Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008031 (chest pain)
 17,248 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The acute phase reactant, alpha-1-acid glycoprotein, binds to a number of basic antiarrhythmic drugs, including lidocaine, quinidine, propranolol, imipramine and disopyramide. Binding to alpha-1-acid glycoprotein accounts for a decrease in free drug fraction and may alter the expected concentration: response relation of drugs particularly when there are unpredictably large or rapid changes in alpha-1-acid glycoprotein. To determine the time course and magnitude of alpha-1-acid glycoprotein for 1 month after acute myocardial infarction (AMI), blood samples were collected from 27 patients, 14 with AMI and 13 with a chest pain syndrome but no AMI. Patients with AMI had a significant increase in alpha-1-acid glycoprotein after 72 hours (mean 153 +/- 35 mg/dl) (p less than 0.05), and the maximum was observed on day 7 (mean 165 +/- 53 mg/dl) (p less than 0.05), returning to baseline by 28 days. There was no significant change in alpha-1-acid glycoprotein in patients with chest pain but no AMI. Regression analysis showed a significant relation between creatine kinase (p less than 0.005) and lactic dehydrogenase (p less than 0.001) vs alpha-1-acid glycoprotein indicating alpha-1-acid glycoprotein concentration is high in patients with large AMI. Changes in binding resulting from alpha-1-acid glycoprotein during AMI could account for misinterpretation of total drug concentration and response to antiarrhythmic drugs acutely, during convalescence and at discharge.
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PMID:Time course of alpha-1-acid glycoprotein and its relation to myocardial enzymes after acute myocardial infarction. 402 63

Serum propranolol concentration, elimination t 1/2, and protein binding were studied after a combined intravenous/oral regimen in 20 subjects with myocardial infarction (MI) and 15 with chest pain (CP). There was 1000% interindividual variation in propranolol concentrations in each group. In the MI group, mean total serum propranolol concentrations were greater than 100 nmol/l, except at 7 hr, when there was a trough not present in subjects with CP. Mean elimination t 1/2 s in subjects with MI (7.2) and CP (7.4 hr) did not differ. There were significantly higher alpha 1-acid glycoprotein concentrations and reduced percent unbound propranolol 27 hr after infarction. Free propranolol concentrations were lower 7 and 11 hr after dosing in the MI group, but concentrations thereafter were of the same order as those in subjects with CP. The only significant difference in any of the hemodynamic measurements was at 7 hr, when blood pressure was higher in the MI group. We conclude that propranolol kinetics were altered in subjects with MI and suggest that the regimen could be improved by increased propranolol dosage at commencement of therapy.
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PMID:Propranolol disposition after acute myocardial infarction. 646 93

In 15 patients with confirmed myocardial infarction, alpha-1-acid glycoprotein rose significantly from 117 mg/dL at admission to 140 mg/dL at 36 hours (p less than 0.01), but not in 15 age- and sex-matched patients with chest pain only. Twelve patients were given prolonged infusions of lidocaine (2 mg/min). In patients with myocardial infarction, the rise in plasma alpha 1-acid glycoprotein concentration was associated with increased lidocaine binding and a rise in total lidocaine concentrations between 12 and 48 hours (p less than 0.05). Because of the binding changes, however, the rise in free drug concentration (31.2%) was significantly less than the 56.3% rise in total drug level (p less than 0.05). No changes in alpha 1-acid glycoprotein or lidocaine disposition were seen between 12 and 48 hours in the control subjects. Our results show that the rise in alpha 1-acid glycoprotein after myocardial infarction is associated with lidocaine accumulation, but increased plasma binding attenuates the rise in free drug. This suggests that the toxicologic implications of lidocaine accumulation may have been exaggerated and therapeutic monitoring of total plasma levels may be misleading.
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PMID:Increased alpha-1-acid glycoprotein and lidocaine disposition in myocardial infarction. 721 79

