Biomedical subjects
Publications and source records attributed to J P Joseph.
Peribulbar anaesthesia has been recommended as a safer alternative to retrobulbar anaesthesia. We report a case of perforation of the globe sustained during peribulbar anaesthesia which resulted in blindness. Orbital injections are potentially dangerous, be they peribulbar or retrobulbar. To minimise the risk, short, blunt needles are advocated for the peribulbar route.
The chemoattractant activity for ocular fibroblasts of the aqueous humor of patients undergoing glaucoma surgery was evaluated in 48-well microchemotaxis chambers and compared with control specimens from patients undergoing cataract extractions. All specimens were chemoattractant, but those from patients who had previously undergone glaucoma surgery that had failed were of significantly greater activity than the controls'. This chemoattractant activity is primarily chemotactic. It consists of heat-stable and heat-labile components. The predisposition of a patient to sustain failed glaucoma drainage surgery may be related to the chemoattractant activity of his aqueous humor, since strongly chemoattractant aqueous humor may encourage fibrosis at the operation site.
1. Single neuron activity was recorded from the prefrontal cortex of two macaque monkeys during the performance of a task involving spatial sequencing. The monkeys faced a panel displaying a central fixation point and three fixed targets (two lateral and one above the point of fixation). In the first phase of each trial, the three targets were turned on in random order: in the second phase, the animal had to press each target, still lighted, in the order of their illumination. Thus, successful performance of the task depended strongly on temporal memory. The animals were fitted with DC-EOG electrodes. 2. Three hundred and two task-related neurons were recorded in the superior arcuate area and caudal part of sulcus principalis. Among the cells whose pattern of activity appeared to be related to the sequencing task, five classes were distinguished: Visual tonic (VT), fixation, context, saccade related and visual phasic cells. In addition, a small number of cells appeared to be related to other aspects of the behavior, but not to the sequencing task. Our present analysis concentrates on two groups of sequencing task-related cells (VT and context cells). 3. The VT cells (35/302-11.5%) were recorded exclusively from the superior arcuate area. All VT cells increased their firing rate (sustained activation) during fixation of the central fixation point (FP) following onset of one of the three targets used, specific for a given cell (directional or spatial selectivity). In one group of VT cells, a shift in the eye position towards the specific peripheral target resulted in the return of the cells' firing rate to the pre-trial level. In the other group of VT cells, reset of the firing rate to pre-trial level was not related to the onset of fixation of the peripheral target. Sustained activation of the VT cells depended also on the sequential order of illumination of the specific target (temporal selectivity). In twenty-four cells (68.5% of VT cells) sustained activation was observed when the target came first in the sequence. Onset of the target in the second or third rank elicited either no response or only a short lasting phasic activation. In the remaining eleven cells (31.5% of VT cells), sustained activation was only observed when the target came second in a given sequence. The firing of the VT cells was correlated with the animals' performance of the task.(ABSTRACT TRUNCATED AT 400 WORDS)
This study demonstrates that aqueous humour derived from patients undergoing cataract extraction contains chemoattractants for ocular fibroblasts. The chemoattractant activity is independent of the surgical approach to obtaining the specimen as well as the surgeon operating. Studies in rabbits demonstrate that the chemoattractant activity is not artefactually produced by aqueous sampling and confirm the integrity of the blood-aqueous barrier. Substances responsible for this activity have molecular weights greater than 30,000; they are deactivated by low pH but retain activity at high pH. Identification of the chemoattractants in aqueous humour may allow pharmacological manipulation of would healing in relation to trabeculectomies.
Unit activity was recorded in the prefrontal cortex of rhesus monkeys during performance of a delayed task with two motor responses, a saccade and an arm movement, to a complex pattern of auditory and visual stimuli. The peculiarity of the paradigm was that onset of the different sensory stimuli, orienting saccade and arm movement, were dissociated in time and occurred at prefixed time intervals. Two hundred and sixteen task-related units were recorded. The data show that the dorsolateral part of the prefrontal cortex plays a crucial role in temporal organization of visually guided behaviour. This cortical area contains the neural substrate of an encoding strategy for remembered or current events and objects in the behavioural surround that are not, as yet, foveated. This encoding mechanism subserves a particular cognitive process. Whether events or objects are, or are not, encoded depends on their significance for future behaviour. While foveation deletes their neural trace, it activates a class of cells that appear involved in the preparation of arm movements towards the foveated region. The destruction of these two complementary mechanisms would disrupt the organism's capacity to integrate temporally and spatially discontinuous information for performance of goal-directed acts.
