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At least 109 records · Page 6Linked to original sources
PubMed2002

A novel recessive hyperekplexia allele GLRA1 (S231R): genotyping by MALDI-TOF mass spectrometry and functional characterisation as a determinant of cellular glycine receptor trafficking.

Hyperekplexia or startle disease (stiff baby syndrome, STHE) is a hereditary neurological disorder characterised by an exaggerated startle response and infantile muscle hypertonia. Several autosomal dominant and recessive forms of the disorder have been associated with point mutations in GLRA1, the human gene encoding the alpha 1 subunit of the inhibitory glycine receptor. Here, we describe a recessive point mutation (C1073G) in exon 7 of GLRA1 leading to an amino acid exchange of serine 231 to arginine in transmembrane region TM1. The mutation was detectable by restriction digest analysis of genomic PCR amplimers by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF-MS). Genotyping of family members was performed using an allele specific primer extension assay in combination with MALDI-TOF-MS and confirmed by conventional DNA sequencing. These studies demonstrate the broad applicability of MALDI-TOF-MS as a comparative screening tool applicable to the analysis of allelic gene variants. In comparison to the wild type alpha 1 subunit, biochemical, electrophysiological, and confocal microscopy data indicate a reduced integration of functional alpha 1(S231R) glycine receptors into the cell surface membrane upon recombinant expression. Apparently, the amino acid exchange S231R influences glycine receptor biogenesis and cellular trafficking by introducing a positive charge into transmembrane region TM1.

Base Sequence↗
PubMed2004

Intravesical therapy options for neurogenic detrusor overactivity.

STUDY DESIGN: Review article. SETTING: Neuro-Urology, Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland. OBJECTIVES: This review considers intravesical treatment options of neurogenic detrusor overactivity and discusses the underlying mechanism of action, clinical safety and efficacy, and the future trends. METHODS: The available literature was reviewed using medline services. RESULTS: Oral anticholinergic drugs are widely used to treat detrusor overactivity, but they are ineffective in some patients or cause systemic side effects such as blurred vision or dry mouth. As an alternative, topical therapy strategies have been suggested to achieve a profound inhibition of the overactive detrusor and to avoid high systemic drug levels. Currently available intravesical treatment options either act on the afferent arc of the reflex such as local anaesthetics or vanilloids or on the efferent cholinergic transmission to the detrusor muscle such as intravesical oxybutynin or botulinum toxin. Although an established and effective therapy, intravesical oxybutynin is not widely used. Evidence for clinical significance of intravesical atropine and local anaesthetic is missing. Intravesical capsaicin has been shown to improve clinical and urodynamic parameters, but cause pain in some patients. The intravesical instillation of resiniferatoxin and the injection of botulinum-A toxin into the detrusor muscle are promising new options; however, randomised placebo-controlled studies to prove their safety and efficacy are still missing. CONCLUSION: Intravesical treatment strategies in patients with neurogenic detrusor overactivity may provide alternatives to established therapies such as oral anticholinergics. The selectivity of the intravesical treatment and the reduction or even the absence of side effects are major advantages of this topical approach.

Administration, Intravesical↗
PubMed2003

Neuromuscular treatments for speech and swallowing: a tutorial.

Despite the proliferation of oral motor therapies, much controversy exists regarding the application and benefit of neuromuscular treatments (NMTs) such as strength training for alleviating dysarthria and/or dysphagia. Not only is limited empirical support available to validate the use of NMTs, but clinicians may also lack the foundational information needed to judge the theoretical soundness of unstudied treatment strategies. This tutorial reviews the theoretical foundations for several NMTs, including active exercises, passive exercises, and physical modalities. It highlights how these techniques have been used to address neuromuscular impairments in the limb musculature and explores potential applications to the speech and swallowing musculature. Key issues discussed in relation to active exercise are the selection of treatment targets (e.g., strength, endurance, power, range of motion), specificity of training, progression, and recovery. Factors influencing the potential effectiveness of passive exercises and physical modalities are presented, along with discussion of additional issues contributing to the controversy surrounding oral motor therapies.

Deglutition Disorders↗
PubMed2002

Clinical elements for the neuromuscular stimulation and functional electrical stimulation protocols in the practice of neurorehabilitation.

The physicians and their multidisciplinary teams involved in the clinical practice of neurological rehabilitation have more and more opportunities to apply neuromuscular stimulation (NMS) and functional electrical stimulation (FES) of peripheral nerves as a part of their daily practice. In this article, we outline clinical protocols of NMS and FES in the following clinical conditions of upper motor neuron dysfunction: to prevent consequences of disuse of the neuromuscular system of the upper motor neuron, to facilitate recovery processes of impaired upper motor neuron functions due to acute and/or subacute neurological conditions, to maintain or enhance the trophic state of the muscle, to modify altered control of muscle tone, to modify altered patterns of automatic and volitional functional movements, to enhance functional movement of the single joint muscle group within intact functional multijoint movement, and to modify altered neurocontrol of posture, locomotion, and skillful movements. We emphasize the importance of understanding the motor control alteration while developing clinical protocols and defining the goals. It is very important to be aware that similar clinical findings and due to the same cause can have different features of residual motor control, and therefore potentials for recovery or modification can be very different.

