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Biomedical subjects

A Giovanni

Publications and source records attributed to A Giovanni.

At least 19 recordsLinked to original sources

Estimating hydroxyl radical content in rat brain using systemic and intraventricular salicylate: impact of methamphetamine.

Free radicals have been implicated in the etiology of many neurodegenerative conditions. Yet, because these species are highly reactive and thus short-lived it has been difficult to test these hypotheses. We adapted a method in which hydroxyl radicals are trapped by salicylate in vivo, resulting in the stable and quantifiable products, 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA. After systemic (100 mg/kg i.p.) or intraventricular (4 mumol) administration of salicylate, the amount of DHBA in striatal tissue correlated with tissue levels of salicylate. After systemic salicylate, the ratio of total DHBA to salicylate in neostriatum was at least 10-fold higher than that observed after central salicylate. In addition, systemic salicylate resulted in considerably higher concentrations of 2,3- and 2,5-DHBA in plasma than in brain. Therefore, a large portion of the DHBA present in brain after systemic salicylate may have been formed in the periphery. A neurotoxic regimen of methamphetamine increased the concentration of DHBA in neostriatum after either central or systemic administration of salicylate. The increase in 2,3-DHBA after the central administration of salicylate was significant at 2 h, but not at 4 h, after the last dose of methamphetamine. These results suggest that (1) when assessing specific events in brain, it is preferable to administer salicylate centrally, and (2) neurotoxic doses of methamphetamine increase the hydroxyl radical content in brain in a time-dependent manner.

Animals

[Objective vocal evaluation of dysphonia by simultaneous measurement of acoustic and aerodynamic parameters with the EVA device].

Authors present the analysis of the voice in 88 normal subjects and 159 dysphonic patients by simultaneously measurements of Jitter (acoustical short-term indicator of aperiodicity) and "Glottal Leakage" (aerodynamic parameter calculated by the ratio of Oral Airflow and Intensity). All the measurements were performed, with EVA apparatus, on the most stable part of a steady-state vowel /a/. The reference method was the rating by a jury along a global perceptual scale. Statistical tests confirm that Jitter and "Glottal Leakage" are relevant to evaluate the quality of the voice. Discriminant analysis allows to find out a fairly-good rate of discrimination of 63.1% (Randomly rating would have been 25%) The authors conclude on the interest of such a protocol and present suggestions to improve it by taking in count phénomena during the vocal attack and middle-term variations.

Acoustics

[Phonetic results after surgery of laryngotracheal stenoses in children].

The quality of the results of laryngotracheoplasties is clear evidence of the progress made in the treatment of stenoses involving the larynx and the trachea in children. the surgeon is no longer limited to helping the child breath correctly via the natural airways but can also concentrate on phonatrics since dysphonia is frequent after laryngotracheoplasty. Vocal production of 23 children who had undergone surgery for laryngotracheal stenosis was evaluated subjectively by a panel of listeners and objectively on the basis of the pitch and intensity of the voice, rate of speech and maximal time of phonation. In 11 children over the age of 5 years, assisted assessment of the voice completed the study. In 69.5% of the cases, the voice was subjectively considered to be satisfactory. Voice was considered clear in 52% of the cases. Speech flow was impaired in 39% due to frequent breath taking. Objective parameters revealed that pitch was slightly impaired (256 Hz) with a tendancy to normalize near puberty. The intensity of the voice (77 dB) and mean maximum phonation time (7 s) decreased. The phonotary quotient (270 ml/sec), jitter (1.4%) and leakage of the glottis (2.02 cm3/dB/s) were slightly above the normal range. The spectra of the voices were richly furnished with harmonics up to about 1 000 Hz above which air noises increased. An attempt was made to correlate the analysis of the voice with the characteristics of the stenosis and with the therapeutic methods used. The results would suggest the iatrogenic nature of prolonged canulation and of increasing the size the size of the posterior cricoid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

[Reconstructive anterior frontal laryngectomy. Long-term results in T2 glottic cancers].

Between 1982 and 1992, we performed near total laryngectomy with epiglottic reconstruction in 142 patients with state T1 and T2 according to the 1987 Union Internationale contre le Cancer. In this paper, we report our experience with 61 T2 patient who were followed-up 5 years or until death. Actuarial survival was 83%. Actuarial tumor control was obtained in 91%. There were no post-operative mortalities and follow-up was usually simple. All patients underwent decanulation and were able to eat by normal track. The main drawback of this technique is speech disability. We use near total laryngectomy with epiglottic reconstruction in certain T2 patients selected according to local extension. This choice is justified by good functional results and an excellent local control. The contraindications are age over 75 years, poor patient cooperation, cardiac or pulmonary disease, fixation of the arytenoids, subglottic extension of more than 1 cm in front and 0.5 cm laterally, and extensive involvement of the ventricular folds or anterior commissure.