Migration and contraction are fibroblast activities in scar tissue formation which may contribute towards the failure of trabeculectomies. We attempted to modify the migration and contraction of Tenon's capsule fibroblasts in vitro using the drugs taxol, cytochalasin B and colchicine. Migration assays were conducted in 48-well micro-chemotaxis chambers, using rabbit aqueous humour which has been previously identified as a powerful chemoattractant for Tenon's fibroblasts, and fibronectin as the stimuli for migration. All three drugs inhibited the migration of fibroblasts to both fibronectin and aqueous humour, with maximal activity seen at 10(-6)M (taxol), 10(-5)M (cytochalasin B), and 10(-3) M (colchicine). In a single cell contractile assay in which contraction of whole fibroblasts was initiated with exogenous adenosine triphosphate (ATP), taxol and colchicine showed anticontractile activity, maximal at 10(-5)M and 10(-3)M respectively, but cytochalasin B was ineffective. The significance of the activities of these drugs in relation to their proposed use for improving the success of trabeculectomies is discussed.
The effect of the retinoids, retinol and all-trans acid, was assessed in vitro on the migration of rabbit Tenon's capsule fibroblasts, with a view to using these drugs as inhibitors of fibrosis in relation to trabeculectomies. No inhibition of fibroblast migration was demonstrated, and in fact retinol significantly enhanced both the random and directed migration of these cells (p less than 0.001 and p less than 0.01, respectively). This study emphasises the importance of using appropriate cells when investigating the effects of drugs on wound healing.
Trabeculectomy fails to control the intra-ocular pressure adequately in a proportion of patients. Approaches to solving this problem have involved modifications of surgery, histological studies of tissue from failed and functioning blebs, animal studies, and in vitro investigations of some of the basic processes of wound healing. This paper reviews the current state of investigations in these disciplines with particular reference to wound healing in this specialised site.
1. Unit activity was recorded in the prefrontal cortex of Rhesus monkeys during performance of a delay task with two motor components, an ocular saccade and an arm movement, following a complex pattern of auditory and visual stimuli. A special feature of the paradigm was that onsets of the different sensory stimuli, orienting saccade and arm movement were dissociated in time at predetermined time intervals. 216 task-related units were recorded. Discussion of the data focuses on two groups of cells the activity of which is modified by the saccade: the signal-related pre-saccadic tonic cells and the post-saccadic tonic cells. 2. Activity of signal-related pre-saccadic tonic cells was initiated with the onset of peripheral stimuli, visual and/or auditory, and terminated with an orienting saccade. Spatial selectivity was a feature of most units. They seemed to encode the region of space cued by the stimulus. 3. Many units were visually responsive. Activation of these depended both upon retinal locus of the stimulus and the requirement they imposed on subsequent behavior. Termination of their activity demanded foveation of some visual targets, not necessarily the one which had initiated their response. 4. The majority of these signal-related pre-saccadic tonic cells responded to onset of auditory stimuli. The termination of tonic activity in these cells with foveation of the region in space from which the signal originated suggests a spatial memory process that is no longer used when the visual fixation response can signal equivalent spatial information.(ABSTRACT TRUNCATED AT 250 WORDS)
Some of the chemotactic and chemokinetic properties of rabbit Tenon's fibroblasts were examined in a 48-well micro-chemotaxis chamber. Normal rabbit aqueous humour, fibronectin, and fibroblast conditioned medium were used in the assay, and all were shown to be chemoattractant. In addition, aqueous humour was shown to be powerfully chemotactic. Since the failure of human trabeculectomies is associated with migration of fibroblasts to the operation site, the study of the chemoattractant influences acting on these cells may allow manipulation of their behaviour in order to influence favourably the outcome of surgery.
