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Biomedical subjects

P Gauthier

Publications and source records attributed to P Gauthier.

At least 73 records · Page 4Linked to original sources

Activity of medullary respiratory neurons regenerating axons into peripheral nerve grafts in the adult rat.

Autologous segments of peroneal nerve were implanted into the medulla oblongata of young adult rats. To investigate activity of medullary respiratory neurons regenerating axons into these grafts, unitary recording from single fibers was performed on small strands teased from the grafts. Spontaneous activity was observed in teased fibers in 7 of 9 grafts recorded 2-5 months after graft implantation. Respiratory-related activity was found in 5 of these grafts and could in most cases be characterized as emanating from medullary respiratory neurons other than cranial motoneurons. The integrity of the input connections to the neurons that had regenerated axons was manifested by normal patterns of unitary respiratory-related activity and by the responsiveness of firing patterns of these neurons to lung hyperinflation and to the inspiratory off-switch effect induced by vagal stimulation. No spontaneous respiratory activity was found in fibers teased from any of the 10 grafts studied 9-11 months after implantation. Five of these grafts were blind-ended as were the 2-5-month grafts; the other 5 grafts formed bridges between the medulla and C4 ventral horn. No physiologic evidence of functional connections with phrenic motoneurons was found in these bridge grafts. These experiments indicate that physiologic function is maintained or regained in some respiratory neurons regenerating axons into peripheral nerve grafts but that this function is not indefinitely preserved in the absence of functional reconnection with an appropriate target.

Action Potentials↗

Efficacy of sequential cyclical hormonal therapy in endometrial cancer and its correlation with steroid hormone receptor status.

Forty-six eligible women with metastatic endometrial cancer were randomly allocated to receive monthly cycles of either CAF (cyclophosphamide, adriamycin, 5-fluorouracil) or CAF plus Provera 200 mg daily for 3 weeks followed cyclically by Tamoxifen 20 mg daily for 3 weeks. Overall response rates of 15 and 43% were seen with CAF and CAF plus hormonal therapy. Using a multivariate analysis of the results, this difference is significant (P value 0.05). In 8 patients with operable endometrial cancer, negative estrogen receptor concentration (ER less than 15 fmole/mg protein) and Grade 3 disease, the clinical course was aggressive in 4 patients with systemic and local relapse. In 10 other similar patients (negative ER and Grade 3) who received adjuvant cyclical hormonal therapy only 1 relapsed and the other 9 are disease-free for an average of more than 31 months. Sequential cyclical hormonal therapy with ER and progesterone receptor analysis has a place in the management of endometrial carcinoma.

Adenocarcinoma↗

Adrenomedullary pressor responses to stimulation of the rostral hypothalamus in the rat: influence of adrenaline-induced vasodilation and reflex cardioinhibition.

Electrical stimulation (100 Hz, 1 ms, 150 microA, 10 s) of the anterior hypothalamus in chloralose-anesthetized rats evoked a biphasic pressor response consisting of an initial sharp rise in arterial pressure at the onset of stimulation, followed by a second elevation after cessation of the stimulus. This response was accompanied by an increase in plasma noradrenaline and adrenaline levels. Peripheral sympathectomy with guanethidine selectively abolished the primary phase of the biphasic pressor response, while bilateral removal of the adrenal medulla eliminated only the secondary component. After alpha-adrenergic blockade with phentolamine, the primary phase of the stimulation-induced response was reduced while the secondary pressor component was blocked and replaced by a significant hypotension. The intravenous administration of sotalol enhanced the secondary pressor component without affecting the stimulation-induced plasma noradrenaline and adrenaline responses. After treatment with atropine, the secondary pressor effect was also potentiated, as the reflex bradycardia normally associated with the response was eliminated. A subsequent administration of sotalol in these rats further potentiated the secondary pressor component to stimulation. In rats treated with atropine and sotalol, the sympathetic vasomotor and the adrenomedullary pressor responses could be dissociated according to thresholds and stimulus frequency or current-response characteristics. The results suggest that in intact rats, adrenaline-induced vasodilation and reflex cardiac inhibition contribute to either reduce or mask the adrenomedullary component of the biphasic pressor response evoked by stimulation of the anterior hypothalamus. The study also raises the hypothesis of a dual regulation of both components of the sympathetic system in the anterior hypothalamic region.

