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Biomedical subjects

P Gauthier

Publications and source records attributed to P Gauthier.

At least 19 recordsLinked to original sources
PubMed2006

Diaphragm recovery by laryngeal innervation after bilateral phrenicotomy or complete C2 spinal section in rats.

This study aimed to highlight the functional aspects of diaphragm reinnervation by laryngeal motoneurons after bilateral phrenicotomy or complete cervical transection. The left recurrent laryngeal nerve was connected to the left phrenic nerve in 14 rats. Five months later, all bridged rats presented a substantial ipsilateral diaphragm recovery (74.2 +/- 10% of contralateral activity) whereas the diaphragm remained paralysed in non-bridged rats (n = 5/5). After additional right phrenicotomy, functional breathing persisted in bridged rats whereas all non-bridged died. After complete C2 spinal transection, diaphragm respiratory discharges persisted in bridged rats. The reinnnervation by laryngeal motoneurons was confirmed by retrograde labeling, stimulus-elicited diaphragm response by vagal stimulation and diaphragm inactivation after vagotomy. In conclusion, the recurrent-phrenic nerve anastomosis induces a reliable functional diaphragm outcome even after contralateral diaphragm denervation or complete high cervical spinal cord injury, and could be considered as a clinical repair strategy for re-establishing diaphragm autonomy following spinal cord trauma.

Anastomosis, Surgical↗
PubMed2006

A new model of upper cervical spinal contusion inducing a persistent unilateral diaphragmatic deficit in the adult rat.

Research on spinal cord trauma requires models reflecting the contusion mechanisms encountered in clinical situation. The aim of this study was to develop in the adult rat a reproducible model of upper cervical spinal cord contusion inducing persistent unilateral diaphragm deficit. After dura and pia matter removal, weight drop and compression were targeted at the ventro-lateral funiculi which contain the bulbospinal descending respiratory pathways that command the phrenic motoneurons innervating the diaphragm. At 7 days post-injury, the left diaphragm activity recorded in contused rats (27.4 +/- 5.1% of the contralateral activity) was significantly lower than in the sham group (97.6 +/- 1.2%). This respiratory deficit still persisted 1 month later. Histology showed a reproducible left C2-lateralized lesion that involved both white and gray matter including the ventro-lateral funiculi. This C2 contusion model provides a basis for testing both regenerative and neuroprotective strategies aimed at improving functional respiratory recovery after spinal cord trauma.

Animals↗
PubMed2006

Adjuvant therapy for patients with stage I papillary serous endometrial cancer.

Uterine papillary serous carcinoma (UPSC) is an aggressive variant of endometrial cancer characterized by a high recurrence rate and poor prognosis. Several studies have demonstrated that UPSC has a tendency to manifest with extra-uterine disease, even for tumors which appear to be limited to the endometrium. The data on adjuvant chemotherapy for stage I UPSC are limited, and the available studies are generally under-powered to assess if chemotherapy improves survival. However, we believe that, patients with UPSC should receive complete surgical staging, including omentectomy and peritoneal biopsies, and then until the results of larger series or randomized controlled trials will be available, we feel that combined radiotherapy and chemotherapy is justified for all stage I UPSC.

Combined Modality Therapy↗
PubMed2006

Use of rotary fluidized-bed technology for development of sustained-release plant extracts pellets: potential application for feed additive delivery.

The aim of this study was to develop sustained release plant extracts as a potential alternative to antibiotic growth promoters for growing pigs. Pellets with a core based on microcrystalline cellulose and 3 active compounds (eugenol, carvacrol, and thymol) were prepared using rotary fluidized-bed technology. Two particle sizes were produced that had a mean size of approximately 250 and 500 mum. Results show the process was able to produce pellets with a spherical and homogenous form when 10% of the active compounds were incorporated into the core. When active compounds were increased to 20%, the pellet became stickier, and the yield decreased from 90 to 65%. Different amounts of coating in the form of an aqueous-based ethylcellulose (EC) dispersion (Surelease) were applied to the core to modify the release of active compounds. The efficacy of the coating was evaluated in vitro using a flow-through cell apparatus. The time to achieve 50 and 90% dissolution increased with the increase in particle size (P < 0.05) and the increase in EC-coating level from 10 to 20% (wt/wt; P < 0.05), indicating the ability of the process to slow release depending on particle size and the amount of polymer applied. Differences in the release of the active compounds were observed in the same formulation of pellets, except for the formulation with small 10%-EC-coated particles, in which the active compounds were rapidly dissolved (more than 85% in 15 min or less). For all other formulations, the dissolution time for eugenol was always faster than for thymol or carvacrol. The close monitoring of plant extract behavior in the gastrointestinal tract could become a key factor in the continued use of phyto-molecules as alternatives to antibiotic growth promoters and in optimizing the balance between cost and efficacy. Different microencapsulation technologies can be used, of which the rotary fluidized bed warrants consideration because of the quality of the products obtained.

