Erregung und lähmung, eine allgemeine physiologie der reizwirkungen,

The greater part of the contents of this book was included in the author's Silliman lectures, delivered at Yale in October, 1911, and published under title: Irritability, a physiological analysis of the general effect of stimuli in living substances, New Haven, 1913; but sufficient material has been added to make a practically new work. cf. Vorwort.

A spectator

Color photograph of a spectator at a showing, pictured between Kevorkian's paintings "Paralysis" and "Four Presidents and a God." Photo dated June 1985. Caption by Ava Janus

Dynamics of motor nerve terminal remodeling unveiled using SNARE-cleaving botulinum toxins: the extent and duration are dictated by the sites of SNAP-25 truncation

Nerve sprouts emerge from motor nerve terminals following blockade of exo-endocytosis for more than 3 days by botulinum neurotoxin (BoNT), and form functional synapses, albeit temporary. Upon restoration of synaptic activity to the parent terminal 7 and 90 days after exposure to BoNT/F or A respectively, a concomitant retraction of the outgrowths was observed. BoNT/E caused short-term neuroparalysis, and dramatically accelerated the recovery of BoNT/A-paralyzed muscle by further truncation of SNAP-25 and its replenishment with functional full-length SNARE. The removal of 9 C-terminal residues from SNAP-25 by BoNT/A leads to persistence of the inhibitory product due to the formation of a nonproductive SNARE complex(es) at release sites, whereas deletion of a further 17 amino acids permits replenishment and a speedy recovery. (C) 2003 Elsevier Science (USA). All rights reserved.

Limitations to global disease control

In October 2000, Australia was declared poliomyelitis-free” by the World Health Organisation. This declaration followed some extensive six years of surveillance of all cases of acute flaccid paralysis, by the Poliomyelitis Expert Surveillance Committee (Centre for Disease Control, Commonwealth Department of Health and Aged Care, Canberra), chaired by the author. There have been seven attempts in the history of the world to eliminate a disease from the earth’s surface. The dramatic failure of five of these, the success of global smallpox eradication, and current successes and difficulties in the case of attempts to eliminate poliomyelitis worldwide, lead one to an analysis of the factors which led both to success and to failure. The global eradication of a specific disease is one of the most important endeavours which the international community can undertake. This audit reviews the details of such approaches; that such might be used as tools for the future.

Mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13

Distal spinal muscular atrophy is a heterogeneous group of neuromuscular disorders caused by progressive anterior born cell degeneration and characterized by progressive motor weakness and muscular atrophy, predominantly in the distal parts of the limbs. Here we report on chronic autosomal recessive distal spinal muscular atrophy in a large, inbred family with onset at various ages. Because this condition had some of the same clinical features as spinal muscular atrophy with respiratory distress, we tested the disease gene for linkage to chromosome 11q and mapped the disease locus to chromosome 11q13 in the genetic interval that included the spinal muscular atrophy with respiratory distress gene (D11S1889-D11S1321, Z(max) = 4.59 at theta = 0 at locus D11S4136). The sequencing of IGHMBP2, the human homologue of the mouse neuromuscular degeneration gene (nmd) that accounts for spinal muscular atrophy with respiratory distress, failed to detect any mutation in our chronic distal spinal muscular atrophy patients, suggesting that spinal muscular atrophy with respiratory distress and chronic distal spinal muscular atrophy are caused by distinct genes located in the so-me chromosomal region. In addition, the high intrafamilial variability in age at onset raises the question of whether nonallelic modifying genes could be involved in chronic distal spinal muscular atrophy.

Getting muscles moving again after botulinum toxin: novel therapeutic challenges

The use of botulinum neurotoxins for the treatment of muscle hyperactivity and spasticity disorders has been remarkably successful, owing to the abilities of the toxins to elicit prolonged localized paralysis and the rarity of serious adverse effects. However, botulinum toxins are the most deadly protein toxins known, and existing antidotes possess limited effectiveness. Paradoxically, in situ, the intoxicated motoneuron does not die. It reacts by emanating a sprouting network known to implement new functional synapses, leading to resumption of neurotransmission. Recent studies have highlighted ways of accelerating this natural recovery process to overcome paralysis successfully. Developing new therapeutic strategies and treatments for botulism will require more research into the molecular understanding of this 'naturally occurring' recovery process.

