Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the UK, the Committee for Safety of Medicines (CSM) issued a warning in October 1995 about the possible increased risk of nonfatal deep venous thrombosis (DVT) among users of oral contraceptives (OCs) containing the third generation progestogens, desogestrel and gestodene. Subsequent media coverage increased the number of consultations and enquiries about these OCs. CSM had concluded that, overall, the third generation OCs are safe. CSM recommended their continued use. Nevertheless, many women stopped using them and induced abortions increased by 11%. In April 1996, the Committee for Proprietary Medicinal Products issued a more cautious statement about the OCs and called for further evaluation. Chance, confounding, and bias may account for the increased risk observed in the studies in question. Yet, it is possible that these OCs may increase the risk of DVT. The increased risk may be offset by a reduced risk of acute myocardial infarction. Physicians need to conduct careful and thorough counseling and to allow the patient to be involved and to take responsibility in making a decision about OC use. They should document all counseling with a note that the patient understands and accepts the increased risk of DVT. They should not prescribe the third generation OCs to women with any of the absolute contraindications to OC use (ischemic heart disease, hypertension, atherogenic lipid disorders, focal or crescendo migraine, cigarette smoking, transient ischemic attacks, past cerebral/subarachnoid hemorrhage, history of vascular thrombosis, prothrombotic abnormalities [e.g., Factor V Leiden], conditions predisposing to thrombosis [e.g., systemic lupus erythematosus], and obesity. Women who are intolerant of second generation OCs may prefer third generation OCs. Physicians should selectively screen women with a family history of a first-degree relative younger than 45 with thromboembolism for Factor V Leiden. They should also screen for protein C, protein S, and antithrombin III deficiency and for acquired antiphospholipid antibodies.
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PMID:Oral contraceptives and the risk of DVT. 898 64

Electrocardiographic (ECG) findings of pulmonary embolism (PE) include S1Q3T3 pattern, right bundle-branch block, right-axis deviation, and T-wave inversion in medial precordial leads. We report other uncommon ECG changes associated with various symptoms during recurrent PE as documented by computed tomography (CT) scans in a single patients. An 83-year-old woman was admitted with PE secondary to deep venous thrombosis in the left leg. During episodes of chest pain, ECG showed QTc prolongation (480 ms) with new T-wave inversion in leads III, aVF, and V1-V3, and ST-segment depression in leads V5-V6. Despite adequate anticoagulant therapy, recurrent episodes of PE occurred in the hospital. When the patient experienced sudden chest tightness, ECG showed a new S-wave notch in lead V1 and clock-wise rotation with sinus tachycardia. She also experienced transient syncope with hypotension. At this time, ECG showed transient atrioventricular junctional rhythm followed by sinus arrest, and CT scan showed a new massive embolus in the main pulmonary trunk with right ventricular dilatation, as demonstrated by echocardiography. The mechanism responsible for QTc prolongation with ST-T changes, the S-wave notch in lead V1 with clockwise rotation, or atrioventricular junctional rhythm with sinus arrest during PE may be associated with myocardial ischemia, acute right ventricular overload, or vagal reflex, respectively.
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PMID:Uncommon electrocardiographic changes corresponding to symptoms during recurrent pulmonary embolism as documented by computed tomography scans. 982 4

The mechanism of arterial thrombosis, including coronary thrombosis, is different from that of thrombosis which occurs at sites of blood stasis such as deep venous thrombosis. Considering the onset of arterial thrombus formation, soluble coagulant factors may not play important roles for its onset since they are diluted by the effect of blood flow and cannot reach high enough concentrations to form insoluble fibrin. Platelets, which can stick to damaged vascular lumen even in the presence of shearing effects of blood flow, may play a crucial role in the onset of arterial thrombus formation. Thus, the mechanism of platelet thrombus formation should be assessed in the presence of blood flow. However, current dogma that fibrinogen binding to activated GP IIb/IIIa is the final common pathway for platelet thrombus formation was developed by using the function assay system of aggregometer, in which the effects of blood flow were not seriously considered. We are proposing in this review that plasma ligand protein of von Willebrand factor (vWF) and its interactions with platelet GP lb and GP IIb/IIa, which become apparent only in assays systems under influence of high shear rates of flow condition such as flowchambers or coneplate viscometers, are the key events leading to the onset of arterial thrombosis. A better understanding of the vWF-mediated mechanism of platelet thrombus formation is important for the development of better clinical tools to prevent ischemic heart disease as well as for a complete understanding of the mechanism of coronary thrombosis.
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PMID:Coronary thrombosis. Effects of blood flow on the mechanism of thrombus formation. 992 90

