Biomedical subjects

W R Ferrell

Publications and source records attributed to W R Ferrell.

At least 73 records · Page 4Linked to original sources

PubMed1989

Capsaicin suppresses substance P-induced joint inflammation in the rat.

Intra-articular injection of 20 micrograms substance P in rat knee joints results in a pronounced inflammatory response. However, prior intra-articular injection of 1% capsaicin solution (1-5 weeks previously) virtually abolishes this response. This is not a neurotoxic effect of capsaicin on nerve fibres as denervation of the knee produces no alteration of the response to injected substance P. The potent effect of capsaicin on substance P-mediated inflammation cannot be attributed to depletion of mast cells by this treatment as the mast cell degranulator compound 48/80 injected into capsaicin pre-treated knees still gives rise to a marked inflammatory response. Compound 48/80 does not activate nerve fibres to cause release of substance P as it is equally effective in eliciting an inflammatory response in the presence of 100 micrograms of the substance P antagonist D-Pro4, D-Trp7,9,10 SP(4-11) in the synovial cavity. The results suggest that capsaicin may act by depleting substance P receptors in joint tissue.

Animals↗

PubMed1989

Interactive, mathematical, and sequential consultative methods in diagnosing renal masses on excretory urograms.

Using the clinical setting of diagnosing renal masses on excretory urograms, we compared the diagnostic efficacy and costs resulting from different consultative methods. These included face-to-face interactive consultation, mathematical combination of a fixed number of radiologists' confidence judgments, and computerized sequential decision making. This last method mathematically combines a variable number of individual judgments into an aggregate diagnosis based on diagnostic certainty. Six radiologists interpreted 42 proven urograms individually, with face-to-face consultation for selected cases, and interactively in groups of three. Individual diagnostic probability estimations were mathematically combined for the mathematical and sequential models. All models of consultation resulted in both higher diagnostic accuracy and lower costs than individual radiologists interpreting urograms alone. While the sequential model provided the highest diagnostic efficacy, it was only slightly more accurate than the other models tested. Radiologists interactively consulting on cases they considered difficult was the least costly method, approximating the projected costs of sequential decision making. Interactive consultation among radiologists is a cost-effective practice; sequential decision-making is a promising technique for improving diagnostic efficacy and reducing costs, and further evaluation is warranted.

Carcinoma, Renal Cell↗

PubMed1989

Factors affecting the accuracy of position matching at the proximal interphalangeal joint in human subjects.

1. The ability of normal subjects to match finger position at the proximal interphalangeal (PIP) joint was tested under a number of different conditions. One finger (target finger) was passively displaced in a pseudorandom manner whilst the other (matching) finger was actively positioned by the subject. 2. Digital nerve block of the target finger resulted in the matching finger only being displaced through a small range ('range compression') whilst anaesthesia of the matching finger produced the opposite effect ('range expansion'). 3. When the finger is unanaesthetized, the velocity of displacement of the target finger from one position to the next does not affect the accuracy of position matching. However, during digital nerve block of the target finger, matching errors increase with decreasing velocity. 4. The impairment of matching performance during digital nerve block is due specifically to loss of input from receptors in and around the PIP joint, as anaesthesia of the tip of the finger to produce any significant decrement in matching accuracy. 5. The results show that muscle receptors contribute to position sense at this joint but are not the exclusive source of proprioceptive sensations.

Fingers↗

PubMed1989

Adrenoceptor profile of blood vessels in the knee joint of the rabbit.

1. An in vitro preparation of the rabbit knee joint, perfused with oxygenated Locke solution, was used to assess the nature of adrenoceptors within articular blood vessels. 2. Dose/response relationships were obtained to intra-arterial injection of alpha- and beta-adrenoceptor agonists. 3. Adrenaline and noradrenaline produced a similar pattern of increasing constriction of articular vessels with increasing dose of drug. 4. The alpha 1-agonist, phenylephrine, also produced dose-dependent constrictor responses, but the alpha 2-agonist; clonidine, had no effect. The alpha 2-agonist UK-14304 did, however, produce modest vasoconstriction which was not greatly altered by the alpha 1-blocker prazosin. The constrictor effect of noradrenaline was abolished by both the alpha 1,2-blocker phenoxybenzamine and by prazosin but not by the alpha 2-blocker rauwalscine. 5. The beta-adrenoceptor agonist, isoprenaline, had little effect at a dose of 10(-6) M or lower, but gave rise to a constrictor effect at higher concentrations. This response was blocked by phenoxybenzamine but not by the beta 1,2-blocker propranolol, suggesting that the constrictor effect was mediated via alpha-adrenoceptors. 6. The results suggest that alpha 1- and alpha 2-adrenoceptors are present within articular blood vessels, but that beta-receptors are absent. The effects of noradrenaline appear to be mediated principally via alpha 1-adrenoceptors.

