucos estudos epidemiológicos em ventilação mecânica. O objetivo deste estudo foi demonstrar como a ventilação mecânica vem sendo realizada nas UTI brasileiras. MÉTODO: O estudo foi realizado com prevalência de um dia em 40 UTI, com 390 pacientes internados, sendo 217 em ventilação mecânica. Os resultados medidos foram a caracterização dos pacientes ventilados, sua distribuição pelo Brasil, as causas da ventilação mec? (more) ?nica, os principais modos ventilatórios usados, os parâmetros ventilatórios mais importantes e a fase de desmame da ventilação mecânica. RESULTADOS: As medianas da idade dos pacientes ventilados, do escore APACHE II, e do tempo de ventilação mecânica foram, respectivamente, de 66 anos, 20 pontos e 11 dias. A ventilação mecânica foi determinada pela insuficiência respiratória aguda (IRA) em 71% dos pacientes, o coma em 21,2%, a doença pulmonar obstrutiva crônica em 5,5% e a doença neuromuscular em 2,3%. A ventilação controlada a volume (VCV) (30%), a ventilação com pressão de suporte (PSV) (29,5%) e a ventilação controlada à pressão (PCV) (18%) foram as mais utilizadas, sendo que no desmame predominou a PSV (63,5%). A mediana do volume corrente foi maior nos pacientes em VCV (8 mL/kg). As medianas de pressão inspiratória máxima (30 cmH2O) e de pressão positiva no fim da expiração (PEEP) (8 cmH2O) foram maiores nos pacientes em PCV. CONCLUSÕES: O predomínio de pacientes ventilados nas UTI foi indicado pela sua maior gravidade clínica e pelo maior tempo de internação. A IRA foi a principal indicação de ventilação mecânica. VCV e PSV ventilaram mais pacientes, sendo a PSV na fase de desmame ventilatório. Abstract in english BACKGROUND AND OBJECTIVES: There are few epidemiological studies in mechanical ventilation, and the aim of the study is to show how this procedure is being used in Brazil. METHODS: A 1-day point prevalence study was performed in 40 ICUs, with 390 patients; 217 of these patients were in mechanical ventilation. The results evaluated were the characteristics of ventilated patients, their distribution in Brazil, the mechanical ventilation's causes, the main ventilatory modes, (more) the more important ventilators settings, and the weaning stage of mechanical ventilation. RESULTS: The median age of the ventilated patients was 66 years old. The median APACHE II was 20, while the median time of mechanical ventilation was 11 days. Acute respiratory failure occurred in 71% of the patients, coma in 21.2%, acute exacerbation of chronic respiratory failure in 5.5%, and the neuromuscular disease in 2.3%. The volume-controlled ventilation (VCV) (30%), the pressure support ventilation (PSV) (29.5%), and the pressure-controlled ventilation (PCV) (18%) were the ventilatory modes most used; the PSV had been the main mode in weaning (63.5%). The median of tidal volume (8 mL/kg) was higher in VCV. The median of maximal inspiratory pression (30 cmH2O) and the median of positive end-expiration pressure (PEEP) (8 cmH2O) were higher in PCV. CONCLUSIONS: The predominance of ventilated patients in ICUs was marked by clinical severity of them, and a longer hospital stay time; acute respiratory failure was the principal mechanical ventilation cause; VCV and PSV ventilated more patients, with PSV being more used in weaning patients.

As the number of new transgenic mouse models of human neuromuscular disease continues to increase, the development of sophisticated electrophysiologic techniques for assessing the peripheral nervous system in these models has become important. Neuromuscular junction (NMJ) dysfunction, in particular, is often not detectable by morphologic or other techniques. To enable sensitive testing of murine NMJ function, we developed and tested a method for stimulated single fiber electromyography (S-SFEMG) in the gastrocnemius muscles of anesthetized mice. Jitter was assessed by measuring the mean consecutive latency difference (MCD) of single fiber responses to sciatic nerve stimulation at 2 HZ. Mean MCD values in normothermic mice were in the range of 6-8 micros for different strains, with no MCD values exceeding 25 micros. Reduced core temperature (to 29 degrees--30 degrees C) resulted in increased jitter, whereas intubation and mechanical ventilation of mice did not alter these values. Intraperitoneal and intravenous injection of vecuronium, however, resulted in progressively increased jitter followed by blocking in continuously monitored fibers. These observations validate the utility of S-SFEMG in mice as an index of NMJ function under a variety of physiologic conditions, and suggest that a high safety factor for neuromuscular transmission exists at mouse NMJs. Copyright 2001 John Wiley & Sons, Inc.

Rodents fed alpha-tocopherol (alphaT)-depleted diets develop neuromuscular deficits. Unequivocal role of alphaT in the prevention of these deficits is confounded by possible neurotoxic oxidant products generated, ex vivo in alphaT-depleted diets. The discovery that large doses of alphaT could ameliorate neuromuscular deficits, attributed to very low serum alphaT caused by mutations in either the microsomal triglyceride transfer protein or the alphaT-transfer protein (alphaTTP), underscores the necessity of alphaT for neuromuscular health in humans. The discovery of human alphaTTP provided physiological relevance to biochemical data from rodents documenting alphaT-binding transfer protein, expressed exclusively in liver. The cloning of alphaTTP gene and the creation of alphaTTP-knockout mice allowed to achieve severe systemic alphaT deficiency in brain and muscles, possibly at birth, eliminating the possible confounding effects of ex vivo-generated oxidant products in vitamin E-stripped diets. alphaTTP-knockout mice have proven useful models to discover alphaT-regulated phenotypes and molecular actions of alphaT in vivo. The results suggest that antioxidant and non-antioxidant actions of alphaT in vivo may not be mutually exclusive. These studies also suggest that low levels of dietary alphaT can achieve in excess of nanomolar alphaT levels in tissues and maintain normal neuromuscular functions. This is consistent with biochemical and crystallographic data of alpha-TTP and of other alphaT-binding proteins that have dissociation constants in nanomolar range. Molecular mechanisms that cause a long delay for the development of deficiency symptoms remain enigmatic. It is likely that alphaT is metabolically stable in post-mitotic neurons and myocytes and, if it undergoes redox-cycling in vivo, a large repertoire of alphaT-regenerating systems maintains its biological activity before it is totally depleted. PMID:20187127

BACKGROUND: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique with the potential to enhance the efficacy of traditional therapies such as neuromuscular electrical stimulation (NMES). Yet, concurrent application of tDCS/NMES may also activate homeostatic mechanisms that block or reverse effects on corticomotor excitability. It is unknown how tDCS and NMES interact in the human primary motor cortex (M1) and whether effects are summative (increase corticomotor excitability beyond that of tDCS or NMES applied alone) or competitive (block or reduce corticomotor excitability effects of tDCS or NMES applied alone). OBJECTIVE: To investigate corticomotor excitability in response to NMES after concurrent application of tDCS protocols that enhance (anodal tDCS) or suppress (cathodal tDCS) excitability of M1. METHODS: We used transcranial magnetic stimulation (TMS) to examine corticomotor excitability before and after the concurrent application of: i) NMES with anodal tDCS; and ii) NMES with cathodal tDCS. Effects were contrasted to four control conditions: i) NMES alone, ii) anodal tDCS alone, iii) cathodal tDCS alone, and iv) sham stimulation. RESULTS: Concurrent application of two protocols that enhance excitability when applied alone (NMES and anodal tDCS) failed to induce summative effects on corticomotor excitability, as predicted by homeostatic plasticity mechanisms. Combined cathodal tDCS and NMES suppressed the enhanced excitation induced by NMES, an effect that might be explained by calcium dependent anti-gating models. CONCLUSIONS: These novel findings highlight the complex mechanisms involved when two neuromodulatory techniques are combined and suggest that careful testing of combined interventions is necessary before application in clinical contexts. PMID:23088854

The Lucia jig is a technique that promotes neuromuscular reprogramming of the masticatory system and allows the stabilization of the mandible without the interference of dental contacts, maintaining the mandible position in harmonic condition with the musculature in normal subjects or in patients with temporomandibular dysfunction (TMD). This study aimed to electromyographically analyze the activity (RMS) of the masseter and temporal muscles in normal subjects (control group) during the use of an anterior programming device, the Lucia jig, in place for 0, 5, 10, 20 and 30 minutes to demonstrate its effect on the stomatognathic system. Forty-two healthy dentate individuals (aged 21 to 40 years) with normal occlusion and without parafunctional habits or temporomandibular dysfunction (RDC/TMD) were evaluated on the basis of the electromyographic activity of the masseter and temporal muscles before placement of a neuromuscular re-programming device, the Lucia jig, on the upper central incisors. There were no statistically significant differences (p jig changed the electromyographic activity by promoting a neuromuscular reprogramming. In most of the time periods, it decreased the activation of the masticatory muscles, showing that this device has wide applicability in dentistry. The use of a Lucia jig over 0, 5, 10, 15, 20 and 30 minutes did not promote any statistically significant increase in muscle activity despite differences in the data, thus showing that this intra-oral device can be used in dentistry. PMID:23019085

The neuromuscular blocker advisory system (NMBAS) is a computer program developed to provide advisory guidance to anesthesiologists on the timing and dose of rocuronium to paralyze patients during surgery. It is believed that the use of such a system will administer the minimally effective amount of drug, maintaining the patient in a state of paralysis that is useful for surgery yet easily reversible. This will improve patient safety and result in more efficient care. In this paper we present the NMBAS, its basic methodology, and its development though a pilot study. Novel methods of handling neuromuscular response data are presented, including relaxation measurement and the enhanced-train-of-four sensing modality. New methods of handling nonlinearities at the neuromuscular junction to allow application of adaptive control techniques are presented. A novel form of modelling combining model swapping and RLSE adaptation to accommodate the patient variation seen with NMB drugs is introduced. A pilot study testing the NMBAS was undergone to prepare the NMBAS for application in a full clinical trial, in which patients undergoing prostate brachytherapy surgeries using rocuronium for intubation were admitted. PMID:18164511

Objective:To determine the effectiveness of vestibular-specific neuromuscular training on motor skills, balance and health-related quality of life in children with hearing impairment.Design:Controlled, randomized, preliminary study.Setting:Rehabilitation school for children with hearing impairment.Subjects and intervention:Twenty-three children with mean age of 7.5-8.1 years with hearing impairment were randomized to either the intervention or the control group. Children in the experimental group (n = 11) participated in vestibular-specific neuromuscular training for six weeks and the children in the control group continued their regular activities followed at school.Outcome measures:Measurement of motor skills (Test of Gross Motor Development-2), postural control (Pediatric Reach Test, One Leg Standing Balance Test and postural sway meter) and health-related quality of life (PedsQL Generic Core Scale).Results:Following intervention, the scores of motor skills (Test of Gross Motor Development P = 0.02; throw for distance P = 0.042; kick for distance P = 0.08; jump for distance P = 0.001; 15-yard dash P = 0.001), postural control measures (Pediatric Reach Test P = 0.001; One Leg Standing Test P = 0.03; and anteroposterior sway (eyes open P = 0.007, eyes closed P = 0.03); mediolateral sway (eyes open P = 0.014, eyes closed P = 0.017) and health-related quality of life (P = 0.01) improved significantly in the experimental group and not in the control group.Conclusion:The findings of the study suggest that vestibular-specific neuromuscular training programme may improve the motor skills, balance and health-related quality of life in children with hearing impairment. PMID:23076993

Abstract in portuguese JUSTIFICATIVA E OBJETIVOS: A potencialização da procainamida sobre o bloqueio neuromuscular produzido pela d-tubocurarina já está comprovada, porém o mecanismo é controverso. O objetivo do estudo foi avaliar a influência da procainamida no bloqueio neuromuscular produzido pelo rocurônio e investigar os mecanismos desta interação. MÉTODO: Foram utilizados 15 ratos (250 a 300 g) em preparação descrita por Bülbring. Formaram-se os seguintes grupos (n = 5 cada): (more) procainamida - 20 µg.mL-1 (Grupo I); rocurônio - 4 µg.mL-1 (Grupo II) e rocurônio - 4 µg.mL-1 e procainamida - 20 µg.mL-1 (Grupo III). Avaliaram-se: 1) a amplitude das contrações musculares sob estimulação indireta em cada grupo, antes e após a adição dos fármacos; 2) os potenciais de placa terminal em miniatura (PPTM); 3) a eficácia da 4-aminopiridina na reversão do bloqueio neuromuscular. O mecanismo da interação foi estudado em Biventer cervicis (n = 5) e diafragma de rato desnervado (n = 5), observando-se a influência da procainamida na resposta à acetilcolina antes e após a adição da procainamida. RESULTADOS: A procainamida isoladamente não alterou as respostas neuromusculares. O bloqueio produzido com o Grupo III foi de 68,6% ± 7,1%, com diferença significativa (p = 0,0067) em relação ao Grupo II (10,4% ± 4,5%), revertido pela 4-aminopiridina. A procainamida ocasionou aumento na freqüência dos PPTM, seguido de bloqueio revertido pela 4-aminopiridina. Em Biventer cervicis a procainamida aumentou a resposta à ação de contração da acetilcolina, resultado não observado com o diafragma desnervado. CONCLUSÕES: A procainamida potencializou o bloqueio produzido pelo rocurônio. As alterações observadas com PPTM e Biventer cervicis identificaram ação pré-sináptica. O antagonismo da 4-aminopiridina sobre o bloqueio dos PPTM sugeriu dessensibilização dos receptores pela procainamida. Abstract in spanish JUSTIFICATIVA Y OBJETIVOS: La potenciación de la procainamida sobre el bloqueo neuromuscular producido por la d-tubocurarina ya está comprobada, pero sin embargo el mecanismo es controvertido. El objetivo del estudio fue el de evaluar la influencia de la procainamida en el bloqueo neuromuscular producido por el rocuronio e investigar los mecanismos de esa interacción. MÉTODO: Se utilizaron 15 ratones (250 a 300 g) en preparación descrita por Bülbring. Se formaron lo (more) s siguientes grupos (n = 5 cada): procainamida - 20 µg.mL-1 (Grupo I); rocuronio - 4 µg.mL-1 (Grupo II) y rocuronio - 4µg.mL-1 y procainamida - 20µg.mL-1 (Grupo III). Se evaluó: 1) la amplitud de las contracciones musculares bajo la estimulación indirecta en cada grupo, antes y después de la adición de los fármacos; 2) los potenciales de placa terminal en miniatura (PPTM); 3) la eficacia de la 4-aminopiridina en la reversión del bloqueo neuromuscular. El mecanismo de la interacción se estudió en Biventer cervicis (n = 5) y diafragma de ratón desnervado (n = 5), observándose la influencia de la procainamida en la respuesta a la acetilcolina antes y después de la adición de la procainamida. RESULTADOS: De forma aislada, la procainamida no alteró las respuestas neuromusculares. El bloqueo producido con el Grupo III fue de 68,6% ± 7,1%, con una diferencia significativa (p = 0,0067) con relación al Grupo II (10,4% ± 4,5%), revertido por la 4-aminopiridina. La procainamida ocasionó un aumento en la frecuencia de los PPTM, seguido de bloqueo revertido por la 4-aminopiridina. En Biventer cervicis, la procainamida aumentó la respuesta a la acción de contracción de la acetilcolina, resultado no observado con el diafragma desnervado. CONCLUSIONES: La procainamida potenció el bloqueo producido por el rocuronio. Las alteraciones observadas con PPTM y Biventer cervicis identificaron una acción presináptica. El antagonismo de la 4-aminopiridina sobre el bloqueo de los PPTMs sugirió la desensibilización de los receptores por la procainamida. Abstract in english BACKGROUND AND OBJECTIVES: It has already been proved that procainamide potentiates the neuromuscular blockade of d-tubocurarine; however, the mechanism of this potentiation is controversial. The aim of this study was to assess the influence of procainamide on the neuromuscular blockade produced by rocuronium and investigate the mechanisms of this interaction. METHODS: Fifteen rats (250 to 300 g) were used in the preparation described by Bülbring. They were divided in th (more) ree groups (n = 5 each): procainamide - 20 µg.mL-1 (Group I); rocuronium - 4 µg.mL-1 (Group II); and rocuronium - 4 µg.mL-1 and procainamide - 20 µg.mL-1 (Group III). The following parameters were evaluated: 1) amplitude of muscle contractions under indirect stimulation, before and after the administration of the drugs; 2) miniature end plate potentials (MEPPs); and 3) the efficacy of 4-aminopyridine in reverting the muscular blockade. The mechanism of the interaction was studied in Biventer cervicis (n = 5) and in the denervated rat diaphragm (n = 5), observing the influence of procainamide in the response to acetylcholine. RESULTS: Procainamide alone did not change the neuromuscular responses. Group III presented a 68.6% ± 7.1% blockade, which represented a statistically significant difference (p = 0.0067) when compared with Group II (10.4% ± 4.5%), which was reverted by 4-aminopiridine. Procainamide increased the frequency of the MEPP, followed by a blockade that was reverted by 4-aminopiridine. In Biventer cervicis, procainamide increased the contraction in response to acetylcholine, which was not observed in the denervated diaphragm. CONCLUSIONS: Procainamide potentiated the blockade caused by rocuronium. The changes observed with MEPP and Biventer cervicis identified pre-synaptic action. The antagonism of 4-aminopiridine on the blockade of the MEPP suggested receptor desensitization by procainamide.

... Huston LJ, Wojtys EM. Neuromuscular performance characteristics in elite female athletes. Am J Sports Med 1996;24:427-436. ... Huston LJ, Wojtys EM. Neuromuscular performance characteristics in elite female athletes. Am J Sports Med 1996;24:427-436. ...

We successfully performed transection of the innominate artery in a patient with a neuromuscular disorder through minimally invasive access after confirming the anatomical relationships of the vessel using 3-dimensional multidetector-row computed tomographic angiography. A 16-year-old girl with spinal muscular atrophy type 1 had been on long-term mechanical ventilation with a tracheostomy. She had scoliosis and tracheomalacia. Bronchoscopy showed a flattened and narrow lower trachea and an anterior pulsatile compression by the innominate artery. She underwent transection of the innominate artery to prevent tracheoinnominate artery fistula formation. Based on preoperative 3-dimensional multidetector-row computed tomographic angiography images, the innominate artery was transected through a ...

Temporomandibular disorders are a group of chronic and painful conditions in the masticatory musculature and temporomandibular joint. The pathological mechanisms underlying temporomandibular disorders remain to be clarified; however, it is known that disturbances in neurophysiological, cognitive, behavioral and neuromuscular functions are involved in the development and persistence of such disorders. In addition, it has been suggested that neuropathological changes in the central nervous system are involved in the development of temporomandibular disorders. This review describes changes in the cortical machinery in patients with temporomandibular disorders by comparing neuromagnetic signals between healthy subjects and patients elicited by observing jaw opening movements made by another person.   

