The pathophysiology of demyelination and its implications for the symptomatic treatment of multiple sclerosis.
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Biomedical subjects
Publications and source records attributed to T A Sears.
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1. The external surface of the rib cage and abdominal wall in anaesthetized cats was surgically exposed in order to record their movements cinematographically in spontaneous breathing and in paralysed cats, during artificial positive pressure ventilation. 2. Cine-stereophotography was used to allow the recording of the movements of a set of markers placed on the external surface of the trunk wall and the corresponding stereometric data were numerically and graphically processed into three-dimensional drawings. The cine-film frames corresponding to the phases of maximum inflation and deflation of the lungs were analysed to reveal the changes in configuration associated with the respiratory movements of the trunk wall. 3. The changes in shape of the diaphragm and the diaphragm and the displacements of the abdominal viscera between extreme inflation and deflation were recorded by X-ray photography. 4. During spontaneous inspiratory movements, the ribs rotated outwards and rostrally about the costovertebral joints, bringing about an increase in the transverse dimensions of the cage all along its length; these movements were accompanied by a clear-cut caudad displacement of the sternum, caused by the straightening of the costal cartilages and by the widening of the angles defined at sternochondral joints between the sternum and each of the costal cartilages. 5. Neuromuscular blockade abolished muscle tone in the trunk wall, allowing the weight of the viscera markedly to deform its configuration. 6. The inspiratory rib movements of the paralysed animal during artificial inspiration were similar to those during spontaneous breathing but the movements of the sternum were inverted and showed small cranial displacements. 7. The loss of muscular tone under neuromuscular blockade made the abdominal wall more compliant than the rib cage to the positive lung pressure and allowed greater mobility of the viscera with consequent distortion of the shape of the diaphragm. 8. The role of rib cage muscle tone in meeting requirements of purely configurational character in such a shell-like structure is discussed in relation to the optimal mechanical performance of the diaphragm.
A brief review is given of experimental studies on 'apneusis' (Lumsden) and the role these have played in the conceptual development of the ideas relating to the nervous mechanism of breathing. It is suggested that the terms "apneustic," "pneumotaxic," and "respiratory" (inspiratory or expiratory) centers should be abandoned in view of the convoluted epistemology of the concepts they represent. New experiments on expiratory apneusis are described, involving sagittal incisions of the brain stem in the vicinity of the obex, which have allowed study of the brain stem-mediated effects of CO2 on expiratory motoneurons, under steady-state conditions. These experiments reveal the existence of a CO2-dependent tonic excitation of expiratory motoneurons that, it is argued, depends on a simple pathway between peripheral and central chemoreceptors and expiratory bulbospinal neurons. The possible synaptic mechanisms underlying the production of CO2-dependent appneusis are discussed in relation to peripheral chemoreceptors and illustrated in relation to a model motoneuron.
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1. The hypothesis is advanced that the joint occurrence of unitary excitatory post-synaptic potentials e.p.s.p.s) evoked in motoneurones by branches of common stem pre-synaptic fibres causes short-term synchronization of their discharge during the rising phases of the unitary e.p.s.p.s. 2. This hypothesis was tested using the pre- and post-stimulus time (PPST) histogram to detect synchronized firing among groups of intercostal motoneurones discharging in response to their natural synaptic drives. 3. Motor nerve action potentials were recorded monophasically from nerve filaments of the external intercostal muscles of anaesthetized, paralysed cats maintained on artificial ventilation. 4. Computer methods were used to measure peak spike amplitude, spike amplitude, spike interval and filament identification for simultaneous recordings from four filaments. The spike amplitude histograms were derived for each filament and groups of spikes were selected for analysis. 5. With spikes of one group designated as 'stimuli' (occurring at zero time) and those of a second as 'response' the PPST histogram was computed with different time bin widths. 6. With bin widths of 100 and 10 msec the central respiratory periodicity was apparent in the PPST histogram. With 1.0 msec bins the PPST histogram showed a narrow central peak extending to +/- 3.0 msec at its base. This 'short-term synchronization' supports the hypothesis of joint firing due to common presynaptic connectivity. 7. It was shown that detection of short-term synchronization was critically dependent on a sufficient quantity of data but that provided a simple criterion of adequate counts per bin in the PPST histogram was met, short-term synchronization could be detected between intercostal motoneurones of the same and adjacent segments.
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