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排序方式: 共有911条查询结果,搜索用时 437 毫秒
41.
Christophe Tistaert Tycho Heimbach Binfeng Xia Neil Parrott Tanay S. Samant Filippos Kesisoglou 《Journal of pharmaceutical sciences》2019,108(1):592-602
Food can alter the absorption of orally administered drugs. Biopharmaceutics physiologically based pharmacokinetic (PBPK) modeling offers the possibility to simulate a compound's pharmacokinetics under fasted or fed states. To advance the utility of PBPK modeling, with a view to regulatory impact, we have pooled our experience across 4 pharmaceutical companies to propose a general multistep PBPK workflow leveraging pre-existing clinical data for immediate-release formulations of Biopharmaceutics Classification System I and II compounds. With this strategy, we wish to promote pragmatic PBPK approaches for compounds where absorption is well understood, that is, compounds with moderate-to-high permeability that are not substrates for uptake transporters. Five case studies demonstrate how food effect can be well predicted using appropriately established and validated models. The case studies integrate solubility and dissolution data for initial model development and apply a “middle-out” validation with clinical data in one prandial state. Then, whenever possible, a validation against both fasted and fed state data is recommended before application of the models prospectively for to-be-marketed formulations. Thus, when combined with limited clinical data, PBPK models could be used to simulate outcomes for new doses, formulations, or active pharmaceutical ingredient forms, in lieu of a clinical food-effect study. 相似文献
42.
Ashley Parrott Rachel Lombardo Nicole Brown Justin T. Tretter Laura Riley Kathryn Nicole Weaver 《American journal of medical genetics. Part A》2020,182(5):1243-1248
Cantu syndrome is a rare autosomal dominant disorder caused by missense variants in ABCC9 and KCNJ8. It is characterized by hypertrichosis, neonatal macrosomia, coarse facial features, and skeletal anomalies. Reported cardiovascular anomalies include cardiomegaly, structural defects, collateral vessels, and rare report of arteriovenous malformation (AVM). Arterial dilation is reported in a few individuals including one with surgical intervention for a thoracic aortic aneurysm. The natural history of this aortopathy including the rate of progression or risk for dissection is unknown and longitudinal patient data is unavailable. We present data from vascular imaging in three individuals with genetically confirmed Cantu syndrome over 3 to 14 years of follow‐up. All patients had generally stable aortic dilation, which did not reach the surgical threshold, including one individual followed closely through pregnancy. In adulthood, one individual had a maximum ascending aortic measurement of 4.2 cm. Two pediatric patients had aortic root or ascending z‐scores of approximately +3. A large asymptomatic pelvic AVM was identified in one individual on head‐pelvis MRI. While the data reported in these individuals is reassuring regarding the risk for progressive disease, further data from additional individuals with Cantu syndrome is needed to best inform screening recommendations, improve understanding of dissection risk, and guide management. 相似文献
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46.
Mary J. Naus Marilyn D. Ishler Charlotte E. Parrott Stephanie A. Kovacs 《Journal of clinical psychology》2009,65(12):1350-1359
A model of cancer as a chronic illness is proposed as a new direction for quality of life research. In the cancer survivor adaptation (CSA) model, adjustment to cancer survivorship is a life-long process involving three interacting components. Personal context incorporates cancer survivorship and personal characteristics across biological, psychological, and social domains. The adaptation process involves a specific cognitive mechanism of change, where the ongoing appraisal of goals and world assumptions occur in the context of the cancer survivor's personal memories and sense of self. Finally, quality of life outcomes are viewed as multidimensional and personally weighted for importance, with expectations for both positive and negative physical, emotional, cognitive, and spiritual adjustments over time. Research and clinical implications are explored. © 2009 Wiley Periodicals, Inc. J Clin Psychol 65: 1–10, 2009. 相似文献
47.
Carol S Weisman Marianne M Hillemeier Gary A Chase Dawn P Misra Cynthia H Chuang Roxanne Parrott Anne-Marie Dyer 《Women's health issues》2008,18(1):17-25
PURPOSE: This study examines nonpregnant women's beliefs about whether or not they can influence their future birth outcomes with respect to the baby's health and factors associated with internal locus of control for birth outcomes. Perceived internal control of birth outcomes could be a predisposing factor for use of preconception care, which is recommended for all women of childbearing age by the Centers for Disease Control and Prevention. The overall hypothesis is that internal control of birth outcomes is a function of prior pregnancy experiences, current health status and stress levels, access to health care, and sociodemographics. METHODS: Data are from the Central Pennsylvania Women's Health Study random digit dial telephone survey of 2,002 women ages 18-45; the analytic sample is 614 nonpregnant women with current reproductive capacity who reported that they are considering a future pregnancy. Internal control of birth outcomes is measured using 1) a 4-item Internal Control of Birth Outcomes Scale, 2) a single-item measure of Preconceptional Control, and 3) a score reflecting high internal control on both of these measures. FINDINGS: In multiple logistic regression analyses, internal control of birth outcomes is positively associated with older age (35-45 vs. 18-34 years), higher education (some college or more), marital status (currently married or living with a partner), and higher self-rated physical health status on the SF-12v2 (but not mental health status or psychosocial stress). Previous adverse pregnancy outcomes and current access to health care have no association with internal control for birth outcomes. CONCLUSION: Variables associated with internal control of birth outcomes among women contemplating a future pregnancy are primarily sociodemographic and physical health related. Educational and social marketing efforts to increase women's use of preconception care may be particularly important for women who are likely to have lower internal control, including younger, less educated, unmarried, and less healthy women. 相似文献
48.