Animal Feed↗
PubMed2005

[Transplantation of olfactory glial cells after spinal injury. I--From experimental data to repair strategy after central injury].

Ensheathing olfactory glial cells (OEC) can be considered, with stem cells, as the other most important cell type for developing therapeutic cellular transplantation strategies following lesion of the central nervous system (CNS) and particularly in the case of spinal cord injury. OECs are macroglial cells whose precursors are located in the olfactory mucosa. OEC ensheath the axons of the sensory olfactory neurons, from the peripheral mucosa to the central olfactory bulbs. These glial cells constitute one of the rare macroglial cells which, after removal in the adult mammal, can survive in culture and multiply. After post-traumatic transplantation in the CNS, these cells have induced several instances of functional recovery after injury of different neural systems. The "OEC transplantation effect" consists in modifying the central inhibitory environment to make it more propitious for axonal regrowth and cell survival (reduction of the glial scar; releasing of numerous survival and neurotrophic factors, and of surface, extracellular matrix and adhesion molecules). In addition to the fact that OEC can ensheath and/or myelinate central axons, migrate in the CNS and accompany the growing axons over a relatively long distance, they also can be obtained from olfactory mucosa. OEC thus constitute a preferential candidate for autologous transplantation for the purposes of repair.

Age Factors↗
PubMed2005

[Transplantation of olfactory ensheathing cells after spinal injury. II--Experimental variability and clinical perspectives].

Over recent years, a certain number of experimental investigations have studied the effect of the transplantation of olfactory ensheathing glial cells (OEC) after spinal traumatism in animal, the rat in particular. Some of these studies have reported improvements in motor (mainly locomotor, postural and respiratory) and sensory function. While these new data provide additional support for the interest of the strategy of EOC transplantation to minimise the incapacitating effects of spinal pathologies in clinical therapy, it nonetheless remains necessary to continue experiments on animal models in order to better understand and master certain important points: beneficial effects according to the nature and composition of the transplants; therapeutic impact according to the type of pathology and the nature of the traumatism; influence of the dose effect; migration of the transplanted OECs (distance, pathways); active principles of the transplants; beneficial effect on various functions, in particular at the level of the vesico-sphincteric area; long-term innocuousness; long-term posttraumatic efficacy. Although therapeutic trials are in progress in certain countries (Australia, China, Portugal), it would nonetheless appear essential that these somewhat obscure points should be better understood before any clinical application might be seriously envisaged, in order to respect the principles of precaution, maximum efficacy and observance of the prevailing ethical rules.

Animals↗
PubMed2004

Deflagration-to-detonation transition in inertial-confinement-fusion baseline targets.

By means of highly resolved one-dimensional hydrodynamics simulations, we provide an understanding of the burn process in inertial-confinement-fusion baseline targets. The cornerstone of the phenomenology of propagating burn in such laser-driven capsules is shown to be the transition from a slow unsteady reaction-diffusion regime of thermonuclear combustion (some sort of deflagration) to a fast detonative one. Remarkably, detonation initiation follows the slowing down of a shockless supersonic reaction wave driven by energy redeposition from the fusion products themselves. Such a route to detonation is specific to fusion plasmas.

Journal Article↗
PubMed2004

Isolation and characterisation of a human anti-idiotypic scFv used as a surrogate tumour antigen to elicit an anti-HER-2/neu humoral response in mice.

