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1.
Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT1 ) receptors in rabbit aorta and human recombinant AT1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'2 = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [125 I]AII binding to rabbit aortic membranes (AT, receptors) and [125 I][Sar1 , Ile8 ]AII binding to human recombinant AT1 receptors in a concentration-dependent manner with IC50 values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [125 I)AII binding to bovine cerebellum membranes (ÀT2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [125 I]AII binding assay and insurmountable AT1 receptor antagonism in the functional study. 相似文献
2.
P. Neary C. Hurson D. O. Briain A. Brabazon D. Mehigan T. V. Keaveny S. Sheehan 《Colorectal disease》2007,9(2):166-172
OBJECTIVE: Colonic infarction is a recognized complication of abdominal aortic aneurysm (AAA) surgery. The clinical difficulty in establishing the diagnosis combined with the patient's poor physiological status is usually associated with a fatal outcome. We assessed our experience with this problem to identify a possible risk factor profile for these patients. METHOD: Patients records were identified from the operative logs, intensive care unit, Hospital Inpatient Enquiry system and vascular unit databases over a 6-year period. RESULTS: A total of 405 patients underwent AAA repair during this period; 140 as emergency ruptures. Nine patients were identified from the databases with known colonic infarction (2.2%). One was a woman. The mean age was 70 years. Seven patients had emergency ruptures (5%). Twenty independent risk factors were analysed using univariate and multivariate logistic regression models. Significant risk factors identified by using a multivariate analysis included the nature of the presenting patient, preoperative hypotension, prolonged cross-clamp time, intra-operative ischaemia and postoperative acidosis. Confirmatory diagnosis was made by colonoscopy in eight patients. One patient survived following the salvage surgery. The mean duration of survival was 10.5 days. The overall mortality was 89% of patients. CONCLUSION: In our unit infrarenal AAA repair has a 2.2% rate of colonic infarction. A definitive diagnosis is best made by colonoscopy. A risk factor profile for the development of colonic infarction may be constructed on the basis of specific clinical parameters. Earlier intervention on the basis of this profile may ultimately reduce the current excessive mortality. 相似文献
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S M Kieran R A Cahill I Browne S J Sheehan D Mehigan M C Barry 《European journal of vascular and endovascular surgery》2006,32(3):305-308
INTRODUCTION: Concern about the potential detrimental side-effects of beta-blockade on pulmonary function often dissuades against their perioperative use in patients undergoing major arterial surgery (especially in those with chronic obstructive pulmonary disease (COPD)). In this study we aimed to establish prospectively the clinical relevance of these concerns. METHODS: After ethics committee approval and individual informed consent, the pulmonary function of twenty patients (mean age 68.7 years (range 43-82), 11 males) scheduled to undergo non-emergency major vascular surgery was studied by recording symptoms and spirometry before and after institution of effective beta-blockade. Fifteen patients (75%) had significant smoking histories (mean pack years/patient=50), while 12 (60%) had COPD. RESULTS: All patients tolerated effective beta-blockade satisfactorily without developing either subjective deterioration in symptoms or significant change on spirometry. The mean change in FEV1 following adequate beta-blockade was 0.05+/-0.24 liters (95% CI -0.06 to +1.61), p=0.35, giving a mean percentage change of 3.18%+/-11.66 (95% CI -2.26 to 8.62). CONCLUSIONS: Previously held concerns about worsening pulmonary function through the short-term use of beta-blockers should not dissuade their perioperative usage in patients with peripheral vascular disease. Furthermore, the accuracy of pulmonary function tests in preoperative assessment and risk stratification also appears unaffected by this therapy. 相似文献
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W C Levy A F Jacobson M D Cerqueira D T Matsuoka F H Sheehan J R Stratton 《Journal of nuclear medicine》1992,33(9):1642-1647
The effects of region of interest (ROI) selection and correction for Compton-scattered photons using a buildup factor on radionuclide left ventricular volumes calculated by the Links method were compared in 19 humans with contrast ventriculography and in phantoms. Three different methods of ROI selection were compared: a manual ROI, a second derivative ROI and a 50% count-threshold ROI. In phantoms without Compton scatter correction, volumes were overestimated by 30% (manual ROI), 20% (derivative ROI) and 1% (count threshold ROI). In subjects, results without Compton scatter correction were similar with overestimates of 50% (manual ROI) and 20% (derivative ROI) and an underestimate by 3% (count threshold method). Correction for Compton-scattered photons with the use of a phantom-derived buildup factor resulted in improved accuracy for the manual ROI (+15%) and the derivative ROI (0%). A 50% count threshold ROI following interpolative background subtraction allows the accurate calculation of cardiac volumes without the need for scatter correction, while a second derivative ROI method requires a correction for Compton scatter with the use of a buildup factor. 相似文献
7.
