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Curriculum↗
Biomedical subjects
T R Nichols
Publications and source records attributed to T R Nichols.
Mechanical analysis of heterogenic inhibition between soleus muscle and the pretibial flexors in the cat.
1. The role of proprioceptive pathways linking the direct antagonists soleus (S) and tibialis anterior (TA) muscles in governing the mechanical properties of the ankle joint were studied in the decerebrate cat. Actions of these heterogenic pathways were compared with those between S and extensor digitorum longus (EDL), a muscle that also acts at the metatarsophalangeal joint. These neurally mediated interactions between S and either TA or EDL were studied by applying controlled length changes to the isolated tendons of pairs of these muscles and recording the resulting changes in force. The muscles were activated with the use of electrically evoked crossed-extension reflexes, flexion reflexes, and brain stem stimulation. 2. Heterogenic inhibition from TA or EDL onto S was well developed whether S was initially quiescent or activated by a crossed-extension reflex. The inhibition persisted for the duration of the stretch of TA or EDL. During a crossed-extension reflex, TA did not generate background force, but brief stretch reflexes could be obtained. During flexion reflexes, stretch reflexes in S were usually abolished, and heterogenic inhibition from S to TA was weak or absent. 3. The strength of the heterogenic inhibition onto S was dependent on the initial length and activation level of TA and EDL. Changes in flexor length or activation level per se did not alter the background force or strength of the stretch reflex in S. Even taking into account the variation of strength of inhibition with the initial state of the muscle of origin, the strength of the inhibition was stronger from TA to S than the other way around. 4. The contributions of heterogenic inhibition from TA and EDL to S were independent in the sense that these components summed linearly with each other and with the autogenic reflex in S. In addition, the magnitude of the inhibition from TA to S was proportional to the amplitude of stretch for low to intermediate levels of initial force in S. The inhibition appeared to affect the mechanical responses of S essentially as rapidly as the stretch reflex in this muscle. 5. The heterogenic inhibition from TA to S was reduced or abolished by intravenous injections of strychnine but unaffected by injections of picrotoxin or bicuculline. These results, together with the observation that the inhibition sums linearly with the stretch reflex, suggest that the mechanism of this heterogenic inhibition is glycinergic and postsynaptic and, therefore, may include Ia-disynaptic reciprocal inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)
2-Amino-5-phosphonovalerate↗
The organization of heterogenic reflexes among muscles crossing the ankle joint in the decerebrate cat.
1. Mechanical actions of heterogenic (intermuscular) reflexes arising from proprioceptors in flexor and extensor ankle muscles were measured in intercollicular and premammillary decerebrate cats. Length inputs were applied to the freed tendons of one of a pair of muscles crossing the ankle joint and resulting changes in force in both muscles were measured. Interactions between autogenic and heterogenic reflexes were studied by applying length changes to both muscles. 2. A consistent asymmetry was observed in the heterogenic inhibition between the single-joint antagonists soleus and tibialis anterior (TA). Inhibition from soleus to TA was weak or absent during the reflex activation of TA. In contrast, a strong heterogenic inhibition was consistently observed from TA to soleus during the activation of soleus by a crossed-extension reflex. The effect of this inhibition in the intact joint is to increase the apparent mechanical stiffness of soleus. 3. Mutual synergism among soleus, medial gastrocnemius (MG) and lateral gastrocnemius (LG) was demonstrated only at low to moderate forces by the observation of excitatory reflexes among them. During a naturally or electrically evoked crossed-extension reflex, however, a unidirectional inhibitory reflex from MG and LG to soleus was observed. This inhibition increased with force in MG or LG. These results suggest that the knee and ankle joints become more tightly linked mechanically at high forces since the stiffness of the biarticular gastrocnemius muscle predominates over that of the uniarticular soleus. 4. Under quiescent conditions (no resting muscle activation), mutual synergism was obeyed among the ankle extensors soleus, LG and MG and also between the pretibial flexors TA and extensor digitorum longus (EDL). Moreover, inhibition was generally observed between a pretibial flexor and an ankle extensor. Departures from this expected pattern of heterogenic reflexes occurred when the muscle groups were activated by crossed-extension and flexion reflexes. Reflexes onto soleus, TA and EDL reversed in sign or increased in magnitude. 5. The observed patterns of reflex connectivity among the ankle flexors and extensors were similar in both intercollicular and premammillary preparations, although changes in reflex strength were sometimes noted in cases where a second, lower transection was performed during the experiment. 6. It is argued from the large magnitudes of certain heterogenic reflexes that the mechanical response properties of muscles crossing the ankle joint in the intact animal are not dominated by autogenic reflexes and intrinsic mechanical properties.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Neurologic complications of endocarditis: a 12-year experience.
