Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the effect of antibodies directed against a leukocyte adhesion molecule (ICAM-1) in an embolic model of stroke followed by thrombolysis with tissue plasminogen activator (tPA). To test whether reperfusion injury after ischemia was related to white cell adhesion, microclots were injected into carotid circulation. The conditions examined were control, alpha-ICAM 5 min following ischemia, tPA 30 min after ischemia, and the combination of alpha-ICAM and tPA. alpha-ICAM and tPA both increased the amount of clot necessary to produce permanent neurological damage. Combined therapy was no more effective than either substance alone. A similar outcome was obtained when tPA was delayed until 90 min postischemia. When thrombolysis was delayed 3 h following embolism, neither tPA nor the tPA/alpha-ICAM combination reduced neurological damage. Thus, the alpha-ICAM antibody and tPA each effectively reduced neurological damage but the interaction was not significant.
 ...
PMID:Monoclonal antibody to the ICAM-1 adhesion site reduces neurological damage in a rabbit cerebral embolism stroke model. 809 42

Vascular occlusion has a central role in the pathophysiology of sickle cell disease (SCD) and, although there is little evidence that thrombosis alone is responsible, patients with sickle cell disease are known to have an ill-defined but increased thrombotic risk. The most serious complication of this in childhood is stroke which occurs in 7-10% of children and a further 14% have asymptomatic cerebrovascular disease (CVD) on imaging. We have performed a comprehensive profile of coagulation inhibitors and markers of thrombin generation in 96 children (83 nontransfused [NTx] and 13 transfused [Tx]) with steady-state SCD and 18 healthy sibling controls. The levels of protein S (free and total) and heparin cofactor II were reduced in both the NTx and Tx groups compared to controls and protein C and APC resistance ratios were reduced in the NTx group only. Antithrombin levels were not different from controls. Thrombin-antithrombin complexes and prothrombin fragment F1+2 were increased in both patient groups. In the NTx subgroups with or without CVD there were no differences for any of the parameters measured except for lower haemoglobin levels and higher white cell counts in those with asymptomatic CVD. We conclude that children with SCD have a reduction in levels of the majority of the coagulation inhibitors and increased thrombin generation in the steady-state and these are only partially reversed by transfusion. However, these abnormalities do not appear to play a primary role in the development of cerebrovascular disease.
 ...
PMID:Prothrombotic changes in children with sickle cell disease: relationships to cerebrovascular disease and transfusion. 988 16

Diseases of the cardiovascular system such as coronary heart disease, hypertesion, peripheral occlusive arterial disease, and their final or lethal states (acute myocardial infarction, apoplectic stroke, congestive heart failure) occur 3 to 4 times more frequently than lung cancer in heavy smokers. Cigarette smoking impairs the courses of the microcirculation by an elevated viscosity of the blood or plasma, by a diminished deformability of the red blood cells, by elevated white cell counts, by activation of several blood clotting factors such as factor XIII and von Willebrand factor, by an elevated aggregability of the blood platelets, and by an increased uptake of fibrinogen into the endothelium of the blood vessels. After cessation of smoking these effects are widely normalized even though nicotine is still administered. Proposals for the cessation of smoking and for the use of nicotine replacement (patch, chewing gum, etc.) were offered because the inhaled tobacco smoke mainly damages health while the smokers are addicted only by nicotine. A less restrictive distribution of nicotine preparations for replacement therapy should enable the heavy smoker in his first phase of smoking cessation to combine the nicotine administration with reduced cigarette smoking. Each decrease in the carbon monoxide content of the expired air with subsequent decrease in the carboxyhemoglobin content of the blood possibly diminishes the risk of cardiovascular events. This way of treatment gives new opportunities for the treatment of the smoking patient for every physician.
 ...
PMID:[Smoking, cardiovascular diseases and possibilities for treating nicotine dependence]. 1019 69

