Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enalapril is an effective agent in the treatment of mild to severe hypertension. It is equally effective in elderly and young adult patients but appears to be more effective in white than in black hypertensive patients. Following treatment with enalapril, an assessment of maximum exercise performance found a decrease in total peripheral resistance without significant changes in cardiac output, heart rate, or stroke volume compared with pretreatment values. In addition, there have been reports of reversal of left ventricular hypertrophy in enalapril-treated hypertensive patients. Enalapril is also effective and well tolerated in hypertensive patients with renal impairment of varying etiology. The most common adverse experiences reported in controlled clinical trials were headache (5.2%), dizziness (4.3%), and fatigue (3.0%). In high-risk hypertensive patients, no enalapril-treated neutropenia, proteinuria, dysgeusia, or ageusia were reported. It may be concluded that the benefit-to-risk ratio of enalapril is among the best of the antihypertensive therapies currently available.
J Cardiovasc Pharmacol 1990
PMID:Enalapril: benefit-to-risk ratio in hypertensive patients. 169 15

Platelets and neutrophils accumulate rapidly in infarcted myocardium. Although antineutrophil agents reduce the size of the infarcted area, this is not observed with antiplatelet drugs. The possibility that myocardial ischemia-induced platelet deposition was secondary to a neutrophil-mediated event was assessed by injecting prostacyclin-washed autologous 111In-labeled platelets and measuring the amount of radioactivity in different regions of the heart following 90-min occlusion of the left anterior descending coronary artery followed by reperfusion for periods up to 5 h. Platelet deposition during the reperfusion phase was linear with time and similar to the time course of neutrophil accumulation. There was a transmural distribution of radioactivity across the myocardium where the "zone" between infarcted and risk regions, called the "interface," greater than infarct greater than risk greater than normal. Neutropenia (21 +/- 2% control levels), induced with specific sheep anti-dog neutrophil antiserum, had minimal effects on platelet aggregation ex vivo, but significantly reduced platelet accumulation in the ischemic myocardium following 5-h reperfusion and abolished the transmural platelet distribution. These results suggest that myocardial platelet deposition is secondary to a neutrophil-mediated event in this occlusion-reperfusion model of myocardial injury. Interactions between platelets and neutrophils at the site of tissue damage may influence the process of myocardial ischemic injury.
J Cardiovasc Pharmacol
PMID:Neutrophil depletion suppresses 111In-labeled platelet accumulation in infarcted myocardium. 241 99

Complement activation and pulmonary leukostasis with neutropenia occur in hemodialysis and filtration leukapheresis, with attendant pulmonary dysfunction. Wondering whether similar phenomena might attend cardiopulmonary bypass (CPB), we studied 34 patients undergoing coronary artery bypass operations. As in the other extracorporeal circulation systems, neutropenia (mean 44.7% +/- 4.3% SEM of prebypass PMN count) occurred during the first half hour of bypass and then a rebound neutrophilia followed. CH50 and C3H50 fell 22% to 25% (p for CH50 less than 0.01) during bypass, but C3 conversion and C5a were not demonstrable in patient plasmas. Nonetheless, polymorphonuclear neutrophils (PMNs) harvested late in bypass showed low adherence to nylon and selective chemotactic and aggregative insensitivity to C5a--functional aberrations which are seen after exposure to activated complement. Furthermore, smaller infusions of activated complement into animals produced neutropenia than were required to achieve a detectable [C5a] in the plasma. We conclude that neutropenia during CPB probably results from complement activation below the threshold of detection; complement-stimulated PMNs deserve study as possible mediators of tissue injury occurring during CPB.
J Thorac Cardiovasc Surg 1981 Mar
PMID:Complement activation and neutropenia occurring during cardiopulmonary bypass. 697 Mar 4