We reviewed the neurologic complications in 113 patients with native and 62 patients with prosthetic valve endocarditis. Neurologic complications occurred with the same frequency (35.3% vs 38.7%) and distribution among the two groups. Death occurred in 20.6% of patients with neurologic complications and in 13.6% of patients without neurologic complications (p = 0.23). Staphylococcus aureus endocarditis correlated statistically with the development of neurologic complications (p less than 0.01) and death (p less than 0.01). Among 50 patients discharged from the hospital after receiving only medical treatment for native valve endocarditis, and followed for a mean period of 48 months, there was one patient with mitral valve prolapse and stroke. We conclude that (1) neurologic complications occur with the same frequency in native and prosthetic valve endocarditis, (2) S aureus endocarditis increases the risk of neurologic complications and death, (3) mortality is not significantly increased in patients with neurologic complications, and (4) an episode of treated native valve endocarditis does not increase the natural history of stroke in valvular disease.
Anticoagulants↗
A technique for measuring the mechanical actions of heterogenic (intermuscular) reflexes in the decerebrate cat.
Two muscle pullers were used to study the natural mechanical actions of autogenic reflexes, which arise from muscle receptors and feed back to the muscle of origin, and heterogenic reflexes, which feed back to muscles other than the muscle of origin. In the study reported here, the reflexes associated with muscles which act about the ankle joint of the decerebrate cat were investigated. Actions of autogenic pathways were measured by imposing length changes on the muscle and recording the resulting changes in force and EMG (electromyogram). Actions of heterogenic reflexes for pairs of muscles were measured by imposing appropriate combinations of length changes on the muscle of origin and on the muscle receiving the heterogenic reflex. In some cases, length changes were applied in such a way as to mimic normal mechanical coupling to evaluate the physiological importance of the reflexes, while in other cases the tests departed from normal coupling to address questions about mechanisms of reflex action. It was found that several pairs of muscles could be studied in a single experiment so that supraspinal influences on the pattern of spinal reflex connectivity can be conveniently evaluated.
Animals↗
The association of atopic diseases with endometriosis.
Comparisons of the incidence of health-related problems were conducted between women with demonstrable endometriosis (N = 88) and a control group (N = 88). Increased incidence of respondents' reports of allergic manifestations (p less than .005) were found. Directions for further research are suggested.
Candidiasis↗
Resetting of resultant stiffness in ankle flexor and extensor muscles in the decerebrate cat.
Flexor (tibialis anterior, TA, and extensor digitorum longus, EDL) and extensor (soleus, SOL) muscles in the decerebrate cat were subjected to length changes and the force responses were measured. Resultant muscular stiffness, which arises from the mechanical reaction of muscle fibers contracting prior to the length change and from a change in force due to reflex action, was calculated by dividing the changes in force by the corresponding length changes. As shown previously in the premammillary preparation, resultant stiffness was usually higher in SOL than in TA or EDL. Following an intercollicular transection in some preparations, resultant stiffness increased markedly for TA but not substantially for SOL. During continuous electrical stimulation in the magnocellular red nucleus in premammillary preparations, resultant stiffness of SOL decreased for a wide range of forces while EDL responses were unaffected. These results show that reflex gain is not determined solely by the level of motoneuronal excitability but also by a descending control from the brainstem, and that the lower resultant stiffness in flexors compared to extensors in the decerebrate cat is set by this control system and not by inherent differences in the strength of autogenetic reflex pathways for the two muscles.
