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 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antiphospholipid syndrome has received considerable attention from the medical community because of its association with a number of serious clinical disorders, including arterial and venous thromboembolism, acute ischemic encephalopathy, recurrent pregnancy loss, thrombocytopenia, and livido reticularis. It can occur within the context of several diseases, mainly autoimmune disorders, and is then called secondary antiphospholipid syndrome. However, it may be also be present without any recognizable disease, or so-called primary antiphospholipid syndrome. There is no defined racial predominance for primary antiphospholipid syndrome, although a higher prevalence of systemic lupus erythematosus (SLE) occurs in African Americans and the Hispanic population. Multiple terms exist for this syndrome, some of which can be confusing. Lupus anticoagulant syndrome, for example, is a misleading term, because patients may not necessarily have SLE, and it is associated with thrombotic rather than hemorrhagic complications. To avoid further confusion, antiphospholipid syndrome is currently the preferred term for this clinical syndrome. Antiphospholipid antibodies are found in 1% to 5% of young healthy control subjects; however, the incidence increases with age and coexistent chronic disease. The syndrome occurs most commonly in young to middle-aged adults; however, it also can occur in children and the elderly. Among patients with SLE, the prevalence of antiphospholipid antibodies is high, ranging from 12% to 30% for anticardiolipin antibodies, and 15% to 34% for lupus anticoagulant antibodies. In general, anticardiolipin antibodies occur approximately five times more often then lupus anticoagulant in patients with antiphospholipid syndrome. This syndrome is the most common cause of acquired thrombophilia, associated with either venous or arterial thrombosis or both. It is characterized by the presence of antiphospholipid antibodies, recurrent arterial and venous thrombosis, and spontaneous abortion. Rarely, patients with antiphospholipid syndrome may have fulminate multiple organ failure, or catastrophic antiphospholipid syndrome. This is caused by widespread microthrombi in multiple vascular beds, and can be devastating. Patients with catastrophic antiphospholipid syndrome may have massive venous thromboembolism, along with respiratory failure, stroke, abnormal liver enzyme concentrations, renal impairment, adrenal insufficiency, and areas of cutaneous infarction. According to the international consensus statement, at least one clinical criterion (vascular thrombosis, pregnancy complications) and one laboratory criterion (lupus anticoagulant, antipcardiolipin antibodies) should be present for a diagnosis of antiphospholipid syndrome. The hallmark result from laboratory tests that defines antiphospholipid syndrome is the presence of antibodies or abnormalities in phospholipid-dependent tests of coagulation, such as dilute Russell viper venom time. There is no consensus for treatment among physicians. Overall, there is general agreement that patients with recurrent thrombotic episodes require life-long anticoagulation therapy and that those with recurrent spontaneous abortion require anticoagulation therapy and low- dose aspirin therapy during most of gestation. Prophylactic anticoagulation therapy is not justified in patients with high titer anticardiolipin antibodies with no history of thrombosis. However, if a history of recurrent deep vein thrombosis or pulmonary embolism is established, long-term anticoagulant therapy with international normalized ratio (INR) of approximately 3 is needed.
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PMID:Antiphospholipid syndrome. 1467 58

Though many neurological deficits have been described in the antiphospholipid syndrome (APS), only stroke is well established and accepted as a diagnostic criterion in this disease. We review clinical data obtained from a large series of cases regarding stroke, dementia, epilepsy, chorea, migraine, white matter disease and behavioral changes in APS or linked to laboratory criteria such as antiphospholipid antibodies (aPL). The contribution of animal models to our understanding of these manifestations of APS is stressed, especially regarding the cognitive and behavioral aspects for which we have established model systems in the mouse. These models utilize immunization of mice with beta2-glycoprotein I, a central autoantigen in APS, which induces persistent high levels of aPL. These mice develop hyperactive behavior after a period of four to five months as well as deficits in learning and memory and are potentially valuable as a system in which to study the pathogenesis and treatment of cognitive and behavioral aspects of APS. Another model we have developed, in which IgG from APS patients induce depolarization of brain synaptoneurosomes, may serve as a model for the pathogenesis of epilepsy in APS.
Lupus 2003
PMID:CNS dysfunction in the antiphospholipid syndrome. 1471 9