Axonal regeneration and lack of astrocytic gliosis in EphA4-deficient mice

Spinal cord injury usually results in permanent paralysis because of lack of regrowth of damaged neurons. Here we demonstrate that adult mice lacking EphA4 (-/-), a molecule essential for correct guidance of spinal cord axons during development, exhibit axonal regeneration and functional recovery after spinal cord hemisection. Anterograde and retrograde tracing showed that axons from multiple pathways, including corticospinal and rubrospinal tracts, crossed the lesion site. EphA4 -/- mice recovered stride length, the ability to walk on and climb a grid, and the ability to grasp with the affected hindpaw within 1-3 months of injury. EphA4 expression was upregulated on astrocytes at the lesion site in wild-type mice, whereas astrocytic gliosis and the glial scar were greatly reduced in lesioned EphA4-/- spinal cords. EphA4 -/- astrocytes failed to respond to the inflammatory cytokines, interferon-gamma or leukemia inhibitory factor, in vitro. Neurons grown on wild-type astrocytes extended shorter neurites than on EphA4 -/- astrocytes, but longer neurites when the astrocyte EphA4 was blocked by monomeric EphrinA5-Fc. Thus, EphA4 regulates two important features of spinal cord injury, axonal inhibition, and astrocytic gliosis.

Angiostrongrylus cantonensis as a cause of cerebrospinal disease in a yellow-tailed black cockatoo (Calyptorhynchus funereus) and two tawny frogmouths (Podargus strigoides)

A captive yellow-tailed black cockatoo (Calyptorhynchus funereus) and 2 free-living tawny frogmouths (Podargus strigoides), both native Australian species, were presented with neurologic signs including depression and pelvic limb paresis and paralysis. Despite supportive treatment, all 3 birds died or were euthanatized. On histologic examination, sections of metastrongyloid nematode larvae were found in the central nervous system of all 3 birds, whereas intact larvae, identified as Angiostrongylus cantonensis, were recovered from the brain and spinal cord of 2 birds. Angiostrongylus cantonensis, the rat lungworm. has an obligatory migratory phase through the host's central nervous system, which can cause severe pathologic lesions. Natural infections in accidental hosts have been documented only in mammals, and to our knowledge, angiostrongyliasis in avian hosts has not been previously reported.

Suspected fibrocartilaginous embolism in a cat

A 12-year-old cat was presented to the University of Queensland's Small Animal Teaching Hospital with a 1-day history of left herniparesis of acute onset, with no evidence of trauma or toxin exposure. Neurological examination findings were consistent with a lesion in the caudal left cervical spinal cord (C6 to C8), which was non-painful and had not progressed since the onset of clinical signs. No other abnormalities were found, although myelography showed a mild swelling involving the caudal cervical and cranial thoracic spinal segments. A diagnosis of suspected fibrocartilaginous embolism was made on the basis of the history, clinical presentation and diagnostic tests results, making this case the first report of a suspected fibrocartilaginous embolism in a cat that returned to normal function.

Proteins in the saliva of the Ixodida (ticks): Pharmacological features and biological significance

The saliva of ticks (Suborder Ixodida) is critical to their survival as parasites. A tick bite should result in strong responses from the host defence systems (haemostatic, immune and inflammatory) but tick saliva appears to have evolved to counter these responses. We review current knowledge of tick saliva components, with emphasis on those molecules confirmed to be present in the secreted saliva but including some that have only been confirmed to be present in salivary glands. About 50 tick saliva proteins that are well described in the literature are discussed. These saliva components include enzymes, enzyme inhibitors, amine-binding proteins and cytokine homologues that act as anti-haemostatic, anti-inflammatory or immuno-modulatory agents. Sequence comparisons are illustrated. The importance of tick saliva and the significance of the findings to date are also discussed. (C) 2006 Elsevier Ltd. All rights reserved.

World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines for evaluating the efficacy of acaricides against ticks (Ixodidae) on ruminants

These guidelines have been prepared to assist in the planning, conduct and interpretation of studies for the assessment of the efficacy of acaricides (excluding vaccines and other bio-control agents) against single and multi-host ticks (Ixodidae) on ruminants. Information is provided on the selection of animals, dose determination, dose confirmation and field studies, record keeping and result interpretation. The use of pen facilities is advocated for dose determination and confirmation studies for defining therapeutic and persistent efficacy. A minimum of two studies per tick species for which claims are sought is recommended for each dose determination and dose confirmation investigation. If dose confirmation studies demonstrate greater than 95% efficacy the sponsor may proceed to field studies, where a minimum of two studies per geographical location is preferred to confirm the therapeutic and persistent efficacy under field conditions. If dose confirmation studies demonstrate less than 95% efficacy then longer-term field studies can be conducted over two tick seasons with a minimum of two studies per geographical location. These studies can incorporate other control methods such as tick vaccines, to demonstrate stable long-term tick management. Specific advice is also given on conducting studies with paralysis ticks. These guidelines are also intended to assist investigators on how to conduct specific experiments, to provide specific information for registration authorities involved in the decision-making process, to assist in the approval and registration of new acaricides, and to facilitate the worldwide adoption of standard procedures. (c) 2005 Elsevier B.V. All rights reserved.