Whole-body vibration (WBV) is a relatively novel form of exercise used to improve neuromuscular performance in healthy individuals. Its usefulness as a therapy for patients with neurological disorders, in particular spinal cord injury (SCI), has received little attention in clinical settings and, surprisingly, even less in animal SCI models. We performed severe compression SCI at a low-thoracic level in Wistar rats followed by daily WBV starting 7 (10 rats) or 14 (10 rats) days after injury (WBV7 and WBV14, respectively) and continued over a 12-week post-injury period. Rats with SCI but no WBV training (sham, 10 rats) and intact animals (10 rats) served as controls. Compared to sham treated rats, WBV did not improve BBB score, plantar stepping or ladder stepping during the 12-week period. Accordingly, WBV did not significantly alter plantar H-reflex, lesion volume, serotonergic input to the lumbar spinal cord nor cholinergic or glutamatergic inputs to lumbar motoneurons at 12 weeks after SCI. However, compared to sham, WBV14, but not WBV7, significantly improved body weight support (rump-height index) during overground locomotion and overall recovery between 6 - 12 weeks and also restored the density of synaptic terminals in the lumbar spinal cord at 12 weeks. Most remarkably, WBV14 lead to a significant improvement of bladder function at 6 - 12 weeks after injury. These findings provide the first evidence for functional benefits of WBV in an animal SCI model and warrant further preclinical investigations to determine mechanisms underpinning this non-invasive, inexpensive and easily delivered potential rehabilitation therapy for SCI. PMID:23157611

Anterior cruciate ligament (ACL) injuries are commonly incurred by recreational and professional women athletes during non-contact jumping maneuvers in sports like basketball and volleyball, where incidences of ACL injury is more frequent to females compared to males. What remains a numerical challenge is in vivo calculation of ACL strain and internal force. This study investigated effects of increasing stop-jump height on neuromuscular and bio-mechanical properties of knee and ACL, when performed by young female recreational athletes. The underlying hypothesis is increasing stop-jump (platform) height increases knee valgus angles and external moments which also increases ACL strain and internal force. Using numerical analysis tools comprised of Inverse Kinematics, Computed Muscle Control and Forward Dynamics, a novel approach is presented for computing ACL strain and internal force based on (1) knee joint kinematics and (2) optimization of muscle activation, with ACL insertion into musculoskeletal model. Results showed increases in knee valgus external moments and angles with increasing stop-jump height. Increase in stop-jump height from 30 to 50 cm lead to increase in average peak valgus external moment from 40.5 ± 3.2 to 43.2 ± 3.7 Nm which was co-incidental with increase in average peak ACL strain, from 9.3 ± 3.1 to 13.7 ± 1.1%, and average peak ACL internal force, from 1056.1 ± 71.4 to 1165.4 ± 123.8 N for the right side with comparable increases in the left. In effect this study demonstrates a technique for estimating dynamic changes to knee and ACL variables by conducting musculoskeletal simulation on motion analysis data, collected from actual stop-jump tasks performed by young recreational women athletes. PMID:22527014

Study design:Survey and long-term clinical post-trial follow-up (interviews/correspondence) on nine chronic, post spinal cord injury (SCI) tetraplegics.Objective:To assess feasibility of the use of Electroencephalography-based Brain–Computer Interface (EEG–BCI) for reaching/grasping assistance in tetraplegics, through a robotic arm.Settings:Physical and (neuromuscular) Rehabilitation Medicine, Cardiology, Neurosurgery Clinic Divisions of TEHBA and UMPCD, in collaboration with ‘Brain2Robot’ (composed of the European Commission-funded Marie Curie Excellence Team by the same name, hosted by Fraunhofer Institute-FIRST), in the second part of 2008.Methods:Enrolled patients underwent EEG–BCI preliminary training and robot control sessions. Statistics entailed multip...

Summary The body of the vertebra can be affected in the majority of the conditions involving the lumbar spine. Multiple references, both books and periodicals, have been reviewed, and the anatomical factors responsible for the vertebral body integrity in the lumbar spine have been included under the following important areas, namely, morphology, development, genetics, microscopic examination using histology, structural architecture, blood supply, neuromuscular control, and biomechanics. Introduction The anatomy provides a three-dimensional frame work to support the interaction between the physiological and pathological alterations. The body of the vertebra can be affected in a majority of acute or chronic conditions involving the lumbar spine. The etiology of these conditions is multifacto...

Hemiparesis-disability and muscle weakness of 1 side of the body-is a common consequence of stroke. High-intensity strength training may be beneficial to regain function, but strength coaches in the field of rehabilitation need evidence-based guidelines. The purpose of this study was to evaluate the effect of intensive physical rehabilitation on neuromuscular and functional adaptations in outpatients suffering from hemiparesis after stroke. A within-subject repeated-measures design with the paretic leg as the experimental leg and the nonparetic leg as the control leg was used. Eleven outpatients with hemiparesis after stroke participated in 12 weeks of intensive physical rehabilitation comprising unilateral high-intensity strength training with near-maximal loads (4-12 repetition maximum) and body weight supported treadmill training. At baseline and 12-week follow-up, the patients went through testing consisting of isokinetic muscle strength, neuromuscular activation measured with electromyography (EMG), electrically evoked muscle twitch contractile properties, and gait performance (10-m Walk Test and 6-min Walk Test). After the 12-week conditioning program, knee extensor and flexor strength increased during all contraction modes and velocities in the paretic leg. Significant increases were observed for agonist EMG amplitude at slow concentric and slow eccentric contraction. Twitch torque increased, whereas twitch time-to-peak tension remained unchanged. By contrast, no significant changes were observed in the nonparetic control leg. Gait performance increased 52-68%. In conclusion, intensive physical rehabilitation after stroke leads to clinically relevant neuromuscular improvements, leading to increased voluntary strength during a wide range of contraction modes and velocities, and improved gait velocity. Strength training coaches working in the field of rehabilitation can use this knowledge to safely and efficiently add high-intensity strength training to existing rehabilitation paradigms.

AbstractBACKGROUND: Treatment regimens for childhood acute lymphoblastic leukemia (ALL) contain neurotoxic agents that may interfere with neuromuscular health. In this study, the authors examined associations between neuromuscular impairments and physical function and between neuromuscular impairments and doses of vincristine and intrathecal methotrexate used to treat leukemia among survivors of childhood ALL. METHODS: ALL survivors >10 years from diagnosis participated in neuromuscular performance testing. Treatment data were abstracted from medical records. Regression models were used to evaluate associations between treatment factors, neuromuscular impairments, and physical performance. RESULTS: Among 415 survivors (median age, 35 years; age range, 21-52 years), balance, mobility, and 6...

This study evaluated the electromyographic (EMG) characteristics of masticatory muscles in patients with fixed implant-supported prostheses according to All-on-Four(®) principles and in control healthy dentate subjects. Twenty-six subjects aged 50-74 years were examined. Eighteen were edentulous and had been successfully rehabilitated with (i) mandibular All-on-Four(®) implant-supported fixed prostheses and maxillary complete dentures (10 patients) and (ii) mandibular and maxillary All-on-Four(®) implant-supported fixed prostheses (eight patients). Eight reference subjects had natural dentition. Surface EMG recordings of the masseter and temporalis muscles were performed during maximum voluntary teeth clenching and during unilateral gum chewing. All values were standardised as percentage of a maximum clenching on cotton rolls. During clenching, a good global neuromuscular equilibrium was found in all participants. During chewing, all groups had similar values of working-side muscle activities and of chewing frequency. No significant differences in the analysed EMG parameters were found between the patients with mandibular and maxillary All-on-Four(®) implant-supported prostheses and the reference subjects. In contrast, standardised pooled muscle activities and standardised muscular activities per cycle were larger in patients with a maxillary removable prosthesis than in control subjects (Kruskal-Wallis test, P patients wearing a complete maxillary denture showed a poor neuromuscular coordination with altered muscular pattern and lower values of the index of masticatory symmetry than dentate control subjects (P edentulous patients with reduced residual bone volume. PMID:22957827

Neuromuscular disorders affect the peripheral nervous system and muscle. The principle effect of neuromuscular disorders is therefore on the ability to perform voluntary movements. Neuromuscular disorders cause significant incapacity, including, at the most extreme, almost complete paralysis. Neuromuscular diseases include some of the most devastating disorders that afflict mankind, for example motor neuron disease. Neuromuscular diseases have onset any time from in utero until old age. They are most often genetic. The last 25 years has been the golden age of genetics, with the disease genes responsible for many genetic neuromuscular disorders now identified. Neuromuscular disorders may be inherited as autosomal dominant, autosomal recessive, or X-linked traits. They may also result from m...

Brain-computer interfaces (BCIs) acquire brain signals, analyze them, and translate them into commands that are relayed to output devices that carry out desired actions. BCIs do not use normal neuromuscular output pathways. The main goal of BCI is to replace or restore useful function to people disabled by neuromuscular disorders such as amyotrophic lateral sclerosis, cerebral palsy, stroke, or spinal cord injury. From initial demonstrations of electroencephalography-based spelling and single-neuron-based device control, researchers have gone on to use electroencephalographic, intracortical, electrocorticographic, and other brain signals for increasingly complex control of cursors, robotic arms, prostheses, wheelchairs, and other devices. Brain-computer interfaces may also prove useful for rehabilitation after stroke and for other disorders. In the future, they might augment the performance of surgeons or other medical professionals. Brain-computer interface technology is the focus of a rapidly growing research and development enterprise that is greatly exciting scientists, engineers, clinicians, and the public in general. Its future achievements will depend on advances in 3 crucial areas. Brain-computer interfaces need signal-acquisition hardware that is convenient, portable, safe, and able to function in all environments. Brain-computer interface systems need to be validated in long-term studies of real-world use by people with severe disabilities, and effective and viable models for their widespread dissemination must be implemented. Finally, the day-to-day and moment-to-moment reliability of BCI performance must be improved so that it approaches the reliability of natural muscle-based function. PMID:22325364

Myasthenia Gravis (MG) patients with antibodies against the muscle specific tyrosine kinase (MuSK+) typically present with focal fatigue and atrophy of the facial and bulbar muscles, along with unbeneficial reactions upon administration of acetylcholinesterase inhibitors (AChEIs). This study addresses the neurophysiological characteristics in facial versus limb muscles, before and after intraperitoneal injection of AChEIs, in mice immunized with MuSK. We performed in-vivo neurophysiological examinations in the masseter and gastrocnemius muscles of mice with MuSK+experimental autoimmune MG (EAMG) and in healthy control mice before and after administration of AChEIs. Abnormal spontaneous activity (fibrillations) was observed in the masseter muscle of MuSK+mice. Furthermore, 94% of MuSK-immunized mice displayed so called extra discharges (EDs) upon administration of a therapeutic AChEI dose, in contrast to 22% of the control mice, indicating neuromuscular hyperactivity. These findings support functional denervation in the masseter muscle and neuromuscular hypersensitivity already at a standard dose of AChEIs in MuSK+EAMG. PMID:22251934

Abstract in portuguese Desenvolveu-se uma técnica de bloqueio peribulbar comparando-a à técnica de anestesia oftálmica com bloqueio neuromuscular parcial em cães submetidos à facectomia extracapsular. Doze cães, de diferentes raças, foram alocados em dois grupos (G1 e G2) e anestesiados com acepromazina (0,05mg/kg, IV) e propofol (5mg/kg, IV) e mantidos com isofluorano sob ventilação espontânea. Os cães do G1 receberam o bloqueio peribulbar com ropivacaína 0,75%, e os do G2 o bloqu (more) eio neuromuscular parcial com brometo de pancurônio (0,01mg/kg, IV). Utilizaram-se, como parâmetros comparativos, escores de posicionamento do globo ocular, controle do reflexo oculocardíaco e pressão intraocular (mmHg). Foi possível propor uma técnica eficaz para cães baseando-se na técnica de bloqueio peribulbar posterior realizada no homem. Em ambos os grupos, o globo ocular permaneceu centralizado. Não ocorreram alterações eletrocardiográficas atribuídas ao reflexo oculocardíaco. Houve redução significativa da pressão intraocular em G1 após o bloqueio (10,7±0,6 e 14,7±0,6). Conclui-se que o bloqueio peribulbar proporcionou condições cirúrgicas apropriadas para a realização da facectomia, com a vantagem de promover bloqueio sensitivo do olho. Abstract in english A peribulbar block technique was developed and its clinical efficacy was compared with neuromuscular blockade in dogs undergoing cataract surgery. Twelve dogs of different breeds were randomly and equally allocated in two groups. After given acepromazine (0.05mg/kg, IV), anesthesia was induced with propofol (5mg/kg, IV) and maintained with isoflurane in oxygen during spontaneous breathing. A peribulbar block with 0.75% ropivacaine was performed in G1 dogs while partial ne (more) uromuscular blockade with pancuronium (0.01mg/kg IV) was provided in G2 dogs. Globe position scores, oculocardiac reflex, and intra-ocular pressure (mmHg) were evaluated at pre-defined intervals during surgery. Peribulbar blocks were successful performed according to posterior peribulbar block described in humans. In both groups, the globe was centralized and globe position scores did not differ between groups. The intra-ocular pressure was significantly lower in G1 after the block (10.7±0.6 vs 14.7±0.6). There were no electrocardiographycal changes attributed to the oculocardiac reflex. In conclusion, satisfactory surgical conditions were provided by the peribulbar block. This technique can be used as an alternative to the use of neuromuscular blocking agents in dogs undergoing cataract surgery, with the advantage of providing analgesia of the eye.

Problems occurred with train-of-four (TOF) monitoring during prolonged therapy with nondepolarizing neuromuscular blocking agents (NNMBAs). A previously healthy 25-year-old male with metastatic testicular teratocarcinoma was paralyzed with an atracurium infusion to facilitate mechanical ventilation. Dosage titration was initially based on clinical assessment; however, on day 4 of atracurium, TOF monitoring was initiated. During days 4 to 10 of atracurium therapy, TOF monitoring correlated well with clinical assessment of the depth of paralysis. On day 13, atracurium was discontinued and a pancuronium infusion was initiated. During the 9 days of pancuronium therapy, TOF monitoring suggested overparalysis on several occasions (no thumb twitch at 80 mamp of ulnar nerve stimulation) despite clinical evidence of spontaneous movement or respirations. The patient was edematous and had extremely dry skin during some of these instances of inappropriate TOF response. Although these problems were rectified, TOF response continued to be erroneous. Thus we had to rely primarily on clinical assessment to monitor the duration of NNMBA therapy. This case demonstrates that TOF data and clinical assessment of neuromuscular blockade may not always correlate. PMID:7479211

Fatigue post-stroke is a disabling and persistent symptom affecting many stroke survivors. Despite its high prevalence, the pathophysiology underlying this phenomenon remains obscure. The aim of the present study was to investigate the origins of neuromuscular fatigue post-stroke. Ten chronic stroke survivors and 10 controls sustained an isometric contraction at 30% of maximal voluntary contraction (MVC) with the ankle dorsiflexors. Motor evoked potential (MEP), cortical silent period (SP), voluntary activation, M wave and contractile properties were evaluated before, during and after fatigue among the paretic, non-paretic and control limbs. The pattern of response to fatigue in the non-paretic and control limbs was comparable; therefore, results are presented between the paretic and non-p...

The aim of this review was to describe the current evidence-based knowledge of the epidemiology, prevalence, incidence, risk factors and genetic associations of drug allergy. Articles published between 1966 and 2010 were identified in MEDLINE using the key words adult, adverse drug reaction reporting systems, age factors, anaphylactoid, anaphylaxis, anaesthetics, antibiotics, child, drug allergy, drug eruptions, ethnic groups, hypersensitivity, neuromuscular depolarizing agents, neuromuscular nondepolarizing agents, sex factors, Stevens Johnson syndrome and toxic epidermal necrolysis. Additional studies were identified from article reference lists. Relevant, peer-reviewed original research articles, case series and reviews were considered for review. Current epidemiological studies on adverse drug reactions (ADRs) have used different definitions for ADR-related terminology, often do not differentiate immunologically and non-immunologically mediated drug hypersensitivity, study different study populations (different ethnicities, inpatients or outpatients, adults or children), utilize different methodologies (spontaneous vs. non-spontaneous reporting, cohort vs. case-control studies), different methods of assessing drug imputability and different methods of data analyses. Potentially life-threatening severe cutaneous adverse reactions (SCAR) are associated with a high risk of morbidity and mortality. HLA associations for SCAR associated with allopurinol, carbamazepine and abacavir have been reported with the potential for clinical use in screening prior to prescription. Identification of risk factors for drug allergy and appropriate genetic screening of at-risk ethnic groups may improve the outcomes of drug-specific SCAR. Research and collaboration are necessary for the generation of clinically-relevant, translational pharmacoepidemiological and pharmacogenomic knowledge, and success of health outcomes research and policies on drug allergies.

