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排序方式: 共有367条查询结果,搜索用时 15 毫秒
1.
David G Witte Michael E Brune Sweta P Katwala Ivan Milicic Deanne Stolarik Yu-Hua Hui Kennan C Marsh James F Kerwin Michael D Meyer Arthur A Hancock 《The Journal of pharmacology and experimental therapeutics》2002,300(2):495-504
Fiduxosin is a new alpha(1)-adrenoceptor antagonist targeted for the treatment of symptomatic benign prostatic hyperplasia. The purpose of this study was to determine and compare the potencies of the alpha(1)-adrenoceptor antagonists terazosin, doxazosin, tamsulosin, and fiduxosin, based on relationships between plasma drug concentrations and blockade of phenylephrine (PE)-induced intraurethral (IUP) and mean arterial pressure (MAP) responses after single oral dosing in conscious male beagle dogs. Magnitude of blockade and plasma concentrations were evaluated at selected time points over 24 h. All drugs produced dose-dependent antagonism of PE-induced IUP and MAP responses. When IUP and MAP blockade effects were plotted against drug plasma concentrations, direct relationships were observed that were well described by the sigmoidal maximal effect model. IUP IC(50) values for terazosin, doxazosin, tamsulosin, and fiduxosin were 48.6, 48.7, 0.42, and 261 ng/ml, respectively. MAP IC(50) values were 12.2, 13.8, 1.07, and 1904 ng/ml, respectively. Uroselectivity index values, defined as MAP IC(50)/IUP IC(50), were 0.25, 0.28, 2.6, and 7.3, respectively. These results extend previous observations with terazosin in this model, showing that doxazosin exhibits a uroselectivity index comparable to terazosin, consistent with the lack of alpha(1)-adrenoceptor subtype selectivity or uroselectivity of these drugs. Tamsulosin, an alpha(1a)-/alpha(1d)-subtype selective agent, had an index value approximately 10-fold greater than the nonselective drugs. Based on its pharmacokinetic profile and a relative uroselectivity 29-fold greater than the nonselective drugs, fiduxosin is expected to exhibit greater selectivity for urethral compared with vascular alpha(1)-adrenoceptors in human and should be a novel, long-acting, uroselective alpha(1)-adrenoceptor antagonist. 相似文献
2.
Muda M He C Martini PG Ferraro T Layfield S Taylor D Chevrier C Schweickhardt R Kelton C Ryan PL Bathgate RA 《Molecular human reproduction》2005,11(8):591-600
LGR7 and LGR8 are G protein-coupled receptors that belong to the leucine-rich repeat-containing G-protein coupled receptor (LGR) family, including the thyroid-stimulating hormone (TSH), LH and FSH receptors. LGR7 and LGR8 stimulate cAMP production upon binding of the cognate ligands, relaxin and insulin-like peptide 3 (INSL3), respectively. We cloned several novel splice variants of both LGR7 and LGR8 and analysed the function of four variants. LGR7.1 is a truncated receptor, including only the N-terminal region of the receptor and two leucine rich repeats. In contrast, LGR7.2, LGR7.10 and LGR 8.1 all contain an intact seven transmembrane domain and most of the extracellular region, lacking only one or two exons in the ectodomain. Our analysis demonstrates that although LGR7.10 and LGR8.1 are expressed at the cell surface, LGR7.2 is predominantly retained within cells and LGR7.1 is partially secreted. mRNA expression analysis revealed that several variants are co-expressed in various tissues. None of these variants were able to stimulate cAMP production following relaxin or INSL3 treatment. Unexpectedly, we did not detect any direct specific relaxin or INSL3 binding on any of the splice variants. The large number of receptor splice variants identified suggests an unforeseen complexity in the physiology of this novel hormone-receptor system. 相似文献
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6.
