Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gallium-67 scans have been widely employed in patients with sarcoidosis as a means of indicating alveolitis and the need for corticosteroid therapy. Observation of 32 patients followed 3 or more years after gallium scans showed no correlation between findings and later course: of 10 patients with pulmonary uptake, 7 recovered with minor residuals; of 18 patients with mediastinal of extrathoracic uptake, 10 had persistent or progressive disease; of 4 patients with negative initial scans, 2 had later progression. The value of gallium-67 scans as an aid to diagnosis was studied in 40 patients with extrapulmonary sarcoidosis. In 12 patients, abnormal lacrimal, nodal, or pulmonary uptake aided in selection of biopsy sites. Gallium-67 scans and serum ACE levels were compared in 97 patients as indices of clinical activity. Abnormal gallium-67 uptake was observed in 96.3% of the tests in active disease, and ACE level elevation occurred in 56.3%. In 24 patients with inactive or recovered disease, abnormal gallium-67 uptake occurred in 62.5% and ACE level elevation in 37.5%. Gallium-67 scans have a limited but valuable role in the diagnosis and management of sarcoidosis.
 ...
PMID:Assessment of gallium-67 scanning in pulmonary and extrapulmonary sarcoidosis. 301 58

Digitalis has been widely used in the treatment of cardiac disease for more than 200 years. The present article reviews the current role of digitalis in the management of heart failure and atrial fibrillation (AF) in light of recent study findings. Generally, first-line therapy for the management of heart failure due to systolic dysfunction should include an ACE inhibitor and a diuretic. In patients who remain symptomatic despite the use of these drugs, the addition of digoxin should be considered. Because digoxin has been shown to reduce the number of hospital admissions attributable to worsening heart failure, more liberal use of digoxin in the management of heart failure may be justified. Digoxin may be adequate as monotherapy for ventricular rate control in patients with chronic AF, particularly in sedentary and elderly patients. A beta-blocker or calcium antagonist (either alone or in combination with digoxin) is indicated when digoxin is ineffective for ventricular rate control. Digoxin is ineffective in restoring sinus rhythm, preventing paroxysms or controlling rate in paroxysmal AF. The elderly are at an increased risk of digoxin toxicity. Low dosages of digoxin appear to be effective in the treatment of heart failure due to systolic dysfunction and may reduce the incidence of digitalis toxicity in these patients. In elderly patients with AF and inadequate rate control who are receiving digitalis monotherapy, adding another atrioventricular nodal blocking drug may be more appropriate than increasing the digoxin dose, in order to avoid toxic digoxin levels.
 ...
PMID:When, and when not, to use digoxin in the elderly. 920 47

Aging and hypertension are associated with a progressive decline in renal blood flow and renal function. As a result, physicians planning therapeutic strategies to control blood pressure need to consider these changes and how they relate to potassium homeostasis, particularly in elderly patients. Commonly used antihypertensive drugs such as beta-blockers, angiotensin converting enzyme inhibitors and potassium-sparing diuretics need to be used with increasing caution in patients with declining renal function. This is especially important in patients with diabetes who may also have type IV renal tubular acidosis, and in patients given concomitant therapy with non-steroidal anti-inflammatory drugs. Other therapies such as calcium channel blockers, particularly those that gate atrioventricular nodal conduction, also need to be used with care in people with significant renal insufficiency and hyperkalemia, as this clinical scenario may result in a greater risk of complete heart block.
 ...
PMID:Non-diuretic-based antihypertensive therapy and potassium homeostasis in elderly patients. 943 77

Drugs classified as calcium channel blockers (CHBs) are now among the most frequently prescribed drugs for the treatment of cardiovascular disease. Although the currently available CCBs have major differences in their structural and cardiovascular effects, they share the common property of blocking the transmembrane flow calcium ions through voltage gated L-type channels. These drugs have been approved for the treatment of hypertensive heart disease: they reduce left ventricular hypertrophy and improve its sequelae, such as ventricular dysrhythmias, impaired filling and contractility, and myocardial ischemia. Long-acting CCBs have been shown to reduce mortality and morbidity in elderly patients with systolic hypertension, appear to be extremely useful in patients with cyclosporin-induced hypertension, and can be used as alternatives to ACE inhibitors in patients with hypertension and concomitant diabetes mellitus, renal disease, Raynaud's phenomenon or migraine. Long-acting dihydropyridine have been shown to be effective and safe in the treatment classic angina pectoris and vasospastic angina, supraventricular arrhythmias, particularly reentrant AV-nodal tachycardia, others to be beneficial in patients with congestive heart failure, and all of them have potential for decreasing atherogenesis.
 ...
PMID:[Calcium channel blockers in the treatment of cardiovascular disease]. 1157 40