Standard antifungal medical therapy of invasive pulmonary aspergillosis that occurs in immunocompromised patients with hematologic diseases with neutropenia or in liver transplant recipients results in less than a 5% survival. In view of these dismal mortality rates, we adopted an aggressive approach with resection of the involved area of lung along with systemic antifungal therapy when localized invasive pulmonary aspergillosis developed in these patients. Between January 1987 and December 1993, 14 patients with hematologic diseases and 2 liver transplant recipients underwent resection of acute localized pulmonary masses suggestive of invasive pulmonary aspergillosis a median of 7.5 days (range 1 to 45 days) after the diagnosis was clinically suggested and confirmed by chest computed tomographic scans. Operative procedures done included two pneumonectomies, one bilobectomy with limited thoracoplasty, nine lobectomies, and five wedge resections (one patient with hematologic disease had two procedures). All patients were treated before and after the operation with antifungal agents. Nine (64%) of 14 patients with hematologic disease and 2 (100%) of 2 liver transplant recipients survived the hospitalization with no evidence of recurrent Aspergillus infection after a median 8 months of follow-up (range 3 to 82 months). The five hospital deaths (all patients with hematologic diseases) occurred a median of 20 days after operation from diffuse alveolar hemorrhage in three, graft-versus-host disease in one, and multiple organ system failure with presumed disseminated Aspergillus infection in one. Four of the five deaths were in patients with allogeneic bone marrow transplants. Two of the three patients requiring resection of multiple foci of infection died, as did the only patient who was preoperatively ventilator dependent. In immunocompromised patients with hematologic diseases or liver transplantation with invasive pulmonary aspergillosis, early pulmonary resection should be strongly considered when the characteristic clinical and radiographic pictures appear.
J Thorac Cardiovasc Surg 1995 Jun
PMID:Pulmonary resection for invasive Aspergillus infections in immunocompromised patients. 777 82

Polymorphonuclear neutrophils (PMNs) may contribute to organ injury in both hemorrhagic and endotoxic shock. Both models of shock exhibit a "flight of the leukocytes," but the mechanisms for entrapment of leukocytes in the microcirculation differ. The objective of this study was to investigate lipopolysaccharide (LPS)-induced shock and hemorrhagic shock with similar survival rates, in terms of circulating PMNs, activated circulating PMNs, plasma tumor necrosis factor (TNF) activity, and PMN adhesion. In the LPS protocol, rats received 6.5 mg/kg E. coli LPS i.v., which resulted in 50% survival. In the hemorrhagic shock protocol, rats were maintained for 3 h at 40 mm Hg mean arterial pressure, and survival during a 24-h observation period was 40%. LPS injection and hemorrhage caused rapid neutropenia in survivors and nonsurvivors. Low circulating PMN counts persisted during hypotension in the hemorrhagic protocol and among nonsurvivors in the LPS protocol, but in both protocols a tendency toward significantly higher circulating PMN counts in survivors compared with nonsurvivors was found. In both protocols, survivors had significantly lower fractions of circulating activated PMNs and lower adhesion of circulating PMNs to nylon fibers. In the LPS protocol, higher plasma TNF activity was found in nonsurvivors than in survivors, but no TNF activity in plasma could be found throughout the hemorrhagic protocol. These results indicate that nonsurvivors in both shock models exhibit higher levels of PMN activation. No correlation was detected between PMN activation and plasma TNF activity to suggest that TNF serves as the primary mediator of circulating PMN activation.
J Cardiovasc Pharmacol 1995
PMID:Neutrophil activation, tumor necrosis factor, and survival after endotoxic and hemorrhagic shock. 869 57

Release of calprotectin and interleukin-8 (IL-8), changes in leukocyte counts and subsets and influence of extracorporeal ultrafiltration were evaluated during and after cardiopulmonary bypass (CPB) in 18 children undergoing open-heart surgery for congenital heart anomalies. Ultrafiltration was used in nine cases and nine were controls. Calprotectin concentration rose after start of CPB, peaking 48 hours postoperatively, with no significant intergroup difference. Positive correlation was found between duration of CPB and calprotectin (peak level and accumulated total). Circulating IL-8 was detected in all patients perioperatively, peaking at wound closure in the ultrafiltration group and at termination of bypass in the controls. CPB duration correlated significantly to peak level and accumulated total of IL-8. Seven of nine ultrafiltrate samples contained IL-8 at levels similar to the plasma concentration. Changes in white cell counts were mainly attributable to neutrophils. The two subgroups did not differ significantly in neutrophil counts. Neutropenia found after 10 minutes of CPB was replaced by neutrophilia, with maximal values postoperatively. Calprotectin and IL-8 thus were released into the circulation during CPB in children. Ultrafiltration did not affect the plasma concentrations of these substances, and only IL-8 was detected in the ultrafiltrate.
Scand J Thorac Cardiovasc Surg 1996
PMID:Release of interleukin-8 and calprotectin during and after paediatric cardiopulmonary bypass with and without ultrafiltration. 885 75

