NMDA receptor-mediated glutamate toxicity of cultured cerebellar, cortical and mesencephalic neurons: neuroprotective properties of amantadine and memantine.

Effects of amantadine and memantine on NMDA receptor-mediated glutamate toxicity were studied in cultured cerebellar, cortical and mesencephalic neurons. Both drugs protected cerebellar and cortical neurons against glutamate toxicity, memantine being consistently more effective than amantadine but less effective than MK-801. Glutamate toxicity of dopaminergic neurons in mesencephalic cultures was only mildly attenuated by memantine but was also only incompletely blocked by MK-801. These findings suggest that adamantanamines act by inhibiting NMDA receptor-mediated excitatory neurotransmission. However, since non-NMDA receptors appear to be principal mediators of glutamate toxicity of dopaminergic mesencephalic neurons, adamantanamines may fail to protect the nigrostriatal neurons which specifically degenerate in Parkinson's disease.

Failure of a protein synthesis inhibitor to modify glutamate receptor-mediated neurotoxicity in vivo.

The delayed neuronal death (DND) resulting from brief forebrain ischemia has recently been reported to be markedly attenuated by parenteral administration of the reversible protein synthesis inhibitor, anisomycin. Previous work suggests that ischemia-induced DND is mediated by glutamate acting at one or more glutamate receptors, since glutamate receptor antagonists have been reported to reduce ischemia-induced DND. Consequently, we tested whether anisomycin could modify DND induced by direct intracerebral administration of the excitotoxins, N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxasole (AMPA) or kainic acid. Anisomycin, administered parenterally, in multiple doses did not alter DND induced by any of these excitotoxins, nor did combined parenteral and direct intracerebral injection of anisomycin protect against DND induced by AMPA. Thus, neurotoxicity induced by direct intracerebral administration of NMDA, AMPA or kainic acid does not appear to require de novo protein synthesis, and, therefore, is not likely to be mediated by the expression of a programmed cell death cascade.

MK-801 and memantine protect cultured neurons from glutamate toxicity induced by glutamate carboxypeptidase-mediated cleavage of methotrexate.

Cleavage of methotrexate into glutamate and diaminomethylpteroate by intrathecal glutamate carboxypeptidase is a new approach to the treatment of acute methotrexate neurotoxicity. The simulation of glutamate carboxypeptidase rescue from high-dose methotrexate in neuron astrocyte cocultures of rat cerebellum or cerebral cortex resulted in a selective, concentration-dependent neurotoxicity. The neurotoxicity was caused by the enzymatic release of glutamate from methotrexate at lower concentrations of methotrexate, and by both glutamate and diaminomethylpteroate at concentrations of methotrexate exceeding 200 microM. The good neuroprotection afforded by MK-801 and memantine suggested that glutamate toxicity was mediated by N-methyl-D-aspartate receptors. Methotrexate alone was not toxic to astrocytes, neurons, or the neurite networking. [3H]thymidine and [3H]deoxyuridine incorporation studies showed that astrocyte proliferation in the presence of methotrexate was maintained by the reutilization of pyrimidine bases for DNA synthesis. N-methyl-D-asparate receptor antagonists should be coadministered in future experimental and clinical trials examining intrathecal glutamate carboxypeptidase rescue of methotrexate toxicity.

The glutamate receptor of the Qp-type activates protein kinase C and is regulated by protein kinase C.

In striatal neurons in primary culture quisqualate potently stimulated the formation of inositol phosphates via a metabotropic receptor we recently termed Qp in order to distinguish it from the classical ionotropic quisqualate receptor termed Qi. Here we show that 10 microM of quisqualate activated in a rapid and transient manner protein kinase C as assessed by its translocation from the cytosolic to the membrane fraction. As 10 microM alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), the Qi specific agonist, was without effect, this translocation was most probably mediated by the Qp receptor. Phorbol 12,13-dibutyrate blocked in a dose-dependent manner the Qp receptor-induced inositol phosphate formation (IC50 = 2 +/- 0.4 nM). The inactive ester 4 alpha-phorbol-12,13-didecanoate was without effect. Very low concentrations of staurosporine completely reversed the phorbol 12,13-dibutyrate-induced blockade (IC50 = 2.2 +/- 1.3 nM). It can therefore be concluded that the Qp receptor is able to activate protein kinase C and that the activity of this metabotropic receptor is regulated by protein kinase C.

