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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment options in acute stroke are limited by a dearth of safe and effective regimens for recanalization of an occluded cerebrovascular tributary, as well as by the fact that patients present only after the occlusive event is established. We hypothesized that even if the site of major arterial occlusion is recanalized after stroke, microvascular thrombosis continues to occur at distal sites, reducing postischemic flow and contributing to ongoing neuronal death. To test this hypothesis, and to show that microvascular thrombosis occurs as an ongoing, dynamic process after the onset of stroke, we tested the effects of a potent antiplatelet agent given both before and after the onset of middle cerebral arterial (MCA) occlusion in a murine model of stroke. After 45 min of MCA occlusion and 23 h of reperfusion, fibrin accumulates in the ipsilateral cerebral hemisphere, based upon immunoblotting, and localizes to microvascular lumena, based upon immunostaining. In concordance with these data, there is a nearly threefold increase in the ipsilateral accumulation of 111In-labeled platelets in mice subjected to stroke compared with mice not subjected to stroke. When a novel inhibitor of the glycoprotein IIb/IIIa receptor (SDZ GPI 562) was administered immediately before MCA occlusion, platelet accumulation was reduced 48%, and fibrin accumulation was reduced by 47% by immunoblot densitometry. GPI 562 exhibited a dose-dependent reduction of cerebral infarct volumes measured by triphenyltetrazolium chloride staining, as well as improvement in postischemic cerebral blood flow, measured by laser doppler. GPI 562 caused a dose-dependent increase in tail vein bleeding time, but intracerebral hemorrhage (ICH) was not significantly increased at therapeutic doses; however, there was an increase in ICH at the highest doses tested. When given immediately after withdrawal of the MCA occluding suture, GPI 562 was shown to reduce cerebral infarct volumes by 70%. These data support the hypothesis that in ischemic regions of brain, microvascular thrombi continue to accumulate even after recanalization of the MCA, contributing to postischemic hypoperfusion and ongoing neuronal damage.
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PMID:Reduced microvascular thrombosis and improved outcome in acute murine stroke by inhibiting GP IIb/IIIa receptor-mediated platelet aggregation. 976 22

Beta 2-glycoprotein I (beta2-GPI) is an antigenic target recognised by antiphospholipid antibodies found in association with the antiphospholipid syndrome (APS). In this study, the prevalence of Immunoglobulin M (IgM) and IgA anti-beta2-GPI antibodies was examined in APS patients and compared with IgG antibodies. In addition the value of measuring antibody isotypes and IgG subclass was investigated in the laboratory diagnosis of APS. A solid phase enzyme linked immunosorbent assay was established to measure IgG, IgM and IgA and IgG subclass antibodies to beta2-GPI in patients with APS and a variety of other thrombotic and non-thrombotic disorders. Raised levels of IgM anti-beta2-GPI antibodies were observed in 65% of patients with APS, 21% with systemic lupus erythematosus (SLE), 23% with rheumatoid factor, 4% with stroke, 5% carotid artery stenosis (CAS), 17% with a biological false positive serology for syphilis, 43% with infectious mononucleosis (IM) and 27% with human immunodeficiency virus (HIV). The median value for IgM antibodies to beta2-GPI for all these groups ranged from 2 to 7 arbitrary units (AU). Elevated levels of IgA antibodies to beta2-GPI were found in patients with APS (47%), SLE (13%), rheumatoid factor (26%), CAS (48%), stroke (25%), VDRL false positive serology for syphilis (33%), IM (47%) and HIV (7%). The median value of IgA antibodies to beta2-GPI in all of these groups ranged from 2 to 4 AU. Conversely the median value for IgG anti-beta2-GPI in APS patients was 112 AU compared to 1-4 AU in the other conditions examined. The presence of IgM and IgA antibodies to beta2-GPI was much less specific and sensitive for APS than IgG, with raised levels of these isotypes seen in a variety of thrombotic and non-thrombotic disorders. Elevated levels of IgG1, IgG2, IgG3 and IgG4 antibodies to beta2-GPI were detected in APS patients. While all four IgG anti-beta2-GPI antibody subclasses were represented in APS patients there appeared to be a significant overall skewing towards to the IgG2 subclass.
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PMID:Anti-Beta 2-glycoprotein I antibody isotype and IgG subclass in antiphospholipid syndrome patients. 1068 Jul 49

