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

The use of first generation plasminogen activators, urokinase, streptokinase and tissue plasminogen activator has revolutionized thrombolytic therapy for myocardial infarction and ischaemia, and potentially stroke. However, thrombolytic therapy employing these activators is limited by reocclusion of the very arteries being opened, which follows in a small but significant number of patients. The development of second generation plasminogen activators, e.g. staphylokinase and anisoylated plasminogen streptokinase activator complex, has not alleviated the problems encountered with classical plasminogen activators. It is now widely recognized that aberrant platelet aggregation induced primarily by thrombin, rather than plasmin, is one of the major causes of recurrent thrombosis following pharmacologic thrombolysis. Agents that (a) inhibit enzymatic and/or coagulant activity of thrombin, (b) block binding of thrombin to its receptor, and (c) interfere with the generation of thrombin by the prothrombinase complex may compromise haemostasis resulting in haemorrhage. We recently demonstrated that thrombin-induced platelet aggregation is accompanied by cleavage of aggregin, a putative ADP-receptor on the platelet surface, and that these events are indirectly mediated by intracellularly activated calpain expressed on the surface. In this review, we discuss the known mechanisms of thrombin-induced platelet aggregation and suggest relative advantages of potential pharmacological agents, being developed in our laboratory, over those that have been previously developed and tested. These inhibitors selectively prevent aggregation of platelets induced by thrombin by inhibiting calpain expressed on the surface. Moreover, one of these inhibitors which blocks thrombin-induced platelet aggregation does not interfere with other platelet responses mediated by thrombin or platelet aggregation induced by other agonists, such as, ADP, collagen, phorbol myristate acetate and thromboxane A2 mimetics. This selectivity could reduce the chances of perturbing the formation of a haemostatic plug.
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PMID:Reocclusion after thrombolytic therapy: strategies for inhibiting thrombin-induced platelet aggregation. 832 74

This report describes an unusual case of secondary nocturnal enuresis presumptively secondary to progressive bradycardia from complete heart block. Congenital complete heart block occurs in approximately 1 of 22,000 livebirths and is typically associated with structural congenital heart disease or maternal collagen vascular diseases. It can be entirely asymptomatic during infancy and childhood, depending in part on the escape rate and rhythm and other hemodynamic variables. The case described above was not diagnosed until the patient coincidentally underwent cardiac monitoring. The picture was confusing initially, as a tricyclic antidepressant medication had been ingested. Heart block is one of the known cardiovascular effects of tricyclic antidepressant overdose. However, the conduction disturbance should have resolved as the drug was excreted from the body. As children with congenital complete heart block get older, the ventricular escape rate typically decreases. In addition, as activity increases with age, more demand is placed for cardiac output. The resting end-diastolic volume is increased to elevate stroke volume in compensation for lower heart rate. As the escape rate decreases and the metabolic demand increases, patients with congenital complete heart block then may begin to develop symptoms. Typical symptoms in children include dizziness, Stokes-Adams syncopal attacks, fatigue, daytime somnolence, and other somatic complaints. Bedwetting has not been reported as an initial symptom, but in this case is likely secondary to the excessive somnolence and difficulty with arousal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nocturnal enuresis secondary to heart block: report of cure by cardiac pacemaker implantation. 833 31

Platelet aggregation was examined in 43 patients after ischemic stroke and in 16 healthy subjects using multiparametric aggregation index (MAI). The value of MAI was significantly higher in stroke patients (3.15 in patients and 0.92 l/mumol in controls, p < 0.0001). Patients who had increased MAI (n = 26) were treated with a daily dose of 100 mg acetilsalicylic acid (ASA). Platelet activity was measured before and on the 7th and 28th day of treatment measuring three parameters: MAI, spontaneous dysaggregation and collagen induced aggregation. All 3 methods showed a significant decrease in platelet aggregation on the 7th day of treatment, but further changes were not found on the 28th day. Serum levels of thromboxane-A2 (TXA2) and prostacycline (PGI2) metabolites (TXB2 and 6-keto-prostaglandin-F1 alpha) were determined before and on the 28th day of treatment. The effect of 100 mg ASA per day proved to be selective: comparing the serum levels before and after treatment, a significant decrease of TXB2 concentration was found without changes in the concentration of 6-keto-prostaglandin-F1 alpha. Evaluating MAI and the value of dysaggregation might reflect ineffectiveness of antiplatelet therapy in patients not responding to a daily dose of 100 mg of ASA. For these patients the increase of the daily dose of ASA, or changing to another antiplatelet drug might be recommended.
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PMID:[Low doses of acetylsalicylic acid effectively inhibits thrombocyte aggregation after ischemic stroke]. 871 38

