Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analgesic nephropathy is part of a wider clinical syndrome associated with the abuse of APC compounds, that is, a minimum total intake of 2 kg of aspirin or phenacetin. Ischaemic heart disease and premature aging are newly recognized aspects of the analgesic syndrome. The diagnosis of analgesic nephropathy can be made precisely by the radiological demonstration of renal papillary necrosis. The most important aspect of management of established analgesic nephropathy and renal insufficency is total avoidance of all non-steroid antiinflammatory agents and this is commonly associated with stabilization or improvement in renal function. In the APC mixture, aspirin appears to be the major nephrotoxic agent while phenacetin and paracetamol play a secondary and synergistic role in the nephrotoxicity.
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PMID:Analgesic nephropathy. 108 2

The clinical characteristics of supraventricular tachyarrhythmias (SVTA) and their relation to left ventricular dysfunction were assessed in 208 consecutive patients with recent myocardial infarction. Arrhythmias were quantified on hospital discharge by 24 hour electrocardiographic recording. All the variables were evaluated between the second and the fourth week after infarction. SVTA occurred in 113 (54%) patients: Supraventricular premature beats (SVPB) in 49 (24%), frequent or repetitive SVPB in 37 (18%), atrial or junctional tachycardia in 23 (11%), atrial flutter or fibrillation in 4 (2%). Most of these arrhythmias occurred in the absence of symptoms, and the most complex forms were always selflimiting. No relation was found among the presence of different forms of SVTA and sex, coronary risk factors, previous history of ischemic heart disease, type or site of acute myocardial infarction, NYHA functional class. Age, left atrial dimension (LAD), cardio-thoracic ratio (CTR) and left ventricular ejection fraction (LVEF) at rest differed significantly among three groups of patients: those without SVTA, those with SVPB less than 100 per hour and those with frequent-repetitive SVPB or atrial-junctional tachycardia. The more SVTA complexity, the worse LAD, CTR, LVEF and the higher the age. Multivariate discriminant analysis showed that CTR was directly and LVEF inversely related to the occurrence of SVPB less than 100 per hour, while the presence of frequent-repetitive SVPB or supraventricular tachycardia was closely related to increasing age, LAD, CTR and decreasing LVEF. Patients with atrial fibrillation always showed the worst values of LAD, CTR, LVEF and age. The results of the present study show that different types of SVTA occurring at discharge from hospital after myocardial infarction are clinically benign, but always suggestive of different degrees of left ventricular dysfunction.
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PMID:The relation between supraventricular tachyarrhythmias and left ventricular dysfunction after acute myocardial infarction. 326 15

To investigate whether resistance to activated protein C (APC resistance) because of a mutation in the factor V gene (factor V Leiden) leads to a decrease in life expectancy, we analyzed overall and cause-specific mortality in 171 parents whose offspring carried this mutation. Compared with the Dutch general population, and after adjustment for age, sex, and calendar period, we found no excess deaths in the parents (standardized mortality ratio [SMR], 1.0; 95% confidence interval [CI], 0.8 to 1.2). The cause-specific SMR for malignant neoplasms (1.0; 95% CI, 0.6 to 1.4), diseases of the circulatory system (1.0; 95% CI, 0.7 to 1.4), and cerebrovascular disease (1.0; 95% CI, 0.4 to 1.9) also did not differ from unity. The SMRs for diseases of the respiratory system (1.4; 95% CI, 0.6 to 2.6) and for ischemic heart diseases (1.1; 95% CI, 0.7 to 1.7) were slightly increased. Under the age of 45 years, there was a ninefold increase of dying from ischemic heart disease. Thromboembolic complications were mentioned only once (venous embolism or thrombosis) as an underlying ("primary") cause of death (SMR, 2.3; 95% CI, 0.1 to 13.0) and three times (pulmonary embolisms) as a contributing ("secondary") cause of death (SMR, 1.5; 95% CI, 0.3 to 4.4). We conclude that there is no major effect of APC resistance on life expectancy. Therefore, long-term anticoagulation in carriers of factor V Leiden, on the basis of the carrier state alone, is not indicated.
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PMID:Mortality and causes of death in families with the factor V Leiden mutation (resistance to activated protein C). 905 17

