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BACKGROUND: Perioperative strategies can significantly influence long-term cancer outcomes. Dexmedetomidine, an α2-adrenoceptor agonist, is increasingly used perioperatively for its sedative, analgesic, anxiolytic, and sympatholytic effects. Such actions might attenuate the perioperative promotion of metastases, but other findings suggest opposite effects on primary tumour progression. We tested the effects of dexmedetomidine in clinically relevant models of dexmedetomidine use on cancer metastatic progression. METHODS: Dexmedetomidine was given to induce sub-hypnotic to sedative effects for 6-12 h, and its effects on metastasis formation, using various cancer types, were studied in naïve animals and in the context of stress and surgery. RESULTS: Dexmedetomidine increased tumour-cell retention and growth of metastases of a mammary adenocarcinoma (MADB 106) in F344 rats, Lewis lung carcinoma (3LL) in C57BL/6 mice, and colon adenocarcinoma (CT26) in BALB/c mice. The metastatic burden increased in both sexes and in all organs tested, including lung, liver, and kidney, as well as in brain employing a novel external carotid-artery inoculation approach. These effects were mediated through α2-adrenergic, but not α1-adrenergic, receptors. Low sub-hypnotic doses of dexmedetomidine were moderately beneficial in attenuating the deleterious effects of one stress paradigm, but not of the surgery or other stressors. CONCLUSIONS: The findings call for mechanistic translational studies to understand these deleterious effects of dexmedetomidine, and warrant prospective clinical trials to assess the impact of perioperative dexmedetomidine use on outcomes in cancer patients.

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The perceptual GIRBAS scale for deviant voice quality was tested in 5 different institutes on 943 voice patients. Each voice was evaluated separately by 2 professionals. The interrater and intrarater correlation is satisfactory for G, R and B. Experience with the scale significantly improves the interrater agreement. Further, GIRBAS/acoustical correlations were investigated by using the multidimensional voice program (MDVP) of Kay. Principal component analysis allows reduction of 21 MDVP parameters to 5 clinically relevant clusters, with a typical acoustical measurement for each of them. The GIRBAS scale seems to be a valuable instrument for clinical practice.

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The purpose of this study is to examine the most reliable and valid way for rating and comparing videolaryngostroboscopic recordings with a differentiated protocol. 30 high quality videostroboscopic recordings (2-5 minutes) of all kinds of vocal fold pathology were rated independently by 7 experienced laryngologists/phoniatricians, using a standardized and exhaustive protocol form. Interobserver agreement is high for amplitude, mucosal wave, and type of closure/symmetry, is satisfactory for regularity, consistency and vibration of the lesion (if any), and is rather moderate to low for grade of glottic closure and symmetry. As a general rule, raters trained with the protocol form show higher agreement than raters without such experience. Intraobserver consistency is good for all parameters.

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The perceptual GRBAS scale for deviant voice quality (completed with a "I" parameter: Instability = fluctuation of voice quality over time) was tested in 5 different institutes on 943 voice patients. Each voice was evaluated separately by 2 professionals. The interrater correlation reaches 0.87 for G (grade), 0.70 for R (roughness), 0.69 for B (breathiness) and 0.65 for A/S (asthenicity/strain). Experience with the scale significantly improves the interrater agreement. The intrarater correlation (80 voices; time interval 2-6 months) is systematically slightly stronger than the interrater correlation. Further, GIRBAS/acoustical correlations were investigated on 80 pathological voices, by using the Multidimensional Voice Program (MDVP) of Kay. Principal component analysis allows reduction of 21 MDVP parameters to 5 clinically relevant aspects, with a typical acoustical measurement for each of them. The strongest correlations are found between G and Shimmer/Noise to harmonics ratio, R and Jitter, and B and Shimmer. As tremor and diplophonia are easily identified perceptually and acoustically, it seems useful to add this information respectively to AS and R. The GIRBAS scale seems to be a valuable instrument for clinical practice.