To evaluate the role of bispectral index monitoring as an adjunct to balanced anesthesia in patients with myasthenia gravis undergoing transsternal thymectomy without the use of neuromuscular blocking agents, 10 patients were enrolled into this prospective observational study. After oral midazolam premedication, general anesthesia was induced with fentanyl, propofol, and sevoflurane. Tracheal intubation was performed without neuromuscular blocking agents. During maintenance, continuous monitoring of physiological and bispectral index parameters was used to titrate the doses of remifentanil, propofol, and sevoflurane. Sevoflurane concentration and propofol doses were adjusted to achieve bispectral index values in the high 30s to low 40s. Propofol was discontinued when the sternum was approximated. Remifentanil infusion was stopped on subcutaneous tissue closure, and sevoflurane was switched off when nearing completion of skin closure. Tracheal extubation was performed when extubation criteria were met. On extubation, bispectral index levels were above 90. The median time from extubation to discontinuation of propofol was 28 +/- 4 min, that of remifentanil was 21 +/- 4 min, and it was 9 +/- 5 min for sevoflurane. Bispectral index monitoring provided excellent hemodynamic control during surgery, and allowed early problem-free tracheal extubation. PMID:19713336

A role for neuromuscular activity in the maintenance of skeletal muscle properties has been well established. However, the role of activity-independent factors is more difficult to evaluate. We have used the spinal cord isolation model to study the effects of chronic inactivity on the mechanical properties of the hindlimb musculature in cats and rats. This model maintains the connectivity between the motoneurons and the muscle fibers they innervate, but the muscle unit is electrically "silent". Consequently, the measured muscle properties are activity-independent and thus the advantage of using this model is that it provides a baseline level (zero activity) from which regulatory factors that affect muscle cell homeostasis can be defined. In the present paper, we will present a brief review of our findings using the spinal cord isolation model related to muscle mechanical and fiber type properties. PMID:12697552

Myasthenia gravis is a disorder of neuromuscular transmission caused by autoimmune mechanisms. We reported a possible association between seropositive myasthenia gravis and Kaposi's sarcoma in a HIV-negative subject and the observed interactions between the treatment regimen for these two conditions. A 62-year-old man came to our attention for ocular myasthenia gravis. He suffered from a classic form of Kaposi's sarcoma since about 1 year. When myasthenic symptoms worsened, the patient was started on prednisone and azathioprine. The patient had a significant worsening of Kaposi's sarcoma, so prednisone and azathioprine were reduced and he was treated with vinblastine, with improvement both in dermatologic than in neurological symptomatology. We propose some considerations: the potential correlation between Kaposi's sarcoma and myasthenia gravis through immunological mechanism; myasthenia gravis as a paraneoplastic manifestation of Kaposi's sarcoma, and the role of an antitumoral agent as a treatment for both the conditions. PMID:23010878

The relationships between structure and function of the contractile apparatus of the trunk musculature in the chaetognath Sagitta setosa, were studied by electron microscopy and mechanical recordings. We also investigated the nature of the neuromediator at the synaptic level. Contraction, relaxation and stretch can be explained on the sliding model basis. The primary filaments are linked to a large Z line, via C filaments. These C filaments vary in length according to the mechanical states of the contractile apparatus. These muscles are directly excitable by electrical current, high K(+) solutions induced depolarization, or exogenous acetylcholine. The characteristics of the unitary contractile response (twitch) and the effects of the frequency of stimulation set up the contractions of Sagitta among the fastest in the animal kingdom. Acetylcholine appears to be the best candidate for the mediator released at the neuromuscular junction. Its effect on the post-junctional membrane seems to require a receptor of the nicotinic type. PMID:18620186

Children who require prolonged respiratory support often have to spend their whole lives in the hospital. It is important, however, for these children to have time with their families in their own homes. Home mechanical ventilation can make it possible. In Japan, the concept of home mechanical ventilation has just begun to open up. We reported five cases of home mechanical ventilation for children by using a portable respirator (Bennett, Companion 2800). Two cases of these were patients with hypoxic ischemic encephalopathy. The others were cases with neuro-muscular diseases (Werdnig-Hoffmann disease, mitochondrial myopathy, myotubular myopathy). Before taking the patients out, parents received a training in nursing procedures and in skillful use of the ventilator and equipment. The patients went out on excursions 17 times, and were released for home stay a total of 25 times. Initially, 12 excursions were undertaken with doctors or nurses in attendance; later, however, all of the home stays and 5 of the excursions were carried out successfully by the family only. They went to places such as their own home, a park, a zoo, an aquarium and a museum. The average time was 4.6 hours (3-8 hours) for excursions, and 1.8 days (1-7 days) for home stays. Questioning of family revealed that home mechanical ventilation accelerated the social and emotional development of these children whose condition necessitated respiratory support, especially patients with neuro-muscular diseases. It also revealed that family could accept the patient as a member with more familiarity and with more ease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2803812

This good laboratory practice (GLP) study of aluminum salts in Sprague–Dawley rats was conducted according to double-blind, vehicle-controlled randomized design by exposing offspring to aluminum citrate in-utero, through lactation, and then in drinking water post-weaning. Three dose levels were used: 30, 100, 300 mg Al/kg bw/day, in addition to control groups that received either water or a sodium citrate solution (27.2 g/L). Endpoints were assessed in both female and male pups: behavioral (motor activity, T-maze, auditory startle, the Functional Observational Battery (FOB) with domains targeting autonomic function, activity, neuromuscular function, sensimotor function, and physiological function), cognitive function (Morris swim maze), brain weight, clinical chemistry, hematology, ...

The aim of the present study was to investigate the histological, biochemical and ultrastructural effects of occlusal alteration induced by unilateral exodontia on medial pterygoid muscle in guinea pigs, Cavia porcellus. Thirty (n=30) male guinea pigs (450g) were divided into two groups: experimental-animals submitted to exodontia of the left upper molars, and sham-operated were used as control. The duration of the experimental period was 60 days. Medial pterygoid muscles from ipsilateral and contralateral side were analyzed by histological (n=10), histochemical (n=10), and ultrastructural (n=10) methods. The data were submitted to statistical analysis. When the ipsilateral side was compared to the control group, it showed a significantly shorter neuromuscular spindle length (PP>0.05). In ...

Micturition is a natural event occurring several times a day, the result of a complex and partially unknown physiology. It involves different muscles (striated and smooth) as well as the central and autonomic nervous systems in an innate voiding reflex. This reflex is controlled after 2 years of age. If there is a failure or dysfunction of one of these elements, a miction disorder may appear. Two types of miction disorders are identified: neuromuscular disorders of the bladder and defective central control. Multiple factors such as constipation, bladder irritation, or an increase in abdominal pressure can interfere with the voiding reflex. The new international definitions and classifications of voiding disorders allow an easier clinical approach through careful and complete questioning an...

Philodryas olfersii is responsible for most colubrid snakebites in Brazil. In this work, we examined the ability of an ethanolic extract from Mikania laevigata (guaco) leaves to protect against the in vitro neuromuscular activity of P. olfersii venom in mouse phrenic nerve-diaphragm (PND) and chick biventer cervicis (BC) preparations. M. laevigata extract caused moderate twitch-tension facilitation at low concentrations (107.4 +/- 6.2% with 20 @ml/ml and 118.9 +/- 9.3% with 40 @ml/ml in PND, and 120.7 +/- 7.7% with 40 @ml/ml and 114.5 +/- 4.4% with 50 @ml/ml in BC after 120 min; n = 4-6, mean +/- SEM). In PND, the ethanol alone (40 @ml/ml, n = 4) did not change the twitch-tension when compared with control. However, in BC, the ethanol produced a higher facilitation when compared to control...

The development of effective treatments for neuromuscular diseases is a significant challenge due to difficulties in identifying adequate numbers of patients for clinical trials. Low patient numbers in these rare diseases also has an effect when establishing sound clinical practices based on experience gained from patients with similar diagnosis. The Muscular Dystrophy Association of New Zealand (MDA), working in consort with interested clinicians has established the New Zealand Neuromuscular Disease (NZ NMD) Registry in order to help address these problems. The NZ NMD Registry is exceptional in that it comprises one registry for all neuromuscular conditions and will significantly benefit both patients with neuromuscular disease and their clinicians.

Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is anchored to the synaptic basal lamina via a triple helical collagen Q (ColQ) in the form of asymmetric AChE (AChE/ColQ). The C-terminal domain of ColQ binds to MuSK, the muscle-specific receptor tyrosine kinase, that mediates a signal for acetylcholine receptor (AChR) clustering at the NMJ. ColQ also binds to heparan sulfate proteoglycans including perlecan. Congenital defects of ColQ cause endplate AChE deficiency. A single intravenous administration of adeno-associated virus serotype 8 (AAV8)-COLQ to Colq-/- mice rescued motor functions, synaptic transmission, and the ultrastructure of NMJ. We also injected AAV1-COLQ-IRES-EGFP to the left tibialis anterior and observed colocalization of AChE/ColQ at all the examined NMJs of the non-injected limbs. Additionally, injection of purified recombinant AChE/ColQ protein complex into gluteus maximus accumulated AChE in non-injected forelimbs. These observations suggest that the tissue-targeting signal of ColQ can be exploited to specifically deliver the transgene product to the target tissue. MuSK antibody-positive myasthenia gravis (MG) accounts for 5-15% of autoimmune MG. As AChR deficiency is typically mild and as cholinesterase inhibitors are generally ineffective or worsen myasthenic symptoms, we asked if the patient's MuSK-IgG interferes with binding of ColQ to MuSK. In vitro overlay of AChE/ColQ to muscle sections of Colq-/- mice revealed that MuSK-IgG blocks binding of ColQ to the NMJ. In vitro plate-binding of MuSK to ColQ disclosed that MuSK-IgG exerts a dose-dependent block of MuSK-ColQ interaction. In addition, passive transfer of MuSK-IgG to mice reduced the size and density of ColQ to ?10% of controls and had a lesser effect on the sizes and densities of AChR and MuSK. Elucidation of molecular mechanisms of specific binding of ColQ to the NMJ enabled us to ameliorate devastating myasthenic symptoms of Colq-/- mice and to reveal bases of anti-MuSK MG. PMID:22981737

Unique unaffected skeletal muscle fibres, unlike necrotic torso and limb muscles, may pave the way for a more detailed understanding of the molecular pathogenesis of inherited neuromuscular disorders and help to develop new treatment strategies for muscular dystrophies. The sparing of extraocular muscle in Duchenne muscular dystrophy is mostly attributed to the special protective properties of extremely fast-twitching small-diameter fibres, but here we show that distal muscles also represent a particular phenotype that is more resistant to necrosis. Immunoblot analysis of membranes isolated from the well established dystrophic animal model mdx shows that, in contrast to dystrophic limb muscles, the toe musculature exhibits an up-regulation of the autosomal dystrophin homologue utrophin and a concomitant rescue of dystrophin-associated glycoproteins. Thus distal mdx muscle groups provide a cellular system that naturally avoids myofibre degeneration which might be useful in the search for naturally occurring compensatory mechanisms in inherited skeletal muscle diseases.

AbstractBackground: Extremity injury with ischaemia is the most common pattern of vascular trauma and is a challenge for surgeons who must make decisions about the timing and mechanism of limb reperfusion. In modern military conflicts, effective use of limb tourniquets and rapid transport of the injured have increased the number of casualties who reach a medical service with potentially survivable vascular trauma. This report provides a review of extremity ischaemia and reperfusion following vascular trauma. Methods: A review was undertaken of extremity vascular injury with ischaemia, including a focus on adjuncts aimed at reducing reperfusion injury and improving neuromuscular recovery and limb salvage. Results: Findings from basic and clinical research support the need to restore perfusi...

Age-related declines in neuromuscular function are well-documented, though the mechanisms underlying these deficits are unclear. Specific changes in corticospinal and intracortical neurophysiology may contribute, but have not been well studied, especially in lower extremity muscles. Furthermore, variations in physical activity levels may potentially confound the interpretation of neurophysiologic findings. Therefore, the purpose of this study was to quantify differences in transcranial magnetic stimulation (TMS) measures of corticospinal and intracortical excitability of the quadriceps between healthy, active older and younger adults. Twenty younger (age: 25.2+/-2.4 years; body mass index [BMI]: 22.1+/-3.0kg/m^2; 11 males and 9 females) and twenty older (age: 67.7+/-5.5 years; BMI: 26.8+/-...

Purpose: Eyelid dysmotility may result from trauma, tumors, inflammation, infection, and a variety of other conditions. In these cases, a mechanical effect is disrupting a normal neuromuscular apparatus. Dysmotility can also be caused by paralytic eyelid disorders; included in this broad category are neurologic and myogenic disorders of eyelid opening and/or closure. Secondary effects include spastic eyelid closure and synkinesis syndromes. These conditions, by definition, are disorders of movement, and can only be studied adequately using dynamic imaging techniques. Methods: A comprehensive literature search was performed on PubMed. Ninety abstracts were reviewed. Results: Dynamic eyelid imaging has evolved dramatically over the past two decades, at least partially due to the rise of inex...

Abstract Background: The patient's individual anemia tolerance is pivotal when blood transfusions become necessary, but are not feasible for some reason. To date, the effects of neuromuscular blockade (NMB) on anemia tolerance have not been investigated. Methods: 14 anesthetized and mechanically ventilated pigs were randomly assigned to the Roc group (3.78 mg/kg rocuronium bromide followed by continuous infusion of 1 mg/kg/min, n = 7) or to the Sal group (administration of the corresponding volume of normal saline, n = 7). Subsequently, acute normovolemic anemia was induced by simultaneous exchange of whole blood for a 6% hydroxyethyl starch solution (130/0.4) until a sudden decrease of total body O2 consumption (VO2) indicated a critical limitation of O2 transport capacity. The Hb concent...

We present two cases showing significantly prolonged action of vecuronium from magnesium treatment after general anesthesia for urgent cesarean section. The serum magnesium levels were maintained at a therapeutic range for severe eclampsia in one patient (5.6 mg.dl(-1)) and for tocolysis in another with placenta previa totalis (6.9 mg.dl(-1)). The obstetrics-specific emergency in each patient led us to proceed with general anesthesia but using reduced-dose vecuronium, which failed to prevent prolongation of the neuromuscular block. As a result, the patients received prolonged mechanical ventilation. Our cases underscore the need for anesthesiologists as well as obstetricians to be aware of the prolongation of the action of nondepolarizing muscle relaxants as a result of magnesium treatment. PMID:16421674

GNE Myopathy is a rare neuromuscular worldwide autosomal recessive disease, which is very common among Persian Jews. The disorder results from mutations in the gene UDP N-Acetylglucosamine 2-epimerase/N-Acetylmannosamine kinase (GNE). To date, over 60 different mutations in GNE have been reported to cause the disease worldwide, but a single homozygous mutation, M712T, has been identified in all patients of Persian descent, 10 amino acids before the end of the protein. The same mutation was found in other Jews and non-Jews families in the Middle East therefore we term it the Middle East mutation. The mechanism leading from GNE mutations to the myopathy phenotype is not yet understood. Since the disease is recessive, it most likely results from the lack of wild type GNE protein; therefore th...

The use of alcohol is often intimately associated with sport, and the association is particularly strong in football. As well as providing a source of energy, alcohol (ethanol) has metabolic, cardiovascular, thermoregulatory, and neuromuscular actions that may affect exercise performance. Its actions on the central nervous system, however, result in decrements in skill and behavioural changes that may have adverse effects on performance. There is also evidence of dose-dependent decrements in aerobic capacity. Although the mechanisms are not well understood, the aftermath of alcohol use (hangover) may also adversely affect performance for many hours after intoxication. Alcohol intoxication may adversely affect the player's dietary choices by displacing carbohydrate from the diet at a time when restoration of glycogen stores should be a priority. PMID:16766502

Organophosphorous pesticides and nerve agents inhibit the enzyme acetylcholinesterase at neuronal synapses and in neuromuscular junctions. The resulting accumulation of acetylcholine overwhelms regulatory mechanisms, potentially leading to seizures and death from respiratory collapse. While current therapies are only capable of reducing mortality, elevation of the serum levels of the related enzyme butyrylcholinesterase (BChE) by application of the purified protein as a bioscavenger of organophosphorous compounds is effective in preventing all symptoms associated with poisoning by these toxins. However, BChE therapy requires large quantities of enzyme that can easily overwhelm current sources. Here, we report genetic optimization, cloning and high-level expression of human BChE in plants. Plant-derived BChE is shown to be biochemically similar to human plasma-derived BChE in terms of catalytic activity and inhibitor binding. We further demonstrate the ability of the plant-derived bioscavenger to protect animals against an organophosphorous pesticide challenge. PMID:20353404

Pompe disease (glycogen storage disease type II) is an autosomal recessive neuromuscular disorder arising from a deficiency of lysosomal acid a-glucosidase (GAA). Accumulation of autophagosomes is a key pathological change in skeletal muscle fibers and fibroblasts from patients with Pompe disease and is implicated in the poor response to enzyme replacement therapy (ERT). We previously found that mutant GAA-induced endoplasmic reticulum (ER) stress initiated autophagy in patient fibroblasts. However, the mechanism of induction of autophagy in fibroblasts from Pompe disease patients lacking ER stress remains unclear. In this study, we show that inactivated Akt induces ER stress-independent autophagy via mTOR suppression in patient fibroblasts. Activated autophagy as evidenced by increased le...

Surgical procedures can be accomplished successfully in patients with uremia provided certain principles of perioperative management are observed. Preoperative dialysis minimizes the biochemical derangements and improves fluid balance, hypertension and hemostasis. Drug schedules are adjusted in consideration of abnormal metabolism in renal disease. Anesthetic management is modified in recognition of potentially adverse or altered activity of anesthetic agents and neuromuscular relaxants. The lightest plane of anesthesia consistent with expeditious operative technique is maintained, since adequate tissue oxygenation is dependent upon increased cardiac output in these invariably anemic patients. Intraoperative hyperventilation sustains the usual compensatory mechanism for uremic metabolic acidosis in the conscious patient, thereby averting increments in serum potassium levels associated with increasing acidosis. Postoperative morbidity may include shunt thrombosis, infection, impaired wound healing, bleeding, pericarditis, pleuritis and pancreatitis. Hypervolemia and hyperkalemia are best managed by early postoperative dialysis. A period of nutritional support using intravenous essential L-amino acids and hypertonic glucose appears promising, especially when gastrointestinal dysfunction exists. PMID:403628

The peripheral synapses between motoneurons and skeletal muscle fibers, the neuromuscular junctions, are ideal to investigate the general principles of synaptogenesis that depend on the interaction of activity-dependent and activity-independent signals. Much has been learned from gene "knock out" mouse models that helped to identify major synaptic regulators. The "knock out" approach, however, may not distinguish between changes arising from the disruption of molecular signaling pathways and changes caused by the absence of synaptic transmission. To circumvent these problems, postsynaptic activity was modulated in mouse models by specifically targeting endplate receptors or the activity of synaptic regulators such as MuSK. Both regulators have multiple functions and acetylcholine receptors are not just signal transducers but regulate the localization and architecture of endplates. The results show that detailed analysis of mouse models will help to understand the complexity in mechanisms that regulate synaptic remodeling. PMID:23032192

Human progeroid syndromes and premature aging mouse models present as segmental, accelerated aging because some tissues and not others are affected. Skeletal muscle is detrimentally changed by normal aging but whether it is an affected tissue in progeria has not been resolved. We hypothesized that mice which mimic Hutchinson?Gilford progeria syndrome would exhibit age-related alterations of skeletal muscle. Zmpste24 ?/? and Zmpste24 +/+ littermates were assessed for skeletal muscle functions, histo-morphological characteristics, and ankle joint mechanics. Twenty-four-hour active time, ambulation, grip strength, and whole body tension were evaluated as markers of neuromuscular performance, each of which was at least 33% lower in Zmpste24 ?/? mice compared with littermates (p?Zmpste24 ?/? mi...

SummarySpinal muscular atrophy (SMA) is a motor neuron disease caused by deficiency of the ubiquitous survival motor neuron (SMN) protein. To define the mechanisms of selective neuronal dysfunction in SMA, we investigated the role of SMN-dependent U12 splicing events in the regulation of motor circuit activity. We show that SMN deficiency perturbs splicing and decreases the expression of a subset of U12 intron-containing genes in mammalian cells and Drosophila larvae. Analysis of these SMN target genes identifies Stasimon as a protein required for motor circuit function. Restoration of Stasimon expression in the motor circuit corrects defects in neuromuscular junction transmission and muscle growth in Drosophila SMN mutants and aberrant motor neuron development in SMN-deficient zebrafish. ...

