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Biomedical subjects

J Magnan

Publications and source records attributed to J Magnan.

At least 19 recordsLinked to original sources

[Vestibular compensation. Clinical value of its dynamic study].

Vestibular compensation consists of all the processes of neurological reorganization that allow recovering balance after a unilateral vestibular lesion. According to its etiology, the peripheral lesion may be more or less severe, may evolve more or less rapidly, and be more or less reversible. Therefore, it will have a characteristic "pattern" in time, which enables us to classify the kinetic aspects of peripheral pathology. Vestibular compensation, which responds to these variations in the sensitivity of the posterior labyrinth, is a slowly progressive adaptation mechanism. This compensation will progressively reduce the musculotonic asymmetry affecting the postural muscles and the eye muscles, and it can therefore be studied on the basis of the velocity of the spontaneous nystagmus as measured in the dark. We can then define a "vestibular compensation rate" at a given moment. To achieve this, a diagram (E. UMER) is proposed to represent the lesion and the rate of vestibular compensation and to study their mutual relationships. The dynamic study of vestibular compensation and the measurement of its "time constant" than have threefold merits for diagnosis, prognosis and treatment.

Adaptation, Physiological

Evaluation of closed sterile prefilled humidification.

A closed sterile prefilled humidifier ('Aquapak 310') and a multiple-use humidifier ('Nebal 2') were evaluated in hospital departments to determine their susceptibility to bacterial contamination and cost. No bacterial contamination was found in the 389 samples of 'Aquapak 310' water. However, 54/164 (32.9%) samples of 'Nebal 2' water were found to be contaminated. Pseudomonas aeruginosa was the bacterium most often isolated. The cost analysis was highly influenced by the average use time. In the haemodialysis and respiratory medicine departments the average use times for the 'Aquapak 310' +/- SD were 61.6 +/- 36.2 days and 4.1 +/- 1.7 days, respectively. Using the 'Aquapak 310' system, there was a 51% financial saving in the haemodialysis department but a 2% loss in the respiratory medicine department. In these two departments we found a similar cost saving as far as staff time was concerned (88% vs. 89%). The major difference came from the cost of consumables: 26% saving in the haemodialysis department vs. 70% loss in the respiratory medicine department. Use of the prefilled sterile humidifiers represents a three-fold benefit, a lower infection risk for the patient, an important financial saving in the haemodialysis department and a decreased staff work load.

Cost-Benefit Analysis

Vestibular neurotomy by retrosigmoid approach: technique, indications, and results.

During the past 15 years, 96 retrosigmoid vestibular neurotomies have been used in the surgical management of incapacitating Meniere's disease for the control of vertigo and preservation of hearing. This posterior approach of the pontocerebellar angle gives the best view on the acousticofacial nerve bundle, through a 2 x 2 cm suboccipital craniotomy immediately behind the mastoid and sigmoid sinus. Then the vestibular nerve is easily identified, separated from the cochlear nerve and sectioned, the facial nerve not being at risk, as it lies much deeper. Actually, the majority of authors agree that vestibular neurotomy is the most effective surgical treatment in relieving disabling vertigo (96% of cases) with serviceable hearing, but few surgeons know that the retrosigmoid approach is simpler and more reliable than the middle fossa or retrolabyrinthine approaches, with a low incidence of complications. The purpose of this paper is to emphasize the routine use of the retrosigmoid approach.

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[Anatomo-pathology of cholesteatoma].

The authors, from their own histopathological studies and from an overview of otological literature focus the controversial problems about the so-called disease cholesteatoma. The history of cholesteatoma has been marked out by pathologic data which, initially caused the cholesteatoma to be identified as a keratinized squamous tumor. This misnomer will however be retained because of it long-established usage. "Skin in the wrong place" in the middle ear summarizes this clinical entity. Electron microscopic observations provide arguments in favour of the migratory theory and the invasion of the epidermis from the bottom of the external ear canal into the middle ear cavity (identical fine morphology between skin and cholesteatoma, presence of Langerhans and Merkel cells, sharp junction between the advancing front of the cholesteatoma and the middle ear mucosa). Recent immunohistological techniques allow consideration of cholesteatoma as a self-induced inflammatory process in response to tissular and cellular conflicts. A cholesteatoma could be merely a non-healing wound process and a disease of epidermal growth control occurring in the middle ear space. The logical principles governing cholesteatoma surgery, suggested by these biological considerations, are: total removal of cholesteatoma matrix, prevention of cholesteatoma recurrence by a careful respect of the barrier separating the middle ear mucosa from the skin-lined bony external ear canal, maintenance of good healing conditions for both mucosa in a closed well-ventilated middle ear and epidermis in a harmonious anatomical external canal.