In patients with transient ischemic attack (TIA) or ischemic stroke of noncardiac origin, antiplatelet drugs are able to decrease the risk of stroke by 11% to 15%, and decrease the risk of stroke, myocardial infarction (MI), and vascular death by 15% to 22%. Aspirin leads to a moderate but significant reduction of stroke, MI, and vascular death in patients with TIA and ischemic stroke. Low doses are as effective as high doses, but are better tolerated in terms of gastrointestinal side effects. The recommended aspirin dose, therefore, is between 50 and 325 mg. Bleeding complications are not dose-dependent, and also occur with the lowest doses. The combination of aspirin (25 mg twice daily) with slow-release dipyridamole (200 mg twice daily) is superior compared with aspirin alone for stroke prevention. Ticlopidine is effective in secondary stroke prevention in patients with TIA and stroke. For some end points, it is superior to aspirin. Due to its side-effect profile (neutropenia, thrombotic thrombocytopenic purpura ), ticlopidine should be given to patients who are intolerant of aspirin. Prospective trials have not indicated whether ticlopidine is suggested for patients who have recurrent cerebrovascular events while on aspirin. Clopidogrel has a better safety profile than ticlopidine. Although not investigated in patients with TIA, clopidogrel should also be effective in these patients assuming the same pathophysiology than in patients with stroke. Clopidogrel is second-line treatment in patients intolerant for aspirin, and first-line treatment for patients with stroke and peripheral arterial disease or MI. A frequent clinical problem is patients who are already on aspirin because of coronary heart disease or a prior cerebral ischemic event, and then suffer a first or recurrent TIA or stroke. No single clinical trial has investigated this problem. Therefore, recommendations are not evidence-based. Possible strategies include the following: continue aspirin, add dipyridamole, add clopidogrel, switch to ticlopidine or clopidogrel, or switch to anticoagulation with an International Normalized Ratio (INR) of 2.0 to 3.0. The combination of low-dose warfarin and aspirin was never studied in the secondary prevention of stroke. In patients with a cardiac source of embolism, anticoagulation is recommended with an INR of 2.0 to 3.0. At the present time, anticoagulation with an INR between 3.0 and 4.5 cannot be recommended for patients with noncardiac TIA or stroke. Anticoagulation with an INR between 3.0 and 4.5 carries a high bleeding risk. Whether anticoagulation with lower INR is safe and effective is not yet known. Treatment of vascular risk factors should also be performed in secondary stroke prevention.
Curr Treat Options Cardiovasc Med 2002 Oct
PMID:Antithrombotic Secondary Prevention After Stroke. 1219 15

Cardiomyopathies are the most common disorders resulting in heart failure, with dilated cardiomyopathy being responsible for the majority of cases. Other forms of cardiomyopathy, especially hypertrophic forms, are also important causes of heart failure. The mortality rate due to cardiomyopathy in the USA is over 10,000 deaths per year, and the costs associated with heart failure are approximately 200 million US dollars per year in the USA alone. Over the past few years, breakthroughs have occurred in understanding the basic mechanisms of these disorders, potentially enabling clinicians to devise improved diagnostic strategies and therapies. As at least 30 to 40% of cases are inherited, it is now imperative that the genetic basis for these disorders is clearly recognized by caregivers and scientists. However, it has also become clear that these diseases are genetically highly heterogeneous, with multiple genes identified for each of the major forms of cardiomyopathy, and most patients having private mutations. These data suggest that the genetic diagnosis of most patients with cardiomyopathy will be impractical with current technologies. However, there are a few exceptions, such as patients with X-linked cardiomyopathies, with or without the concomitant abnormalities of cyclic neutropenia and 3-methylglutaconic aciduria, or patients with cardiomyopathy associated with conduction disease: these appear to be associated with mutations in a small subset of genes, and can be investigated by certified diagnostic laboratories. This review will summarize current knowledge of the genetics of inherited cardiomyopathies and how findings from research laboratories may be translated into the diagnostic laboratory.
Expert Rev Cardiovasc Ther 2004 Sep
PMID:Genetics of inherited cardiomyopathies. 1535 Jan 70