Adult

[Surgical approach of the petrous vertical segment and upper cervical internal carotid].

The main obstacle to successful management of aneurysms involving the high cervical internal carotid artery (ICA) is to obtain an adequate exposure. In this report we describe our experience in 5 patients presenting carotid aneurysms at the skull base, intermediately below the carotid foramen. Exposure is achieved in two stages. The cervical stage consists in resection of the styloid processes and muscles followed by anterior displacement of the mandibular condyle. This exposes the vertical segment of the petrous ICA. The petrous stage consists in partial petrectomy exposing the jugular bulb and the third segment of the facial nerve. Using this route, the vertical intrapetrous segment of the ICA can be drilled away without damaging the middle ear. In our series, no vascular complications occurred. Damage involving the facial glossopharyngeal and vagal nerves is discussed. This approach appears to be a suitable alternative to the conventional infratemporal approach which sacrifices the middle ear.

Adolescent

Studies on species sensitivity to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Part 1: Systemic administration.

Several parameters necessary for the expression of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity to dopaminergic neurons were examined in both mice and rats in order to determine if differences in these processes might underlie the marked differences in the sensitivity of the two species to the neurotoxic effects of MPTP. Monoamine oxidase-B activity was greater in brain tissues from rats than from mice. The kinetics of 1-methyl-4-phenylpyridinium (MPP+) uptake into neostriatal synaptosomal preparations from the two species were similar. Brain and neostriatal levels of MPP+ were 2-fold higher in rats after the administration of MPTP at 60 mg/kg and were 10 to 20 times higher in rats than in mice after MPTP treatment which produced similar decrements in the content of neostriatal dopamine. MPP+ concentrations in the extracellular fluid of the neostriatum of the two species were similar after the administration of the same dose of MPTP (40 mg/kg). However, this dose induced a 40-fold increase in neostriatal dopamine efflux in mice, whereas in rats only a 3-fold increase was observed. In addition, pretreatment of rats with guanethidine, a ganglionic blocking agent, permitted the use of high doses of MPTP which resulted in substantial damage to the striatal dopaminergic nerve terminals. It is concluded that nigrostriatal dopaminergic neurons in the rat require exposure to a much higher concentration of MPP+ than do those in mice for the induction of toxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Studies on species sensitivity to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Part 2: Central administration of 1-methyl-4-phenylpyridinium.

There are marked species differences in susceptibility to the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice are sensitive, whereas rats are relatively insensitive to MPTP. In these two species, the effects of peripherally administered MPTP or intrastriatally infused 1-methyl-4-phenylpyridinium (MPP+) were examined to identify potential underlying mechanisms responsible for their difference in susceptibility to MPTP. In vivo intrastriatal microdialysis and an MPP+ 2-day test/challenge paradigm were used to monitor dopamine efflux as an indicator of the neurotoxic effects of MPTP or MPP+. By using this method, the EC50 for neurotoxicity by an intrastriatal infusion of MPP+ in mice was 0.4 mM, whereas it was 10-fold higher in rats (4.3 mM). In addition, by using the traditional postmortem examination, neostriatal dopamine was depleted markedly in mice (> or = 80%), but only depleted marginally in rats in which MPP+ was infused into the neostriatum. These data indicate that rats are relatively insensitive to MPTP as compared to mice, because they are less sensitive to MPP+ whether it is formed in vivo from MPTP administered systemically or administered directly into neostriata. Thus, there appears to be a fundamental difference in the susceptibility of the nigrostriatal systems in these two species to the neurotoxic consequences of MPP+ exposure.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

[Nodules and paranodular lesions: a trial of anatomo-clinical correlation].

The use of increasingly powerful diagnostic tools has enabled the laryngologist to refine the diagnosis of nodular lesions, and, within this group, to isolate clinical variations, paranodular lesions, mucosal thickening, mucosal pseudo-cysts. Systematic comparison between the clinical and anatomopathological diagnosis of the lesions operated upon does not make it possible to establish a strict correlation between the clinical and the histological aspects. Nevertheless, histology appears to throw light on the physiopathology of such lesions within the field of dysfunctional laryngopathies.

Fiber Optic Technology

[Multiparameter analysis of dysphonia using the equipment Physiologia].