Cell Movement

Demonstration of the heterogeneity of the kappa-opioid receptors in guinea-pig cerebellum using selective and nonselective drugs.

In guinea-pig cerebellum, saturation studies reveal that the nonselective opioid [3H]ethylketazocine has a binding capacity (R) of 6.79 pmol/g tissue which is similar to the sum of the individual R values of the mu-, delta- and kappa 1-selective opioids. Conversely, the binding parameters of the nonselective opioid [3H]bremazocine are best-fitted to a two-site model (Kd1 = 0.12 nM, R1 = 11.3 pmol/g tissue; Kd2 = 6.03 nM, R2 = 9.09 pmol/g tissue) with an R TOTAL value of 20.3 pmol/g tissue which is statistically different from the R value of [3H]ethylketazocine or the sum of R mu + R delta + R kappa 1. This suggests that [3H]bremazocine labels additional opioid binding sites. After suppression of the mu-, delta- and kappa 1-receptors, [3H]bremazocine binding is then best-fitted to a one-site model with a Kd value of 1.48 nM and an R value of 11.2 pmol/g tissue. Competition studies done against the binding of [3H]U69593 indicate that the opioid receptors labelled with this ligand are related to the kappa 1-receptor subtype. However, competition studies performed against the binding of [3H]bremazocine (under suppressed conditions) display a pharmacological profile related to another subtype of kappa-receptors previously described in guinea-pig brain as the kappa 2-receptors.

Animals

Quantitative analysis of multiple kappa-opioid receptors by selective and nonselective ligand binding in guinea pig spinal cord: resolution of high and low affinity states of the kappa 2 receptors by a computerized model-fitting technique.

The binding characteristics of selective and nonselective opioids have been studied in whole guinea pig spinal cord, using a computer fitting method to analyze the data obtained from saturation and competition studies. The delineation of specific binding sites labeled by the mu-selective opioid [3H]D-Ala2,MePhe4,Gly-ol5-enkephalin (Kd = 2.58 nM, R = 4.52 pmol/g of tissue) and by the delta-selective opioid [3H]D-Pen2, D-Pen5-enkephalin (Kd = 2.02 nM, R = 1.47 pmol/g of tissue) suggests the presence of mu and delta-receptors in the spinal cord tissue. The presence of kappa receptors was probed by the kappa-selective opioid [3H]U69593 (Kd = 3.31 nM, R = 2.00 pmol/g of tissue). The pharmacological characterization of the sites labeled by [3H]U69593 confirms the assumption that this ligand discriminates kappa receptors in guinea pig spinal cord. The benzomorphan [3H]ethylketazocine labels a population of receptors with one homogeneous affinity state (Kd = 0.65 nM, R = 7.39 pmol/g of tissue). The total binding capacity of this ligand was not different from the sum of the binding capacities of mu, delta-, and kappa-selective ligands. Under mu- and delta-suppressed conditions, [3H]ethylketazocine still binds to receptors with one homogeneous affinity state (Kd = 0.45 nM, R = 1.69 pmol/g of tissue). Competition studies performed against the binding of [3H]ethylketazocine under these experimental conditions reveal that the pharmacological profile of the radiolabeled receptors is similar to the profile of the kappa receptors labeled with [3H]U69593. Saturation studies using the nonselective opioid [3H]bremazocine demonstrate that this ligand binds to spinal cord membranes with heterogeneous affinities (Kd1 = 0.28 nM, R1 = 7.91 pmol/g of tissue; Kd2 = 3.24 nM, R2 = 11.2 pmol/g of tissue). The total binding capacity obtained with [3H]bremazocine (Rtotal = 19.1 pmol/g of tissue) was different from either the sum of the binding capacities of mu-, delta, and kappa-selective ligands or the binding capacity of [3H]ethylketazocine obtained under unsuppressed conditions. These results suggest that [3H]bremazocine labels additional opioid sites, namely the kappa 2 receptors, in contrast to kappa 1 sites labeled with [3H]U69593. In experimental conditions where the binding of [3H]bremazocine at mu, delta, and kappa 1 receptors was quenched by selective blockers, [3H]bremazocine recognizes the kappa 2 receptors with one homogeneous affinity state (Kd = 3.45 nM, R = 8.23 pmol/g of tissue). However, competition studies suggest that some opioids bind to these kappa 2 receptors with heterogeneous affinity states (high and low affinity states), whereas others bind with one apparently homogeneous affinity state.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