Single cell activity was recorded from the Anterior Suprasylvian (ASS) gyrus of cats trained to orient their gaze toward visual or auditory stimuli. Sixty-five fixation cells were activated or suppressed as long as the animals were attentive to a particular region of space in the tangential or in the radial direction. Most of these fixation cells were neither light nor sound sensitive. Fifty-five cells were activated in relation to saccades. Fourteen neurons were active before and 41 after the onset of saccades. Nineteen neurons were also active with spontaneous eye movements in the dark. Fifteen neurons were seemingly related to vergence. They were not light-sensitive. They were preferentially activated by visual stimuli moving in the radial direction either towards or away from animal's face. Fifty light-sensitive neurons responded to moving stimuli. Only two neurons responded to onset of eccentric stationary light-stimuli. Fifty-one neurons showed a modulation in relation to vestibular stimulation. A majority showed, in addition, a vestibulo-collic response. These data suggest that the ASS gyrus in cats has a major role in the construction of the behavioral space.
Extracellular activity of single neurons in the pars reticulata of the Substantia Nigra (SNpr) was recorded in cats during drinking. Two groups of cells were distinguished: I. Somatosensory cells which responded by a short decrease in firing rate to the arrival of water against the upper lip. We suggest that these stimulus-related responses reflect a complex process linked to preparation of buccolingual movements. II. Action-related cells which were de-activated at the beginning or during the entire drinking period but without modulation in relation to the individual movements of jaws and tongue. We suggest that de-activation of these cells during drinking operates as a gating mechanism which allows implementation of complex motor sequences by cortical and/or subcortical structures.
Single unit activity was recorded in the Substantia Nigra pars reticulata (SNpr) of cats trained to orient their gaze toward visual and/or auditory targets. Cells in the SNpr have a steady high rate of spontaneous activity ranging from 35 to 120 spikes per second. The neurons respond to sensory stimuli or in relation to saccadic eye movements with a decrease or a cut-off of the spontaneous discharge. Among 109 cells recorded in the SNPR 60 were responsive to visual stimuli (mean latency = 118 ms). Most of the receptive fields which were plotted were large encompassing part of the ipsilateral field. Thirty nine (39) cells were responsive to auditory stimuli (mean latency = 81 ms). A majority of these cells showed a better response for stimuli located in the contralateral hemifield. In a few cells, the sensory responses were modulated by the subsequent orienting behavior of the animals. Thirty one (31) cells showed a response in relation to saccades. These units typically stopped discharging between 50 and 300 ms prior to the onset of the saccade. 39% of these units also responded in relation to spontaneous saccades in the dark. 61% of the saccadic cells also responded to sensory stimuli in the absence of saccades. Six (6) cells were found to respond to active head movements. These results are discussed in the framework of the role that the basal ganglia might have in the selection of the sensory stimuli that trigger orienting behaviors.
Guided and reflex eye movements were studied in cats trained to make orienting saccades toward visual and auditory targets. Injections of a GABA-agonist (Muscimol) or GABA-antagonists (Bicuculline and Picrotoxin) were made in the Substantia Nigra pars reticulata (SNpr). Bicuculline and Picrotoxin, whether unilaterally or bilaterally injected had no effect on the posture nor the oculomotor performance of the animals. Neck muscle activity remained symmetrical. Unilateral injections of Muscimol produced oro-facial akinesia, reduction of the number of eye movements, contralateral head turning, visual neglect mostly (but not only) for ipsilateral visual space. Balance between the gains of the vestibulo-ocular reflex (VOR) in the two directions of movement was changed. Gain was decreased for the ipsilateral rotation. The optokinetic nystagmus (OKN) was not affected. Contralateral neck muscles were hypertonic. After bilateral injections of Muscimol, the cats did not orient. The VOR was normal when the injections induced no postural asymmetry. Hypertony was bilateral. Implications of these results for the role of the basal ganglia in motor control are discussed. We suggest that in Parkinson's disease the fixed inhibitory drive of the SNpr on the tectum and on the thalamus is disrupted.
