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Jana Kristin Eckert Julia Kahle Andreas Bck Kathrin Zeber Kathrin Urner Wolfgang Greiner Simone Kreimeier Kirsten Beyer Josefine Dobbertin-Welsch Eckard Hamelmann Ines Gellhaus Christina Schorlemer Michael Kabesch Parastoo Kheiroddin Erika von Mutius Martin Depner Daniel Walter Gesine Hansen Stephanie DeStefano Sabine Schnadt Bianca Schaub 《Pediatric allergy and immunology》2022,33(1):e13652
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Priya S. Shankarappa Cody J. Peer Arman Odabas Cynthia L. McCully Rafael C. Garcia William D. Figg Katherine E. Warren 《Cancer chemotherapy and pharmacology》2020,85(5):1003-1007
Pexidartinib (PLX3397) is a colony-stimulating factor-1 receptor (CSF-1R) inhibitor under clinical evaluation for potential CNS tumor treatment. This study aims to evaluate plasma pharmacokinetic parameters and estimate CNS penetrance of pexidartinib in a non-human primate (NHP) cerebrospinal fluid (CSF) reservoir model. Five male rhesus macaques, each with a previously implanted subcutaneous CSF ventricular reservoir and central venous lines, were used. NHPs received a single dose of 40 mg/kg pexidartinib (human equivalent dose of 800 mg/m2), administered orally as 200 mg tablets. Serial paired samples of blood and CSF were collected at 0–8, 24, 48, and 72 h. Pexidartinib concentrations were assayed by Integrated Analytical Solutions, Inc. (Berkeley, CA, USA) using HPLC/MS/MS. Pharmacokinetic (PK) analysis was performed using noncompartmental methods. Samples from four NHPs were evaluable. Average (± SD) plasma PK parameters were as follows: Cmax = 16.50 (± 6.67) μg/mL; Tmax = 5.00 (± 2.58) h; AUClast = 250.25 (± 103.76) h*μg/mL; CL = 0.18 (± 0.10) L/h/kg. In CSF, pexidartinib was either quantifiable (n = 2), with Cmax values of 16.1 and 10.1 ng/mL achieved 2–4 h after plasma Tmax, or undetected at all time points (n = 2, LLOQCSF = 5 ng/mL). Pexidartinib was well-tolerated in NHPs, with no Grade 3 or Grade 4 toxicities. The CSF penetration of pexidartinib after single-dose oral administration to NHPs was limited. 相似文献
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Oliver Sartor MD Daniel Heinrich MD Neil Mariados MD Maria José Méndez Vidal MD Daniel Keizman MD Camilla Thellenberg Karlsson MD Avivit Peer MD Giuseppe Procopio MD Stephen J. Frank MD Kalevi Pulkkanen MD Eli Rosenbaum MD Stefano Severi MD José Trigo MD Lucia Trandafir MD Volker Wagner MD Rui Li MS Luke T. Nordquist MD 《The Prostate》2019,79(14):1683-1691
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Benedikt W. Burkhardt Andreas Simgen Matthias Dehnen Gudrun Wagenpfeil Wolfgang Reith Joachim M. Oertel 《The spine journal》2019,19(4):587-596
BACKGROUND CONTEXT
Anterior cervical discectomy and fusion (ACDF) without and with cervical plating (ACDF+CP) are accepted surgical techniques for the treatment of degenerative cervical disc disorders. The effect of CP on the development of adjacent segment degeneration (ASD) remains unclear.PURPOSE
To assess whether CP accelerates the degeneration of the adjacent and adjoining segments.STUDY DESIGN/SETTING
This is an imaging cohort study.PATIENT SAMPLE
Retrospectively, a total of 84 patients who underwent ACDF or ACDF+CP were identified. At final follow-up, an MRI was performed and evaluated in this study.MATERIALS AND METHODS
An MRI of 84 patients who underwent ACDF (46 patients) and ACDF+PS (38 patients) was performed. The mean follow-up was 24 years (17–45 years). None of the patients had a repeat procedure in the cervical spine. The grade of degeneration of the segments adjacent and adjoining to the fusion was assessed via a five-step grading system (segmental degeneration index, or SDI) that includes disc signal intensity, anterior and posterior disc protrusion, narrowing of the disc space, and foraminal stenosis. Furthermore, the disc height (DH) and sagittal segmental angle (SSA) of fused segments were measured.RESULTS
A significantly (p<.001) greater SDI was identified at the caudal adjacent segment following ACDF compared to ACDF+CP. No other significant differences were identified in patients following ACDF and ACDF+CP. Between 50% and 96% of all segments showed severe degenerative changes according to SDI. There was no significant difference in DH between the patients following ACDF and ACDF+CP. The SSA in patients who underwent ACDF+CP was significantly greater than in the ACDF patients (p=.002).CONCLUSIONS
In this cohort of patients, cervical plating had no significant impact on segmental degeneration and decrease of DH in the adjacent and adjoining segments. ACDF+CP seem to preserve the lordotic alignment more with respect to the SSA than ACDF. 相似文献9.
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