Tensiomyography is a non-invasive method of neuromuscular assessment used to measure muscle action characteristics, muscle tone, and muscle fiber type, and provides information on acute and chronic responses of muscle to different training loads. The aims of the present study were: to analyse differences in muscle response and mechanical characteristics of two major muscles of the lower extremity in a large group of Spanish soccer players according to playing position, and to provide group norms against which clinical findings may be compared. Data were collected from 78 professional soccer players (age 26.6+/-4.4years; height: 179.2+/-5.3cm; body mass: 75.8+/-5.3kg). Tensiomyography was recorded from the rectus femoris (RF) and biceps femoris (BF) muscles after 2days without take part in ...

Abstract in portuguese Quando da utilização de bloqueadores neuromusculares, já foi enfatizado na literatura médica humana, que é de vital imporância a monitoração do bloqueio neuromuscular e que estes agentes nunca devem ser utilizados sem a mesma. O objetivo deste estudo foi o de avaliar o uso do monitor da transmissão neuromuscular TOF-Guard em eqüinos. Para tanto, doze eqüinos foram separados aleatoriamente para receberem como bloqueadores neuromusculares o pancurônio ou o atrac (more) úrio. Todos os eqüinos foram pré-medicados com romifidina, induzidos com diazepam e quetamina e mantidos com halotano. Foi administrado o atracúrio ou o pancurônio, seguindo-se a apnéia e início da ventilação mecânica controlada. O tempo entre a administração do relaxante muscular e a obtenção de um bloqueio máximo (T1=0), o retorno do T1 para 25% e da razão do TOF para 0,7 e o tempo do retorno do T1 de 25 para 75% foram mensurados. Concluiu-se que é de grande importância a monitoração do bloqueio neuromuscular quando da utilização de um bloqueador neuromuscular não-despolarizante, uma vez que ela torna o ato anestésico e cirúrgico mais seguro, com a utilização de doses adequadas que inviabilizam a superficialização do bloqueio durante o procedimento cirúrgico. O monitor TOF-Guard mostrou ser uma boa opção para a monitoração do bloqueio neuromuscular em eqüinos. Abstract in english It has been emphasized in the human medical literature, that when using a neuromuscular blocking agent, it is of vital importance the monitoring of the neuromuscular block and that these agents should never be used without it. The purpose of this study was to evaluate the use of the neuromuscular transmission monitor TOF-Guard in horses. Twelve horses were randomly assigned whether to receive pancuronium or atracurium as the neuromuscular blocking agent. All horses were p (more) re-medicated with romifidine, anaesthesia induced with diazepam and ketamine and maintenance with halothane. Abolition of spontaneous ventilation was accomplished by the administration of atracurium or pancuronium. The time from injection of the muscle relaxant agent to the onset of maximum block (T1=0), recovery of T1 to 25% and the recovery of TOF ratio to 0.7 were recorded, as was the time for recovery of T1 from 25 to 75%. It was concluded that it is very important the neuromuscular transmission monitoring during the use of a nondepolarizing neuromuscular blocking agent, since it provides a safer anaesthetic and surgical procedure with the use of adequate dosages and due to the impossibility of a superficialization of the neuromuscular blockade during a surgical procedure. The TOF-Guard showed to be a good option for neuromuscular monitoring in horses.

The present study was designed to explore the inhibitory mechanism by nitric oxide (NO) of the tachykininergic neuro-muscular transmissions in the hamster ileum. In the presence of guanethidine (1 ?M), atropine (0.5 ?M), nifedipine (0.1 ?M) and apamin (100 nM), electrical field stimuli (EFS; 0.5 msec duration, 15 V) evoked non-adrenergic, non-cholinergic excitatory junction potentials (EJPs) in circular smooth muscle cells. The EJPs were markedly inhibited by the tachykinin NK1 receptor antagonists [D-Pro4, D-Trp7,9]-SP(4–11) (3 ?M). Both the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 200 ?M) and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 ?M), did not affect on the resting membrane potentials, but enhanced the tachykininergic EJPs. In the presence of L-NAME (200 ?M), exogenously applied NO (10 ?M) and the membrane permeable analogue of guanosine 3':5'-cyclic monophosphate (cGMP), 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP, 3 mM), significantly inhibited the tachykininergic EJPs. Application of EFS (0.5 msec duration, 15 V) with trains of 20 pulses at 20 Hz increased amount of released substance P (SP). The release of SP was further increased by the treatment of L-NAME or ODQ, but markedly reduced by exogenously applied NO and 8-Br-cGMP. These results suggest that the endogenous NO may inhibit the tachykininergic neuro-muscular transmissions by the decrease of SP release from the tachykininergic neurons, possibly through a guanylate cyclase-cGMP-dependent mechanism in the hamster ileum.   

The calcium-regulated transcription factor NFAT is emerging as a key regulator of neuronal development and plasticity but precise cellular consequences of NFAT function remain poorly understood. Here, we report that the single Drosophila NFAT homolog is widely expressed in the nervous system including motor neurons and unexpectedly controls neural excitability. Likely due to this effect on excitability, NFAT regulates overall larval locomotion and both chronic and acute forms of activity-dependent plasticity at the larval glutamatergic neuro-muscular synapse. Specifically, NFAT-dependent synaptic phenotypes include changes in the number of pre-synaptic boutons, stable modifications in synaptic microtubule architecture and pre-synaptic transmitter release, while no evidence is found for synaptic retraction or alterations in the level of the synaptic cell adhesion molecule FasII. We propose that NFAT regulates pre-synaptic development and constrains long-term plasticity by dampening neuronal excitability. PMID:21185939

A brain-computer interface (BCI) may be used to control a prosthetic or orthotic hand using neural activity from the brain. The core of this sensorimotor BCI lies in the interpretation of the neural information extracted from electroencephalogram (EEG). It is desired to improve on the interpretation of EEG to allow people with neuromuscular disorders to perform daily activities. This paper investigates the possibility of discriminating between the EEG associated with wrist and finger movements. The EEG was recorded from test subjects as they executed and imagined five essential hand movements using both hands. Independent component analysis (ICA) and time-frequency techniques were used to extract spectral features based on event-related (de)synchronisation (ERD/ERS), while the Bhattacharyya distance (BD) was used for feature reduction. Mahalanobis distance (MD) clustering and artificial neural networks (ANN) were used as classifiers and obtained average accuracies of 65 % and 71 % respectively. This shows tha...

Embryos of the teleost Fundulus heteroclitus are shown to be useful model systems for monitoring the effects of xenobiotic compounds on development. Fourteen different substances were tested: malathion, aroclor, aldrin, diquat, parathion, pentachlorophenol, sevin, toxaphene, lindane, 2,4-D, DDT, paraquat, 2,4,5-T, and aminotriazole. Concentrations used for each of these was from 0.01 to 10.0 ppm in the incubation dishes. The variety of effects on development observed depended on the compound and its concentration. These effects included inhibition of gastrulation, abnormal axis formation, diminished pigmentation, slowed rate of development, reduced frequency of hatching, loss of neuromuscular control, and reduction or inhibition of heart beat. Possible modes of action of some of these compounds are discussed. It is also shown that embryogenesis is not always the most susceptible part of the organism's life cycle.

The glottis is composed of muscular, cartilaginous, and other viscoelastic tissues which perform some of our most important, complex, coordinated, and life-sustaining functions. Dominated by the thyroarytenoid muscles and associated glottic closure muscles, the larynx is involved in respiration, swallowing, voicing, coughing, valsalva, vomiting, laughing, and crying. With respiration continuing in the background, all other “secondary” laryngeal events seamlessly occur. When the delicate balance of coordinating these events is disrupted by disease or disorder, many of these tasks are compromised. Due to the complex innervation of these volitional and reflexive tasks with brainstem central pattern generators, primary sensorimotor areas and importantly, limbic areas, failure can occur due to disease, anatomic compromise, and even emotional state. Understanding the level of sensori-motor control and interaction among systems that share these laryngeal neuromuscular substrates will improve the diagnostic and therapeutic skill of the clinician when treating compromise of laryngeal function. PMID:2203180

This study aimed to evaluate the effectiveness of a whole-body vibration training program to improve neuromuscular performance in young elite female athletes. Twenty-three women basketball players (14-18 years old) were randomly assigned to a control group (CG, n = 11) or to a whole-body vibration group (WBVG, n = 12). During the study period, both groups continued their usual training program, but the WBVG also underwent a 15-week vibration training program. We analyzed the countermovement jump test (CMJ), the 1-leg hop test for the right leg and for the left leg, and the single-limb standing balance for both legs and with eyes open and closed at 3 time points: before training (T1), after an 8-week training period (T2), and after a further 7-week training period (T3). Compared with the CG, CMJ increased significantly in the WBVG from T1 to T2 (6.47%, p female basketball players. PMID:22446665

ArtinM and Jacalin (JAC) are lectins from the jackfruit (Artocarpus integrifolia) that have important role in modulation of immune responses to pathogens. Neospora caninum is an Apicomplexa parasite that causes neuromuscular disease in dogs and reproductive disorders in cattle, with economic impact on the livestock industry. Hence, we evaluated the adjuvant effect of ArtinM and JAC in immunization of mice against neosporosis. Six C57BL/6 mouse groups were subcutaneously immunized three times at 2-week intervals with Neospora lysate antigen (NLA) associated with lectins (NLA+ArtinM and NLA+JAC), NLA, ArtinM and JAC alone, and PBS (infection control). Animals were challenged with lethal dose of Nc-1 isolate and evaluated for morbidity, mortality, specific antibody response, cytokine producti...

Abstract Introduction: Alterations in surface electromyographic (sEMG) signals of the abductor pollicis brevis muscle were evaluated in 24 non-manual workers and 40 manual workers (25 asymptomatic and 15 reporting CTS symptoms). Methods: The initial value (IV) and the normalized rate of change (NRC) of average rectified value (ARV), mean frequency of the power spectrum (MNF), and muscle fiber conduction velocity (MFCV) were calculated during contractions at 20% and 50% of maximal voluntary contraction (MVC). Neuromuscular efficiency (NME) and kurtosis of the sEMG amplitude distribution were estimated. Results: With respect to controls, manual workers showed higher NME, lower ARV IV, and reduced myoelectric manifestations of fatigue (lower MNF NRC for both contraction levels, and lower MFCV...

The reserve pool (RP) and readily releasable pool (RRP) of synaptic vesicles within presynaptic nerve terminals, at crayfish and larval Drosophila neuromuscular junctions (NMJs), were examined for physiological differentiation into distinctly separate functional groups. These NMJs are glutamatergic and produce graded excitatory postsynaptic potentials (EPSPs). The packaging of glutamate was perturbed by blocking the vesicular glutamate transporter (VGlut) with bafilomycin A1. Various frequencies of motor nerve stimulation, exposure time, and concentration of bafilomycin A1 were examined. The low-output tonic opener NMJs in crayfish exposed to 4mM bafilomycin A1 and 20-Hz continuous stimulation decreased the EPSP amplitude to 50% in 30min with controls lasting 3h. After activity and bafilom...

Lack of dystrophin in Duchenne muscle dystrophy (DMD) and in the mutant mdx mouse results in progressive muscle degeneration, structural changes at the neuromuscular junction, and destabilization of the nicotinic acetylcholine receptors (nAChRs). One-third of DMD patients also present non-progressive cognitive impairments. Considering the role of the cholinergic system in cognitive functions, the number of nAChR binding sites and the mRNA levels of ?4, ?2, and ?7 subunits were determined in brain regions normally enriched in dystrophin (cortex, hippocampus and cerebellum) of mdx mice using specific ligands and reverse-transcription polymerase chain reaction assays, respectively. Membrane preparations of these brain regions were obtained from male control and mdx mic...

Fifteen children with bilateral lower limb disability were fit alternately with plastic/metal (PM) and leather/metal (LM) knee-ankle-foot orthoses. Fit was maintained by periodic growth adjustments. Gait, activities of daily living, and subjective reactions were gathered for each orthosis type. Despite previous anecdotal reports and expert opinion to the contrary, no overall differences were found between the two types of orthoses. Several specific differences were revealed, however; most children preferred the PM orthoses, saying they were lighter and more easily donned and doffed; the PM orthoses also controlled hip and knee sagittal motion and foot valgus/varus during gait more effectively. Individual biomechanical, neuromuscular and psychologic attributes of the disabled child must be carefully matched with the technical attributes of each orthotic option to effect an optimal prescription. PMID:3401365

By means of the intracellular recording technique, the effect of aureofuscin (20 micrograms/ml, oversaturation solution) on the ACh release from motor nerve terminals and on muscle cell membrane potential were investigated in phrenic nerve diaphragm preparations of the mice. The results showed that (a) aureofuscin reduced the resting membrane potential of the muscle cell slightly; (b) the frequency of miniature end-plate potentials and the mean quantal content of end-plate potentials increased at first and then recovered approximately to the control level; (c) the depolarization produced by aureofuscin in the muscle cell membrane was reversible and the aureofuscin-invoked facilitation in miniature end-plate potential discharges was Ca(2+)-dependent; and (d) aureofuscin did not block neuromuscular transmission. PMID:1664976

The aim of this study was to examine effects of 21-week twice weekly strength (ST), endurance (ET) and combined (ST?+?ET 2?+?2 times a week) (SET) training on neuromuscular, endurance and walking performances as well as balance. 108 healthy men (56.3???9.9?years) were divided into three training (ST; n?=?30, ET; n?=?26, SET; n?=?31) groups and controls (C n?=?21). Dynamic 1RM and explosive leg presses (1RMleg, 50%1RMleg), peak oxygen uptake using a bicycle ergometer (VO2peak), 10?m loaded walking time (10WALK) and dynamic balance distance (DYND) were measured. Significant increases were observed in maximal 1RMleg of 21% in ST (p?p?p?=?0.005) and 10.2% in SET (p?VO2peak increased by 12.5% in ET (p?=?0.001) and 9.8% in SET (p?p?p?=?0.003) and also in DYND of ?10.3% in ST (p?=?0.002) and ?8% ...

Motoneuron (MN) dendrites may be changed from a passive to an active state by increasing the levels of spinal cord neuromodulators, which activate persistent inward currents (PICs). These exert a powerful influence on MN behavior and modify the motor control both in normal and pathological conditions. Motoneuronal PICs are believed to induce nonlinear phenomena such as the genesis of extra torque and torque hysteresis in response to percutaneous electrical stimulation or tendon vibration in humans. An existing large-scale neuromuscular simulator was expanded to include MN models that have a capability to change their dynamic behaviors depending on the neuromodulation level. The simulation results indicated that the variability (standard deviation) of a maintained force depended on the leve...

Anterior cruciate ligament (ACL) neuromuscular training programs have demonstrated beneficial effects in reducing ACL injuries, yet further evaluation of their effects on biomechanical measures across a sports team season is required to elucidate the specific factors that are modifiable. The purpose of this study was to evaluate the effects of a 10-week off-season neuromuscular training program on lower extremity kinematics. Twelve Division I female soccer players (age: 19.2 ± 0.8 years, height: 1.67 ± 0.1 m, weight: 60.2 ± 6.5 kg) performed unanticipated dynamic trials of a running stop-jump task pretraining and posttraining. Data collection was performed using an 8-camera Vicon system (Los Angeles, CA, USA) and 2 Bertec (Columbus, OH, USA) force plates. The 10-week training program consisted of resistance training 2 times per week and field training, consisting of plyometric, agility, and speed drills, 2 times per week. Repeated measures analyses of variance (ANOVAs) were used to assess the differences between pretraining and posttraining kinetics and kinematics of the hip, knee, and ankle at initial contact (IC), peak knee flexion (PKF), and peak stance. Repeated measures ANOVAs were also used to assess isometric strength differences pretraining and posttraining. The alpha level was set at 0.05 a priori. The training program demonstrated significant increases in left hip extension, left and right hip flexion, and right hip adduction isometric strength. At IC, knee abduction angle moved from an abducted to an adducted position (-1.48 ± 3.65° to 1.46 ± 3.86°, p = 0.007), and hip abduction angle increased (-6.05 ± 4.63° to -10.34 ± 6.83°, p = 0.007). Hip abduction angle at PKF increased (-2.23 ± 3.40° to 6.01 ± 3.82°, p = 0.002). The maximum knee extension moment achieved at peak stance increased from pretraining to posttraining (2.02 ± 0.32 to 2.38 ± 0.75 N·m·kg?¹, p = 0.027). The neuromuscular training program demonstrated a potential positive effect in altering mechanics that influence the risk of incurring an ACL injury. PMID:21921815

Sex steroids affect the motivation to court mates, but less is known about how they influence motor movements associated with courtship behavior. Steroidal control of motor function may be especially important for species in which courtship requires superior strength, stamina, and neuromuscular coordination. Here we use the golden-collared manakin (Manacus vitellinus) to examine whether the neuromuscular circuitry that controls motoric aspects of courtship activity is sensitive to androgens. Males of this tropical species attract mates by rapidly jumping among branches in a courtship arena and using their wings to produce loud wing snaps. Testosterone activates this display via the androgen receptor (AR), and past work reveals that manakins injected with radio-labeled T ((3)H-T) accumulate radioactivity in the spinal cord. Thus, we used quantitative PCR to measure AR, estrogen receptor-? (ER-?) subtype, and aromatase (AROM) mRNA in spinal cords of male and female manakins and zebra finches. Expression of AR, but not ER-? or aromatase, was higher throughout the manakin spinal cord compared with the zebra finch. Next, we tested whether AR-expressing skeletal muscles are innervated by motor and sensory neurons that also express AR. To do this, we backfilled spinal neurons by injecting fluorescent tracers into select AR-sensitive wing and leg muscles of wild caught male and female manakins. We then removed these spinal cords and measured AR expression with in situ hybridization. Both sexes showed abundant AR mRNA in the cervical and lumbosacral spinal enlargements as well as in dorsal root ganglia attached to these enlargements. Together our findings suggest that androgens act widely on peripheral motor and sensory circuits in golden-collared manakins to influence wing snapping displays. PMID:22635677

The objectives of the study were to evaluate factors associated with work ability and musculoskeletal symptoms among food industry workers, to evaluate thermal and neuromuscular responses during repetitive work in the cold and to find out whether cold-induced deterioration in neuromuscular...

Vertebrates display diverse patterns of neuromuscular innervation, but little is known about how such diversity is generated. In mammals, neuromuscular junctions form predominantly at equatorial locations, giving rise to a focal innervation pattern along a central endplate band. In addition, vertebr...

This study describes the effects of Bothrops marajoensis venom (Marajó lancehead) on isolated neuromuscular preparations of chick biventer cervicis (CBC) and mouse phrenic nerve-diaphragm (PND). At low concentrations (1µg/ml for CBC and 5µg/ml for PND), the venom exhibited a neuromuscular blocking w...

