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31.
OJ D'Cruz TK Venkatachalam Z Zhu MJ Shih FM Uckun 《Canadian Metallurgical Quarterly》1998,59(3):503-515
Detergent-based vaginal microbicides, in addition to their high contraceptive failure rates, cause mucosal erosion and local inflammation that might increase the risk of heterosexual human immunodeficiency virus (HIV) transmission. In a systematic effort to identify a microbicide contraceptive potentially capable of preventing the sexual transmission of HIV as well as providing fertility control, a series of novel aryl phosphate derivatives of 5-bromo-6-methoxy-3'-azido-3'-deoxythymidine (AZT; zidovudine) were synthesized and examined for dual anti-HIV and sperm-immobilizing activity (SIA). Whereas AZT displayed potent anti-HIV activity (IC50 = 0.006 microM) but lacked SIA (EC50 > 300 microM), two 5-bromo-6-methoxy-aryl phosphate derivatives of AZT, compounds WHI-05 and WHI-07, exhibited potent anti-HIV activity as well as SIA. The IC50 (HIV) and EC50 (SIA) values for WHI-07 were 439-fold and 13.5-fold lower, respectively, than those for the detergent-based virucidal spermicide, nonoxynol-9 (N-9). Sperm motion kinematics using computer-assisted sperm motion analysis combined with confocal laser scanning microscopy, high-resolution low-voltage scanning, and transmission electron microscopy demonstrated that both WHI-05 and WHI-07 cause a complete and irreversible loss of sperm motility in a concentration- and time-dependent fashion without concomitantly affecting the sperm acrosomal membrane integrity. In experiments designed to assess the fertilizing capacity of treated sperm, preincubation of sperm with either compound resulted in a concentration-dependent loss of the ability to adhere to and penetrate zona-free hamster eggs as well as inhibition of binding to human zona. WHI-07 applied intravaginally prior to artificial insemination of epididymal sperm drastically reduced fertility in hormonally primed CD-1 mice. Unlike the intravaginal application of N-9, repetitive intravaginal application of WHI-07 did not damage the vaginal epithelium or cause local inflammation. Structure-function relationship analyses showed that the addition of bromo-methoxy functional groups to AZT was essential for, and the aryl phosphate derivatization contributory to, the SIA of both compounds. Compounds WHI-05 and WHI-07 may be useful as dual-function vaginal contraceptives for women who are at high risk for acquiring HIV/acquired immunodeficiency virus syndrome by heterosexual vaginal transmission. 相似文献
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DL McKinzie KL Nowak L Yorger WJ McBride JM Murphy L Lumeng TK Li 《Canadian Metallurgical Quarterly》1998,22(5):1170-1176
The alcohol-deprivation effect (ADE) was examined under 4-hr operant and 24-hr free-choice alcohol access in the alcohol-preferring (P) rat after deprivation intervals from 2 to 4 weeks. Results indicated that adult male P rats responding for 6 weeks on a concurrent FR-5/FR-1 schedule of reinforcement for alcohol and water, respectively, and then deprived of alcohol for 2 weeks, demonstrated a 40% increase in alcohol responding during the first 60 min of alcohol reinstatement. The alcohol deprivation effect was temporary, however, as responding did not differ from baseline levels on the second day of reinstatement. In a second experiment, weanling male and female P rats received 7 weeks of continuous access to alcohol, beginning at 21 days of age, and were then deprived of alcohol for 4 weeks. On the first day of alcohol reinstatement, P rats exhibited a 40% to 45% increase from baseline alcohol drinking levels, with alcohol intake returning to baseline levels by the 3rd day of reinstatement. Although alcohol intake was higher in females than in males when adjustment was made for body weight, there were no gender differences in the magnitude of the alcohol deprivation effect. Taken together, these results indicate that the ADE is a long-lasting phenomenon that occurs under both operant and continuous access conditions in the P rat, and thus these rats may be useful models for the study of factors involved in relapse of alcohol drinking. 相似文献
