Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014118 (endocarditis)
 15,629 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 56-year-old man with heparin-induced thrombocytopenia with thrombosis syndrome (HITTS) received anticoagulation with recombinant hirudin (lepirudin) for emergency coronary artery bypass graft (CABG) surgery and aortic valve replacement. The patient experienced life-threatening refractory bleeding that was successfully treated with recombinant factor VIIa. He had a history of infective endocarditis that resulted in severe aortic insufficiency, three-vessel coronary artery disease, and acute renal failure requiring hemodialysis. The patient was transferred from another hospital for the emergency surgery, but before his transfer, he developed HITTS secondary to therapeutic heparin for a deep vein thrombosis of the lower extremity. The presence of HITTS, the urgent nature of the case, and the availability of the direct thrombin inhibitor led the surgical team to select lepirudin for anticoagulation to facilitate cardiopulmonary bypass. After separation from cardiopulmonary bypass, the patient was in a coagulopathic state due to the inability to reverse the lepirudin and the slowed elimination of the drug secondary to inadequate renal function. As a result, the patient experienced excessive generalized oozing that was unresponsive to traditional therapies and blood product transfusions. Recombinant factor VIIa 35 microg/kg was given as rescue therapy. The bleeding slowed, which allowed placement of chest tubes and closing of the sternum. The patient was transferred to the intensive care unit in stable condition with no evidence of thrombosis in the freshly placed bypass grafts or on the bioprosthetic valve. Recombinant factor VIIa appears to be a suitable option as salvage therapy in patients with refractory bleeding secondary to anticoagulation with a direct thrombin inhibitor during cardiac surgery.
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PMID:Recombinant factor VIIa for refractory bleeding after cardiac surgery secondary to anticoagulation with the direct thrombin inhibitor lepirudin. 1655 18

Cardiac causes of ischemic stroke lead to severe neurological deficits from large intracranial artery occlusion compared to small vessel ischemic stroke. The most common cause of cardioembolic stroke is atrial fibrillation (AF), which has an increasing incidence with age. AF stroke trials demonstrate that anti-coagulation is superior to anti-platelet therapy in terms of ischemic stroke prevention. Recently, warfarin was compared with dabigatran, an oral, direct thrombin inhibitor, and was found to be at least equally effective in reducing ischemic stroke with less intracranial bleeding risk. Future research is investigating other direct thrombin inhibitors as potential alternatives to warfarin, which has a narrow therapeutic index, requires frequent blood monitoring, has multiple drug interactions, and a higher rate of intracranial bleeding. Other causes of cardioembolic stroke include myocardial infarction, left ventricular thrombus, reduced ejection fraction, valvular abnormalities, and endocarditis. Patent foramen ovale is a common finding on echocardiograms in patients with and without stroke (up to 20% of the population), and it is a controversial source of cryptogenic stroke. The best way to prevent cardioembolic stroke remains early detection and treatment of AF, and treating the underlying stroke mechanism. Cardiac magnetic resonance imaging is an emerging technology and reveals some sources of cardiac embolism missed by echocardiography, and might provide an additional diagnostic tool in investigating cardioembolic stroke.
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PMID:Prevention of cardioembolic stroke. 2163 39

Acute bacterial endocarditis is a rapid, difficult to manage, and frequently lethal disease. Potent antibiotics often cannot efficiently kill Staphylococcus aureus that colonizes the heart's valves. S. aureus relies on virulence factors to evade therapeutics and the host's immune response, usurping the host's clotting system by activating circulating prothrombin with staphylocoagulase and von Willebrand factor-binding protein. An insoluble fibrin barrier then forms around the bacterial colony, shielding the pathogen from immune cell clearance. Targeting virulence factors may provide previously unidentified avenues to better diagnose and treat endocarditis. To tap into this unused therapeutic opportunity, we codeveloped therapeutics and multimodal molecular imaging to probe the host-pathogen interface. We introduced and validated a family of small-molecule optical and positron emission tomography (PET) reporters targeting active thrombin in the fibrin-rich environment of bacterial colonies. The imaging agents, based on the clinical thrombin inhibitor dabigatran, are bound to heart valve vegetations in mice. Using optical imaging, we monitored therapy with antibodies neutralizing staphylocoagulase and von Willebrand factor-binding protein in mice with S. aureus endocarditis. This treatment deactivated bacterial defenses against innate immune cells, decreased in vivo imaging signal, and improved survival. Aortic or tricuspid S. aureus endocarditis in piglets was also successfully imaged with clinical PET/magnetic resonance imaging. Our data map a route toward adjuvant immunotherapy for endocarditis and provide efficient tools to monitor this drug class for infectious diseases.
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PMID:Multimodal imaging of bacterial-host interface in mice and piglets with Staphylococcus aureus endocarditis. 3314 23