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The botulinum toxin is a highly potent neurotoxin, used since several years in the treatment of the focal musculary dystonias. We define the laryngeal dystonia as a clinical entity, which is represented by a spasmodic dysphonia or an inspiratory dyspnea without dysphonia, related to a specific dystonia of the thyroarytenoid muscles. The laryngeal functional exploration (i.e. fibroscopy, videostroboscopy, acoustic analysis, computerized voice analysis), the neurological and electrophysiological assessment allow to make diagnosis and evaluation of the therapeutical results of this rare laryngeal neurologic disease which was relatively misunderstood until now. There are several clinical types of spasmodic dysphonia: adductor form (with a jerky voice, pitch beaks, vocal arrests and pneumophonatory incoordination); abductor form (with a breathy voice of very low intensity) and mixed types which can be difficult to identify. Since 1989, we have treated 55 laryngeal dystonias with local intra-muscular botulinum toxin injection: 48 spasmodic dysphonia and 7 inspiratory dyspnea without dysphonia, with hyperactivity of the thyroaryténoïd muscles. We present our therapeutical protocol and results which are good in 87% of cases.

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We report the successful treatment of three patients with adduction spasmodic dysphonia by direct injection of botulinum toxin into the vocal cord(s). This was achieved under electromyographic control, and this and other otolaryngeal techniques were used to monitor treatment and study this often puzzling condition.

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We have all noticed that there was no coincidence between the conventional audiometric tests--tonal, vocal, Metz tests--and the degree of impairment of understandability in noisy environments that the patients report. Some of them handle this problem better than these conventional tests suggest, others less well. The aim of this study is to take account of this dominating functional complaint: impairment in noisy conditions, and to assess it in order to follow up its evolution after medical, surgical and prosthetic treatments. The aim of the authors has been to describe an easy examination to be implemented in any ENT surgery fitted with a free-field vocal testing equipment. The results show that this test cas differentiate between "noise-resistant" subjects and those that do not "resist" well. The discussion defines the limitations of this test, which are due to its deliberate simplicity, and the caution required for its psychoacoustic and physiological interpretation. The conclusion confirms its merits, since it can discriminate and help choose more accurate tests--temporal tests, frequency selectiveness charts, twin-ear tests, cognitive AEP.

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A behavioral syndrome consisting of 5-hydroxytryptamine (5-HT)-dependent behaviors (e.g. forepaw treading, retropulsion and splayed hindlimbs) as well as hyperthermia occurred after bilateral injection of the (6S, 10bR)-(+)-enantiomer of McN-5652-Z into the cerebral ventricles in pargyline-treated rats. Both the behavioral syndrome and hyperthermia produced by (+)-McN-5652-Z were counteracted by parachlorophenylalanine or ketanserin. The (6R, 10bS)-(-)-enantiomer of McN-5652-Z influenced neither behavior nor body temperature. The enantiomers of McN-5652-Z differed also in their ability to inhibit ex vivo binding of paroxetine in rat frontal cortex and hypothalamus, in vitro uptake of 5-HT in rat blood platelets, and 5-HT-induced contraction of rat vascular smooth muscle, with (+)-McN-5652-Z being most active. No difference was observed between the effects of (+)- and (-)-McN-5652-Z on 5-HT metabolism by rat brain monoamine oxidase. Molecular models of N-protonated enantiomers having a cis B,C-ring juncture and a B-ring chair conformation were differentiated using a hypothetical model of the 5-HT uptake area. The findings indicate that the enantiomers of McN-5652-Z are useful tools for studying the stereoselectivity of behavioral and pharmacological effects exerted by serotonergic neurotransmission.

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Spasmodic dysphonia is a focal laryngeal dystonia, a rare form of dystonia. Videostroboscopy, acoustic analysis, computerized voice analysis and over all electrophysiological analysis allow for the study of the different muscles involved in this dysphonia. There are two types of spasmodic dysphonia: adductor spasmodic dysphonia and abductor spasmodic dysphonia. The most efficient therapy nowadays is the injection of botulinum toxin into the thyroarytenoid muscle under fiberoptic visualization. We report 6 patient's cases of spasmodic dysphonia that we have been treating for about 2 years by direct injection of botulinum toxin in the vocal cords.

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The SIVO prosthesis, developed by Pr A. Fourcin (London), is an aid to lip reading for profoundly deaf patients with residual hearing at low frequencies below 500 Hz. This prosthesis reduces the complexity of the acoustic wave of speech to sa simple sinusoidal wave, allowing better perception of the fundamental frequency of the voice and its variations, i.e. pitch and intonation. The inclusion assessment of patients is twofold: evaluation of the perception of language (audiometry and computerised video tests evaluating the capacities for recognition of sounds and for lip reading), evaluation of voice production and language. Orthophonic re-education depends on the results of the various tests performed and is based on computer programmes, allowing better feed-back by visual control. As a result of the progress in computer and video technology, these tests can be standardised and used not only for candidates for the SIVO prosthesis, but also for all profoundly deaf subjects.

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