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排序方式: 共有758条查询结果,搜索用时 31 毫秒
91.
Ryan A. Brawn Andrew Cook Kiyoyuki Omoto Jiyuan Ke Craig Karr Federico Colombo Milena Virrankoski Sudeep Prajapati Dominic Reynolds David M. Bolduc Tuong-Vi Nguyen Patricia Gee Deanna Borrelli Benjamin Caleb Shihua Yao Sean Irwin Nicholas A. Larsen Anand Selvaraj Xuesong Zhao Stephanos Ioannidis 《ACS medicinal chemistry letters》2021,12(1):93
Fibroblast growth factor receptors (FGFR) 2 and 3 have been established as drivers of numerous types of cancer with multiple drugs approved or entering late stage clinical trials. A limitation of current inhibitors is vulnerability to gatekeeper resistance mutations. Using a combination of targeted high-throughput screening and structure-based drug design, we have developed a series of aminopyrazole based FGFR inhibitors that covalently target a cysteine residue on the P-loop of the kinase. The inhibitors show excellent activity against the wild-type and gatekeeper mutant versions of the enzymes. Further optimization using SAR analysis and structure-based drug design led to analogues with improved potency and drug metabolism and pharmacokinetics properties. 相似文献
92.
Indirect reduction and percutaneous screw fixation of displaced tibial plateau fractures. 总被引:9,自引:0,他引:9
K J Koval R Sanders J Borrelli D Helfet T DiPasquale J W Mast 《Journal of orthopaedic trauma》1992,6(3):340-346
Indirect reduction and percutaneous screw fixation were attempted in 20 displaced tibial plateau fractures in 20 patients. Closed, indirect reduction was successful in 18 fractures; two others, both Schatzker type II fractures, required open reduction. The 18 fractures were followed for an average of 16.2 months (range, 12-24 months). Of the fractures successfully reduced with indirect techniques, 13 were reduced anatomically (72.2%), and five were considered nonanatomic (27.8%). Four of the five fractures with a nonanatomic reduction were type II fractures. Clinically, there were six excellent (33%), 10 good (56%), and two fair (11%) results. No fracture lost reduction; no patient developed an infection. Indirect techniques could effectively reduce only split fragments. Depressed fragments could not be reduced reliably with either ligamentotaxis or percutaneous elevation with a tamp. There was no correlation between radiographic reduction and clinical outcome. It did not matter whether two, three, or four screws were used to stabilize the fracture. 相似文献
93.
94.
Resting energy expenditure (REE) and postprandial thermogenesis (PPT) after the ingestion of a mixed test meal (3.56 MJ, 850 kcal) were determined in 7 anorectic patients, 7 very lean women and 8 control women. REE is absolute value was sharply decreased in the anorectics, but did not significantly differ between the very lean and the control subjects. On the other hand, when adjusted for body weight, REE only tended (p = 0.18) to be lower in the anorectics in comparison to the control women. PPT was similar in the anorectics (187.2 +/- 24.6 kJ/4 h) and the controls (200.7 +/- 16.8 kJ/4 h), but lower in the lean subjects (137.5 +/- 20.0 kJ/4h: p less than 0.05) than in the other two groups. The present study shows that the thermic response to the ingestion of a mixed test meal was not decreased in undernourished anorectic patients whereas it was significantly reduced in very lean healthy women. 相似文献
95.
A case of intravascular papillary endothelial hyperplasia in the hypothenar eminence of a 23-year-old female fencer is described. Differential diagnosis with other similar benign and malignant lesions was made using histopathology and immunohistochemistry. The possible post-traumatic proliferative histogenesis is discussed. The non-malignant nature of the mass was confirmed after a three year follow-up. 相似文献
96.
97.