HER-2/neu is a tumour antigen that is overexpressed in human breast tumours. Among the vaccine strategies developed to overcome immune tolerance to self-proteins, vaccination with anti-idiotypic (anti-Id) antibodies has been described as a promising approach for treatment of several malignant diseases. To develop an active immunotherapy for cancer patients positive for HER-2/neu, we investigated immunisation with human anti-Id single-chain fragments (scFv) mimicking the conformation of HER-2/neu protein to induce a humoral response in mice. We selected by phage display two human anti-Id scFv (Ab2beta) directed against trastuzumab F(ab')2 fragments (Ab1), a humanised anti-HER-2/neu monoclonal antibody. Using competitive ELISA and Biacore biosensor analysis, we showed that anti-Id scFv 40 and scFv 69 could inhibit HER-2/neu binding to trastuzumab. Following vaccination of BALB/c mice with the soluble or phage-displayed scFv, Ab3 polyclonal antibodies, and among them Ab1' antibodies able to bind HER-2/neu, were detected in the sera of the immunised mice. These results demonstrate that the human anti-Id scFv could act as a surrogate antigen for HER-2/neu. The present study strongly suggests that the novel 30 kDa human mini-antibody could be used as an anti-idiotype-based vaccine formulation to induce an effective humoral response in patients bearing HER-2/neu-positive tumours.

Animals↗
PubMed2004

Phrenic rehabilitation and diaphragm recovery after cervical injury and transplantation of olfactory ensheathing cells.

Functional respiratory recovery was evaluated by recording diaphragm and phrenic nerve activity several months after cervical cord hemisection followed by olfactory ensheathing cell (OEC) transplantation. The intact side was taken as a control in each rat. Sham-transplanted rats did not recover respiratory activity from the ipsilateral lesioned side. By contrast, ipsilateral phrenic and diaphragmatic activities recovered in transplanted rats amounted to 80.7% and 73% of their controls, respectively. After contralateral acute C1 section eliminating any contralateral influence from crossed compensatory pathways, the ipsilateral phrenic activity remained at 57.5% of the control, indicating that the phrenic recovery originated from the ipsilateral side. Supralesional stimulation in these rats elicited sublesional ipsilateral postsynaptic phrenic responses showing that transplantation helped ipsilateral fibers to again transmit nervous messages to the phrenic target, leading to substantial functional recovery. The origin of mechanisms involved in respiratory recovery (regeneration, resurrection, sprouting, sparing, demasking of latent pathways) is discussed.

Animals↗
PubMed2002

Functional reconnections established by central respiratory neurons regenerating axons into a nerve graft bridging the respiratory centers to the cervical spinal cord.

The present work investigated, in adult rats, the long-term functional properties and terminal reconnections of central respiratory neurons regenerating axons within a peripheral nerve autograft bridging two separated central structures. A nerve graft was first inserted into the left medulla oblongata, in which the respiratory centers are located. Three months later, a C3 left hemisection was performed, and the distal tip of the graft was implanted into the C4 left spinal cord at the level of the phrenic nucleus, a natural central inspiratory target. Six to eight months after medullary implantation, the animals (n = 12) were electrophysiologically investigated to test 1) the phrenic target reinnervation by analyzing the phrenic responses elicited by bridge electrical stimulation and 2) the bridge innervation by unitary recordings of the spontaneous activity of regenerated axons within the nerve bridge. In the control group (n = 6), the medullary site of implantation corresponded to the dorsolateral medulla, a region known to be an unsuitable site for inducing respiratory axonal regrowth after nerve grafting. Stimulation of the nerve bridge never elicited phrenic nerve response, and no respiratory units were found within the nerve bridge. In the experimental group (n = 6), the proximal tip of the nerve bridge was implanted within the ventrolateral medulla at the level of the respiratory centers. Electrical stimulation of the nerve bridge induced phrenic nerve responses that reflected a postsynaptic activation of the phrenic target. Subsequent unitary recordings from teased fibers within the bridge revealed the presence of regenerated inspiratory fibers exhibiting discharge patterns typical of medullary inspiratory neurons, which normally make synaptic contacts with the inspiratory phrenic target. These results indicate that, when provided with an appropriate denervated target, central respiratory neurons with regenerated axons along a nerve bridge can remain functional for a long period and can make precise and specific functional reconnections with central homotypic target neurons.

Animals↗
PubMed2002

Regeneration of acutely and chronically injured descending respiratory pathways within post-traumatic nerve grafts.