Adrenergic alpha-Agonists↗

PubMed1989

The effect of loading on position sense at the proximal interphalangeal joint of the human index finger.

1. Proprioceptive acuity was tested at the proximal interphalangeal joint of the index finger of normal subjects. 2. Examination of the ability of the subjects to match finger positions (position matching procedure) revealed that digital nerve block (DNB) of the finger resulted in characteristic alignment errors at the extremes in all subjects. 3. When one finger (target finger) is positioned close to full extension, all subjects hyperextended the anaesthetized matching finger, whilst target finger positioning towards full flexion resulted in hyperflexion of the matching finger. At intermediate positions the pattern of matching errors was more variable but tended to be consistent for a given subject. 4. When the matching finger was isotonically loaded into flexion, there was little change in matching performance for most subjects. However, when the matching finger was anaesthetized, such loading now produced clear alteration in performance in all subjects. This indicates that muscle receptors contribute to proprioceptive sensations at this joint, but require other afferent sources to optimally resolve position when the finger is loaded. 5. Two other test procedures (angle reproduction and assigned positions) were assessed and compared with the results obtained by the position matching technique. Although alterations in proprioceptive performance during DNB could be detected with these procedures, they tended to be less sensitive than the position matching procedure.

Adult↗

PubMed1989

Inhibition of carrageenan induced inflammation in the rat knee joint by substance P antagonist.

The pathophysiology of acute joint inflammation remains unclear. Evidence is available to suggest a neurally mediated component to the inflammatory process. Acute joint inflammation in the rat knee, induced by intra-articular injection of 2% carrageenan, was reduced by 44% in animals whose knee had previously been injected with 1% capsaicin, while chronic joint denervation produced a 37% reduction. These results indicate a significant neurogenic component in this model of acute joint inflammation. Substance P may be the mediator of this response as intra-articular injection of this agent provoked an acute inflammatory response. Pretreatment of the test knee with the substance P antagonist d-Pro4,d-Trp7 9 10-SP(4-11), however, resulted in a 93% reduction of the inflammatory response to carrageenan. This unexpectedly large effect suggests that this substance P antagonist blocks both neurogenic and non-neurogenic mediators of inflammation. Sympathetic efferent fibres innervating the knee joint were not found to contribute to the neurogenic component of the inflammatory process.

Animals↗

PubMed1989

Detection of pneumothorax: comparison of digital and conventional chest imaging.

To investigate radiologists' performance at interpreting digital radiographic images, we compared the detectability of pneumothoraces on computed radiographic chest images with 0.2-mm pixel size (2.5 Ip/mm) with their detectability on matched conventional screen-film images (5 Ip/mm). Eight radiologists reviewed 50 computed and 50 screen-film chest radiographs from 25 patients with pneumothoraces and 25 patients with other (or no) abnormalities. Four of the readers who best detected pneumothoraces on screen-film examinations performed worse when interpreting computed radiographic studies; the other four readers detected pneumothoraces similarly with both techniques. No relationship was found between the size of a pneumothorax and its likelihood of detection by either technique. These results raise concerns about implementing computed radiography for comprehensive chest imaging.

Adult↗

PubMed1988

Responses of quadriceps motor units to mechanical stimulation of knee joint receptors in the decerebrate cat.

Recordings were obtained from single quadriceps motor units in decerebrate cats. Tonic discharges were induced in these units by stretch applied to the patellar tendon. The activity of these motor units was examined during repetitive mechanical indentation of the posterior aspect of the knee joint capsule. The amplitude of indentation could be graded to regularly elicit a volley of one or more action potentials from afferents travelling in the posterior articular nerve (PAN). Either repetitive indentation at a fixed frequency or random indentation resulted in entrainment of motor unit discharge with a latency of 6.5-17 ms from the onset of the first PAN spike. This effect was achieved in one case by a single joint afferent. Usually two or more afferents were required to produce entrainment. This effect was mediated by joint receptors as its reversibly abolished by application of lignocaine to the joint nerve. The modal reflex latency suggests that group II joint afferents were responsible for this effect. Stimulation of some areas of the joint capsule readily produced motor unit entrainment whereas other areas did not although PAN afferents were also activated at the latter sites, suggesting inhomogeneity in the synaptic actions of joint afferents.

