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

Obesity is an epidemic disease that threatens to inundate health care resources by increasing the incidence of diabetes, heart disease, hypertension, and cancer. These effects of obesity result from two factors: the increased mass of adipose tissue and the increased secretion of pathogenetic products from enlarged fat cells. This concept of the pathogenesis of obesity as a disease allows an easy division of disadvantages of obesity into those produced by the mass of fat and those produced by the metabolic effects of fat cells. In the former category are the social disabilities resulting from the stigma associated with obesity, sleep apnea that results in part from increased parapharyngeal fat deposits, and osteoarthritis resulting from the wear and tear on joints from carrying an increased mass of fat. The second category includes the metabolic factors associated with distant effects of products released from enlarged fat cells. The insulin-resistant state that is so common in obesity probably reflects the effects of increased release of fatty acids from fat cells that are then stored in the liver or muscle. When the secretory capacity of the pancreas is overwhelmed by battling insulin resistance, diabetes develops. The strong association of increased fat, especially visceral fat, with diabetes makes this consequence particularly ominous for health care costs. The release of cytokines, particularly IL-6, from the fat cell may stimulate the proinflammatory state that characterizes obesity. The increased secretion of prothrombin activator inhibitor-1 from fat cells may play a role in the procoagulant state of obesity and, along with changes in endothelial function, may be responsible for the increased risk of cardiovascular disease and hypertension. For cancer, the production of estrogens by the enlarged stromal mass plays a role in the risk for breast cancer. Increased cytokine release may play a role in other forms of proliferative growth. The combined effect of these pathogenetic consequences of increased fat stores is an increased risk of shortened life expectancy.
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PMID:Medical consequences of obesity. 1518 Oct 27

A total of 360 pediatric patients aged 1 month to 18 years were diagnosed as having thrombosis between January 1998 and April 2003. Of these patients, those aged 11-18 years (n=131) were regarded as adolescents and the rest as children. The proportion of adolescents in the whole group excluding the neonates was 36%. The peak age of diagnosis in adolescents was 11-14 years, comprising 58% of all thrombotic events in adolescents. In 73% of the adolescents, there was at least one risk factor. The four most common underlying disorders were infection, malignancy, connective tissue and cardiac disorders, in decreasing order of frequency. In children, on the other hand, infection was followed by congenital heart disease, malignancy and liver disease. Three common types of thrombosis in adolescents were deep venous thrombosis, cerebro-vascular events and portal venous thrombosis, while cerebro-vascular events were the most common in children. The frequency of factor V G1691A mutation in the adolescents (22.1%) was significantly higher than that found in a group of healthy controls (7.4%) and this mutation was associated with a 3.6-fold increase in the risk of developing thrombosis (95% confidence interval, 1.4-9.0). The carrier frequency of prothrombin G20210A mutation (3.1%) in adolescents did not differ significantly from that of the healthy population (2.3%) and no association was observed between this mutation and a risk of developing thrombosis in this group (odds ratio, 1.3; 95% confidence interval, 0.2-7.5). The rate of recurrent thrombosis was 6%.
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PMID:Analysis of some clinical and laboratory aspects of adolescent patients with thrombosis. 1561 20

Mild elevations in liver chemistry tests such as alanine transaminase and aspartate transaminase can reveal serious underlying conditions or have transient and benign etiologies. Potential causes of liver transaminase elevations include viral hepatitis, alcohol use, medication use, steatosis or steatohepatitis, and cirrhosis. The history should be thorough, with special attention given to the use of medications, vitamins, herbs, drugs, and alcohol; family history; and any history of blood-product transfusions. Other common health conditions, such as diabetes, heart disease, and thyroid disease, can cause or augment liver transaminase elevations. The recent American Gastroenterological Association guideline regarding the evaluation and management of abnormal liver chemistry tests proposes a practical, algorithmic approach when the history and physical examination do not reveal the cause. In addition to liver chemistries, an initial serologic evaluation includes a prothrombin time; albumin; complete blood count with platelets; hepatitis A, B, and C serologies; and iron studies. Depending on the etiology, management strategies may include cessation of alcohol use, attention to medications, control of diabetes, and modification of lifestyle factors such as obesity. If elevations persist after an appropriate period of observation, further testing may include ultrasonography and other serum studies. In some cases, biopsy may be indicated.
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PMID:Mildly elevated liver transaminase levels in the asymptomatic patient. 1579 89

