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Biomedical subjects

J M Chung

Publications and source records attributed to J M Chung.

At least 91 records · Page 5Linked to original sources

Evaluation of omeprazole as a treatment for gastric and prepyloric ulcer in Korean patients.

The healing efficacy of omeprazole was assessed in 57 Korean patients with endoscopically-proven gastric (GU) and/or prepyloric (PPU) ulcers of at least 5 mm diameter. Fifty-three patients presented with GU, two with PPU and two with both types of ulcer. The maximum ulcer diameter was 5-10 mm in 27 patients and greater than 10 mm in 30 patients. All patients received 20 mg of omeprazole each morning for 4-8 weeks depending on ulcer healing. Ulcer healing rates were comparable using both 'intention to treat' (IT) and 'per protocol' (PP) analyses. Following the IT approach 82% (47 of 57) of patients were healed at 4 weeks and 98% (56 of 57) at 8 weeks. Following the PP approach, the corresponding healing rates were 83% (44 of 53) and 98% (55 of 56), respectively. Smoking was found to have a significant effect on ulcer healing at 4 weeks (P = 0.03), with 96% (26 of 27) of non/occasional smokers healed versus only 69% (18 of 26) of daily/heavy smokers. Ulcer size did not have a significant effect on healing, however. Ulcer symptoms, reported by all patients at entry, disappeared rapidly after commencement of omeprazole therapy. Only four patients reported mild symptoms at 4 weeks and no symptoms were reported at 8 weeks. No clinically significant changes in haematology or clinical chemistry (other than a rise in leucocytes in one patient) and no serious adverse events were observed. In conclusion, omeprazole 20 mg each morning was found to be safe and highly effective for treatment of gastric and prepyloric ulcer in Korean patients, producing a 98% healing rate. Symptom relief was rapid and the drug was well tolerated.

Adult↗

Proportion and location of spinal neurons receiving ventral root afferent inputs in the cat.

Spinal neurons receiving ventral root afferent inputs were investigated in anesthetized and paralyzed cats. We were concerned with the afferent fibers in the ventral root that travel distally and then enter the spinal cord through the dorsal root. The questions to be answered included the proportion and distribution of spinal neurons receiving ventral root afferent inputs and their peripheral input characteristics. The 1.7 ventral root was cut near the spinal cord and the distal stump was stimulated while making a systematic search for neurons in the entire gray matter of the ipsilateral spinal cord that responded to the stimulation. The following conclusions were made: (i) the afferent fibers in the cat ventral root enter the spinal cord through the dorsal root and evoke a variety of responses (excitation, inhibition, or mixed) in a large proportion of spinal neurons (about 20%): (ii) these responses seem to be mediated largely by spinal mechanisms: (iii) spinal neurons receiving ventral root afferent inputs are situated in a wide region of the ventral spinal cord: (iv) ventral root fibers in a single root enter the spinal cord and exert their responses over a large region of the spinal cord (at least two spinal segments rostrally and caudally): (v) some of the spinal neurons that responded to ventral root stimulation were found to be ascending tract cells, suggesting that ventral root afferent inputs can reach supraspinal structures: (vi) ventral root afferent fibers converge onto spinal neurons that have a variety of peripheral receptive field characteristics: and (vii) with some exceptions, most neurons receiving ventral root inputs were excited best by mechanical and/or thermal noxious stimuli applied to the periphery.

Afferent Pathways↗

Differential inhibition produced by peripheral conditioning stimulation on noxious mechanical and thermal responses of different classes of spinal neurons in the cat.