Motor unit number estimation - A Bayesian approach

All muscle contractions are dependent on the functioning of motor units. In diseases such as amyotrophic lateral sclerosis (ALS), progressive loss of motor units leads to gradual paralysis. A major difficulty in the search for a treatment for these diseases has been the lack of a reliable measure of disease progression. One possible measure would be an estimate of the number of surviving motor units. Despite over 30 years of motor unit number estimation (MUNE), all proposed methods have been met with practical and theoretical objections. Our aim is to develop a method of MUNE that overcomes these objections. We record the compound muscle action potential (CMAP) from a selected muscle in response to a graded electrical stimulation applied to the nerve. As the stimulus increases, the threshold of each motor unit is exceeded, and the size of the CMAP increases until a maximum response is obtained. However, the threshold potential required to excite an axon is not a precise value but fluctuates over a small range leading to probabilistic activation of motor units in response to a given stimulus. When the threshold ranges of motor units overlap, there may be alternation where the number of motor units that fire in response to the stimulus is variable. This means that increments in the value of the CMAP correspond to the firing of different combinations of motor units. At a fixed stimulus, variability in the CMAP, measured as variance, can be used to conduct MUNE using the "statistical" or the "Poisson" method. However, this method relies on the assumptions that the numbers of motor units that are firing probabilistically have the Poisson distribution and that all single motor unit action potentials (MUAP) have a fixed and identical size. These assumptions are not necessarily correct. We propose to develop a Bayesian statistical methodology to analyze electrophysiological data to provide an estimate of motor unit numbers. Our method of MUNE incorporates the variability of the threshold, the variability between and within single MUAPs, and baseline variability. Our model not only gives the most probable number of motor units but also provides information about both the population of units and individual units. We use Markov chain Monte Carlo to obtain information about the characteristics of individual motor units and about the population of motor units and the Bayesian information criterion for MUNE. We test our method of MUNE on three subjects. Our method provides a reproducible estimate for a patient with stable but severe ALS. In a serial study, we demonstrate a decline in the number of motor unit numbers with a patient with rapidly advancing disease. Finally, with our last patient, we show that our method has the capacity to estimate a larger number of motor units.

ASPECTOS PSICODINÂMICOS E ADAPTATIVOS DE PAIS E MÃES DE CRIANÇAS DIAGNOSTICADAS COM PARALISIA CEREBRAL

Diante do sofrimento e das questões enfrentadas por pais e mães de crianças diagnosticadas com paralisia cerebral, o presente trabalho estudou aspectos psicodinâmicos e adaptativos. Para tanto, foi realizado estudo clínico, de recorte diagnóstico, em que participaram dois pais e duas mães de crianças com paralisia cerebral que contavam de 1 a 5 anos de idade. Os pais e mães passaram por entrevistas clínicas preventivas orientadas pela EDAO e pela técnica de Desenho-Estória com Tema. A análise do material obtido indicou que todos eles passaram por período de crise após a notícia do diagnóstico da criança e, na atualidade, foram classificados como tendo Adaptação Ineficaz, sendo que os dois pais e uma mãe tinham Adaptação Ineficaz Severa, uma mãe Adaptação Ineficaz Moderada. Com relação aos aspectos intra-píquicos, foram identificadas defesas primitivas nessa lida com o sofrimento ocasionado pela deficiência da criança. Concluiu-se que os recursos internos anteriores ao nascimento da criança e à própria personalidade de cada pai/mãe foi preponderante em sua adaptação e que a paralisia cerebral da criança afetou todos os setores adaptativos dos pais e mães.(AU)

Apoptosis of neurons and oligodendrocytes in the spinal cord of spinal hyperostotic mouse (twy/twy):possible pathomechanism of human cervical compressive myelopathy

Cervical compressive myelopathy is the most serious complication of cervical spondylosis or ossification of the posterior longitudinal ligament (OPLL) and the most frequent cause of spinal cord dysfunction. There is little information on the exact pathophysiological mechanism responsible for the progressive loss of neural tissue in the spinal cord of such patients. In this study, we used the spinal hyperostotic mouse (twy/twy) as a suitable model of human spondylosis, and OPLL to investigate the cellular and molecular changes in the spinal cord. Mutant twy/twy mouse developed ossification of the ligamentum flavum at C2-C3 and exhibited progressive paralysis.

Gene therapy strategies for the treatment of spinal cord injury

Spinal cord injury is a complex pathology often resulting in functional impairment and paralysis. Gene therapy has emerged as a possible solution to the problems of limited neural tissue regeneration through the administration of factors promoting axonal growth, while also offering long-term local delivery of therapeutic molecules at the injury site. Of note, gene therapy is our response to the requirements of neural and glial cells following spinal cord injury, providing, in a time-dependent manner, growth substances for axonal regeneration and eliminating axonal growth inhibitors. Herein, we explore different gene therapy strategies, including targeting gene expression to modulate the presence of neurotrophic growth or survival factors and increase neural tissue plasticity. Special attention is given to describing advances in viral and non-viral gene delivery systems, as well as the available routes of gene delivery. Finally, we discuss the future of combinatorial gene therapies and give consideration to the implementation of gene therapy in humans. © 2014 Future Science Ltd.