The purpose of the multiparametric analysis of the vocal phenomenon is to evidence the instability of the signal in amplitude and in frequency, together with the aerodynamic phenomena related to the glottic air leakage. Statistical analysis has made it possible to establish a correlation between the data of the apparatus, as from 9 variables, and the clinical classification. The main diagnostic categories are relatively close, evidencing the various biomechanical anomalies of the laryngeal vibrator. A certain number of issues remain to be addressed: the physiopathology of the vibrator, the choice of the phonetic sample, and the different methods of instrumental analysis.

Biomechanical Phenomena

[Cholesteatoma of the middle ear in children. Apropos of 80 cases and review of the literature].

Cholesteatoma occurs in 10% of cases of chronic otitis in children. In most children, the clinical form is very similar to acquired cholesteatoma in the adult. However, we observed certain clinical variations in our retrospective series of 80 cases seen in our unit over the past 8 years. In most all cases, otorrhoea and hypoacousia were the presenting signs. The tympanic membrane was fully intact in 10% of the cases raising the possibility of congenital pathogenesis. An analysis of the correlations between per-operative observations and tomodensitometric results was conducted. Closed tympanoplasty, with a second operation 11 months later, was performed in 84% of the cases. Residual cholesteatoma was observed in 41% of the second operations and relapse occurred in 16%. These anatomic and functional findings, compared with those in the literature, demonstrate that no major difference in the published series. Presently the most important point is to separate acquired and congenital forms, which differ in terms of pathogenesis and clinical presentation, but are treated in the same manner. Progress in the treatment of cholesteatoma of the middle ear in children will come from prevention through earlier diagnosis of pathological manifestations in the ear nose and throat, in particular blocked Eustachian tubes, and through follow-up and treatment of pre-cholesteatomous states, as well as further advances in fundamental research.

Adolescent

MK-801 fails to protect against the dopaminergic neuropathology produced by systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice or intranigral 1-methyl-4-phenylpyridinium in rats.

Previous studies from this laboratory demonstrated that (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), an N-methyl-D-aspartate (NMDA) receptor antagonist, did not prevent neurotoxicity to dopaminergic neurons in mice produced by systemic treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, Turski et al. [Nature 349, 414-418 (1991)] reported that extended treatment of rats with NMDA receptor antagonists (six injections at 4-h intervals) did prevent the loss of nigral dopaminergic neurons resulting from an intranigral infusion of 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of MPTP. The present studies examined if a similar extended treatment with MK-801 would protect mice from the neurotoxicity of systemically administered MPTP. Six intraperitoneal injections of MK-801 given at 4-h intervals did not protect mice against the MPTP-induced neostriatal dopamine loss measured 1 week after treatment. In other experiments, designed to replicate and expand on the results of Turski et al. (1991), the extended treatment of rats with MK-801 did not prevent MPP(+)-induced cell loss in the infused substantia nigra pars compacta or the dopamine depletion in the ipsilateral neostriatum at 7-11 days after MPP+ infusion. These results do not support the hypothesis that NMDA receptors are involved with MPTP/MPP(+)-induced neurodegeneration.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

[How to evaluate velar insufficiency?].

The evaluation of velar insufficiency is absolutely necessary in order to assess the results of surgery of the labial palatal cleft. In addition to the clinical examination which remains indispensable, the aerophonometer, applicable to adults and children as from the age of 3, enables simultaneous measurement of the flow of buccal air, the flow of nasal air, and the buccal phonogram. The comparison of the lines, the relation of the nasal air and buccal air flows, upon the emission of two standard sentences with and without nasal components, enables an objective assessment of velar functioning.

Child, Preschool

[A multiparameter method of computer-assisted objective vocal evaluation].

The aim of this study is to validate an aid for the evaluation of dysphonia with objective measurements. We recorded exhaled airflow, fundamental frequency and sound level pressure, for a sustained vowel "a", with 51 dysphonic subjects and 15 normal subjects. The following measurements are made on these three parameters: mean value, standard deviation and coefficient of variation. The exhaled airflow volume was also computed for a duration of 2 seconds. A principal components analysis of the measurements indicated that it is possible to recognise the classes of vocal evaluation and vocal pathology. These findings reinforce on objective aid for the vocal evaluation of dysphonia.

Diagnosis, Computer-Assisted

Correlation between the neostriatal content of the 1-methyl-4-phenylpyridinium species and dopaminergic neurotoxicity following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration to several strains of mice.