Adrenal Medulla↗

Similar poststimulatory pressor responses with different mechanisms in response to excitation of the locus coeruleus before and after acute adrenalectomy.

Electrical stimulation of the locus coeruleus in anesthetized rats evoked a biphasic pressor response consisting of an initial sharp rise in blood pressure at the onset of stimulation, followed by a second elevation after cessation of the stimulus. This response, which was accompanied by an increase in plasma noradrenaline and adrenaline levels, was stable and could be easily reproduced over time. Sympathectomy by administration of guanethidine selectively abolished the primary pressor response. beta-Adrenergic blockade by intravenous administration of sotalol enhanced the secondary pressor response without affecting the primary component. Adrenal demedullation performed 24-48 h before the experiments selectively prevented the secondary pressor component. In contrast, acute adrenalectomy carried out during the experiment to impair the adrenomedullary secretions eliminated the secondary pressor response to stimulation of the locus coeruleus only in sympathectomized or in sotalol-treated rats but not in intact rats in which the response persisted. The latter, however, could be abolished by the administration of either guanethidine or sotalol, and it disappeared following repeated stimulation of the locus coeruleus. The study demonstrates that similar poststimulatory pressor responses with different underlying mechanisms can be elicited on excitation of the locus coeruleus before and after acute adrenalectomy in the rat. The results also suggest that intraneuronal adrenaline may be involved in the response evoked in acutely adrenalectomized animals.

Adrenalectomy↗

Respiratory resetting induced by activation of inspiratory bulbo-spinal neurons.

The respiratory effects elicited by spinal (C2-C3) stimulation at the level of descending inspiratory axons were studied in paralysed, non-vagotomized and artificially ventilated cats anaesthetized with urethane-chloralose. The activation of inspiratory bulbospinal axons in the ventrolateral quadrant was confirmed by recording the ipsilateral phrenic excitation following a single pulse. Brief stimulus trains delivered at the same locus during expiration elicited short- and long-term phrenic activations. The short-term activation consisted of a tetanic orthodromic response. The long-term activation, of central origin, exhibited the same pattern as a spontaneous inspiration and consisted of an inspiratory resetting which necessitated weak anaesthesia and light hypocapnia. Control experiments (restricted lesions of the medulla and the cervical cord, recording of afferent activity in thalamic sensory nuclei, medullary stimulation) revealed that this inspiratory resetting could not be related to appreciable activation of either non-respiratory efferents or spinal afferent pathways studied but was likely to depend on the activation of the descending inspiratory axons. We conclude that the respiratory resetting obtained by spinal stimulation resulted from mass antidromic activation of the inspiratory bulbospinal neurons which thus appear to be involved in the generation of the respiratory rhythm.

Afferent Pathways↗

[Contingent negative variation and late components of evoked potentials during sleep in man].

The aim of this research was to study brain information processing during waking, deep slow sleep (stage IV) and paradoxical sleep (stage V) in humans, by using as a clue endogenous components of the sensory evoked potential, the emitted potential and the contingent negative variation (CNV). Eight subjects underwent three kinds of mixed auditory stimulus couples: (a) SI-SII: 2 identical clicks (50 msec, 5000 Hz); (b) SI-SIII: SIII (50 msec, 500 Hz) different from SI, was during waking, the target stimulus; (c) SI followed by an omitted click. During sleeping, the situation was used without motor response. The contingent negative variation was clearly observed during waking and paradoxical sleep as the evoked potential whose morphology during deep slow sleep was similar to K complexes. The emitted potential was obtained in four subjects out of seven during paradoxical sleep. These results suggest that during wakefulness, the discrimination of an unconditional stimulus involves a conditioning establishment revealed by the CNV and the emitted potential. The fact that the emitted potential and CNV were unavailable during stage IV is an argument in favor of the hypothesis that the conditioning effects disappear during deep slow sleep. The occurrence of CNV and emitted potential during the paradoxical stage of sleep, suggests that a conditioning established during waking can appear during this stage of sleep.

