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71.
Emmanuel Chaubourt Philippe Fossier Grard Baux Christine Leprince Maurice Israël Sabine De La Porte 《Neurobiology of disease》1999,6(6):499
Duchenne muscular dystrophy (DMD), a severe X-linked recessive disorder which results in progressive muscle degeneration, is due to a lack of dystrophin, a membrane cytoskeletal protein. An approach to treatment is to compensate for dystrophin loss with utrophin, another cytoskeletal protein with over 80% homology with dystrophin. Utrophin is expressed, at the neuromuscular junction, in normal and DMD muscles and there is evidence that it may perform the same cellular functions as dystrophin. So, the identification of molecules or drugs that could up-regulate utrophin is a very important goal for therapy. We show that in adult normal and mdx mice (an animal model of Duchenne myopathy) treated with
-arginine, the substrate of nitric oxide synthase (NOS), a pool of utrophin localized at the membrane appeared and increased, respectively. In normal and mdx myotubes in culture,
-arginine, nitric oxide (NO), or hydroxyurea increased utrophin levels and enhanced its membrane localization. This effect did not occur with
-arginine, showing the involvement of NOS in this process. The NO-induced increase in utrophin was prevented by oxadiazolo-quinoxalin-1-one, an inhibitor of a soluble guanylate cyclase implicated in NO effects. These results open the way to a potential treatment for Duchenne and Becker dystrophies. 相似文献
72.
Evaluation of the efficacy, safety and physiological effects of fluvoxamine in social phobia 总被引:1,自引:0,他引:1
DeVane CL Ware MR Emmanuel NP Brawman-Mintzer O Morton WA Villarreal G Lydiard RB 《International clinical psychopharmacology》1999,14(6):345-351
There is no US Food and Drug Administration (FDA) approved treatment for social phobia although data suggest efficacy for several drug classes, including beta-blockers, benzodiazepines, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors (SSRIs). The SSRIs are particularly attractive due to their favourable tolerance and safety profile. An open label trial of fluvoxamine was conducted to evaluate its efficacy and safety in the treatment of social phobia (DSM-III-R) and to assess physiological changes that may accompany treatment. Fifteen non-depressed patients, aged 22-44 years (mean 31.6 years), entered the study. A 5-min performance task (public speaking simulation) preceded and concluded the active treatment period. Cardiovascular monitoring was performed during this time and blood sampled for plasma cortisol and steady-state plasma fluvoxamine concentration (at week 7). Ten patients (5 men and 5 women) completed an active 6 week treatment period of flexible dosing (50-150 mg/day). Five patients failed to complete the study due to drowsiness (n = 2), nausea (n = 1), or were lost to follow-up (n = 2). Analysis of clinical ratings indicated a statistically significant decrease in all scales from baseline to week 7 at the conclusion of the active treatment period. Clinical benefits were still evident at follow-up 1 week after drug discontinuation. Neither physiological effects nor plasma drug concentration correlated with clinical change. Fluvoxamine appeared to be effective and well tolerated in completers. Randomized clinical trials are needed to further demonstrate the efficacy of fluvoxamine in the treatment of social phobia. 相似文献
73.
Abara EO 《The Canadian journal of urology》1996,3(4):282-284
A technique for endoscopic primary re-alignment of ruptured urethra is described. It is safe, simple and may be accomplished under neuroleptic or local anesthesia. Morbidity is low and hospitalization minimal. Any residual stricture can be easily managed endoscopically or by simple dilation. 相似文献
74.
Michel Bolla Béatrice Rostaing-Puissant Serge P. Bottari Monique Chedin Jacqueline Marron-Charriere Marc Colonna Emmanuel Berland Edmond Chambaz 《Breast cancer research and treatment》1996,39(3):327-334
Protein tyrosine kinases (PTKs) are a family of enzymes sharing a highly conserved catalytic domain which phosphorylates substrate proteins on tyrosine residues. PTKs play a major role in the transduction of the mitogenic signal and are involved in the control of cell proliferation, differentiation, and transformation processes. PTKs can be subdivided into two major types: membrane associated PTKs consisting essentially of growth factor receptors (receptor tyrosine kinases or RTKs) and cytosolic PTKs involved in the intracellular transduction of mitogenic and differentiation signals. From January 1988 to January 1992, PTK activity was assayed in cytosolic fractions prepared from 350 T1-T2, N0-N1 M0, breast carcinomas. Enzymatic activity was measured using phosphate transfer from [32P]-ATP to poly-Glu-Tyr as an artificial substrate. According to our previously reported pilot study, we chose a cut-off value of 12 pmol32P incorporated min–1 mg–1 protein, corresponding to the median value. We found positive PTK levels ( 12 pmol/min/mg) to be correlated with a loss of differentiation according to Scarff-Bloom grade (p < 0.001), negative PR (p = 0.03) and ER status (p = 0.04). With a median follow-up of 30 months (0–82), patients with a positive PTK level presented a smaller 3-year disease free survival than in the PTK negative group of patients (p = 0.07). In Cox multivariate analysis including pT, pN, Scarff-Bloom grade, PR and ER, PTK activity does not emerge as a significant prognostic factor. 相似文献
75.