Physicians face a therapeutic dilemma in patients with acute hemorrhagic stroke requiring long-term, high-intensity anticoagulants because this treatment increases the risk of intracranial hemorrhage (ICH) 8- to 11-fold. We retrospectively studied 15 patients with ICH which occurred under anticoagulation with phenprocoumon, with an international norrmalized ratio (INR) of 2.5-6.5 on admission. Hemispheric, thalamic, cerebellar, intraventricular, or subarachnoid hemorrhage without aneurysm occurred. Absolute indications for anticoagulation were double, mitral, or aortic valve replacement, combined mitral valve failure with atrial fibrillation and atrial enlargement, internal carotid artery-jugular vein graft, frequently recurring deep vein thrombosis with risk of pulmonary embolism, and severe nontreatable ischemic heart disease. As soon as the diagnosis of ICH was established, INR normalization was attempted in all patients by administration of prothrombin complex, fresh frozen plasma, or vitamin K. After giving phenprocoumon antagonists (and neurosurgical therapy in four patients) heparin administration was started. Nine patients received full-dose intravenous and six low-dose subcutaneous heparin. The following observations were made: (a) All patients with effective, full-dose heparin treatment with a 1.5- to 2-fold elevation in partial thromboplastin time after normalization of the INR were discharged without complication. (b) Three of four of the patients with only incomplete correction of the INR (> 1.35) experienced relevant rebleeding within 3 days (all patients with an INR higher than 1.5), two of whom were on full-dose heparin. (c) Three of seven of the patients with normalized INR and without significant PTT elevation developed severe cerebral embolism. Although our data are based on a retrospective analysis, they support treatment with intravenous heparin (partial thromboplastin time 1.5-2 times baseline value) after normalization of the INR in patients with an ICH and an urgent need for anticoagulation.
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PMID:Managing the therapeutic dilemma: patients with spontaneous intracerebral hemorrhage and urgent need for anticoagulation. 1078 17

Angiotensin-converting enzyme (ACE) is a well known zinc-metallopeptidase that converts angiotensin I to the potent vasoconstrictor angiotensin II and that degrades bradykinin, a powerful vasodilator, both for regulation of vascular tone and cardiac functions. Other natural substrates of ACE were identified broadening the functions of this enzyme within different physiological contexts such as neuronal metabolism, hematopoiesis, digestion and reproduction. Synthetic substrates were developed for the determination of ACE activity in various biological fluids, mostly human plasma, for the diagnosis of sarcoidosis and other granulomatous diseases. After the successful use of captopril, the first ACE inhibitor in the treatment of hypertension, a number of molecules were synthesized and used in the treatment of congestive heart failure and for preventing cardiac impairment after myocardial infarction. This class of antihypertensive drugs benefited from structural data on carboxypeptidases active site, as ACE molecule has not yet been crystallized. In the last two decades ACE gene has been cloned that allowed the identification (i) of two isoenzymes, one called somatic ACE resulting from gene duplication and primarily expressed in endothelial cells, and the other, called germinative or testicular ACE, resulting from the transcription in the male reproductive system of a more simple gene, (ii) of an hydrophobic C-terminal peptide for membrane-anchoring and specifically cleaved by a metalloprotease to release soluble forms of both isoenzymes, and (iii) of several allelic polymorphisms, one of them consisting of an insertion/deletion (I/D) polymorphism in a short intronic Alu sequence that could account for half the variance in plasma ACE level and resulting in a large inter-individual variability; moreover this I/D polymorphism was proposed as a genetic marker for identifying individuals at high risk of ischemic heart disease and of anticipating in one individual the efficacy of the antihypertensive therapy, although conflicting data arose from the past decade literature. Moreover, ACE gene cloning has confirmed the expression of the enzyme in endothelial cell, in particular as an ecto-enzyme facing the vascular lumen, but not to the same extent with regard to the vascular origin of the cells. Plasma ACE in healthy subjects arises essentially from the endothelium. On the other hand, in granulomatous diseases where a local stimulation of macrophages leads to an abnormal ACE secretion, it can also be found in other biological fluids such as cerebrospinal and broncho-alveolar fluids. Low plasma ACE levels result from endothelium impairment such as in deep vein thrombosis or in endothelio-toxic anticancer therapies. Another cause of low, sometimes undetectable, plasma ACE levels is the use of an ACE inhibitor, but this is without any significance with regard to its clinical benefits. Albeit molecular cloning has provided a number of new details on ACE structure and function, many questions still remain, in particular about its tertiary structure including glycosylations, about its tissue-specific expression and regulation, and also about the exact significance of the I/D polymorphism in cardiovascular pathology including the pharmacogenomic field.
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PMID:New aspects on angiotensin-converting enzyme: from gene to disease. 1200 16

Townsville General Hospital (TGH) has 285 beds and serves a population of approximately 500,0000 in North Queensland. In the period November 1998 until December 1999 there were three acute subdural haematomas (ASDH) related to therapeutic doses of enoxaparin. These culminated in death or severe neurological disability. Unfractionated heparin (UFH) is probably used equivalently in TGH. There were no intracranial haemorrhages in this period with UFH. It is well known low molecular weight heparins (LMWH) have a proven place in the management of deep vein thrombosis (DVT) and ischaemic heart disease (IHD). There may however be some concerns regarding the haemorrhagic complications of therapeutic doses of enoxaparin in the central nervous system.
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PMID:Acute subdural haematomas and enoxaparin. 1209 30

