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151.
Ephraim S. Casper Gary K. Schwartz Bruce Johnson David P. Kelsen 《Investigational new drugs》1992,10(4):313-316
We conducted a phase II evaluation of edatrexate in 17 previously untreated patients with advanced adenocarcinoma of the pancreas; 14 patients had at least one month of therapy. The initial dose was 80 mg/m2iv. Treatment was administered weekly for 5 weeks, then every other week. Toxicity was generally mild. The median WBC nadir was 5.4 (range 0.6–7.4)×103/l, and the median platelet nadir was 164.0 (range 62.0–341.0)×103/l. One patient died with sepsis and gastrointestinal bleeding associated with pancytopenia. Five patients had a mild rash. Nausea occurred in 6 patients, including 3 who had vomiting. In addition, 11 patients complained of vague malaise which seemed to begin within 24–48 hours after administration of edatrexate, and lasted for 2 to 3 days, resolving within 6 days of drug administration. Median survival was 85 days. Although 5 patients had stable disease, including one with relief of pain, no major responses were seen, excluding, with 95% confidence, a response rate in excess of 20%. 相似文献
152.
A novel method for "ghost" artifact suppression is introduced. It suppresses ghosts induced by motion in any direction, as well as other types of quasi-periodic signal modulation. Because it requires neither special hardware nor intensive data processing, it can be easily implemented on conventional magnetic resonance (MR) imagers. The method is based on the concept of decomposition of a ghosted complex image into a ghost mask and ideal image. A set of deliberately designed acquisitions are used to generate a set of ghosted complex images in which the ghost components are related in a simple manner. With use of equations describing image decomposition and ghost correlation, the ideal image can be calculated pixel by pixel. The ideal image obtained (representing the time-averaged spin-density distribution) is shown to be a truer representation of physical reality than the ghost-free image obtained with ordered phase encoding. In this technique, both interview and intraview effects are taken into account. The technique is also useful in simultaneously suppressing ghosts from multifrequency signal modulations such as respiratory and cardiac motions. The method was successfully tested with three time-interleaved, phase-encoding-order-shifted acquisitions. Experimental results have shown that it is a simple but effective technique. 相似文献
153.
Prof. Dr. G. Hildebrandt I. Stratmann 《International archives of occupational and environmental health》1979,43(2):73-83
Summary In 6 night nurses the daily course of body temperature and pulse rate was measured under strict resting conditions immediately after a 7 to 18-day period with night work as well as after a 10-day period of recovery under normal life conditions. Three of the subjects were morning types and three evening types according to the Horne-Östberg-Questionnaire as well as to the phase position of the body temperature cycle.In order to quantify the changes in amplitude, phase position, and frequency a flattening index, a circadian deformation index, and according to the calculated phase shift a corrected deformation index were used. While the evening types reacted with a flattening of their circadian amplitude and thus gained a greater tolerance, the morning types hyper reacted when exposed to the inverse life pattern, developing an increased amplitude and adding to the circadian deformation by ultradian periods. No significant differences could be detected in phase shift. Higher amounts of subjective complaints and deficit of sleep as well as differences in the additionally controlled vigilance functions demonstrated the lower tolerance of the morning types to night work.The discussion concerns the methological basis of a quantitative evaluation of disturbance of the circadian system, and shows off, that the greater tolerance of evening types to night work is based on a lower reagibility of the vegetative functions to changes in the outer environment. 相似文献
154.
RP-HPLC进行甲氨蝶呤血药浓度监测时保留时间校准方法研究 总被引:2,自引:0,他引:2
目的 建立RP—HPLC进行MTX血药浓度监测时保留时间校准方法。方法应用容量因子与流动相比例的三次方多项式模型,建立MTX流动相比例与保留时间的函数,并通过此函数用保留时间求算流动相比例,与理论流动相比例比较,从而计算流动相应该补充组分的量,达到调整保留时间的目的。结果四种不同色谱条件下容量因子与流动相比例的三次方多项式模型拟合关系良好,R0均为1.000,保留时间经校准后RSD为0.9%(n=5)。结论本方法能准确校准因流动相比例引起变化的保留时间,适用于MTX血药浓度监测时保留时间的校准,方法新颖、有效、简单。 相似文献
155.