Animals↗
Family trait analysis: a case-control study of 43 women with endometriosis and their best friends.
Analyses of lineage patterns show that for 43 women with endometriosis who reported that other family members have the disease, the vast majority of these familial cases involve the maternal lineage (79% to 93%). Of these women 34.9% of their mothers and 21.2% of their sisters were affected. With use of these rates, expected rates for first-degree relatives in a general population of women with endometriosis were determined. These rates were 6.2% and 3.8%, respectively; in combination, these rates yield an overall risk of 4.9% for first-degree relatives. Prior studies estimated this overall risk to be 6.9%; however, z scores determined that these rates do not differ statistically. Rates for second-degree maternal relatives are reported for grandmothers and aunts (0.4% compared to 3.1%, respectively), thus expanding results of former studies. In combination, an overall risk of 1.9% is estimated for second-degree relatives, as measured.
Adult↗
Autogenetic reflex action in tibialis anterior compared with that in soleus muscle in the decerebrate cat.
The regulatory actions of autogenetic reflex pathways on the mechanical properties of an ankle flexor (tibialis anterior) and an extensor (soleus) in the premammillary decerebrate cat were studied. The two muscle were isolated in the same cat and each was stretched during its separate activation. The yield in stiffness shown by areflexive muscles during stretch was largely compensated for in tibialis anterior as well as in soleus by reflex action. Resultant (total) stiffness varied by less than a factor of two over a wide range of contractile forces in the two muscles. Further, resultant stiffness increased as stretch amplitude decreased in both muscles, but the variation was less for TA. In most preparations, the resultant stiffness in soleus was significantly larger than the resultant stiffness of tibialis anterior. It is concluded that autogenetic reflexes govern the mechanical properties of both flexors and extensors. In addition, the extensor bias in the decerebrate preparation is due not only to greater activation in extensors but to a greater resultant stiffness as well.
Animals↗
In vitro testing for the risk of arachnoiditis from myelographic contrast media.
The risk of arachnoiditis from aqueous myelographic contrast media has been assayed reliably only in experimental animals. The effect of contrast media on protein and collagen production by fibroblasts in vitro was studied. Iocarmate, metrizamide, and iopamidol added to the culture medium caused cells to produce more protein and collagen. The degree to which the contrast medium stimulated collagen production correlated with the risk of arachnoiditis from the intrathecal use of the contrast medium. In vitro testing appears to be an effective assay for arachnoiditis.
Arachnoiditis↗
The action of puromycin and cycloheximide on the initiation of rapid axonal transport in amphibian dorsal root neurones.
1. Amphibian dorsal root ganglia-sciatic nerve preparations were incubated in vitro and the rapid axonal transport of radioactive labels was studied with a position-sensitive detector and by conventional liquid scintillation analysis. Protein was labelled by exposure of the ganglia to [(35)S]methionine or [(3)H]leucine and lipid was labelled using [(32)P]orthophosphoric acid.2. Protein synthesis was interrupted by exposure of the ganglia to either cycloheximide or puromycin. When ganglia were exposed to either inhibitor prior to or simultaneously with a label, the somal export of both protein and lipid to the axon was reduced by two to three orders of magnitude.3. Using the position-sensitive detector, [(35)S]methionine was observed to be exported from the ninth dorsal root ganglia of Rana catesbiana 3.49+/-1.56 h (+/- S.D.) after exposure, and [(32)P]phosphate 4.46+/-1.85 h after exposure.4. Export of [(35)S]methionine or [(32)P]phosphate was disrupted 3.32+/-1.21 h (+/- S.D.) or 1.93+/-1.04 h respectively after exposure of the ganglia to cycloheximide or puromycin.5. For a given preparation the time required for [(35)S]methionine to be exported was statistically equal to the time required for cycloheximide or puromycin to disrupt export. No such correlation was found to exist for the export of [(32)P]phosphate.6. Analysis revealed that materials labelled with either [(35)S]methionine or [(32)P]phosphate continue to be exported from the ganglia for several hours after the initial disruption in outflow caused by the inhibitors.7. The results do not provide support for the hypothesis of Ambron, Goldman & Schwartz (1975) that a ;key' newly synthesized, and non-storable, polypeptide is added to an already assembled structure to allow rapid axonal transport to be initiated.