Central respiratory neurons, which are acutely axotomized by peripheral nerve grafts implanted at the level of the descending respiratory pathways within the C2 spinal cord, can regenerate their axons within the grafts and still transmit normal physiological messages [Decherchi et al., 1996. Exp. Neurol. 137, 1-14]. The present work investigated the extent to which mature central neurons, acutely or chronically axotomized by a spinal lesion, still maintain the potential to regenerate an axon following post-traumatic nerve grafting within supra-lesional spinal structures and remained functional. This study is an extension of earlier work employing the more chronic lesions, that investigated whether respiratory neurons chronically axotomized by a spinal cord injury can retain the ability to regenerate their axonal process within a post-traumatic peripheral nerve graft. Here implantation was performed into the supra-lesional ventrolateral part of the ipsilateral C2 spinal cord (at the level of the descending respiratory pathways) previously hemisected at the C3 level. In the present study, these post-traumatic peripheral nerve grafts were performed either acutely (group I, n=15, 2.5 h post-injury: acute conditions) or chronically (group II, n=17, 3 weeks; group III, n=6, 3 months: chronic conditions) after the injury.Electrophysiological recording of teased filaments (n=2362) within the post-traumatic peripheral nerve grafts revealed the presence of regenerated nerve fibers with spontaneous unitary impulse traffic (graft units, n=954) in all animals. These graft units were respiratory (n=247) and non-respiratory (n=707). Respiratory discharges originated from central respiratory neurons which remained functional with preserved afferent connections. Except for the group III, post-traumatic C2 peripheral nerve grafts of the groups I and II contained a significantly higher occurrence rate (13.2+/-2% and 11.6+/-1.9%) of respiratory units than C2 spinal peripheral nerve grafts (5.9+/-1.6%) realized without previous CNS injury. The main conclusion of our study is that for a prolonged period of 3 weeks following a spinal cord injury, central respiratory neurons have the potential to remain functional and to regenerate their axonal process within post-traumatic peripheral nerve grafts inserted rostrally to the spinal damage. This indicates that supra-lesional post-traumatic nerve grafts may constitute an efficient delayed strategy for inducing axonal regrowth of chronically axotomized adult central neurons. This suggests that surgical intervention which is not always possible immediately after a spinal cord injury may be satisfactorily carried out after an appropriate delay.

Acute Disease↗
PubMed2001

Study of a GABAC receptor antagonist on sleep-waking behavior in rats.

RATIONALE: gamma-Aminobutyric acid (GABA) is the main inhibitory transmitter of the brain. The involvement of GABAA and GABAB receptors in sleep-waking processes is well established. OBJECTIVES: This research studied the influence of GABAC receptors. METHODS: The rats were randomly infused in the fourth ventricle with vehicle and 25, 50, and 100 micrograms (1,2,5,6,-tetrahydropyridine)-methylphosphinic acid (TPMPA), a specific antagonist of GABAC receptors. RESULTS: Principally at 50 micrograms, the molecule induced an increase of waking from 44.7% to 61.7% (P < 0.003), which was the consequence of enhancement of both active and quiet wakefulness. Total slow wave sleep was decreased, particularly the slow-wave stage from 39% to 27.7% (P < 0.02). Paradoxical sleep was also decreased from 14.5% to 9.1% (P < 0.01). CONCLUSIONS: GABAC receptors are also involved in sleep-waking regulation. Since the sensitivity of GABAC receptors to GABA is much higher than that of GABAA and GABAB receptors, GABAC receptor modulators could be potential medications acting at low doses with fewer side effects.

Animals↗
PubMed2001

Comparative efficacy and safety study of etidronate and alendronate in postmenopausal osteoporosis. effect of adding hormone replacement therapy.