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The purpose of this study was to evaluate the effect of redesigning the education program from individual instructional sessions to a format where the majority of instruction was provided through small group classes. Patient outcomes of lifestyle changes as evidenced by weight loss, improved glycemic control, adoption of a consistent pattern of blood glucose monitoring, and increased physical activity were evaluated using a physician satisfaction survey and a patient satisfaction and lifestyle change survey. The findings indicate that the changes in the education program accommodated a variety of needs; facilitated cost-effectiveness; were convenient for the patients, educators, and physicians; and still promoted adaptive lifestyle changes in behavior leading to improved glycemic control, increased levels of physical activity, and weight loss in persons with type 2 diabetes. 相似文献
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M Dubuc M Talajic D Roy B Thibault TK Leung PL Friedman 《Canadian Metallurgical Quarterly》1998,2(3):285-292
BACKGROUND AND PURPOSE: Accurate contouring of the clinical target volume (CTV) is a fundamental prerequisite for successful conformal radiotherapy of prostate cancer. The purpose of this study was to investigate intra- and inter-observer variability in contouring prostate (P) and seminal vesicles (SV) and its impact on conformal treatment planning in our working conditions. MATERIALS AND METHODS: Inter-observer variability was investigated by asking five well-trained radiotherapists of contouring on CT images the P and the SV of six supine-positioned patients previously treated with conformal techniques. Short-term intra-observer variability was assessed by asking the radiotherapists to contour the P and SV of one patient for a second time, just after the first contouring. The differences among the inserted volumes were considered for both intra- and inter-observer variability. Regarding intra-observer variability, the differences between the two inserted contours were estimated by taking the relative differences in correspondence to the CT slices on BEV plots (antero-posterior and left-right beams). Concerning inter-observer variability, the distances between the internal and external envelopes of the inserted contours (named projected diagnostic uncertainties or PDUs) and the distances from the mean inserted contours (named mean contour distances or MCDs) were measured from BEV plots (i.e. parallel to the CT slices). RESULTS: Intra-observer variability was relatively small (the average percentage variation of the volume was approximately 5%; SD of the differences measured on BEV plots within 1.8 mm). Concerning inter-observer variability, the percentage SD of the inserted volumes ranged from 10 to 18%. Differences equal to 1 cm in the cranio-caudal extension of P + SV were found in four out of six patients. The largest inter-observer variability was found when considering the anterior margin in the left-right beam of P top (MCD = 7.1 mm, 1 SD). Relatively high values for MCDs were also found for P bottom, for the posterior and lateral margins of P top (2.6 and 3.1 mm, respectively, I SD) and for the anterior margin of SV (2.8 mm, 1 SD). Relatively small values were found for P central (from 1.4 to 2.0 mm, 1 SD) and the posterior margin of SV (1.5 mm, 1 SD). CONCLUSIONS: The application of larger margins taking inter-observer variability into account should be taken into consideration for the anterior and the lateral margins of SV and P top and for the lateral margin of P. The impact of short-term intra-observer variability does not seem to be relevant. 相似文献
37.
PK Woodard D Li EM Haacke PJ Dhawale S Kaushikkar B Barzilai AC Braverman PA Ludbrook AN Weiss JJ Brown SA Mirowitz TK Pilgram FR Gutierrez 《Canadian Metallurgical Quarterly》1998,170(4):883-888
OBJECTIVE: Our objective was to study the ability of three-dimensional MR angiography with retrospective respiratory gating to reveal stenoses in proximal coronary arteries on source and projection images. CONCLUSION: Proximal coronary artery stenoses can be identified using three-dimensional MR angiography with retrospective respiratory gating, both with projection images and on source images alone. Reasons for missed lesions included collateral vessels and retrograde flow distal to complete occlusion and volume averaging of vessels with adjacent structures. Causes of false-positive interpretations included small foci of decreased signal intensity distal to complete occlusion, partial volume effects on individual partitions, and regions of distal vessels leaving the imaging plane. 相似文献
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