The objective of this study was to compare the clinical findings, laboratory data, functional outcome and chronic damage in male patients with primary antiphospholipid syndrome (PAPS) and systemic lupus erythematosus (SLE). We studied 29 male patients with PAPS and 44 with SLE. Clinical findings, laboratory data, lupus damage index (SLICC/ACR DI), and functional outcome in PAPS, were analysed in each group. The mean age at diagnosis was 29.8 +/- 10.4 years in patients with PAPS and 26 +/- 10.1 years in SLE patients. The duration of disease was 4.5 +/- 2.6 versus 5.2 +/- 3.8 years in patients with PAPS and SLE, respectively (P = NS). In patients with PAPS the most frequent clinical manifestations were venous thrombosis, thrombocytopenia, and pulmonary thromboembolism. Patients with SLE had joint, skin and renal involvement more frequently than those with PAPS (P = 0.0001). All PAPS patients had anticardiolipin antibodies (aCL), and 14 patients (48%) had lupus anticoagulant (LA). All SLE patients had antinuclear antibodies (ANAs). Anti-dsDNA antibodies were positive in 39% of SLE patients. Five patients died: one with 'catastrophic' APS and four with SLE. SLICC/ACR-DI score in SLE patients was 1.9 (SD = 1). In PAPS patients poor functional outcome was due to myocardial infarction, pulmonary thromboembolism, stroke and mesenteric thrombosis. Lupus nephritis was the principal organ damage in SLE. In conclusion, in male patients with PAPS and SLE, the clinical manifestations were significantly different. Arterial thrombosis was the major cause of functional impairment and permanent organ damage in PAPS. Renal involvement was the major cause of chronic damage in SLE.
Lupus 2004
PMID:Clinical spectrum of males with primary antiphospholipid syndrome and systemic lupus erythematosus: a comparative study of 73 patients. 1487 Sep 12

Antiphospholipid (aPL) antibodies entailing anticardiolipin (aCL) and anti-beta2 glycoprotein I (anti-beta2GPI) antibodies may be involved in a number of vascular diseases including coronary artery diseases (CAD) or stroke. Here we assessed the presence of aPL antibodies in acute coronary syndrome (ACS). The frequency of anti-beta2GPI antibodies was significantly higher (14.4%) in ACS in comparison to control healthy subjects (2%). In addition, serum concentrations of anti-beta2GPI antibodies were also increased in ACS. Anti-beta2GPI antibodies of the IgA isotype might be the most relevant for the onset and outcome of ACS. Regarding subclasses of ACS, anti-beta2GPI IgA antibodies were elevated in unstable angina (UA) and myocardial infarction with ST elevation (STEMI), but not in myocardial infarction without ST elevation (NSTEMI). The involvement of anti-beta2GPI antibodies in ACS was more pronounced in men than women, and in younger rather than older patients. Finally, anti-beta2GPI antibodies in ACS were associated with previous stroke, but not with hypertension or previous myocardial infarction. Thus, anti-beta2GPI antibodies may be involved in the thrombotic events underlying ACS.
Lupus 2004
PMID:Antiphospholipid antibodies in acute coronary syndrome. 1530 68