OBJECTIVES: To compare the efficacy and safety of etidronate and alendronate in patients with postmenopausal osteoporosis and to assess the efficacy of either bisphosphonate in combination with hormone replacement therapy (HRT). PATIENTS AND METHODS: In this pragmatic study, the main efficacy criterion was the mean annual change in bone mineral density (BMD). Patients who had a past or current history of etidronate or alendronate treatment for postmenopausal osteoporosis with at least 18 months follow-up and an evaluation in 1999 were eligible. Recruitment was in an outpatient clinic with a special focus on metabolic bone diseases. Osteoporosis was defined as at least one low-energy fracture or as a lumbar spine or femoral neck BMD decrease to at least 2.5 SD below the mean in young women. HRT was not an exclusion criterion provided treatment duration was longer than 1 year. Etidronate was given cyclically (14-day courses in a dosage of 400 mg/d separated by 76-day intervals with calcium and vitamin D supplementation) and alendronate was given daily in a dosage of 10 mg/d. RESULTS: Of the 99 patients who met our inclusion criteria, 53 received etidronate (including 23 on HRT) and 46 alendronate (18 on HRT). Repeat BMD measurements were obtained in 88 patients, including 11 who stopped their bisphosphonate therapy within the first year of use because of adverse events. Lumbar spine BMD (mean +/- SD) increased significantly both in the etidronate group (+2.1% +/- 0.7%/year) and in the alendronate group (+5.3% +/- 0.9%/year). The increase was significantly greater with alendronate (P< 0.01). The lumbar spine BMD increase was largest in the patients on alendronate and HRT (+6.5% +/- 1.4%/year) and was smallest (and nonsignificant) in the patients on etidronate without HRT (+ 1.2% +/- 0.8%). Femoral neck BMD showed no significant changes in any group. In the intention-to-treat analysis, fractures occurred in 12 etidronate patients (22.6%) and six (13.0%) alendronate patients (nonsignificant). Adverse events requiring bisphosphonate discontinuation before the scheduled date of the follow-up BMD measurement occurred in one patient (1.9%) in the etidronate group (generalized osteomalacia) and in ten patients (21.7%) in the alendronate group (upper or lower gastrointestinal tract symptoms in six and four patients, respectively; P < 0.01). CONCLUSION: Both etidronate and alendronate significantly increased lumbar BMD, but the effect was significantly more marked with alendronate. Conversely, adverse effects, most notably gastrointestinal symptoms, were more common with alendronate, so that premature treatment discontinuation because of adverse events were more common in the alendronate group. Both differences should be taken into account when selecting the best drug for a patient with postmenopausal osteoporosis.

Aged↗
PubMed2001

Studies on the aminopeptidase activities of Porphyromonas gingivalis.

Porphyromonas gingivalis is an asaccharolytic bacterium that requires nitrogen substrates as carbon and energy sources. The aims of this study were to investigate the aminopeptidase activities of P. gingivalis and to evaluate the effect of aminopeptidase inhibitors on bacterial growth. Only arginine aminopeptidase and dipeptidyl aminopeptidase IV activities were detected. Experimental evidence was obtained suggesting that the Arg-gingipains of P. gingivalis can function as both an endopeptidase and an aminopeptidase. Firstly, the arginine aminopeptidase activity was found to be inhibited by leupeptin, a well-known inhibitor of Arg-gingipain activity. Secondly, a preparation of Arg-gingipain activity could hydrolyze the chromogenic substrate for arginine aminopeptidase. Lastly, a mutant of P. gingivalis constructed via gene disruption by use of suicide plasmids and deficient in both Arg-gingipain A and B was also devoid of arginine aminopeptidase activity. To investigate the key role of aminopeptidase activities in growth of P. gingivalis, aminopeptidase inhibitors were incorporated in the culture medium prior to inoculation. Bestatin and actinonin were the only ones to inhibit growth of P. gingivalis. Their mechanism of growth inhibition appears to be different but does not involve inhibition of the two major aminopeptidase activities (arginine aminopeptidase and dipeptidyl aminopeptidase IV).

Adhesins, Bacterial↗
PubMed2000

Effects of aerobic physical exercise in the elderly with type 2 diabetes mellitus.

The objective of this study was to determine the impact of an aerobic physical exercise program in the treatment of a group of elderly patients with type 2 diabetes mellitus (DM) in relation to metabolic control, physical capacity, quality of life (QOL) and attitudes toward diabetes. Patients were randomly assigned to either an experimental (n=19) or a control (n=20) group. The following measurements were conducted at baseline and after week 16: glycosylated hemoglobin (hbA1c), fructosamine, 3 h oral glucose tolerance test, treadmill test (Balke-Naughton), and a questionnaire on QOL and attitudes toward DM. After the intervention, the experimental group showed a significant decrease of glucose excursion during the oral glucose tolerance test (OGTT) (area under the curve) (16.6+/-3.8 vs. 15.3+/-3.1, P<0.05) and an increase in total time on the treadmill (s) (423+/-207 vs. 471+/-230, P<0.05). An improvement in the attitudes toward DM was observed in the experimental group (P=0.01) but not in the control group. Female gender, higher body mass index and hbA1c were factors associated with a response to the intervention. This study suggests that physical exercise has significant effects on glucose excursion during an OGTT and exercise tolerance in elderly patients with type 2 DM.

