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)

Clopidogrel is a new thieno-pyridine derivative and has a more potent inhibitory effect on platelet aggregation, dependent on ADP rather than ticlopidine. In a phase I study performed in Japan, significant inhibition of ADP-induced platelet aggregation and prolongation of bleeding time was observed in the dose range of 25, 50 and 75 mg. These effects were comparable to 200 or 300 mg of ticlopidine. Antithrombotic effects have also been shown in experimental animal models. Clopidogrel is expected to reduce the incidence of neutropenia since smaller doses are sufficient to suppress platelet aggregation compared to ticlopidine. Clopidogrel has been proven to be a potent and well-tolerated antiplatelet agent for atherosclerosis patients at risk of thrombosis, in Europe.
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PMID:[Antiplatelet effect of clopidogrel]. 161 93

Aspirin (acetylsalicylic acid) is effective in reducing vascular outcome events in patients with atherosclerosis: a relative risk reduction of about 30% for stroke, 22% for stroke and death, and 15% for vascular mortality. It is probable that low and high dose aspirin are similar in efficacy. Complications are more frequent with high dose aspirin than with low doses. Four randomised trials evaluating sulfinpyrazone vs placebo, and 3 trials evaluating sulfinpyrazone vs aspirin, showed more cerebrovascular events in the sulfinpyrazone group than in the aspirin and placebo groups. One small trial comparing dipyridamole with placebo in patients with cerebrovascular disease found no difference between the 2 groups in outcome. No other studies have compared dipyridamole alone with placebo or aspirin. The European Stroke Prevention Study II is currently in progress and is comparing dipyridamole + aspirin, dipyridamole, aspirin, and placebo. In the first year, the Ticlopidine Aspirin Stroke Study (TASS) showed a 42% risk reduction for stroke and death using the efficacy analysis and a 47% risk reduction for stroke and stroke death. Ticlopidine was more effective than aspirin in reducing stroke in both males and females. Apart from a reversible severe neutropenia in 0.86% of patients, ticlopidine-related adverse effects were relatively benign and reversible. The Canadian-American Ticlopidine Study (CATS) compared ticlopidine with placebo in patients with completed major strokes. The cumulative event rates for the primary outcome events of stroke, myocardial infarction and vascular death, using the efficacy approach, show clear evidence of separation almost immediately after randomisation, consistent with a constant risk reduction of about 30% in the ticlopidine group. These data provide strong evidence that ticlopidine conveys a clinically important reduction in the risk of thromboembolic events in patients with a history of completed thromboembolic stroke. In conclusion, aspirin is effective in preventing atherothrombotic morbidity and mortality. It reduces the overall vascular event rate by about 25%. Sulfinpyrazone and dipyridamole appear to add nothing important over aspirin alone. Ticlopidine is more effective than aspirin in preventing stroke. The modest, reversible risk of neutropenia, affecting less than 1% of patients, makes the benefit: risk ratio a reasonable one.
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PMID:Antiplatelet therapy in the prevention of stroke. 172 15

Patients with atherosclerotic carotid artery stenosis commonly have arterial disease elsewhere, especially coronary artery disease. The aim of the medical treatment is to reduce the incidence of stroke, myocardial infarction and vascular death. Both primary and secondary prevention of these vascular events requires control of vascular risk factors, particularly lowering elevated blood pressure, lowering of elevated blood cholesterol and stopping smoking. Aspirin and ticlopidine are effective in reducing vascular events in patients with atherosclerosis, with a relative reduction of about 25% for the composite outcome event "stroke, myocardial infarction or vascular death". Whether low dose (less than 100 mg/d), medium (300 mg/d) or high dose (1,000 mg/d or more) of aspirin confer the same degree of protection against vascular events is unclear. The gastrointestinal side effects are greater for the high dose than for the medium dose, but the difference between the medium dose and the low dose is very small. Ticlopidine conveys a modest risk of reversible severe neutropenia and is often used as a second-line drug, but this is a controversial issue. Heparin is often used as a short-term preventive treatment in patients with transient ischaemic attacks or minor stroke, especially in those with "crescendo" transient ischaemic attacks, progressing stroke, severe carotid stenosis or intraluminal thrombus.
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PMID:[Medical treatment of atherosclerotic carotid stenoses]. 815 33