Abstract in spanish La debilidad muscular aguda (DMA) es el síntoma predominante de las urgencias neuromusculares, especialmente si afecta a la musculatura respiratoria u orofaríngea. La DMA es un síndrome plurietiológico y con distintos niveles lesionales en la unidad motora. Dentro del amplio grupo de enfermedades neuromusculares, las que con mayor frecuencia provocan DMA e insuficiencia respiratoria son el síndrome de Guillain-Barré (SGB) y la miastenia gravis (MG). El SGB constituy (more) e la causa más frecuente de parálisis flácida aguda; puede ocasionar fallo respiratorio en un tercio de los casos precisando ventilación mecánica. El diagnóstico preciso de este síndrome permitirá iniciar tratamiento inmunomodulador, que ha demostrado que modifica el curso de la enfermedad. Además, la valoración clínica de los pacientes y el conocimiento de sencillos tests neurofisiológicos y de función respiratoria guiarán la decisión de ventilación mecánica evitando la intubación de urgencia. La urgencia más frecuente que ocasiona la MG es la crisis miasténica, definida por el deterioro en la función bulbar con insuficiencia respiratoria aguda y riesgo de parada respiratoria. Ocurre en un 15-20% de pacientes miasténicos y puede desencadenarse por múltiples factores. Además del diagnóstico preciso de la crisis es importante la supresión de los factores desencadenantes y medidas de soporte ventilatorio. Entre las medidas farmacológicas son la plasmaféresis y las inmunoglobulinas intravenosas los instrumentos más útiles en la actualidad; estos tratamientos no sustituyen la vigilancia intensiva y el reconocimiento de los signos inminentes de fallo respiratorio que implican soporte ventilatorio invasivo o no invasivo. Abstract in english Acute muscle weakness (AMW) is the predominant symptom of neuromuscular emergencies, especially if it affects the respiratory or oropharyngeal musculature . AMW is a multi-etiological syndrome, with different lesion levels in the motor unit. Within the broad group of neuromuscular diseases, those that most frequently provoke AMW and respiratory failure are Guillain-Barré syndrome (GBS) and myasthenia gravis (MG). GBS is the most frequent cause of acute flaccid paralysis; (more) it can cause respiratory failure in a third of cases, making mechanical ventilation necessary. Accurate diagnosis of this syndrome enables immunomodulatory treatment to be started, which has been shown to modify the course of the disease. Besides, clinical evaluation of the patients and knowledge of the simple tests of neurophysiology and respiratory function will guide the decision on mechanical ventilation, avoiding emergency intubation. The most frequent emergency caused by MG is myasthenic crisis, defined by the deterioration in the bulbar function with acute respiratory insufficiency and risk of respiratory stoppage. This occurs in 15-20% of myasthenic patients and can be triggered by numerous factors. Besides early identification of the crisis, it is important to suppress the triggering factors and to provide measure of ventilatory support. Amongst the pharmacological measures, the most useful instruments at present are plasmapheresis and intravenous immunoglobulins; these treatments do not cancel the need for intensive vigilance and of checking for imminent signs of respiratory failure that will involve invasive or non-invasive ventilatory support.

Abstract in portuguese Os autores relatam um quadro manifestado por sintomas neurológicos e musculares em uma mulher de 45 anos, que surgiu após o consumo da carne de polvo comum (Octopus sp.). A paciente apresentou intenso mal estar, parestesias em extremidades e área perioral, fraqueza muscular intensa e hipotensão arterial, seguidos de prurido importante e uma erupção eritêmato-descamativa disseminada tardia. Não foram observadas manifestações gastrintestinais ou febre, o que reduz (more) iu a probabilidade de uma intoxicação alimentar por conservação inadequada do molusco. A presença de sintomas neuro-musculares é sugestiva de ação de neurotoxinas, comprovadamente existentes em muitos gêneros de polvos e que podem ter sido ingeridas através do consumo das glândulas salivares ou acúmulo das toxinas na carne, por algum mecanismo ainda desconhecido. As toxinas dos polvos do gênero Octopus são pouco estudadas e julgamos esta comunicação importante por alertar para a possibilidade do envenenamento nos seres humanos que consomem carne de polvos e ainda sua diferenciação das intoxicações alimentares que ocorrem por conservação inadequada do animal. Abstract in english The authors report neuromuscular manifestations in a 45-year-old woman after consuming octopus meat (Octopus sp.). The patient presented malaise, paresthesias in perioral and extremity areas, intense muscular weakness and arterial hypotension, followed by severe itch and disseminated cutaneous rash. Gastrointestinal manifestations and fever were not observed, reducing the probability of alimentary poisoning. The presence of muscular and neurological symptoms suggests neur (more) otoxin action, which could have been ingested by the victim from the octopus salivary glands or from an accumulation of toxins in the meat, or by an unknown mechanism. There is little known about toxins of the Octopus genus and this communication is important alert to the possibility of poisoning in humans that eat octopus and its differentiation from alimentary poisonings arising from incorrect conservation of seafood.

Abstract in portuguese A propriocepção é um mecanismo neuromuscular que descreve informações neurais originadas nas articulações, músculos e tendões. Este estudo verificou a propriocepção de joelho em jovens e idosas praticantes de exercícios físicos. Participaram do estudo 44 mulheres - 22 idosas (média de idade 69,4 anos) e 22 jovens, idade média 22,5). A propriocepção foi avaliada pelo senso de posição articular, sendo a participante solicitada a reposicionar o membro infe (more) rior dominante previamente estendido ou flexionado pelo avaliador. Os ângulos de flexão e extensão do joelho foram sorteado, utilizando-se nos testes um goniômetro fixo à perna da participante. Considerou-se como variável o valor absoluto do erro, isto é, a diferença em graus entre o ângulo proposto e o ângulo reproduzido pela avaliada. Os dados foram tratados estatisticamente, com nível de significância de p Abstract in english Proprioception is a neuromuscular mechanism that describes neural information originating from the joints, muscles and tendons. This study aimed at verifying proprioception of the knee in young and elderly women with regular physical activity. Subjects were 44 women - 22 elderly, mean age 69.4 years old, and 22 young women, mean age 22.5 years old. Proprioception was assessed by the sense of joint position, the subject being asked to reposition the dominant leg previously (more) flexed or extended by the examiner. Flexion and extension angles were randomized, and measured by means of a goniometer attached to the subject's leg. The variable considered was the absolute error value, that is, the difference between the angle proposed and the angle shown by the subject. Data were statistically analysed and significance level set at p

Abstract in portuguese O tétano acidental, a despeito de ser uma doença prevenível por imunização, ainda é frequente nos países subdesenvolvidos e em desenvolvimento. Sua letalidade ainda é elevada e os estudos sobre a melhor forma de tratamento são escassos. Tendo em vista esta escassez e a importância clínica dessa doença, um grupo de especialistas reunidos pela Associação de Medicina Intensiva Brasileira (AMIB), desenvolveu recomendações baseadas na melhor evidencia disponív (more) el para o manejo do tétano no paciente necessitando cuidados intensivos. As recomendações incluem aspectos relativos à admissão do paciente tetânico na unidade de terapia intensiva, tratamento com imunoglobulinas, tratamento antibiótico, manejo da analgossedação e bloqueio neuromuscular, manejo da disautonomia e especificidades na ventilação mecânica e fisioterapia nesta população especial. Abstract in english Although tetanus can be prevented by appropriate immunization, accidental tetanus continues to occur frequently in underdeveloped and developing countries. Tetanus mortality rates remain high in these areas, and studies regarding the best therapy for tetanus are scarce. Because of the paucity of data on accidental tetanus and the clinical relevance of this condition, the Associação de Medicina Intensiva Brasileira (AMIB) organized a group of experts to develop these gui (more) delines, which are based on the best available evidence for the management of tetanus in patients requiring admission to the intensive care unit. The guidelines discuss the management of tetanus patients in the intensive care unit, including the use of immunoglobulin therapy, antibiotic therapy, management of analgesics, sedation and neuromuscular blockade, management of dysautonomia and specific issues related to mechanical ventilation and physiotherapy in this population.

Abstract in spanish Introducción: La asistencia ventilatoria no invasiva domiciliaria (AVNI) es una modalidad de ventilación mecánica prolongada que puede ser proporcionada a niños con insuficiencia ventilatoria crónica. Objetivo: Describir las características clínicas, resultados en su evolución y calidad de vida relacionada a salud (CVRS) en pacientes ingresados a un programa nacional de AVNI. Pacientes y Métodos: Se revisaron los registros de pacientes del programa durante 24 mes (more) es (2006-2008). Se utilizó un protocolo de seguimiento previamente definido. Resultados: 177 niños, edad promedio 9,7 ± 4,7 años. Catorce fallecieron por causas no relacionadas a la AVNI. Diagnósticos: enfermedad neuromuscular (ENM) 64%, mielomeningocele operado 6%, síndrome apnea obstructiva del sueño 6%, enfermedad del parénquima pulmonar 20% y miscelánea 4%. Respecto al año previo al ingreso las hospitalizaciones disminuyeron de 60 a 21% (p Abstract in english Introduction: Prolonged mechanical ventilation may be provided to children with chronic ventilatory failure as non-invasive ventilatory assistance at home (NIVA). Objective: To describe clinical characteristics, evolution outcomes and Health Related Quality of Life (HRQOL) of pediatric patients admitted into the Chilean NIVA program. Patients and Methods: Medical files of patients included in the program, were reviewed during a period of 24 months (2006-2008), using follo (more) w-up protocols. Results: There were a total of 177 children, with an average age of 9.7 ± 4.7 years. Fourteen patients died of non-related causes. Diagnoses were: neuromuscular disease (NMD) 64%, myelomeningocele 6%, obstructive sleep apnea syndrome 6%, lung disease 20% and miscellaneous 4%. Compared to the previous year, hospitalization decreased from 60 to 21% (p

Abstract in portuguese Existem inúmeras doenças neuromusculares que acometem seres humanos. A grande maioria delas é insuficientemente conhecida quanto a mecanismos fisiopatológicos e tratamentos adequados. A limitação na manipulação experimental em «anima nobili» faz-nos procurar meios alternativos para o estudo dessas doenças, tais como animais experimentais com distúrbios neuromusculares geneticamente transmitidos. Estes mutantes constituem fonte inesgotável e valiosa de informa (more) ções quanto a mecanismos fisiopatogênicos e processos patológicos básicos em doenças neuromusculares. Entre as diversas espécies animais afetadas por distúrbios neuromusculares o camundongo é de particular interesse devido ao seu baixo custo de manutenção, rápida reprodutividade e pequeno tamanho, o que permite amplos estudos morfológicos a custos acessíveis. Nesta revisão analisamos 20 camundongos mutantes com distúrbios afetando nervo periférico, músculo esquelético ou junção neuromuscular. Aspectos genéticos, clínicos e patológicos são discutidos na intenção de oferecer informação atualizada sobre essas mutações animais, muitas das quais de. grande interesse como modelos experimentais de doenças neuromusculares humanas. Abstract in english There are several neuromuscular disorders affecting the human being. Most of these are poorly understood and lack an effective treatment. Due to the limitation of experimental manipulation in «anima nobili», inherited neuromuscular diseases in laboratory animals constitute a valuable source of scientific information. Amongst several animal species affected by neuromuscular disorders the house mouse is of particular interest because of its small size, short pregnancy and (more) low costs of maintanence. In the present review 20 murine mutants with diseases affecting peripheral nerves, skeletal muscles and motor end-plates are tabulated. Genetic, clinical and pathological aspects are discussed aiming to provide information about these mutants which might be of great interest as animal models for human neuromuscular diseases.

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Abstract in portuguese A diminuição da força muscular com o envelhecimento e os baixos níveis de atividade física contribuem para défices funcionais e de equilíbrio. Esta revisão sistemática teve como objetivo analisar os estudos que correlacionaram o treino resistido (TR) isolado, o equilíbrio e a função de idosos saudáveis. A busca nas bases do Google Acadêmico e na BVS levou à seleção de 35 estudos controlados. O TR isolado mostrou ser relevante para a função dos idosos (9 (more) 0% dos estudos) devido sobretudo ao ganho de força e mobilidade. Exercícios de baixa e moderada intensidade tiveram melhores resultados sobre a função de idosas, frágeis e sedentários. Em relação ao equilíbrio, apesar da inconsistência dos dados, o TR parece exercer efeitos positivos, sobretudo devido a fatores neuromusculares. Estudos com parâmetros de treino e amostra uniformes são necessários para melhor comparação dos resultados, sobretudo em idosos com padrão funcional elevado. Abstract in english Muscle strength decrease in aging and low physical activity levels may be an indicator of balance deficits and functional limitations. The purpose of this systematic review was to assess the effects of resistance training (RT) alone on balance performance and functional capacity in healthy elderly. The search in Google Scholar and BVS led to selecting 35 controlled trials. The RT alone showed to have positive effects (90% of the studies) on functional tasks in elderly, as (more) sociated with increases in strength and mobility. Moderate and low-intensity exercise could produce functional capacity benefits in older women, frail and sedentary elderly. Despite the inconsistency of data, resistance training appears to exert positive effects on balance, especially through neuromuscular factors. Standardization of methodology and homogeneity of sampling may ensure greater comparability of results, especially among elderly with high physical functional level.

Purpose/Background: Historically, patellofemoral pain syndrome (PFPS) has been viewed exclusively as a knee problem. Recent findings have suggested an association between hip muscle weakness and PFPS. Altered neuromuscular activity about the hip also may contribute to PFPS; however, more limited data exist regarding this aspect. Most prior investigations also have not concurrently examined hip and knee strength and neuromuscular activity in this patient population. Additional knowledge regarding the interaction between hip and knee muscle function may enhance the current understanding of PFPS. The purpose of this study was to compare hip and knee strength and electromyographic (EMG) activity in subjects with and without PFPS. Methods: Eighteen females with PFPS and 18 matched controls participated in this study. First, surface EMG electrodes were donned on the gluteus medius, vastus medialis, and vastus lateralis. Strength measures then were taken for the hip abductors, hip external rotators, and knee extensors. Subjects completed a standardized stair-stepping task to quantify muscle activation amplitudes during the loading response, single leg stance, and preswing intervals of stair descent as well as to determine muscle onset timing differences between the gluteus medius and vastii muscles and between the vastus medialis and vastus lateralis at the beginning of stair descent. Results: Females with PFPS demonstrated less strength of the hip muscles. They also generated greater EMG activity of the gluteus medius and vastus medialis during the loading response and single leg stance intervals of stair descent. No differences existed with respect to onset activation of the vastus medialis and vastus lateralis. All subjects had a similar delay in gluteus medius onset activation relative to the vastii muscles. Conclusion: Rehabilitation should focus on quadriceps and hip strengthening. Although clinicians have incorporated gluteus medius exercise in rehabilitation programs, additional attention to the external rotators may be useful. Level of Evidence: 4 PMID:9809279

Abstract in spanish La patología neuromuscular en el paciente crítico se desarrolla en dos contextos: enfermedades neurológicas primarias que requieren su ingreso en Medicina Intensiva por necesitar vigilancia estricta o ventilación mecánica y manifestaciones del sistema nervioso periférico secundarias a enfermedades sistémicas críticas. En el primer grupo son las más frecuentes el Síndrome de Guillain-Barré y la Miastenia Gravis y en el segundo la Polineuropatía y la Miopatía d (more) el paciente crítico. El patrón clínico común más frecuente consiste en el desarrollo de un cuadro de acusada debilidad y cuadriparesia cuya manifestación más típica es la necesidad de respiración asistida o la dificultad/imposibilidad para su retirada. Se consideran factores desencadenantes el fracaso multiorgánico y la sepsis en la polineuropatía y los esteroides y bloqueantes neuromusculares en la miopatía, actuando como coadyuvantes en ambos casos la malnutrición, particularmente la hipoalbimunemia, y la hiperglucemia. Considerando que la afectación neuropática y miopática coexisten con frecuencia, se ha acuñado el término polineuromiopatía del paciente crítico. Tanto el Síndrome de Guillain-Barré como la polineuropatía del paciente crítico se localizan a nivel del nervio periférico, por lo que debe efectuarse un diagnóstico diferencial entre ambos. La forma de presentación es diferente ya que el primero es una patología aguda que motiva su ingreso en UCI, mientras que la polineuropatía se adquiere durante la hospitalización. En el primero es frecuente la afectación del sistema nervioso autónomo y la disociación albúmino-citológica en el LCR, lo que no se da en la polineuropatía. Los estudios electrofisiológicos muestran signos de desmelinización con disminución de la velocidad de conducción y normalidad en la amplitud de potenciales motores en el Síndrome de Guillain- Barré frente a velocidad de conducción normal y amplitud reducida de potenciales motores en la polineuropatía axonal. La crisis miasténica afecta a la unión neuromuscular y su diagnóstico suele ser más fácil al tener en la mayoría de los casos un diagnóstico previo de miastenia gravis.La debilidad muscular aumenta durante la actividad repetida (fatiga muscular) y mejora con el reposo. Su confirmación diagnóstica se realiza con el test del edofronio y con la estimulación nerviosa repetitiva, que provoca una rápida disminución del 10-15% en la amplitud de las respuestas provocadas. La miopatía del paciente crítico se localiza en el músculo y provoca una debilidad generalizada con cuadriparesia, muy similar a la de la polineuropatía, que impide o retrasa la desconexión de la ventilación mecánica y que en sus grados avanzados puede provocar un aumento de CPK y mioglobina, junto con alteraciones en la exploración neurofisiológica. Esta última es difícil de discernir de la encontrada en la polineuropatía, aunque la normalidad en los potenciales de acción sensitiva y la redución en el potencial de ación motora con estimulación muscular directa, puede ayudar a diferenciarlos. El pronóstico funcional de las alteraciones musculares primarias suele ser bastante bueno, pero tanto la polineuropatía como la miopatía evolucionan lentamente a lo largo de semanas o meses, pudiendo quedar un importante déficit residual a los dos años en los casos más graves. Abstract in english Neuromuscular pathology in the critically ill patient develops within two settings: primary neurological diseases that require admission in the Intensive Care Medicine Unit for close monitoring or mechanical ventilation, and peripheral nervous system manifestations secondary to critical systemic diseases. The most frequent conditions in the first group are Guillain-Barré syndrome and Myasthenia Gravis, and in the second group, polyneuropathy and myopathy of the criticall (more) y ill patient. The most commonly shared clinical pattern is the development of severe weakness and quadriplegia which most typical manifestation is the need for assisted ventilation and/or weaning difficulty/impossibility. Triggering factors considered are multiorgan failure and sepsis in polyneuropathy, and steroids and neuromuscular blockers in myopathy, with malnutrition, particularly hypoalbuminemia, and hyperglycemia being co-adjuvant in both conditions.Considering that neuropathic and myopathic conditions may frequently coexist, the term polyneuromyopathy of the critically ill patient has been coined. Both Guillain-Barré syndrome and polyneuropathy of the critically ill patient involve peripheral nerves, so that the differential diagnosis has to be made between both.The presenting picture is different, since the former is an acute pathology that motivates ICU admission, whereas the latter is a polyneuropathy acquired during hospitalization. In the former, involvement of the autonomous nervous system and CSF albumin-cytology dissociation are common, which do not occur in polyneuropathy. Electrophysiological studies show demyelinating signs with decreased conduction velocity and normal amplitude of motor potentials in Guillain-Barré syndrome versus normal conduction velocity and reduced amplitude of motor potentials in axonal polyneuropathy. Myasthenic crisis affects the neuromuscular junction and its diagnosis tends to be easier since in most of the cases a previous diagnosis of myasthenia gravis exists.Muscle weakness increases during repeated activity (muscle fatigue) and improves on resting. Diagnostic confirmation is done by means of edrophonium test and by repeated nerve stimulation, which leads to a rapid decrease by 10-15% of the amplitude of evoked responses. Myopathy of the critically ill patient involves the muscle and provokes a generalized weakness with quadriplegia, very similar to that from polyneuropathy, which prevents or delays weaning from mechanical ventilation, and which may lead to CPK and myoglobin increase in more advanced stages, together with changes in neurophysiological examination. The findings of neurophysiological examination are difficult to differentiate from those encountered in polyneuropathy, although normal sensitive action potentials and reduction of motor action potentials with direct muscle stimulation may help in the differentiation. The functional prognosis of primary muscle impairments tends to be quite good, but both polyneuropathy and myopathy resolve very slowly along weeks or months, with the possibility of an important residual deficit within two years in the most severe cases.

