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51.
Amélie Huynh Le Maux Bernadette Pignol Delphine Behr-Roussel Jean-Luc Blachon Pierre-Etienne Chabrier Sandrine Compagnie Philippe Picaut Jacques Bernabé Fran?ois Giuliano Pierre Denys 《Toxins》2015,7(12):5462-5471
Intradetrusor injections of Botulinum toxin A—currently onabotulinumtoxinA—is registered as a second-line treatment to treat neurogenic detrusor overactivity (NDO). The common clinical practice is 30 × 1 mL injections in the detrusor; however, protocols remain variable and standardization is warranted. The effect of reducing the number of injection sites of Dysport® abobotulinumtoxinA (aboBoNTA) was assessed in the spinal cord-injured rat (SCI). Nineteen days post-spinalization, female rats received intradetrusor injections of saline or aboBoNTA 22.5 U distributed among four or eight sites. Two days after injection, continuous cystometry was performed in conscious rats. Efficacy of aboBoNTA 22.5 U was assessed versus aggregated saline groups on clinically-relevant parameters: maximal pressure, bladder capacity, compliance, voiding efficiency, as well as amplitude, frequency, and volume threshold for nonvoiding contractions (NVC). AboBoNTA 22.5 U significantly decreased maximal pressure, without affecting voiding efficiency. Injected in four sites, aboBoNTA significantly increased bladder capacity and compliance while only the latter when in eight sites. AboBoNTA significantly reduced NVC frequency and amplitude. This preclinical investigation showed similar inhibiting effects of aboBoNTA despite the number of sites reduction. Further studies are warranted to optimize dosing schemes to improve the risk-benefit ratio of BoNTA-based treatment modalities for NDO and further idiopathic overactive bladder. 相似文献
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Antonin Levy Cécile Le Péchoux Hitesh Mistry Isabelle Martel-Lafay Andrea Bezjak Delphine Lerouge Laetitia Padovani Paul Taylor Corinne Faivre-Finn 《Journal of thoracic oncology》2019,14(2):294-297
Introduction
The impact of the dose and fractionation of thoracic radiotherapy on the risk of developing brain metastasis (BM) has not been evaluated prospectively in limited stage SCLC patients receiving prophylactic cerebral irradiation (PCI).Methods
Data from patients treated with PCI from the CONVERT trial were analyzed.Results
Four hundred forty-nine of 547 patients (82%) received PCI after completion of chemoradiotherapy. Baseline brain imaging consisted of computed tomographic scans in 356 of 449 patients (79%) and magnetic resonance imaging in 83 of 449 (18%) patients. PCI was delivered to 220 of 273 participants (81%) in the twice-daily (BD) group and 229 of 270 in the once-daily (OD) group (85%; p = 0.49). Total median PCI dose was 25 Gy in both the BD and OD groups (p = 0.74). In patients who received PCI, 75 (17%) developed BM (35 [8%] in OD and 40 [9%] in BD) and 173 (39%) other extracranial progression. In the univariate analysis, gross tumor volume (GTV) was associated with an increased risk of BM (p = 0.007) or other radiological progression events (p = 0.006), whereas in a multivariate analysis both thoracic GTV (tGTV) and ECOG performance score were associated with either progression type. The median overall survival (OS) of patients treated with PCI was 29 months. In the univariate analysis of OS, PCI timing from end of chemotherapy, weight loss of more than 10%, and tGTV were prognostic factors associated with OS. In the multivariate analysis, only tGTV was associated with OS. Delay between end of chemotherapy and PCI was not associated with OS.Conclusions
Patients receiving OD or BD thoracic radiotherapy have the same risk of developing BM. Larger tumors are associated with a higher risk of BM. 相似文献53.
