Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 45-year-old woman, who had had rheumatoid arthritis for 12 years, had three attacks of cerebral embolism over two months and died after the final attack. Intensive clinical laboratory investigations did not disclose any specific origins of emboli, but an autopsy revealed a nodule at the base of the aortic valve which was pathologically proved to be a rheumatoid nodule. The thrombi were present from the distal part of left internal carotid artery up to the proximal part of the left middle cerebral artery. They were rich in fiber, but poorly organized endothelial cell, raising the possibility that they originated from other parts and have recently reached there. On the top of the rheumatoid nodule, a thrombus was present. It was easily ablated and a small amount of fibrin stuck the nodule. Based on these results, we concluded that cerebral emboli were originally generated at the top of a rheumatoid nodule in the heart. In patients with RA, rheumatoid nodules are rarely seen in the heart. If present, they usually cause cardiac failure or atrioventricular block, and seldom result in cerebral infarction. This is the first case in which an autopsy proved rheumatoid nodule in the heart which had caused multiple cerebral emboli. We should consider the possibility of rheumatoid nodules in the heart as an origin of cerebral emboli in patients with rheumatoid arthritis.
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PMID:[An autopsied case of a woman with rheumatoid arthritis attacked by multiple cerebral emboli]. 1662 48

Non-steroidal anti-inflammatory drugs (NSAIDs) represent a clinically important class of agents. NSAIDs are commonly used in treatment of conditions such as headache, fever, inflammation and joint pain. Complications often arise from chronic use of NSAIDs. Gastrointestinal (GI) toxicity in the form of gastritis, peptic erosions and ulcerations and GI bleeds limit usage of NSAIDs. These toxicities are thought to be due to cyclooxygenase (COX)-1 blockade. COX-1 generates cytoprotective prostanoids such as prostaglandin (PG) E2 and prostacyclin (PGI2). COX-2 inhibitors, commonly referred to as coxibs, were developed to inhibit inflammatory prostanoids without interfering with production of COX-1 prostanoids. Concerns over cardiovascular safety, however, have evolved based on the concept of inhibition of COX-2-derived endothelial prostanoids without inhibition of platelet thromboxane A2, leading to increased cardiovascular risk. The Celecoxib Long-Term Arthritis Safety Study (CLASS) trial did not show a significant increase in cardiovascular risk for celecoxib (Celebrex), but results of the Vioxx Gastrointestinal Outcomes Research (VIGOR) study showed an increased cardiovascular risk with long-term daily usage of rofecoxib in patients with rheumatoid arthritis. The Adenomatous Poly Prevention on Vioxx (APPROVe) trial further evaluated cardiovascular effects of rofecoxib and recently led to removal of this drug from the marketplace. Coxibs affect renal function via blockade of normal COX-2 functions. COX-2 expression increases in high renin states and in response to a high-sodium diet or water deprivation. PGI2 and PGE2 are the most important renal prostanoids. PGI2 inhibition results in hyperkalemia. PGE2 inhibition results in sodium retention, which leads to hypertension, peripheral edema and potentially exacerbation of heart failure. This review article discusses beneficial and deleterious effects associated with prostanoids produced by COX-1 and COX-2 in various organs and how blockade of these products translates into clinical medicine.
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PMID:Cyclooxygenase-2 inhibitors: a painful lesson. 1678 94

Conventional systemic treatments for patients with psoriasis are associated with multiple adverse effects that require continuous monitoring. The introduction of new biological agents such as etanercept, a fully human fusion protein, has permitted individualisation of patients' treatment according to disease stage. The drug is a competitive inhibitor of tumour necrosis factor-alpha (TNFalpha) that prevents interaction between this cytokine and its cell surface receptors. Etanercept also modulates the activity of other inflammatory cytokines and does not induce complement-mediated cell lysis in vitro. The main source of information regarding etanercept safety comes from studies in patients with rheumatoid arthritis. The most common adverse effect during drug administration is mild injection site reactions. There is no increase in the overall incidence of infections compared with placebo, although there have been several reports of infections caused by intracellular organisms (Mycobacterium tuberculosis, Listeria monocytogenes, and Mycobacterium avium intracellulare). Therefore, combination of this drug with corticosteroids must be carefully monitored and should be avoided in patients with established sepsis. There are no data showing that treatment with etanercept results in an increase in the occurrence of malignant neoplasms. However, caution is recommended in use of etanercept in patients with a current or past history of demyelinating disease. Etanercept must be used with extreme caution in patients with heart failure because of several reports indicating a worsening or de novo occurrence of congestive heart failure while receiving the drug. Monitoring of autoantibodies is not currently considered necessary as they do not predict response, toxicity or autoimmune events. The presence of non-neutralising antibodies to the TNF receptor fragment or other protein components of etanercept has not been related to a decrease in drug response or adverse reactions. Etanercept does not generally modify the course of inflammatory bowel disease. When combined with other systemic therapies for psoriasis, current data do not show an increase in adverse events. In patients with hepatitis C viral infection, etanercept does not increase transaminase levels or viral load and in some instances has allowed the concomitant use of interferon which had previously been discontinued because of a worsening of psoriasis. Etanercept is rated as a US FDA category B drug in pregnancy. However, its use is not recommended in pregnant women unless the benefit-risk ratio greatly favours its use. Etanercept is not recommended for use in lactating women. Etanercept represents a relevant treatment for psoriasis, efficacious over many weeks and safe but special care should be taken to avoid the potential risks.
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PMID:Safety of etanercept in psoriasis: a critical review. 1687 41