Antibodies to beta(2)-glycoprotein (beta(2)-GPI) have been associated with recurrent thrombotic events in patients with systemic lupus erythematosus. The present study investigated the prevalence of antibodies to beta(2)-GPI in an unselected group of patients with ischemic stroke. One hundred and twenty-one sera from patients with ischemic stroke and 174 control sera from patients with nonischemic neurological disorders (n = 43) and healthy subjects (n = 131) were tested for antibodies to beta(2)-GPI by a solid-phase ELISA. Twenty-nine stroke patients (24%) had antibodies to beta(2)-GPI. Of the 43 patients in the neurological control group, 2 were positive. For comparison between the groups, Fisher's exact test was used for categorical variables and ANOVA for antibody titers. Antibody levels and frequencies of positivity were significantly different between the study groups. None of the sera from the healthy control group had abnormal antibody levels. When risk factors and associated diseases were taken into account, a marginal association was found between the presence of antibodies to beta(2)-GPI and hypertension (p = 0.036). This study demonstrates a significant prevalence of antibodies to beta(2)-GPI in an unselected stroke population.
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PMID:Antibodies to beta(2)-glycoprotein I in ischemic stroke. 1087 35

Traditionally, the identification, epidemiology and spectrum of clinical diseases caused by Granulicatella adiacens and Abiotrophia defectiva are dependent upon their phenotypic characterization. During a 6-year period (July 1995-June 2001), seven and two alpha-haemolytic streptococci were identified as G. adiacens and A. defectiva, respectively, by 16S rRNA gene sequencing. Three patients with haematological malignancies and neutropenic fever had primary bacteraemia. Three patients with valvular problems or congenital heart disease had infective endocarditis. A patient with ischemic heart disease and cerebrovascular accident had infected aortic atheroma with dissection. A patient with recurrent pyogenic cholangitis had acute cholangitis and a patient with polypoid cystitis and benign prostatic hypertrophy had acute prostatitis. Four of the nine patients died, including all three with G. adiacens infective endocarditis or infected atheroma. For the seven G. adiacens isolates, the API 20 STREP system successfully identified one and five isolates as G. adiacens with >95 % and 80-90 % confidence, respectively, whereas the Vitek System (GPI) and ATB Expression system (ID32 STREP) successfully identified none and one isolate as G. adiacens. Of the two A. defectiva isolates, none of the three systems successfully identified either of them as A. defectiva. 16S rRNA gene sequencing is the technique of choice for identifying G. adiacens and A. defectiva, and early surgical intervention should be considered when G. adiacens endocarditis is diagnosed.
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PMID:Granulicatella adiacens and Abiotrophia defectiva bacteraemia characterized by 16S rRNA gene sequencing. 1254 19

BEta(2)-glycoprotein I (beta(2)-GPI) is proteolytically cleaved by plasmin in domain V (nicked beta(2)-GPI), being unable to bind to phospholipids. This cleavage may occur in vivo and elevated plasma levels of nicked beta(2)-GPI were detected in patients with massive plasmin generation and fibrinolysis turnover. In this study, we report higher prevalence of elevated ratio of nicked beta(2)-GPI against total beta(2)-GPI in patients with ischemic stroke (63%) and healthy subjects with lacunar infarct (27%) when compared to healthy subjects with normal findings on magnetic resonance imaging (8%), suggesting that nicked beta(2)-GPI might have a physiologic role beyond that of its parent molecule in patients with thrombosis. Several inhibitors of extrinsic fibrinolysis are known, but a negative feedback regulator has not been yet documented. We demonstrate that nicked beta(2)-GPI binds to Glu-plasminogen with K(D) of 0.37 x 10(-6) M, presumably mediated by the interaction between the fifth domain of nicked beta(2)-GPI and the fifth kringle domain of Glu-plasminogen. Nicked beta(2)-GPI also suppressed plasmin generation up to 70% in the presence of tissue plasminogen activator, plasminogen, and fibrin. Intact beta(2)-GPI lacks these properties. These data suggest that beta(2)-GPI/plasmin-nicked beta(2)-GPI controls extrinsic fibrinolysis via a negative feedback pathway loop.
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PMID:Nicked beta2-glycoprotein I: a marker of cerebral infarct and a novel role in the negative feedback pathway of extrinsic fibrinolysis. 1472 99

