Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The serum lipoprotein(a) [Lp(a)] level is a known risk factor for arteriosclerotic coronary artery disease. However, its association with restenosis after percutaneous transluminal coronary angioplasty (PTCA) is controversial. We hypothesized that the Lp(a) level is a significant risk factor for restenosis after angioplasty through a pathophysiological mechanism leading to excess thrombin generation or inhibition of fibrinolysis. We designed a prospective study of the relation of Lp(a) to outcome after PTCA, in which we measured selected laboratory variables at entry and collected clinical, procedural, lesion-related, and outcome data pertaining to restenosis. Restenosis was defined as >50% stenosis of the target lesion by angiography or as ischemia in the target vessel distribution by radionuclide-perfusion scan. Before the patients underwent PTCA, blood was obtained by venipuncture for measurement of Lp(a), total cholesterol, thrombin-antithrombin (TAT) complex, alpha2-antiplasmin-plasmin (APP) complex, and plasminogen activator inhibitor-1 (PAI-1). Evaluable outcome data were obtained on 162 subjects, who form the basis of this report. Restenosis occurred in 61 subjects (38%). The Lp(a) level was not correlated significantly with TAT, APP, PAI-1, or the TAT-APP ratio. Levels of TAT, APP, and PAI-1 were not statistically different in the patients with versus those without restenosis. The median ratio of TAT to APP was 2-fold higher in the restenosis group, and this difference approached statistical significance (P=0.07). Univariate analysis was performed for the association of clinical, lesion-related, and procedural risk factors with restenosis. Lp(a) levels did not differ significantly in the restenosis versus no-restenosis group, whether assessed categorically (>25 mg/dL versus <25 mg/dL) or as a continuous variable by Mann-Whitney U test. The number of lesions dilated and the lack of family history of premature heart disease were significantly associated with restenosis (P=0.002 and P=0.008, respectively). A history of diabetes mellitus was of borderline significance (P=0.055). By multiple logistic regression analysis, the number of lesions dilated was the only variable significantly associated with restenosis (P=0.03). We conclude that the number of lesions dilated during PTCA is a significant risk factor for restenosis, whereas the serum Lp(a) level was not a significant risk factor for restenosis in our patient population. The TAT to APP ratio merits further study as a possible risk factor for restenosis.
 ...
PMID:Lipoprotein(a) level does not predict restenosis after percutaneous transluminal coronary angioplasty. 971 35

Apolipoprotein (apo) E plays an important role in lipid metabolism, and the major isoforms of apoE (apoE2, apoE3, and apoE4) have significantly different metabolic effects. Apolipoprotein E4 is associated with a higher risk of both heart disease and Alzheimer's disease (AD). Patients homozygous for apolipoprotein E2 are predisposed to type III hyperlipoproteinemia, and apoE2 may be protective against AD. Structure/function studies have proved to be a useful tool in understanding how the different apoE isoforms result in different pathological consequences. As these studies continue, it is essential to have a reliable method to produce large quantities of apoE and mutants of apoE. We describe here a method of apoE production in Escherichia coli strain BL21(DE3). The cDNA from apoE isoforms was inserted into a pET32a vector with a T7 promoter and a fusion partner (thioredoxin). The T7 promoter results in high expression of an easily purified His-tagged fusion protein. A thrombin recognition site was positioned in the expression vector so that only two novel amino acids (Gly-Ser) are added to the amino terminus of apoE following the removal of thioredoxin. Approximately 20 mg of apoE is obtained from a 1-liter culture. The major isoforms of apoE produced with this system were extensively characterized for their ability to bind the low-density lipoprotein (LDL) receptor, for their characteristic lipid association preferences, and for their stability as measured by guanidine denaturation. The recombinant proteins behaved identically to plasma-derived apoE isoforms.
 ...
PMID:Functional characterization of apolipoprotein E isoforms overexpressed in Escherichia coli. 1041 18

