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Identification of a new variant in the YMDD motif of the hepatitis B virus polymerase gene selected during lamivudine therapy 总被引:12,自引:0,他引:12
Niesters HG De Man RA Pas SD Fries E Osterhaus AD 《Journal of medical microbiology》2002,51(8):695-699
A new hepatitis B virus variant selected during lamivudine treatment was detected, in which the methionine (rtM204) in the so-called YMDD motif in the C domain of the catalytic site of the polymerase gene was replaced by a serine (rtM204S). This change simultaneously resulted in a tyrosine-195 into valine variant (sY195V) in the surface protein HBsAg. The detection of this YSDD variant was initially observed, after an increase of HBV DNA levels, by sequencing of amplification products from day 586. A specific RFLP assay was developed that could identify 10% of YSDD-containing variants in the virus pool, which enabled detection of this new variant virus at day 506. However, by cloning several PCR products and sequencing individual recombinant clones, the mutation was first identified at day 477, before a significant increase of HBV DNA was observed in serum. The mutation was followed by a leucine to methionine change at position 180 (rtL180M). The consequences of this mutation for disease management and diagnostic strategies are discussed. 相似文献
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To investigate whether the learning curve of robotic surgery simulator training depends on the probands’ characteristics, such as age and prior experience, we conducted a study of six distinct proband groups, using the da Vinci Skills Simulator: experienced urological robotic surgeons, surgeons with experience as da Vinci tableside assistants, urological surgeons with laparoscopic experience, urological surgeons without laparoscopic experience, and complete novices aged 25 and younger and 40 and older. The results showed that all experienced robotic surgeons reached expert level (>90 %, as defined previously in the literature) within the first three repetitions and remained on a high level of performance. All other groups performed worse. Tableside assistants, laparoscopically experienced surgeons, and younger novices showed a better performance in all exercises than surgeons without laparoscopic experience and older novices. A linear mixed-effects model analysis demonstrated no significant difference in learning curves between proband groups in all exercises except the RW1 exercise for the younger proband group. In summary, we found that performance in robotic surgery, measured by performance scores in three virtual simulator modules using the EndoWrist techniques, was dependent on age and prior experience with robotic and laparoscopic surgery. However, and most importantly, the learning curve was not significantly affected by these factors. This suggests that the da Vinci Skills Simulator? is a useful practice tool for everyone learning or performing robotic surgery, and that early selection of talented surgeons is neither possible nor necessary. 相似文献
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The effects of oral milrinone treatment in cardiomyopathic hamsters with severe congestive heart failure (CHF) were evaluated. Strict criteria based on increase in body weight were established to define day no 1 of treatment. Survival rate of non-treated hamsters (group 1) ranged between 9 and 16 d, mean 12.9 (SEM 0.8) d, after entering the study. Hamsters treated with milrinone in drinking water (group 2a: 0.3 mg.ml-1, or group 2b: 0.6 mg.ml-1) survived between 6 and 36 d, mean 15.0(2.1) d, NS, for group 2a, and between 6 and 47 d, mean 19.6(4.0) d, NS, for group 2b. There was a significant difference between the number of hamsters that survived longer than 16 d between untreated hamsters (group 1, n = 0/12) and hamsters treated with milrinone (groups 2a, b, n = 7/24). There was no significant correlation between survival duration and milrinone daily dose nor between survival and milrinone plasma concentration at death. Milrinone treatment also significantly decreased pulmonary congestion as measured by the number of pigment containing macrophages per alveolus. No other pathological findings were modified by milrinone. It was concluded that, in addition to exerting a beneficial effect on pulmonary congestion, milrinone improved survival in some CHF hamsters. However, more studies are needed to evaluate the possibility of an arrythmogenic potential that might explain why some treated hamsters died earlier than non-treated hamsters. 相似文献