The only drug approved by the US FDA for use in patients with acute ischemic stroke is the thrombolytic, alteplase. Whereas alteplase rapidly restores blood flow, the drug has to be administered within 6 hours after symptom onset and is associated with an increased incidence of intracerebral hemorrhage (ICH). Moreover, transient and permanent re-occlusions associated with increased mortality continue to occur after thrombolysis with alteplase. Platelets are believed to play a pivotal role in the pathogenesis of atherothrombosis and the binding of the platelet glycoprotein (GP) IIb/IIIa receptor to fibrinogen is the final common pathway leading to platelet aggregation and thrombus formation. Antiplatelet agents such as platelet GP IIb/IIIa receptor antagonists have been studied in numerous multicenter, randomized clinical trials in patients with acute coronary symptoms (ACS). The intravenous GP IIb/IIIa receptor antagonists abciximab, eptifibatide and tirofiban are approved by the FDA for use in patients with ACS, and intravenous tirofiban is also approved for use during coronary intervention. Oral GP IIb/IIIa receptor antagonists such as lotrafiban, xemilofiban, sibrafiban and orbofiban have failed to provide myocardial protection in patients with ACS. Compared with ACS, few trials have evaluated the efficacy and tolerability of platelet GP IIb/IIIa receptor antagonists in patients with cerebrovascular syndromes. Agents such as SM-20302, TP201, ME3277, murine 7E3 F(ab')(2 )and SDZ-GPI 562 have been reported to preserve microvascular patency in different animal models of acute ischemic stroke and they may have neuroprotective properties. Platelet GP IIb/IIIa receptor antagonists may be suitable as a single therapeutic or as an adjunct therapeutic to thrombolysis with alteplase for the treatment of stroke. Platelet GP IIb/IIIa receptor antagonists may enhance the efficacy of thrombolytics and reduce potentially fatal adverse effects such as ICH. Preliminary results from the Abciximab in Emergent Stroke Treatment Trial (AbESTT) indicate that abciximab, administered as a bolus dose 0.25 mg/kg followed by 12-hour infusion, was associated with significant improvement in clinical rating scores and no significant increase in bleeding episodes in patients with acute stroke. The tolerability of argatroban in patients with acute stroke is currently being assessed in the multicenter Argatroban in Ischemic Stroke (ARGIS-1) trial.
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PMID:Therapeutic potential of platelet glycoprotein IIb/IIIa receptor antagonists in the management of ischemic stroke. 1472 35

Neuroimmunophilin ligands (NILs) are drugs derived from the immunosuppressant FK506 (tacrolimus) that have been shown to have variable efficacy in reversing neuronal degeneration and preventing cell death. In a wide range of animal models mimicking Parkinson's disease, dementia and even surgical nerve damage they induce re-sprouting, are neurotrophic or prevent nerve damage. The neurotrophic mechanism of action of these compounds is not known and may be dependent on the type of damage and genetic variability at the species or cellular level. Some evidence suggests that NILs may act through a family of proteins called FK506 binding proteins, some of which may regulate steroid hormone receptors. Other evidence suggests that NILs may protect neurons by upregulating the antioxidant glutathione and stimulating nerve regrowth by inducing the production of neurotrophic factors. Initial clinical trials have had mixed success. In one, patients with moderately severe Parkinson's disease showed no overall improvement in fine motor skills following 6 months of treatment by the neuroimmunophilin GPI 1485. But these patients did exhibit decreased loss of dopaminergic nerve terminals with a low dose of GPI 1485 and in fact some increase in dopaminergic terminals within 6 months of the higher dose of GPI 1485 drug treatment. As a result, a second phase II clinical trial using a patient population with less severe degeneration has been initiated concurrent with an investigation of GPI 1485 and other neuroprotective therapies funded by the National Institute of Neurological Disorders and Stroke. Another clinical trial ongoing at this time is exploring the use of a neuroimmunophilin ligand to prevent nerve degeneration and erectile dysfunction resulting from prostatectomy. In summary, neuroimmunophilins show promise to reverse some forms of neurodegeneration but exact factors that predict outcome have not been identified.
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PMID:Neuroimmunophilins: a novel drug therapy for the reversal of neurodegenerative disease? 1545 Mar 48

