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排序方式: 共有92条查询结果,搜索用时 15 毫秒
1.
An IFN-beta-albumin fusion protein that displays improved pharmacokinetic and pharmacodynamic properties in nonhuman primates. 总被引:6,自引:0,他引:6
Cynthia Sung Bernardetta Nardelli David W LaFleur Erich Blatter Marta Corcoran Henrik S Olsen Charles E Birse Oxana K Pickeral Junli Zhang Devanshi Shah Gordon Moody Solange Gentz Lisa Beebe Paul A Moore 《Journal of interferon & cytokine research》2003,23(1):25-36
The long half-life and stability of human serum albumin (HSA) make it an attractive candidate for fusion to short-lived therapeutic proteins. Albuferon (Human Genome Sciences [HGS], Inc., Rockville, MD) beta is a novel recombinant protein derived from a gene fusion of interferon-beta (IFN-beta ) and HSA. In vitro, Albuferon beta displays antiviral and antiproliferative activities and triggers the IFN-stimulated response element (ISRE) signal transduction pathway. Array analysis of 5694 independent genes in Daudi-treated cells revealed that Albuferon beta and IFN-beta induce the expression of an identical set of 30 genes, including 9 previously not identified. In rhesus monkeys administered a dose of 50 microg/kg intravenously (i.v.) or subcutaneously (s.c.) or 300 microg/kg s.c., Albuferon beta demonstrated favorable pharmacokinetic properties. Subcutaneous bioavailability was 87%, plasma clearance at 4.7-5.7 ml/h/kg was approximately 140-fold lower than that of IFN-beta, and the terminal half-life was 36-40 h compared with 8 h for IFN-beta. Importantly, Albuferon beta induced sustained increases in serum neopterin levels and 2',5' mRNA expression. At a molar dose equivalent to one-half the dose of IFN-beta, Albuferon beta elicited comparable neopterin responses and significantly higher 2',5'-OAS mRNA levels in rhesus monkeys. The enhanced in vivo pharmacologic properties of IFN-beta when fused to serum albumin suggest a clinical opportunity for improved IFN-beta therapy. 相似文献
2.
Marni LaFleur Kim E. Reuter Michael B. Hall Hoby H. Rasoanaivo Stuart McKernan Paulo Ranaivomanana Anita Michel Marie Sylvianne Rabodoarivelo Zamin Iqbal Niaina Rakotosamimanana Simon Grandjean Lapierre 《Emerging infectious diseases》2021,27(3):977
We diagnosed tuberculosis in an illegally wild-captured pet ring-tailed lemur manifesting lethargy, anorexia, and cervical lymphadenopathy. Whole-genome sequencing confirmed the Mycobacterium tuberculosis isolate belonged to lineage 3 and harbored streptomycin resistance. We recommend reverse zoonosis prevention and determination of whether lemurs are able to maintain M. tuberculosis infection. 相似文献
3.
This article describes the methods used to complete a recent community health needs assessment study in a rural area. It illustrates the strategic marketing and management value of conducting this type of assessment by examining selected results from the study and discussing their implications for the local health care delivery system. 相似文献
4.
More than 75% of the female respondents in this study would choose a women's health center (WHC) over a standard health facility. Women who worked outside the home perceived a greater WHC need. And almost all respondents were interested in communications from the center via a quarterly newsletter. Significant test results related to age, income, education, and work status as segmentation variables, offering WHC's an opportunity to target their patients with specialized services such as cosmetic surgery, infertility treatment, breast imaging, etc. If enough resources are allocated, a WHC can design itself to attract highly lucrative patients. Little difference was found in the opinions of women regarding the need for a WHC or the core services desired, but the specific service mix decision must be carefully considered when designing a WHC. 相似文献
5.
Mace L Rothenberg Bonnie LaFleur Donna E Levy Mary Kay Washington Sherry L Morgan-Meadows Ramesh K Ramanathan Jordan D Berlin Al B Benson Robert J Coffey 《Journal of clinical oncology》2005,23(36):9265-9274
PURPOSE: The clinical objective of this trial was to evaluate gefitinib in patients with metastatic colorectal cancer that had progressed despite prior treatment. Serial tumor biopsies were performed when possible and analyzed for activation of the epidermal growth factor receptor (EGFR) signaling pathway. Serial serum samples were measured for amphiregulin and transforming growth factor-alpha (TGFalpha). PATIENTS AND METHODS: One hundred fifteen patients were randomly assigned to receive gefitinib 250 or 500 mg orally once a day. One hundred ten patients were assessable for clinical efficacy. Biologic evaluation was performed on paired tumor samples from 28 patients and correlated with clinical outcome. RESULTS: Median progression-free survival was 1.9 months (95% CI, 1.8 to 2.1 months) and 4-month progression-free survival rate was 13% +/- 5%. One patient achieved a radiographic partial response (RR = 1%; 95% CI, 0.01% to 5%). Median survival was 6.3 months (95% CI, 5.1 to 8.2 months). The most common adverse events were skin rash, diarrhea, and fatigue. In the biopsy cohort, expression of total or activated EGFR, activated Akt, activated MAP-kinase, or Ki67 did not decrease following 1 week of gefitinib. However, a trend toward decreased post-treatment levels of activated Akt and Ki67 was observed in patients with a PFS higher than the median, although these did not reach the .05 level of significance. CONCLUSION: Gefitinib is inactive as a single agent in patients with previously treated colorectal cancer. In tumor samples, gefitinib did not inhibit activation of its proximal target, EGFR. Trends were observed for inhibition of downstream regulators of cellular survival and proliferation in patients achieving longer progression-free survival. 相似文献
6.