Action Potentials↗

PubMed1988

Improved imaging diagnosis by sequentially combined confidence judgments.

Consultation among radiologists improves diagnostic efficacy. However, it is unclear in practice when consultation is indicated, and consultation may be logistically difficult. We present a computerized method of noninteractive consultation that supersedes these problems, using radiograph readers' confidence judgments in their decisions. Individual categorical confidence judgments of excretory urogram diagnoses were transformed into diagnostic probabilities, then combined sequentially by computer simulation with other radiologists' probabilities until sufficient group confidence was achieved. Appropriate stopping rules were defined empirically. Analysis of cost effectiveness of this model--considering the cost of sequential interpretations and a range of costs for false-positive and false-negative errors--indicates that mathematically combined sequential decisions are more efficacious and less costly than individuals interpreting urograms alone.

Decision Making, Computer-Assisted↗

PubMed1988

The effect of acute joint inflammation on flexion reflex excitability in the decerebrate, low-spinal cat.

Experiments were performed to investigate whether acute knee joint inflammation, induced by intra-articular injection of carrageenan and kaolin, significantly influences the magnitude of the flexion withdrawal reflex of knee flexors in the decerebrate, low-spinal cat. It was observed that after injection of these inflammatory agents, reflex intensity increased with a time course that matched the development of the inflammatory process, as assessed by monitoring the intra-articular temperature. Control experiments involving intra-articular injection of saline showed neither a rise in intra-articular temperature, nor any change in reflex intensity. The normal pattern of modulation of reflex intensity with changing joint angle was abolished in the inflamed joint with the reflex being equally intense at all positions tested. Abolition of neural activity in the inflamed joint by intra-articular injection of lignocaine resulted in a marked decrease in the reflex back to control values, suggesting that there is no maintained increase in central excitability in the absence of joint afferent input. It was also observed that the spontaneous activity of knee flexor motor units was modulated during continuous passive rotation of the knee, with activity being greater in extension than in flexion. This pattern reversed when the knee was acutely inflamed, but could be returned to the control pattern by joint anaesthesia, although now the response was attenuated when compared to the control.

Animals↗

PubMed1988

Pressures in normal and acutely distended human knee joints and effects on quadriceps maximal voluntary contractions.

Pressures were recorded in ten knees from five subjects with informed consent. Resting intra-articular pressures were found to be sub-atmospheric with a mean value of -5 +/- 1.5 mmHg (S.E. of mean). There was little variation in intra-articular pressure with changing joint angle in the normal joint. Infusion of as small a volume as 5 ml of sterile saline into the joint cavity caused the intra-articular pressure to increase to supra-atmospheric levels. Changing joint angle now produced clear modulations in intra-articular pressure. Pressure increased as the limb was moved out to extension and back to flexion with a minimum occurring in the mid-range. These modulations were more pronounced with active positioning of the joint than with passive positioning. Successive increases in intra-articular volume produced increases in intra-articular pressure as well as the degree of modulation of intra-articular pressure with joint angle. Cyclical flexion-extension movements caused a progressive decrease in the maximum pressure observed in extension. Non-noxious distension of the knee joint caused substantial reductions in the magnitude of isometric and isokinetic maximal voluntary contractions of quadriceps due to a reflex inhibition from joint mechanoreceptor afferents.

Electromyography↗

PubMed1988

Position sense at the proximal interphalangeal joint of the human index finger.

1. The ability of eleven normal subjects to match the position of the proximal interphalangeal joints was tested. The right index finger (target finger) was moved to a given position and the subject was required to match this with the left index finger (matching finger). 2. Digital nerve block of the matching finger resulted in substantial impairment in matching performance in seven out of eight subjects. 3. Anaesthesia of the target finger in two subjects also produced obvious position matching deficit, in a pattern consistent with subjective sensation of target finger position. 4. The effects of digital nerve block were specific, as neither injection of saline into the matching finger, nor anaesthesia of adjacent fingers, impaired performance. 5. In one subject, injection of local anaesthetic into the synovial cavity of the matching finger also resulted in impairment of matching performance, indicating that articular receptors contribute to position sense at this joint. 6. Passive displacement of the matching finger did not produce significantly greater errors than those occurring with active finger positioning either under control conditions or during digital nerve block of the matching finger. 7. Although digital nerve block produced substantial impairment of matching performance, there was not complete loss of proprioceptive sensation, suggesting that muscle receptors also contribute. This was confirmed in experiments where isotonic loading of the matching finger while it was anaesthetized resulted in significant alteration in matching performance compared to anaesthesia alone. 8. It is concluded that no one source of afferent input can be excluded from contributing to proprioception at the index finger. It is likely that under different operating conditions several afferent sources are required to provide optimal proprioceptive resolution.