The immunoconjugate XMMCO-791/RTA consists of ricin A chain bound to a murine monoclonal antibody MoAb 791T. This monoclonal antibody (MoAb) binds to a glycoprotein of 72 kD, which is expressed on human colorectal carcinoma, ovarian carcinoma, and osteogenic sarcoma. XMMCO-791/RTA was tested in a Phase I trial with proposed dose escalation steps of 0.02, 0.04, 0.15, and 0.2 mg/kg per day. Twelve patients with metastatic colorectal carcinoma were treated at 0.02, 0.03, and 0.04 mg/kg per day dose levels administered over 1 hour on days 1-5. Study-related toxicities were hypotension (6 patients); greater than 10% weight gain (6 patients); peripheral edema (9 patients); fever (4 patients); confusion (3 patients); diarrhea (3 patients); proteinuria, as identified by dipstick (3 patients), greater than 0.6 mg/dl decrease in serum albumin (11 patients); greater than 25% decrease in oncotic pressure (10 patients), and a decrease in ionized calcium (8 patients). Six patients received a second course of treatment. HAMA levels developed in 9 patients and titers increased with number of courses administered. Decreased overall toxicity, in comparison to the first course, was noted, but one patient had an allergic-type response (hypotension, crushing chest pain, diaphoresis) after the test dose of the second course (HAMA level > 10,000 IgG). Life-threatening toxicity in the form of fluid shift, resulting in noncardiac pulmonary edema and third-spacing occurred after course 1 in 1 of 3 patients at the 0.04 mg/kg per day level. No further dose escalation was attempted and no antitumor activity was seen.
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PMID:Phase I study of monoclonal antibody-ricin A chain immunoconjugate Xomazyme-791 in patients with metastatic colon cancer. 762 72

During acute myocardial infarction, pre-hospital stage and the first hours after admission are crucial for initiating reperfusion therapy, which is determinant for short- and mid-term survival. Within 12 hours after onset of chest pain, either thrombolysis or primary angioplasty contribute to reduce mortality rate, the earlier being the better. Therapeutic advances, regarding either thrombolysis or angioplasty, are directed towards an earlier, more efficient and stable (without reocclusion) patency of the infarct-related artery. Most promising results so far have been obtained with platelet glycoprotein (GP) IIb/IIIa receptor blockers, in combination with thrombolysis or angioplasty.
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PMID:[Acute myocardial infarction: prehospital phase and first hospital days]. 1073 23

Mortality rates in patients after myocardial infarction (MI) have decreased from a high of >50% in the 1930s to 10-15% currently, and even lower in some clinical trials. At present, much of the research is focused on (1) identifying patients at high risk despite the lack of typical prognosticators of a severe event; and (2) delineating the optimal therapy for patients with unstable angina or non-Q-wave MI. Clinicians are now focusing on acute coronary syndrome. Patients present with (1) minor electrocardiographic abnormalities; (2) chest pain; and (3) possible abnormalities in creatine kinase, creatine kinase-myocardial band, and troponin. The primary goal for these patients is to prevent plaque rupture and its associated morbidity and mortality. Aspirin and heparin are clearly indicated. The glycoprotein (GP) IIb/IIIa receptor inhibitors are even more effective in inhibiting platelet activation. Under what circumstances should these agents be used, and which of the 3 currently available agents is superior? Analysis of the trials addressing these questions clearly demonstrates the importance of these agents in this setting. The choice of agent is still unclear, pending a randomized, interdrug comparison. It also remains to be demonstrated whether low-molecular-weight heparin is superior to standard heparin in this setting and which patients should undergo angiography.
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PMID:Management of intermediate coronary syndrome: role of conservative treatment, glycoprotein IIb/IIIa receptor inhibitors, and direct intervention. 1119 45