HPLC法测定复方西洋参胶囊中人参皂甙Rb1的含量 总被引:1,自引:0,他引:1
目的:建立测定复方西洋参胶囊中人参皂甙Rbl含量的方法。方法:以乙腈—甲醇—水(70:30:15)为流动相,采用高效液相色谱法测定。结果:人参皂甙Rbl在0.03--0.15mg/ml范围内线性良好,回收率为97.8%,RSD=1.0%。样品采用Sep—pakC18柱的固相萃取技术。结论:方法快速、简便,结果准确。 相似文献
156.
157.
甲氨碟呤脂质体的几种制备方法比较 总被引:8,自引:1,他引:8
目的探讨脂质体的制备方法 ,以便在具体工作中根据不同的目的选择适当的制备方法。方法采用逆相蒸发法、注射法、薄膜法和超声法制备包裹了甲氨喋呤和环胞苷的脂质体。对各种方法的关键步骤进行了讨论。结果被包物质如不稳定 ,采用薄膜法轻轻振摇超过 10h ,包封率可比短时间或震荡激烈提高。被包物质如经过短时间的超声和有机溶剂处理 ,采用逆相蒸发法 ,可获得较高包封率。结论根据被包物质的性质及具体工作不同 ,选择适当的脂质体制备方法 ,会得到较高的包封率和工作效率 相似文献
158.
159.
Elin Lindhagen Pernille‐Julia Vig Hjarnaa Lena E. Friberg Scilla Latini Rolf Larsson 《Drug development research》2004,61(4):218-226
When a candidate drug enters clinical trials, decisions regarding dosing are mainly based on animal data. Occasionally, toxicity problems are faced in the clinic because of unexpected species differences in pharmacokinetics or pharmacodynamics between humans and preclinical species. Fludarabine and topotecan are examples of such drugs. In the first clinical trials of the new agent CHS 828, the maximum tolerated dose was reached earlier than expected from animal data. This paper discusses the issue of species differences in the development of anticancer drugs, and preclinical models for detection and quantification of such differences. Pharmacokinetic and hematological toxicity data of CHS 828 from studies in rats and humans are presented. In vitro sensitivity to CHS 828 and some established cytotoxic agents was measured in lymphocytes from humans and rats and in a panel of human and rodent cell‐lines. 10–100 times higher CHS 828 exposure was tolerated by rats than by patients. In both in vitro cell systems, CHS 828 showed higher potency in human cells compared to rodent cells. A species difference was evident also for fludarabine, but not for doxorubicin and cisplatin. CHS 828 pharmacokinetics were similar across species. In conclusion, the lower tolerance of CHS 828 in humans than in rats could be detected in vitro in cultures of peripheral lymphocytes. Preclinical studies of species differences could help the interpretation of in vivo effect studies as well as the choice of starting dose for clinical trials. We suggest peripheral lymphocytes from different species as a potential model system for such studies. Drug Dev. Res. 61:218–226, 2004. © 2004 Wiley‐Liss, Inc. 相似文献
160.
Abstract: Hofmann rearrangement of Nα‐Boc‐l ‐Gln‐OH mediated by a polymer‐supported hypervalent iodine reagent poly[(4‐diacetoxyiodo)styrene] (PSDIB) in water afforded Nα‐Boc‐l ‐α,γ‐diaminobutyric acid (Boc‐Dab‐OH, 1 ) in 87% yield. Nα‐Z‐derivative (Z‐Dab‐OH, 2 ) was prepared with PSDIB in 83% yield. Since the reaction of Nα‐Fmoc‐Gln‐OH by this procedure did not proceed because of the insolubility of Fmoc‐Gln‐OH in aqueous media, we synthesized Fmoc‐Dab(Boc)‐OH ( 5 ) from 2 in 54% yield. Polymyxin B heptapeptide (PMBH) which contains four Dab residues was successfully synthesized in a solution‐phase synthesis. 相似文献