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排序方式: 共有200条查询结果,搜索用时 921 毫秒
21.
G W Rewcastle G J Atwell B C Baguley S B Calveley W A Denny 《Journal of medicinal chemistry》1989,32(4):793-799
In a search for compounds related to flavoneacetic acid with activity against solid tumors, a series of methyl-, methoxy-, chloro-, nitro-, and hydroxy-substituted xanthenone-4-acetic acids have been synthesized and evaluated against subcutaneously implanted colon adenocarcinoma 38 in vivo, using a short-term histology assay as a primary screening system. A major goal of this work was to identify compounds with similar profiles of activity to that of flavoneacetic acid but of higher potency. The level of activity of the compounds appeared to depend more on the nature of the substituent than its positioning, in the order Cl greater than Me, OMe greater than NO2, OH. However, the potency of the compounds was related much more to the position rather than the nature of the substitution, with 5-substituted compounds being clearly the most dose potent. 5-Methylxanthenone-4-acetic acid has a similar level of activity to that of flavoneacetic acid in the test systems employed but is more than 7-fold as dose potent. 相似文献
22.
Potential antitumor agents. 50. In vivo solid-tumor activity of derivatives of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide 总被引:2,自引:0,他引:2
The synthesis, physicochemical properties, and antitumor activity of a series of N-[2-(dialkylamino)alkyl]-acridine-4-carboxamides are reported. The compounds bind to DNA by intercalation, but exist under physiological conditions as monocations due to the weakly basic acridine chromophore (pKa = 3.5-4.5). The acridine-4-carboxamides show very broad structure-activity relationships (SAR) for antileukemic activity, with substituents at nearly all acridine positions proving acceptable. The compounds also show remarkable activity against the Lewis lung solid tumor in vivo, with several analogues capable of effecting 100% cures of the advanced disease. The broad SAR and high solid-tumor activity of the 9-acridine-4-carboxamides imply they should be considered as a completely new class of antitumor agent. 相似文献
23.
Chest radiographs were compared for three groups of children 8-9 years old: 23 survivors of bronchopulmonary dysplasia (BPD), 33 survivors of hyaline membrane disease without BPD, and 35 survivors of premature birth without neonatal respiratory problems. Only four children in the second group and three in the third had abnormal lungs. Linear shadows, apparently representing strands of fibrosis or deep pleural fissuring, were seen more frequently (15 of 23) in the BPD group than in the others (P less than .0001). Seventeen children in the BPD group had definite pulmonary abnormalities, none of them severe. The anteroposterior dimension of the chest in survivors of BPD tended to be decreased (P less than .001 vs that of reported control subjects). 相似文献
24.
Reovirus as an experimental therapeutic for brain and leptomeningeal metastases from breast cancer 总被引:2,自引:0,他引:2
Yang WQ Senger DL Lun XQ Muzik H Shi ZQ Dyck RH Norman K Brasher PM Rewcastle NB George D Stewart D Lee PW Forsyth PA 《Gene therapy》2004,11(21):1579-1589
Brain and leptomeningeal metastases are common in breast cancer patients and our current treatments are ineffective. Reovirus type 3 is a replication competent, naturally occurring virus that usurps the activated Ras-signaling pathway (or an element thereof) of tumor cells and lyses them but leaves normal cells relatively unaffected. In this study we evaluated reovirus as an experimental therapeutic in models of central nervous system (CNS) metastasis from breast cancer. We found all breast cancer cell lines tested were susceptible to reovirus, with > 50% of these cells lysed within 72 h of infection. In vivo neurotoxicity studies showed only mild local inflammation at the injection site and mild communicating hydrocephalus with neither diffuse encephalitis nor behavioral abnormalities at the therapeutically effective dose of reovirus (intracranial) (ie 10(7) plaque-forming units) or one dose level higher. In vivo, a single intratumoral administration of reovirus significantly reduced the size of tumors established from two human breast cancer cell lines and significantly prolonged survival. Intrathecal administration of reovirus also remarkably prolonged survival in an immunocompetent racine model of leptomeningeal metastases. These data suggest that the evaluation of reovirus as an experimental therapeutic for CNS metastases from breast cancer is warranted. 相似文献
25.