Animals↗
Rapid orthograde transport of 32P-labelled material in amphibian sensory axons: a multiwire proportional chamber study.
A multiwire proportional chamber was used to follow the axonal transport of material labelled with [32P]orthophosphate in dorsal root ganglion (DRG)--sciatic nerve preparations of Xenopus laevis and Rana catesbiana. The DRG were exposed to label for a period of 4 h following which there was a period of continued delivery of labelled material to the nerve for up to 18 h. The front of the labelled material in the nerve moved at a velocity of 160--170 mm/24 h at room temperature (22.5--23.5 degrees C). Sectioning the nerve at a proximal position showed that labelled material behind the front moved at a similar rapid velocity. Experiments in which the nerve was sectioned showed that some of the rapidly transported label appeared to be deposited into a relatively stationary phase. Extrapolation of the results indicated that the delay between the presentation of the label to the DRG and the onset of the transport of labelled material in the nerve was 4--6 h. The rapid transport of the label was inhibited by vinblastine sulphate at concentrations of 130--950 microM. Most of the rapidly transported material was found to be in a chloroform-methanol extractable form. In conclusion, 32P labels materials whose transport dynamics are very similar to those observed when [35S]methionine is used as the precursor.
Animals↗
Spinal reflexes as a basis for tremor in the premammillary cat.
A maintained tremor observed in premammillary cats has been studied by varying the load attached to the soleus muscle, by electrical recording, and stimulation. The frequency and amplitude of the tremor varies widely with changes in elastic or inertial loading (springs or flywheels). These variations agree well with predictions based on the idea that the tremor is maintained by relfexes reinforcing a tendency for oscillation in a mass-spring system (which includes the elasticity of the muscle). Spinal stretch reflexes are probably responsible since a relatively fixed delay of 8.5 +/- 2.9 ms is observed between the peaks of recorded afferent and electromyographic activity. Stimulation of the lateral gastrocnemius--soleus nerve completely resets the tremor, again suggesting a reflex origin.
Animals↗
Modifications of ongoing tremors and locomotion by sensory feedback.
In principle tremors can be produced by (1) mechanical oscillators (combination of masses and springs), (2) reflex oscillators arising from sensory feedback pathways, or (3) central oscillators generated by single "pacemaker" neurones or interconnected networks. Recent studies supporting each of these mechanisms under certain conditions are discussed. Differences between these mechanisms are clarified by recent studies in Edmonton on the premammillary cat. This preparation shows a prominent reflexly-induced tremor which can be modified by mechanical loading and electrical stimulation. It also shows spontaneous stepping on a treadmill which is known to be produced by a spinal "stepping generator", but can be modified in interesting ways by sensory perturbations. The applicability of these animal studies to human tremors is considered in relation to preliminary studies in Calgary on patients with Parkinson's disease or essential tremor. We have attempted to modify these tremors by application of torque pulses applied to the wrist. The results are described in terms of a normalized "resetting" index which has a high value (greater than 0.6) for all essential tremor patients studied, and a wide range of values for different parkinsonian patients. The resetting index may be useful in determining the relative importance of peripheral and central factors in producing tremor in a variety of patients.
Animals↗
Stable long-term recordings from cat peripheral nerves.