[Substernal goiter. Report of 212 cases]. / Les goitres plongeants. A propos de 212 cas.

AIM OF THE STUDY: The aim of this retrospective study was to report the results of the surgical treatment in a series of 210 patients operated on for substernal goiters. PATIENTS AND METHOD: From 1982 to 1996, 210 patients with substernal goiters, including 80% of women, were operated on via a cervical approach in 208 cases, via a sternotomy in two cases. Two patients with operative contra-indications were not operated on. Twenty-five were operated on for a substernal recurrence of a goiter. In 160 cases, extraction of the substernal portion was easy. In 48 cases, removal of the substernal portion was facilitated by the discovery of the recurrent nerve at its entering into the larynx and a downward dissection of the tracheal attachments of the lobe. The complete dissection of the cervical portion made easier the ascension of the substernal portion even in very large substernal components. RESULTS: Three papillary carcinomas were diagnosed. A transient laryngeal nerve palsy occurred in 7.2% of the patients and a transient hypoparathyroidism in 13.4%, A definitive laryngeal nerve palsy occurred in 1.2% of the patients, and a persistent hypoparathyroidism in 2.1%. Of the 25 patients who underwent surgery for recurrence of a goiter, three (12%) developed a transient laryngeal nerve palsy, one (4%) a permanent nerve palsy, four (20%) a transient hypoparathyroidism and one (4%) a persistent hypocalcemia. CONCLUSION: CT scan and MRI are the best explorations to evaluate intrathoracic extension of substernal goiters. Thyroidectomy was performed via a cervical incision in 208 patients and via a sternotomy in two patients only. The complete dissection of the cervical portion with discovery of the recurrent nerve at its entering into the larynx, facilitates the ascension of the substernal portion even in very large substernal goiters.

[Basilingual rhabdomyoma treated by endoscopy]. / Rhabdomyome basi-lingual. A propos d'un cas traité par voie endoscopique.

Rhabdomyoma in adults is a rare benign neoplasm of the skeletal muscles generally arising in the pharyngolaryngeal region. These slow-growing tumors remain asymptomatic for a long period. We report a case of basilingual rhabdomyoma. Computed tomography and magnetic resonance imaging demonstrated a well-encapsulated tumor with a line of cleavage between the base of the tongue muscles. Deep transmucosal biopsies were obtained. Well-differentiated skeletal muscle cells with large eosinophilic granulular cytoplasm and cross striations gave the histologic diagnosis. Complete endoscopic resection was successful. The differential diagnoses of rhabdomyoma in adults are myoblastoma or Abrikossof tumor, rhabdomyosarcoma and hibernoma. The risk of late recurrence implies long-term clinical and radiologic follow-up.

[Laryngomucoceles and subtotal C.H.E.P. reconstructive laryngectomy. Report of 6 cases]. / Laryngomucocèles et laryngectomies subtotales reconstructives de type C.H.E.P. A propos de 6 cas.

UNLABELLED: We conducted a retrospective analysis of 131 patients who underwent subtotal CHEP laryngectomy for a tumor of the larynx between 1990 and 1999 in order to determine the incidence of laryngomucocele after surgery. RESULTS: Five patients developed laryngomucocele late after surgery. A sixth patient underwent surgery in another unit. Laryngomucocele developed progressively or was disclosed by acute episodes of dyspnea, requiring tracheotomy again in two cases. One patient developed bilateral mucocele. Three patients had cervicotomy, and three others were treated by CO(2) laser endoscopic marsupialization. DISCUSSION: We discuss the pathophysiology of late laryngomucocele after subtotal laryngectomy and various techniques that can be used to avoid this complication. CONCLUSION: Although exceptional, laryngomucocele generally requires surgical removal by cervicotomy or CO(2) laser endoscopic marsupialization to prevent acute respiratory failure.

[Chemical labyrinthectomy: results and applications]. / Labyrinthectomie chimique. Résultats et intérêt.