Intravascular metallic stents are increasingly used in the non-surgical management of coronary atherosclerosis. Despite intensive anticoagulation, subacute stent thrombosis, which usually has serious clinical consequences, and major haemorrhagic complications remain major problems after stent implantation. In addition, conventional management with anticoagulant therapy requires prolonged hospitalization. In a prospective multicentre study, we investigated the efficacy of a combination of two antiplatelet agents, ticlopidine 500 mg daily and aspirin 200 mg daily, without oral anticoagulation after stent implantation. Since November 1993, 529 consecutive patients, in whom 545 vessels were successfully stented with conventional (non-heparin coated) stents have been enrolled. Stenting was performed as a bailout procedure for failed angioplasty in 112 patients, for a suboptimal result after angioplasty in 314 patients, and electively in the remaining 103 patients. Coronary events related, or possibly related, to stent thrombosis occurred in 5.4% of patients stented as a bailout procedure and in 1.8% of patients stented for a suboptimal result. Serious bleeding complications occurred in 5.4% of patients stented as a bailout procedure and 1.5% of patients stented for a suboptimal result. Neither stent thrombosis nor serious bleeding complications were seen in patients stented electively. Ticlopidine therapy was discontinued in 1.9% of patients due to neutropenia (0.6%) or rash (1.3%). Mean hospital stay decreased from 6.16 +/- 2.14 days to 4.2 +/- 2.15 days during the study period. A combination of two antiplatelet agents can be employed in the vast majority of patients after coronary stent implantation. Subacute stent thrombosis rates and bleeding complications compare favourably with those reported using conventional therapy and the duration of hospitalization is reduced.
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PMID:Combined antiplatelet therapy with ticlopidine and aspirin. A simplified approach to intracoronary stent management. 888 9

1 The rabbit receptor for C5a was cloned from a genomic library and found to be 79.5% identical to the human homologue, the highest degree of similarity found so far in nonprimate laboratory animals. 2 The rabbit C5a receptor stably expressed in RBL cells binds human 125I-C5a (2 nM). Unlabelled C5a and the C-terminal analogue N-acetyl-Tyr-Ser-Phe-Lys-Pro-Met-Pro-Leu-D-Ala-Arg (Ac-YSFKPMPLaR) were found to be competitors of that binding, the peptide analogue retaining approximately 0.1% of the affinity of human C5a. 3 The order of potency human C5a>Ac-YSFKPMPLaR was conserved in bioassays based on rabbits (relaxation of the isolated portal vein and pulmonary artery; acute in vivo neutropenia), but with a decreasing potency gap between the two compounds, a likely consequence of the resistance to peptidases of the analogue. 4 The molecular definition of the rabbit C5a receptor evidenced a high preservation degree of sequence and pharmacologic properties relative to the human ortholog receptor, thus defining a set of molecular tools for the investigation of the role of C5a in physiologic and pathologic models based on the rabbit (e.g. atherosclerosis, inflammation).
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PMID:Cloning and preliminary pharmacological characterization of the anaphylatoxin C5a receptor in the rabbit. 1051 Apr 41

Thrombosis of upper extremity arteries is most commonly due to atherosclerosis of the proximal subclavian artery, trauma, or catheter-related injury. In the absence of an identifiable cause, a search for a hypercoagulable state is indicated. Hematologic manifestations of human immunodeficiency virus (HIV) infection and AIDS are frequent occurrences (Coyle TE. Med Clin N Am 1997;81:449-476). The most important of these are cytopenias (anemia, neutropenia, and thrombocytopenia). The incidence and severity of cytopenia are generally correlated to the stage of the HIV infection. In addition, various coagulation abnormalities have been reported in HIV-infected patients. Apart from thrombocytopenia, these have included a prolonged APTT due to the presence of lupus anticoagulant, an increased prevalence of protein S and heparin cofactor II deficiency, and hypoalbuminemia-related fibrin polymerization defects (Toulon P. Ann Bio Clin (Paris) 1998;56:153-160). HIV infection has also been associated with endothelial dysfunction. Although for the most part asymptomatic, elevated D-dimer levels have been found in HIV-infected patients, suggesting the existence of a prethrombotic state. In fact, clinical thrombosis eventuates in 2% of these patients (Toulon, 1988). Documented thromboses have involved both veins and arteries. We hereby present a patient who developed an acute thrombosis of his brachial artery as the initial manifestation of HIV infection.
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PMID:Acute brachial artery thrombosis as the initial manifestation of human immunodeficiency virus infection. 1081 96