Frailty is a feature of neuromuscular ageing. Here we provide insight into the relative contribution of pre and postsynaptic dysfunction to neuromuscular ageing using the nematode Caenorhabditis elegans. Assays of C. elegans motility highlight a precipitous decline during ageing. We describe a novel deployment of pharmacological assays of C. elegans neuromuscular function to resolve pre and postsynaptic dysfunction that underpin this decreased motility during ageing. The cholinergic agonist levamisole and the cholinesterase inhibitor aldicarb elicited whole worm contraction and allowed a direct comparison of neuromuscular integrity, from 1 to 16 days old: Measurements could be made from aged worms that were otherwise almost completely immobile. The rapidity and magnitude of the drug-induced contraction provides a measure of neuromuscular signalling whilst the difference between levamisole and aldicarb highlights presynaptic effects. Presynaptic neuromuscular transmission increased between one and five days old in wild-type but not in the insulin/IGF1 receptor mutant daf-2 (e1370). Intriguingly, there was no evidence of a role for insulin-dependent effects in older worms. Notably in 16 day old worms, which were virtually devoid of spontaneous movement, the maximal contraction produced by both drugs was unchanged. Taken together the data support a maturation of presynaptic function and/or upstream elements during early ageing that is lost after genetic reduction of insulin signalling. Furthermore, this experimental approach has demonstrated a counterintuitive phenomenon: In aged worms neuromuscular strength is maintained despite the absence of motility. PMID:23038730

Abstract In this review we present an overview of quality of life (QOL) and QOL measures in neuromuscular disorders. We discuss the characteristics of QOL measures used in neuromuscular research, highlighting differences between generic versus disease-specific and global versus health-related QOL instruments. The phenomenon of response shift is reviewed. Commonly used QOL instruments are reviewed for amyotrophic lateral sclerosis, muscle diseases, myasthenia gravis, and polyneuropathy. We also review some of what is known about QOL for patients with these neuromuscular disorders. Muscle Nerve 46: 9-25, 2012

ABSTRACT: This project endeavored to create an educational module including methodology to instruct physical medicine and rehabilitation residents in the evaluation and appropriate treatment of patients with neuromuscular disorders. It further sought to verify acquired competencies in neuromuscular rehabilitation through objective evaluation methodology. An American Association of Neuromuscular and Electrodiagnostic Medicine board-certified physician with 10 yrs of clinical experience in neuromuscular and general rehabilitation trained 19 residents using a standardized competency-based module. The residents were trained through clinical training, lectures, and review of self-assessment examination concepts from the American Academy of Physical Medicine & Rehabilitation syllabus provided in the Archives of Physical Medicine and Rehabilitation. After delivery of the educational module, knowledge acquisition and skill proficiency were measured in (1) completion of neuromuscular history and physical examination satisfactorily, (2) diagnosis and ability to design a patient care management plan via chart stimulated recall examinations, (3) physician-patient interaction via patient surveys, (4) physician-staff interaction via 360-degree global ratings, and (5) ability to write a comprehensive patient care report and to document a patient care management plan in accordance with Medicare guidelines via written patient reports. Assessment tools developed for this program address the basic competencies outlined by the Accreditation Council for Graduate Medical Education. To test the success of the standardized educational module, data were collected on an ongoing basis. The objective measures compared resident self-assessment examination scores in neuromuscular rehabilitation before and after the institution of the comprehensive neuromuscular competency module in the residency program. Nineteen (100%) of 19 residents successfully demonstrated proficiency in every segment of the evaluation module by the end of the postgraduate year 2 inpatient neuromuscular rehabilitation rotation. Furthermore, the residents' proficiency, as demonstrated by the evaluation after the implementation of the standardized educational module, positively correlated with an increase in the residents' self-assessment examination scores in neuromuscular rehabilitation compared with the residents' scores before the educational module implementation throughout all 3 yrs of training. Resident proficiency in the skills and knowledge pertaining to neuromuscular rehabilitation were objectively verified after completion of the standardized educational module. Validation of the assessment tool is evidenced by the collected data correlating with significantly improved self-assessment examination scores, as outlined in the "RESULTS" section. In addition, the clinical development tool was validated by the residents being individually observed performing history and physical examinations and being deemed competent by the American Association of Neuromuscular and Electrodiagnostic Medicine board-certified physical medicine and rehabilitation physician. The standardized educational module and evaluation methodology provide a potential framework for the definition of baseline competency in the clinical training area of neuromuscular rehabilitation. PMID:23128327

This study investigated the use of center of mass (COM) acceleration feedback for improving performance of a functional neuromuscular stimulation (FNS) control system to restore standing function to a subject with complete, thoracic-level spinal cord injury (SCI). The approach for linearly relating changes in muscle stimulation to changes in COM acceleration was verified experimentally and subsequently produced data to create an input-output map driven by sensor feedback. The feedback gains were systematically tuned to reduce upper extremity (UE) loads applied to an instrumented support device while resisting external postural disturbances. Total body COM acceleration was accurately estimated (> 89% variance explained) using three-dimensional (3-D) outputs of two accelerometers mounted on the pelvis and torso. Compared to constant muscle stimulation employed clinically, feedback control of stimulation reduced UE loading by 33%. COM acceleration feedback is advantageous in constructing a standing neuroprosthesis since it provides the basis for a comprehensive control synergy about a global, dynamic variable and requires minimal instrumentation. Future work should include tuning and testing the feedback control system during functional reaching activity that is more indicative of activities of daily living. PMID:22987499

Background Achilles tendinopathies are characterised by pain and reduced function, and heavy-load exercises have been shown to be effective in the treatment of painful chronic Achilles tendinopathies. However, basic information is needed on how the biomechanics and neuromuscular control of the exercise are affected by Achilles tendon pain. Objective The authors aimed to determine the effects of experimental Achilles tendon pain on motor function during one-legged weight bearing ankle plantar and dorsal flexion exercises. Methods In a crossover study, with 16 healthy subjects tested on two different days separated by 1 week, three-dimensional ground reaction forces, ankle joint kinematics and surface electromyography (EMG) of the lower leg muscles were recorded during one-legged full weight-bearing ankle plantar (concentric) and dorsal (eccentric) flexion exercises. Measurements were done before, during and after either experimental Achilles tendon pain or a non-painful control condition. Pain was induced by intratendinous injections of hypertonic saline with isotonic saline injections as control. Joint kinematics, ground reaction force frequency contents and average EMG amplitudes were calculated. Results Compared with the control condition experimental Achilles tendon pain reduced the EMG activity in agonistic, synergistic and antagonistic muscles, and increased the ground reaction force frequency content around 10 Hz, during both eccentric and concentric movement phases. Conclusions These data show that experimental Achilles tendon pain causes widespread and reduced motor responses with functional effects on the ground reaction force.

Membrane potential was recorded intracellularly near presynaptic terminals of the excitor axon of the crayfish opener neuromuscular junction (NMJ), while transmitter release was recorded postsynaptically. This study focused on the effects of a presynaptic calcium-activated potassium conductance, gK(...

Utrophin is the autosomal homologue of dystrophin, the protein product of the Duchenne's muscular dystrophy (DMD) locus. Utrophin expression is temporally and spatially regulated being developmentally down-regulated perinatally and enriched at neuromuscular junctions (NMJs) in adult muscle. Synaptic...

The substances which block sympathetic postganglionic transmission, xylocholine, bretylium and guanethidine, also block neuromuscular and sympathetic ganglionic transmission. To see if these last properties were related to the sympathetic blocking property, phenyltrimethylammonium, which blocks the ...

Scoliosis in fish is caused by several diverse agents that possibly act on the central nervous system, neuromuscular junctions, or ionic metabolism. The organochlorine pesticide Kepone induces scoliosis in the sheepshead minnow. Some effects associated with Kepone-induced scolios...

...toxicological endpoint and can include tremors, nervousness, insomnia, neuromuscular changes (such as weakness, muscle atrophy...parties, such as strikes, sabotage, operator intoxication or insanity, and a variety of other eventualities, must be a...

To explore the possibility that overproduction of neuronal acetylcholinesterase (AChE) confers changes in both cholinergic and morphogenic intercellular interactions, we studied developmental responses to neuronal AChE overexpression in motoneurons and neuromuscular junctions of AChE-transgenic mice...

ties to anabolic hormones such as growth hormone and the somato- medins; (2) ..... treating neuromuscular disorders (Herbison et al., 1971, 1983;. Laughman et al., 1983). ..... crew demonstrated potassium deficiency and had marked difficulty ...

Abstract in portuguese Miastenia grave é doença neuromuscular caracterizada por excessiva fatigabilidade da junção muscular e envolve, particularmente, músculos inervados por nervos cranianos. Acredita-se que o defeito esteja localizado na junção neuromuscular. Os autores estudaram os achados histoquímicos e e morfométricos em 4 pacientes com miastenia grave mostrando que as fibras do tipo II eram significativamente menores que as fibras do tipo I. Abstract in english Myasthenia gravis is a neuromuscular disease characterized by excessive fatigability of muscle function and particularly involves muscles innervated by the cranial nerves. It is believed that the defect is in the neuromuscular junction. The authors studied histochemical and morphometric findings in 4 patients with myasthenia gravis showing that the type II fibres were significantly smaller than the type I fibres.

... completely paralyzed from severe neuromuscular disorders such as Lou Gehrig's disease, brainstem stroke, or high-level spinal cord injury. ... spinal injuries, and amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease) are also responsible for this bleak condition. "It ...

Standard innominate osteotomies that are recommended for treatment of the typical form of developmental dysplasia of the hip are not recommended for dysplasia associated with neuromuscular disorders. A periacetabular osteotomy that permitted accurate correction of the posterolateral acetabular defic...

Immunoblot characterization and immunofluorescence localization of dystrophin are presented for 76 human patients with various neuromuscular diseases. Normal dystrophin (shown by immunoblotting) was invariably visualized as a continuous, peripheral membrane immunostaining of myofibers. Biochemical a...

Objective: To investigate perceived health and its relation to residual paresis from polio, late onset neuromuscular symptoms following poliomyelitis (LSP), and sex, in a population based sample of polio survivors.

Descent — Drogue chute opening will apply transverse g of short duration ...... The resultant acceleration direction is directly a function of lift-to-drag ..... Neuromuscular response (electromyography). 4. ...... Climbing of ladders, stairs or ramps ...

An area in medicine that appears suitable to man-machine principles is rehabilitation research, particularly when the motor aspects of the body are involved. If one considers the limb, whether functional or not, as the machine, the brain as the controller and the neuromuscular system as the man-machine interface, the human body is reduced to a man-machine system that can benefit from the principles behind such systems. The area of rehabilitation that this paper deals with is that of an arm amputee and his prosthetic device. Reducing this area to its man-machine basics, the problem becomes one of attaining natural multiaxis prosthetic control using Electromyographic activity (EMG) as the means of communication between man and prothesis. In order to use EMG as the communication channel it must be amplified and processed to yield a high information signal suitable for control. The most common processing scheme employed is termed Mean Value Processing. This technique for extracting the useful EMG signal consists of a differential to single ended conversion to the surface activity followed by a rectification and smoothing.

[Purpose] This study examined whether motor imagery leads to a decrease in the temporal process in terms of the onset of muscle activation and reaction time according to acquisition of motor skills in a serial reaction time (SRT) task. [Subjects] Forty one healthy, right-handed subjects with no history of neurological, orthopedic, or psychiatric disorders were enrolled in this study. The subjects were assigned randomly to the motor training group (n=13), motor imagery group (n=14), and control group (n=11). [Methods] After six visual stimuli, the subjects were instructed to move or press a moveable arm/button according to the corresponding stimuli. However, the motor imagery group performed the task without actual movement in the same task paradigm. The kinetic parameters (i.e. muscle activation and movement initiation) were analyzed before and after the training/controlled session over three consecutive days with two repetitions per day for each group. [Results] After motor skill acquisition, the motor training group and motor imagery group showed a significant decrease in processing times between the visual stimuli and two predetermined onsets, which consisted of the onset of muscular activation and reaction time. However, there were no significant changes in the control group. [Conclusion] The decrease in processing time through motor imagery can be attributed to the rapid onset of muscle activation and movement initiation, which might be induced by neuromuscular adaptation in the motor performance phase. Furthermore, we assumed that imagining the performance of a motor task could contributes to improving the motor performance in motor sequential learning.   

Hamstring injuries are common. The hamstrings and gluteus maximus (GM) work as synergists during hip extension. When contraction of GM is delayed relative to Biceps Femoris (BF) the hamstrings may be predisposed to injury due to increased demand. This study investigated whether specific training affected neuromuscular control of BF and GM during Prone Hip Extension (PHE). Twenty healthy volunteers were randomly allocated to the intervention or the control group. Mean onset times for BF and GM during PHE were recorded via surface electromyography (sEMG). The intervention group performed a 10min exercise with focus on proximal to distal muscle activation involving abdominal hollowing and active GM contraction prior to PHE. The control group undertook an exercise which included only PHE. Post exercise descriptive analysis indicated that the intervention exercise reduced the delay of GM firing relative to BF, however, when baseline differences between the two groups are taken into account as a covariant, the difference attributable to the intervention is not statistically significant (P=0.166). The results suggest that a short duration exercise intervention has the potential to alter the timing of activation of GM relative to BF during PHE but this needs validation through future research. PMID:19679506

Simultaneous electrophysiological and behavioral studies were performed on juvenile Japanese medaka (Oryzias latipes) exposed to representative neurotoxic organic chemicals at sublethal concentrations. Non-invasive recordings were made of the electrical impulses generated within giant neuronal Mauthner cells, associated interneurons or motoneurons, and musculature, all of which initiate the startle or escape response in fish. Timing in milliseconds between these electrical sequelae was measured for each fish before and at 24 and 48 hours exposure to a chemical. Also noted was the number of startle responses to number of stimuli ratio (R/S). Other groups of medaka were fed to bluegills and consumption times recorded to assess their ability to escape predation. These results were compared to neurophysiological effect levels. Phenol, 2,4-dinitrophenol, chlorpyrifos, fenvalerate, and 1-octanol impaired the ability of medaka to escape predation at all concentrations. Medaka were more susceptible to predation in high concentrations of carbaryl and strychnine, but less susceptible at low concentrations, whereas the reverse was true for endosulfan. The variety of neurological effects detected at these concentrations suggest that different mechanisms may be responsible. Phenol and strychnine affected Mauthner cell to motoneuron transmission, chlorpyrifos and carbaryl showed neuromuscular effects, and R/S was affected by most chemicals. Although a variety of neurotoxic mechanisms were examined, the exposure threshold for significant effects for each specific compound was found to be consistent for both the neurophysiological and behavioral endpoints.

Anaphylaxis is a fulminant, unexpected, immunoglobulin E-mediated allergic reaction that can be triggered by multiple agents. Common causative agents include neuromuscular blocking drugs, latex, antibiotics, colloids, hypnotics, and opioids. Fentanyl citrate, however, is an extremely unusual cause of anaphylaxis. Pulmonary edema, although uncommon in anaphylaxis, can be a prominent feature, as was in one of the patient. An adverse drug reaction is a noxious or unintended reaction to a drug that is administered in standard doses by the proper route for the purpose of prophylaxis, diagnosis, or treatment. Reactions are classified into two major subtypes: type A, which are dose dependent and predictable; and type B, which are not dose dependent and unpredictable. Unpredictable reactions include immune (allergic) or no immune drug hypersensitivity reactions and are related to genetic susceptibilities or undefined mechanisms (formally called idiosyncratic and intolerance reactions). A drug allergy is always associated with an immune mechanism for which evidence of drug-specific antibodies or activated T lymphocytes can be shown. In the last few years, many novel drugs have entered clinical practice (i.e., biologic agents) generating novel patterns of drug hypersensitivity reactions. As old drugs continue to be used, new clinical and biologic techniques enable improvement in the diagnosis of these reactions. PMID:22988407

The present study examined the fatigue development in muscle mechanical properties with emphasis on rapid force characteristics and neuromuscular activity in response to high level soccer match play. Young elite soccer players (n=9) were tested before (CON) and after (POST) a soccer match for maximal knee extensor and flexor isometric strength (MVC) and contractile rate of force development (RFD) with synchronous surface electromyography (EMG) recording. Furthermore, maximal vertical jump power and related parameters were assessed. Isometric knee extensor and flexor MVC decreased approximately 10% (p< or =0.01) along with a right-shift in the moment-time curve. RFD decreased approximately 9% (0-200 ms) for the knee flexors while there was a tendency towards reduced RFD during knee extension following soccer match play. Similar reductions were observed for some but not all selected EMG parameters during the MVC and RFD tests. Mechanical jump parameters generally remained unchanged post match play. This study is the first to examine the fatigue induced changes in rapid muscle force production (RFD) induced by soccer match play. The observed decrement in rapid muscle force capacity is likely to have negative impact on performance in explosive playing actions (i.e. accelerations, kicking, sprinting) that typically is involved in soccer match play.