Sitaxsentan is an orally active, selective endothelin-A receptor antagonist that may benefit patients with pulmonary arterial hypertension by blocking the vasoconstrictive effects of endothelin-A receptors, while maintaining the vasodilator and endothelin-1 clearance functions of the endothelin-B receptors. In its first randomized, placebo-controlled study, sitaxsentan improved exercise capacity assessed by the 6-min walk test, New York Heart Association functional class, cardiac index and pulmonary vascular resistance in New York Heart Association Class II, III and IV patients with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension related to connective tissue disease or congenital heart disease. Although doses of 100 and 300 mg once daily demonstrated equivalent efficacy, the lower dose had a better safety profile. Additional studies are ongoing to assess the relative safety and efficacy of 50 and 100 mg once-daily dosing. The most common side effects include rhinitis, headache, peripheral edema, chest pain, nausea, constipation, increased prothrombin time/international normalized ratio (in patients on warfarin), flushing and insomnia. As with other endothelin receptor antagonists, increases in hepatic transaminases have been observed with sitaxsentan. Initial studies using the selective oral endothelin-A receptor antagonist sitaxsentan in pulmonary arterial hypertension patients have revealed a favorable risk-benefit therapeutic profile with the 100 mg once-daily dose.
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PMID:Sitaxsentan: a novel endothelin-A receptor antagonist for pulmonary arterial hypertension. 1629 89

The prevalence of hypertension and cardiovascular disease increases dramatically after menopause in women, implicating estrogen as having a protective role in the cardiovascular system. However, recent large clinical trials have failed to show cardiovascular benefit, and have even demonstrated possible harmful effects, of opposed and unopposed estrogen in postmenopausal women. While these findings have led to a revision of guidelines such that they discourage the use of estrogen for primary or secondary prevention of heart disease in postmenopausal women, many investigators have attributed the negative results in clinical trials to several flaws in study design, including the older age of study participants and the initiation of estrogen late after menopause.Because almost all clinical trials use oral estrogen as the primary form of hormone supplementation, another question that has arisen is the importance of the route of estrogen administration with regards to the cardiovascular outcomes. During oral estrogen administration, the concentration of estradiol in the liver sinusoids is four to five times higher than that in the systemic circulation. This supraphysiologic concentration of estrogen in the liver can modulate the expression of many hepatic-derived proteins, which are not observed in premenopausal women. In contrast, transdermal estrogen delivers the hormone directly into the systemic circulation and, thus, avoids the first-pass hepatic effect.Although oral estrogen exerts a more favorable influence than transdermal estrogen on traditional cardiovascular risk factors such as high- and low-density lipoprotein-cholesterol levels, recent studies have indicated that oral estrogen adversely influences many emerging risk factors in ways that are not seen with transdermal estrogen. Oral estrogen significantly increases levels of acute-phase proteins such as C-reactive protein and serum amyloid A; procoagulant factors such as prothrombin fragments 1+2; and several key enzymes involved in plaque disruption, while transdermal estrogen does not have these adverse effects.Whether the advantages of transdermal estrogen with regards to these risk factors will translate into improved clinical outcomes remains to be determined. Two ongoing clinical trials, KEEPS (Kronos Early Estrogen Prevention Study) and ELITE (Early versus Late Intervention Trial with Estradiol) are likely to provide invaluable information regarding the role of oral versus transdermal estrogen in younger postmenopausal women.
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PMID:Effects of transdermal estrogen replacement therapy on cardiovascular risk factors. 1639 17

The objective of this study was to investigate the correlation between factor XIII (FXIII) activity and disseminated intravascular coagulation (DIC) parameters and also to evaluate the clinical usefulness of DIC diagnosis. Citrated plasma from eighty patients with potential DIC was analyzed for FXIII activity. The primary patient conditions (48 male and 32 female, mean age, 51 years) were malignancy (n = 29), infection (n = 25), inflammation (n = 6), heart disease (n= 3), thrombosis (n = 2), injury (n = 2), and other miscellaneous conditions (n = 13). FXIII testing was performed using the CoaLinkTM FXIII Incorporation Assay Kit (PeopleBio Inc.). Among 80 patients who were suspected to have DIC based on clinical analysis, 46 (57.5%) fulfilled the overt DIC criteria (DIC score > = 5) according to the International Society of Thrombosis and Haemostasis. FXIII levels in the plasma were significantly decreased in overt DIC compared to non-overt DIC patients (mean 75.1% and 199.7% respectively, p < 0.0001). Interestingly, we found a significant inverse correlation between DIC scores and FXIII activity. In addition, FXIII activity significantly correlated with other hemostatic markers that included platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, and D-dimer. FXIII levels were significantly lower in patients with liver or renal dysfunction. In conclusion, FXIII cross-linking activity measurements may have differential diagnostic value as well as predictive value in patients who are suspected to have DIC.
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PMID:Plasma factor XIII activity in patients with disseminated intravascular coagulation. 1664 48