[Otospongiosis: different surgical technics, identical results. Why?].

Both platinectomy and platinotomy are currently used to treat otosclerosis surgically. Though the techniques are different from one another, especially by the new area ratio between tympanic membrane and stapes foot-plate, the results are similar. It should be clear that the simple "piston model" of the tympanic ossicular system cannot explain this results. If, for the seesaw mechanical view, a vibratory molecular system conducting acoustic energy is substituted, a pertinent explanation can be given for this result. Thus, understanding of the pattern motion of the tympanic ossicular system has to change drastically.

Ear, Middle

[Retraction pockets, pathological entity?].

Retraction pockets are not a pathological entity per se but take after various ear diseases, with which they share the same morphological eardrum alterations. The authors believe that any holistic evaluation of retraction pockets, as though these were forming a single group of like pathogenic origin, i.e., tubal dysfunction, would be artificial and raise therapeutic problems. The statistical analysis of the causes for retraction pocket formation provides little information. Otologists are still looking into chronic otitis media and cholesteatoma as a possible, long-suspected, unproved etiology. Electron microscopy and, more particularly, istological-enzymological analyses of mounts prepared by the authors have shown, in some cases, the anomalous presence, in the pocket, of Langerhans' cells, which the authors consider as strongly indicative of cholesteatoma. While confirming the clinical diagnosis, anatomopathological examination allows to differentiate poor-prognosis retraction pockets from benign ones. The pathogenesis of these pockets is still poorly understood. It is the authors' contention that tympanic invagination is more likely traceable to some biopathological/biochemical phenomenon than to occupational mechanical disorders involving the tube. The clinical characteristics of retraction pockets are the basis for their classification into three groups, according to their evolutional tendency. Thus, developing cholesteatomas bear a poor prognosis; sequelae of benign otitis are associated with small risk; lastly, there is a small group of pockets the evolution of which is hard to specify. The authors believe that such differentiation between retraction pockets is mandatory to have a clear picture of therapeutic indications, and to assess the various outcomes.

Cholesteatoma

[Endoscopy of the eustachian tube. 1st evaluation].

The authors present a novel, original method for exploration of the middle ear cavity using Eustachian tube endoscopy. The diameter of the fibre optic tube was only 0.9 mm, hence the term micro-endoscopy. This endoscopic procedure was used during surgery for chronic otitis, where there was evidence of tubal etiology which required confirmation. The preliminary results are presented.

Ear Diseases

Evidence for the presence of mu- and kappa- but not of delta-opioid sites in the human fetal brain.