Between 30 and 50% of patients with rheumatoid arthritis (RA) have cardiac involvement but only 2 to 10% have clinical manifestations. The authors report the results of a retrospective study of 5 cases of aortic regurgitation (AR) requiring valve replacement. There were 4 women and 1 man with an average age of 48.4 years. The average duration of the RA was 19.6 years. All patients had cardiac failure. Aortic valve replacement was performed in all cases, with bioprostheses in 4 out of 5 patients. The histopathological examination of the valves showed a rheumatoid nodule in 3 cases and non-specific lesions in one case. In the fifth patient, rheumatoid serology was positive in the pericardial effusion. The average interval between the onset of symptoms and cardiac surgery was 3.6 months (range 1 to 6 months) There were 3 deaths at 3 days, 20 months and 10 years, two patients survive after 12 and 14 years. The characteristic rapid progression of this form of AR, which may be life-threatening, should be emphasised.
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PMID:[Valve replacement for aortic regurgitation associated with rheumatoid arthritis: a series of 5 cases]. 1687 16

The risk of cardiovascular disease is increased in patients with rheumatoid arthritis (RA). Although the pathogenesis of cardiovascular disease in patients with RA is largely unknown, evidence to date indicates that it involves complex interactions between the traditional and nontraditional cardiovascular risk factors as well as various medications commonly used for the treatment of RA patients. This review provides an overview of the clinical studies that demonstrate increased risk of coronary heart disease and heart failure in patients with RA and also discusses the potential role of the various risk factors.
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PMID:Rheumatoid arthritis and the heart. 1692 38

Chronic low-grade inflammation was recognized during the past decade as an important risk factor for the development of atherosclerosis and, more recently, for the development of heart failure. Patients with rheumatoid arthritis (RA) are at increased risk of morbidity and mortality from ischemic cardiovascular events and heart failure. Epidemiologic and clinical studies indicate that RA is an independent risk factor for cardiovascular disease, which suggests that chronic exposure to high levels of inflammatory mediators contributes to this enhanced risk. The relative contribution of conventional risk factors to the acceleration of cardiovascular disease does not seem to be increased in patients with RA compared with control populations. Nonetheless, some preclinical laboratory measures of risk factors (e.g. insulin sensitivity) are adversely modulated in the context of the highly inflammatory rheumatoid microenvironment. Discerning the net effect of RA therapies on cardiovascular disease is also challenging because, theoretically, their biologic effects could either promote or attenuate atherosclerosis and ventricular dysfunction; however, available data suggest a beneficial effect on cardiovascular morbidity and mortality in patients with RA. This review provides an overview of the potential influence of RA and its treatment on the development and progression of cardiovascular disease, and outlines some preliminary recommendations for prevention and management of this complication in patients with RA.
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PMID:Therapy Insight: managing cardiovascular risk in patients with rheumatoid arthritis. 1693 11