Electric Stimulation Therapy↗
PubMed2003

Effect of graduated elastic compression stockings on leg symptoms and signs during exercise in patients with deep venous thrombosis: a randomized cross-over trial.

Graduated elastic compression stockings (ECS) are often prescribed after deep venous thrombosis (DVT) to alleviate acute symptoms and to prevent and treat post-thrombotic syndrome (PTS). In patients with DVT, leg symptoms tend to worsen with exercise. The effects of ECS use during exercise have not been studied. Objectives were to determine whether ECS improve symptoms and signs and increase exercise capacity when worn during treadmill exercise by patients with prior DVT, with or without PTS. The methods employed a randomized cross-over trial. We recruited subjects who had a first episode of unilateral DVT at least 1 year earlier and categorized them as having, or not having, the PTS using a validated scale. Subjects underwent two identical treadmill exercise sessions at least 1 week apart, and were randomly assigned to wear knee-length 30 mmHg ECS on the affected leg during one of the two sessions. Venous symptoms, leg volume, leg circumference and calf muscle flexibility were measured in the affected leg before and after both exercise sessions. Subjects achieved similar percentage maximum predicted heart rates during both sessions. Comparing the ECS to no ECS session, there were no significant differences in treadmill time (21.2 vs. 21.2 min, P = 0.94), gain in leg volume (71 vs. 73 mL, P = 0.83), or change in soleus or gastrocnemius flexibility, whether or not PTS was present. Symptoms in general worsened slightly with exercise regardless of whether or not ECS were worn and did not differ according to PTS status. Per-subject analysis showed that use of ECS resulted in global improvement of symptoms in 25% of subjects, global worsening in 33% of subjects, and had no or inconsistent effects in 42% of subjects. Whether or not PTS was present, the use of ECS during exercise by patients with prior DVT did not improve symptoms and signs during exercise or increase exercise capacity.

Adult↗
PubMed2002

Treatment of detrusor-sphincter dyssynergia by pudendal nerve block in patients with spinal cord injury.

OBJECTIVE: To study the effects of pudendal nerve block with phenol on detrusor-sphincter dyssynergia in patients with spinal cord injury (SCI). DESIGN: Before-after trial performed by using a consecutive sample. SETTING: Rehabilitation hospital affiliated with a medical school. PATIENTS: Twenty-two male SCI patients (mean age, 46.3+/-11.9y; mean duration postinjury, 2.7y) with voiding dysfunction resulting from external urethral sphincter hypertonicity. INTERVENTION: Pudendal nerve block with 5% phenol solution under the guidance of electric stimulator. MAIN OUTCOME MEASURES: Outcomes were measured using (1) postvoid residual volume, maximal detrusor pressure, leak point pressure, bladder volume at the first uninhibited contraction, maximal bladder capacity, and urethral pressure profile; (2) rectoanal rest and squeeze pressures; and (3) quality of life measures for urination, quantified by the Quality of Life Index (QLI). Changes in bowel habit or autonomic dysreflexia were recorded. RESULTS: The mean decrease in postvoid residual volume was 242.8mL (mean decrease, 66%) after treatment (P<.001). The mean reduction in leak point pressure and maximal detrusor pressure were 37.1cmH(2)O and 43.3cmH(2)O, respectively (P<.05). The mean QLI significantly improved from -.74+/-.38 to.42+/-.47 (P<.001). The rectoanal pressures showed no significant difference. No complaints of fecal incontinence or other complications were noted after treatment. CONCLUSION: Pudendal nerve block performed by using 5% phenol solution was safe, easy to perform, and effective as a treatment for detrusor-sphincter dyssynergia in selected patients with SCI.

Adult↗
PubMed2006

Rho kinase as a novel molecular therapeutic target for hypertensive internal anal sphincter.

BACKGROUND & AIMS: An increase in Rho kinase (ROK) activity has been associated with agonist-induced sustained contraction of the smooth muscle, but its role in the pathophysiology of spontaneously tonic smooth muscle is not known. METHODS: Present studies examined the effects of ROK inhibitor Y-27632 in the tonic smooth muscle of the rat internal anal sphincter (IAS) versus in the flanking phasic smooth muscle of the rectum. In addition, studies were performed to determine the relationship between the decreases in the basal IAS tone and the ROK activity. Confocal microscopic studies determined the cellular distribution of the smooth muscle-predominant isoform of ROK (ROCK-II) in the smooth muscle cells (SMCs). RESULTS: In in vitro studies using neurohumoral inhibitors and tetrodotoxin and the use of SMCs demonstrate direct relaxation of the IAS SMCs by Y-27632. The ROK inhibitor was more potent in the IAS than in the rectal smooth muscle. The IAS relaxation by Y-27632 correlated specifically with the decrease in ROK activity. Confocal microscopy revealed high levels of ROCK-II toward the periphery of the IAS SMCs. In in vivo studies, the lower doses of Y-27632 caused a potent and selective decrease in the IAS pressures without any adverse cardiovascular systemic effects. The ROK inhibitor also caused potent relaxation of the hypertensive IAS. CONCLUSIONS: RhoA/ROK play a crucial role in the maintenance of the basal tone in the IAS, and ROK inhibitors have a therapeutic potential in the IAS dysfunction characterized by the hypertensive IAS.