Contingent Negative Variation↗

Peripheral and central mechanisms of the pressor response elicited by stimulation of the locus coeruleus in the rat.

Electrical stimulation of the pontine nucleus locus coeruleus (LC) caused an increase of the arterial blood pressure in anesthetized rats, and elevated plasma noradrenaline (NA) and adrenaline (A) levels. The stimulation-induced pressor response was characteristically biphasic and consisted of a sharp rise in arterial pressure at the onset of the stimulation, followed by a second elevation at the end of the stimulus. Bilateral adrenalectomy or adrenal demedullation completely blocked the secondary phase of the pressor response elicited by stimulation, but did not affect the primary phase. The latter was specifically eliminated by the destruction of the peripheral sympathetic vasomotor axons with intravenous 6-hydroxydopamine (6-OHDA). The active sites eliciting the secondary adrenomedullary pressor component appeared to be restricted to the nucleus LC, whereas the primary sympathetic vasomotor response could be elicited from sites in and around the nucleus. After brain transection at the midbrain level, stimulation of LC failed to evoke the adrenomedullary pressor response, while the sympathetic vasomotor component was not affected. Similarly, destruction of brain NA neurons by intraventricular administration of 6-OHDA did not change the sympathetic vasomotor response, but virtually abolished the adrenal response. The results demonstrate that the pressor response to stimulation of LC in the rat is due to both increased sympathetic vasomotor activity and CA released from the adrenal medulla. The study also provides evidence suggesting that the noradrenergic LC cell group play an important role in the activation of the adrenal medulla, but is not essential for the activation of the sympathetic vasoconstrictor fiber system.

Adrenal Medulla↗

Identification of histopathologic risk groups in stage IB squamous cell carcinoma of the cervix.

This study was undertaken to identify histopathologic risk factors in 100 women with stage IB squamous cell carcinoma of the cervix treated surgically. Histologic factors included maximum depth of stromal invasion, presence of lymph-vascular invasion, mitotic activity, nature of the tumor-stromal borders, plasma cell-lymphocyte stromal response, histologic grade, and metastases to regional lymph nodes. Using a multifactorial analysis, the maximum depth of stromal invasion was found to be the most important prognostic indicator (P less than .0001). The depth of invasion also correlated significantly with the presence of nodal metastases (P less than .0001), lymph-vascular space invasion (P = .0003), and "spreading" versus "pushing" borders (P = .0315). The number of mitoses, grade of tumor, or plasma cell-lymphocyte stromal response did not correlate significantly with depth of stromal invasion. Lymph-vascular involvement, although present in 59% of the patients, did not significantly affect survival. Depth of stromal invasion and lesion diameter were combined to constitute three risk groups: Patients with small size cervical tumors (less than 2 cm), regardless of depth of stromal invasion, as well as patients with intermediate size lesions (2.1 to 3 cm) with stromal invasion less than or equal to 1.5 cm, constituted a low-risk group; the intermediate-risk group was comprised of those patients with cervical lesions between 2.1 and 3 cm in size and deep stromal invasion (greater than 1.5 cm), as well as those patients with large cervical lesions (greater than 3.0 cm) and stromal invasion less than or equal to 1.5 cm.2+ (greater than 3 cm) and deep stromal invasion (greater than 1.5 cm).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Inspiratory on-switch evoked by stimulation of the mesencephalon: activity of phrenic and laryngeal motoneurones.