The relationship between each of haemoglobin concentration (Hb), red cell count (RCC), white cell count (WBC), platelet count (PLT), mean corpuscular volume (MCV), red cell width difference (RWD), and average number of acute admissions per year (AVEADM), were determined in a cross-sectional study of 128 Afro-Caribbean sickle cell anaemia patients attending the Sickle Cell Disease Clinic of Central Middlesex Hospital in London for a mean of 7.6 patient-years. The diagnosis of sickle cell anaemia was made by both haematological and DNA analyses. The haematological parameters were determined using Coulter S automated counter during the steady state periods while the AVEADM was computed from all admissions for painful crisis, acute anaemia and acute chest syndrome, priapism, and acute stroke. Haemoglobin F level was determined by HPLC. Analysis was done in the paediatric and adult patients separately. There were no significant correlations between any of the parameters and AVEADM in the paediatric group. In adult patients, there was significant positive correlation (P < 0.05) between WBC and AVEADM. WBC has a negative correlation with Hb concentration and HbF level. WBC 10 x 10(9)/L and above is associated with Hb and HbF level below the mean for the group. WBC is lower but not significantly, in patients with single alpha-gene deletion than in those without deletion (P = 0.06). This study suggests that higher WBC count may suggest possible increased hospital admission, lower Hb concentration, and lower HbF level, in adult patients, and that, as a single parameter it can be of value in the assessment of patients with sickle cell anaemia. Possible mechanisms for these findings are also suggested.
 ...
PMID:The predictive value of white cell count in assessing clinical severity of sickle cell anaemia in Afro-Caribbeans patients. 1137 63

Flow cytometric studies suggest that platelets are activated in ischaemic stroke or transient ischaemic attack (TIA). However, few studies have measured circulating leucocyte-platelet complexes in this patient population. Whole blood flow cytometry was used to quantify the expression of CD62P-, CD63-, and PAC1-binding, and the percentages of leucocyte-platelet complexes in acute (1-27 d, n = 79) and convalescent (79-725 d, n = 70) ischaemic cerebrovascular disease (CVD) patients compared with controls without CVD (n = 27). We performed a full blood count, and measured plasma levels of soluble P-selectin, soluble E-selectin, and von Willebrand factor antigen (VWF:Ag) as additional markers of platelet and/or endothelial cell activation. The median percentage CD62P expression and the median percentage monocyte-platelet complexes were higher in both acute and convalescent CVD patients than controls (P </= 0.02). The mean white cell count and mean VWF:Ag levels were significantly elevated in the acute and convalescent phases after ischaemic stroke or TIA (P </= 0.02). Otherwise, there was no significant increase in any other marker of platelet or endothelial activation in CVD patients. There was a positive correlation between the percentage expression of CD62P and the percentages of both neutrophil-platelet and monocyte-platelet complexes in the acute phase, and the percentages of all leucocyte-platelet complexes in the convalescent phase after ischaemic CVD. This study provides evidence for ongoing excessive platelet and/or endothelial activation in ischaemic CVD patients despite treatment with antithrombotic therapy.
 ...
PMID:Platelet degranulation and monocyte-platelet complex formation are increased in the acute and convalescent phases after ischaemic stroke or transient ischaemic attack. 1518 Aug 68

There is current interest in the associations of circulating inflammatory markers (C-reactive protein, fibrinogen, white cell count, albumin, erythrocyte sedimentation rate, the factor VIII:von Willebrand factor complex, the tissue plasminogen activator:plasminogen activator inhibitor type 1 complex, fibrin D-dimer) not only with prognosis in acute coronary syndromes and acute stroke, but also in prediction of cardiovascular events in the general population. Recent meta-analyses of long-term prospective studies have established their associations with coronary heart disease (CHD) events, which may be cause, consequence or coincidence. These markers are also associated in epidemiologic studies of general populations with many cardiovascular risk factors (which may confound their associations with CHD risk), and also with asymptomatic arterial disease (of which they be consequences: 'reverse causality'). The causality of their associations with cardiovascular events is questioned by their lack of specificity for risk of cardiovascular events; and by the lack of association of their functional genotypes with CHD in 'Mendelian randomized trials'. Hence, proof of causality awaits testing in randomized-controlled trials of long-term selective reduction by future agents. Markers are of little additional predictive value to current cardiovascular risk scores, and it is premature to advocate their use in screening for cardiovascular risk prior to careful evaluation of costs, risks, and benefits.
 ...
PMID:Circulating inflammatory markers and risks of cardiovascular and non-cardiovascular disease. 1610 27

The Caerphilly Prospective Study demonstrates a paradoxical association of increased ischaemic stroke risk with decreased whole blood adenosine diphosphate (ADP) induced platelet sensitivity. A reanalysis of this association examines whether other haematological indices and prevalent disease at baseline may explain this finding. There were 1506 men free of clinical cardiovascular disease at baseline, with 85 men manifesting a first ischaemic stroke event over 8.3 years of follow-up in this population-based prospective cohort study. Using two different approaches, the paradoxical findings are confirmed and associations are slightly stronger after accounting for red cell, platelet, and white cell indices. A U-shaped relation of stroke with platelet count is noted. These findings are consistent with the existence of sub-clinical endothelial disease and compensatory mechanisms down-regulating ADP-induced aggregation sensitivity. They support an allostasis model of causality for understanding the paradox. A public health approach to prevention could have measurable impact if intervention strategies can be developed to alter early stages of disease appropriate to such mechanisms of causation.
 ...
PMID:Platelet aggregation in whole blood is a paradoxical predictor of ischaemic stroke: Caerphilly Prospective Study revisited. 1619 61