Amides↗
PubMed2006

Contribution of 5-HT2A receptor in nematode infection-induced murine intestinal smooth muscle hypercontractility.

BACKGROUND & AIMS: Enteric nematode infection induces a smooth muscle hypercontractility that depends on interleukin (IL)-4 and IL-13 activation of the signal transducer and activator of transcription (STAT) 6. Serotonin (5-HT) is involved in the physiologic regulation of gut function. The present study investigated the contribution of 5-HT and its receptors in nematode-induced intestinal smooth muscle hypercontractility. METHODS: Mice were infected with Nippostrongylus brasiliensis (N brasiliensis) or Heligmosomoides polygyrus (H polygyrus) or injected intravenously with IL-13. Segments of jejunum were suspended in organ baths, and smooth muscle responses to 5-HT were determined in the presence or absence of specific 5-HT antagonists. IL-4, IL-13, and 5-HT receptor messenger RNA expressions were determined by real-time quantitative polymerase chain reaction. RESULTS: 5-HT evoked a modest contraction of smooth muscle in wild-type (WT) mice that was unaltered by the 5-HT2A antagonist ketanserin. N brasiliensis infection induced a smooth muscle hypercontractility to 5-HT that was abolished by 5-HT(2A) antagonists but not by other 5-HT antagonists. Infection-induced up-regulation of 5-HT2A expression was correlated with the smooth muscle hypercontractility to 5-HT. The infection-induced up-regulation of 5-HT2A in WT mice was observed also in IL-4(-/-) mice but was not seen in IL-13(-/-) or STAT6(-/-) mice. In addition, smooth muscle responses to 5-HT and 5-HT2A expression in WT mice were also enhanced by IL-13 or H polygyrus infection. CONCLUSIONS: These data show that 5-HT2A is one of the molecules downstream from STAT6 activation that mediates changes in smooth muscle function. 5-HT2A represents a novel therapeutic target for modulating immune-mediated effects on intestinal motility.

Animals↗
PubMed1980

Ultrastructural pathology of skin biopsy and fibroblast enzyme studies in a case of GM2-gangliosidosis with deficient hexosaminidase A and thermolabile hexosaminidase B.

A 2 year-old non-Jewish boy had muscle hypertonia, a black cherry spot, dementia, and seizures. His skin biopsy showed membranous cytoplasmic bodies in axonal terminals and zebra body-like inclusions in Schwann cells. Biochemically, a deficiency of Hex A and two separate Hex B peaks indicated a type 1 (B variant, Tay Sachs) like subvariant of GM2-gangliosidosis.

Axons↗
PubMed1993

Development of muscle power in preterm infants: individual trajectories after term age.

In a longitudinal study individual trajectories were traced for the developing relationship between active and passive muscle power in preterm (n = 37) and fullterm (n = 20) infants from term to 24 weeks (corrected) age. Such trajectories should enable the identification of those infants at highest risk for later neurological dysfunctions. This contention is supported by the findings of this study: those preterm infants who showed marked discrepancies between the two sorts of muscle power or rigidity in both beyond 12 weeks corrected age were most likely to manifest neurological problems at 52 weeks of age.

Female↗
PubMed1999

Functional magnetic resonance imaging of the human motor cortex before and after whole-hand afferent electrical stimulation.

Electrical stimulation of the whole hand using a mesh-glove has been shown to improve volitional movement of the hand and arm, and decrease muscle hypertonia after hemispherical stroke in patients who have reached a recovery plateau. The goal of this study was to investigate the effect of stimulation of the nerve afferents of the hand on brain cortical activity elicited by whole-hand subthreshold stimulation for sensation in humans with intact nervous systems. Brain cortical activity in 6 healthy subjects (30-45 years) was studied using blood oxygenation level-dependent functional Magnetic Resonance Imaging during a test motor task, finger-to-thumb tapping and after 20 minutes of mesh-glove stimulation of the resting hand prior to performance of an identical motor task, to test the changes in the conditioned motor task established after 20 minutes of mesh-glove stimulation. Fifteen contiguous echo-planar sequences parallel to the bicommissural plane were acquired for functional magnetic resonance. Post-processing of image data included correction of motion artefacts and calculation of correlation coefficients between the signal intensity of pixels during rest and finger tapping and a rectangular reference wave function. The functional Magnetic Resonance Imaging examinations revealed a signal increase in the primary and secondary motor and somatosensory areas when comparing the number of activated pixels during test and conditioned motor tasks. Our preliminary study indicated that change occurred in a definite pattern in the region of the regional cerebral blood flow of the brain cortex after mesh-glove whole-hand stimulation at the subthreshold level for sensation. We assumed that this increase in regional cerebral blood flow also reflected augmented neuronal activity.

Adult↗