1. This study was undertaken to determine whether the AT1 receptor directly contributes to hypertension-induced cardiac hypertrophy and gene expressions. 2. Stroke-prone spontaneously hypertensive rats (SHRSP) were given orally an AT1, receptor antagonist (losartan, 30 mg kg-1 day-1), an angiotensin converting enzyme inhibitor (enalapril 10 mg kg-1 day-1), a dihydropyridine calcium channel antagonist (amlodipine, 5 mg kg-1 day-1), or vehicle (control), for 8 weeks (from 16 to 24 weeks of age). The effects of each drug were compared on ventricular weight and mRNA levels for myocardial phenotype- and fibrosis-related genes. 3. Left ventricular hypertrophy of SHRSP was accompanied by the increase in mRNA levels for two foetal phenotypes of contractile proteins (skeletal alpha-actin and beta-myosin heavy chain (beta-MHC)), atrial natriuretic polypeptide (ANP), transforming growth factor-beta-1 (TGF-beta 1) and collagen, and a decrease in mRNA levels for an adult phenotype of contractile protein (alpha-MHC). Thus, the left ventricle of SHRSP was characterized by myocardial transition from an adult to a foetal phenotype and interstitial fibrosis at the molecular level. 4. Although losartan, enalapril and amlodipine lowered blood pressure of SHRSP to a comparable degree throughout the treatment, losartan caused regression of left ventricular hypertrophy of SHRSP to a greater extent than amlodipine (P < 0.01). 5. Losartan significantly decreased mRNA levels for skeletal alpha-actin, ANP, TGF-beta 1 and collagen types I, III and IV and increased alpha-MHC mRNA in the left ventricle of SHRSP. Amlodipine did not alter left ventricular ANP, alpha-MHC and collagen types I and IV mRNA levels of SHRSP. 6. The effects of enalapril on left ventricular hypertrophy and gene expressions of SHRSP were similar to those of losartan, except for the lack of inhibition of collagen type I expression by enalapril. 7. Unlike the hypertrophied left ventricle, there was no significant difference between losartan and amlodipine in the effects on non-hypertrophied right ventricular gene expressions of SHRSP. 8. Our results show that hypertension causes not only left ventricular hypertrophy but also molecular transition of myocardium to a foetal phenotype and interstitial fibrosis-related molecular changes. These hypertension-induced left ventricular molecular changes may be at least in part mediated by the direct action of local angiotensin II via the AT1, receptor.
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PMID:Effects of an AT1 receptor antagonist, an ACE inhibitor and a calcium channel antagonist on cardiac gene expressions in hypertensive rats. 876 77

Cerebral infarction before the age of 45 years accounts for 4-6% of all strokes. The etiology remains unexplained in a significant proportion of patients even after extensive investigations. The reported risk factors of this age group are cardiopathies, hypertension, smoking, hypercholesterolemia, reduction of anticoagulant proteins, hypercoagulable states, antiphospholipid antibodies primary syndrome, antiphospholipid antibodies secondary syndrome, some hemoglobinopathies, hyperviscosity syndromes, vasculitis, collagen vascular diseases, fibromuscular dysplasia, arterial dissections, migraine, myopathy encephalopathy lactic acidosis stroke like episodes, homocystinuria, familial amyloid angiopathy, microangiopathy with retinopathy encephalopathy and deafness, systemic lupus erythematosus, use of cocaine, traumas or manipulations of neck, AIDS. From 1/1/94 to 04/30/95 we observed 19 patients with cerebral infarctions and 9 patients with transitory ischemic attacks in young people. The aim of our study was to apply a diagnostic protocol by sequential tests of first level and second level. According to this protocol we found that the more common risk factors were ischemic cardiopathy, hypertension, smoking and hypercholesterolemia. Moreover we observed other independent risk factors, although less frequent, like the antiphospholipid antibodies, neurolupus, AIDS, deficit of protein S.
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PMID:[The application of a new diagnostic protocol for stroke in the young]. 876 46