The risk of venous or arterial thrombosis is routinely assessed by clinical variables (risk factors) supplemented by measurement of blood lipids and glucose for arterial thrombotic events. Haematological tests that might play a role in risk prediction include haemostatic variables, haematocrit and inflammatory markers (erythrocyte sedimentation rate, plasma viscosity, white cell count). Recent epidemiological studies of these phenotypes and related genotypes are reviewed. For the risk prediction of first venous thrombosis, screening for thrombophilias in 'high-risk' situations does not appear clinically effective or cost-effective; with the possible exception of women considering oral hormone replacement therapy. General screening after a first venous event to predict recurrence (or risk in asymptomatic relatives) does not appear effective; with the possible exception of d-dimer, which requires further study. For risk prediction of first arterial thrombosis, screening adds little to prediction by current clinical risk scores. Screening of persons after a first arterial event, or with atrial fibrillation (e.g. with D-dimer for stroke prediction), requires further study. In conclusion, haematological tests have very limited roles in the prediction of cardiovascular risk, and should only be used according to evidence-based guidelines. The need for management studies is highlighted.
 ...
PMID:Can haematological tests predict cardiovascular risk? The 2005 Kettle Lecture. 1664 25

Although pyelonephritis is a common disease, it escapes clinical detection in an undesirably high proportion of patients. The present unsatisfactory diagnostic position would be much improved by widespread screening of patients by simple yet reasonably accurate methods. Bacterial counts by the pour-plate technique and estimates of the white cell excretion per hour or day, while undoubtedly of diagnostic value, are probably unsuitable for use on a wide scale. In an attempt to find more convenient procedures a simplified stroke-plate method of bacterial counting and a simplified quantitative white cell count method were devised and applied to over 1,000 mid-stream urine samples from 398 patients. Good correlation was obtained between the simpler stroke-plate method of bacterial counting and the more time-consuming pour-plate method. The quantitative white cell procedure was a much more sensitive index of pyuria than wet-film microscopy, and comparison with the bacterial count results showed that it gave a useful indication of urinary infection. It is suggested that a quantitative bacterial count should replace non-quantitative culture methods when urinary infection is suspected and that the quantitative white cell count should be performed as a routine part of the initial clinical and laboratory assessment of all patients, followed by a bacterial count if pyuria is revealed. Experience has shown that routine urine microscopy by a precise method leads to the detection of many cases of occult urinary infection.
 ...
PMID:Simplified quantitative methods for bacteriuria and pyuria. 1681 Sep 93

Melatonin is a highly effective treatment in different animal models of excitotoxicity or ischemia/reperfusion injury. Due to a lack of patentability, commercial sponsors are not interested in funding clinical evaluations of melatonin. Investigators may initiate small-scale clinical evaluation, and intravenous (i.v.) administration is appropriate in acute stroke patients. Institutional Review Boards may require proper preclinical evaluation of the preparation. In this pharmacokinetic and safety study, melatonin in propylene glycol was evaluated in adult male Sprague-Dawley rats. Following a single i.v. injection at 5 or 15 mg/kg, plasma concentrations of melatonin increased to 39 and 199 million pg/mL at 2 min and 128,000 and 772,000 pg/mL at 120 min. Within 60 min of injection, the blood pressure, heart rate and body temperature remained unaffected. Melatonin at 5 mg/kg did not influence the complete blood counts at 60 min, but melatonin at 15 mg/kg had some effects on the differential white cell and platelet counts. Melatonin at 5 or 15 mg/kg slightly elevated some liver enzymes at 60 min of injection, and melatonin at higher dose also elevated plasma creatinine and lactate dehydrogenase levels. At 24 hr after completion of six daily injections of melatonin, there was a 5.5% reduction in body weight. Gross postmortem examination and histological examination of the brain, kidney, liver and spleen did not reveal any evidence of toxicity. In conclusion, melatonin in propylene glycol markedly elevates plasma levels of melatonin with no serious toxicity. This preparation should be further evaluated in human patients.
 ...
PMID:Preclinical evaluation of pharmacokinetics and safety of melatonin in propylene glycol for intravenous administration. 1701 90


<< Previous 1 2 3 Next >>