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排序方式: 共有172条查询结果,搜索用时 15 毫秒
1.
K Stubbs LA Martin DC Dimmitt N Pready WF Hahne 《Canadian Metallurgical Quarterly》1997,37(10):926-936
In previous studies, dolasetron was shown to have both renal and hepatic elimination mechanisms. This study was conducted to determine the impact of varying degrees of hepatic dysfunction on the pharmacokinetics and safety of dolasetron and its reduced metabolites. Seventeen adults were studied: six healthy volunteers (group I), seven patients with mild hepatic impairment (Child-Pugh class A; group II), and four patients with moderate to severe hepatic impairment (Child-Pugh class B or C1; group III). Single 150-mg doses of dolasetron mesylate were administered intravenously and orally, with a 7-day washout period separating treatments. After intravenous administration, no differences were observed between healthy volunteers and patients with hepatic impairment in maximum plasma concentration (Cmax), areas under the plasma concentration-time curve (AUC), or elimination half-life (t1/2) of intact dolasetron. No significant differences were found in Cmax, AUC, or apparent clearance (C(lapp)) of hydrodolasetron, the primary metabolite of dolasetron. The mean t1/2 increased from 6.87 hours in group I to 11.69 hours in group III. After oral administration, C(lapp) of hydrodolasetron decreased by 42%, and Cmax increased by 18% in patients with moderate to severe hepatic impairment. There were less changes in patients with mildly hepatic impairment. Total percentage of dose excreted as metabolites was similar for healthy volunteers and patients with hepatic impairment, although urinary metabolite profiles differed slightly. Dolasetron was well tolerated and there were no apparent differences in adverse effects between groups or treatments. Because hepatic impairment did not influence Cl(app) of hydrodolasetron after intravenous administration, and the range of plasma concentrations of hydrodolasetron after oral administration was not different from those observed in healthy volunteers, dosage adjustments are not recommended for patients with hepatic disease and normal renal function. 相似文献
2.
Platelet aggregation is known to be inhibited by ethanol, and this has been suggested to be one of the attenuating effects
of ethanol in cardiovascular disease. Recent studies have implicated an inhibition of phospholipase A2 induced arachidonic acid release, since the production of prostanoids that are formed from arachidonic acid and are involved
in the aggregation process has been shown to be diminished by ethanol. Phospholipase A2 is found in platelets in both a cytosolic form, from where it may translocate to the plasma membrane to release arachidonic
acid, and in a secretory form which is released extracellularly upon activition. In the present study, the effect of ethanol
on the secretion of phospholipase A2 and on its activity was determined. It was found that ethanol inhibited trast, the activity of the cytosolic form of phospholipase
A2 was inhibited by ethanol. 相似文献
3.
Excision of perianal fistulas using a 1.064 micron wavelength neodymium:yttrium aluminum garnet (ND:YAG) contact tipped laser with primary wound closure was used to treat 20 dogs with perianal fistulas. Overall, 19 of 20 (95%) dogs had resolution of fistulas after one or more ND:YAG treatments. The period of resolution ranged from 10 to 42 months with a mean of 22.9 months. Sixteen of 20 (80%) dogs had resolved fistulas after one laser excision. Three of the four recurrences underwent additional laser treatments with successful results. The total number of laser procedures ranged from one to three with a mean of 1.2 procedures. Postoperatively, anal tone as judged by digital rectal examination was reduced in about 60% of the cases, but clinical evidence of fecal incontinence only occurred in four of 20 cases. This was managed effectively with diet modification. The tendency toward loss of anal tone or fecal incontinence depended on the severity of preexisting anal stenosis. On a client survey, 19 of 20 owners believed that their animals experienced less pain during defecation after surgery and rated the results as excellent or good. The overall success rate using ND:YAG laser excision compared very favorably with previously reported studies of other methods of treatment for perianal fistulas in dogs. 相似文献
4.
A novel miniature multilayer MMIC CPW single side band CPW mixer for up conversion at 44.5 GHz 总被引:1,自引:0,他引:1
Hettak K. Morin G.A. Stubbs M.G. 《Microwave and Wireless Components Letters, IEEE》2005,15(9):606-608
This letter presents the results of a novel miniature single sideband (SSB) subharmonic direct upconverter GaAs MMIC developed in multilayer coplanar waveguide. The mixer uses 50 MHz I and Q signals to directly modulate the second harmonic of a 22.25 GHz carrier, producing the required 44.55 GHz RF output. Two pairs of antiparallel diodes reduce feedthrough of the fundamental 22.25 GHz signal to the RF output while novel coplanar waveguide/asymmetric coplanar stripline, centre conductor based structures provide matching. This 1.7/spl times/1.7 mm/sup 2/ chip also uses a previously developed, reduced size Wilkinson divider based on asymmetric coplanar stripline and a reduced size three-dimensional 90/spl deg/ coupler. 相似文献
5.
