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991.
α-Alkylation of amino acid derivatives: Synthesis and chiral resolution of [C]β-aminoisobutyric acid
A synthesis of 11C-labeled β-aminoisobutyric acid ([11C]β-AIB) and its enantiomeric resolution by high performance liquid chromatography (HPLC) are reported. β-Alanine ethyl ester 2 was converted to benzaldimine-β-alanine ethyl ester 3 in 87% yield. Treatment of the imine derivative 3 with lithium diisopropylamide (1.1 eq) in tetrahydrofuran at −78 °C, followed by addition of cold iodomethane (1.1 eq) produced the α-methylated benzaldimine-β-alanine ethyl ester 4 in 73% chemical yield. Deprotection of the amino group by acidic hydrolysis followed by basic hydrolysis of the ester group produced the desired product 1 in 37% chemical yield. Labeling was accomplished using [11C]methyl iodide. The radiola-beled product was purified by HPLC using a semipreparative reversed-phase C-18 column and 2 mM phosphate buffer (pH 5.9) as the mobile phase. The synthesis time was 35–40 min including HPLC purification, with 20–60% radiochemical yield (decay corrected). Radiochemical purity was >99%, with average specific activity being 450 mCi/μmol. Enantiomers of β-AIB were well separated by analytical HPLC using a chiral column and aqueous perchloric acid as the mobile phase. (S)-β-AIB was eluted at 17.4 min and the (R)-enantiomer was eluted at 20.0 min when the jacketed column was maintained at low temperature by circulation of ice-cold water, and the pH of the mobile phase was 1.05. 相似文献
992.
993.
Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. The Netherlands and Canadian Formoterol Study Investigators 总被引:3,自引:2,他引:1
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T. van der Molen D. S. Postma M. O. Turner B. M. Jong J. L. Malo K. Chapman R. Grossman C. S. de Graaff R. A. Riemersma M. R. Sears 《Thorax》1997,52(6):535-539
BACKGROUND: The long acting beta 2 agonist formoterol has proved to be an effective bronchodilator with a prolonged action of 12-14 hours. However, the precise role of formoterol in the maintenance treatment of asthma is still under debate. A study was performed to investigate the efficacy and safety of treatment with formoterol for six months in subjects with asthma. METHODS: In a multicentre double blind, placebo controlled, parallel group study 239 subjects with mild to moderate asthma were randomly assigned to treatment with either inhaled formoterol 24 micrograms twice daily (n = 125) or placebo (n = 114) during eight months. The study consisted of a four week run in period, a 24 week treatment period, and a four week washout period. All subjects were using regular inhaled corticosteroids (100-3200 micrograms daily) but were still needing at least five inhalations of short acting beta 2 agonist per week for symptom relief. The study was performed in 10 outpatient clinics in Canada, and five outpatient clinics and one coordinating centre for 44 Dutch general practitioners in The Netherlands. Twice daily self-reported peak expiratory flow (PEF) measurements, symptom scores, and rescue beta 2 agonist use during the last 28 treatment days compared with baseline values were used as main outcome measures. Spirometric values were measured at entry, at the start of treatment, after four, 12 and 24 weeks of treatment, and after four weeks washout. RESULTS: One hundred and twenty five subjects received formoterol 24 micrograms twice daily via Turbohaler and 114 received placebo. Baseline FEV1 was 67.1% predicted and mean bronchodilator reversibility was 26%. The mean total asthma symptom score was 3.6 (maximum possible 21). A significant decrease in symptoms in favour of formoterol (difference from placebo -0.64, 95% CI -0.04 to -1.23, p = 0.04) was observed. Compared with placebo, morning PEF increased (difference from placebo 28 l/min, 95% CI 18.3 to 37.7, p = 0.0001) and the use of short acting beta 1 agonists decreased (daytime difference from placebo -1.1 inhalation, 95% CI -1.4 to -0.7, p = 0.0001) in the formoterol group. PEF returned to baseline following discontinuation of formoterol, as did asthma symptom scores. Thirty three patients treated with formoterol and 32 treated with placebo required treatment with prednisolone during the study (58 and 55 courses, respectively). CONCLUSIONS: Adding formoterol 24 micrograms twice daily by Turbohaler to inhaled corticosteroids was effective in improving symptom scores and morning PEF, and decreasing the use of rescue beta 2 agonists. There was no apparent loss of asthma control during 24 weeks of treatment with formoterol.
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994.