The anxiolytic profile of dexmedetomidine, a novel, highly-selective 2-adrenergic agonist, was examined in rats in the elevated plus-maze test when administered either alone or in combination with the benzodiazepine agonist midazolam. Dexmedetomidine, 0.1–10 µg/kg, was inactive in modifying the rats' behavioral response in this test. Midazolam, 0.1–10 mg/kg, dose-dependently produced an anxiolytic-like profile characterized by an increased time spent in the open arms of the elevated plus-maze. A combination of dexmedetomidine 0.5 µg/kg and midazolam 0.5 mg/kg produced a synergistic interaction. This heterergic interaction of dexmedetomidine on midazolam's anxiolytic-like profile was dose-dependently blocked by pretreatment with an 2-adrenergic antagonist, atipamezole, 10–50 µg/kg, and a benzodiazepine antagonist flumazenil, 1.0 and 10 mg/kg, but not by the 1-adrenergic antagonist, prazosin, 0.1–10 mg/kg. While the transmembrane signal transduction pathways for benzodiazepine- and 2-agonist responses do not share any molecular component, there does appear to be crosstalk between these two systems. These may involve GABA or noradrenergic downstream effects of either dexmedetomidine or midazolam, respectively. 相似文献
76.
Romand R Sapin V Ghyselinck NB Avan P Le Calvez S Dollé P Chambon P Mark M 《The European journal of neuroscience》2000,12(8):2793-2804
77.
Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients with relapsed acute promyelocytic leukemia. 总被引:9,自引:0,他引:9
Emmanuel Raffoux Philippe Rousselot J?el Poupon Marie-Thérèse Daniel Bruno Cassinat Richard Delarue Anne-Laure Taksin Delphine Réa Agnès Buzyn Annick Tibi Geneviève Lebbé Patricia Cimerman Christine Chomienne Jean-Paul Fermand Hugues de Thé Laurent Degos Olivier Hermine Hervé Dombret 《Journal of clinical oncology》2003,21(12):2326-2334
PURPOSE: Arsenic trioxide (ATO) is capable of inducing a high hematologic response rate in patients with relapsed acute promyelocytic leukemia (APL). Preclinical observations have indicated that all-trans-retinoic acid (ATRA) may strongly enhance the response to ATO. PATIENTS AND METHODS: Between 1998 and 2001, we conducted a randomized study of ATO alone versus ATO plus ATRA in 20 patients with relapsed APL, all previously treated with ATRA-containing chemotherapy. The primary objective was to demonstrate a significant reduction in the time necessary to obtain a complete remission (CR) in the ATO/ATRA group compared with the ATO group. Secondary objectives were safety and molecular response. RESULTS: The CR rate after one ATO with or without ATRA induction cycle was 80%. Clinical and pharmacokinetic observations indicated that the main mechanism of action of ATO in vivo was the induction of APL cell differentiation. Hematologic and molecular response, time necessary to reach CR, and outcome were comparable in both treatment groups. Of 16 CR patients, three patients who reached a molecular remission after one induction cycle had all received chemotherapy for a treatment-induced hyperleukocytosis. Three additional patients who received further additional ATO with or without ATRA cycles converted later to molecular negativity. CONCLUSION: ATRA did not seem to significantly improve the response to ATO in patients relapsing from APL. Other potential combinations, including ATO plus chemotherapy, have to be tested. 相似文献
78.
Thierry Andre Philippe Colin Christophe Louvet Erik Gamelin Olivier Bouche Emmanuel Achille Nicolas Colbert Catherine Boaziz Pascal Piedbois Nicole Tubiana-Mathieu Arnaud Boutan-Laroze Michel Flesch Marc Buyse Aimery de Gramont 《Journal of clinical oncology》2003,21(15):2896-2903
PURPOSE: This randomized, 2 x 2 factorial study compared a semimonthly (LVFU2) with a monthly (FULV) regimen of fluorouracil and leucovorin and 24 versus 36 weeks of each regimen as adjuvant treatment of patients with stage II (Dukes' B2) and III (Dukes' C) colon cancer. PATIENTS AND METHODS: LVFU2 was administered semi-monthly for 2 consecutive days as dl- or l-leucovorin (200 or 100 mg/m2, respectively) as a 2-hour infusion, followed by a 400 mg/m2 FU bolus and 600 mg/m2 of FU as a 22-hour continuous infusion. FULV was administered monthly for 5 consecutive days as a 15-minute infusion of dl- or l-leucovorin, followed by 400 mg/m2 of FU as a 15-minute infusion. RESULTS: A total of 905 patients were randomly assigned. The median follow-up was 41 months. Disease-free survival was similar between the LVFU2 and FULV groups (127 v 124 events; hazard ratio [HR] = 1.04; P =.74) and between 24 and 36 weeks of therapy (128 v 123 events; HR = 0.94; P =.63). Analysis of overall survival showed a slight excess in the number of deaths in LVFU2 compared with FULV (73 v 59), but this difference was not statistically significant (HR = 1.26; 95% confidence interval, 0.90 to 1.78; P =.18). The most commonly observed grade 3 to 4 toxicities were neutropenia, diarrhea, and mucositis. Toxicities were significantly lower in the LVFU2 group (all toxicities, P <.001). CONCLUSION: Our data confirm that LVFU2 is less toxic than FULV. At a median follow-up of 41 months, no statistically significant difference could be detected in disease-free or overall survival between the treatment groups or treatment durations. 相似文献
79.
