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D M Floyd S D Kimball J Krapcho J Das C F Turk R V Moquin M W Lago K J Duff V G Lee R E White 《Journal of medicinal chemistry》1992,35(4):756-772
As part of a program to discover potent antihypertensive analogues of diltiazem (3a), we prepared 1-benzazepin-2-ones (4). Benzazepinones competitively displace radiolabeled diltiazem, and show the same absolute stereochemical preferences at the calcium channel receptor protein. Derivatives of 4 containing a trifluoromethyl substituent in the fused aromatic ring show potent and long-acting antihypertensive activity. Studies of the metabolism of 4 lead to the metabolically stable antihypertensive calcium channel blockers 5a and 5c. Benzazepinone 5a is a longer acting and more potent antihypertensive agent than the second generation diltiazem analogue TA-3090 (3e). 相似文献
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George Karpati Djordje Ajdukovic Douglas Arnold Robert B. Gledhill Ronald Guttmann Paul Holland Penelope A. Koch Eric Shoubridge Desmond Spence Michel Vanasse Gordon V. Watters Michael Abrahamowicz Catherine Duff Ronald G. Worton 《Annals of neurology》1993,34(1):8-17
One biceps muscle of 8 patients with Duchenne muscular dystrophy was injected at 55 sites with a total of 55 million viable, purified, and contamination-free normal myoblasts (myoblast transfer). The other biceps of each patient was injected with a placebo to serve as a control. The procedure was blinded to the patients, parents, and investigators. Myoblasts derived from a biopsy specimen of the fathers were cultured and purified under strict conditions and carefully screened for microbial contamination. All patients received cyclophosphamide for immunosuppression for 6 or 12 months. No serious complications were observed after myoblast transfer, indicating that the procedure is safe. The overall therapeutic efficiency of myoblast transfer was poor as judged by the results in maximal voluntary force generation, dystrophin content of the muscle, magnetic resonance imaging of the muscle, and the lack of donor-derived DNA and dystrophin messenger RNA in the injected muscle. An improved efficiency of the take of myoblasts might be achieved by using younger cells and injecting the myoblasts with a myonecrotic agent (to increase the prevalence of regeneration) and a basal laminal fenestrating agent. 相似文献
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A double-crossover trial comparing the effects of topical carteolol and placebo on intraocular pressure. 总被引:1,自引:1,他引:0 下载免费PDF全文
The effect of topical carteolol 2% on the intraocular pressures of 12 patients suspected of having glaucoma was measured in a double-crossover trial of six weeks' duration. Carteolol produced a significant reduction in intraocular pressure (p less than or equal to 0.001), when compared with placebo. This represented reductions of 11% and 14%, after one and two weeks of treatment. 相似文献
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B Garcia R Zhong J Wijsman P Wang H Chen F Sutherland J Duff D Grant 《Transplantation proceedings》1990,22(6):2469-2470
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A comparison of the effects of oral nadolol and topical timolol on intraocular pressure, blood pressure, and heart rate. 总被引:1,自引:1,他引:0 下载免费PDF全文
We compared the effects of oral nadolol 20 mg once daily and topical timolol 0.25% twice daily on the intraocular pressures of 22 glaucoma suspects, in a 12 week double-masked crossover study. Both nadolol and timolol reduced intraocular pressure (p less than 0.001). The reductions in intraocular pressure did not differ significantly after two weeks and four weeks of treatment. Nine of these subjects underwent treadmill exercise tests in order to compare the effects of nadolol and timolol on the cardiovascular system. The effects of the two treatments on blood pressure were comparable, but nadolol caused a significantly greater reduction in heart rate than timolol at rest (p less than 0.05). Nadolol reduces intraocular pressure effectively and may prove a useful alternative treatment for chronic simple glaucoma. 相似文献
9.
Chad Galer Anthony Yonkers Wallace Duff Barbara Heywood 《Otolaryngology--head and neck surgery》2007,136(2):241-245
OBJECTIVE: To examine the clinical significance of acoustic data recorded by the SNAP home polysomnography system (SNAP Laboratories, Glenview, IL). STUDY DESIGN AND SETTING: Retrospective analysis of SNAP data from 59 patients undergoing evaluation for sleep apnea at the University of Nebraska Medical Center and an associated private practice in Omaha, NE. RESULTS: Snoring did not correlate with anthropometric variables such as body mass index and neck circumference. Statistical analysis showed no correlation between respiratory disturbance index and the maximum or average loudness of snoring. Average loudness was predictive of the presence of sleep apnea. Spectral analysis of snoring sonography found that the proportion of snoring events associated with a palatal source correlated strongly with the loudness of snoring. CONCLUSION: These data suggest that analysis of snoring has limited utility in the evaluation of the patient with sleep apnea but may be able to select patients who would benefit from palatal procedures to reduce snoring. 相似文献
10.
Estrogen-induced transcortin increase and progesterone and cortisol interactions: implications from pregnancy studies 总被引:1,自引:0,他引:1
J J Evans I L Sin G B Duff C M Frampton 《Annals of clinical and laboratory science》1987,17(2):101-105
The concentrations of progesterone, cortisol, estradiol, and transcortin binding capacity (TBC) were measured in plasma samples of women during normal pregnancy. Between 10 weeks and 20 weeks gestation, the mean of TBC increased linearly, and the mean increase in TBC for a given estradiol increment was constant until the estradiol concentrations reached approximately 30 nmol per liter. The results were consistent with the increase in TBC having been induced by estradiol; however, there was an inherent upper limit of response. Progesterone and cortisol were each linearly related to TBC, but the ratios of progesterone:TBC and cortisol:TBC showed no systematic trend throughout the period studied, and there was no systematic relationship between TBC and the progesterone:cortisol ratio. There was, however, a linear relationship between TBC and the progesterone + cortisol sum, such that a unit increase in TBC was accompanied by an approximate unit increase in the total concentration of the two main transcortin binding steroids. Some cases of spontaneous abortion or habitual abortion might be due to aberrant metabolic influence on progesterone of binding protein; in the instances studied, no evidence was found for this. 相似文献