In anaesthetized cats (chloralose-urethan) the effects of brief tetanic electrical stimulation (50 to 100 ms) of the mesencephalic central gray matter and reticular formation on the inspiratory on-switch were studied during the expiratory (E) phase on the gross and unitary activities of phrenic, laryngeal inspiratory and laryngeal expiratory nerves. On the inspiratory laryngeal and phrenic nerves, stimulation elicited a short latency gross response concomitant with the train: the inspiratory Primary Response (Prim.R.) which is followed by an inspiratory Patterned Response (Patt.R.) of longer duration which corresponded to the inspiratory on-switch. The Patt.R. generally appeared from the Prim.R. within a latent period (Silent Phase: Sil.P.) as long as 100 ms. On the expiratory laryngeal nerve, stimulation elicited a brief activation (expiratory Prim.R.) concomitant with the beginning of the inspiratory laryngeal Prim.R. and which rapidly stopped as the latter continued during the stimulus train. The inspiratory Prim.R. corresponded to a simultaneous activation of both early and late (so defined during their spontaneous discharge) inspiratory motoneurones. The laryngeal motoneurones were more strongly activated than the phrenic ones. During the inspiratory Patt.R. all the phrenic motoneurones presented a recruitment delay earlier, compared with the spontaneous one, whereas the recruitment drastically changed from an inspiratory laryngeal motoneurones to another. Thus, the two pools of motoneurones presented different properties of activation. During the inspiratory Sil.P. no concomitant expiratory laryngeal activation was observed when most of the inspiratory motoneurones were inactive. As some inspiratory laryngeal motoneurones did not stop firing, the existence of some central respiratory neurones exhibiting a similar persistent activity and subserving the inspiratory on-switch mechanisms may be hypothesized.

Animals↗

Inspiratory on-switch evoked by mesencephalic stimulation: activity of medullary respiratory neurones.

The activity of medullary inspiratory and expiratory neurones was studied in urethan-chloralose anaesthetized cats during stimulus-evoked inspiratory phase (inspiratory on-switch). All neurones were characterized according to their axonal destination (i.e. bulbospinal neurons or vagal motoneurones) or the absence of such axonal projections (i.e. propriobulbar neurones), and to their location in the dorsal or ventral respiratory nuclei. The inspiratory on-switch effects were elicited during expiration (E phase) by brief tetanic electrical stimulation (50 to 100 ms duration; 0.5 mA; 300 Hz) delivered to the mesencephalic periaqueductal central gray and the adjacent reticular formation. The evoked inspiratory effects observed on the phrenic nerve discharge consisted of: an immediate response (latency 20 +/- 5 ms) of stable duration related to the stimulus (primary response: Prim.R.), a delayed response (patterned response: Patt.R.) appearing after a latent period (silent phase: Sil.P.) of 100 ms maximal duration. The later the stimulus in the E phase, the longer was the duration of the Patt.R. (300 to 1000 ms). The stimulation evoked an earlier activation of the inspiratory bulbospinal neurons (latency 12 +/- 6 ms) than that obtained in the phrenic nerve (Prim.R.). Hence, the Prim.R. originated from the bulbospinal pathway and not from a pathway directly impinging on the motoneurones. Conversely during stimulation very few inspiratory propriobulbar neurones were activated and no expiratory neurone discharged. During the phrenic Sil.P., 46% of the inspiratory bulbospinal neurones continued to discharge with a firing rate lower than that during the stimulus train, while most of the inspiratory propriobulbar and expiratory neurones were not active. During the Patt.R. all inspiratory bulbospinal neurones discharged early and were strongly activated whatever the Patt.R. duration whereas the expiratory neurones were not active. Inspiratory propriobulbar neurones were either not recruited or recruited later, and the number of active neurones increased as the duration of the Patt.R. lengthened. Our results suggest that the eliciting of the stimulus-evoked inspiration (Patt.R.) primarily depends on the activation of the inspiratory bulbospinal neurones. These neurones therefore would not only be the output neurones of the medullary respiratory centres, but they would serve other roles such as building up of the excitation in other respiratory neurones, thus acting as a component of the inspiratory ramp generator.