A procedure has been developed for the stable long-term recording of nerve signals in unanesthetized mammals, which should have wide application in basic research on the nervous system and also in clinical areas such as the derivation of control signals for powered prostheses. Methods are fully described for constructing devices consisting of (1) Silastic nerve cuffs containing three or more electrodes, (2) coiled leads insulated with Silastic which extend from the cuffs to an integrated circuit socket, (3) a vitreous carbon transcutaneous connector which surrounds the integrated circuit socket and makes a good interface with the skin. Neural activity has been recorded from mammalian nerves for many months during normal behaviour. The peak-to-peak amplitude and latency of the recorded compound action potentials remain stable and may continue at a constant level more or less indefinitely. A tripolar recording configuration between a central lead and the two end leads, which are connected together, permits good rejection of EMG signals from surrounding muscles. The amplitude of single unit potentials increases as the square of the conduction velocity of the nerve fibre. Thus, the largest nerve fibres will dominate the signals recorded during behaviour. The reasons for premature termination of a few experiments are given together with methods for overcoming these problems. For example, platinum-iridium electrodes remain relatively stable, whereas silver wires tend to fracture after being in an animal for several months. This and other relationships are discussed which permit an optimal design of nerve cuffs for a given recording situation.
Action Potentials↗
Improvement in linearity and regulation of stiffness that results from actions of stretch reflex.
We studied stretch reflexes of soleus muscles of intercollicularly decerebrated cats using a new technique for estimating the component of a stretch reflex that results from the purely mechanical properties of the active muscle (mechanical response). The difference between a net stretch reflex and its underlying mechanical response provided a direct measure of reflex action. 1. The relative contributions of reflex action and the mechanical response are different for stretch and release. With stretch, reflex action is generally large and the mechanical response small. The opposite is true with release. The property that remains relatively constant, when stretch and release are compared, is the net stiffness in opposition to length change. We concluded that reflex action compensates for variations in the inherent stiffness of the muscle. 2. Compensation is effective over a range of intermediate values of initial force, but it fails whenever the reflex force approaches zero or the maximal force at that length. 3. Reflex action is capable of modifying muscular force within 22 ms of the onset of length change. This indicates that even during a fast gallop, there is sufficient time for reflex action. 4. The mechanical properties of the active soleus muscle are highly nonlinear; e.g., muscular stiffness becomes negative transiently during stretch. In stable decerebrate preparations we found that reflex action resulted in a considerable improvement in linearity. 5. Our results support two complementary hypotheses: a) stiffness may be the regulated property of the stretch reflex, and b) the main function of autogenetic reflexes may be to conpensate for variations in the properties of skeletal muscle rather than to oppose changes in load.
Animals↗
Principles underlying new methods for chronic neural recording.
Chronic recording is possible from nerve fibers which have grown through holes in an insulating medium (regeneration electrodes) or which are enclosed by an insulating sheath (cuff electrodes). Use of three electrodes in a balanced configuration permits good rejection of electromyographic (EMG) signals and other sources of electrical interference (fluorescent lights, 60 Hz signals from the mains, etc.). Equations are derived and tested for predicting the amplitude and form of the signals expected for a given cuff length and diameter. These equations can be used to design electrode units optimally for a given application. Finally, the use of transformers permits the neural signals to be carefully matched to the recording apparatus and further optimizes the neural signal-to-noise and signal-to-EMG ratios. Use of these methods in several physiological and clinical applications, as well as potential abuses, are discussed.
Animals↗
Reflex compensation for variations in the mechanical properties of a muscle.
Soleus muscles of anesthetized cats were stretched and released by different amounts while their motor axons were stimulated. Muscle force increased, then gave way in response to large stretch. In the presence of active stretch reflexes in decerebrate cats, the give in force was absent. We demonstrate that autogenetic reflexes can compensate for variations in muscular stiffness revealed when responses to stretch and release are compared.
Animals↗