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排序方式: 共有207条查询结果,搜索用时 15 毫秒
201.
C. Giuliano F. Fiore A. Di Marco J. Padron Velazquez A. Bishop F. Bonelli 《Xenobiotica; the fate of foreign compounds in biological systems》2013,43(10-11):1035-1054
The disposition of compound A, a potent inhibitor of the hepatitis C virus (HCV) NS5B polymerase, was characterized in animals in support of its selection for further development. Compound A exhibited marked species differences in pharmacokinetics. Plasma clearance was 44?ml?min?1?kg?1 in rats, 9?ml?min?1?kg?1 in dogs and 16?ml?min?1?kg?1 in rhesus monkeys. Oral bioavailability was low in rats (10%) but significantly higher in dogs (52%) and monkeys (26%). Compound A was eliminated primarily by metabolism in rats, with biliary excretion accounting for 30% of its clearance. Metabolism was mainly mediated by cyclohexyl hydroxylation, with N-deethylation and acyl glucuronide formation constituting minor metabolic pathways. Qualitatively, the same metabolites were identified using in vitro systems from all species studied, including humans. The low oral bioavailability of compound A in rats was mostly due to poor intestinal absorption. This conclusion was borne out by the findings that hepatic extraction in the rat was only 30%, intraperitoneal bioavailability was good, and compound A was poorly absorbed from the rat isolated intestinal loop, with no detectable intestinal metabolism. Compound A was not an inhibitor of major human cytochrome P450 enzymes, indicating minimal potential for clinical drug–drug interactions. The metabolic clearance of compound A in rat, dog and monkey hepatocytes correlated with the systemic clearance observed in these species. Since compound A was very stable in human hepatocytes, the results suggest that it will be a low clearance drug in humans. 相似文献
202.
B. Simon V. Treat C. Marco D. Rosenberg J. Joseph B. Hipszer Y. Li I. Chervoneva L. Padron‐Massara S. Jabbour 《International journal of clinical practice》2008,62(12):1858-1863
Objective: To evaluate and compare glucose variability, hypoglycaemic events and daily glycaemic control in well‐controlled (HbA1c ≤ 7%), type 1 diabetic patients treated with either continuous subcutaneous insulin infusion (CSII) using lispro or multiple daily insulin injection (MDI) using glargine once daily and lispro with meals. Research design and methods: A total of 16 patients with type 1 diabetes receiving treatment with either CSII (eight patients) or MDI (eight patients), all with HbA1c levels < 7%, wore a continuous glucose monitoring system sensor for 3 days to compare the number, duration, timing and severity of hyperglycaemic and hypoglycaemic episodes. Results: There were several more episodes of hyperglycaemic [blood glucose (BG) ≥ 180 mg/dl] and hypoglycaemic (BG ≤ 60 mg/dl) excursions observed in patients treated with CSII than MDI. Glycaemic exposure over 150 mg/dl was similar between the two groups. Maintenance of near‐euglycaemia as determined by the average amount of time spent within the glucose range of 80–140 mg/dl was marginally significantly better for the MDI than for the CSII group. Although the CSII group had significantly more hypoglycaemic episodes below 60 mg/dl, the average duration of hypoglycaemia was not significantly different for the two groups. Similar percentages of nocturnal hypoglycaemia were seen. There were no reported major adverse events throughout the duration of the study. Conclusion: Well‐controlled type 1 diabetic patients treated with MDI had fewer hyperglycaemic and hypoglycaemic excursions than patients treated with CSII. 相似文献
203.
