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排序方式: 共有300条查询结果,搜索用时 15 毫秒
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Martine Ghin Dominik Lott Herv Farine Milena Issac Daniel Strasser Patricia Sidharta Jasper Dingemanse 《Basic & clinical pharmacology & toxicology》2019,124(6):711-721
ACT‐774312 is an antagonist of the chemoattractant receptor‐homologous molecule expressed on T helper (Th) 2 cells (CRTH2), in development for the treatment of nasal polyposis or other allergic and type‐2 inflammatory diseases. Placebo, single doses of 1‐1000 mg, or multiple doses of 30‐500 mg either once or twice daily for 4 days of ACT‐774312 were administered orally to healthy subjects. The single‐ and multiple‐dose pharmacokinetics (PK) of ACT‐774312 were dose proportional and characterized by a time to attainment of maximum plasma concentrations between 1 and 3 hours and a terminal elimination half‐life of about 12 hours In the presence of food, tmax was delayed by 1 hour and exposure to ACT‐774312 slightly decreased. Full blockade (>90% of the maximum effect, Emax) of CRTH2 as measured in a whole blood internalization assay was observed after 50 mg ACT‐774312 twice daily and lasted for at least 9 hours The relationship between ACT‐774312 concentration and CRTH2 blockade was described by a Emax model. The estimated twice‐daily dose of ACT‐774312 at which full blockade of CRTH2 is achieved at trough in at least 80% of subjects was estimated at 109 mg. Administration of ACT‐774312 was safe and well tolerated at all doses. For none of the recorded adverse events, a relationship to dose was discerned, and there were no clinically relevant findings on the measured ECG, clinical laboratory and vital signs variables. The observed PK, pharmacodynamics and safety profile warrant further development of ACT‐774312. 相似文献
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A prospective randomized trial of the surgical blood order equation for ordering red cells for total hip arthroplasty patients 总被引:1,自引:0,他引:1
GA Nuttall ; PJ Santrach ; WC Oliver Jr ; MH Ereth ; TT Horlocker ; ME Cabanela ; RT Trousdale ; S Bryant ; TW Currie 《Transfusion》1998,38(9):828-833
BACKGROUND: The majority of crossmatched blood is for surgical patients, and most of it is never transfused. An alternative system for ordering red cell (RBC) units, called the surgical blood order equation (SBOE), which incorporates specific patient variables for surgical patients, has been developed. STUDY DESIGN AND METHODS: A prospective double-blind randomized trial compared the SBOE with the maximal surgical blood order schedule (MSBOS) system for ordering allogeneic RBC units in 60 patients undergoing total hip arthroplasty. Autologous RBCs were available for none of the patients. RESULTS: There were no differences in patient demographic, surgical, or laboratory variables at any time. The median number (range) of allogeneic RBC units ordered was 2 (2-3) for the MSBOS and 0 (0-3) for the SBOE (p<0.0001). The SBOE ordered the correct number of RBC units for 58 percent of patients, while the MSBOS did so for 7 percent (p<0.0001). The SBOE had a lower crossmatch-to-transfusion ratio than the MSBOS (0.83 vs. 4.12). Costs were also lower with the SBOE. CONCLUSION: Incorporation of patient factors in the use of the SBOE system resulted in increased efficiency of blood-ordering practices for total hip arthroplasty. 相似文献
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Kenneth F Koral Yuni Dewaraja Jia Li Qiang Lin Denise D Regan Kenneth R Zasadny Stephen G Rommelfanger Issac R Francis Mark S Kaminski Richard L Wahl 《Journal of nuclear medicine》2003,44(3):457-464
A study of the use of (131)I-labeled tositumomab, preceded by an unlabeled tositumomab predose, for therapy of 76 previously untreated non-Hodgkin's lymphoma patients has been completed at the University of Michigan. Fifty-two of the 76 treated patients were imaged once during therapy with SPECT to assist in dosimetric estimation. In this article, the patient's average tumor dose, estimated by a hybrid method using that SPECT, is compared with the same statistic estimated by pretherapy conjugate views. METHODS: The SPECT activity-quantification procedure used 3-dimensional CT-to-SPECT image registration. Daily pretherapy conjugate-view images provided the shape of the time-activity curve for the hybrid dose estimation. RESULTS: With the hybrid method, the mean of the patient's average tumor dose over 8 patients using only their axillary tumors (162 cGy) was very significantly lower (P < 0.0001) than the mean over 47 patients using only their evaluated chest, abdominal, and pelvic tumors (624 cGy) for unknown reasons. Excluding axillary tumors as a best case for prediction, there still was considerable overlap in the distribution of a patient's average tumor dose over 38 patients who went on to a complete response (CR) and that from 9 patients who went on to a partial response (PR) using either method. However, a high value of the patient's average tumor dose was correctly associated with a CR for 15 of 16 patients (94%) with hybrid SPECT and for 9 of 12 patients (75%) with conjugate views. Also, the mean of the patient's average tumor dose for the CR patients was larger than the mean for PR patients; the P value was 0.18 with hybrid SPECT and 0.25 with conjugate views. A multiple logistic regression analysis combining the dose, tumor burden, and level of lactate dehydrogenase as explanatory variables for response did not yield statistical significance with either method. CONCLUSION: Patients with evaluated tumors that receive the highest tumor radiation dose are most likely to achieve a CR. Dosimetry based on a combination of pretherapy conjugate views and intratherapy SPECT provides somewhat better correspondence between the patient's average tumor dose and his or her degree of response compared with dosimetry from pretherapy conjugate views alone. Statistical significance for the correspondence is not reached either with the dosimetric method or with either method in combination with the tumor burden and level of lactate dehydrogenase. 相似文献
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Anand Raman Issac K Oommen T K Gundu Rao D N Sharma 《Applied radiation and isotopes》2002,57(1):93-97
ESR studies of irradiated lyoluminescence (LL) phosphor, trehalose dihydrate showed a linear free radical growth up to a dose of 11 kGy. The LL output measured under oxygen equilibrated conditions showed an extension of the dosimetric response from 0.6 to 6 kGy. ESR spectral analysis indicates the formation of two radical species viz., 'a' and 'b' and their involvement in the LL process. The estimated free radical concentrations of radicals 'a' and 'b' were found to be 6.81 x 10(15) and 1.35 x 10(16) g(-1), respectively, for a gamma dose of 10.8 kGy. 相似文献
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