A carefully taken history and clinical examination are necessary for assessing the relative benefits and risks of estrogen replacement therapy for an individual patient. The patient's weight, blood pressure and urine need to be checked. Benefits of estrogen replacement are seen in relation to vasomotor symptoms, atrophy of the genital tract, bone metabolism, psychological symptoms, libido, skin, and cardiovascular effects. Estrogens are contraindicated with a history of previous deep vein thrombosis, ischemic heart disease or carcinoma of the breast. Care needs to be taken with liver disease, hyperlipidemias, diabetes, gallbladder disease, gross obesity, or in heavy smokers. Progesterones should always be administered if the uterus is present to prevent endometrial hyperplasia and adenocarcinoma. When properly selected and carefully monitored, many women may be relieved of unnecessary suffering due to menopause.
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PMID:Estrogen replacement therapy: its benefits and risks. 1227 83

Although renal failure has classically been associated with a bleeding tendency, thrombotic events are common among patients with end-stage renal disease (ESRD). A variety of thrombosis-favoring hematologic alterations have been demonstrated in these patients. In addition, "nontraditional" risk factors for thrombosis, such as hyperhomocysteinemia, endothelial dysfunction, inflammation, and malnutrition, are present in a significant proportion of chronic dialysis patients. Hemodialysis (HD) vascular access thrombosis, ischemic heart disease, and renal allograft thrombosis are well-recognized complications in these patients. Deep venous thrombosis and pulmonary embolism are viewed as rare in chronic dialysis patients, but recent studies suggest that this perception should be reconsidered. Several ESRD treatment factors such as recombinant erythropoietin (EPO) administration, dialyzer bioincompatibility, and calcineurin inhibitor administration may have prothrombotic effects. In this article we review the pathogenesis and clinical manifestations of thrombosis in ESRD and evaluate the evidence that chronic renal failure or its management predisposes to thrombotic events.
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PMID:Thrombosis in end-stage renal disease. 1471 19

As part of the National Surgical Adjuvant Breast and Bowel Project, a controlled clinical trial known as the Breast Cancer Prevention Trial (BCPT) was conducted to assess the effectiveness of tamoxifen as a preventive agent for breast cancer. In addition to the incidence of breast cancer, data were collected on several other, possibly adverse, outcomes, such as invasive endometrial cancer, ischemic heart disease, transient ischemic attack, deep vein thrombosis and/or pulmonary embolism. In this article, we present results from an illustrative analysis of the BCPT data, based on a new modeling technique, to assess the effectiveness of the drug tamoxifen as a preventive agent for breast cancer. We extended the flexible model of Gray (1994, Spline-based test in survival analysis, Biometrics 50, 640-652) to allow inference on multiple time-to-event outcomes in the style of the marginal modeling setup of Wei, Lin, and Weissfeld (1989, Regression analysis of multivariate incomplete failure time data by modeling marginal distributions, Journal of the American Statistical Association 84, 1065-1073). This proposed model makes inference possible for multiple time-to-event data while allowing for greater flexibility in modeling the effects of prognostic factors with nonlinear exposure-response relationships. Results from simulation studies on the small-sample properties of the asymptotic tests will also be presented.
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PMID:Inference in spline-based models for multiple time-to-event data, with applications to a breast cancer prevention trial. 1496 64

Systemic lupus erythematosus (SLE) is a multifactorial polysystemic autoimmune disorder. Although life expectance in SLE has been improved by adequate immune suppressive therapy, the importance of chronic renal failure has not been reduced. Among late complications of the disease accelerated atherosclerosis attempts increasing attention. Dyslipoproteinemia and increased concentration of lipoproteins are important risk factors of atherosclerotic cardiovascular complication in SLE. Serum lipid parameters of 50 patients with lupus were examined in the present work. Thirty patients had histologically proven lupus nephritis (LN+), while the other group did not have renal involvement (LN-). Serum triglyceride, total cholesterol, LDL-C and apolipoprotein B (apoB) concentrations were significantly higher in the lupus nephritis (LN+) group. On the other hand, HDL-C and apoAI levels were also elevated in patients with LN. As a consequence of that, LDL-C/HDL-C and the apoB/apoAI ratios did not differ between patients with or without kidney involvement. This concluded the authors to measure the concentration of lipoprotein (a) in SLE patients, as Lp(a) is known to be an independent risk factor of atherosclerosis. Results indicated a significantly increased Lp(a) concentration in patients with lupus nephritis as compared to the LN- group. All but 2 patients without kidney involvement had lower than 100 mg/L Lp(a) concentration, while 27% of patients with lupus nephritis has an Lp(a) level between 100-300 mg/L. Further more, Lp(a) concentration was higher than 300 mg/L in 13% of the LN+ group. In a good correlation of these observations patients with nephritis suffered more frequently from deep venous thrombosis and ischaemic heart disease. The frequencies of hypertension and non-insulin dependent diabetes mellitus were slightly elevated in patients with nephritis. Present results suggest the importance of elevated lipoprotein (a) concentration in patients with lupus nephritis, further increasing the risk of athero-thrombotic cardiovascular complications.
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PMID:[Lipid profile in patients with systemic lupus erythematosus, with special focus on lipoprotein(a) in lupus nephritis]. 1502 32


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