Young MR Neville BW Chi AC Lathers DM Gillespie MB Day TA 《Clinical & experimental metastasis》2007,24(2):131-139
Patients with premalignant oral lesions have varying levels of risk of developing oral squamous cell carcinoma (OSCC), whose
aggressiveness requires increased motility. Not known is if and how premalignant oral lesion cells acquire the increased motility
characteristic of OSCC. This was addressed by immunohistochemical analysis of banked premalignant lesion tissues and by functional
analyses using cultures established from premalignant oral lesions and OSCC. These studies showed premalignant oral lesion
cells and OSCC to be more motile than normal keratinocytes. Concomitantly, levels of ceramide were reduced. The activity of
the protein phosphatase PP-2A, which restricts motility and which can be activated by ceramide, was also diminished. This
was due to IL-10 released from premalignant lesion cells. Treatment with a membrane-permeable ceramide restored PP-2A activity
and blocked migration. These studies show an autocrine motility-stimulatory pathway that is mediated in premalignant lesion
cells by IL-10 through its reduction of ceramide levels and inhibition of PP-2A activity. 相似文献
7.
Sleep Simone L. Skelly Deanne Love Robert M. George Roy 《Lasers in medical science》2022,37(3):1843-1853
Lasers in Medical Science - Dental pulp cells are a source of multipotent mesenchymal stem cells with a high proliferation rate and multilineage differentiation potential. This study investigated... 相似文献
8.
Claire E. Kelly Deanne K. Thompson Jian Chen Elisha K. Josev Leona Pascoe Megan M. Spencer‐Smith Chris Adamson Chiara Nosarti Susan Gathercole Gehan Roberts Katherine J. Lee Lex W. Doyle Marc L. Seal Peter J. Anderson 《Human brain mapping》2020,41(3):684-696
This study in children born extremely preterm (EP; <28 weeks’ gestational age) or extremely low birth weight (ELBW; <1,000 g) investigated whether adaptive working memory training using Cogmed® is associated with structural and/or functional brain changes compared with a placebo program. Ninety‐one EP/ELBW children were recruited at a mean (standard deviation) age of 7.8 (0.4) years. Children were randomly allocated to Cogmed or placebo (45‐min sessions, 5 days a week over 5–7 weeks). A subset had usable magnetic resonance imaging (MRI) data pretraining and 2 weeks posttraining (structural, n = 48; diffusion, n = 43; task‐based functional, n = 18). Statistical analyses examined whether cortical morphometry, white matter microstructure and blood oxygenation level‐dependent (BOLD) signal during an n‐back working memory task changed from pretraining to posttraining in the Cogmed and placebo groups separately. Interaction analyses between time point and group were then performed. There was a significant increase in neurite density in several white matter regions from pretraining to posttraining in both the Cogmed and placebo groups. BOLD signal in the posterior cingulate and precuneus cortices during the n‐back task increased from pretraining to posttraining in the Cogmed but not placebo group. Evidence for group‐by‐time interactions for the MRI measures was weak, suggesting that brain changes generally did not differ between Cogmed and placebo groups. Overall, while some structural and functional MRI changes between the pretraining and posttraining period in EP/ELBW children were observed, there was little evidence of training‐induced neuroplasticity, with changes generally identified in both groups. Trial registration Australian New Zealand Clinical Trials Registry, anzctr.org.au ; ACTRN12612000124831. 相似文献
9.
Geographic “cohorting,” “co-location,” “regionalization,” or “localization” refers to the assignation of a hospitalist team to a specific inpatient unit. Its benefits may be related to the formation of a team and the additional interventions like interdisciplinary rounding that the enhanced proximity facilitates. However, cohorting is often adopted in isolation of the bundled approach within which it has proven beneficial. Cohorting may also be associated with unintended consequences such as increased interruptions and increased indirect care time. Institutions may increase patient loads in anticipation of the efficiency gained by cohorting—leading to further increases in interruptions and time away from the bedside. Fragmented attention and increases in indirect care may lead to a perception of increased workload, errors, and burnout. As hospital medicine evolves, there are lessons to be learned by studying cohorting. Institutions and inpatient units should work in synergy to shape the day-to-day work which directly affects patient and clinician outcomes—and ultimately culminates in the success or failure of the parent organization. Such synergy can manifest in workflow design and metric selection. Attention to workloads and adopting the principles of continuous quality improvement are also crucial to developing models of care that deliver excellent care.Geographic “cohorting,” “co-location,” “regionalization,” or “localization” refers to the practice of assigning a hospitalist team to a specific inpatient unit with the expectation that the majority of the team’s patients will be on their assigned unit. The benefits are thought to be rooted in the enhanced physical proximity between clinicians, bedside nurses, patients, and the interprofessional team—with gains expected in efficiency, communication, collaboration, and patient centeredness.1,2 Pre-pandemic, cohorting was adopted by nearly a third