Journal Article↗
PubMed2000

Regrowth of acute and chronic injured spinal pathways within supra-lesional post-traumatic nerve grafts.

The present work investigates the extent to which mature central neurons acutely or chronically axotomized by a spinal lesion still maintained the potential to regenerate an axon following post-traumatic nerve grafting within supra-lesional spinal structures. In adult rats, a C3 cervical hemisection (injury) was made and an autologous segment of the peroneal nerve was implanted 2mm rostrally into the ventrolateral part of the ipsilateral C2 spinal cord. Nerve graft implantations were carried out acutely at the time of injury (group I, acute conditions) or chronically, three weeks post-injury (group II, chronic conditions). Central neurons axotomized by the spinal lesion were labeled by True Blue injected at the lesion site at the time of trauma. Central neurons regenerating axons within the nerve grafts were labeled with either horseradish peroxidase (only in group I, n=4) or Nuclear Yellow (group I, n=3 and group II, n=6) applied two to four months post-grafting to the distal cut end of the nerve grafts. Neurons with dual staining (True Blue/Nuclear Yellow) represented central regenerating neurons which were previously axotomized by the spinal lesion and which had retained the capacity for axonal regeneration for a delayed period after injury. In group I (acute injury conditions), all types of labeled cells were found to be scattered with a clear bimodal distribution within the spinal cord and the brainstem. No labeled cells were found within the motor cortex. There was no statistically significant difference between horseradish peroxidase and all cells containing Nuclear Yellow (Nuclear Yellow and True Blue/Nuclear Yellow). In group II (chronic injury conditions), Nuclear Yellow- and True Blue/Nuclear Yellow-labeled cells had a similar dual distribution to that of group I, but were found to be significantly less represented (P=0.019). These differences are discussed in terms of capacity for cell survival and axonal regrowth after acute and chronic injury. The main conclusion is based on the evidence of dual staining of central neurons in both groups, which demonstrates that brainstem and spinal neurons involved in acute and chronic axotomy after spinal C3 lesion can survive the trauma and still maintain the capacity to regenerate lesioned axons within nerve grafts inserted rostrally (C2 spinal cord) to the primary site of injury. Although exhibited to a lesser extent in chronic than in acute conditions, this capacity was found to occur for as long as three weeks post-injury. These results indicate that supra-lesional post-traumatic nerve grafts may constitute an efficient delayed strategy for inducing axonal regrowth of chronically axotomized adult central neurons. We suggest that surgical intervention, which is not always possible immediately after a spinal cord injury, may be satisfactorily carried out after an appropriate delay.

Animals↗
PubMed2000

[Effect of a multi-strategic group program on performance of the activities of daily living for elderly people with mild cognitive deficits.

OBJECTIVE: The goal of this study was to determine the impact of a group activity program on the level of functioning of a person in instrumental activities of daily living (IADL). This program was specifically designed for people with mild cognitive deficiencies living at home and attending a day centre. METHOD: Using a single subject design of AB type, eleven persons were assigned randomly to a experimental group (n = 7) and to a control group (n = 4). Their cognitive functioning was found to be between the 5th and the 25th percentile on the Modified Mini-Mental State Examination (3MS), which corresponds to stage 3 on the Reisberg Scale. The 18 week long multi-strategic program consisted of two weekly meetings of one and a half hours each. This program included physical exercises, psychomusical techniques, cognitive games and tasks related to IADL. The level of functioning of the subjects in their IADL was measured six times at home using the Assessment of Motor and Process Skills (AMPS), before, during and after the program. FINDINGS: The data derived from each subject were presented as a graphical analysis. Following the application of the program, more of the participants, as compared to the control subjects, improved their functioning in terms of IADL. CONCLUSION: The findings of this study suggest that it would be possible to use coping strategies in the early stages of cognitive deficits.

Activities of Daily Living↗