Abnormal platelet function has been hypothesised to play a role in the haemostatic abnormalities in cyanotic congenital heart disease (CCHD) patients. Using whole blood flow cytometry we found that platelets from cyanotic patients were hyperreactive and we related such hyperreactivity directly to young age, unoperated state, high haematocrit, reduced saturation with oxygen and low platelet count. Circulating platelets from CCHD children showed significantly enhanced P-selectin expression (P<0.004) and remained more reactive to 0.2 IU/ml thrombin, 1-8 microM TRAP and 2-4 microM ADP (P<0.04), especially in younger (0-3-year-olds) patients. Such a platelet 'priming' largely concerned CCHD children who were not subjected to modified Blalock-Taussig shunts in the past (non-MBTS). Only non-MBTS cyanotic children, but not MBTS-operated patients, showed significantly higher platelet reactivity compared to controls in response to ADP or 1 microM TRAP with respect to P-selectin expression (p<0.05) and in response to all examined agonists with respect to GPIb expression (P<0.045). The enhanced P-selection expression in MBTS-operated CCHD children and reduced GPIb expression in non-MBTS patients, especially in younger patients, were positively associated with the occurrence of the polymorphic variant Pl(A2) of platelet membrane glycoprotein IIIa gene. Altered blood morphology parameters (elevated RBC, Hb, Hct and MCHC, for all P<0.0005) in CCHD children correlated with the enhanced degranulation of circulating blood platelets and their hyperreactivity in response to some agonists (P<0.05). Overall, our data encourage the reasoning that circulating platelets are remarkably hyperreactive in non-MBTS cyanotic children, which are at higher risk to often encounter platelets activation in circulation. It seems unlikely that the apparently unchanged platelet reactivity in MBTS-operated children is due to the advantageous effects of the shunt, since these patients showed neither altered haematological parameters nor improved oxygen carrying capacity. Otherwise, it may rather result from more frequent episodes of platelet degranulation and preactivation in the past, and/or post-operative enhanced platelet consumption.
 ...
PMID:Activation of circulating platelets and platelet response to activating agents in children with cyanotic congenital heart disease: their relevance to palliative systemic-pulmonary shunt. 1139 41

Atrial fibrillation (AF) is an important risk factor for stroke. According to a pooled analysis of controlled clinical trials with warfarin, anticoagulation therapy reduces stroke risk by 62%. However, clinicians must decide whether the benefit of long-term anticoagulation therapy with available agents outweighs the risk of bleeding for individual patients. Guidelines issued by the American College of Chest Physicians and by the joint American College of Cardiology, American Heart Association, and the European Society of Cardiology task force recommend antithrombotic therapy to protect AF patients from stroke based on risk-stratification algorithms. Risk factors for stroke AF patients include age > or =75 years; hypertension; thyrotoxicosis; diabetes; cardiovascular disease; congestive heart failure; and history of stroke, transient ischemic attack, or thromboembolism. Patients at high risk for stroke experience greater absolute benefit from anticoagulation therapy than patients at low risk. The guidelines are consistent in recommendations for high-risk patients (warfarin therapy, international normalized ratio 2.0 to 3.0) and low-risk patients (aspirin 325 mg), but differ for intermediate-risk patients with diabetes or heart disease. The guidelines continue to evolve, and future guidelines are likely to incorporate new clinical data, including the CHADS(2) algorithm for determining risk and the results of the Atrial Fibrillation Follow-up Investigation of Rhythm Management trial, the Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation study, and the Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation II to V trials.
 ...
PMID:Comparing the guidelines: anticoagulation therapy to optimize stroke prevention in patients with atrial fibrillation. 1502 46

Unfractionated heparin (UFH) is immunogenic, and heparin-dependent antibodies can be demonstrated 5 to 10 days postoperatively in 25% to 50% of adult postcardiac surgery patients. In a minority of these cases (1% to 3% if UFH is continued longer than 1 week) these antibodies strongly activate platelets, causing thrombocytopenia and massive thrombin generation (HIT syndrome). HIT is an intensely procoagulant disorder, and in adult cardiac surgery patients carries both significant thrombotic morbidity (38% to 81%) and mortality (28%). Despite the ubiquitous use of UFH in pediatric intensive care units, and the repeated and sustained exposures to UFH in neonates and young children with congenital heart disease, HIT has been infrequently recognized and reported in this patient population. However, emerging experience at our institution and elsewhere suggests that HIT is significantly under-recognized in pediatric congenital heart disease patients, and may in fact have an incidence and associated thrombotic morbidity and mortality in this patient group comparable to that seen in adult cardiac surgery patients. This article will review HIT in pediatric patients with congenital heart disease and emphasize the special challenges posed in clinical recognition, laboratory diagnosis, and treatment of HIT in this patient group. We will also outline our experience with the off-label use of the direct thrombin inhibitor, argatroban, in pediatric patients with HIT.
 ...
PMID:Heparin-induced thrombocytopenia (HIT) in pediatric cardiac surgery: an emerging cause of morbidity and mortality. 1528 65

Thromboembolic risk of atrial flutter (AFl) types has not been elucidated sufficiently in previous reports. The authors classified the patients according to surface electrocardiogram and electrophysiologic characteristics as those with typical AFl (37 patients, 78.4% male, mean age 59.8 +/-9.5 years) and atypical AFl (13 patients, 69.2% male, mean age 60.9 +/-6.9 years) and compared them regarding some clinical, echocardiographic, and hematologic parameters. An age- and gender-matched control group composed of 20 individuals without any organic heart disease in sinus rhythm was chosen (80% male, mean age 60.3 +/-7.9 years). Clinical features such as age, gender, organic heart disease, hypertension, diabetes mellitus, AFl duration, and the prevalence of paroxysmal atrial fibrillation were similar in both AFl groups. Echocardiographic parameters such as left ventricular ejection fraction, left atrial (LA) diameter, LA spontaneous echo contrast, and LA appendage emptying velocities were similar in both AFl groups. Fibrinogen, fibrin D-dimer, and thrombin-antithrombin III levels reflecting coagulation system activity were found to be increased in the patients with atypical AFl when compared with those with typical AFl and the control group (p < 0.001). In Pearson's correlation analysis, significant correlation between these hematologic markers and clinical and echocardiographic parameters were not found (p > 0.05). The coagulation system activity was found to be increased in patients with atypical AFl. Thus, anticoagulation due to the increased thromboembolic risk should be considered in patients with atypical AFl.
 ...
PMID:Do different atrial flutter types carry the same thromboembolic risk? 1619 99