The aim of this study was to examine whether detection of coronary calcium and the autoimmune response associated with atherosclerosis, either solely or in combination, are different in patients with typical and atypical chest pain. Coronary calcium as detected by spiral computerized tomography and levels of antibodies against cardiolipin (CL), oxidized low-density lipoprotein (ox-LDL), and beta2-glycoprotein-I (beta2-GPI) were studied in patients with typical chest pain (n = 52), atypical chest pain (n = 19), or without chest pain (n = 21). Patients with typical chest pain had higher mean levels of coronary calcium (expressed as natural transformation of total coronary calcium score) compared with patients with atypical chest pain and controls (5.04 vs 3.21 and 2.75, respectively; p < 0.001). The levels of anti-CL were (mean +/- SD of optical density multiplied by 1,000): 262 +/- 140, 170 +/- 82, and 230 +/- 115 for patients with typical chest pain, atypical chest pain, and controls, respectively (p = 0.016). No significant difference was found between groups regarding anti-ox-LDL and anti-beta2-GPI autoantibody levels. In the typical chest pain group, there was a higher prevalence of high total coronary calcium scores (p = 0.03) and high anti-CL levels (p = 0.01) than in the atypical chest pain group. Eighteen of 52 patients with typical chest pain (35%) had both high calcium scores and high antibody levels, whereas none of the 19 patients (0%) who had atypical chest pain had high levels of both (p = 0.003). A combination of both coronary calcium and anti-CL was associated with higher area under the receiver operator characteristic curves than for each separately. High coronary calcium scores or high anti-CL levels are found more often in typical than in atypical chest pain patients, but a combination of high levels of both can better differentiate typical from atypical chest pain patients.
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PMID:Coronary calcium and anti-cardiolipin antibody are elevated in patients with typical chest pain. 1111 3

Myocardial ischaemia activates blood platelets and cardiac sympathetic afferents, which mediate chest pain and cardiovascular reflex responses. We have demonstrated that activated platelets stimulate ischaemically sensitive cardiac sympathetic afferents. Platelets absorb and release 5-hydroxytryptamine (5-HT) when they are activated. In the present study we hypothesized that, by releasing 5-HT, activated platelets stimulate cardiac afferents during ischaemia through a 5-HT(3) receptor mechanism. Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were obtained from cats. Activation of platelets in PRP was induced by thrombin (5 units ml(-1)) or collagen (2 mg kg(-1)). Using high-performance liquid chromatography, we observed that the concentration of 5-HT was increased significantly in suspensions of platelets activated with thrombin (PRP+thrombin, 28 +/- 1.7 microM) or collagen (PRP+collagen, 27 +/- 2.5 microM) compared with suspensions of unactivated platelets (PRP+saline, 2.3 +/- 0.8 microM) and PPP. During myocardial ischaemia and reperfusion, tirofiban, a specific inhibitor of platelet glycoprotein (GP) IIb-IIIa receptors (100 microg kg(-1), I.V., followed by 5 microg kg(-1) min(-1)), significantly reduced the increase in the concentration of 5-HT in cardiac venous plasma from ischaemic region. Nerve activity of single-unit cardiac afferents was recorded from the left sympathetic chain (T2-T5) in anaesthetized cats. Eighty ischaemically sensitive and seven ischaemically insensitive cardiac afferents were identified. Tirofiban reduced the ischaemia-related increase in activity of seven cardiac sympathetic afferents by 50 %. Injection of 1.5 ml of PRP+collagen or PRP+thrombin into the left atrium (LA) increased activity of 16 cardiac afferents. Tropisetron (300 microg kg(-1), I.V.), a selective 5-HT(3) receptor antagonist, eliminated the afferent's responses to platelets activated with collagen or thrombin. Moreover, LA injection of 5-HT (20-40 microg kg(-1)) and PBG (100 microg kg(-1)), a 5-HT(3) receptor agonist, stimulated nine ischaemically sensitive cardiac sympathetic afferents, significantly increasing the activity of these afferents. However, injection of alpha-M-5-HT (100 microg kg(-1), LA), a 5-HT(2) receptor agonist, stimulated only two of the nine ischaemically sensitive cardiac afferents, and thus did not significantly alter impulse activity of this group of afferents. Both the 5-HT(1) (5-CT, 100 microg kg(-1), LA) and 5-HT(4) receptor agonists (SC53116, 100 microg kg(-1), LA) did not stimulate any of the nine afferents tested. Tropisetron (300 microg kg(-1), I.V.) also eliminated the response of seven ischaemically sensitive cardiac afferents to exogenous 5-HT and attenuated the ischaemia-related increase in activity of nine cardiac sympathetic afferents by 41 %. Conversely, LA injection of 5-HT (40 microg kg(-1)) did not stimulate any of seven ischaemically insensitive cardiac afferents, although this group of afferents consistently responded to bradykinin (3 microg, LA). These data indicate that during myocardial ischaemia the activated platelets stimulate cardiac sympathetic afferents, at least in part, through a 5-HT(3) receptor mechanism.
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PMID:Activated platelets contribute to stimulation of cardiac afferents during ischaemia in cats: role of 5-HT(3) receptors. 1241 32