Worldwide, over 400,000 patients have been treated with tumour necrosis factor (TNF)-alpha antagonists for indications that include rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis and ankylosing spondylitis. Since their approval, concerns regarding safety have been raised. There is a risk of re-activation of granulomatous diseases, especially tuberculosis, and measures should be taken for detection and treatment of latent tuberculosis infections. Preliminary data suggest that anti-TNF therapy may be safe in chronic hepatitis C. However, TNF-alpha antagonists have resulted in re-activation of chronic hepatitis B if not given concurrently with antiviral therapy. Solid tumours do not appear to be increased with anti-TNF therapy. Variable rates of increased lymphoma risk have been described with anti-TNF therapy compared with the general population, although no increased risk was found compared with a rheumatoid arthritis population. Large phase II and III trials with TNF-alpha antagonists in advanced heart failure have shown trends towards a worse prognosis, and should therefore be avoided in this population. Both etanercept and infliximab are associated with the formation of autoantibodies, and these autoantibodies are rarely associated with any specific clinical syndrome. Rare cases of aplastic anaemia, pancytopenia, vasculitis and demyelination have been described with anti-TNF therapy. This chapter will discuss the safety profile and adverse events of the three commercially available TNF-alpha antagonists: etanercept, infliximab and adalimumab. The data presented in this review have been collected from published data, individual case reports or series, package inserts, the Food and Drug Administration postmarketing adverse events surveillance system, and abstracts from the American College of Rheumatology and European Congress of Rheumatology meetings for 2005.
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PMID:Problems encountered during anti-tumour necrosis factor therapy. 1697 37

Tumor necrosis factor (TNF)-alpha has been thoroughly investigated and established as a pivotal component of the inflammatory cascade. This review encompasses the safety and efficacy of TNF antagonists in rheumatoid arthritis, the interplay between rheumatoid arthritis and heart failure, as well as presentation of the available preclinical and clinical data discussing the use of anti-TNF therapy in patients with chronic heart failure. There is well-documented evidence for the role of anti-TNF-alpha in rheumatoid arthritis, in contrast to the controversial role of anti-TNF-alpha in heart failure. In animal models and small-scale clinical trials, anti-TNF therapy showed some promise in treating chronic heart failure, whereas larger, multicenter, randomized, placebo-controlled clinical trials (i.e., RECOVER [Research into Etanercept Cytokine Antagonism in Ventricular Dysfunction] and RENAISSANCE [Randomized Etanercept North American Strategy to Study Antagonism of Cytokines]) failed to show a statistically significant difference in composite clinical function score for anti-TNF therapy versus placebo. Future investigation is needed to determine if individualized dosing of anti-TNF therapy is necessary and whether or not treating patients with earlier-stage disease will show a benefit.
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PMID:Recent advances of TNF-alpha antagonists in rheumatoid arthritis and chronic heart failure. 1747

Chronic heart failure is debilitating, often fatal, expensive to treat and common. In most patients it is a late consequence of myocardial infarction (MI). The intracellular signals following infarction that lead to diminished contractility, apoptosis, fibrosis and ultimately heart failure are not fully understood but probably involve p38-mitogen activated protein kinases (p38), a family of serine/threonine kinases which, when activated, cause cardiomyocyte contractile dysfunction and death. Pharmacological inhibitors of p38 suppress inflammation and are undergoing clinical trials in rheumatoid arthritis, Chrohn's disease, psoriasis and surgery-induced tissue injury. In this review, we discuss the mechanisms, circumstances and consequences of p38 activation in the heart. The purpose is to evaluate p38 inhibition as a potential therapy for ischaemic heart disease.
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PMID:Potential of p38-MAPK inhibitors in the treatment of ischaemic heart disease. 1776 16

Tumor necrosis factor-alpha (TNFalpha) antagonists including antibodies and soluble receptors have shown remarkable efficacy in various immune-mediated inflammatory diseases (IMID). As experience with these agents has matured, there is an emerging need to integrate and critically assess the utility of these agents across disease states and clinical sub-specialties. Their remarkable efficacy in reducing chronic damage in Crohn's disease and rheumatoid arthritis has led many investigators to propose a new, 'top down' paradigm for treating patients initially with aggressive regimens to quickly control disease. Intriguingly, in diseases such as rheumatoid arthritis and asthma, anti-TNFalpha agents appear to more profoundly benefit patients with more chronic stages of disease but have a relatively weaker or little effect in early disease. While the spectrum of therapeutic efficacy of TNFalpha antagonists widens to include diseases such as recalcitrant uveitis and vasculitis, these agents have failed or even exacerbated diseases such as heart failure and multiple sclerosis. Increasing use of these agents has also led to recognition of new toxicities as well as to understanding of their excellent long-term tolerability. Disconcertingly, new cases of active tuberculosis still occur in patients treated with all TNFalpha antagonists due to lack of compliance with recommendations to prevent reactivation of latent tuberculosis infection. These safety issues as well as guidelines to prevent treatment-associated complications are reviewed in detail in this article. New data on mechanisms of action and development of newer TNFalpha antagonists are discussed in a subsequent article in the Journal. It is hoped that these two review articles will stimulate a fresh assessment of the priorities for research and clinical innovation to improve and extend therapeutic use and safety of TNFalpha antagonism.
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PMID:TNFalpha blockade in human diseases: an overview of efficacy and safety. 1791 45


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