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MA Nowak AL Lloyd GM Vasquez TA Wiltrout LM Wahl N Bischofberger J Williams A Kinter AS Fauci VM Hirsch JD Lifson 《Canadian Metallurgical Quarterly》1997,71(10):7518-7525
Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus. 相似文献
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FJ Overdyk PM Gramling-Babb JR Handy NI Faller MJ Miller 《Canadian Metallurgical Quarterly》1997,84(1):213-215
Robertsonian translocations, although relatively common as a constitutional genetic aberration, are rarely encountered in leukaemia. We report a case of acute myeloid leukaemia which showed an acquired Robertsonian translocation in the form of der(14;21) by cytogenetic analysis of leukaemic cells. This was confirmed by the PHA-stimulated culture of peripheral blood lymphocytes. A review of the literature identifies only eight reported cases of acquired Robertsonian translocations in leukaemia. In the majority of cases the Robertsonian translocation occurs as a secondary change in a complex abnormal clone, whereas in two out of nine patients reported, including ours, it is found as a sole karyotypic abnormality. 相似文献
5.
JB Kamien WK Bickel BJ Smith GJ Badger JR Hughes 《Canadian Metallurgical Quarterly》1997,58(4):983-991
The percentage of long-term survivors after intensive chemotherapy and the outcome of MDS patients who achieve partial remission (PR) with intensive chemotherapy (IC) are not known. Between 1981 and 1996 we treated 99 patients with de novo MDS who had high-risk MDS or progression to AML, with IC. 41 (41%) achieved CR, 16 (16%) achieved partial remission (PR), 26 (26%) had failure, and 16 (16%) died in aplasia. Eight of the patients who achieved CR were autografted, three were allografted and the remaining cases received moderate consolidation chemotherapy. After IC, the 16 PR patients fulfilled the criteria for RA in 15 cases and CMML in one case. Median PR duration was 17 months, and three PR were > 3 years (39, 50+, 82+ months). Median actuarial survival of patients who achieved PR and CR was 18 months and 20 months from the onset of IC, respectively (difference not significant). Of the 71 patients treated before 1993, with sufficient follow-up, 10 (14%) had survived > 4 years (long-term survivors). Four of them were alive in first CR after 49+ to 110+ months and probably cured, two were alive in PR after 50+ and 82+ months and four had died after 49-78 months. Long-term survivors were characterized by a significantly higher incidence of RAEB-T at diagnosis, and with normal or favourable cytogenetic findings. In patients with RAEB-T at diagnosis included before 1993, 8/23 (35%) cases who had no unfavourable karyotype had survived > 4 years. Our findings suggest that MDS patients who achieve PR with IC, and not only those who achieve CR, can benefit from this type of treatment. The percentage of long-term survivors remains low, however, and is almost restricted to patients with RAEB-T at diagnosis and no unfavourable karyotype. 相似文献
6.
Carcinoma of the prostate, that is adenocarcinoma, is one of the most common malignancies in the male with an estimated incidence for 1991 of 122,000 new cases. On the other hand, squamous cell carcinoma of the prostate, with a median incidence of .5%-1% of all prostatic malignancies, has a similar clinical presentation but differs in treatment response and prognosis. We herein present one case of this histological pattern and review the literature pertaining to it. 相似文献
7.
JR Hamilton 《Canadian Metallurgical Quarterly》1997,11(1):94-98
OBJECTIVES: To identify knowledge levels of academic surgeons about Food and Drug Administration (FDA) and Institutional Review Board (IRB) regulations for clinical research and to determine whether being a member in an IRB, conducting or participating in clinical trials, or being a member in surgical societies affected knowledge levels. DESIGN: Survey of surgical department faculty members in 20 universities. RESULTS: Sixty-five responses were received from 14 sites. Overall mean (+/- SEM) correct score was 6.7 +/- 0.2 of a possible 20 points. The best predictor of overall score was being a primary investigator of a clinical trial (P < .001), followed by being or having been a member of an IRB (P < or = .02). The total mean score of members of the Surgical Infection Society (8.2 +/- 0.5) was significantly higher (P < .001) than that of nonmembers (6.1 +/- 0.2), a phenomenon not observed with other surgical societies. In certain hypothetical clinical scenarios, all respondents were mistakenly willing to conduct clinical trials without obtaining appropriate approval from the FDA. Four (22%) of 18 IRB member respondents and 16 (25%) of the 65 respondents were willing to conduct human research without appropriate approval from patients, the IRB, or both. CONCLUSIONS: Knowledge deficits exist in the academic surgical community about the role and requirements of the FDA and local IRBs for conducting clinical research. Further study is required to determine the reasons for this deficit and to identify appropriate interventions. 相似文献
8.
Malloy B.A. Lloyd E.L. Soffa M.L. 《Parallel and Distributed Systems, IEEE Transactions on》1994,5(5):498-508
A new approach is given for scheduling a sequential instruction stream for execution “in parallel” on asynchronous multiprocessors. The key idea in our approach is to exploit the fine grained parallelism present in the instruction stream. In this context, schedules are constructed by a careful balancing of execution and communication costs at the level of individual instructions, and their data dependencies. Three methods are used to evaluate our approach. First, several existing methods are extended to the fine grained situation. Our approach is then compared to these methods using both static schedule length analyses, and simulated executions of the scheduled code. In each instance, our method is found to provide significantly shorter schedules. Second, by varying parameters such as the speed of the instruction set, and the speed/parallelism in the interconnection structure, simulation techniques are used to examine the effects of various architectural considerations on the executions of the schedules. These results show that our approach provides significant speedups in a wide-range of situations. Third, schedules produced by our approach are executed on a two-processor Data General shared memory multiprocessor system. These experiments show that there is a strong correlation between our simulation results, and these actual executions, and thereby serve to validate the simulation studies. Together, our results establish that fine grained parallelism can be exploited in a substantial manner when scheduling a sequential instruction stream for execution “in parallel” on asynchronous multiprocessors 相似文献
9.
JC Posnick MD Wells JM Drake JR Buncic D Armstrong 《Canadian Metallurgical Quarterly》1993,19(5):260-266
Fibrous dysplasia is an abnormal fibroosseous process of bone of unknown cause. The incidence of skull involvement varies, painless enlargement being the most common presenting symptom. Change in vision is a rare but recognized finding. We report a 3-year-old boy with extreme fibrous dysplasia involving the skull base, who presented with blindness. He underwent exposure osteotomies of the frontal bones and orbits to provide access for skull base tumor removal. The orbital roofs were reconstructed with microplate-fixed cranial grafts. One and one half years after tumor excision followed by immediate reconstruction, the boy retains facial symmetry, and his ocular function has not deteriorated. 相似文献
10.
The aim of this study was to compare the sensitivities of commercial monoclonal antibody pools to be used as an initial rapid screen for detection of viral antigens in respiratory secretions. The availability of commercial monoclonal antibodies has dramatically improved the detection of viruses by immunofluorescence techniques in exfoliated cells obtained from respiratory secretions. Several companies have recently introduced monoclonal antibody pools to detect the presence of respiratory viruses in a single preparation. Ninety-four stored slide preparations that had previously been examined by individual monoclonal antibodies were tested using three commercial monoclonal antibody pools produced by Sanofi (UK), Dako (UK), and Quadratech (UK). These monoclonal antibody pools had a sensitivity of 79.6%, 90.9%, and 100%, respectively, when compared with the original results. The overall intensity of immunofluorescence was also examined. 相似文献