CT-based delineation of lymph node levels and related CTVs in the node-negative neck: DAHANCA, EORTC, GORTEC, NCIC,RTOG consensus guidelines. 总被引:25,自引:0,他引:25
Vincent Grégoire Peter Levendag Kian K Ang Jacques Bernier Marijel Braaksma Volker Budach Cliff Chao Emmanuel Coche Jay S Cooper Guy Cosnard Avraham Eisbruch Samy El-Sayed Bahman Emami Cai Grau Marc Hamoir Nancy Lee Philippe Maingon Karin Muller Hervé Reychler 《Radiotherapy and oncology》2003,69(3):227-236
BACKGROUND AND PURPOSE: The appropriate application of 3-D CRT and IMRT for HNSCC requires a standardization of the procedures for the delineation of the target volumes. Over the past few years, two proposals--the so-called Brussels guidelines from Grégoire et al., and the so-called Rotterdam guidelines from Nowak et al.--emerged from the literature for the delineation of the neck node levels. Detailed examination of these proposals however revealed some important discrepancies. MATERIALS AND METHODS: Within this framework, the Brussels and Rotterdam groups decided to review their guidelines and derive a common set of recommendations for delineation of neck node levels. This proposal was then discussed with representatives of major cooperative groups in Europe (DAHANCA, EORTC, GORTEC) and in North America (NCIC, RTOG), which, after some additional refinements, have endorsed them. The objective of the present article is to present the consensus guidelines for the delineation of the node levels in the node-negative neck. RESULTS AND CONCLUSIONS: First a short discussion of the discrepancies between the previous Brussels and the Rotterdam guidelines is presented. The general philosophy of the consensus guidelines and the methodology used to resolve the various discrepancies are then described. The consensus proposal is then presented and representative CTVs that are consistent with these guidelines are illustrated on CT sections. Last, the limitations of the consensus guidelines are discussed and some concerns about the direct applications of these guidelines to the node-positive neck and the post-operative neck are described. 相似文献
80.
Estrogen receptor negative and progesterone receptor positive primary breast cancer: Pathological characteristics and clinical outcome 总被引:9,自引:0,他引:9
Agnès Bernoux Patricia de Cremoux Christine Lainé-Bidron Emmanuel C. Martin Bernard Asselain Henri Magdelénat 《Breast cancer research and treatment》1998,49(3):219-225
The expression of estrogen (ER) and progesterone (PgR) receptors was analyzed in a retrospective series of 3000 patients who had operable primary breast cancer. Patients were stratified according to ER and PgR status and the study was focused on the two groups (ER–PgR+ and ER–PgR–) of patients whose tumors contained low levels of ER (< 15 fmol/mg protein), regarding potential response to endocrine therapy. The comparison of clinical or histological characteristics between ER–PgR+ and ER–PgR– patients was analyzed as well as the disease-related death and survival. The mean follow-up was 86.3 months. Among the 529 ER–patients, 62 were PgR+ (12%), whereas 467 were PgR– (88%). The ER–PgR+ and ER–PgR– populations represented 2% and 15.6% of the overall population, respectively. In ER– tumors, the PgR status was significantly related to: age, menopausal status, tumor size, SBR grade, and histological type, but not to the type of surgical treatment or to lymph node involvement. ER–PgR+ tumors had smaller size (64% T1 vs 43%) (p=0.004) and were more frequently grade I (28% vs 12%) than ER–PgR– ones (p < 0.001). In addition, the patients with ER–PgR+ tumors were significantly younger (49.4 years vs 58.4 years; p < 0.0001), and were more frequently premenopausal (76% vs 36%; p < 0.001). The disease-free interval and the metastasis-free survival tended to be worse for ER–PgR– than for ER–PgR+ patients, but the difference was not statistically significant at 10 years. However, a small but significant difference in overall survival, in favor of the PgR+ group, was observed between the two groups during the first 5 years (p=0.03).We conclude that in combination with ER, PgR status defines a group of patients with clinical and biological specificity, which could be considered for specific endocrine therapy. 相似文献