The presence of multiple opioid binding sites in human fetal brain at 20 weeks gestational age was determined using the following selective tritiated ligands: D-Ala2, N-MePhe4, Gly-ol5-enkephalin (DAGO) for the mu-type, D-Pen2, D-Pen5-enkephalin (DPDP) for the delta-type and U-69,593 for the kappa-type. [3H]DAGO and [3H]U-69,593 each bind to a single class of high-affinity sites in membrane preparations with respective Kd values of 0.96 +/- 0.33 nM and 0.57 +/- 0.20 nM. The binding capacity for [3H]DAGO is 1.38 +/- 0.21 pmol/g tissue whereas [3H]U-69,593 has a binding capacity of 1.04 +/- 0.22 pmol/g tissue. Using DPDP we did not detect any specific high-affinity binding sites in human fetal brain. The non-selective tritiated opioid ethylketazocine (EKC) labels a homogenous class of sites with a Kd of 0.17 +/- 0.01 nM and a binding capacity of 2.15 +/- 0.15 pmol/g tissue, a value that is not statistically different from the total capacity obtained with [3H]DAGO and [3H]U-69,593. Competition studies using selective unlabeled opioids against the binding of [3H]-DAGO, [3H]U-69,593 or [3H]EKC indicate that opioid sites present in human fetal brain possess similar pharmacological characteristics to those found in human and mammalian adult brain. The results of this study present the first evidence for the presence of mu- and kappa-type opioid sites in human fetal brain and this may support the postulated role of the opioid system in the neurobiological development.

Benzeneacetamides

Pharmacological characterization of the binding of [3H]bremazocine in guinea-pig brain: evidence for multiplicity of the kappa-opioid receptors.

In guinea-pig brain, [3H]bremazocine has a binding capacity of 27.2 pmol/g wet tissue, which is statistically different from that of [3H]ethylketazocine (14.7 pmol/g wet tissue) or the sum of the individual binding capacities of mu-, delta-, and kappa-selective ligands (15.0 pmol/g wet tissue). Saturation studies of [3H]bremazocine performed in the presence of unlabelled mu-, delta-, and kappa-blockers still reveal a homogeneous population of binding sites. [3H]Bremazocine under suppressed conditions displays at these sites a Kd of 2.51 nM with a binding capacity of 9.15 pmol/g wet tissue. We have performed the pharmacological characterization of these additional opioid binding sites. Displacement curves measured with a number of opioid substances were all best fitted to a one-site model. The stereoselectivity of these additional sites was demonstrated by using two groups of stereoisomers. Oripavine and benzomorphan opioids were among the most potent drugs at the [3H]bremazocine sites (mu + delta + kappa suppressed). Diprenorphine, bremazocine, cyclazocine, and ethylketazocine displayed apparent affinities constants (1/Ka) of 8.66, 7.57, 21.4, and 38.0 nM, respectively at those sites. The kappa-selective drugs U50488, U69593, PD117302, and tifluadom were inhibitors of the binding of [3H]bremazocine at these sites with apparent affinities of 113, 268, 76.9, and 47.9 nM. All mu- or delta-selective drugs tested in this study have caused weak or no inhibition of the binding. Correlation analyses were done between the different affinities measured at the [3H]bremazocine sites (mu + delta + kappa suppressed) and those observed at the known mu-, delta-, and kappa-sites of the guinea-pig brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Diagnostic and therapeutic problems in dissociated forms of Menière's disease].

The authors report the cases of 5 subjects who presented with incapacitating vertigo which was attributed to a dissociated form of Meniere's disease. They stress the difficulty, in these circumstances, in making a precise diagnosis which can only in fact be confirmed with the benefit of a longer follow up. They stress the value of systematically combining frequency analysis with measurement of maximal slow phase velocity during vestibular testing. This allowed better precision in terms of topographical diagnosis. All subjects underwent vestibular neurotomy via the retro-sigmoid approach. The procedure did not alter hearing and compensation occurred within the usual delay. The question therefore arises as to when is the best time to intervene in patients presenting with vertigo of peripheral origin with preserved hearing.

Audiometry

Binding of the non-selective opioid [3H]etorphine in the human fetal central nervous system.

The existence of specific, high-affinity opioid binding sites was demonstrated in 21-week-old human fetuses with the use of tritiated etorphine, a non-selective opioid ligand. Binding capacities measured in the brain, the cerebellum and the spinal cord give values of 2.83, 3.71 and 5.42 pmol/g of tissue. Kd values do not vary from one region to the other and are respectively 0.29, 0.35 and 0.33 nM. These results are compared with the characteristics of opioid binding sites found in adults.

