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排序方式: 共有1088条查询结果,搜索用时 15 毫秒
21.
Chorvat RJ Bakthavatchalam R Beck JP Gilligan PJ Wilde RG Cocuzza AJ Hobbs FW Cheeseman RS Curry M Rescinito JP Krenitsky P Chidester D Yarem JA Klaczkiewicz JD Hodge CN Aldrich PE Wasserman ZR Fernandez CH Zaczek R Fitzgerald LW Huang SM Shen HL Wong YN Chien BM Arvanitis A 《Journal of medicinal chemistry》1999,42(5):833-848
The synthesis and CRF receptor binding affinities of several new series of N-aryltriazolo- and -imidazopyrimidines and -pyridines are described. These cyclized systems were prepared from appropriately substituted diaminopyrimidines or -pyridines by nitrous acid, orthoester, or acyl halide treatment. Variations of amino (ether) pendants and aromatic substituents have defined the structure-activity relationships of these series and resulted in the identification of a variety of high-affinity agents (Ki's < 10 nM). On the basis of this property and lipophilicity differences, six of these compounds (4d,i,n,x, 8k, 9a) were initially chosen for rat pharmacokinetic (PK) studies. Good oral bioavailability, high plasma levels, and duration of four of these compounds (4d,i,n,x) prompted further PK studies in the dog following both iv and oral routes of administration. Results from this work indicated 4i,x had properties we believe necessary for a potential therapeutic agent, and 4i1 has been selected for further pharmacological studies that will be reported in due course. 相似文献
22.
Objective
To investigate age and sex differences in the utilisation of hospital services for ischaemic heart disease.Design
Analysis of routine mortality data and hospital activity data.Setting
South West Thames Regional Health Authority.Subjects
Residents of the South West Thames Regional Health Authority who in 1991 either died from ischaemic heart disease or were admitted to an NHS hospital in England and Wales with a main diagnosis of ischaemic heart disease.Main outcome measures
Ratio of consultant episodes to deaths from ischaemic heart disease (as a proxymeasure of the utilisation of hospital care), and the percentages of consultant episodes in which further investigation (angiography or catheterisation) or revascularisation treatment (coronary artery bypass grafting or angioplasty) were carried out.Results
The ratio of episodes to deaths was similar in men and women (odds ratio for men vs. women 0.96, 95% confidence intervals 0.90 to 1.03). The percentage of episodes in which further investigation was carried out was higher in men than women (odds ratio for men vs. women 1.46, 95% confidence intervals 1.25 to 1.70) as was the percentage of episodes in which revascularisation treatment was carried out (odds ratio for men vs. women 1.46, 95% confidence intervals 1.20 to 1.77). The ratio of episodes to deaths, the percentage of episodes in which further investigation was carried out, and the percentage of episodes in which revascularisation treatment was carried out all declined with age (all p values <0.001).Conclusions
Women with ischaemic heart disease are as likely as men to be admitted to hospital, but afteradmission are less likely to undergo further investigation and revascularisation treatment. Elderly patients with ischaemic heart disease are less likely than younger patients to be admitted to hospital; after admission, they are also less likely to undergo further investigation and revascularisation treatment. Further research is needed to determine whether these age and sex differences in the use of hospital services are clinically justified. 相似文献23.
Congenital pulmonary atresia with ventricular septal defect: angiographic and surgical correlates 总被引:1,自引:0,他引:1
Of 181 patients with severe congenital pulmonary atresia and ventricular septal defect or "type IV truncus" (an obsolete term), all but 11% had true central pulmonary arteries. These arteries were demonstrable by large serial biplane angiograms using multiple selective injections into collateral vessels, frequent photographic subtraction, and occasional pulmonary vein-wedge angiograms. These techniques are extremely important for accurate diagnosis and in planning corrective or palliative surgery, which was done in 77% of patients with pulmonary arteries. 相似文献
24.
Aldrich NE 《Health facilities management》1991,4(7):52, 54, 56
25.
Clinical measurement, statistical analysis, and risk-benefit: controversies from trials of spinal injury 总被引:3,自引:0,他引:3
Bracken MB Aldrich EF Herr DL Hitchon PW Holford TR Marshall LF Nockels RP Pascale V Shepard MJ Sonntag VK Winn HR Young W 《The Journal of trauma》2000,48(3):558-561
BACKGROUND: The National Acute Spinal Cord Injury Studies have been a series of trials assessing the role of pharmacologic agents in the prevention of secondary neuronal damage after acute spinal cord injury. METHODS: The trials were multicenter randomized, controlled studies. RESULTS: Two trials have demonstrated the efficacy of high-dose methylprednisolone in improving neurologic and functional recovery and have shown a reassuring safety profile. CONCLUSION: This study responds to a recent commentary on these trials and examines in particular the roles of clinical measurement, statistical analysis, and risk benefit in assembling evidence for or against innovative therapies. 相似文献
26.