Depth spike activity was evaluated from medial temporal lobe sites using computer spike recognition techniques in all-night sleep records derived from 10 patients with medically refractory complex partial seizures. Sleep stages were classified into 1 of 4 groups: wakefulness, REM sleep, light sleep and deep sleep. Some disturbance in the periodicity of the sleep cycle was noted in most patients, but the relative proportions of REM sleep, light sleep and deep sleep were close to that reported for normals. Depth spike activity was observed to be most frequent in a majority of sites during deep sleep in 6 patients and during light sleep in 3 patients. In 1 patient equal numbers of sites showed maximal activation during light sleep and deep sleep. In 4 patients, certain sites in the more epileptogenic lobe demonstrated a maximal rate during waking or REM sleep. All patients reported in this study were considered to be suitable for temporal lobectomy. In contrast to the results obtained from a previous study, the side with the site demonstrating maximal mean spike rate did not necessarily correspond to the side chosen for lobectomy. Significant correspondence across patients between the more epileptogenic lobe and maximal spike rate was not found during waking and was further reduced during light sleep and deep sleep. The correspondence was, however, significant during REM sleep and for the side containing the site demonstrating the smallest activation in mean spike rate during light sleep or deep sleep relative to waking. These results indicate that an analysis of sleep induced changes in depth spike activity can be useful in improving predictions concerning epileptogenicity. Quantification of other aspects of the interictal EEG, such as background activity, may further improve such predictions.
The effects of increasing the brain monoamine content on the three types of localized rhythms identified in somatic area I ("mu-type rhythms") were studied in freely moving cats. Increases in brain monoamines (catecholamines and serotonin) were produced by injecting L-Dopa and 5-HTP, L-tyrosine, L-tryptophan and tryptamine were also tested. It is concluded that the two subsets of rhythms, one accompanying high levels of alertness and vigilance and the other appearing during quiet wakefulness, are related to the catecholaminergic systems, while those characterizing drowsiness seem to be controlled by a serotoninergic system. The latter, however, is distinct from that controlling slow sleep.
In freely moving cats, systemic administration of Chlorpromazine (CPZ) and Haloperidol (HP), two neuroleptics which presumably block catecholamine receptors, leads to a suppression of the waking mu-type rhythms. There is a clear difference, however, in that CPZ leads to slow wave sleep while HP only induces sustained drowsiness. The difference in their action is tentatively explained by their differential effect on an enzyme that is not involved in the metabolism of biogenic amines, tryptophan pyrrolase. We suggest that it is through this pathway that CPZ might increase and HP might decrease brain tryptophan and thereby lead to opposite changes in brain 5-HT content.
A spatio-temporal analysis of the successive and simultaneous components of the pattern-evoked potential recorded on the scalp, and of their modifications according to which part of the visual field is stimulated, was carried out with 20 'normal' subjects, in order to shed some light on their most probable sites of origin. The stimulus consisted in the onset of a 20 degree checkerboard presented in runs of 75 stimuli each. Its duration was 750 msec and its frequency of occurrence was random (about 1 every 1500 msec). Twelve different visual field situations were recorded: whole field, half fields and quadrants and stimuli limited to the fovea, to the macula and to extramacular areas. Data were collected from 9 active electrodes (in line, forming a cross montage), and various reference electrodes (ear lobes, Fz, non-cephalic). Eye movements were simultaneously recorded. The electrophysiological data were digitized on line and processed by computer in the form of averaged spatio-temporal maps. In addition to the classical posterior components which peak on the midline (N 60, N 140, and P 200) or less than 4 cm away on both sides (P 90), a late negative wave (LN 210) was differentiated which peaked lower than the inion and more than 8 cm away from the midline on both hemispheres. The large inter-individual variability of the spatio-temporal organization of these components under the same conditions, as well as its very good intra-individual reproducibility, were emphasized. Interpreted on the basis of a simple dipole sheet model of the visual cortex, the changes observed for each component in the 12 experimental situations led to the following suggestions: only the first component N 60 could reflect the activity of the part of area 17 emerging on the convexity, whereas P 90 (Jeffreys' CI) is more likely to originate in area 19 and the midline components N 140 and P 200 in area 18. The topography and reactivity of LN 210 could fit with the hypothesis that it reflects activity of the infero-temporal cortex.