The only major and potentially fatal risk for patients with atrial fibrillation is the development of systemic thromboembolism. Stroke occurs five times more frequently in patients with atrial fibrillation than in comparable patients in sinus rhythm. The yearly incidence of stroke in atrial fibrillation largely depends on the underlying heart disease: from 0.5% in "lone" atrial fibrillation up to 20% in rheumatic heart valve disease. Oral anticoagulation with vitamin K antagonists dramatically reduces the stroke risk by two-thirds, but is a laborious and patient-unfriendly therapy. Oral direct thrombin blockers and oral factor Xa antagonists, both without therapy monitoring, may replace warfarin for this indication, but there are safety and efficacy issues to be resolved. Oral antiplatelet agents are effective, but clearly less than warfarin. Angiotensin receptor blockers are currently under investigation. Routine electrocardioversion for atrial fibrillation does not reduce the stroke risk, but promising techniques include electroablation of the left atrium and occlusion of the left atrial appendage.
 ...
PMID:Stroke prevention in atrial fibrillation. 1651 85

Reports on the use of recombinant activated factor VII (rFVIIa) to counteract hemorrhagic shock in neonates and preterm infants are increasing. rFVIIa enhances thrombin generation in situations with impaired thrombin formation and, since thrombin has a crucial role in providing hemostasis, rFVIIa is regarded as a general hemostasis agent. Full thrombin generation is necessary for the formation of a stable fibrin plug resistant to premature fibrinolysis. Antifibrinolytic drugs are not recommended for the treatment of acute bleeding. We report four neonates (one with massive postsurgical hemorrhage after ileostomy and three with severe pulmonary hemorrhage in the course of mechanical ventilation for meconium aspiration syndrome, congenital heart disease and during postoperative resuscitation after cardiac surgery for congenital heart disease) who were successfully treated with multiple administration of rFVIIa (120 microg/kg per dose) and antifibrinolytic therapy - aminocaproic acid (100 mg/kg per dose). In a fibrinolytic environment therapeutic concentrations of rFVIIa may sometimes be insufficient to produce adequate amounts of thrombin necessary for stable clot structure. Laboratory data in three of our patients with pulmonary hemorrhage (low fibrinogen levels with slightly prolonged prothrombin time) supported this thesis, so we blocked fibrinolysis with aminocaproic acid and achieved a complete clinical and laboratory therapeutic effect.
 ...
PMID:Successful use of recombinant activated FVII and aminocaproic acid in four neonates with life-threatening hemorrhage. 1678 19

In this investigation, we examined the relationship among three thrombin inhibitors, antithrombin III (ATIII), heparin cofactor II (HCII), and alpha-2-macroglobulin (alpha2M), and several clinical tests of heparin's effect in pediatric patients with congenital heart disease undergoing cardiopulmonary bypass. One hundred eighteen children were stratified into six age groups: <1 mo, 1-3 mo, 3-6 mo, 6-12 mo, 12-24 mo, and >10 yr. Baseline ATIII, HCII, and alpha2M values were measured. Baseline celite- and kaolin-activated clotting times (ACT) were also measured and repeated 3 min after a standard heparin dose of 400 U/kg. Differences in ACT values before and after heparin administration and a heparin dose-response relationship were calculated for each patient. Kaolin-activated ACT tests showed less variation after heparin administration than celite-activated tests. In contrast to what has been demonstrated in adults, ATIII showed no positive correlation with the clinical tests of heparin's effect nor did the other thrombin inhibitors. Additionally, patients <1 mo old had unexpectedly low levels of alpha2M accompanying their expected low levels of ATIII and HCII. Our findings raise concerns about the ability of heparin to adequately anticoagulate these neonates during cardiopulmonary bypass and, consequently, challenge the accuracy of ACT prolongation to truly reflect the extent of their anticoagulation.
 ...
PMID:Clinical measures of heparin's effect and thrombin inhibitor levels in pediatric patients with congenital heart disease. 1705 45

Severe postoperative coagulopathy developed in a child with congenital heart disease due to a factor V inhibitor from repetitive exposure to bovine topical thrombin. This case report alerts pediatric providers to consider these inhibitors when postoperative coagulopathy occurs. Potential treatment options are reviewed.
 ...
PMID:Postoperative coagulopathy in a pediatric patient after exposure to bovine topical thrombin. 1738 85


<< Previous 1 2 3 4 Next >>