Binding Sites

[3H]U69,593 binding in guinea-pig brain: comparison with [3H]ethylketazocine binding at the kappa-opioid sites.

[3H]U69,593 and [3H]ethylketazocine (mu + delta suppressed) binding was measured in homogenates of guinea-pig brain. Both ligands bind with high affinity to a single class of opioid sites. The relative equilibrium dissociation constant (KD) for [3H]U69,593 is 1.15 nM, while [3H]ethylketazocine has a KD value of 0.33 nM. Their respective maximum binding capacities are 4.49 and 4.48 pmol/g of wet tissue. Various mu-selective, delta-selective, kappa-selective, and nonselective opioids were tested in competition studies against the binding of [3H]U69,593 or [3H]ethylketazocine (in the presence of mu- and delta-blockers) to measure their relative affinity. [D-Ala2, MePhe4,Gly5-ol]enkephalin (mu-selective) has low affinity (600-3000 nM) and [D-Pen2,D-Pen5]enkephalin and [D-Ser2, Leu5, Thr6]enkephalin (delta-selective) have very low affinities (greater than 20,000 nM) at the sites labelled with [3H]U69,593 or [3H]ethylketazocine. On the other hand, unlabelled U69,593, U50,488H, and tifluadom (all three kappa-selective substances) display high affinity (1-5 nM) at those sites. Nonselective opioids, such as bremazocine, levorphanol, and ethylketazocine show similar affinities at the sites labelled with [3H]U69,593 and at the sites labelled with [3H]ethylketazocine. These data indicate that [3H]U69,593 is a selective high-affinity ligand for the same sites that are labelled with [3H]ethylketazocine (in the presence of mu- and delta-blockers) and that these are kappa-sites.

Benzeneacetamides

Localization of kappa opioid receptor binding sites in human forebrain using [3H]U69,593: comparison with [3H]bremazocine.

1. The autoradiographic distribution of kappa opioid receptor binding sites in human brain was examined using two radiolabeled probes, namely [3H]U69,593 and [3H]bremazocine. 2. [3H]U69,593 binding was performed in the absence of blockers for other sites, while [3H]bremazocine binding was investigated in the presence of saturating concentrations of mu and delta blockers to ensure selective labeling of kappa opioid receptors. 3. Our results show that the autoradiographic distribution of [3H]U69,593 and [3H]bremazocine (plus blockers) binding sites is identical, with high densities of sites found in deep cortical layers and claustrum. 4. This indicates that [3H]U69,593 is a highly selective ligand of the kappa opioid receptor type.

Autoradiography

Autoradiographic distribution of multiple classes of opioid receptor binding sites in human forebrain.

Receptor binding parameters and autoradiographic distribution of various opioid receptor sites have been investigated in normal human brain, post-mortem. [3H]DAGO, a highly selective mu ligand, binds to a single class of high affinity (Kd = 1.1 nM), low capacity (Bmax = 160 fmol/mg protein) sites in membrane preparations of frontal cortex. These sites show a ligand selectivity profile that resembles that of the mu opioid receptor. On the other hand, [3H]bremazocine, in presence of saturating concentrations of mu and delta blockers, appears to selectively bind to a single population of kappa opioid sites (Kd = 0.13 nM; Bmax = 93.0 fmol/mg protein) in human frontal cortex. Whole hemisphere in vitro receptor autoradiography reveals that [3H]DAGO-mu, [3H]DSLET-delta and [3H]bremazocine (plus blockers)-kappa binding sites are discretely and differentially distributed in human forebrain. In the cortex, mu sites are concentrated in laminae I and IV, delta sites in laminae I and II while kappa sites are found in deeper layers (laminae V and VI). In subcortical nuclei, high densities of mu and delta sites are seen in the caudate and putamen while high amounts of kappa sites are present in the claustrum and amygdala. The nucleus basalis of Meynert is enriched in all three classes of sites while the globus pallidus only contains moderate densities of kappa sites. Thus, the possible alterations of these various classes of opioid receptors in neurological and psychiatric diseases certainly deserve further investigation.

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