Abstract: The optimal timing of systemic cyclophosphamide, methotrexate, 5-fluorouracil (CMF) chemotherapy and local radiation in adjuvant breast cancer has been a debatable subject. To evaluate the Lankenau Hospital experience with sequential CMF chemotherapy followed by radiation in the adjuvant therapy of stage I and stage II breast cancer we reviewed the records of patients at our center. This group of 34 patients was treated in a homogenous manner, all receiving standard CMF for six cycles followed by radiotherapy after lumpectomy with axillary lymph node dissection. The radiation course was 5040cGy to the entire breast (28 fractions in 45 elapsed days) followed by a boost to the tumor site of 1800cGy in 10 fractions. Thirty-four patients were identified and followed for an average of 5 years (range 1.5–11.5 years). One patient had local recurrence and with subsequent treatment is disease-free at 5 years postrecurrence (8 years from initial diagnosis). Two deaths were not breast-cancer related (1 myocardial infarction at year 3, 1 melanoma at year 7.5). The estimated probability of no relapse at 5 years and 8 years by Kaplan-Meier analysis is 79% and 60% respectively. Overall and disease-free survival in this group of patients treated with breast-conserving surgery and CMF chemotherapy followed by radiation is excellent. There appears to be no detriment to delaying radiotherapy until full doses of systemic treatment are given as local recurrence was rare (6%) and was amenable to further treatment. 相似文献
995.
Levodopa improves physical fatigue in Parkinson's disease: a double-blind, placebo-controlled, crossover study. 总被引:1,自引:0,他引:1
Jau-Shin Lou Greg Kearns Theodore Benice Barry Oken Gary Sexton John Nutt 《Movement disorders》2003,18(10):1108-1114
We quantitatively investigated the effect of carbidopa/levodopa (25/100) on physical fatigue during finger tapping and force generation in a double-blind, placebo-controlled crossover study. Parkinson's disease (PD) subjects were randomly assigned to carbidopa/levodopa or placebo for Visit 1 or 2 and participated in the following two studies: (1) Finger tapping. Twenty-five PD patients used their index fingers to strike two keys 20 cm apart on a musical instrument digital interface (MIDI) keyboard. The slopes of the regression line of dwell time and movement time were used to assess the rate of fatigue development. (2) Force generation. Twelve PD patients contracted the wrist extensors maximally to obtain a baseline maximum voluntary contraction (BMVC) force. Then they repetitively contracted the wrist extensors at 50% of the BMVC for 7 seconds and rested for 3 seconds. An interval maximum voluntary contraction (IMVC) was measured every three repetitions. Fatigue was defined as an IMVC of less than 60% of the BMVC. The slope of the regression line of IMVC was used to assess the rate of force decline. These two studies were repeated 1 hour after carbidopa/levodopa (25/100) or placebo. Subjects filled out the Multidimensional Fatigue Inventory (MFI) at the beginning of the first visit. Results showed that the slope of dwell time decreased with levodopa but not with placebo (P = 0.004). The rate of force decline also decreased with levodopa but not with placebo (P = 0.01). The subscores in the dimension of physical fatigue in the MFI did not correlate with the rate changes in dwell time or the rate changes in force decline. We concluded that (1) levodopa improves physical fatigue in finger tapping and force generation, (2) physical fatigue in Parkinson's disease is at least partially related to dopamine deficiency, and (3) the MFI measures different aspects of physical fatigue compared with those measured by finger tapping and force generation. 相似文献
996.
W E Berdel S de Vos J Maurer D Oberberg Z von Marschall J K Schroeder J Li W D Ludwig E D Kreuser E Thiel 《Cancer research》1992,52(12):3498-3502
The growth of a panel of eight different human glioblastoma cell lines was examined in a human tumor cloning assay in agar, a tritiated thymidine uptake assay, and by counting cell numbers, in cultures performed in the absence or presence of increasing concentrations (1 to 100 ng/ml) of recombinant human stem cell factor (SCF). Growth of 7 of 8 cell lines was not significantly and reproducibly affected by recombinant human SCF. However, growth of the CRL 1620 cell line could be stimulated up to 5-fold by the cytokine. In contrast to the other cell lines investigated, CRL 1620 expressed the c-kit protooncogene assessed on the mRNA and protein level. Furthermore, SCF-induced proliferation of CRL 1620 cells was sensitive to the tyrosine kinase inhibitor erbstatin. Our data suggest that SCF can be operative in growth modulation of malignant cells outside the hematopoietic system, and this finding should be further studied for its possible clinical implications. 相似文献
997.
998.
999.
David S. K. Lu Shantanu Sinha John Lucas Keyvan Farahani Robert Lufkin Klaus Lewin 《Journal of magnetic resonance imaging : JMRI》1997,7(2):303-308
The purpose of this study was to test the feasibility of MR-guided percutaneous ethanol ablation of liver tissue on a .2-T open MR scanner. Needles were placed by MR guidance first into an ex vivo sheep liver and then into livers of three anesthetized pigs, and injection of 10 ml of 96% alcohol was performed. T1 fast low-angle shot (FLASH), T2 turbo spin echo (TSE), and T1 spin echo (SE) images were obtained after incremental volumes of injection. In one pig, simultaneous injection of saline into normal liver was also performed with subsequent pathological correlation. Ethanol-infiltrated liver was hypointense to liver on all sequences, whereas saline caused no tissue signal changes on T1 SE and either isointense or hyperintense changes on T2 TSE images. Pathological examination confirmed ethanol-induced acute liver changes as compared with the control. MR guidance of needle placement and monitoring of ethanol effects on liver tissue is feasible. This may have implications for potential MR-guided hepatic tumor ablation. 相似文献
1000.