Photolysis of amiodarone, an antiarrhythmic drug.
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Biomedical subjects
Publications and source records attributed to M Verrier.
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The autoradiographic method has been used in the Rat to map active regions in the olfactory bulb after a pulse of 14C-2-deoxyglucose with electrical stimulation of the lateral olfactory tract. The highest optical densities were found at the external plexiform, mitral, internal plexiform and granular layers; the lowest was found in the glomerular layer.
The effects of diazepam on reflex pathways in patients having complete spinal lesions and in patients having incomplete lesions of the spinal cord or multiple sclerosis are compared to determine whether diazepam has an action at spinal level. The drug produced no significant alteration in the excitability of the monosynaptic arc in the patients with complete spinal lesions. In contrast, in the group with incomplete spinal lesions or multiple sclerosis, diazepam reduced the excitability of the monosynaptic arc. This action did not appear to result from a reduction in fusimotor drive. Diazepam also reduced the tonic vibration reflex in this group. It is postulated that these effects may be due to a supraspinal action of the drug.
Descending bulbospinal pathways that employ specific neurotransmitter substances are known to be capable of modulating segmental reflex activity in the experimental animal. To determine whether this might also occur in man correlations have been sought between the activity in spinal reflex pathways and the lumbar cerebrospinal fluid (CSF) concentrations of 5-hydroxyindolacetic acid (5-HIAA), 3 methoxy-4-hydroxyphenylglycol (MHPG), and homovanillic acid (HVA) in 12 patients with complete or virtually complete spinal lesions. The concentrations of 5-HIAA and MHPG in lumbar CSF ARE REDUCED AFTER COMPLETE OR VIRTUALLY COMPLETE SPINAL LESIONS IN MAN. This may occur within 18 days of the lesion. MHPG concentrations appear to be inversely related to the level of the lesion. The HVA concentration in lumbar CSF is reduced when there is obstruction of the CSF pathways. No relationship could be demonstrated between the concentrations of 5-HIAA or MHPG in lumbar CSF and the activity in the spinal monosynaptic pathway (estimated from the proportion of the motoneurone pool activated by the Achilles tendon reflex or H reflex) or the activity of a spinal inhibitory mechanism (estimated by the degree of vibratory inhibition of the monosynaptic reflex). Patients with a tonic vibration reflex (TVR) tended to have higher MHPG levels. There appeared to be an association between low CSF HVA and enhanced vibratory inhibition of the monosynaptic reflex in the nine patients whose spinal lesions were complete.
In an attempt to clarify the neurophysiologic changes that may follow a cerebral lesion in man, we have studied patients with recent and with long-standing hemiplegia from cerebral infarction. In patients with recent cerebral lesions, inhibition of the monosynaptic reflex by vibration is enhanced. In patients with long-standing cerebral lesions, this inhibitory mechanism is less effective and a comparison of the electrically and mechanically induced monosynaptic reflexes suggests that fusimotor drive may be increased. Related clinical findings are reduced muscle "tone" immediately after the lesion and increased muscle "tone" and exaggerated tendon jerks in patients with long-standing hemiplegia.
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The direct effect of diazepam on skeletal muscle has been examined in 15 patients with neurological lesions resulting in spasticity. Diazepam 15-30 mg. IV reduced the amplitude of the compound action potential of the direct muscle response (M response) and the isometric twitch tension. It is postulated that diazepam may affect the contractile properties of muscle and, possibly, the electrical properties of the muscle membrane. These peripheral effects may contribute to the reported clinical benefits of the drug in patients with spasticity including those patients with complete spinal lesions.
A study has been made of the neurophysiological changes that follow spinal cord lesions in man. The Achilles tendon reflex (ATR) is used to estimate transmission in the Ia monosynaptic pathway, and the tonic vibration reflex (TVR) to estimate transmission in the Ia polysynaptic pathway to motoneurons. The inhibition of the H reflex by vibration is used as an estimate of presynaptic inhibition of the Ia monosynaptic pathway. Immediately following a complete lesion of the spinal cord presynaptic inhibition of the Ia monosynaptic pathway appears to be greatly increased. This enhanced inihibition may last several months but it eventually declines and in some instances becomes less than normal. Transmission in the Ia polysynaptic pathway is permanently abolished by a complete spinal lesion. A hypothesis is developed from these findings to explain the evolution of some of the clinical features that follow complete spinal lesions in man. Distinct differences are observed when the spinal lesion is incomplete. Transmission in the Ia polysynaptic pathway may be preserved and there may be no increase in presynaptic inhibition. These differences may depend upon the integrity of certain spinal long tracts which cannot be tested clinically.
The effect of diazepam on presynaptic inhibition in man has been examined in 5 patients with complete spinal transections and 7 patients with incomplete lesions. The inhibition of the H reflex by vibration applied to the tendo Achilles was used to assess presynaptic inhibition of the Ia monosynaptic pathway. Diazepam increased this inhibition in the patients with incomplete lesions, but had no significant effect on the inhibition in the patients with complete spinal transections. Evidently diazepam can enhance presynaptic inhibition in man. The effect, however, cannot be demonstrated in patients with longstanding complete spinal lesions possibly because of some alteration in the segmental presynaptic inhibitory mechanism in this group.
The neurophysiological effects of prolonged cooling were examined in seven patients with complete spinal lesions. The twitch tension of the soleus muscle, the direct (M-wave) and relfex (H-wave) response to electrical stimulation of the popliteal nerve, the Achilles tendon reflex (ATR) and the degree of inhibition of the H-wave by muscle vibration were recorded before and after a minimum of forty-five minutes cooling of the calf. Changes in the configuration of the M-wave occurred, suggesting that cooling results in slowing of conduction in muscle or motor nerve fibers. Prolongation of the twitch contraction and half relaxation time was observed, implying that the contractile mechanism of the muscle is affected. A significant decrease in the ATR/M ratio was observed, indicating that cooling, in addition, affects the muscle spindle or its connections. No significant alterations in the H/M ratio or in the degree of suppression of the H-wave by vibration were observed.
A further attempt has been made to define the receptor responsible for the inhibition of monosynaptic reflexes by vibration in man. Vibration of the tendo Achillis will produce inhibition of the H reflex even when the muscles of the anterior compartment of the leg are denervated or blocked with local anaesthetic, implying that there are receptors in the posterior compartment capable of producing this effect. However, there is evidence that vibration spreads through the limb. The inhibition is greater when the anterior compartment is innervated indicating that there is a contribution from receptors in this compartment. Stretching the muscles of the posterior compartment alone, or the muscles of the anterior and posterior compartments reciprocally does not influence the inhibition of the monosynaptic reflex by vibration. These observations support the contention that the reduction of the monosynaptic reflex by vibration in man is due to presynaptic inhibition resulting from activation of primary spindle endings.
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