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排序方式: 共有737条查询结果,搜索用时 15 毫秒
41.
Hicks KO Myint H Patterson AV Pruijn FB Siim BG Patel K Wilson WR 《International journal of radiation oncology, biology, physics》2007,69(2):560-571
PURPOSE: To compare oxygen dependence and tissue transport properties of a new hypoxia-activated prodrug, PR-104A, with tirapazamine, and to evaluate the implications for antitumor activity when combined with radiotherapy. METHODS AND MATERIALS: Oxygen dependence of cytotoxicity was measured by clonogenic assay in SiHa cell suspensions. Tissue transport parameters were determined using SiHa multicellular layers. Spatially resolved pharmacokinetic (PK) and pharmacodynamic (PD) models were developed to predict cell killing in SiHa tumors and tested by clonogenic assay 18 h after treatment with the corresponding phosphate ester, PR-104. RESULTS: The K-value (oxygen concentration to halve cytotoxic potency) of PR-104A was 0.126 +/- 0.021 microM (10-fold lower than tirapazamine at 1.30 +/- 0.28 microM). The diffusion coefficient of PR-104A in multicellular layers (4.42 +/- 0.15 x 10(-7) cm2 s(-1)) was lower than that of tirapazamine (1.30 +/- 0.05 x 10(-6) cm2 s(-1)) but PK modeling predicted better penetration to hypoxic cells in tumors because of its slower metabolism. The tirapazamine PK/PD model successfully predicted the measured activity in combination with single-dose radiation against SiHa tumors, and the PR-104A model underpredicted the activity, which was greater for PR-104 than for tirapazamine (at equivalent host toxicity) both with radiation and as a single agent. CONCLUSION: PR-104/PR-104A has different PK/PD properties from tirapazamine and superior activity with single-dose radiotherapy against SiHa xenografts. We have inferred that PR-104A is better able to kill cells at intermediate partial pressure of oxygen in tumors than implied by the PK/PD model, most likely because of a bystander effect resulting from diffusion of its activated metabolites from severely hypoxic zones. 相似文献
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Lindegaard J Gerard JP Sun Myint A Myerson R Thomsen H Laurberg S 《Clinical oncology (Royal College of Radiologists (Great Britain))》2007,19(9):738-741
Although contact radiotherapy was developed 70 years ago, and is highly effective with cure rates of over 90% for early rectal cancer, there are few centres that offer this treatment today. One reason is the lack of replacement of ageing contact X-ray machines, many of which are now over 30 years old. To address this problem, the International Contact Radiotherapy Evaluation (ICONE) group was formed at a meeting in Liverpool in 2005 with the aim of developing a new contact X-ray unit and to establish clinical protocols that would enable the new machine to safely engage in the treatment of rectal cancer. As a result of these efforts, a European company is starting production of the new Papillon RT-50 machine, which will be available shortly. In addition, the ICONE group is planning an observational study on contact X-ray and transanal endoscopic microsurgery (CONTEM) for curative treatment of rectal cancer. This protocol will ensure standardised diagnostic procedures, patient selection and treatment in centres across the world and the data will be collected prospectively for analysis and audit. It is hoped that the CONTEM trial will provide the scientific evidence that is needed to obtain a broader acceptance of local contact radiotherapy as a treatment option for selected cases with early stage rectal cancer. 相似文献
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Pharmacokinetics of Mefloquine Combined with Artesunate in Children with Acute Falciparum Malaria 总被引:5,自引:3,他引:2
Ric Price Julie A. Simpson Paktiya Teja-Isavatharm Myint Myint Than Christine Luxemburger D. Gray Heppner Tan Chongsuphajaisiddhi Franois Nosten Nicholas J. White 《Antimicrobial agents and chemotherapy》1999,43(2):341-346
Combining artemisinin or a derivative with mefloquine increases cure rates in falciparum malaria patients, reduces transmission, and may slow the development of resistance. The combination of artesunate, given for 3 days, and mefloquine is now the treatment of choice for uncomplicated multidrug-resistant falciparum malaria acquired on the western or eastern borders of Thailand. To optimize mefloquine administration in this combination, a prospective study of mefloquine pharmacokinetics was conducted with 120 children (4 to 15 years old) with acute uncomplicated falciparum malaria, who were divided into four age- and sex-matched groups. The patients all received artesunate (4 mg/kg of body weight/day orally for 3 days and mefloquine as either (i) a single dose (25 mg/kg) on day 2 with food, (ii) a split dose (15 mg/kg on day 2 and 10 mg/kg on day 3) with food, (iii) a single dose (25 mg/kg) on day 0 without food, or (iv) a single dose (25 mg/kg) on day 2 without food. Delaying administration of mefloquine until day 2 was associated with a mean (95% confidence interval) increase in estimated oral bioavailability of 72% (36 to 109%). On day 2 coadministration with food did not increase mefloquine absorption significantly, and there were no significant differences between patients receiving split- and single-dose administration. In combination with artesunate, mefloquine administration should be delayed until the second or third day after presentation. 相似文献
46.
The link between both high and low blood pressure (BP) levels and cognitive impairment in later life has been reported in several studies. The mechanisms for this link are unclear but may be related to abnormalities in brain blood flow control. Our previous work has shown that cerebral autoregulation (CA) is unimpaired in both young and older people with hypertension at rest and that ageing does not appear to impact on the increase in the cerebral blood flow response to increased metabolic demand of neurones and other cells of the nervous system due to heightened activity (Neurovascular Coupling, NVC). Nonetheless, it is plausible that NVC efficiency becomes compromised during mental activity in older people with hypertension and that certain classes of anti-hypertensive agents may exacerbate the situation by reducing both NVC and CA contributing to cognitive decline. Such a link would have a major impact on prescribing patterns for anti-hypertensive medication. 相似文献
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Myint PK Luben RN Welch AA Bingham SA Wareham NJ Khaw KT 《The American journal of clinical nutrition》2008,87(1):64-69
BACKGROUND: The relation between plasma vitamin C and risk of stroke remains unclear. Although clinical trials showed no significant benefit of vitamin C supplementation in reducing stroke risk, they were not able to examine the relation between plasma vitamin C concentrations and stroke risk in a general population. OBJECTIVE: The objective was to examine the relation between baseline plasma vitamin C concentrations and risk of incident stroke in a British population. DESIGN: A population-based prospective study was conducted in 20,649 men and women aged 40-79 y without prevalent stroke at baseline and participating in the European Prospective Investigation into Cancer-Norfolk prospective population study. The participants completed a health questionnaire and attended a clinic during 1993-1997 and were followed up for incident strokes through March 2005. RESULTS: Over 196,713 total person-years (average follow-up: 9.5 y), 448 incident strokes occurred. In a Cox proportional hazards model, persons in the top quartiles of baseline plasma vitamin C concentrations had a 42% lower risk (relative risk: 0.58; 95% CI: 0.43, 0.78) than did those in the bottom quartile, independently of age, sex, smoking, body mass index, systolic blood pressure, cholesterol, physical activity, prevalent diabetes and myocardial infarction, social class, alcohol consumption, and any supplement use. Similar results were obtained after exclusion of persons with illnesses, users of ascorbic acid-containing supplements, and persons with a history of early strokes during the initial 2 y of follow-up. CONCLUSIONS: Plasma vitamin C concentrations may serve as a biological marker of lifestyle or other factors associated with reduced stroke risk and may be useful in identifying those at high risk of stroke. 相似文献
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