Despite the introduction of a variety of new classes of drugs for the management of heart failure, digoxin continues to have an important role in long-term outpatient management. A wide variety of placebo-controlled clinical trials have unequivocally shown that treatment with digoxin can improve symptoms, quality of life, and exercise tolerance in patients with mild, moderate, or severe heart failure. These benefits are evident regardless of the underlying rhythm (normal sinus rhythm or atrial fibrillation), etiology of the heart failure, or concomitant therapy (eg. ACE inhibitors). Unlike other agents with positive inotropic properties, digoxin does not increase all-cause mortality and has a substantial benefit in reducing heart failure hospitalizations. Consensus guidelines have recently been published by the Heart Failure Society of America and the American College of Cardiology/American Heart Association, and they contain the following recommendations for digoxin treatment: 1. Digoxin should be considered for the outpatient treatment of all patients who have persistent symptoms of heart failure (NYHA class II-IV) despite conventional pharmacologic therapy with diuretics, ACE inhibitors, and a beta-blocker when the heart failure is caused by systolic dysfunction (the strength of evidence = A for NYHA class II and III; strength of evidence = C for NYHA class IV). 2. Digoxin is not indicated as primary treatment for the stabilization of patients with acutely decompensated heart failure. (Strength of evidence = B). Digoxin may be initiated after emergent treatment of heart failure has been completed in an effort to establish a long-term treatment strategy. 3. Digoxin should not be administered to patients who have significant sinus or atrioventricular block, unless the block has been treated with a permanent pacemaker (strength of evidence = B). The drug should be used cautiously in patients who receive other agents known to depress sinus or atrioventricular nodal function (such as amiodarone or a beta-blocker) (strength of evidence = B). 4. The dosage of digoxin should be 0.125-0.25 mg daily in the majority of patients (strength of evidence = C). The lower dose should be used in patients over 70 years of age, those with impaired renal function, or those with a low lean body mass. Higher doses (eg, digoxin 0.375-0.50 mg daily) are rarely needed. Loading doses of digoxin are not necessary during initiation of therapy for patients with chronic heart failure. 5. Serial assessment of serum digoxin levels is unnecessary in most patients. The radioimmunoassay was developed to assist in the evaluation of toxicity, not the efficacy of the drug. There appears to be little relationship between serum digoxin concentration and the drug's therapeutic effects. 6. Digoxin toxicity is commonly associated with serum levels >2 ng/mL but may occur with lower digoxin levels if hypokalemia, hypomagnesemia, or hypothyroidism coexist. Likewise, the concomitant use of agents such as quinidine, verapamil, spironolactone, flecainide, and amiodarone can increase serum digoxin levels and increase the likelihood of digoxin toxicity. 7. For patients with heart failure and atrial fibrillation with a rapid ventricular response, the administration of high doses of digoxin (>0.25 mg daily) for the purpose of rate control is not recommended. When necessary, additional rate control should be achieved by the addition of beta-blocker therapy or amiodarone (strength of evidence = C). If amiodarone is added, the dose of digoxin should be reduced. Digitalis preparations are now entering their fourth century of clinical use for the treatment of chronic heart failure symptoms. Its clinical efficacy can no longer be doubted and its safety has been verified by the multicenter DIG trial. Future advances in pharmacogenetics should facilitate identification of those patients most likely to benefit from its pharmacologic effects.
 ...
PMID:Digoxin remains useful in the management of chronic heart failure. 1269 28

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with substantial cardiovascular morbidity and mortality. The arrhythmia can be initiated and/or maintained by rapidly firing foci, single- and multiple-circuit reentry. Once initiated, AF alters atrial electrical and structural properties (atrial remodeling) in a way that promotes its own maintenance and recurrence and may alter the response to antiarrhythmic drugs. Thus, initial episodes of paroxysmal (self-terminating) AF lengthens to the point where the arrhythmia becomes persistent (requires cardioversion to restore sinus rhythm) and permanent. AF usually requires a trigger for initiation and a favorable electrophysiological and/or anatomical substrate for maintenance. The substrate includes both cardiovascular (coronary artery disease, valvular heart disease, heart failure, hypertension, dilated cardiomyopathy) and non cardiovascular diseases (thyrotoxicosis, pulmonary diseases). Accordingly, the initial step in patients with AF requires a careful assessment of symptoms and identification of underlying reversible triggers and potentially modifiable underlying structural substrate and treat them aggressively. In contrast to other cardiac arrhythmias, antiarrhythmic drugs (ADs) are the mainstay of therapy. Long-term treatment of AF is directed to restore and maintain the sinus rhythm with class I and III ADs (rhythm-control) or to allow AF to persist and ensure that the ventricular rate is controlled (rate-control) with atrioventricular nodal blocking drugs (digoxin, beta-blockers, verapamil, diltiazem) and prevent thromboembolic complications with anticoagulants. However, the long-term efficacy of ADs for preventing AF recurrence is far from ideal, because of limited efficacy (AF recurs in at least one-half of the patients) and potential side effects, particularly proarrhythmia. Thus, the choice of the appropriate AD will depend on the temporal pattern of the arrhythmia, the presence of associated diseases, easy of administration and adverse effects profile, particularly the risk of proarrhythmia. The recent finding that angiotensin converting enzyme inhibitors and beta-blockers reduce the incidence of AF in patients post myocardial infarction with left ventricular dysfunction confirmed the importance of targeting the underlying arrhythmogenic substrate. This review focuses on the mechanisms underlying AF and the mechanism of action and the efficacy and safety profile of the ADs used in the treatment of atrial fibrillation. The advantages and disadvantages of rhythm and rate control, the role pill in a pocket concept and the role of the new ADs are dicussed.
 ...
PMID:Pharmacological approaches in the treatment of atrial fibrillation. 1475 23