Animals↗

Catecholamines and serotonin in the rat central nervous system after 6-OHDA, 5-7-DHT and p-CPA.

The norepinephrine (NE), epinephrine (EPI), dopamine (DA) and serotonin (5-HT) contents were measured radioenzymatically in seven anatomically defined regions (frontal cerebral cortex, hippocampus, hypothalamus, midbrain, pons-medulla oblongata, cerebellum and spinal cord) in adult normal animals, after treatment with the tryptophan hydroxylase inhibitor p-chlorophenylalanine (p-CPA), and after the intraventricular administration of either 6-hydroxydopamine (6-OHDA) or 5,7-dihydroxytryptamine (5,7-DHT). The effects of p-CPA seemed not restricted to 5-HT, since reductions in catecholamine (CA) content were detected in several regions. After 5,7-DHT given under desimipramine (DMI) protection, comparable reductions in 5-HT levels were obtained but the changes in CA were less severe than after p-CPA. The neurotoxin 6-OHDA decreased the CA in all regions but also 5-HT content in hippocampus, hypothalamus and pons-medulla. The significance and the interpretation of these changes are discussed in relation to the specificity of the drugs employed, together with an assessment of the local monoamine turnover and the possible functional effects of monoamine interactions in the CNS.

5,7-Dihydroxytryptamine↗

Effects of sino-atrial ischaemia on the heart rate response to phasic burst stimulation of the right cervical vagus in the dog.

The effects of occluding sinus node arteries on the pacemaker responses to graded phasic burst stimulation of the right cervical vagus were studied in anaesthetised dogs. In six dogs (Group I), phase response curves (vagally affected atrial cycle plotted against the phase of the stimulus in the cycle) to 1, 3 and 5 pulse burst stimulations were determined at control and hourly for 3 h after the occlusion. In four dogs, the occlusion produced a slowing of the heart rate, a shift of pacemaker outside sinus node region and a displacement of the phase response curves upward and to the right. Identical stimulation bursts resulted in significantly longer atrial cycles than at control, and bursts introduced with a longer phase remained effective and resulted in significantly longer atrial cycles than the maximum one reached at control. However, when the vagal responses were corrected for occlusion-induced changes in spontaneous PP intervals, the occlusion was found not to significantly affect the vagal responses except to increase their variability. Time-related differences in the effects of the occlusion were not statistically significant. In six control dogs (Group II) submitted to the same protocol, occlusion excepted, the vagal response curves changed very little over the 3 h experiments, thus confirming the stability of the experimental preparation used and of the vagal responses obtained in the absence of ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Post-myringotomy care: a prospective study.

Children with tympanostomy tubes have always been considered somewhat handicapped in regard to swimming and bathing. Their parents had to maintain constant surveillance to prevent then from getting water in their ears. A prospective study involving more than 1,000 children was conducted between June 1981 and August 1982 on two groups of randomly selected patients to determine the prevalence of suppurative otitis media and its relationship to bathing and swimming. One group had to follow strict rules to prevent water entering the ear (bathing caps, earplugs) whereas the other group was allowed to bathe and swim without any precaution upon the condition of using a polymyxin B/gramicidin ear drop combination at bedtime on the day they swam. The study shows no increase in prevalence of suppurative otitis media in the "open canal" group as compared to the "closed canal" group. Furthermore, the monthly distribution of infections shows a relatively evan distribution throughout the year. This study implies that swimming and bathing are safe for the vast majority of children with tympanostomy tubes and thus simplifies enormously the post-myringotomy care for the child, the parents, and the physician.