Aspirin inhibits platelet activation by irreversibly inhibiting platelet cyclooxygenase and thromboxane production, and reduces the odds of serious vascular events (stroke, myocardial infarction or vascular death) by about one quarter in a range of patients with symptomatic atherosclerosis at high risk of a subsequent event. The adenosine diphosphate (ADP) receptor antagonists clopidogrel and ticlopidine are significantly more effective than aspirin in high-risk vascular patients, further reducing the odds of serious vascular events by about 10% (95% CI 2-19%) over the benefit provided by aspirin. The ADP receptor antagonists are also associated with a significant 30% reduction in the odds of gastrointestinal haemorrhage (odds ratio 0.71, 95% CI 0.59-0.86). Ticlopidine increases the odds of skin rash and of diarrhoea by more than twofold compared with aspirin, whereas clopidogrel is associated with a one-third increase in the odds of rash and of diarrhoea. Only ticlopidine increases the odds of neutropenia compared with aspirin. There is no clear evidence as yet for the benefit of dipyridamole or an oral GP IIb/IIIa receptor antagonist as single antiplatelet agents in atherothrombotic patients. Amongst high vascular risk patients, the combination of low-dose aspirin and high-dose dipyridamole is associated with about a 10% (95% CI 0-20%) reduction in the odds of a serious vascular event. Most of this reduction is due to a 23% reduction in non-fatal stroke. The size of this estimate continues to be investigated in an ongoing study of patients with transient ischaemic attack and stroke. The combined use of aspirin and ticlopidine is markedly superior to heparin, warfarin and aspirin for reducing thrombotic complications after coronary artery stenting. Clopidogrel plus aspirin has been shown to be safer than aspirin and ticlopidine in coronary stenting, and is now under long-term evaluation in unstable angina, and other conditions in which patients are at high risk of atherothrombotic events.
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PMID:Current oral antiplatelet agents to prevent atherothrombosis. 1131 17

Cardiolipin (CL), the signature phospholipid of mitochondrial membranes, is crucial for both mitochondrial function and cellular processes outside of the mitochondria. The importance of CL in cardiovascular health is underscored by the life-threatening genetic disorder Barth syndrome (BTHS), which manifests clinically as cardiomyopathy, skeletal myopathy, neutropenia, and growth retardation. BTHS is caused by mutations in the gene encoding tafazzin, the transacylase that carries out the second CL remodeling step. In addition to BTHS, CL is linked to other cardiovascular diseases (CVDs), including cardiomyopathy, atherosclerosis, myocardial ischemia-reperfusion injury, heart failure, and Tangier disease. The link between CL and CVD may possibly be explained by the physiological roles of CL in pathways that are cardioprotective, including mitochondrial bioenergetics, autophagy/mitophagy, and mitogen activated protein kinase (MAPK) pathways. In this review, we focus on the role of CL in the pathogenesis of CVD as well as the molecular mechanisms that may link CL functions to cardiovascular health.
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PMID:The Role of Cardiolipin in Cardiovascular Health. 2630 Dec 54

Neutrophils are a key component of innate immunity. Individuals with low neutrophil count are susceptible to frequent infections. Linkage and association between congenital neutropenia and a single rare missense variant in TCIRG1 have been reported in a single family. Here, we report on nine rare missense variants at evolutionarily conserved sites in TCIRG1 that are associated with lower absolute neutrophil count (ANC; p = 0.005) in 1,058 participants from three cohorts: Atherosclerosis Risk in Communities (ARIC), Coronary Artery Risk Development in Young Adults (CARDIA), and Jackson Heart Study (JHS) of the NHLBI Grand Opportunity Exome Sequencing Project (GO ESP). These results validate the effects of TCIRG1 coding variation on ANC and suggest that this gene may be associated with a spectrum of mild to severe effects on ANC.
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PMID:Association Between Absolute Neutrophil Count and Variation at TCIRG1: The NHLBI Exome Sequencing Project. 2722 98

The anti-apoptotic protein myeloid cell leukemia 1 (Mcl-1) plays an important role in survival and differentiation of leukocytes, more specifically of neutrophils. Here, we investigated the impact of myeloid Mcl-1 deletion in atherosclerosis. Western type diet fed LDL receptor-deficient mice were transplanted with either wild-type (WT) or LysMCre Mcl-1fl/fl (Mcl-1-/-) bone marrow. Mcl-1 myeloid deletion resulted in enhanced apoptosis and lipid accumulation in atherosclerotic plaques. In vitro, Mcl-1 deficient macrophages also showed increased lipid accumulation, resulting in increased sensitivity to lipid-induced cell death. However, plaque size, necrotic core and macrophage content were similar in Mcl-1-/- compared to WT mice, most likely due to decreased circulating and plaque-residing neutrophils. Interestingly, Mcl-1-/- peritoneal foam cells formed up to 45% more multinucleated giant cells (MGCs) in vitro compared to WT, which concurred with an increased MGC presence in atherosclerotic lesions of Mcl-1-/- mice. Moreover, analysis of human unstable atherosclerotic lesions also revealed a significant inverse correlation between MGC lesion content and Mcl-1 gene expression, coinciding with the mouse data. Taken together, these findings suggest that myeloid Mcl-1 deletion leads to a more apoptotic, lipid and MGC-enriched phenotype. These potentially pro-atherogenic effects are however counteracted by neutropenia in circulation and plaque.
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PMID:Low human and murine Mcl-1 expression leads to a pro-apoptotic plaque phenotype enriched in giant-cells. 3160 24


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