The authors present a plan for pharmacological treatment of pressure sores in patients affected by neurological pathologies: cerebrovascular accidents, head injuries, spinal cord injuries. This plan is easily applicable to all pressure sores included between first and third degree of the Reuler and Cooney classification. Authors identified some drugs specifically usefull in different cutaneous lesion degrees. Skin lesions and employed medicines are described as follows: Erythema: semi occlusive bandage with porous adsorbing membrane. This dressing must be left in for five days at least. Excoriation: bactericidal or bacteriostatic medicines if it's situated in a non pressed area while the same dressing utilized for erythema if it's localized in a pressed area. Pressure sores: if there is local infection cleanse the wound from bacterial defilement using topic antibiotics apply compresses with vitamin C if the cutaneous lesion is larger than deeper, Cadexomero lodico if it's deeper than larger. Fistulas: wadding with tablets of collagen. Necrobiosis: complete or partial surgical removal of eschar preceded by the use of enzymatic drugs when eschar is firmly adherent to subcutaneous tissues. The first group collects 9 patients with stroke and head injury: 8 with sacral and 1 with heel pressure sores. First degree pressure sores heal within 45 days and third degree lesions within 160 days. The second group collects 10 spinal cord injury patients mostly with complete lesion among which: 7 sacral, 1 heel, 1 ischiatic and 1 malleolar lesions. First degree pressure sores heal within 30 days, third degree pressure sores heal within 200 days. Healing time are considered acceptable. Pressure sores recovery swiftness can be related to different factors such as pressure sores sterness, neurological pathology and arising of clinical complication (hyperthermia, infections, low serum albumin values, etc).
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PMID:[The treatment of decubitus lesions]. 876 88

Defibrotide, a polydeoxyribonucleotide, has been found to modulate endothelial cell function, causing an increase in tissue plasminogen activator (t-PA) levels, a decrease in plasminogen activator inhibitor (PAI) levels, and an increase in prostaglandin I2 (PGI2) formation in humans. Defibrotide has no direct anticoagulant effect but has a synergistic action with heparin. A strong antithrombotic effect has been observed in animal models. Thus, defibrotide has a beneficial effect in cases of deep venous thrombosis (DVT), peripheral obliterative vascular disorder (POVD), stroke, vasculitis, and thromboembolism. Defibrotide also inhibits platelet function and activation. A significant decrease in platelet aggregate formation on the suture line in microarterial anastomosis in rats is one way defibrotide can inhibit platelet function and activation. In humans, a slight prolongation' of the lag period in collagen-induced aggregation has been observed. In addition, a slight decrease in the maximum amplitude of the secondary wave of ADP and adrenalin-induced aggregations was also found. Platelet adhesion is diminished, the platelet differential count on formvar membrane is altered, and platelet aggregate formation is significantly inhibited. With an increase in platelet cyclic AMP (cAMP) content and a decrease in malonyl dialdehyde (MDA) and thromboxane B2 (TXB2) formation, the levels of platelet secretion products such as PF-4 and beta-thromboglobulin (beta-TG) in plasma decreased progressively. It was also demonstrated that the 14C-glucose transport defect of the platelet membrane of atherosclerotic patients was partially corrected with defibrotide treatment.
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PMID:Effect of defibrotide on platelet function. 880 24

Recent epidemiologic studies have consistently shown that moderate intake of alcoholic beverages protect against morbidity and mortality from coronary heart disease and ischemic stroke. By contrast, alcohol drinking may also predispose to cerebral hemorrhage. These observations suggest an effect of alcohol similar to that of aspirin. Several studies in humans and animals have shown that the immediate effect of alcohol, either added in vitro to platelets or 10 to 20 min after ingestion, is to decrease platelet aggregation in response to most agonists (thrombin, ADP, epinephrine, collagen). Several hours later, as, in free-living populations deprived of drinking since the previous day it is mostly secondary aggregation to ADP and epinephrine and aggregation to collagen that are still inhibited in alcohol drinkers. By contrast, in binge drinkers or in alcoholics after alcohol withdrawal, response to aggregation, especially that induced by thrombin, is markedly increased. This rebound phenomenon, easily reproduced in rats, may explain ischemic strokes or sudden death known to occur after episodes of drunkenness. The platelet rebound effect of alcohol drinking was not observed with moderate red wine consumption in man. The protection afforded by wine has been recently duplicated in rats by grape tannins added to alcohol. This protection was associated with a decrease in the level of conjugated dienes, the first step in lipid peroxidation. In other words, wine drinking does not seem to be associated with the increased peroxidation usually observed with spirit drinking. Although further studies are required, the platelet rebound effect of alcohol drinking could be associated with an excess of lipid peroxides known to increase platelet reactivity, especially to thrombin.
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PMID:Effects of alcohol on platelet functions. 881 72