Non-steroidal antirheumatics (NSA) belong to the most often prescribed drugs. Certain observation studies indicate that they are used by 20 to 30% of population of developed countries. The most common NSA's adverse effects are gastrointestinal complications. Coxibs have been developed as an alternative to conventional non-selective NSA; with similar efficacy, they should reduce the risk of development of gastrointestinal complications. In the few last years, possible toxicity of coxibs and other non-steroidal antirheumatics has been widely discussed. The VIGOR study, which was performed 6 years ago, showed five times higher incidence of nonfatal myocardial infarction in patients with rofecoxib therapy as compared with naproxen. Afterwards, there was much debate about rofecoxib, and coxibs in general, whose cardiotoxicity was supported and confuted at the same time. Possible cardioprotective effect of naproxen was discussed too. Later on, results of the APPROVE study (Adenoma Polyp Prevention on Vioxx) made Merck & Co., Inc. withdraw rofecoxib from all markets voluntarily. In the end of 2004, three controversial studies on celecoxib were published. Although the first study (Adenoma Prevention with Celecoxib study, APC) showed higher cardiovascular risk of celecoxib, the second study (Prevention of Adenomatosus Polyps, PreSAP) did not verify these results. Surprisingly, the third study (Alzheimer Disease and Prevention Trial, ADAPT) proved 50% increase of the risk of cardiovascular (CV) toxicity of naproxen. In the last year, researchers have tried to decide whether CV toxicity is a class effect of coxib group or a class effect of all NSA. Many observation studies proved higher CV risk both of coxibs (particularly rofecoxib) and non-selective NSA including naproxen. These new findings moved the American FDA (Food and Drug Administration) to publish guidance concerning higher CV risk of all coxibs and NSA. For the time being, the EMEA (European Agency for Evaluation of Medicinal Products) does not change its attitude to NSA; coxibs are contraindicated in patients with ischemic heart disease, cerebrovascular disease and peripheral artery disease; they should be used with caution in high-risk patients. Final assessment of the problems of CV toxicity of NSA and coxibs will be a case of a long-term randomized study focused on the incidence of cardiovascular adverse effects.
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PMID:[Problems of cardiovascular toxicity of coxibs and non-selective NSA]. 1696 8

The association of statins with markers of inflammation, vasoconstriction, and coagulation was evaluated in 325 patients with abdominal aortic aneurysm with respect to statin treatment or not. Variables evaluated included routine laboratory markers, lipids, homocysteine, endothelin-1, matrix metalloproteinases (MMP)-2 and -9, and activated protein C-protein C inhibitor (APC-PCI) complex. Statin-treated patients were more often male (85% vs 75%; P = .024) and had ischemic heart disease (57% vs 19%; P < .0001). They showed lower levels of cholesterol (P < .0001), homocysteine (P = .027), MMP-9 (P = .038), and endothelin-1 (P = .005), and higher levels of APC-PCI complex (P = .042). Differences persisted in logistic regression for cholesterol (P < .0001), APC-PCI complex (P = .034), and homocysteine (P = .021). Statin-treated patients with abdominal aortic aneurysm show higher APC-PCI complex and lower homocysteine levels. Whether this translates into lower risk for aneurysm expansion or rupture will be evident from further follow-up.
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PMID:Associations between statin treatment and markers of inflammation, vasoconstriction, and coagulation in patients with abdominal aortic aneurysm. 1862 84

Currently available drugs for the acute treatment of migraine, i.e. ergot alkaloids and triptans, are cranial vasoconstrictors. Although cranial vasoconstriction is likely to mediate-at least a part of-their therapeutic effects, this property also causes vascular side-effects. Indeed, the ergot alkaloids and the triptans have been reported to induce myocardial ischemia and stroke, albeit in extremely rare cases, and are contraindicated in patients with known cardiovascular risk factors. In view of these limitations, novel antimigraine drugs devoid of vascular (side) effects are being explored. Currently, calcitonin gene-related peptide (CGRP) receptor antagonists, which do not have direct vasoconstrictor effects, are under clinical development. Other classes of drugs, such as 5-HT(1F) receptor agonists, glutamate receptor antagonists, nitric oxide synthase inhibitors, VPAC/PAC receptor antagonists and gap junction modulators, have also been proposed as potential targets for acute antimigraine drugs. Although these prospective drugs do not directly induce vasoconstriction, they may well induce indirect vascular effects by inhibiting or otherwise modulating the responses to endogenous vasoactive substances. These indirect vascular effects might contribute to the therapeutic efficacy of the previously mentioned compounds, but may alternatively also lead to vascular side-effects. As described in the current review, some of the prospective antimigraine drugs with a proposed non-vascular mechanism of action may still have direct or indirect vascular effects.
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PMID:Potential mechanisms of prospective antimigraine drugs: a focus on vascular (side) effects. 2113 Aug 7