Antiphospholipid antibodies are the hallmark of the antiphospholipid syndrome which is characterized by thrombosis. There are currently data supporting an association between these autoantibodies and atherosclerosis as well. Human studies suggest that anti-cardiolipin and anti-beta2-glycoprotein-I antibodies are elevated in patients having coronary artery disease compared with controls. Anti-cardiolipin antibodies are also associated with typical chest pain, significant coronary artery stenosis on angiography and prediction of myocardial infarction. Laboratory studies and murine models support the pro-atherogenic role of these autoantibodies, as they are involved in uptake of oxidized LDL into macrophages, and immunization of mice with them results in enhanced atherosclerosis. There is some evidence that high anti-beta2-glycoprotein-I antibodies can present a risk factor for atherosclerosis, but more epidemiological data are required in order to confirm whether the pro-atherogenic properties of anti-phospholipid antibodies signifies an independent risk factor for atherosclerosis and its complications.
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PMID:Antiphospholipid antibodies: are they pro-atherogenic or an epiphenomenon of atherosclerosis? 1263 97

A prospective observational study was conducted in 2,007 patients experiencing chest pain to determine impact of local quality improvement (QI) measures on the use of glycoprotein (GP) IIb/IIIa inhibitors in the ED treatment of high-risk patients with non-ST-segment elevation acute coronary syndromes (ACS). Patients with injury on the initial ECG or new sustained injury on continuous ECG were excluded. QI interventions were as follows: control (0-4 mo): no interventions (standardized protocols and prewritten orders in place 4 months prior); phase I (5-8 mo): simple education/awareness program with posted drug information pamphlets and eligibility criteria; phase II (9-12 mo): mandated QI form with real-time feedback and focused one-on-one physician education championed by an ED physician QI advocate. A total of 179 (8.9%) of the study patients met predefined high-risk criteria. Of these, a total of 41 (23.0%) patients had GP IIb/IIIa inhibitor therapy initiated in the ED. Percent of high-risk patients receiving therapy increased from 6.0% during the control phase to 16.1% during phase I and 50.9% during phase II. After controlling for patient demographics, patients treated during phase I had a 2.8 times increased odds (95% confidence interval CI: 0.8-10.3; P =.11 [not significant]) of receiving GP IIb/IIIa inhibitor relative to the control phase, and patients treated during phase II had a 20.2 times increased odds (95% CI: 6.1-66.9; P <.0001) of treatment. In conclusion, local QI measures incorporating standardized protocols, preprinted orders, physician education, and interactive feedback championed by an ED QI physician advocate can increase early use of GP IIb/IIIa inhibitors in the ED treatment of high-risk patients presenting with chest pain.
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PMID:Early use of glycoprotein IIb/IIIa inhibitors in the ED treatment of non-ST-segment elevation acute coronary syndromes: a local quality improvement initiative. 1289 87


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