During the last few decades, the prognosis for patients with systemic lupus erythematosus (LE) has changed from high early mortality to a more chronic longterm course. Although the prevalence of LE has been estimated at 20-50/100,000, data concerning the situation of LE patients in Germany are sparse. Since 2001, a documentation within the German Lupus Self-Help Organisation scheduled for a period of 10 years (LULA) has been recording at the patient level the actual status and the long-term course of a large group of LE patients. A questionnaire adapted from the German rheumatological database is updated once a year and sent to all members.In 2001, 1033 members participated in the documentation. Of these, 92.2% were women (mean age 45.8 years) with a mean disease duration of 9.9 years. 37.6% were employed, and 24.5% were on early retirement. 50.2% rated their overall health status as "not so good" or "poor". Most were receiving treatment with [hydroxy-]chloroquine (35.2%) or azathioprine (21.9%), while 67.9% were receiving corticosteroids. The most frequent comorbidities reported were hypertension (33%), scarring skin disease (24.4%), osteoarthritis (25.2%), osteoporosis (24%), psychiatric disorders/depression (22.9%) and chronic renal disease (22%). Thromboembolic events were reported in 18.5%, myocardial infarction in 2.3% and stroke in 4.8% of cases. Concerning their main contact person for health care, 63.6% specified the rheumatologist. In comparison with other cohort studies and in particular with the German rheumatological database, the data provided exclusively by patients are feasible. Concerning the severity of their disease, their treatment and their global assessment of health status, LULA participants are comparable with other LE patients and can be seen as representative of LE patients in Germany. Further assessment especially of long-term data are needed to obtain additional insights into the burden of the disease and the need for special medical care.
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PMID:[Lupus in Germany: analysis within the German lupus self-help organization (LULA)]. 1579 77

Bleeding is a rare manifestation of lupus anticoagulant-antiphospholipid syndrome unless associated with coagulation factor deficiency, thrombocytopenia, or intrinsic vascular defect. The authors report the clinical and laboratory findings in a 16-year-old boy with potent lupus anticoagulant who initially presented with recurrent epistaxis, hematuria, and gastrointestinal bleeding. Lupus anticoagulant potently inhibited assay systems for coagulation factors, but levels of factors II, IX, and XI appeared to be decreased (2-5% of mean normal levels). Within 2 weeks after diagnosis, spontaneous subdural hematomas developed. During hemostatic therapy, including plasmapheresis and infusions of recombinant activated factor VII and activated prothrombin complex concentrate, an ischemic stroke developed. Subsequent multifocal recurrent ischemic strokes developed despite immunosuppression. This case shows that lupus anticoagulant or antiphospholipid antibodies can cause both hemorrhagic and thrombotic complications in the same patient and may, in some patients, have multiple target antigens (eg, coagulation factors II, IX, XI).
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PMID:Antiphospholipid syndrome with catastrophic bleeding and recurrent ischemic strokes as initial presentation of systemic lupus erythematosus. 1601 34

The objective of the study was to determine the clinical differences at diagnosis and during follow-up between male and female patients with primary antiphospholipid syndrome (PAPS). We analysed 68 patients, 30 males and 38 females diagnosed and followed between 1990 and 2003. Patients with antiphospholipid syndrome associated with systemic lupus erythematosus at onset and during follow-up were excluded. The mean age at diagnosis was 31.4 +/- 11 years in males and 35.7 +/- 11 years in females (NS). The follow-up after diagnosis was 8.7 +/- 3.1 years in males and 9.2 +/- 2.9 years in females (NS). We did not find significant differences between the two groups with respect to venous and arterial thrombosis. However, in female patients, stroke was more prevalent than in male patients (12/38 versus 3/30, P = 0.03). In contrast, we found a significant prevalence of severe gastrointestinal complications in male compared to female patients (7/30 versus 1/38, P = 0.009). One male patient died due to catastrophic antiphospholipid syndrome. This study suggests that clinical course in patients with PAPS may be different with significant prevalence of central nervous system involvement in females and gastrointestinal involvement in males. Factors such as accelerated atherosclerosis, hormones, related to gender could be the explanation of these findings.
Lupus 2005
PMID:The impact of gender on clinical manifestations of primary antiphospholipid syndrome. 1617 32