Frank Xiaoqing Liu Arshia Ghaffari Harman Dhatt Vijay Kumar Cristina Balsera Eric Wallace Quresh Khairullah Beth Lesher Xin Gao Heather Henderson Paula LaFleur Edna M. Delgado Melissa M. Alvarez Janett Hartley Marilyn McClernon Surrey Walton Steven Guest 《Medicine》2014,93(28)
Patients presenting late in the course of kidney disease who require urgent initiation of dialysis have traditionally received temporary vascular catheters followed by hemodialysis. Recent changes in Medicare payment policy for dialysis in the USA incentivized the use of peritoneal dialysis (PD). Consequently, the use of more expeditious PD for late-presenting patients (urgent-start PD) has received new attention. Urgent-start PD has been shown to be safe and effective, and offers a mechanism for increasing PD utilization. However, there has been no assessment of the dialysis-related costs over the first 90 days of care.The objective of this study was to characterize the costs associated with urgent-start PD, urgent-start hemodialysis (HD), or a dual approach (urgent-start HD followed by urgent-start PD) over the first 90 days of treatment from a provider perspective.A survey of practitioners from 5 clinics known to use urgent-start PD was conducted to provide inputs for a cost model representing typical patients. Model inputs were obtained from the survey, literature review, and available cost data. Sensitivity analyses were also conducted.The estimated per patient cost over the first 90 days for urgent-start PD was $16,398. Dialysis access represented 15% of total costs, dialysis services 48%, and initial hospitalization 37%. For urgent-start HD, total per patient costs were $19,352, and dialysis access accounted for 27%, dialysis services 42%, and initial hospitalization 31%. The estimated cost for dual patients was $19,400.Urgent-start PD may offer a cost saving approach for the initiation of dialysis in eligible patients requiring an urgent-start to dialysis. 相似文献
7.
Successful pharmacotherapy requires patient compliance with the therapeutic regimen. The rate of non-compliance has been reported to be as low as 15% in some studies and the costs of non-compliance have been estimated to be between $396 and 792 million. Compliance, adherence, and persistence are defined. Subjective and objective methods used to measure compliance are reviewed. Subjective methods include patient self-reporting and physician estimates; these methods are generally inexpensive but have been shown to be unreliable. Objective methods include pill counting, electronic monitoring devices, and data reviews; these methods vary in cost and reliability. 相似文献
8.
The field of health outcomes research has increased the utilization of health-related quality-of-life (HRQoL) instruments to document economic, clinical, and humanistic outcomes (ECHO). The Medical Outcomes Study Short Form 36-item Questionnaire (MOSSF-36, SF-36) has been utilized extensively in many disease states for this purpose, although it is not validated for use in chronic pain patients. The Total Outcomes of Pain Survey (TOPS) incorporates all the domains of the SF-36, and includes additional domains relevant in the management of chronic pain patients. The TOPS is well validated in these patients. In addition to its utility as an outcomes research tool, the TOPS is sensitive enough to document clinical changes in individual patients, making it a useful assessment tool for clinicians. 相似文献
9.
Deane NG Lee H Hamaamen J Ruley A Washington MK LaFleur B Thorgeirsson SS Price R Beauchamp RD 《Cancer research》2004,64(4):1315-1322
Transgenic mice that overexpress cyclin D1 protein in the liver develop liver carcinomas with high penetrance. Transforming growth factor beta (TGF-beta) serves as either an epithelial cell growth inhibitor or a tumor promoter, depending on the cellular context. We interbred LFABP-cyclin D1 and Alb-TGF-beta1 transgenic mice to produce cyclin D1/TGF-beta1 double transgenic mice and followed the development of liver tumors over time, characterizing cellular and molecular changes, tumor incidence, tumor burden, and tumor physiology noninvasively by magnetic resonance imaging. Compared with age-matched LFABP-cyclin D1 single transgenic littermates, cyclin D1/TGF-beta1 mice exhibited a significant increase in tumor incidence. Tumor multiplicity, tumor burden, and tumor heterogeneity were higher in cyclin D1/TGF-beta1 mice compared with single transgenic littermates. Characteristics of cyclin D1/TGF-beta1 livers correlated with a marked induction of the peripheral periductal oval cell/stem cell compartment of the liver. A number of cancerous lesions from cyclin D1/TGF-beta1 mice exhibited unique features such as ductal plate malformations and hemorrhagic nodules. Some lesions were contiguous with the severely diseased background liver and, in some cases, replaced the normal architecture of the entire organ. Cyclin D1/TGF-beta1 lesions, in particular, were associated with malignant features such as areas of vascular invasion by hepatocytes and heterogeneous hyperintensity of signal on T2-weighted magnetic resonance imaging. These findings demonstrate that TGF-beta1 promotes stem cell activation and tumor progression in the context of cyclin D1 overexpression in the liver. 相似文献
10.