SUMMARY AT A GLANCE: This study identifies factors associated with weaning success and mortality in a cohort of patients admitted to Australia's first specialised ventilation weaning unit. It reports a ward-based model of care that safely achieved a high rate of weaning success for patients who had previously failed to wean from mechanical ventilation in an ICU setting. ABSTRACT: Background and Objective:? Weaning from invasive mechanical ventilation (IMV) in specialised weaning units has been demonstrated to be safe and cost-effective. Success rates and outcomes vary widely, probably relating to patient factors and unit expertise. Methods:? An audit was undertaken of patients admitted for weaning from IMV at the Austin Hospital Ventilation Weaning Unit (VWU) between March 2002 and January 2008. Weaning success, complications and both in-hospital and long-term mortality were examined and regression analysis was undertaken to examine factors related to these outcomes. Results:? 78 patients were admitted to the VWU after a median of 27 days of IMV at their referring centre. Weaning success rate (ventilator free or nocturnal non-invasive ventilation only) was 78.2% (n=61). Inpatient mortality was 10.2% (n=8) and serious complications were infrequent. Progressive neuromuscular disease (OR 0.10) and sepsis during admission to the VWU (OR 0.09) were predictive of weaning failure at discharge. Increasing age (HR 1.93) and referral from rural or outer metropolitan centres (HR 3.57 and 2.37 respectively) were associated with increased long-term mortality. A diagnosis of either stable (HR 0.19) or progressive neuromuscular disease (HR 0.27) was associated with lower long-term mortality when compared to patients with COPD (HR 1.00). Overall survival at 12 months following discharge from the VWU was 66.7% (n=52) with most survivors residing in the community. Conclusions:? High rates of weaning success with infrequent complications and low mortality were achieved in this specialised non-ICU-based weaning unit. The VWU may provide a useful template for the development of similar units elsewhere. © 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology. PMID:22985330

Venom (10-100 @mg/ml) from Bothrops alcatraz, a pitviper from the Alcatrazes Archipelago off the coast of southeastern Brazil, caused progressive, irreversible neuromuscular blockade in chick isolated biventer cervicis preparations. The venom also inhibited contractures to exogenous ACh (110 @mM) and KCl (20 mM), caused myofiber damage and increased creatine kinase release. Commercial bothropic antivenom raised against mainland Bothrops species neutralized the neuromuscular activity, depending on the venom concentration.

More patients survive critical illness, which emphasises the need to assess outcome measures other than mortality. A prolonged decline in physical function is frequently observed after discharge in the critically ill. Neuromuscular dysfunction and muscle atrophy incurred during intensive care may prolong convalescence after discharge. Thus, strategies to counteract neuromuscular dysfunction and to improve physical outcome may reduce the overall burden of critical illness. This review describes the most common predisposing factors and discusses preventative measures and interventions.

Abstract in portuguese OBJETIVO: Avaliar a influência de duas freqüências de estimulação na instalação do bloqueio neuromuscular induzido por pancurônio e rocurônio em diafragma de ratos. MÉTODOS: Os diafragmas foram submetidos a uma freqüência de estimulação indireta de 0.1 e 1Hz (Grupos I e II, respectivamente). Os animais foram divididos em subgrupos (n=5) de acordo com o bloqueador neuromuscular a ser utilizado (pancurônio-2µg/mL e rocurônio-4µg/mL). A amplitude das respos (more) tas musculares foi avaliada 5, 15 e 30 minutos após a adição do bloqueador neuromuscular à preparação. RESULTS: A redução na intensidade da contração foi maior (p Abstract in english PURPOSE: To evaluate the influence of two stimulation frequencies on the installation of neuromuscular blockade produced by pancuronium and rocuronium on the rat diaphragm. METHODS: Diaphragms were submitted to an indirect frequency stimulation of 0.1 and 1Hz (Groups I and II, respectively). Subgroups were formed (n=5) according to the neuromuscular blocker employed (pancuronium-2µg/ml and rocuronium-4µg/ml). The twitch height depression was evaluated at 5, 15 and 30 mi (more) nutes after adding the neuromuscular blocker. RESULTS: The decrease in twitch height was greater (p

Abstract in spanish En este trabajo se pretende actualizar el tema de la Miastenia Gravis enfatizando en el diagnóstico y manejo tanto en la comunidad como en las salas de terapia intensiva. Se comentan los principales métodos diagnósticos aceptados internacionalmente y de igual forma las medidas terapéuticas aprobadas por la evidencia. Se comentan además algunos de los principales retos y controversias relacionadas con el diagnóstico y el tratamiento. La Miastenia Gravis es una enferm (more) edad autoinmune, frecuente y controlable, muchos de sus síntomas y signos pueden confundirse con varias afecciones neurológicas, por lo que su diagnóstico precoz es de suma importancia para la realización de la timectomía en el más breve plazo, sobre todo en aquellos pacientes menores de sesenta años y con expectativa de vida superior a los diez años. En ausencia de un marcador biológico más específico para el diagnóstico, se recomienda la utilización de los criterios clínicos mencionados, aunque es de esperar en los próximos años una verdadera revolución en la comprensión de la fisiología de la unión neuromuscular y del síndrome miasténico en particular. Abstract in english In this work we intend to update the topic of Myasthenia Gravis emphasizing in diagnosis and management as much in the community as in the intensive care units. Main diagnostic methods accepted internationally are commented and in equal form the therapeutic measures approved by the evidence, it is also commented some of the main challenges and controversies related with diagnosis and treatment. Myasthenia Gravis is an autoimmune, frequent and controllable disease, many of (more) its symptoms and signs may become confused with several neurological affections, that is why its precocious diagnosis is of supreme importance for the realization of the thymectomy in the briefest term, mainly in those patients smaller than sixty years and with life expectancy superior to ten years. In absence of a more specific biological marker for diagnosis, we recommend the use of the clinical criteria mentioned, although it is hope that in the next years a true revolution in the physiology comprehension of the neuromuscular junction and of the myasthenic syndrome particularly.

Abstract in portuguese Empregou-se a estimulação elétrica neuromuscular (EENM) de baixa freqüência no músculo quadríceps femoral de cães com atrofia induzida e avaliou-se a ocorrência de ganho de massa nessa musculatura. Foram utilizados oito cães com pesos entre 15 e 30kg, distribuídos aleatoriamente em dois grupos denominados de I ou controle e II ou tratado. A articulação femorotibiopatelar esquerda foi imobilizada por 30 dias pelo método de transfixação percutânea tipo II, (more) com retirada de aparelho de imobilização após esse período. Decorridas 48 horas da remoção, foi realizada a EENM nos cães do grupo II, cinco vezes por semana, com intervalo de 24 horas cada sessão, pelo período de 60 dias. Foram avaliadas a circunferência da coxa, a goniometria do joelho, a análise clínica da marcha, as enzimas creatina-quinase (CK) e aspartato-amino-transferase (AST) e a morfometria das fibras musculares em cortes transversais do músculo vasto lateral colhido mediante biópsia muscular. A EENM foi empregada no músculo quadríceps femoral na freqüência de 50Hz, duração de pulso de 300 milisegundos e relação de tempo on/off de 1:2. Quanto à morfometria das fibras do músculo vasto lateral, no grupo tratado houve aumento significativo (P Abstract in english Low frequency neuromuscular electrical stimulation (NMES) was used on the femoral quadriceps of dogs with induced muscular atrophy and the occurrence of gain in mass in these muscles was evaluated. Eight dogs from 15 to 30kg were randomly distributed in two groups named I, or control; and II, or treated. For the induction of muscular atrophy, the left femoral-tibial-patellar joint was immobilized for 30 days by percutaneous transfixation type II. After 30 days, the immobi (more) lization device was removed. The NMES treatment began 48 hours after the removal of the immobilization device of the dogs of group II, and it was carried out five times per week with an interval of 24 hours between each session, for 60 days. The following parameters were measured: thigh circumference, goniometry of the knee, clinical gait analysis, creatine kinase (CK) and aspartate aminotransferase (AST) enzymes, and morphometry of the muscular fibers in transversal cuts of the vastus lateralis muscle collected through muscular biopsy. The NMES was applied on the femoral quadriceps at a frequency of 50 Hz, with pulse duration of 300 milliseconds, and the on/off time was at a proportion of 1:2. Regarding the morphometry of the vastus lateralis fibers, a significant increase (P

Abstract in portuguese A utilização de manobras de alongamento é um dos recursos mais utilizados na prática de reabilitação. Porém, alguns parâmetros, como a freqüência, não têm sido estudados quando se utilizam as técnicas de facilitação neuromuscular proprioceptiva (FNP). O objetivo deste estudo foi analisar a freqüência ótima visando aumentar a flexibilidade dos músculos isquiotibiais, medida pela amplitude ativa de extensão do joelho. Selecionaram-se 36 sujeitos do sexo (more) feminino (média de idade (DP) de 21,7 (1,9) anos), com limitação da flexibilidade dos músculos isquiotibiais. Os sujeitos foram distribuídos aleatoriamente em quatro grupos (n = 9). Os três grupos de alongamento receberam a intervenção cinco dias por semana durante duas semanas consecutivas. O quarto grupo, que serviu como controle, não foi alongado. Os grupos de alongamento com FNP variaram quanto à freqüência em uma, três e seis manobras por sessão. Uma análise de variância (ANOVA) foi utilizada para as medidas iniciais e finais (p Abstract in spanish El uso de maniobras de alongamiento es uno de los recursos más utilizados en la práctica de rehabilitación. Sin embargo, algunos parámetros, como frecuencia, no se estudian cuando se utilizan las técnicas de facilitación neuromuscular propioceptiva (FNP). El objetivo de este estudio ha sido analizar la frecuencia óptima buscando aumentar la flexibilidad de los músculos isquio tibiales, medida por la amplitud activa de extensión de la rodilla. Se seleccionaron 36 (more) individuos del sexo femenino (con edad media (DP) de 21,7 (1,9) años), con limitación de flexibilidad de los músculos isquio tibiales. Los individuos fueron distribuidos aleatoriamente en cuatro grupos (n = 9). Los tres grupos de alongamiento recibieron intervención cinco días por semana durante dos semanas consecutivas. El cuarto grupo que sirvió como control, no fue alongado. Los grupos de alongamiento con FNP variaron en relación a la frecuencia en una, tres y seis maniobras por sesión. Un análisis de varianza (ANOVA) se usó para las medidas iniciales y finales (p Abstract in english Stretching techniques are one of the most used devices in rehabilitation practice. However, some parameters such as frequency have not been studied when proprioceptive neuromuscular facilitation (PNF) techniques are used. The purpose of this study was to analyze in the short and middle-terms the optimal frequency to increase hamstring muscle flexibility, measured by knee extension range of motion (ROM). Thirty-six female subjects were selected, (mean (SD) age 21.7 (1.9) y (more) ears) with limited hamstring muscle flexibility. The subjects were randomly assigned to four groups (n = 9). The three stretching groups received the intervention five days a week for two consecutive weeks. The three PNF stretching groups alternated concerning frequency with one, three, and six maneuvers per session. Analysis of variance (ANOVA) was used for the first and final measures (

Introduction: Age-related decreases in tongue muscle mass and strength have been reported. It may be possible to prevent age-related tongue muscle changes using neuromuscular electrical stimulation (NMES). Our hypothesis was that alterations in muscle contractile properties and myosin heavy chain composition would be found after NMES. Methods: Fifty-four young, middle-aged, and old 344/Brown Norway rats were included in this study. Twenty-four rats underwent bilateral electrical stimulation of the hypoglossal nerves for 8 weeks and were compared with control or sham rats. Muscle contractile properties and myosin heavy chain (MHC) in the genioglossus (GG), styloglossus (SG), and hyoglossus (HG) muscles were examined. Results: Compared with unstimulated control rats, we found reduced muscle fatigue, increased contraction and half-decay times, and increased twitch and tetanic tension. Increased type I MHC was found, except for in GG in old and middle-aged rats. Conclusion: Transitions in tongue muscle contractile properties and phenotype were found after NMES. Muscle Nerve, 2012. PMID:23169566

This study was undertaken to investigate and compare the effects of proprioceptive neuromuscular facilitation (PNF) stretching and static stretching on maximal voluntary contraction (MVC). Thirteen male university students (age, 20 ± 1 years; height, 172.2 ± 4.6 cm; weight, 68.4 ± 6.7 kg; mean ± SD) completed three different conditions on three non-consecutive days in randomized order: static stretching (SS), PNF stretching (PNF), and no stretching (control, CON). Each condition consisted of a 5-minute rest accompanied by one of the following activities: (a) control, (b) static stretching, or (c) PNF stretching. The hip flexion range of motion (ROM) was evaluated immediately before and after the activity. The MVC of knee flexion was then measured. Surface electromyography was recorded from the biceps femoris and vastus lateralis muscles during MVC tests and stretching. Although increases in ROM were significantly greater after PNF than after SS (P < 0.01), the decreases in MVC were similar between the two treatments. These results suggest that, although PNF stretching increases ROM more than static stretching, PNF stretching as well as static stretching is detrimental to isometric maximal strength. PMID:22395281

Myasthenia gravis (MG) is a T cell-dependent and B cell-mediated autoimmune disease of neuromuscular junctions and cytokines may play a crucial role in the pathogenesis and perpetuation of MG. MicroRNAs (miRNAs) have been implicated as fine-tuning regulators controlling diverse biological processes at the level of posttranscriptional repression. Dysregulation of miRNAs has been described in various disease states. In this study, miRNA microarrays identified let-7 family to be decreased in peripheral blood mononuclear cells (PBMCs) from MG patients compared to the healthy controls. We next demonstrated the differential expression of let-7 family in larger samples by quantitative real-time PCR. Using a combination of bioinformatics and molecular approaches, we confirmed IL-10 as a target for let-7c. IL-10 expression also showed a negative correlation with let-7c expression in PBMCs from MG patients. Further experiments revealed that induced levels of IL-10 were inversely related to let-7c levels. We also showed that let-7c could regulate IL-10 expression in Jurkat cells. In summary, our results suggest that abnormal expression/regulation of microRNAs may contribute to or be indicative of the initiation and progression of MG. PMID:22835429

The purpose was to study the effect of a sling exercise training (SET)-based core stability program on maximal throwing velocity among female handball players. Twenty-four female high-school handball players (16.6 ± 0.3 years, 63 ± 6 kg, and 169 ± 7 cm) participated and were initially divided into a SET training group (n = 14) and a control group (CON, n = 10). Both groups performed their regular handball training for 6 weeks. In addition, twice a week, the SET group performed a progressive core stability-training program consisting of 6 unstable closed kinetic chain exercises. Maximal throwing velocity was measured before and after the training period using photocells. Maximal throwing velocity significantly increased 4.9% from 17.9 ± 0.5 to 18.8 ± 0.4 m·s in the SET group after the training period (p < 0.01), but was unchanged in the control group (17.1 ± 0.4 vs. 16.9 ± 0.4 m·s). These results suggest that core stability training using unstable, closed kinetic chain movements can significantly improve maximal throwing velocity. A stronger and more stable lumbopelvic-hip complex may contribute to higher rotational velocity in multisegmental movements. Strength coaches can incorporate exercises exposing the joints for destabilization force during training in closed kinetic chain exercises. This may encourage an effective neuromuscular pattern and increase force production and can improve a highly specific performance task such as throwing. PMID:20581697

Abstract in portuguese A Distrofia Muscular de Duchenne (DMD) é uma doença hereditária de tipo neuromuscular e progressiva, que ocorre durante a infância, afetando aproximadamente 1 em 3500-6000 meninos nascidos vivos. O gene DMD que codifica a distrofina, uma proteína estrutural do músculo, está localizado no braço curto do cromossomo X na região p21, pode sofrer mutações diferentes que causam perda parcial ou total da proteína que causa DMD e outras doenças relacionadas como a di (more) strofia muscular de Becker, uma distrofia de forma mais branda. Esta é uma doença incapacitante caracterizada pela deterioração progressiva dos músculos e nos estágios avançados da doença ocorrem geralmente, complicações cardiorrespiratórias as quais são os principais motivos que causam a morte do paciente. Do ponto de vista da reabilitação, que visa retardar a progressão da doença, foram desenvolvidas uma série de estratégias de tratamento e abordagem envolvendo equipes multidisciplinares; estas vão desde o trabalho no ginásio com terapeutas para esticar á prescrição de cadeiras de rodas e formulação de ventilação mecânica não-invasiva, É bem sabido que, se não mudam as bases genéticas da doença, melhorar significativamente a independência do paciente, facilitam os cuidados pelos familiares e cuidadores e melhorar a qualidade de vida. Abstract in spanish La Distrofia Muscular de Duchenne (DMD) es una enfermedad hereditaria de tipo neuromuscular progresiva, que se presenta durante la infancia; afecta aproximadamente 1 de cada 3500 a 6000 niños varones nacidos vivos. El gen DMD que codifica para la distrofina, una proteína estructural del músculo, se localiza en el brazo corto del cromosoma X en la región p21, puede sufrir diferentes mutaciones ocasionando la pérdida parcial o total de la proteína lo que origina la DM (more) D y otras enfermedades relacionadas como la Distrofia Muscular de Becker, que es una distrofia de forma más leve. Esta es una enfermedad discapacitante que se caracteriza por un deterioro progresivo de los músculos, y en las etapas avanzadas de la enfermedad se presentan generalmente complicaciones cardiorespiratorias que son las causas principales que ocasionan la muerte al paciente. Desde el punto de vista de la rehabilitación, cuyo objetivo es retrasar la progresión de la enfermedad, se han venido desarrollado una serie de estrategias de tratamiento y manejo que involucran grupos multidisciplinarios; éstas van desde trabajo en gimnasio con terapeutas para estiramientos hasta prescripción de sillas de ruedas y formulación de ventilación mecánica no invasiva, que si bien se sabe no modifican las bases genéticas de la enfermedad, sí mejoran de forma importante la independencia del paciente, facilitan los cuidados por parte de la familia y los cuidadores y permiten una mejor calidad de vida. Abstract in english Duchenne Muscular Dystrophy (DMD) is a type of severe neuromuscular disease that occurs during childhood. It affects approximately 1 in 3500 to 6000 live male births; it is associated with the recessive X chromosome, and it manifest itself in a slightest way as Becker Muscular Dystrophy, due to a mutation in the dystrophin gene located in Xp21. This is a disabling disease that inevitably occurs until a progressive deterioration of the muscles leads to the patient's death, (more) usually from cardiorespiratory complications. From the point of view of rehabilitation, a series of management strategies have been developed in multidisciplinary groups ranging from gym work with stretch therapists to wheelchair prescriptions, and the development of noninvasive mechanical ventilation which, while they do not modify the genetic basis of the disease, do significantly improve the patient's independence as well as the care given by family and caregivers, and provide a better quality of life.