Thymic function after hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency 总被引:21,自引:0,他引:21
Patel DD Gooding ME Parrott RE Curtis KM Haynes BF Buckley RH 《The New England journal of medicine》2000,342(18):1325-1332
BACKGROUND: Immune function can be restored in infants with severe combined immunodeficiency by transplantation of unfractionated bone marrow from HLA-identical donors or T-cell-depleted marrow stem cells from haploidentical donors, with whom there is a single haplotype mismatch, without the need for chemotherapy before transplantation or prophylaxis against graft-versus-host disease. The role of the thymus in this process is unknown. METHODS: We analyzed the phenotypes of circulating T cells and the proliferative responses of peripheral-blood mononuclear cells to phytohemagglutinin in 83 patients with severe combined immunodeficiency who received allogeneic marrow transplants without T-cell ablation from related donors over an 18-year period. We also tested for the presence of episomes of T-cell antigen receptors (extrachromosomal DNA circles formed during intrathymic T-cell development) to assess thymus-dependent T-cell reconstitution. RESULTS: Before and early after transplantation, the numbers of circulating T cells were low, with a predominance of mature CD45RO+ T cells (primarily resulting from the transplacental transfer of maternal cells); T-cell antigen-receptor episomes were undetectable in peripheral-blood mononuclear cells. In 73 of the infants, thymus-derived T cells expressing CD45RA and T-cell antigen-receptor episomes were detected within three to six weeks after transplantation. The mean (+/-SD) value for thymus-dependent T-cell antigen-receptor episomes peaked (at 7311+/-8652 per microgram of peripheral-blood mononuclear-cell DNA) 1 to 2 years after transplantation and declined to low levels (less than 100 episomes per microgram of DNA) within 14 years, as compared with a gradual decline from birth to the age of about 80 years in normal subjects. CONCLUSIONS: The vestigial thymus in infants with severe combined immunodeficiency is functional and can produce enough T cells after bone marrow transplantation to provide normal immune function. 相似文献
49.
Parrott J Boyd RN Dobson F Lancaster A Love S Oates J Wolfe R Nattrass GR Graham HK 《Journal of pediatric orthopedics》2002,22(5):660-667
Radiologic measures of migration percentage (MP) and acetabular index (AI) taken from plain radiographs of the pelvis are the most commonly used tools for determining hip displacement and management options in children with cerebral palsy and spastic hip disease. This study determined interrater and intrarater reliability of MP and AI on pelvic radiographs chosen to represent a wide range of age (11 months to 8 years 5 months), MP (0%-56%), and AI (9 degrees -33 degrees ). The study demonstrated that an experienced rater would be expected to measure MP on a single radiograph to within +/-5.8% of the true value and a change in MP between two radiographs taken at different times to within +/-8.3% of the true value. Similarly for AI, the measurement error for a typical rater would be within +/-2.6 degrees on a single reading and +/-3.7 degrees if recording change between two occasions. The authors believe that the results indicating true change are acceptable in clinical practice, provided treatment decisions are based on a series of radiographs taken at 6-month intervals, methods and training are standardized, and consistent raters are used. 相似文献
50.
BACKGROUND: Research has demonstrated that alcohol-related aggression is modulated by anger-based personality traits. However, it is unclear how anger, as a concomitant of aggression, is affected by an interaction among these variables. The present study evaluated the effects of alcohol, anger-based traits, and physical provocation on anger. METHODS: Participants were 136 male social drinkers who completed measures designed to assess trait anger and anger expression styles and were assigned to an alcohol or no-alcohol control beverage group. Participants engaged in a competitive reaction time task in which electric shocks were received from a fictitious opponent. Participants' experience of anger was assessed unobtrusively via the Facial Action Coding System. RESULTS: Intoxicated participants displayed more facial expressions of anger than sober participants. Interactive effects between anger expression styles and beverage group also were detected in that, among intoxicated participants, a positive relationship between facial expressions of anger and the tendency to express anger outwardly was found after high, but not low, provocation. This relationship was not observed at either provocation level in the no-alcohol control group. Similarly, whereas participants' tendency to control anger resulted in fewer facial expressions of anger by intoxicated participants, no such relationship was found among sober participants. CONCLUSIONS: Findings suggest that alcohol intoxication facilitates the experience of anger after provocation and enhances the relationship between state anger and behavioral tendencies to control anger expression. 相似文献