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Biomedical subjects

M C Brown

Publications and source records attributed to M C Brown.

At least 181 records · Page 10Linked to original sources

Short- and long-term effects of paralysis on the motor innervation of two different neonatal mouse muscles.

1. A study was made of short- and long-term effects of paralysis induced by type A botulinum toxin on the development of innervation of mouse muscles. The toxin was injected locally over the tensor fasciae latae (t.f.l.) and gluteus muscles at various times after birth, and the innervation was later examined by intracellular recording and by a histological technique using a reduced silver stain for axons.2. Paralysis induced at 0-4 days of age delayed but did not prevent the eventual elimination of nearly all focal multiple innervation in gluteus muscle fibres, whereas in t.f.l. up to 50% of the fibres remained focally innervated by more than one axon for at least 120 days. There was an associated reduction in the number of muscle fibres in t.f.l. of between 50 and 70%. The biggest reduction in the number of gluteus fibres was under 40%.3. In the t.f.l., paralysis begun at 6-9 days caused the extent of single-site polyneuronal innervation to increase above the level existing at the time of paralysis. Histologically this increase was seen to be due at least in part to the stimulation of nodal sprout growth from a limited number of nodes.4. Motor nerve terminal sprouts were evoked by paralysis at all ages. In mice injected before 4 days of age recovery from the toxin occurred rapidly and without the formation of ectopic synapses by sprouted motor terminals; however, intrafusal motor nerves also sprouted and established a permanent ectopic innervation on surrounding extrafusal muscle fibres.5. The following conclusions are drawn. (a) In some but not all muscles, neonatally induced paralysis can not only temporarily halt elimination of polyneuronal innervation but actually lead to an increase; it is suggested tentatively that this occurs only during the neonatal period because of the availability at that time of endoneurial pathways associated with normal polyneuronal innervation, rather than because of any special neuronal growth potential then. (b) Permanent establishment of focal polyneuronal innervation is due not to stability of presynaptic elements maintained past a critical developmental stage but is associated with substantial losses of muscle fibres, leading to a high ratio of nerve fibres to muscle fibres.

Aging↗

Nerve growth from nodes of Ranvier in inactive muscle.

Paralysis of mouse gluteus maximus muscles with botulinum toxin not only evoked the expected sprouting from nerve terminals but also induced growth from some nodes of Ranvier close to the endplate region. This finding shows that nerve degeneration is not essential for nodal sprouting and supports the hypothesis that inactive muscle liberates a motor nerve growth factor.

Animals↗

Inner hair cell responses to the velocity of basilar membrane motion in the guinea pig.

Triangular wave acoustic stimulation at 200 Hz produced the expected square wave cochlear microphonic at the round window membrane and within the scala media. Intracellular recordings from inner hair cells (IHC) of the first cochlear turn showed a combination waveform having both spike impulse and square wave features. The IHC response suggests a sensitivity of these cells to both the displacement and to the velocity of basilar membrane motion.

Acoustic Stimulation↗

An assessment of the spread of the signal for terminal sprouting within and between muscles.

Certain muscles of the mouse and rat have been studied in order to assess how far a signal from denervated muscle can spread to elicit terminal sprouting from intact endplates. Denervation of the muscles surrounding the rat foot 4th lumbrical muscle caused no terminal sprouting in the 4th lumbrical itself. In the hemidenervated mouse gluteus maximus terminal sprouting was restricted to the central region of the muscle where innervated and denervated fibres intermingle. There was no enhancement of such sprouting if the underlying and closely apposed gluteus medius was simultaneously denervated. Hemidenervation of the mouse diaphragm and interscutularis, where intact endplates lie near to denervated muscle fibres, produced no terminal sprouting. Hemidenervation of the mouse platysma, where intact endplates often lie adjacent to denervated muscle fibres, similarly produced no significant response. However, all muscles were capable of producing extensive terminal sprouting in response to paralysis induced by botulinum toxin. The stimulus for terminal sprouting produced by an inactive muscle fibre must therefore be effective only on the fibre's own terminal or immediately adjacent terminals.

Animals↗

The public finance of medical and dental care in Newfoundland--some historical and economic considerations.

The article discusses the evolution of Newfoundland's health care system from the turn of the century to the present. During this time there were considerable changes in social conditions, political arrangements and the availability of public monies, all of which influenced the structure of the health care sector. In general terms, Newfoundland's health care system shifted from one involving low expenditures and many British type institutions to one involving high expenditures and American type institutions. The evidence suggests that the changes have been particularly beneficial for Newfoundland's merchant class, including the doctors and dentists, although some benefits have also accrued to patients and fishermen.

Financing, Government↗

Restoration of focal multiple innervation in rat muscles by transmission block during a critical stage of development.