Azimilide is an investigational Class III antiarrhythmic that has been developed for treating both supraventricular and ventricular tachyarrhythmias. Similar to other Class III antiarrhythmics, azimilide prolongs myocardial repolarization in a dose-dependent manner by increasing the action potential duration, QT interval, and effective refractory period. The most frequent reported side effect is headache, with rare serious adverse events of early reversible neutropenia and Torsades de Pointes. In long-term follow up, the patient withdrawal rate has been low. Azimilide has very predictable pharmacokinetics, is predominantly hepatically metabolized, and has no significant drug interactions with digoxin or warfarin. In animal models, azimilide has been shown to be very effective in suppressing both atrial and ventricular tachyarrhythmias, decreasing the defibrillation energy requirement, and preventing post-myocardial infarction ventricular tachycardia and fibrillation. Clinically, in a series of 4 double-blind, randomized, placebo-controlled trials, the Azimilide Supraventricular Arrhythmia Program which included over 1000 patients and approximately 70% with structural heart disease, azimilide showed a significant prolongation in the time to first recurrence of paroxysmal supraventricular tachycardia or atrial fibrillation/flutter. With respect to ventricular tachyarrhythmias, the AzimiLide post-Infarct surVival Evaluation Trial was a large randomized, multinational, prospective, placebo-controlled study in recent survivors of myocardial infarction at high risk for sudden cardiac death. After 1 year of follow-up, this study showed no statistical difference in all-cause mortality between placebo and azimilide. However, azimilide did statistically reduce the incidence of new atrial fibrillation. Further trials are necessary to evaluate the efficacy of azimilide in patients with symptomatic ventricular arrhythmias.
Curr Drug Targets Cardiovasc Haematol Disord 2005 Feb
PMID:Azimilide, a novel oral class III antiarrhythmic for both supraventricular and ventricular arrhythmias. 1572 Feb 25

Patients experiencing stroke or transient ischemic attack (TIA) are at high risk for recurrent (secondary) strokes, which comprise 29% of all strokes in the United States. Current recommendations for prevention of secondary stroke from the American College of Chest Physicians (ACCP) call for the broad use of platelet antiaggregation (antiplatelet) agents for patients with a history of noncardioembolic stroke or TIA. Five agents--aspirin, ticlopidine, clopidogrel, extended-release dipyridamole (ER-DP), and triflusal--have demonstrated efficacy in large-scale clinical studies in the prevention of recurrent vascular events and/or stroke in patients with a history of stroke. The results of the following studies are reviewed and compared: the Swedish Aspirin Low-Dose Trial (SALT), the United Kingdom Transient Ischaemic Attack (UK-TIA) Aspirin Trial, Dutch Transient Ischemic Attack (Dutch TIA) study (aspirin), the Canadian American Ticlopidine Study (CATS), the Ticlopidine Aspirin Stroke Study (TASS), the African American Antiplatelet Stroke Prevention Study (AAASPS) (ticlopidine), the Clopidogrel versus Aspirin in Patients at Risk of Recurrent Ischemic Events (CAPRIE) trial, the Management of Atherothrombosis With Clopidogrel in High-Risk Patients study (MATCH) (clopidogrel), the second European Stroke Prevention Study (ESPS2) (aspirin plus ER-DP), and the Triflusal versus Aspirin in Cerebral Infarction Prevention (TACIP) study. In comparative monotherapy studies of patients with previous stroke, ticlopidine demonstrates statistically significant improved efficacy over aspirin, and clopidogrel demonstrates nonsignificant slight improvement over aspirin for the prevention of ischemic cardiac and cerebrovascular events; however, the adverse event profile of ticlopidine (including rash, diarrhea, and neutropenia) will probably limit its long-term use. Among combination approaches, only aspirin plus ER-DP has demonstrated statistically significant, clinically meaningful additive benefit over monotherapy with each agent. Clopidogrel plus aspirin did not significantly improve preventive efficacy and increased the risk of serious side effects, including life-threatening bleeding episodes. The 15,500-patient PRoFESS (the Prevention Regimen for Effectively Avoiding Second Strokes) study, with results expected in 2008, will directly compare aspirin plus ER-DP with clopidogrel monotherapy for the prevention of recurrent stroke and should provide statistically robust estimates of comparative efficacy for the development of improved recommendations.
J Cardiovasc Pharmacol Ther 2005 Sep
PMID:Review of antiplatelet therapy in secondary prevention of cerebrovascular events: a need for direct comparisons between antiplatelet agents. 1621 Dec 3


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