A series of novel, highly potent and selective agonists for the kappa-opioid receptor. 总被引:4,自引:4,他引:0
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A. G. Hayes P. J. Birch N. J. Hayward M. J. Sheehan H. Rogers M. B. Tyers D. B. Judd D. I. Scopes A. Naylor 《British journal of pharmacology》1990,101(4):944-948
1. This paper describes the opioid receptor pharmacology and in vivo activity of several novel benzene-acetamidopiperidine and benzeneacetamidopiperazine analogues. 2. These compounds all showed potent, naloxone-reversible, full agonist activity in the field-stimulated rabbit vas deferens, indicating that they are kappa-opioid agonists; but showed very little activity in the rat or hamster vas deferens, indicating good selectivity with regard to mu- and delta-opioid receptors. 3. They were all potent antinociceptive agents, the most potent compound, GR 103545, having an ED50 value in the mouse abdominal constriction test of 0.25 micrograms kg-1 s.c. The compounds also produced sedation and diuresis, but had little effect on respiration rate or gastrointestinal motility. 4. It is concluded that the seven novel compounds described are all potent and selective agonists for the kappa-opioid receptor. 相似文献
8.
Early beneficial effect of streptokinase on left ventricular function in acute myocardial infarction 总被引:1,自引:0,他引:1
F H Sheehan C Thery P Durand M E Bertrand E L Bolson 《The American journal of cardiology》1991,67(7):555-558
The effect of intravenous streptokinase therapy on the time course of functional recovery was investigated in a controlled study of 64 patients randomized within 3 hours after the onset of acute myocardial infarction (AMI). Contrast ventriculography was performed 1 to 4 days after AMI and repeated 5 weeks later. Wall motion was analyzed by the centerline method in the central infarct, peripheral infarct and noninfarct regions. In patients with ventriculographic data at the early catheterization, streptokinase-treated patients had less severe hypokinesia in the central infarct region than control patients (-2.9 +/- 0.9 [n = 29] vs -3.4 +/- 0.7 standard deviations below normal [n = 21], p less than 0.05). The benefit of streptokinase was more marked in the peripheral infarct region (-1.5 +/- 0.7 vs -2.1 +/- 0.6, p less than 0.001). As a result, the ejection fraction was slightly higher in treated versus control groups (46 +/- 10 vs 43 +/- 7%, respectively; difference not significant). At 5 weeks, function in the streptokinase and control groups had diverged further because of continued improvement in the streptokinase-treated patients. This study shows that streptokinase benefits left ventricular (LV) function by 1 to 4 days after AMI, earlier than previously reported. The benefit was not limited to the peripheral infarct region, where ischemia might have been less severe, but was also seen in the central infarct region. The implication is that thrombolytic therapy can improve LV function during the period of myocardial stunning, while myocardial function is still recovering. 相似文献
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10.
Joachim Schofer Rolf Spielmann Florence H. Sheehan Maren Lampe Michael Schlüter Detlef G. Mathey 《The International Journal of Cardiac Imaging》1988,3(4):203-208
In 32 patients with acute myocardial infarction, who had undergone successful intracoronary thrombolysis, the results of regional wall motion measured from contrast cineangiograms 10 to 21 days after thrombolysis were related to the results of thallium single-photon emission computed tomography (SPECT) after intravenous dipyridamole. Wall motion was measured by means of the centerline method, and thallium defect size was estimated by comparing the patient's circumferential profile with that of 20 normals. No correlation was found between ejection fraction or regional wall motion and thallium defect size. The time from symptom onset to thrombolysis was inversely correlated with the degree of hypokinesis (r=–0.51) but not with thallium defect size. In patients treated within 3 hours, hypokinesis was significantly less than in patients treated later (–1.1±0.6 SD vs –2.2±0.8 SD, p<0.01) whereas thallium defect size was not significantly different in both groups. It is concluded that, in patients after thrombolysis, thallium defect size determined by SPECT does not reflect the degree of left ventricular dysfunction. 相似文献