1. The soleus, extensor digitorum longus and peroneus tertius muscles of the hind leg were paralysed by botulinum toxin injection in neonatal rats varying in age from 8 to 31 days. The soleus muscle was similarly paralysed in adult rats.2. Muscles were excised after different periods of block, neuromuscular transmission was assessed in vitro, and the nerve terminal size and amount of terminal sprouting and multiple innervation determined histologically using silver (Ag) and zinc iodide-osmium (ZIO) tetroxide stains.3. Recovery from the block induced by botulinum toxin was more rapid in immature multiply-innervated muscles than in muscles of older rats in which all multiple innervation had been eliminated.4. Terminals in muscles blocked during the first month after birth grew rapidly in size and developed a characteristic granulose morphology in the first few days following the block. This change did not occur in fully adult rat solei.5. Sprouts growing from the terminals were infrequent in muscles paralysed before day 16. Terminal sprouts were more frequent in muscles paralysed between 16 and 31 days of age, but were very infrequent in adult solei.6. In confirmation of Thompson, Kuffler & Jansen (1979) paralysis begun at 10 days was followed initially by a continued fall in multiple innervation detected electrophysiologically. After 2 days the percentage of muscle fibres with more than one input rose. The extra inputs did not come from terminal sprouts. They innervated the single synaptic site on each muscle fibre as they do during normal synaptogenesis.7. The amount of multiple innervation regained 5-10 days after the start of paralysis became progressively less the later paralysis started and was approximately equal to the level existing at the time the block was begun. Thus paralysis starting on or after day 16 (when all excess inputs have normally withdrawn) caused no return of multiple innervation.8. The return of multiple inputs and the swelling of the nerve terminals are presumably responses of the motoneurone to growth stimuli from inactive muscle. It is not clear whether the return of multiple innervation in the 10-15 day old rats is due to reactivation of inputs still in close contact with the end-plate before withdrawal or to regrowth of partly retracted nerve branches.9. A parallel is drawn between the limited period when inactivity can reinstate multiple innervation, and the critical period in the developing visual cortex.

Aging↗

Role of degenerating axon pathways in regeneration of mouse soleus motor axons.

1. The recovery of tension in mouse soleus was assayed 1-5 days after crushing the extramuscular nerve in muscles which had been previously either denervated by nerve crush, partly denervated by spinal nerve root section, or paralysed by I.M. injection of botulinum toxin. Recovery of tension following nerve crush in contralateral control muscles from the same mice was also measured. The muscles were then stained with zinc iodide-osmium and examined in the light microscope. 2. Recovery in control muscles began at about 50 hr after crush and was nearly complete by 5 days. Recovery began at about 50 hr after crush and was nearly complete by 5 days. Recovery began about 10 hr earlier and was more rapid in muscles denervated by crushing the muscle nerve 4 days before recrushing at the same site. 3. Paralysis 12 days earlier by intramuscular injection of botulinum toxin did not enhance recovery after nerve crush. The axons remained following partial denervation 6 days before nerve crush also regenerated at a rate similar to controls. 4. It is concluded that (1) nerves regenerate more quickly down a pre-degenerated pathway, (2) chromatolysis does not significantly enhance reinnervation, and (3) each motor axon regenerating after a crush is constrained to follow its own denervated pathway back into the muscle. 5. Histology was consistent with these conclusions, and also showed that end-plates in control muscles reinnervated after short periods of denervation were normal in appearance and possessed little "escaped' nerve growth. This was in contrast to end-plates which had been regenerated in muscle after a preceding nerve crush, botulinum toxin paralysis or partial denervation. This suggests that growth from nerve terminals is controlled locally within a muscle.

Animals↗

Postsynaptic transmission block can cause terminal sprouting of a motor nerve.

Sprouting of mouse soleus motor nerve terminals can be evoked by daily intramuscular injections of purified alpha-bungarotoxin. This finding supports the hypothesis that an important stimulus to terminal sprouting in partial denervation and presynaptic nerve blockade is a product of inactive muscle fibers.

Animals↗

Detection of urethral incompetence in women using the fluid-bridge test.

A new test for detecting urethral incompetence during coughing has been used in the investigation of women with urinary incontinence. The test detects fluid descending into the urethra and the results is positive a "fluid-bridge" is established between the bladder and a test point in the urethra. For the purpose of this study the test point selected was 0.5 cm from the urethrovesical junction. Sixty-seven incontinent patients and 23 women with normal urinary control were studied. Thirty-nine of the 67 incontinent women had a positive fluid-bridge test compared with only one of the women in the control group. The difference between the test results in the 2 group was highly significant (P < 0.001). In the incontinent patients a diagnosis was made after cystometry had been performed and after the urethral closure pressure profile had been measured. In 46 (69%) of these 67 patients there was agreement between the the diagnosis made following these urodynamic investigations and the one made from the new test. The advantages and shortcomings of the new method are compared with those of other stress tests in current use.