The effect of conditioning stimulation of a peripheral nerve on responses of spinal neurons (dorsal horn cells and motoneurons) was studied in 16 decerebrate-spinal cats. The activity of dorsal horn cells was recorded with a microelectrode at the lumbosacral spinal cord and the single-unit activity of motoneurons was recorded from a filament of ventral rootlet divided from either the L7 or S1 ventral root. The responses of spinal neurons were evoked by noxious and innocuous mechanical stimuli and by noxious thermal stimuli applied to the receptive fields. The peripheral conditioning stimulation was applied to the tibial nerve with repetitive electrical pulses (2 Hz) at an intensity either suprathreshold for A delta or C fibers for 5 min. Applying conditioning stimulation to a peripheral nerve produced a powerful inhibition of the responses elicited by noxious stimuli, suggesting this inhibition is an antinociceptive effect. The inhibition produced by peripheral conditioning stimulation was differentially greater on the responses to noxious than to innocuous stimuli. Based on the results obtained from conditioning stimulation with graded strengths, afferent inputs from both myelinated and unmyelinated fibers seem to contribute to the production of the antinociceptive effect. The magnitude of the antinociceptive effect is bigger for the responses to noxious thermal than to mechanical stimuli. Furthermore, the reflex activity recorded in motor axons seemed to be more sensitive than in dorsal horn cells to the antinociceptive effect.

Animals↗

Many ventral root afferent fibers in the cat are third branches of dorsal root ganglion cells.

The arrangement of the ventral root afferent fibers was investigated in anesthetized and paralyzed cats. Single unit activity was recorded from a fascicle of the distal stump of the cut S1 dorsal root. Activity was elicited by stimulating the distal stump of the cut S1 ventral root. Attempts were then made to collide this activity with that elicited by stimulation of the S1 spinal nerve. Single unit activity elicited by ventral root stimulation was recorded from a total of 33 axons. In 17 of these, the activity collided with that elicited by peripheral stimulation. These results indicate that more than half the sampled population of ventral root afferent fibers are branches of dorsal root ganglion cells that have at least 3 processes: one in the dorsal root, one in the ventral root and one in a peripheral nerve. In 10 of these units, the conduction velocity of each of 3 processes was determined using the collision technique. The conduction velocities differed in the processes of a given ganglion cell, with conduction in the ventral root process generally being the slowest. The change in conduction velocity along the length of the ventral root was examined by comparing latency differences for the unit activity elicited by ventral root stimulation at different sites in the same root separated by known distances. The conduction velocity was found not to be uniform along the course of the ventral root. In many cases, the conduction velocity slowed down as the fiber approached the spinal cord. We conclude from the present study that many ventral root afferent fibers are the third branches of dorsal root ganglion cells that also have processes in the dorsal root and in a peripheral nerve. The sizes of each of these 3 processes of the dorsal root ganglion cell may differ; the ventral root process tends to be the smallest and is usually unmyelinated. Furthermore, many of the ventral root afferent fibers may taper as they approach the spinal cord.

Action Potentials↗

Ascending spinal pathway for arterial pressor response elicited by ventral root afferent inputs in the cat.

In an attempt to localize the spinal ascending pathway for ventral root afferent inputs, changes in ventral root stimulation-evoked arterial blood pressure responses were observed in anesthetized cats after selective spinal lesions. The results of these experiments indicate that the ascending spinal pathways responsible for the pressor response lie in the dorsal-most part of the lateral funiculus. The pathway was found to be bilateral, and it is likely to occupy the same area throughout the entire length of the spinal cord.

Afferent Pathways↗

Correlation of cell body size, axon size, and signal conduction velocity for individually labelled dorsal root ganglion cells in the cat.

Measurements of cell body and peripheral and central axon sizes were made for primary sensory neurons outlined by the intracellular injection of HRP. Conduction velocities were also measured on the outlined processes. The sensory neurons were then subdivided into A and C cells on the basis of the conduction velocity of the impulses carried by the processes of these cells. Central processes of both A and C cells are smaller than the peripheral processes, but the size differential is greater for the C cells. For A cells there is a linear relation between the size of the peripheral axon and the conduction velocity of the impulses carried by these axons, but the confidence limits are wide. For C cells there is a linear relation between the size of the central process and conduction velocity of the impulses carried by the processes, but for the peripheral processes two aberrant processes resulted in no correlation between process size and conduction velocity. For A cells, the size of the central and peripheral processes and the conduction velocity of the impulses carried by the peripheral processes are linearly correlated with cell body size. By contrast no such correlations can be demonstrated for C cells. This presumably implies an important difference in that the size of the cell body is correlated with axon size and impulse conduction velocity for A cells but not for C cells. A widely accepted generalization is that large sensory cells give rise to myelinated axons and small sensory cells to unmyelinated axons. In this study, myelinated and unmyelinated are defined on the basis of impulse conduction velocity. For those cells that are clearly large (greater than 50 microns in diameter), the conduction velocity of the impulses carried by their processes is always greater than 2.5 m/s, and for those cells that are clearly small (less than 35 microns in diameter), the conduction velocity is always less than 2.5 m/s. Thus for these cells the above generalization holds. For the intermediate-sized cells (35-50 microns), however, the size of the cell body bears no predictable relation to the conduction velocity of the impulses carried by those processes, and thus to whether the axons are myelinated or unmyelinated. Thus the above generalization does not hold for this intermediate group of cells, and since there are many cells in this size range, we feel that the generalization that large cells give rise to myelinated axons and small cells to unmyelinated axons is an oversimplification.