Cristiano Giardiello Alessandro Borrelli Eufemia Silvestri Valentina Antognozzi Giuseppe Iodice Michele Lorenzo 《Obesity surgery》2012,22(12):1916-1919
Background
The positioning of an intragastric saline-filled balloon has been developed as temporary and reversible therapeutic option for treatment of morbid obesity. Recently, an air-filled balloon was also developed. The aim of this study is to prospectively compare these two devices in terms of weight loss parameters, safety, and tolerance.Methods
Sixty patients were randomized into two groups: group A (Bioenterics Intragastric Balloon?CBIB; n?=?30; 20?F/10?M, mean age 36.7?±?10.9; mean BMI 46.5?±?5.9) and group B (Endobag-Heliosphere; n?=?30; 20?F/10?M, mean age 37.8?±?10.6; mean BMI 46.1?±?5.6). All patients of both groups were sedated with midazolam (5?mg)?+?Propofol (2?mg/kg i.v.). The Heliosphere Bag was air-filled with 950?ml while BIB? was inflated with 500?ml of saline and 10?ml of methylene blue. Percentage of excess weight loss (%EWL) and body mass index (BMI) were evaluated. Student t test, Fisher exact test, and ?? 2 test were used for statistical analysis.Results
Similar weight loss parameters were observed in patients treated with liquid or air-filled balloon at time of removal: mean BMI was 40.8?±?6.2 and 41.9?±?6.5(p?=?ns), and mean %EWL was 20?±?12 and 18?±?14 (p?=?ns) in groups A and B, respectively. Significant longer extraction time, with high patient discomfort, was observed in group B due to difficult passage through the cardia and the lower pharynx.Conclusions
Air-filled balloon can be another valid therapeutic option in the temporary treatment of obesity, but at this time, the quality of the device must be improved to ameliorate the patient compliance at removal and avoid the spontaneous deflations. 相似文献98.
Borrelli J De S VanPelt M 《The Journal of the American Academy of Orthopaedic Surgeons》2012,20(7):472-477
Cuboid fracture accounts for a minority of all foot fractures in adults and often is indicative of a multiply injured foot. Understanding the normal anatomy and function of the cuboid and its relation to foot biomechanics is necessary for appropriate management. Clinical evaluation includes history, physical examination, and thorough assessment of the skin and soft tissues. Plain radiographs and CT are helpful in preoperative planning. Cuboid fractures may be managed either nonsurgically (splinting or casting) or surgically (closed reduction and external fixation or open reduction and internal fixation). Careful handling of the soft tissues is important, as is restoration of articular congruity, lateral column length, and a stable midfoot. Postoperative care consists of prolonged immobilization followed by 3 months of progressive weight bearing. Published reports of long-term outcomes and functional postoperative assessments are lacking. 相似文献
99.
Guerrero M Athota K Moy J Mehta LS Laguens R Crottogini A Borrelli M Corry P Schoenherr D Gentry R Boura J Grines CL Raff GL Shanley CJ O'Neill WW 《Journal of interventional cardiology》2008,21(3):242-251
BACKGROUND: Vascular endothelial growth factor (VEGF)-165 promotes cardiomyogenesis in chronic myocardial ischemia and nonreperfused myocardial infarction (MI). It is unknown whether this effect is present in reperfused MI. We sought to investigate the effect of VEGF-165 gene therapy on cardiomyogenesis after reperfused MI. METHODS AND RESULTS: Twenty-four Yucatan minipigs underwent thoracotomy and a vascular clamp was placed in the left circumflex artery. Reperfusion was reestablished after 90 minutes, and VEGF-165 gene therapy or placebo was administered. A replication-deficient recombinant human adenovirus serotype 5 was used for gene transfer (Ad5-VEGF165). The same viral vector devoid of VEGF gene (Ad5-beta-galactosidase) was used as placebo. Two administration routes were tested, intramyocardial (IM) injection and circumflex intracoronary (IC) infusion. The pigs were assigned to one of the following groups: IM Ad5-VEGF165 (n = 6), IM Ad5-betaGal (n = 6), IC Ad5-VEGF165 (n = 6), and IC Ad5-betaGal (n = 6). All pigs received 5-bromo-2'-deoxyuridine (BrdU) 250 mg IV twice a week to label cells undergoing DNA replication. The hearts were explanted at 4 weeks. BrdU-labeled cardiomyocytes in the peri-infarct area were counted by a pathologist blinded to group assignment. The number of BrdU-labeled cardiomyocytes per million cells was 4-fold higher in the group receiving IM VEGF-165 (64 +/- 11.4) vs. IM placebo (16 +/- 10.6), P = 0.034. No difference in infarct size or ventricular function was observed between the groups. CONCLUSIONS: IM VEGF-165 gene therapy promotes cardiomyogenesis in reperfused MI. However, no benefit in infarct size or cardiac function was observed at 4 weeks. The origin of these cells remains unknown and needs to be determined. 相似文献
100.