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.
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PMID:Successful use of recombinant activated FVII and aminocaproic acid in four neonates with life-threatening hemorrhage. 1678 19

Although a significant minority of patients with cyanotic congenital heart disease (CCHD) are thrombocytopenic, the pathogenesis and prevalence have not been established. This study was designed to address these 2 issues. We included 105 patients with CCHD (60 men and 45 women; aged 21 to 54 years). Systemic arterial oxygen saturations were 69% to 78%. Hematocrits were 62% to 74% with normal iron indexes. In 26 of 105 patients (25%), platelet counts were <100x10(9)/L. The diagnosis was Eisenmenger syndrome in all 26 patients with thrombocytopenia. Platelet production was determined by flow cytometric reticulated platelet counts. Megakaryocyte mass was determined indirectly by thrombopoietin levels. Disseminated intravascular coagulation was based on prothrombin time, activated partial thromboplastin time, and D-dimers. Platelet activation was determined by levels of platelet factor 4 and beta thromboglobulin. Reference ranges were derived from 20 normal acyanotic controls. A reduction in absolute reticulated platelet counts implied decreased platelet production (p<0.001). Normal thrombopoietin levels implied normal megakaryocyte mass. Normal prothrombin time, activated partial thromboplastin time, and D-dimers excluded disseminated intravascular coagulation. Normal platelet factor 4 and beta thromboglobulin indicated absent or minimal platelet activation. Twenty-five percent of the patients with CCHD were thrombocytopenic because platelet production was decreased despite normal megakaryocyte mass. We hypothesized that right-to-left shunts deliver whole megakaryocytes into the system arterial circulation, bypassing the lungs where megakaryocytic cytoplasm is fragmented into platelets, thus reducing platelet production. In conclusion, platelet counts in CCHD appear to represent a continuum beginning with low normal counts and ending with thrombocytopenia.
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PMID:Pathogenesis of thrombocytopenia in cyanotic congenital heart disease. 1682 3

The strong activation of the clotting cascade that occurs during total hip arthroplasty places patients at increased risk for venous thromboembolism. The risk is higher in those patients with the following predisposing factors, listed in approximate order of importance: hip fracture; malignancy, particularly if associated with chemotherapy; antiphospholipid syndrome; immobility; history of venous thromboemholism; administration of tamoxifen; raloxifene; oral contraceptives or estrogen; morbid obesity; stroke; atherosclerosis; and an American Society of Anesthesiologists physical status classification of 3 or greater. The following risk factors are weak or controversial: advanced age; diabetes mellitus; congestive heart disease; atrial fibrillation; varicose veins; and smoking. However, 50% of patients who develop thromboembolism after total hip arthroplasty have no clinical predisposing factors. In a matched, controlled study, we defined the major genetic predispositions that increase the risk of venous thromboembolism after total hip arthroplasty: deficiency of antithrombin III (< 75%) and protein C (< 70%), and prothrombin gene mutation. Preoperative genetic screening in conjunction with the recognized clinical risk factors can help categorize postoperative venous thromboembolism risk and differentiate patients who can be protected with milder and safer prophylaxis (eg, aspirin, intermittent pneumatic compression) compared with those at higher risk who need to be anticoagulated.
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PMID:Thromboembolic disease after total hip arthroplasty: who is at risk? 1700 73

A 2-year-old girl with tetralogy of Fallot presented with diffuse cranial infarct after cardiac angiography. Heterozygosity for factor V Leiden and prothrombin 20210A mutations were detected. The authors suggest that if thrombosis develops in patients with congenital heart disease, genetic risk factors should be evaluated.
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PMID:Diffuse cerebral infarct associated with factor V Leiden and prothrombin 20210A mutations in a patient with tetralogy of Fallot. 1855 May 88


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