Action Potentials↗

Inhibition and excitation of the nociceptive flexion reflex by conditioning stimulation of a peripheral nerve in the cat.

A previous study in our laboratory showed a long-lasting, naloxone-reversible inhibition of the flexion reflex after prolonged repetitive stimulation of a peripheral nerve in the spinal cat. The present study employed a special pattern of conditioning stimulation for a shorter period (200 s) to determine the time course of the inhibition and the afferent fibers responsible for the inhibition. We stimulated the common peroneal nerve in 10 decerebrated and spinalized cats to elicit the flexion reflex, which we recorded as single-unit activity from filaments of the L7 ventral root. The C fiber-evoked late component of the flexion reflex was compared before, during, and after conditioning electrical stimulation applied to the tibial nerve. Stimulating the tibial nerve at an intensity that excited only A alpha beta fibers produced weak inhibition of the flexion reflex; increasing intensity above the threshold for A delta fibers produced much greater inhibition. Inhibition began during the first 10 s of conditioning stimulation and was maximum at about 100 s. Stimulation at a suprathreshold intensity for C fibers, however, produced an initial transient excitation, lasting 10 to 20 s, followed by inhibition. Intravenous injection of naloxone (0.05 mg/kg) produced no observable changes in this inhibition and excitation. These results suggest that conditioning stimulation of a peripheral nerve inhibits the flexion reflex. This inhibition has a short latency; the afferent fibers seem to be A delta fibers. In addition, input from afferent C fibers may trigger a mechanism that produces facilitation of the reflex. The differences in recovery time course and in sensitivity to naloxone suggest that two different mechanisms may be responsible for the fast-onset inhibition and the previously observed long-lasting inhibition produced after prolonged conditioning stimulation.

Animals↗

Spinal entry route for ventral root afferent fibers in the cat.

Twelve anesthetized and paralyzed cats were used to study the spinal entry routes of ventral root afferent fibers. In all animals, the spinal cord was transected at two different levels, L5 and S2. The L5 through S2 dorsal roots were cut bilaterally, making spinal cord segments L5-S2 neurally isolated from the body except for the L5-S2 ventral roots. From this preparation, a powerful excitation of the discharge rate of motor neurons and dorsal horn cells within the isolated spinal segments was observed after intraarterial injection of bradykinin (50 micrograms in 0.5 ml saline). This excitation of the spinal neurons can be considered the most convincing evidence of the potential physiologic role of the ventral root afferent fibers entering the spinal cord directly through the ventral root, because the apparent route of neuronal input from the periphery is through the ventral roots. However, additional control experiments conducted in the present study showed that the excitation persisted even after cutting all ventral roots within the isolated spinal segments, indicating that excitation was not mediated by the ventral roots. Furthermore, direct application of bradykinin on the dorsal surface of the spinal cord also increased the motoneuronal discharge rate, suggesting that excitation of spinal neurons produced by intraarterial injection of bradykinin is due to a direct action of bradykinin on the spinal cord. Thus, we provided an alternate explanation for the most convincing evidence indicating that physiologically important ventral root afferent fibers enter the spinal cord directly through the ventral root. Based on existing experimental evidence, it is likely that the majority of physiologically active ventral root afferent fibers travel distally toward the dorsal root ganglion and then enter the spinal cord through the dorsal root.

Action Potentials↗

Blood pressure response evoked by ventral root afferent fibres in the cat.