Abstract in spanish Introducción: El Programa Chileno de Ventilación No Invasiva en domicilio (AVNI) extendió su cobertura utilizando generadores de flujo con presión bi-nivelada (BiPAP) en niños con ventilación mecánica prolongada (VMP) y traqueostomía (TQT). Objetivo: Reportar la experiencia de esta estrategia describiendo criterios de selección, modalidades de uso y tecnologías complementarias. Pacientes y Métodos: Estudio descriptivo, transversal y prospectivo durante un año (more) desde Junio 2006, en 20 pacientes manejados en el Hospital Josefina Martínez, otros centros de la red asistencial del Ministerio de Salud y en domicilio. Se registraron las características clínicas, modos ventilatorios, evolución y complicaciones. Resultados: La mediana de edad fue de 3,5 años (rango 3 meses a 17 años). La duración de la VMP fue lm a 5a, 6 pacientes (30%) se encuentran en domicilio y 14 (70%) hospitalizados. La principal causa para VMP fue enfermedad neuromuscular (14, 70%). No hubo mortalidad y 4 pacientes tuvieron complicaciones menores. Conclusión: El BiPAP a través de TQT, usado con criterios estrictos de selección, es un método de VMP que puede ser factible. Se requieren estudios comparativos para definir costos, beneficios y riesgos de estos equipos comparándolos con ventiladores licenciados para soporte vital. Abstract in english Background: The Chilean Program of Noninvasive Home Ventilation started using flow generating equipment with differential pressure at 2 levels (BiPAP) through tracheostomies for prolonged mechanical ventilation (PMV). Objective: Describe the experience of this ventilatory support, reporting selection criteria, procedure and technological requirements. Method: Descriptive-transversal study that includes 20 patients treated at Hospital Josefina Martínez, other pediatric ho (more) spitals and at home, for 12 months since June 2006. The clinical features, ventilation support, technical characteristics, follow-up and complications were reported. Results: The mean age was 3.5 years-old (range 3 months - 17 years). The duration of PMV ranged between 1 month to 5 years. Six patients (30%) are at home and 14 (70%) are hospitalized. In 14 patients (70%), the need of PMV was due to neuromuscular diseases. There was no mortality related to the use of Bipap through tracheostomy; only 4 patients had minor complications. Conclusions: This report suggests that the use of BiPAP through tracheostomy in patients with selection criteria is an applicable PVM method. However, comparative systematic trials are necessary to define costs, benefits and risks of this type of ventilation.

OBJECTIVE: The integrated prospective payment program (IPP), which encourages the integrated care of mechanically ventilated patients in order to reduce the heavy utilization of high-cost intensive care units, has been implemented by Taiwan's Bureau of National Health Insurance since July 2000. The aim of this study was to assess the impact of this program on weaning, hospital stay, mortality and cost for patients requiring prolonged mechanical ventilation (PMV). DESIGN AND SETTING: A dataset of 1,000,000 randomly selected insurance holders from the National Health Research Insurance, Taiwan, was retrospectively analyzed. 7,967 adult patients (age, > 17 years) who required PMV (duration, >or= 21 days) were enrolled over a 6 year period. Measurement and Main Results: There were 3275 patients on PMV before (1997-1999) and 4,692 patients on PMV after (2001-2003) the IPP implementation. After IPP implementation, PMV was found to be required in patients with a significantly higher age, lower urbanization level, higher income status and a higher prevalence of neuromuscular disease (p<0.001). In-hospital mortality was similar between this two periods (17.2% before vs. 16.2% after, p=0.255); but the weaning rate was significantly lower in the latter period (68.1% vs. 64.2%, p<0.001). Total length of hospital stay (LOS, 75.3 d vs. 95.1 d, p<0.001), and duration of mechanical ventilation usage (55.8 d vs. 71.6 d, p<0.001) were both significantly higher after the IPP implementation. Total hospitalization cost in the PMV patients was significantly lower after IPP implementation. CONCLUSION: Implementations of the IPP program reduced the total hospitalization cost, increased the duration of mechanical ventilation usage and LOS, and reduced the weaning rate in PMV patients. PMID:23050858

Increasing evidence demonstrates that modulating the cGMP-dependent protein kinase G (PKG) pathway produces an array of behavioral phenotypes in the fruit fly, Drosophila melanogaster. Altering PKG activity, either genetically via the foraging (for) gene or using pharmacology, modifies tolerance to acute abiotic stresses such as hyperthermia and hypoxia. PKG signaling has been shown to modulate neuroprotection in many experimental paradigms of acute brain trauma and chronic neurodegenerative diseases. However, relatively little is known about how this stress-induced neuroprotective mechanism affects neural communication. In this study, we investigated the role PKG activity has on synaptic transmission at the Drosophila larval neuromuscular junction (NMJ) during acute oxidative stress and found that the application of 2.25mM hydrogen peroxide (H(2)O(2)) disrupts synaptic function by rapidly increasing the rate of neuronal failure. Here, we report that reducing PKG activity through either natural genetic variation or an induced mutation of the for gene increases synaptic tolerance during acute oxidative conditions. Furthermore, pharmacological manipulations revealed that neurotransmission is significantly extended during acute H(2)O(2) exposure upon inhibition of the PKG pathway. Conversely, activation of this signaling cascade using either genetics or pharmacology significantly reduced the time until synaptic failure. Therefore, these findings suggest a potential role for PKG activity to regulate the tolerance of synaptic transmission during acute oxidative stress, where inhibition promotes functional protection while activation increases susceptibility to neurotransmission breakdown. PMID:23136350

Myotonic dystrophy (DM), an autosomal dominant neuromuscular disease, is caused by a CTG-repeat expansion, with affected individuals having {ge}50 repeats of this trinucleotide, at the DMPK locus of human chromosome 19q13.3. Severely affected individuals die early in life; the milder form of this disease reduces reproductive ability. Alleles in the normal range of CTG repeats are not as unstable as the (CTG){sub {ge}50} alleles. In the DM families, anticipation and parental bias of allelic expansions have been noted. However, data on mechanism of maintenance of DM in populations are conflicting. We present a maximum-likelihood model for examining segregation distortion of CTG-repeat alleles in normal families. Analyzing 726 meiotic events in 95 nuclear families from the CEPH panel pedigrees, we find evidence of preferential transmission of larger alleles (of size {le}29 repeats) from females (the probability of transmission of larger alleles is .565 {plus_minus} 0.03, different from .5 at P {approx} .028). There is no evidence of segregation distortion during male meiosis. We propose a hypothesis that preferential transmission of larger CTG-repeat alleles during female meiosis can compensate for mutational contraction of repeats within the normal allelic size range, and reduced viability and fertility of affected individuals. Thus, the pool of premutant alleles at the DM locus can be maintained in populations, which can subsequently mutate to the full mutation status to give rise to DM. 31 refs., 1 fig., 5 tabs.

Congenital knee dislocation is a rare anomaly associated with a variety of neuromuscular diseases and deformities. The etiology of this condition remains unclear, but it is usually associated with a variety of disorders, such as Larsen's syndrome, arthrogryposis, spondyloepiphyseal dysplasia, Ehlers-Danlos syndrome, Down syndrome, and Streeter's dysplasia. It is rarely an isolated entity, and 60% of patients with congenital knee dislocation had additional congenital anomalies, most commonly hip dysplasia. The ideal method of treatment is debated. No current treatment algorithms address anterior cruciate ligament (ACL) elongation and its role in recurrent deformity or hyperextension. This article describes 2 patients who underwent open reduction of the knee for recurrent and neglected congenital knee dislocations. An ACL shortening and reinforcement technique is described. Both patients' treatment consisted of V-Y advancement of the extensor mechanism, soft tissue release, anterior capsulotomy, and posterior capsulorrhaphy. Anterior cruciate ligament shortening and reinforcement using an iliotibial band physeal-sparing technique was performed. The technique improved maintenance of reduction and prevented hyperextension of the knee. Anterior cruciate ligament elongation is an underemphasized anatomical feature associated with congenital knee dislocation. Due to its role in the prevention of anterior subluxation of the tibia and its effect on knee stability, incompetence should be addressed at the time of open reduction. The presence of an intact ACL with a congenital knee dislocation does not preclude management of anterior instability. Competence of the intact ACL should be addressed following reduction. PMID:22784907

There are many environmentally important chemicals which exhibit potent effects on the nervous system. Since nerve excitation takes place in a fraction of a second, electrophysiological methods provide the authors with the most straightforward approach to the study of the mechanisms of action of environmental toxicants on the nervous system. Aquatic animals such as crayfish, lobster, squid, and marine snails represent extremely useful materials for such electrophysiological studies, because much of the authors knowledge of nerve excitation is derived from those animals. Nerve excitation takes place as a result of opening and closing of ion channels of the membrane. These functions are independent of metabolic energy, and can be measured most effectively by voltage clamp techniques as applied to the giant axons of the crayfish and the squid. Patch clamp techniques developed during the past 10 years have added a new dimension to the electrophysiological investigation. These techniques allow them to measure the activity of individual ion channels, thereby making it possible to analyze the interaction of toxic molecules directly with single ion channels. Examples are given summarizing electrophysiological studies of environmental neurotoxicants. The abdominal nerve cords and neuromuscular preparations isolated from the crayfish are convenient materials for bioassay of certain environmental toxicants such as pyrethroids, chlorinated hydrocarbons, and other insecticides. Only a small fraction of the flux through the sodium channel, less than 1%, must be modified by pyrethroids for the animal to develop symptoms of poisoning. Such a toxicological application from channel to animal is important is understanding the potent toxic effect.

Chronic idiopathic intestinal pseudo-obstruction (CIIP) is a rare and severe clinical syndrome characterized by symptoms and signs of intestinal occlusion, in the absence of any mechanical obstruction of the gut lumen. In the attempt to identify the genetic basis of CIIP, we analyzed a Turkish pedigree with a high degree of consanguinity in which three siblings presented with a syndromic form of CIIP. All affected family members were characterized by recurrent, self-limiting subocclusive episodes, long-segment Barrett esophagus, and a variety of minor cardiac valve or septal defects. In some patients full-thickness intestinal biopsy samples were obtained and tissues were processed for immunohistochemistry using antibodies to different markers of the intestinal neuromuscular tract. Full-thickness biopsies of the gut wall showed abnormalities of both the neural and muscular components suggesting an underlying intestinal neuro-myopathy. Blood samples were collected for DNA extraction from each available family member and DNAs were genotyped using 382 microsatellites spanning the entire genome with the aim to take advantage of the homozygosity mapping approach. Linkage analysis identified a new syndromic locus on chromosome 8q23-q24 (multipoint LOD score=5.01). Our data strongly support the presence of a new genetic locus associated with CIIP, long-segment Barrett esophagus, and cardiac involvement on chromosome 8. PMID:17487221

Facioscapulohumeral dystrophy (FSHD) is one of the most common inherited neuromuscular disorders, with an estimated prevalence of 1:20,000. The disease is autosomal dominant, although 10-30% of cases appear to arise from a de novo mutation. The disease presents with a characteristic pattern of weakness which affects predominantly the face and scapular stabilizer muscles. Symptoms usually begin in childhood, and >90% of patients have some evidence of disease on examination by age 20. The course of the disease is slowly progressive, although many patients have long periods of relatively stable function. The cause of the disease is unknown, but recent studies have demonstrated genetic linkage to a locus on the long arm of chromosome 4 (4q35). Probes from this region detect an EcoR1 "short fragment" that cosegregates with FSHD in familial cases and appears de novo in most sporadic cases. Although the size of the small fragment correlates inversely with disease severity, the exact relationship of the fragment to the pathogenesis of the clinical disease is unclear, and a specific FSHD gene has not been identified. FSHD is currently untreatable. Few therapeutic trials of the disorder, have been conducted, largely because little is known about the underlying mechanisms of muscle injury in this disease. PMID:10711987

Most studies on the effect of aging on esophageal motor function have shown that peristaltic function deteriorates with age. Esophageal motor function is traditionally studied by means of manometry and radiography. Distension of the esophagus with evaluation of active and passive mechanical parameters have become available during recent years. In this study, we did a manometric swallow analysis and used the distension method to study esophageal properties and function during aging. An impedance planimetric probe with a bag for distension was placed in the distal esophagus of 25 healthy volunteers with a median age of 35 (range 23-86) years. Distensions were done at an infusion rate of 25 ml min(-1) with and without relaxation of neuromuscular activity with butylscopolamine. The infusion was reversed when moderate pain was experienced by the subjects. Swallow-induced contraction amplitudes decreased as function of age for persons older than 40 years (P < 0.05). The total and passive tension showed an exponential increase as function of the change in radius, whereas the active tension increased until it reached a local maximum point. The maximum active tension deteriorated as a function of age after the age of 40 years (P < 0.05). Furthermore, esophagus became stiffer with age. In conclusion, age-related changes of increased stiffness and reduced primary and secondary peristalsis were found in the human esophagus with a deterioration of esophageal function after the age of 40 years. Such changes may contribute to the high prevalence of reflux disease in elderly. PMID:18461452

Abstract in portuguese OBJETIVOS: Em passado não remoto, a incidência de náuseas e vômitos no pós-operatório (NVPO) ainda alcançava 40% a 50%. Publicações mais recentes indicam que a freqüência desta complicação ainda é considerável: 20% a 30%. O presente estudo teve como objetivo avaliar, em pacientes submetidos à anestesia geral, o impacto da administração oral de ondansetrona na incidência de NVPO. MÉTODOS: Foram incluídos 178 pacientes em estudo prospectivo, randomizado (more) , controlado e duplo-cego, divididos em dois grupos (ondansetrona=89 e placebo= 89), utilizando-se comprimidos de dissolução oral rápida, especialmente preparados para este estudo. A medicação foi administrada entre 30 e 60 minutos antes da indução anestésica. Anotou-se fatores que pudessem influenciar o evento, como gênero, idade, antecedentes de discinesia ou NVPO, tabagismo, tipo de cirurgia, índice de massa corpórea, reversão do bloqueio neuromuscular com neostigmine e intensidade da dor pós-operatória. RESULTADOS: Não houve diferença significativa entre os grupos referentes aos fatores anotados, exceto tabagismo e índice de massa corpórea, que prevaleceu no grupo placebo. Estes fatores não interferiram na análise dos resultados. Observou-se NVPO em 23 (26%) pacientes do grupo ondansetrona e 38 (43%) pacientes do grupo placebo (p Abstract in english OBJECTIVES: Not so many years ago, the incidence of postoperative nausea and vomiting used to reach 40% to 50%. More recent publications indicate that this complication still reaches considerable frequency: 20 to 30%. The present study had the objective of evaluating the impact of oral administration of ondansetron on the incidence of postoperative nausea and vomiting among patients submitted to general anesthesia. METHODS: This was a prospective, randomized, controlled, (more) double-blind study. It included 178 patients divided into two groups: Ondansetron (n = 89) and Placebo (n = 89). Fast-dissolving oral tablets specially prepared for this study were utilized. The medication was administered between 60 and 30 minutes before anesthesia was induced. Factors with possible influence on the event were noted down, such as gender, age, history of dyskinesia or postoperative nausea and vomiting, smoking, type of surgery, body mass index, reversal of neuromuscular blockade using neostigmine, and the severity of postoperative pain. RESULTS: There was no significant difference between the characteristics of the groups regarding the factors annotated, except in relation to smoking and body mass index, which were greater in the Placebo group. These factors did not interfere in the analysis of the results. Postoperative nausea and vomiting were observed in 23 patients (26%) of the Ondansetron group and 38 patients (43%) of the Placebo group (p

Study Design. Controlled intervention with group randomization.Objective. To investigate the effectiveness of a 6-month neuromuscular exercise (NME) and counseling program for reducing the incidence of low back pain (LBP) and disability in young conscripts with a healthy back at the beginning of their compulsory military service.Summary of Background Data. Basic military training is physically demanding on the back and requires adequate physical fitness. LBP causes significant morbidity and absence from military service.Methods. Participants were conscripts of four successive age cohorts (n = 1409). In the pre-study year, before adoption of the intervention, two successive cohorts of conscripts of four companies (n = 719) were followed prospectively for 6 months to study the baseline incidence of different categories of LBP. In the intervention year, conscripts (n = 690) of two new cohorts of the same companies (intervention group: anti-tank, engineer; control group: signal, mortar) were followed for 6 months. The intervention program aimed to improve conscripts' control of their lumbar neutral zone (NZ), and specifically to avoid full lumbar flexion in all daily tasks.Results. Total number and incidence of off-duty days due to LBP were significantly decreased in the intervention companies compared to controls (adjusted hazard ratio = 0.42, 95% confidence interval = 0.18 to 0.94, p = 0.035). The number of LBP cases, number of health clinic visits due to LBP, and number of the most severe cases showed a similar decreasing trend, but without statistical significance.Conclusions. These findings provide evidence that exercise and education to improve control of the lumbar NZ have a prophylactic effect on LPB-related off-duty service days in the military environment when implemented as part of military service among young healthy men. PMID:22941095

Altering neurotransmitter levels within the nervous system can cause profound changes in behavior and neuronal function. Neurotransmitter transporters play important roles in regulating neurotransmitter levels by performing neurotransmitter reuptake. It was previously shown that mutations in the Drosophila inebriated (ine)-encoded neurotransmitter transporter cause increased neuronal excitability. Here we report a further functional characterization of Ine. First we show that Ine functions in the short-term (time scale of minutes to a few hours) to regulate neuronal excitability. Second, we show that Ine is able to control excitability from either neurons or glia cells. Third, we show that overexpression of Ine reduces neuronal excitability. Overexpression phenotypes of ine include: delayed onset of long-term facilitation and increased failure rate of transmitter release at the larval neuromuscular junction, reduced amplitude of larval nerve compound action potentials, suppression of the leg-shaking behavior of mutants defective in the Shaker-encoded potassium channel, and temperature-sensitive paralysis. Each of these overexpression phenotypes closely resembles those of loss of function mutants in the para-encoded sodium channel. These data raise the possibility that Ine negatively regulates neuronal sodium channels, and thus that the substrate neurotransmitter of Ine positively regulates sodium channels. PMID:11880499

Utrophin is normally confined to the neuromuscular junction (NMJ) in adult muscle and partially compensates for the loss of dystrophin in mdx mice. We show that Akt signaling and utrophin levels were diminished in sarcospan (SSPN)-deficient muscle. By creating several transgenic and knockout mice, we demonstrate that SSPN regulates Akt signaling to control utrophin expression. SSPN determined ?-dystroglycan (?-DG) glycosylation by affecting levels of the NMJ-specific glycosyltransferase Galgt2. After cardiotoxin (CTX) injury, regenerating myofibers express utrophin and Galgt2-modified ?-DG around the sarcolemma. SSPN-null mice displayed delayed differentiation after CTX injury caused by loss of utrophin and Akt signaling. Treatment of SSPN-null mice with viral Akt increased utrophin and restored muscle repair after injury, revealing an important role for the SSPN-Akt-utrophin signaling axis in regeneration. SSPN improved cell surface expression of utrophin by increasing transportation of utrophin and DG from endoplasmic reticulum/Golgi membranes. Our experiments reveal functions of utrophin in regeneration and new pathways that regulate utrophin expression at the cell surface. PMID:22734004