of the non-teaching services of US hospital medicine groups surveyed.3 Cohorting is complex and like therapeutic decisions is associated with benefits, risks, and unintended consequences. Examining this complexity provides insights that may allow us to design better models of care.Each inpatient unit can be viewed as a clinical microsystem—the functional unit of the entire organization—the place where the work happens and where the outcomes that coalesce into the success or failure of the organization originate.4 Models of care utilizing bundled unit-based interventions to improve the care of hospitalized patients have demonstrated improvements in lengths of stay, costs of care, and mortality.5,6 In these models, cohorting was deployed alongside other mutually reinforcing interventions such as interdisciplinary rounding and leadership dyads, which become practical only when the proximity facilitated by cohorting and the creation of a team is assured. Yet, the adoption of unit-based interventions to improve care appears to be piece-meal across institutions with few deploying a bundled approach and many instituting cohorting alone.3A survey of hospitalists in the USA revealed that the strong positive perceptions of cohorting cluster around the benefits of collaboration with bedside nursing colleagues, improved nursing satisfaction, increased patient centeredness, and improved efficiency and team building. Strong negative perceptions were reported around increases in interruptions, erosion of group camaraderie, discontinuity in patient care, and issues related to implementation. Academic practices and longer durations of cohorting were associated with positive perceptions while higher patient loads were associated with negative perceptions.2 Studies investigating the impact of cohorting as a stand-alone intervention have shown some results supporting and others refuting these perceptions.The proportion of bedside nursing colleagues agreeing with the statement “I experience good collaboration with house staff” increased from 10 to 40% following the implementation of cohorting.7 More patients perceived that their physicians spent more than four minutes with them and discussed their anxiety and emotions following cohorting.7 Cohorting has also been associated with increases in the likelihood of repeated visits to a patient in a day and increased time spent on the unit.8Cohorting, however, is not a panacea—with the gains accompanied by downsides. Despite intending to foster patient-centered care, cohorting has not been associated with improvements in Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores and in some settings may be associated with increases in length of stay. 9–11 In a single-center time-motion study, cohorted hospitalists were interrupted as often as once every eight minutes—rates similar to those seen in Emergency Department settings—and were also noted to spend more time in computer interactions than their non-cohorted counterparts.8 These findings are consequential—interruptions erode attention, increase perceived workload, increase the risk of errors, and increase the time it takes to complete tasks.12 Tasks that detract from direct patient care contribute to burnout—rates of which have increased among hospitalists since the onset of the pandemic. 13 Fragmented attention can lead to bias and failure to recognize the declining trajectory of a patient.14 Interruptions, inattention, and their consequences are difficult to measure—with few studies in hospital medicine quantifying their burden and impact. With careful attention to design and implementation, cohorting may be successful in improving communication without increasing unnecessary interruptions—but such refinement requires close monitoring and continuous improvement which are often lacking in strained hospital medicine environments.Workload, communication, and outcomes are inexorably linked in hospital medicine. While cohorting may be associated with modest increases in the duration of each patient care encounter, these gains are fragile—and may be easily lost or reversed by increases in patient loads.8 The evidence also suggests that while cohorting increases shallow availability or “reachability” and the quantity of communication, it may not alone ensure deeper interpersonal communication or improve the quality of communication.14,15 Perversely, this increased reachability and decreased travel time may be used to rationalize increases in daily patient loads for cohorted teams. A focus on increasing productivity in turn may further increase interruptions, decreasing attention and impacting downstream outcomes that are not routinely monitored—such as the quality of communication, cognitive load, cognitive bias, diagnostic errors, and satisfaction with a job well done.“Every system is perfectly designed to get the results it gets”—and it is time to scrutinize the systems in which hospitalists work every day. The complexities of geographic cohorting we have examined provide insights that may allow us to design better models of care. We propose attention to the following principles (Fig. (Fig.11):
- Strengthening synergies between the clinical microsystem and the institution
- 2.Defining and standardizing measures of success to reflect shared priorities
- 3.Re-imagine and re-define optimal workload
- 4.Adopting a continuous quality improvement approach to drive improvements
10.
Uwe Koetter Marilyn Barrett Svenja Lacher Aliaa Abdelrahman Deanne Dolnick 《Journal of ethnopharmacology》2009