Systemic arterial blood pressure changes in response to stimulation of the distal stump of the cut spinal ventral root were investigated in anaesthetized, vagotomized, and carotid sinus-denervated cats. Low intensity electrical stimulation (less than 20 T, where T is threshold intensity) of the ventral root caused a rise in blood pressure. This elevation was abolished by paralysing the muscles with gallamine. This pressor response has been reported previously, and it is likely to be evoked by afferents excited by the contracting muscle. High intensity electrical stimulation (500 T) of the ventral root caused a second and marked pressor response. This was not affected by muscular paralysis or by cutting the sciatic nerve, but it was abolished by cutting the dorsal root. Threshold intensity for the second component of the pressor response was within the same range as the intensity needed for activation of C fibres in the ventral root, ranging between 200 T and 300 T. This response was graded with increasing stimulus intensity, and it showed both spatial and temporal summation. From the above results, we conclude that non-myelinated fibres in feline spinal ventral root course distally to the dorsal root ganglion and then enter the spinal cord via the dorsal root. Activation of these fibres results in a marked elevation of the systemic arterial blood pressure as in other somato-sympathetic reflexes induced by peripheral C fibre activation.

Action Potentials↗

Classification of primate spinothalamic and somatosensory thalamic neurons based on cluster analysis.

Data analyzed in this study were derived from the responses of 128 spinothalamic tract (STT) cells and 110 thalamic neurons recorded in 75 anesthetized monkeys. A k-means cluster analysis, a nonhierarchical clustering technique, was performed using the relative magnitudes of responses to a graded series of innocuous and noxious mechanical stimuli applied to the receptive field. For comparison, a parallel analysis was performed based on definitions of low-threshold (LT), wide dynamic range (WDR), and high-threshold (HT) cells used by our laboratory. For 128 STT cells, a classification scheme with three clusters was found statistically to be the best. This yielded groups of 22, 57, and 49 cells in clusters 1, 2, and 3, respectively. Cluster 1 cells were activated best by low-intensity mechanical stimuli, whereas cluster 3 cells were activated primarily by nociceptive stimuli. Cluster 2 cells had intermediate characteristics. When the classification scheme based on the cluster analysis was compared with the classification of the same neurons as LT, WDR, and HT cells, cluster 1 cells were divided into LT and WDR cells, whereas cluster 2 and 3 cells included WDR and HT cells. For 110 thalamic neurons, a classification scheme with five clusters was found statistically to be the best. Clusters 1-5 contained 25, 34, 17, 10, and 24 cells, respectively. Response characteristics of cells in each group indicated a gradual change in sensitivity to higher intensities of peripheral input from cluster 1 to 5. When this classification scheme was compared with the classification scheme previously used by our laboratory, cluster 1 cells belonged to the LT group, clusters 2 and 3 split into LT and WDR cells, and clusters 4 and 5 included WDR and HT cells. It is concluded that a classification scheme based on a cluster analysis of the responses of neurons to standardized stimuli may provide an objective and functionally meaningful way to categorize somatosensory neurons.

Animals↗

Response characteristics of neurons in the ventral posterior lateral nucleus of the monkey thalamus.