The study of IgG and IgM anti-cardiolipin antibodies (IgG/IgM aCL) is now well accepted and is routinely used in the risk assessment of various conditions associated with thrombosis. The aim of the study was to define whether the investigation of aCL is sufficient by itself to evaluate a risk of ischemic stroke. Frequency of aCL and anti-beta2-glycoprotein I (beta2-GPI) antibodies was prospectively investigated in 96 patients with ischemic stroke and in 119 controls by ELISA. In ischemic stroke patients IgG aCL were found in 36%, the IgM-aCL were found in 58%, the IgG-IgM-aCL were found in 43%. The levels of both antibodies were higher in patients with ischemic stroke than in controls (p < 0.01). In controls, IgM-aCL were positive in 2% and IgG-aCL antibodies were negative. IgG-beta-GPI Abs were found in ischemic patients in 19% and IgM-beta2-GPI Abs in 37%. The IgG-IgM-anti-beta2-GPI Abs were found in 24% patients. They were negative in controls. There was a correlation between levels of aCL and anti-beta2-GPI Abs for both isotypes (r = 0.728) but not between IgG- and IgM-beta2-GPI Abs. IgG-aCL test was more sensitive for ischemic stroke than the IgG-beta2-GPI Abs test (71.4%, respectively 65.7%) but less specific (66.8%, respectively 88.6%). The sensitivity of anti-beta2-GPI Abs for ischemic stroke was increased when both isotypes were tested. These results showed that aCL and anti-beta2-GPI Abs could be pathogenetically important for ischemic stroke and that anti-beta2-GPI Abs testing might contribute to a better evaluation of ischemic stroke.
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PMID:Study of anti-cardiolipin and anti-beta2-glycoprotein I antibodies in patients with ischemic stroke. 1552 3

Western medicine was introduced to Taiwan in 1865 when Dr. James L. Maxwell, a missionary doctor of the English Presbyterian Church, established a hospital in nowadays Tainan. The period of the missionary medicine lasted for over 30 years until Japanese took over. During this period, however, official records of diseases in Taiwan that were based on Western medicine were scanty or not available. Fortunately, port surgeons stationing respectively in Tamsui and Kelung in the north and in Takow and Taiwan-fu in the south reported semi-annually diseases seen in the ports, foreign communities and missionary hospitals that they volunteered to work. The diseases reported by port surgeons were either cases or summary of cases with classification and statistics. Their medical reports covered from 1871 to 1900. The data show that neurological diseases and/or disorders in the late 19th century Taiwan were uncommon, comprising only 2-3% of total diseases. The data further show that common neurological diseases were leprosy, opium smoking, syphilitic dementia (GPI), paralysis, hysteria, neuralgia, epilepsy, mania, sciatica, meningitis and ataxia. Stroke was uncommon while Parkinson's disease and Alzheimer's disease were not mentioned, indicating that neurological diseases related to old age and neurodegeneration were not yet a threat to health. Similarly, headache, insomnia, anxiety and depression, hallmark of functional disorders of the modern society, were also not mentioned, suggesting that these disorders were indeed rare or did not cause sufficient concern for patients to seek help from doctors of Western medicine.
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PMID:[Neurological diseases in late 19th century Taiwan--medical reports of the Chinese Imperial Maritime Customs]. 1642 51

Functional recovery following acute CNS injury in humans, such as spinal cord injury and stroke, is exceptionally limited, leaving the affected individual with life-long neurological deficits such as loss of limb movement and sensation leading to a compromised quality of life. As yet, there is no effective treatment on the market for such injuries. This lack of functional recovery can at least in part be attributed to the restriction of axonal regeneration and neuroplasticity by several CNS myelin proteins that have been shown to be potent inhibitors of neurite outgrowth in vitro, namely myelin-associated glycoprotein (MAG), Nogo-A and oligodendrocyte myelin glycoprotein (OMgp). Nogo-A contains multiple neurite outgrowth inhibitory domains exposed on the surface of myelinating oligodendrocytes located within its amino-terminal region (amino-Nogo-A) and C-terminal region (Nogo-66). Although structurally dissimilar; Nogo-66, MAG and OMgp exert their inhibitory effects by binding the GPI-linked neuronal Nogo-66 receptor (NgR) that transduces the inhibitory signal to the cell interior via transmembrane co-receptors LINGO-1 and p75(NTR)or TROY. Although the receptor(s) for amino-Nogo-A are unknown, amino-Nogo-A and NgR ligands mutually activate the small GTPase RhoA. Consistent with their neurite outgrowth inhibitory function, approaches counter-acting Nogo-A using function-blocking antibodies, NgR using peptide antagonists and receptor bodies or RhoA using deactivating enzymes have been shown to significantly enhance axonal regeneration and neuroplasticity leading to improved functional recovery in animal models of acute CNS injury. These in vivo findings thus provide a sound basis for the development of an effective treatment for acute CNS injuries in humans.
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PMID:Targeting the Nogo-A signalling pathway to promote recovery following acute CNS injury. 1769 15


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