Baths↗

Inspiratory on-switch evoked by stimulation of mesencephalic structures: a patterned response.

The effects of brief tetanic electrical stimulation (50 to 100 ms) of the mesencephalic central gray matter and reticular formation on the inspiratory "on-switch" mechanism were studied during expiration (E phase) in cats anaesthetized with urethan-chloralose. Stimulation during the E phase evoked powerful effects on the phrenic nerve discharge comprising (1) a primary response (Prim. R.) during the train; (2) a patterned response (Patt. R.) resembling that of the normal inspiratory (I) phase and lasting 170 to 1,000 ms. The patterned response corresponded to activation of the inspiratory on-switch (E-I switching) and appeared either immediately after the Prim. R. or within a latent period of 100 ms. The primary response was always obtained during the E phase whatever the stimulation intensity (0.1-1.0 mA). The patterned response was a function (a) of the stimulus time: the later the stimulus in the E phase, the longer the duration of the response; (b) of the stimulus intensity: with 1.0 mA current strength the response was obtained throughout the E phase; with weaker stimuli (0.4 to 0.5 mA) the response was always evoked by trains delivered early (0-300 ms) or late (1,000-1,800 ms) in the E phase; while it occurred irregularly to stimulation in the middle (300-1,000 ms) of the E phase. These results indicate that: (a) the system which promotes inspiration is progressively rather than abruptly depressed at the beginning of expiration, followed by a progressive inspiratory-promoting facilitation at the end of expiration; (b) the patterned response, mostly independent of the stimulus parameter, is not stereotyped and displays considerable plasticity.

Animals↗

Central respiratory drive and recruitment order of phrenic and inspiratory laryngeal motoneurones.

Central respiratory drive and recruitment order of phrenic motoneurones and inspiratory laryngeal motoneurones were studied in anaesthetized, paralyzed and artificially ventilated cats. Unitary activities of pairs of motoneurones originating from the same population were recorded on thin filaments. Differences of recruitment during inspiration enabled distinction to be made between early (E) and late (L) recruited motoneurones. 'On-line' cross-correlation analyses were performed on either homogeneous pairs (2E or 2L) or heterogeneous pairs (1E and 1L). In 14/30 pairs of phrenic motoneurones and 26/32 pairs of inspiratory laryngeal motoneurones cross-correlation analysis revealed a bell-shaped increase of probability of firing whose characteristics indicate synchronization by central shared excitatory inputs originating from central respiratory drive. For phrenic motoneurones synchronization appeared mainly in homogeneous pairs (2E:7/11; 2L:5/9) whereas motoneurones of heterogeneous pairs rarely shared the same central respiratory drive (2/10). For inspiratory laryngeal motoneurones, cases of synchronization were equally obtained in homogeneous (2E:8/10; 2L:14/16) and heterogeneous (4/6) pairs. These results suggest that differences of recruitment order during inspiration are related: (i) for phrenic motoneurones, partly to differences of excitability but mainly to a dual central respiratory drive which is assumed to divide the population into two components; (ii) for inspiratory laryngeal motoneurones to differences of excitability since all the motoneurones share the same drive.

Animals↗

Onset and control of expiratory laryngeal discharge: cross-correlation analysis.

In anaesthetized, paralysed and artificially ventilated cats, spontaneous activity of pairs of expiratory laryngeal motoneurones was recorded and submitted on line to cross-correlation analysis in order to reveal the underlying mechanisms which govern their discharge. In 45/52 pairs, flat cross-correlograms were obtained suggesting independency between the expiratory laryngeal motoneurones. Synchronization by common central respiratory drive was never observed. This negative result is in agreement with the post-inhibitory rebound hypothesis put forward to explain the discharge of expiratory laryngeal motoneurones. In 7/52 pairs, cross-correlation revealed a bell-shaped increase of probability of firing which is relevant with broad synchronization of the discharges by common peripheral afferents.

Animals↗