The activity of 132 neurons in the caudal part of the ventral posterior lateral nucleus (VPLc) of the thalamus was recorded from 23 anesthetized monkeys. All single thalamic units that could be excited by electrical search stimuli applied to the contralateral sciatic nerve were investigated. Responses of these cells to mechanical, thermal, and electrical stimuli applied in the periphery indicated that at least half of the sampled cells were nociceptive. Based on responses to graded mechanical stimuli applied to the periphery, 110 of the sampled cells that received a predominant input from cutaneous receptive fields were classified. There were 56 low-threshold, 39 wide dynamic range, and 15 high-threshold cells. The same neurons were also classified into five mechanical types based on a cluster analysis: types 1-5 contained 25, 34, 17, 10, and 24 cells, respectively. The fact that about half the population of cells belonged to either the wide dynamic or the high threshold group (or mechanical types 3-5) suggested that a large population of VPLc neurons respond to mechanical nociceptive stimuli either exclusively or preferentially. Responses of 63 thalamic neurons were tested to noxious heat pulses applied to their cutaneous receptive fields with a contact thermostimulator. Of these, 47 cells were excited, whereas only 16 cells did not respond. The peripheral nerve that innervated the receptive field of each of 82 thalamic neurons was stimulated with graded strengths to activate A fibers only or both A and C fibers. All tested cells responded to peripheral A fiber volleys. In addition, 42 of these cells responded to peripheral C fiber volleys. The C fiber responses could be either short lasting (a few hundreds of milliseconds) or long lasting (up to several seconds). The recording sites of 80 cells were reconstructed. Of these, 78 were in the VPLc nucleus and the remaining two were in the reticular nucleus of the thalamus. No obvious relationship between the response characteristics and the locations of the cells within the VPLc nucleus was found. Sampled thalamic units had a variety of sources of input from the periphery, including both cutaneous and/or deep tissue receptive fields. The majority of the cells, however, had exclusively cutaneous receptive fields. The sizes of the cutaneous receptive fields were often very small, so that nearly half (41%) of the receptive fields of cells sampled occupied an area of skin smaller than half the foot.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

The long-latency component of cerebral evoked potentials in anesthetized cats.

A late component of the cortical evoked potential elicited by somatosensory afferent input was studied in cats anesthetized with alpha-chloralose. Cortical evoked potentials were recorded from the somatosensory-motor cortex during stimulation of the sural nerve with graded intensities. The stimulus intensity was adjusted to activate A alpha beta fibers only, then both A alpha beta and A delta fibers, and both A and C fibers, as judged by afferent volleys monitored from the sural nerve proximal to the stimulating site. In addition to early components reported previously, a very late component was identified at a latency of 400 to 600 msec following stimulation of the sural nerve with intensities above threshold for A delta fibers. A further increase in stimulation intensity to include activation of C fibers did not reveal any more components. This late component was depressed by a systemic intravenous injection of morphine (2 mg/kg), and intravenous naloxone (0.1 mg/kg) reversed the effect of morphine. The late component of the evoked potential could also be recorded from subcortical tissue after decortication of the sensorimotor cortex. From these results, it appears that a very late component of the cortical evoked potential can be recorded from cats anesthetized with alpha-chloralose. The late component is evoked by activation of peripheral A delta fibers. Furthermore, its morphine sensitivity suggests that this component may be elicited by nociceptive afferent fibers. If further investigations prove this, the late component, which is analogous to human long-latency potentials, could be used in an experimental model for pain research.

Animals↗

Actions of opioids on primate spinothalamic tract neurons.

The effects of iontophoretically applied opiates were tested on 24 spinothalamic tract cells in 12 anesthetized monkeys. The drugs used were chosen because of their agonist actions on different classes of opiate receptors (mu, morphine; kappa, dynorphin; delta, methionine enkephalinamide; sigma, N-allylnormetazocine or SKF 10047 and phencyclidine). The actions of the opiate drugs were generally inhibitory, although excitatory or mixed effects were sometimes seen, especially with morphine and dynorphin. Drug effects could change, depending on the position of the iontophoretic electrode array or on the current employed. Naloxone sometimes antagonized the action of the opiate drugs used, but naloxone did not seem to be a drug suited for iontophoretic application. A number of explanations are discussed to explain the variable actions of the opiate drugs.

Animals↗

Flexion reflex elicited by ventral root afferents in the cat.

To investigate the physiological role of ventral root afferent fibers, the ventral root was stimulated in spinal cats in an attempt to elicit the flexion reflex, a common nociceptive spinal reflex. The flexion reflex was elicited by stimulating the distal stump of the cut L7 or S1 ventral root and recorded from the proximal stump of the cut S1 ventral root. In 12 of the 14 cats studied, the flexion reflex was recorded as a compound action potential. The finding was confirmed by recording single-unit activity from 5 units in two cats. These results suggest that the ventral root afferent fibers exert a variety of physiological effects that include eliciting such spinal reflexes as the flexion reflex. The responsible fibers in the ventral root travel distally towards the dorsal root ganglion to enter the spinal cord through the dorsal root.

Action Potentials↗