A case of 80-year-old woman with marked hyperkalemia in the course of chronic treatment with angiotensin converting enzyme (ACE) inhibitors and spironolactone is presented. AAI pacemaker was implanted three months ago. The ECG revealed a nodal rhythm, ineffective AAI pacing and other typical features of hyperkalemia. After normalisation of potassium level the ECG changes disappeared. Potential mechanism of the nodal rhythm during ineffective atrial pacing is discussed.
 ...
PMID:[Ineffective atrial pacing and cardiac arrest in a 80-year old woman with hyperkalemia]. 1616 57

Atrial fibrillation is a common and in most patients recurrent arrhythmia. Atrial fibrillation can increase mortality and causes at times severe symptoms in affected patients. Timely initiation of sustained oral anticoagulation is indicated in patients with atrial fibrillation at risk for stroke to prevent thromboembolic complications. Patients at risk for stroke can be identified by clinical characteristics using validated score systems, e.g., the CHADS(2) score or the Framingham score. Drugs that slow AV nodal conduction can improve symptoms associated with high ventricular rate. Cardioversion can acutely terminate atrial fibrillation in almost all patients, but many patients suffer from recurrent atrial fibrillation. The prevention of arrhythmia recurrences ("rhythm control therapy") is indicated in patients with severe arrhythmia-related symptoms. Antiarrhythmic drugs can approximately double the maintenance rate of sinus rhythm. Other drugs that were not primarily developed as antiarrhythmic agents, e.g., ACE inhibitors, sartans, and possibly statins, can further improve maintenance of sinus rhythm in selected patient groups. Catheter-based isolation of the pulmonary veins is a recently developed intervention that can cure some forms of atrial fibrillation. It is likely that a multimodal therapeutic approach will in the future allow rhythm control therapy to become more effective.
 ...
PMID:[Treatment of atrial fibrillation]. 1763 95

Primary diffuse large B-cell lymphomas of different immune-privileged sites (IP-DLBCLs) share many clinical and biological features, such as a relatively poor prognosis, preferential dissemination to other immune-privileged sites, and deletion of the HLA region, which suggests that IP-DLBCL represents a separate entity. To further investigate the nature of IP-DLBCL, we investigated site-specific genomic aberrations in 16 testicular, nine central nervous system (CNS), and 15 nodal DLBCLs using array CGH. We also determined minimal common regions of gain and loss. Using robust algorithms including multiple testing procedures and the ACE-it script, which is specifically designed for this task, the array CGH data were combined with gene expression data to explore pathways deregulated by chromosomal aberrations. Loss of 6p21.32-p25.3, including the HLA genes, was associated with both types of IP-DLBCL, whereas gain of 2p16.1-p25.3 was associated with nodal DLBCL. Gain of 12q15-q21.1 and 12q24.32-q24.33 was associated with CNS DLBCL and gain of 19q13.12-q13.43 with testicular DLBCL. Analysis of candidate genes in site-specific regions and minimal common regions revealed two major groups of genes: one involved in the immune response, including regulation of HLA expression, and the other involved in apoptosis, including the p53 pathway. Many of these genes were also involved in homozygous deletions or high-level gains. The presence of both shared and site-specific aberrations in CNS and testicular DLBCLs underlines the concept of IP-DLBCL but also indicates that IP-DLBCLs of the CNS and testis do not form a single entity. The observed aberrations emphasize the importance of the deregulation of anti-tumour immune response and apoptosis pathways.
 ...
PMID:Genomic alterations and gene expression in primary diffuse large B-cell lymphomas of immune-privileged sites: the importance of apoptosis and immunomodulatory pathways. 1872 69