P Stubbs M Seed D Lane P Collinson F Kendall M Noble 《Canadian Metallurgical Quarterly》1998,19(9):1355-1364
AIMS: Raised lipoprotein(a) concentrations are considered to be a risk factor for atherothrombotic diseases. We examined whether baseline concentrations were a risk factor for an adverse outcome in patients admitted with acute coronary syndromes. METHODS AND RESULTS: Five hundred and nineteen patients admitted with suspected acute coronary syndromes were studied and followed prospectively for a median of 3 years. The prognostic significance of a baseline lipoprotein(a) concentration of > or = 30 mg x dl(-1) or lower for subsequent cardiac death was assessed in patients with myocardial infarction (266) and unstable angina (197) and compared with other variables in regression models. In patients with myocardial infarction, a baseline lipoprotein(a) concentration of > or =30 mg x dl(-1) was associated with a 62% increase in subsequent cardiac death compared to the lower concentration group (29.8% vs 18.6%, Log rank P=0.04). In a multivariate regression model a baseline lipoprotein(a) concentration of > or = 30 mg x dl(-1) retained its significance as an independent predictor of cardiac death (P=0.037). In patients with unstable angina, baseline concentrations of > or = 7.9 mg x dl(-1) were found to be significant predictors of cardiac death in univariate (P=0.021) and multivariate (P=0.035) regression models. CONCLUSION: Baseline lipoprotein(a) concentrations in patients admitted with acute coronary syndromes are associated with an increased risk of cardiac death. For patients with myocardial infarction a concentration of > or = 30 mg x dl(-1) appears appropriate as a risk discriminator; for patients admitted with unstable angina, however, much lower concentrations of lipoprotein(a) appear to be prognostically important. 相似文献
6.
OBJECTIVE: To test whether isoenergetic isoenergetically-dense doses of dietary 1-monoglyceride or triglyceride differentially influence appetite and meal-to-meal energy intake in man. DESIGN: Six men and six women were each studied twice in a 2 d protocol. On day 1 (maintenance day) they were fed a medium fat (MF) maintenance diet (MF: 40% fat, 47% carbohydrate and 13% protein by energy) calculated at 1.6 x resting metabolic rate (RMR). On day 2 (manipulation day) at 08.30 h subjects consumed a high-fat breakfast designed to contain 80-85% of RMR, composition 10% protein, 56% fat and 34% carbohydrate by energy, with 65% of energy for fat derived as either 1-monoglyceride or triglyceride. Food and energy intake were monitored at lunch (given at 12.30pm) and throughout the remainder of the day. During this time subjects had ad libitum access to isoenergetic, isoenergetically dense MF (40:47:13) foods (550kJ/100g), until 22.30pm). Subjective hunger and satiety were tracked hourly, during waking hours. RESULTS: There was no significant effect of fat type on food or energy intake at lunch or during the ad libitum period. There was no diet effect on subjective hunger (F(1,10)0.00; P= 0.975) in the inter-meal periods of morning or afternoon, nor during the whole day. Subjects found both diets to be similarly pleasant (F(1,61)0.84;P= 0.364). Men and women responded similarly, except that men ate more on all occasions than women. CONCLUSIONS: This study suggests that when a large dose of l-monoglyceride or triglyceride is incorporated into a breakfast meal, it behaves in a manner that is very similar to triglyceride in terms of the effects on hunger, appetite or feeding behaviour. 相似文献
7.
Dr. Travis Coyle Dr. Liang Wu Dr. Aleksandra W. Debowski Prof. Gideon J. Davies Dr. Keith A. Stubbs 《Chembiochem : a European journal of chemical biology》2019,20(11):1365-1368
The sugar fucose plays a myriad of roles in biological recognition. Enzymes hydrolyzing fucose from glycoconjugates, α-l -fucosidases, are important targets for inhibitor and probe development. Here we describe the synthesis and evaluation of novel α-l -fucosidase inhibitors, with X-ray crystallographic analysis using an α-l -fucosidase from Bacteroides thetaiotamicron helping to lay a foundation for future development of inhibitors for this important enzyme class. 相似文献
8.
The objective of this study was to elucidate the role of hydroxyvalerate (HV) composition in polyhydroxy butyrate valerate (PHBV) copolymer film on the degradation of copolymer and osteoblastic cell activity. Degradation was studied by monitoring time‐dependent changes in mass and chemical composition of the macroporous films. The mass loss of PHBV film upon 19 weeks of exposure to pH 7.4 phosphate buffer medium was found to range from 2.8% to 9.2% with a strong dependence on the original composition of the copolyester film and morphology. Tapping mode atomic force microscopy (TMAFM) was used to examine the roughness change of polyester films due to exposure to buffer medium. Chemical analysis of the degraded film was carried out using NMR to aid in the interpretation of the mass loss and TMAFM data. The NMR results showed a significant decrease in the mol % of HV content in the degraded PHBV film. Additionally, we established that UMR‐106 cell proliferation on macroporous PHBV matrix is minimally enhanced by the HV content of PHBV copolymer. Information provided by this study can be used in the selection of appropriate PHBV copolymer for clinical use where the biopolymer needs to remain physically intact and chemically unchanged during the intended period of biomedical application. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 相似文献
10.
Contrary to common belief, back pain amongst young people is a frequent phenomenon. Epidemiological studies have found high prevalence rates of back pain amongst schoolchildren. The investigation reported here aims to validate children's self-reporting and the observation of sitting postures to establish the intensity, duration and frequency of exposure in the classroom. The sitting postures of 18 children were recorded using three methods, the portable ergonomic observation method (PEO), video analysis and self-report. The three methods were compared. PEO was significantly correlated with video analysis of the sitting postures after development of the method. Self-report was not significantly correlated with video analysis of the sitting postures. Therefore PEO was selected as the main observation tool in further analysis of children's sitting posture in schools in South-East England as part of a large research programme investigating back pain amongst schoolchildren. 相似文献