Adult↗

PubMed1987

The effect of digital nerve block on position sense at the proximal interphalangeal joint of the human index finger.

Position matching at the proximal interphalangeal joint of the index finger in human subjects was tested by passive displacement of the right (target) finger and active matching of the left index finger. In 5 subjects it was found that position matching was grossly impaired after digital nerve block of the matching finger. Typically, subjects hyperextended the matching finger when the target finger was held in extension and hyperflexed the matching finger when the target finger was held in flexion. These results suggest that even with active positioning, joint and cutaneous receptors importantly contribute to the awareness of position at this joint.

Adult↗

PubMed1987

The effect of mechanical stimulation of knee joint afferents on quadriceps motor unit activity in the decerebrate cat.

The present experiments demonstrate that repetitive activation of as few as two joint afferents by an imposed mechanical stimulus results in entrainment of stretch-induced firing of quadriceps motor units. There is no significant input from extracapsular receptors as the effect is abolished during local anaesthetic block of the joint nerve. These results indicate that joint receptors can exert potent effects on motoneurone excitability which may be of considerable functional significance.

Animals↗

PubMed1987

The effect of acute joint distension on mechanoreceptor discharge in the knee of the cat.

Recordings were obtained from afferents travelling in the posterior articular nerve of the cat knee joint. These arose from tonically active slowly adapting mechanoreceptors which were located in the joint capsule and whose conduction velocities were in the group II range. Intraarticular fluid injection resulted in enhancement of receptor discharge. Both the static index (adapted discharge 2 s after ramp displacement) and the dynamic index (difference between peak discharge during joint displacement and that occurring 0.5 s later) increased after injection. However, whereas the dynamic index increased by three- to fivefold the static index never exceeded a twofold increase. Incremental rise of intra-articular volume resulted in progressive increase in both parameters at all angular velocities. Thus both position and velocity sensitivity are enhanced by the acute introduction of fluid into the synovial cavity.

Animals↗

PubMed1987

The role of joint receptors in human kinaesthesia when intramuscular receptors cannot contribute.

1. Kinaesthetic acuity was tested at the distal interphalangeal joint of the middle finger when the hand was postured so that the joint was effectively disengaged from its muscular attachments. Subjects were required to detect the direction of 5 deg movements applied at different angular velocities from a mid-position under control conditions, after intra-articular injection of a plasma expander and after intra-articular injection of a local anaesthetic. 2. Kinaesthetic performance was enhanced after the injection of a plasma expander and deteriorated after injection of local anaesthetic. This deterioration could not be explained by spread of the local anaesthesic from the injection site on the dorsum of the joint. 3. The results suggest that the discharge of joint receptors can produce perceived signals of joint movement. Under normal conditions these receptors may duplicate the kinaesthetic input from muscle spindle endings.

Anesthetics, Local↗

PubMed1986

Conditioning of crossed extensor reflex pathways by independent natural stimulation of labyrinth, neck and elbow joint afferents.

The present experiments demonstrated that labyrinth, neck and elbow joint afferents interact to influence the excitability of crossed extensor reflex pathways projecting to triceps brachii in decerebrate cats. Reflex excitability was dependent on head, neck and elbow position such that it was increased when the elbow was held at full flexion and either the head maintained side down or the neck rotated side up. Such interaction between these afferents is likely to be important in postural control.

Animals↗

PubMed1986

The interrelation of neural discharge, intra-articular pressure, and joint angle in the knee of the dog.

Single- and multi-unit recordings were obtained from the medial articular nerve (m.a.n.) of knee joints in the anaesthetized dog. The single-unit recordings were confined to low threshold (group I and II) articular mechanoreceptors. Multi-unit recordings revealed that the m.a.n. discharge was maximal in extension, submaximal in flexion, and minimal at intermediate angles, i.e. a U-shaped profile. Subatmospheric intra-articular pressures do not appear to influence the m.a.n. discharge. Intra-articular infusion of even small quantities of fluid, although not affecting the U-shaped profile, reversed the m.a.n. discharge pattern with maximum neural activity occurring in flexion and being submaximal in extension. Recordings from single units indicated that the enhanced discharge after fluid infusion was a result of increased discharge frequency and 'recruitment' of individual afferents.

Action Potentials↗