Adult↗

Nodal and terminal sprouting from motor nerves in fast and slow muscles of the mouse.

1. A study of nodal and terminal sprouting in fast and slow muscles of the mouse hind limb has been made using the zinc iodide and osmium tetroxide stain. 2. The terminal sprouting normally elicited by botulinum toxin injection can be prevented by regular and frequent direct electrical stimulation of the muscle fibres. But the number of end-plates innervated by nodal sprouts in partly denervated spinal preparations was not reduced by direct muscle stimulation. 3. In leg muscles given varying doses of botulinum toxin the amount of terminal sprouting was linearly related to the degree of paralysis. In partly denervated muscles neither the amount of terminal sprouting nor the amount of nodal sprouting was correlated with the degree of denervation. 4. Partial denervation causes relatively more nodal sprouting in the fast muscles peroneus tertius and extensor digitorum longus than in the slower soleus muscle, which itself has considerably more terminal sprouting than the others. The fast muscles can develop as much terminal sprouting as the soleus only in response to full paralysis with botulinum toxin. 5. No evidence could be found for a sprouting signal generated or spreading within the spinal cord. 6. It is concluded in confirmation of earlier work (Duchen & Strich, 1968; Brown & Ironton, 1977 a) that the source of the signal for terminal sprouting is denervated or otherwise inactivated muscle fibres, whose action is boosted by the presence of degenerating nervous tissues. It is suggested that fast muscles probably have less terminal sprouting when partly denervated than slow muscles (a) because of the longer time it takes a fast muscle to undergo the changes associated with inactivity and (b) because of their higher resistance to the effects of nerve degeneration. It does not seem that the signal for nodal sprouting comes from the muscle fibres but further experimentation is needed to establish this firmly.

Acetylcholine↗

Changing trends in hypertension detection and control: the Chicago experience.

Of 177,692 persons screened in 1977 as part of an ongoing City-Wide Hypertension Screening Program in Chicago, 14,988 (8.4%) had diastolic blood pressure (BP) greater than or equal to 95 mm Hg as compared to 13.2% of a similar population in 1976. Only 7% (3,910) of the hypertensive population (diastolic BP greater than or equal to 95 mm Hg or presently on antipressor drugs) had previously undetected hypertension in contrast to 11.9% (4,184) the year before and 48.7% in the same community in 1972. Conversely, 73.2% (40,738) had adequately controlled blood pressure as contrasted to 59.3% (20,897) the previous year and 20.6% in 1972. Of the remaining hypertensives, 7.5% (4,201) were known but not treated and 12.3% (6,824) were under treatment but not controlled in contrast to 12.1% (4,251) and 16.8% (5,905) respectively the year before. This upward trend in controlled hypertension was present in all strata of the population.

Adolescent↗

A central role for denervated tissues in causing nerve sprouting.

One of the oldest known forms of neuronal plasticity is the ability of peripheral nerves to grow and form functional connections after damage to neighbouring axons. Yet the source of the signal which elicits this "sprouting" remains unknown. In mammalian muscles, paralysis-which gives rise to many of the changes which occur in denervated muscles-causes motor nerve terminals to sprout. Could the inactive muscle fibres (rather than nerve degeneration products, another likely source) be responsible for some of the sprouting found in partial denervation? We confirm in this paper that direct stimulation of a partially denervated muscle inhibits sprouting and show that stimulation does so by activating the denervated fibres. Consequently after partial denervation the same signal as that which causes terminal sprouting in a paralysed muscle is able to spread from the denervated muscle fibres to the nerves on the innervated fibres and initiate terminal sprouting.

Animals↗

Schistosoma mansoni: activity responses in vitro to praziquantel.

The effects of praziquantel, a novel antischistosomal compound, on the activity of adult Schistosoma mansoni (Liverpool strain) in vitro were investigated. Worm activity was modified at all concentrations of praziquantel. High concentrations (above 0.5 microgram/ml) produced rapid paralysis, whilst low concentrations of praziquantel stimulated worm activity. It is concluded that such activity modification could lead to worm displacement in vivo.

Animals↗

Activity of Schistosoma mansoni over a ten-hour period in vitro, and its modification by oxamniquine.

The activity of pairs of adult Schistosoma mansoni maintained in a continuous flow culture system was monitored for ten hours using the ultrasound method of Brown, Norman, Bell and Chavasse (1978). The results of 75 experiments were collated by computer to demonstrate the average effect of oxamniquine on worm activity in vitro at concentrations from 0.2 microgram/ml to saturation. The averaging technique indicates that oxamniquine concentrations down to 0.2 microgram/ml modify worm activity in vitro.

Activity Cycles↗