In the present study we observed pronounced differences in the capacity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce dopaminergic neurotoxicity in several strains of mice. For example, there was no MPTP-induced decrement in neostriatal dopamine content in Ace Swiss-Webster mice and a 92% decrement in Taconic Farms C57 bl mice. Several parameters which could possibly explain this differential sensitivity to MPTP were studied. These include: 1) neostriatal monoamine oxidase-B (MAO-B) activity; 2) the capacity of neostriatal synaptosomes prepared from the mouse strains to accumulate 1-methyl-4-phenylpyridinium (MPP+), the major metabolite of MPTP formed via oxidation by MAO-B; and 3) the neostriatal MPP+ content after MPTP administration to the mice. There were no significant differences in the Km values for MAO-B in the neostriatum among the strains of mice examined. Neostriatal Vmax values for MAO-B differed somewhat among the strains, with a low of 2915 +/- 172 nmol/g of tissue per hr (CD-1 mice from Charles River) and a high of 3884 +/- 203 nmol/g of tissue per hr (C57 bl mice from Taconic Farms). However, Vmax values for MAO-B in the mouse strains did not correlate significantly with the relative sensitivity of the strains to MPTP. There were no significant differences in the capacity of neostriatal synaptosomes prepared from the mouse strains to accumulate MPP+. Studies on the metabolism of MPTP after peripheral administration revealed that there was a significant (P less than .01) positive correlation between the relative sensitivity of the mouse strains to MPTP and their neostriatal MPP+ content after MPTP administration.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine- and 1-methyl-4-(2'-ethylphenyl)-1,2,3,6-tetrahydropyridine-induced toxicity in PC12 cells: role of monoamine oxidase A.

The toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-(2'-ethylphenyl)-1,2,3,6-tetrahydropyridine (2'Et-MPTP), and their corresponding pyridinium species was studied in the rat pheochromocytoma PC12 cell line. MPTP and its analogues are known to be metabolized by monoamine oxidase (MAO) to dihydropyridinium intermediates which are further transformed, either enzymatically or spontaneously, into pyridinium species. MAO activity in PC12 cells is almost exclusively of the A form, and 2'Et-MPTP is a good substrate for both MAO-A and MAO-B. In contrast, MPTP is a poor substrate for MAO-A, but a good substrate for MAO-B. 2'Et-MPTP caused considerably more cell death than MPTP in the PC12 cells. However, 1-methyl-4-(2'-ethylphenyl)pyridinium and 1-methyl-4-phenylpyridinium, the corresponding pyridinium species formed from 2'Et-MPTP and MPTP, respectively, were equipotent as toxins. The toxic effects of the tetrahydropyridines and their corresponding pyridiniums were both concentration- and time-dependent. Measurements of the levels of the pyridinium species formed and the remaining tetrahydropyridine in the media indicated that 2'Et-MPTP was converted about five to seven times more readily into its toxic pyridinium species than was MPTP. There was, moreover, an excellent correlation between amount of pyridinium formed and cell death. There was also a parallel between the capacity of clorgyline and pargyline, irreversible MAO inhibitors, to decrease the formation of the pyridinium species and their capacity to protect against the toxic actions of the tetrahydropyridines. These data are consistent with the concept that the MAO-A-dependent formation of the pyridinium species from the tetrahydropyridine is a prerequisite for toxicity in PC12 cells.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

[Treatment of laryngotracheal stenoses in children].

Over a period of 5 years, from 1984 to 1989, 35 children were treated surgically for a laryngo-tracheal stenosis, 27 by an external approach, 8 by endoscopy with the CO2 laser. Of the children, 25 (71%) were under 5 years old at the time of treatment and 77% of the stenoses (n = 27) corresponded to a post-intubation and/or tracheotomy acquired etiology. Based on the classification of stenoses according to the extent of the impairment of the aerial lumen, the authors stress the value of conservative treatment (endoscopy) in Stage I (less than 70%, n = 8), and of treatment using the external approach in Stage II (between 70% and 90%, n = 12), in Stage III (between 90% and 99%, n = 12) and Stage IV (complete obstruction, n = 3). The technique most widely used currently is laryngo-tracheoplasty with the insertion of costal cartilage (n = 17). Analysis of the results shows that decannulation was successful in 85% of the cases. With respect to the management of stenoses in the new-born baby, the authors report on their recent experience with laryngo-trachoe-fissure in 6 cases as an alternative either to tracheotomy in difficult extubations, or to laryngo-tracheoplasty when the child's weight is particularly low.

Adolescent

Studies with the neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and several of its analogs.

The nigrostriatal dopaminergic neurotoxicity of MPTP was prevented in mice in a dose-dependent manner by the monoamine oxidase-B (MAO-B) inhibitor deprenyl. This finding, combined with other observations, points out the important role of MAO-B in the bioactivation of MPTP. In the present study, some comparisons between MPTP and several of its structural analogs will be presented.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine