Digoxin did not reduce overall mortality, but it reduced the rate of hospitalization both overall and for worsening heart failure. These findings define more precisely the role of digoxin in the management of chronic heart failure.
Blood platelets from 10 normal human subjects have been examined with a sensitive differential interference contrast (DIC) microscope . The entire transformation process during adhesion to glass is clearly visible and has been recorded cinematographically, including the disk to sphere change of shape, the formation of sessile protuberances, the extension and retraction of pseudopodia, and the spreading, ruffling, and occasional regression of the hyalomere . The exocytosis of intact dense bodies can be observed either by DIC microscopy, or by epifluorescence microscopy in platelets stained with mepacrine . Details offluorescent flashes indicate that the dense bodies usually release their contents extracellularly, but may do so intracytoplasmically under the influence of strong, short wavelength light on some preparations of mepacrine-stained platelets . The release of one or more dense bodies leaves a crater of variable size on the upper surface of the granulomere . Such craters represent the surface component of the open canalicular system and their formation and disappearance can be directly observed . Because these techniques permit quantitation of several parameters of motility which are not readily observable by other techniques, it is suggested that high extinction DIC microscope examination may become a rapid and useful method of studying congenital and acquired platelet disorders . Many features of platelet transformation have been confirmed and extended by scanning electron micrographs . These can in turn be interpreted by reference to time-lapse films of living platelets.KEY WORDS platelets " transformation release reaction -exocytosis pseudopodia motility -DIC microscopy scanning electron microscopy It has been known since the last century that platelets (thrombocytes) undergo a change of shape (transformation) as part of their role in hemostasis (for reviews, see references 19, 20, 22, 51, 60, 66, and 67) . Light microscope observation established that platelets formed spiky protuberances and gradually spread on glass surfaces in imitation of their spreading on damaged vascular endothelia (9) . However, the resolution and sen-J . CELL BIOLOGY C The Rockefeller University Press "
1. Sealey JE, Laragh JH. Aliskiren, the first renin inhibitor for treating hypertension: reactive renin secretion may limit its effectiveness.
The use of antiplatelet agents, specifically the thienopyridines, has become a standard of care in the approach to the patient presenting with an acute coronary syndrome. These drugs irreversibly inhibit the platelet by permanently binding to the surface P2Y12 receptor and blocking the downstream fibrinogen cross-linking between platelets, which leads to aggregation and thrombus. However, currently available therapeutic choices are limited by potential interaction with other medications, slow hepatic conversion to active metabolite, genetic resistance, and narrow therapeutic safety margin. In order to overcome these disadvantages, there has been an interest in developing alternatives to thienopyridines. Recent investigations have included ticagrelor, a reversible inhibitor of the P2Y12 platelet receptor, which appears to have overcome several drawbacks of the current thienopyridines. Its unique pharmacokinetic and pharmacodynamic profiles result in an inhibition of platelet aggregation that is rapid, high, consistent, and less susceptible to interpatient variability than currently available P2Y12 inhibitors. In addition, ticagrelor offers a potential mortality advantage not apparent with current agents. Although questions regarding the nature, magnitude, and clinical significance of several observed adverse effects (dyspnea and ventricular pauses) remain unanswered, it appears that ticagrelor may represent a significant advancement over currently available oral antiplatelet agents.
Postmarketing reports have emerged associating rivaroxaban with drug-induced liver injury (DILI); however, management strategies of patients with suspected rivaroxaban-induced liver injury requiring continued anticoagulation have not been published. The present report describes a 67-year-old male with atrial fibrillation receiving rivaroxaban who developed a 16-fold elevation in alanine transaminase, a nearly two-fold elevation in total bilirubin, and ultrasound confirmed hepatic steatosis. The patient was switched from rivaroxaban to apixaban with subsequent rapid resolution of laboratory abnormalities. Rapid improvement in liver function tests despite use of an alternative factor Xa inhibitor suggests that rivaroxaban's mechanism of hepatotoxicity may be unrelated to its pharmacologic action. When using rivaroxaban, clinicians should be aware of the small but potentially serious risk of DILI. Because most anticoagulants have been associated with DILI, selection of an alternative anticoagulant may be challenging; however, the use of apixaban in this case suggests it may be a reasonable alternative.
Although considerable progress has been made in perfecting the one-stage assay for factor VIII (antihemophilic factor), there remain variables that influence test results within laboratories as well as reproducibility between laboratories which have not been adequately evaluated. The purpose of this paper is to elucidate certain aspects of this assay that have not received adequate consideration and to describe the authors' assay method in order to provide a basis for comparison with results from other laboratories. It appears that variability results from: (1) differences in coagulability of different batches of substrate plasma obtained at different times from the same individual; (2) instability of some batches of stored substrate or standard plasmas; (3) variation in coagulability among vials of stored substrate or standard plasma from the same batch; (4) variation due to non-plasma reagents and instrumentation used to execute the test.
Pharmacologic stress testing uses vasodilators to provide objective evidence of myocardial ischemia. Adenosine and dipyridamole are nonselective adenosine receptor agonists that have been associated with myocardial infarction (MI) during intravenous infusion. Mechanisms postulated for this effect include coronary steal, transmural steal, global hypotension, and direct vasoconstriction. Regadenoson, a direct A2A agonist, was approved for use in stress testing in 2008. We describe a 68-year-old man who presented to our institution with typical angina, relieved by nitroglycerin. He did not have electrocardiogram (ECG) changes suggestive of myocardial pathology, and laboratory testing did not reveal a significant rise in troponin-I levels. To further assess the etiology of his symptoms, he underwent a pharmacologic stress test with regadenoson followed by technetium 99 m sestamibi. Six minutes after regadenoson infusion, the patient developed severe retrosternal chest pain accompanied by ST elevations on ECG. Sublingual nitroglycerin was administered that resolved both the pain and ECG changes. The patient subsequently underwent urgent coronary angiography and was found to have a 95% critical stenosis involving the left anterior descending artery. We conclude this case represents a MI secondary to coronary steal phenomenon induced by regadenoson infusion. Clinicians should be aware this adverse effect can occur despite the improved side-effect profile of regadenoson. Continuous monitoring of vital signs and the ECG with regular assessment of symptoms is imperative to identify this rare but potentially devastating adverse event.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.