GOAL OF THE STUDY: Unilateral Menière's disease can be treated by chemical labyrinthectomy. The goal of this work was to report our clinical experience with chemical labyrinthectomy, and to discuss the respective value of labyrinthectomy and of vestibular neurotomy for treating unilateral Menière's disease. METHODS: Twelve patients underwent chemical labyrinthectomy using middle ear gentamicin infusion. Before treatment, patients had a pure tone audiogram and a vestibular caloric testing. After treatment, patients had a clinical assessment at 1 and 6 months after treatment (pure-tone audiogram, vestibular caloric testing), and answered a questionnaire at 1 and 2 years following the treatment (number of vertigo attacks, ataxia, tinnitus, subjective assessment of the method by the patient). RESULTS: At two years post-treatment, the vertigo cure rate was 91.6% (ABC using AAOO criteria), vestibular function was abolished in 70% of cases, ataxia was reported in 42% of patients, 16.6% of patients had hearing deterioration above 20 dB HL (C following AAOO criteria), tinnitus was decreased in 50% of cases. Of 12 patients, 8 were satisfied. CONCLUSION: Chemical labyrinthectomy cures vertigo in Menière's disease, with similar cure rate than vestibular neurotomy. Minor complications can occur with chemical labyrinthectomy. This method should be used in more patients.

[Isolated facial palsy and occult adenoid cystic carcinoma of the parotid]. / Paralysie faciale isolée et carcinome adénoïde kystique occulte de la parotide.

We report a case of adenoid cystic carcinoma of the parotid disclosed by facial palsy alone. No tumefaction could be detected clinically or at imaging. The diagnosis was established at surgical exploration of the facial nerve. Total extended parotidectomy was completed by radiotherapy of the tumor site.

[Combined approach (endoscopic and external) for the treatment of sinusal mucoceles]. / Indications des voies combinées (endoscopique et externe) dans le traitement des mucocèles sinusiennes.

AIM OF THE STUDY: Determination of the best surgical approach in the treatment of mucocoeles of the sinuses according to their localization. PATIENTS AND METHODS: A retrospective study has been carried out including forty three cases of sinus mucocoeles, surgically treated from 1990 to 1997. These were in descending order, frontal (n = 19), maxillary (n = 10), ethmoïdo-frontal (n = 9), sphenoidal (n = 3) and ethmoidal (n = 2). Surgical treatment was achieved with an exclusive endoscopic approach in 28 cases whereas 15 of them underwent endoscopic surgery associated with an external approach (also called combined technique). Short term complications and recurrence were recorded after a minimum of 6 years follow-up, according to the type of surgery performed and the topography of the mucocoele. RESULTS: Recurrence of mucocoeles is prevented in 95.8% of cases by an exclusive endoscopic treatment in ethmoïdo-frontal, maxillary, sphenoidal and ethmoidal sites. On the other hand, the recurrence rate in mucocoeles involving the frontal sinuses without ethmoidal involvement, was significantly higher when the mucocoele was operated on by an exclusively endoscopic method (25%, p < 0.001) rather than by a combined technique (0%). DISCUSSION AND CONCLUSION: Ethmoido-frontal, maxillary, sphenoidal and ethmoidal mucocoeles are excellent indications for an exclusively endoscopic endonasal surgery. An external approach, combined with endoscopic surgery, is suitable in frontal mucocoeles, especially in distal sites and in case of recurrence.

[Imaging of the hypopharynx, oropharynx and parapharyngeal spaces]. / Imagerie du pharyngolarynx, de l'oropharynx et des espaces parapharyngés.

Progress in upper aerodigestive imaging improved pathologic staging and therapeutic choices. Imaging, especially CT scan is now indispensable for staging the upper aerodigestive cancers. Some anatomic areas must be explored with special attention because of their importance for therapeutic decision.

The N-methyl-D-aspartate antagonist MK-801 fails to protect dopaminergic neurons from 1-methyl-4-phenylpyridinium toxicity in vitro.

Recent reports suggest that NMDA receptor antagonists when administered in vivo can protect dopaminergic neurons from the toxic actions of MPP+. In the present study the possible neuro-protective effects against MPP+ toxicity of the noncompetitive NMDA receptor antagonist MK-801 was studied in primary cultures of fetal rat mesencephalic dopamine neurons. MK-801 failed to protect dopaminergic neurons from MPP+ toxicity at concentrations that completely block NMDA-induced toxicity of these same neurons. In contrast to work carried out in cerebellar granule cells, MPP+ toxicity of mesencephalic dopamine neurons was unaffected by preexposure to subtoxic concentrations of either NMDA or cycloheximide. Our findings suggest that the toxic effects of MPP+ on dopaminergic neurons are not mediated through a direct interaction with the NMDA subtype of glutamate receptor.