Three types of dysfunction of the coronary circulation have been described in experimental models of hypertension associated with left ventricular hypertrophy: (1) reduced coronary reserve, (2) a relative decrease in perfusion of subendocardial layers, (3) a shift to the right, i.e. to higher pressures, of the circulation pressure autoregulation range. These abnormalities are also observed in hypertensive patients, although it is significant that they do not appear to be related to the extent of left ventricular hypertrophy. The exact causes of these abnormalities have yet to be elucidated. Left ventricular hypertrophy does not seem to be an essential factor, although in certain experimental models of hypertension, there does appear to be a mismatch between the development of the coronary vasculature and hypertrophy of the myocytes. The stresses in vessels due to the increase in systolic, and especially intraventricular diastolic pressure can be viewed as additional aggravating factors. The essential abnormalities are structural and/or functional alterations in arterial walls. The structural alterations are reflected by a narrowed lumen due to parietal thickening. This may result from growth of muscle fibres (hypertrophy or hyperplasia) or collagen tissue and/or remodelling of tissues with no overall change in mass. Functionally, the reduced ability of the arteries to stretch, resulting from endothelial alterations may also play a role in the abnormalities observed in hypertensive patients. In our studies, we examined the effect of the antihypertensive drug perindopril on the coronary circulation in renovascular hypertensive rat (two kidneys--1 clip). We found that this inhibitor of angiotensin converting enzyme (ACE) led to a regression of left ventricular hypertrophy with a return to normal of the coronary reserve. Other studies using either this model or the spontaneously hypertensive rate has also pointed to a beneficial action of ACE inhibitors and other antihypertensive agents on the coronary circulation with reversal of the structural alterations in arterioles. Coronary disease is the main cause of mortality in hypertensive patients. Ironically, antihypertensive therapy has yet to live up to its promise of reducing significantly either the incidence or severity of coronary disease in such patients. Specific alterations of the coronary circulation may account for the relative failure of antihypertensive drugs, despite their proven efficacy in other systems (e.g., stroke prevention). The coronary circulation is unique in certain important respects. It is tightly regulated, maintaining an almost constant flow rate over a wide range of aortic arterial pressures (40-160 mmHg). Extraction of oxygen by the myocardium is almost maximal under resting conditions, and so the circulatory reserve depends almost entirely on the capacity to increase blood flow. This reserve is quite large since there may be a 4 to 5-fold increase in coronary flow rate in response to effort. Another significant detail is that myocardial contraction may lead to an interruption of coronary flow, especially in the deep subendocardial layers, which thus tend to be perfused solely during diastole. This last factor can be seen as the Achilles heel of the coronary circulation, which may be severely limited by myocardial hypertrophy, especially in patients with hypertension.
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PMID:Coronary reserve in experimental myocardial hypertrophy. 882 53

We report on two Italian families with an early-adult onset autosomal dominant disorder, characterized by leukoencephalopathy, migraine, psychiatric disturbances, stroke and dementia. These findings fulfill the diagnostic criteria for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) syndrome. Moreover, to confirm the CADASIL gene location to 19p12, we performed a linkage analysis with four microsatellite markers. The results of the genetic study gave positive but not significant lod scores, indicating only weak evidence of a linkage with 19p12. In one autopsy case, we found extensive ischemic changes due to the selective involvement of the small muscular arteries of the cerebral white matter. The lesions consisted of a thickening of the media with deposition of granular eosinophilic material. Ultrastructural examination of the arterial walls showed graded damage to smooth muscle cells, mostly of the longitudinal layer, and an abnormal proliferation of basal lamina components. Immunocytochemical analysis showed strong reactivity using antibodies to collagen IV and smooth myosin proteins. The results suggest a primary involvement of the smooth muscle cells of small cerebral arteries, with a secondary alteration of basal lamina components and elastic tissue.
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PMID:Clinicopathological and genetic studies of two further Italian families with cerebral autosomal dominant arteriopathy. 884 56


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