Etude acoustico-radiologique de la déglutition haute chez des sujets normaux et des patients opérés d un cancer pharyngo-laryngé

Ce travail a utilisé la méthode acoustico-radiologique pour analyser, chez le normal et le laryngectomisé (LT, LSC), le bruit de la déglutition et de ses composantes sonores (CS) pour en rechercher l origine. Les acquisitions étaient réalisées en pré et postopératoire. Le microphone était en regard du cricoïde. Le nombre de CS (N), la durée totale du bruit (DTB), des 3 CS (COP, COS, COL), des intervalles I 1et I2 et les % de présence des CS ont été quantifiés. Sujets normaux : après corrélation acoustico-radiologique, les valeurs normales (ms) étaient COP = 106, COS = 185, COL = 72. COP correspondait à la montée de l os hyoïde et au bolus dans l oropharynx, COS au bolus traversant le sphincter supérieur et COL à l ouverture du larynx, au bolus dans l œsophage. Groupe LSC : en postop, COP était moins présente, COL plus fréquente, COS plus longue. Groupe LT : en postop, N était modifié, COP et COL moins présentes, DTB et COS plus courtes. Des profils types du bruit de déglutition ont été établis.This study analysed the swallowing sound an dits sound component (SC) with the acoustico-radiologic assessment in normal subjects, and in laryngectomized (LT, LSC) patients. The swallowing recordings were made in pre and postoperative period. The microphone was placed near the cricoid cartilage. The number of SC (N), the total duration of the sound (DTB), of the SC (COP, COS, COL) and of the intervals (I1 and I2) and the % of SC presence were quantified. Normal subjects : the durations (ms) were COP = 106, COS = 185, COL = 72. COP was heard during the larynx ascension with the bolus in the oropharynx, COS during the bolus flow through the oesophageal sphincter, COL during the laryngeal opening with the bolus in the oesophagus. LSC group : in postoperative, COP was less frequently heard, COL more frequently, COS was longer. LT group : in postoprative, N was modified, COP and COL were less frequently heard, DTB and COS were shorter. Typical swallowing acoustic profiles were established.TOURS-BU Médecine (372612103) / SudocSudocFranceF

Brain tumor eradication and prolonged survival from intratumoral conversion of 5-fluorocytosine to 5-fluorouracil using a nonlytic retroviral replicating vector

Patients with the most common and aggressive form of high-grade glioma, glioblastoma multiforme, have poor prognosis and few treatment options. In 2 immunocompetent mouse brain tumor models (CT26-BALB/c and Tu-2449-B6C3F1), we showed that a nonlytic retroviral replicating vector (Toca 511) stably delivers an optimized cytosine deaminase prodrug activating gene to the tumor lesion and leads to long-term survival after treatment with 5-fluorocytosine (5-FC). Survival benefit is dose dependent for both vector and 5-FC, and as few as 4 cycles of 5-FC dosing after Toca 511 therapy provides significant survival advantage. In the virally permissive CT26-BALB/c model, spread of Toca 511 to other tissues, particularly lymphoid tissues, is detectable by polymerase chain reaction (PCR) over a wide range of levels. In the Tu-2449-B6C3F1 model, Toca 511 PCR signal in nontumor tissues is much lower, spread is not always observed, and when observed, is mainly detected in lymphoid tissues at low levels. The difference in vector genome spread correlates with a more effective antiviral restriction element, APOBEC3, present in the B6C3F1 mice. Despite these differences, neither strain showed signs of treatment-related toxicity. These data support the concept that, in immunocompetent animals, a replicating retroviral vector carrying a prodrug activating gene (Toca 511) can spread through a tumor mass, leading to selective elimination of the tumor after prodrug administration, without local or systemic pathology. This concept is under investigation in an ongoing phase I/II clinical trial of Toca 511 in combination with 5-FC in patients with recurrent high-grade glioma (www.clinicaltrials.gov NCT01156584)