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Ngoc-Anh T. Nguyen Mickey L. Wells David C. Cooper 《Drug development and industrial pharmacy》1995,21(14):1671-1682
To identify factors affecting the chemical stability and preservative efficacy of lamivudine oral liquid formulations, an optimization study using a central composite design was performed. In this design, five factors, each at three levels, were investigated: pH (4.5, 5.5, and 73, sucrose (5%, 20%. and 50% w/v), propylene glycol (0% 2%, and 5% w/v), glycerin (4% 8%, and 12% w/v). and EDTA (0.100. 0.175, and 0.250 mg/mL). All formulations contained a constant concentration of lamivudine, parabens, and artificial strawberry and banana flavors. All formulations were evaluated for preservative effectiveness against USP and BP standards and for chemical stability at 30°C and 40°C for three months. All formulations were effective against bacteria and yeasts, but indicated reduced preservative effectiveness against the mold Aspergillus niger. Preservative effectiveness improved with increasing pH (4.5 to 7.5) and to a lesser extent with increasing EDTA concentration (0.100 to 0.250 mg/mL). Increasing glycerin concentration (4% to 12% w/v) slightly decreased preservative effectiveness. Over the concentration ranges tested, no change in preservative effectiveness was noted with concentration changes in sucrose or propylene glycol. The pH was the main factor influencing the chemical stability of the drug and preservatives in this study. Lamivudine chemical stability increased with increasing pH from 4.5 to 7.5. Methyl and propylparaben showed extensive degradation at pH 7.5. 相似文献
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Radical abdominopelvic lymphadenectomy for rectal cancer is based on the tenet that removal of all potentially involved lymphatic tissue will yield a lower rate of locoregional failure and improve survival. At centers with extensive experience with the procedure, the operating time is only modestly prolonged compared with conventional resection. Blood loss and postoperative hospitalization are not significantly increased. Urinary dysfunction and impotence associated with radical abdominopelvic lymphadenectomy (as high as 80 percent and 76 percent, respectively, in recent series) have been major deterrents to its more routine application. Preservation of the hypogastric plexus and even selective preservation of a unilateral S4 nerve root have been shown to reduce the occurrence of genitourinary complications. Improved five-year survival of 68 percent and local recurrence rates of 5 to 20 percent for TNM Stage III cancers have been achieved with radical abdominopelvic lymphadenectomy. These results compare favorably with recent trials of adjuvant chemoradiation after conventional resection in stage-matched patients. The rationale, evolution, and application of radical abdominopelvic lymphadenectomy to the surgical management of rectal cancer are critically examined. The potential benefits of radical abdominopelvic lymphadenectomy, which have been demonstrated in nonrandomized trials, should be evaluated in a prospective and properly randomized study to clearly establish or refute its efficacy. 相似文献
69.
GR Bayyari WE Huff RA Norton JK Skeeles JN Beasley NC Rath JM Balog 《Canadian Metallurgical Quarterly》1994,38(4):744-754
Two flocks of Nicholas tom turkeys from separate farms with histories of above-average condemnations for turkey green-liver osteomyelitis complex (TOC) were studied throughout a 16-week growout. Fifty birds from each farm were necropsied each week for 15 weeks, and birds that had green livers, osteomyelitis in the proximal tibia, or swollen joints were cultured for aerobic bacteria along with an equal number of control birds. At processing, TOC lesions and green livers were obtained for bacterial culture and histopathology. Green-liver-associated TOC was not observed until the turkeys were 9 or 10 weeks of age. The incidence of TOC was higher on one farm, which also had a higher incidence of airsacculitis, higher early and weekly mortality, seroconversion to Newcastle disease virus and Mycoplasma meleagridis, and significantly higher average body weights, relative spleen weights, and relative liver weights. Both farms had a high incidence of intestinal lesions and infestation with Ascaridia dissimilis. Histological evaluation of green livers revealed hyperplasia of bile ducts, dilation of sinusoids, and pigment-containing Kupffer's cells, some of which stained positive for iron. The bacterial isolates most frequently cultured from bones and livers were pleomorphic gram-variable coccobacilli, which grew visible colonies only after a series of subcultures and extended incubation. 相似文献
70.
The Pao-Sah model for the long-channel MOSFET is generalized to include MOSFETs with resistive-gate electrodes (RG-MOSFETs). The RG-MOdSFETs current-voltage characteristics are studied using this extended Pao-Sah model. The steady-state operation of the RG-MOSFET can be divided into three regimes, separated by the uniform channel condition and the pinch-off condition, respectively. The regions of operation are discussed, and a simple analytical I -V expression is given for the device 相似文献