Kristoffer NT M?nsson Erica Skagius Ruiz Elisabet Gervind Mats Dahlin Gerhard Andersson 《Journal of medical Internet research》2013,15(12)
Background
Evidence-based psychological treatments, such as cognitive behavior therapy (CBT), have been found to be effective in treating several anxiety and mood disorders. Nevertheless, issues regarding adherence are common, such as poor patient compliance on homework assignments and therapists’ drifting from strictly evidence-based CBT. The development of Internet-delivered CBT (ICBT) has been intensive in the past decade and results show that guided ICBT can be as effective as face-to-face CBT but also indicate a need to integrate the two forms of CBT delivery.Objective
In this study, we developed and tested a new treatment format in which ICBT and face-to-face therapy were blended. We designed a support system accessible via the Internet (using a computer or an Apple iPad) for patients and therapists delivering CBT face-to-face. The support system included basic CBT components and a library of interventions gathered from existing ICBT manuals.Methods
The study involved 15 patients with mild to moderate anxiety or depression (or both). Eight therapists conducted the treatments. All participants were interviewed after the nine-week intervention. Further, patients provided self-reports on clinical measures pre- and post-trial, as well as at a 12-month follow-up.Results
A reduction was found in symptom scores across all measures. The reliable change index ranged from 60% to 87% for depression and anxiety. Large effect sizes (Cohen’s d) ranging from 1.62 (CI 95% 0.59-2.66) to 2.43 (CI 95% 1.12-3.74) were found. There were no missing data and no treatment dropouts. In addition, the results had been maintained at the 12-month follow-up. Qualitative interviews revealed that the users perceived the support system as beneficial.Conclusions
The results suggest that modern information technology can effectively blend with face-to-face treatments and be used to facilitate communication and structure in therapy, thus reducing therapist drift. 相似文献204.
Rami S. Komrokji Maria Corrales‐Yepez Mohamed A. Kharfan‐Dabaja Najla H. Al Ali Eric Padron Dana E. Rollison Javier Pinilla‐Ibarz Ling Zhang Pearlie K. Epling‐Burnette Jeffrey E. Lancet Alan F. List 《American journal of hematology》2012,87(11):1006-1009
We hypothesized that hypoalbuminemia is an independent prognostic factor in patients with myelodysplastic syndromes (MDS). We analyzed records of 767 patients treated at Moffitt Cancer Center between January 2001 and December 2009 to evaluate the relationship between serum albumin (SA) at the time of presentation and overall survival (OS). Patients (median age of 69 years) were stratified into three groups based on SA concentration (≤3.5, 3.6–4.0, and >4.0 g/dL). Two‐thirds of the patients had low or intermediate‐1 International Prognostic Scoring System (IPSS)‐based risk for MDS. Median OS by SA concentration of ≤3.5, 3.6–4.0, and >4.0 g/dL was 11, 23, and 34 months, respectively (P < 0.005), whereas rate of acute myeloid leukemia progression was highest in patients with low SA (≤3.5 g/dL). The SA level offered prognostic discrimination for outcomes within the lower and higher IPSS risk groups, as well as with the MD Anderson risk model. In multivariable analysis, SA was a significant independent co‐variate for OS after adjustment for IPSS, age, serum ferritin, and transfusion dependence (hazard ratio = 0.8; 95% CI 0.6–0.9; P = 0.004). Our findings indicate that hypoalbuminemia is an independent prognostic biomarker that may serve as a surrogate representative of disease biology or comorbidities in patients with MDS. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc. 相似文献
205.
Dental sleep medicine is a rapidly growing field that is in close and direct interaction with sleep medicine and comprises many aspects of human health. As a result, dentists who encounter sleep health and sleep disorders may work with clinicians from many other disciplines and specialties. The main sleep and oral health issues that are covered in this review are obstructive sleep apnea, chronic mouth breathing, sleep‐related gastroesophageal reflux, and sleep bruxism. In addition, edentulism and its impact on sleep disorders are discussed. Improving sleep quality and sleep characteristics, oral health, and oral function involves both pathophysiology and disease management. The multiple interactions between oral health and sleep underscore the need for an interdisciplinary clinical team to manage oral health‐related sleep disorders that are commonly seen in dental practice. 相似文献
206.
207.
CE Beyer Q Lin B Platt J Malberg G Hornby KM Sullivan DL Smith T Lock PJ Mitchell NT Hatzenbuhler DA Evrard BL Harrison R Magolda MN Pangalos LE Schechter S Rosenzweig-Lipson TH Andree 《British journal of pharmacology》2009,157(2):307-319