A Pareek SD Zawar SB Salagre NB Chandurkar ND Karnik 《European journal of medical research》2009,14(7):297-303
Objective
High blood pressure is one of the most important risk factors, directly responsible for increasing the cardiovascular morbidity and mortality. The primary objective was to evaluate the efficacy of metoprolol XL/chlorthalidone against metoprolol XL/hydrochlorothiazide with respect to mean fall in systolic and diastolic blood pressure. The secondary objective was to compare the response rates and to evaluate the tolerability of study medications in patients with mild-tomoderate essential hypertension.Methods
Total 130 eligible patients (65: metoprolol XL 25 mg/chlorthalidone 6.25 mg; 65: metoprolol XL 25 mg/HCTZ 12.5 mg) were enrolled in this randomized, comparative, multicentric, 12-weeks study. Sixty-two patients from each group completed the study. After 4-weeks of treatment, non-responders from chlorthalidone 6.25 mg combination group were shifted to metoprolol XL 50 mg/chlorthalidone 12.5 mg and non-responders from HCTZ 12.5 mg combination group were escalated to metoprolol XL 50 mg/HCTZ 12.5 mg.Results
The study treatment groups were comparable with respect to demography and baseline disease characteristics. Both the starting therapies were comparable with respect to mean fall in SBP (p = 0.788) and DBP (p = 0.939), and response rates (p = 1.0) after 4-weeks of therapy. Also both the step-up therapies showed similar mean fall in SBP (p = 0.277) and DBP (p = 0.507) at the end of 12-weeks. However, significantly more number of patients from chlorthalidone 12.5 mg/metoprolol XL 50 mg group responded to therapy as compared to that from HCTZ 12.5 mg/metoprolol XL 50 mg group (p = 0.045). All the reported adverse events were of mild-to-moderate intensity. There were no clinically significant trends in electrolytes (Na+, K+, Cl-)and fasting blood sugar, evident across the treatment groups.Conclusion
Chlorthalidone in combination with metoprolol XL is as effective and well tolerated as widely used combination of metoprolol XL/HCTZ, thus providing an alternative therapeutic option. 相似文献26.
Oral Diseases (2010) 16 , 136–145 Objective: The oral cavity forms an indispensable part of the human microbiome, for its unique and diverse microflora distributed within various niches. While majority of these organisms exhibit commensalism, shifts in bacterial community dynamics cause pathological changes within oral cavity and distant sites. The aim of this review was to appraise the current and emerging methods of detecting bacteria of the oral cavity paying particular attention to the cultivation independent methods. Design: Literature pertaining to cultivation based and cultivation independent methods of oral bacterial identification was reviewed. Methods: The specific advantages and disadvantages of cultivation based, microscopic, immunological and metagenomic identification methods were appraised. Results: Because of their fastidious and exacting growth requirements, cultivation based studies grossly underestimate the extent of bacterial diversity in these polymicrobial infections. Culture independent methods deemed more sensitive in identifying difficult to culture and novel bacterial species. Conclusion: Apart from characterizing potentially novel bacterial species, the nucleic acid sequence data analyzed using various bioinformatics protocols have revealed that there are in excess of 700 bacterial species inhabiting the mouth. Moreover, the latest pyrosequencing based methods have further broadened the extent of bacterial diversity in oral niches. 相似文献
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29.
Occupational violence (OV) is a daily risk for ED staff. It contributes to staff stress, sick leave, turn‐over and burn‐out, and limits the capacity of staff to provide unimpeded quality care to patients and their families. Many factors contribute to incidents of OV; however, early detection of such risk factors could pre‐empt incidences of OV during ED episodes of care. A five‐stage methodological framework for scoping reviews was used to identify, summarise and synthesise OV risk factors from five key databases. A validated tool was used to appraise the quality of included studies. Independent evaluation by the reviewers was used throughout. Patient factors were extracted and described from 24 methodologically and geographically diverse papers. Methodological quality for these studies varied from moderate to high. A total of 34 OV risk factors were identified. Although there was variation in, and differences between, staff‐perceived and objective (documented) OV risk factors, patient risk factors can be categorised into three main groups: clinical presentation, behaviours and past history. Five existing ED OV risk assessment tools were identified, with limited supporting evidence for each. The results support the development of a reliable and validated OV risk assessment tool to be initiated at triage. 相似文献
30.
D D McPherson M R Johnson N M Alvarez N B Rewcastle S M Collins M L Armstrong R A Kieso L J Thorpe M L Marcus R E Kerber 《Journal of the American College of Cardiology》1992,19(3):593-599
The purpose of this study was to evaluate the in vivo characteristics of coronary atherosclerosis by using high frequency epicardial echocardiography. High frequency epicardial echocardiography was used to evaluate residual lumen and wall morphology at the sites of maximal coronary atherosclerosis in 26 patients undergoing coronary artery bypass grafting. The maximal/minimal wall thickness ratio was 3.1 +/- 0.2 (mean +/- SEM) with a large range (1.3 to 7.5). Portions of the wall were normal in 16 of 31 lesions; the percent normal circumference ranged from 9% to 85%. Maximal/minimal lumen diameter ratio was 1.5 +/- 0.1 (range 1.1 to 2.9). The shape of the residual coronary lumen was noncircular in 16 lesions: oval in 13 and complex in 3. The residual coronary lumen was eccentrically placed within six arteries. These data emphasize the variability of residual lumen and wall geometry in atherosclerosis. 相似文献