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Fledgling cliff swallows were cared for at a rehabilitation facility when clinical signs of ocular disease, characterized by conjunctivitis, epiphora, and hyperaemia of palpebrae and nictitans, were recognized. Treatment consisted of topical and oral antibiotic therapy and one topical steroid administration. However, one cliff swallow died and three were killed due to poor therapeutic response. Conjunctival swabs were obtained ante-mortem from the three cliff swallows and were submitted for mycoplasma culture and molecular diagnostics. Heads of the three birds were fixed in 10% neutral buffered formalin and submitted for histopathologic examination of oculonasal tissues. Mycoplasma cultures and molecular evaluation of isolates identified Mycoplasma sturni, but not Mycoplasma gallisepticum, from each specimen. Histopathologic examination revealed lymphoplasmacytic conjunctivitis, rhinitis and infraorbital sinusitis with follicular lymphoid hyperplasia, epithelial hyperplasia, and protozoal stages compatible with Cryptosporidium spp. arranged in and along the apical surfaces of epithelial cells. Identification of concurrent M. sturni and Cryptosporidium spp. infections in these cliff swallows demonstrates an alternative infectious condition that can produce gross and microscopic lesions comparable with those commonly observed in M. gallisepticum infections of house finches and other passerine species. Conjunctivitis associated with M. sturni and Cryptosporidium spp. in cliff swallows may represent an emerging disease risk to a naïve, high-density and colonial species such as colony-nesting cliff swallows. 相似文献
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Delphine Payros Thomas Secher Michèle Boury Camille Brehin Sandrine Ménard Christel Salvador-Cartier Gabriel Cuevas-Ramos Claude Watrin Ingrid Marcq Jean-Philippe Nougayrède Damien Dubois Antoine Bedu Fabien Garnier Olivier Clermont Erick Denamur Pascale Plaisancié Vassilia Theodorou Jean Fioramonti Ma?wenn Olier Eric Oswald 《Gut microbes》2014,5(3):313-325
The neonatal gut is rapidly colonized by a newly dominant group of commensal Escherichia coli strains among which a large proportion produces a genotoxin called colibactin. In order to analyze the short- and long-term effects resulting from such evolution, we developed a rat model mimicking the natural transmission of E. coli from mothers to neonates. Genotoxic and non-genotoxic E. coli strains were equally transmitted to the offspring and stably colonized the gut across generations. DNA damage was only detected in neonates colonized with genotoxic E. coli strains. Signs of genotoxic stress such as anaphase bridges, higher occurrence of crypt fission and accelerated renewal of the mature epithelium were detected at adulthood. In addition, we observed alterations of secretory cell populations and gut epithelial barrier. Our findings illustrate how critical is the genotype of E. coli strains acquired at birth for gut homeostasis at adulthood. 相似文献
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Stéphanie Oger Delphine Behr-Roussel Diane Gorny Olivier Lecoz Thierry Lebret Yves Denoux Antoine Faix Albert Leriche Chris Wayman Laurent Alexandre François Giuliano 《The journal of sexual medicine》2009,6(3):836-847
IntroductionPhosphodiesterase 5 inhibitors (PDE5) such as sildenafil are first-line treatment for erectile dysfunction (ED). Alpha1 (α1)-adrenoceptor antagonists such as doxazosin are indicated for the treatment of patients with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). ED and LUTS/BPH are conditions that are often associated. Accordingly, α1-adrenoceptor antagonists and PDE5 inhibitors will be often prescribed in real life setting together.AimTo evaluate the effects of the combination of sildenafil and doxazosin on human cavernosal and prostatic tissue.MethodsProstatic and erectile tissues were obtained from nine to 12 patients, respectively. Patients underwent cystoprostatectomy for infiltrating bladder cancer or penile surgery for penile implant, congenital curvature or Peyronie's disease.Main Outcome MeasuresIn organ baths, prostatic and cavernosal strips were submitted to either concentration-response curves (CRC) to phenylephrine (Phe) or norepinephrine (NE), respectively, in presence of vehicle, sildenafil (10?6 M, 10?5 M), doxazosin (10?8 M, 3.10?8 M, or 10?7 M), or a combination of both. Continuous electrical field stimulation (EFS; 32 Hz, 5 ms, 5 seconds, 300 mA) was performed on prostatic strips which were incubated with sildenafil 10?6 M or vehicle before the successive addition of doxazosin (10?7 M, 10?6 M) or vehicle. Cavernosal strips were pre-incubated with doxazosin (10?9 M, 10?8 M) or vehicle, then CRC to sildenafil were constructed on NE (3.10?6 M) precontracted cavernosal strips.ResultsCombination of sildenafil and doxazosin exerted a greater relaxing effect on CRC to Phe or NE compared with each compound alone in both tissues. Sildenafil significantly enhanced the relaxing effect of doxazosin on EFS-induced contractions in prostatic strips. Doxazosin significantly increased the ability of sildenafil to inhibit NE-induced contractions in cavernosal strips.ConclusionsSildenafil and doxazosin reduced adrenergic tone of prostatic and cavernosal smooth muscle and their combination provided a significant benefit when targeting relaxation of both tissues. These experiments provide support for further clinical evaluation of the sildenafil and doxazosin combination in ED patients with LUTS/BPH. Oger S, Behr-Roussel D, Gorny D, Lecoz O, Lebret T, Denoux Y, Faix A, Leriche A, Wayman C, Alexandre L, and Giuliano F. Combination of doxazosin and sildenafil exerts an additive relaxing effect compared with each compound alone on human cavernosal and prostatic tissue. J Sex Med 2009;6:836–847. 相似文献
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