Abstract: We previously reported that the novel dynorphin A (Dyn A, Tyr‐Gly‐Gly‐Phe‐Leu‐Arg‐Arg‐Ile‐Arg‐Pro‐Lys‐Leu‐Lys‐Trp‐Asp‐Asn‐Gln) analog arodyn (Ac[Phe1,2,3,Arg4,d ‐Ala8]Dyn A‐(1–11)NH2, Bennett, M.A., Murray, T.F. & Aldrich, J.V. (2002) J. Med. Chem. vol. 45, pp. 5617–5619) is a κ opioid receptor‐selective peptide [Ki(κ) = 10 nm , Ki ratio (κ/μ/δ) = 1/174/583] which exhibits antagonist activity at κ opioid receptors. In this study, a series of arodyn analogs was prepared and evaluated to explore the structure–activity relationships (SAR) of this peptide; this included an alanine scan of the entire arodyn sequence, sequential isomeric d ‐amino acid substitution in the N‐terminal ‘message’ sequence, NMePhe substitution individually in positions 1–3, and modifications in position 1. The results for the Ala‐substituted derivatives indicated that Arg6 and Arg7 are the most important residues for arodyn's nanomolar binding affinity for κ opioid receptors. Ala substitution of the other basic residues (Arg4, Arg9 and Lys11) resulted in lower decreases in affinity for κ opioid receptors (three‐ to fivefold compared with arodyn). Of particular interest, while [Ala10]arodyn exhibits similar κ opioid receptor binding as arodyn, it displays higher κ vs. μ opioid receptor selectivity [Ki ratio (κ/μ) = 1/350] than arodyn because of a twofold loss in affinity at μ opioid receptors. Surprisingly, the Tyr1 analog exhibits a sevenfold decrease in κ opioid receptor affinity, indicating that arodyn displays significantly different SAR than Dyn A; [Tyr1]arodyn also unexpectedly exhibits inverse agonist activity in the adenylyl cyclase assay using Chinese hamster ovary cells stably expressing κ opioid receptors. Substitution of NMePhe in position 1 gave [NMePhe1]arodyn which exhibits high affinity [Ki(κ) = 4.56 nm ] and exceptional selectivity for κ opioid receptors [Ki ratio (κ/μ/δ) = 1/1100/>2170]. This peptide exhibits antagonistic activity in the adenylyl cyclase assay, reversing the agonism of 10 nm Dyn A‐(1–13)NH2. Thus [NMePhe1]arodyn is a highly κ opioid receptor‐selective antagonist that could be a useful pharmacological tool to study κ opioid receptor‐mediated activities. 相似文献
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30.
Previous studies have not clearly defined the role of cell-mediated immunity in bleomycin-induced lung injury. In this report
the functional activity of T lymphocytes obtained from minced lung preparations, bronchoalveolar lavage, and blood of rabbits
treated with bleomycin was examined in cell proliferation and cell-mediated cytotoxicity assays. Four days after instillation
of bleomycin (10 units/kg) into the right lung, histologic examination revealed mononuclear cell interstitial infiltrates
and alveolar exudates. Right lung bronchoalveolar lavage (BAL) cell counts were similar in both groups, but the percentage
of lymphocytes and neutrophils was elevated in bleomycin-treated groups (25% vs. 7% and 35% vs. 0% respectively;p<0.05). Spontaneous proliferation of cultured BAL and blood lymphocytes was similar in bleomycin-treated rabbits and controls.
After 24 h of incubation with interleukin-2 (IL-2), BAL lymphocytes from bleomycin-treated rabbits had nearly a 4-fold greater
proliferative response than lymphocytes from untreated rabbits. Concanavalin-A-dependent cell-mediated cytotoxicity (CDCMC)
assays were performed to evaluate cytolytic lymphocyte activity. Spontaneous CDCMC activity was not detected in BAL fluid
or in blood lymphocytes from either treated or control animals. After 24 h of incubation with IL-2, significant CDCMC activity
was detected in lung lymphocytes from bleomycin-treated animals, but not in lung lymphocytes from control animals. These results
indicate that stimulated lymphocytes are present in the lungs of rabbits 4 days after exposure to bleomycin.
Presented in part at the American Thoracic Society Annual Meeting, New Orleans, LA, May 1987. 相似文献