Systemic autoimmune disorders are frequently associated to cardiac involvement and to a high prevalence of ischemic coronary events, often occurring at a younger age than in the normal population. Large increase in mortality is related to premature atherosclerosis with coronary artery disease and stroke in patients with connective tissue diseases. Coronary heart disease is responsible for 40-50% of the deaths of patients with rheumatoid arthritis. Transesophageal or transthoracic echocardiography are the most useful and noninvasive techniques able to detect not only valvular abnormalities, embolic sources or pulmonary hypertension, but also left ventricular systolic or diastolic dysfunction. Furthermore, the introduction of new indexes, contrast agents and software increased the accuracy of this technique. It is possible now to evaluate coronary flow reserve by transthoracic echocardiography in patients with systemic autoimmune disease in order to detect microvasculature disorder. However, an ischemic response in a symptomatic patient requires, in most cases, further evaluation with cardiac catheterization. Coronary artery imaging allows confirmation of the presence, extent and position of atheromatous lesions. More recently, other imaging modalities including magnetic resonance and computerized tomography angiography have been developed to allow imaging of the coronary arteries.
Lupus 2005
PMID:Cardiac imaging techniques in systemic autoimmune diseases. 1621 76

High-sensitive C-reactive protein (hs-CRP) is a marker of inflammation which has been shown in several prospective studies to independently predict myocardial infarction, stroke and peripheral artery disease. Patients with antiphospholipid antibodies (aPL) are at increased risk of recurrent thromboembolic events, but the possibility of predicting this risk seems rather limited. Similarities were recently found between aPL and CRP in the pathology of thrombosis. The current study investigated the predictive role of hs-CRP in a cohort of patients with neurological manifestations. A follow-up investigation was done in a cohort of 55 aPL-positive patients with acute manifestations of neurological disease. hs-CRP levels were measured in all patients at enrollment and were compared to the patients' condition after a median period of 32 months. Lupus anticoagulants were detected according to the Standardization of Lupus Anticoagulants (SSC) of the ISTH. Anticardiolipin tests were performed by a beta2-glycoprotein I-dependent enzyme-linked immunsorbent assay (Pharmacia ELISA). hs-CRP was measured by latex-enhanced turbidometry (dimension RXL, Dade Behring). Cerebral infarctions and transient ischemic attacks were the most frequent cerebral events. In patients with aPL, elevated levels of hs-CRP were closely associated with an increased rate of recurrent or residual symptoms (OR, 12.5; 95% CI, 3.72-41.94) and were not related to other risk factors, except smoking (p<0.05). The rate at which a given patient's condition deteriorated was also related to the level of hs-CRP. In patients with antiphospholipid syndrome (APS), elevated levels of hs-CRP may identify a group of patients which is at high risk of recurrent or residual neurological symptoms and which may benefit from more careful follow-up and from antithrombotic therapy.
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PMID:Predictive role of hs-C-reactive protein in patients with antiphospholipid syndrome. 1632 94

Beta2-glycoprotein I (beta2GPI) is a plasma protein suspected to have a role in inhibition of thrombosis. This suspicion is reinforced by the observation that beta2GPI is the major target for autoantibodies in the antiphospholipid syndrome. However, little is known about its circulating levels in common thrombotic diseases or inflammation. We measured beta2GPI levels in 344 healthy controls, 58 normal pregnancies, 102 patients with non-haemorrhagic stroke, 121 patients with acute coronary syndrome and 200 patients with elevated C-reactive protein (CRP). In healthy individuals, we found a strong positive correlation between age and beta2GPI concentration (r = 0.274, P < 0.001) and that beta2GPI levels fall significantly after the eighth week of pregnancy (P = 0.002). We also found significantly reduced levels of beta2GPI in patients with stroke and in elderly patients with myocardial syndrome (P = 0.013 and 0.043). However, in neither group did beta2GPI levels change in the following six months, suggesting that the reduced levels were not a transient post-event phenomenon. In patients with inflammation, beta2GPI levels showed a significant negative correlation with CRP (r = -0.284, P < 0.001) and positively correlated with albumin and transferrin (r = 0.372 and 0.453, respectively with P < 0.001 for both). Furthermore, the largest reduction in beta2GPI levels occurred in patients with the highest CRP values (P < 0.001).
Lupus 2006
PMID:Circulating levels of beta2-glycoprotein I in thrombotic disorders and in inflammation. 1653 79


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