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Biomedical subjects

M Kaste

Publications and source records attributed to M Kaste.

At least 55 records · Page 3Linked to original sources
PubMed2000

Plasminogen activator inhibitor-1 in patients with ischemic stroke.

Low fibrinolytic activity may increase the risk of thrombosis. Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of the fibrinolytic system. We examined the PAI-1 levels in patients with ischemic stroke. Plasma levels of PAI-1 were measured using enzyme-linked immunosorbent assay (ELISA) in 55 consecutive patients (age 60.2 +/- 11.4, 40 males and 15 females) with ischemic stroke. The PAI-1 assessments as well as neurological examinations using validated stroke scales were conducted at admission and 1 week, 1 month, and 3 months after stroke. Sex- and age-matched controls (+/- 4 years) underwent plasma PAI-1 measurement once. Etiology of the stroke was classified using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. All pertinent stroke risk factors were recorded. All patients were contacted 3 years after stroke for recurrent vascular thrombotic disease. The plasma PAI-1 levels were 17.2 +/- 7.8 IU at admission, 11.2 +/- 9.2 IU at 1 week, 14.4 +/- 7.9 IU at 1 month, and 17.8 +/- 7.8 IU at 3 months among patients and 11.8 +/- 9.5 IU among controls (p values are < .002, .7, .12, and < .0005, respectively). As a rule, the neurological scores did not show a correlation to the PAI-1 levels. Presence of diabetes, hypertension, obesity, smoking, anticoagulant treatment, and sleep apnea did not affect the PAI-1 levels at any time point. Females had slightly higher PAI-1 levels. Age was a strong determinant for PAI-1 levels being higher in younger patients at every sampling time point (p values .02, .02, .02, and .03 respectively). The etiology of the ischemic stroke did not have an impact on PAI-1 levels. In 16 patients recurrent thrombosis had occurred. The high PAI-1 levels at admittance may reflect either an acute phase response or a chronic state. Normalized levels at 1 week and 1 month may be due to hospital diet, antithrombotic medication, weight loss, active physical therapy, and better care for diabetes. PAI-1 levels at 3 months after stroke did not predict recurrent thrombosis.

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PubMed2000

The future of stroke treatment.

The concept of the therapeutic window of opportunity in ischemic neuronal injury and understanding the necessity of well organized stroke services revolutionized the management of acute ischemic stroke during the last years of the second millennium. Thrombolysis with IV rt-PA within 3 hours from the onset of symptoms is an established therapy for selected patients. The challenge of stroke therapy at the outset of this millennium is how to translate basic pathophysiologic evidence of ischemic neuronal injury into novel neuroprotective therapies either independently or combined with thrombolysis. Great hopes are placed in identification of pivotal molecular events in ischemic brain tissue and design of effective pharmacological interventions to target them. Aggressive, invasive procedures are also being developed and therapies such as intra-arterial clot lysis, hemicraniectomy and mild hypothermia may improve the bleakest outcomes associated with the most severe forms of ischemic stroke, but their role must be rigorously evaluated. There is, however, no need to wait for future breakthroughs. The existing evidence strongly implies that good care of patients with stroke starts with organization of the entire stroke chain; from the prehospital scene, through the emergency room, to the stroke unit. Without structured stroke services no pharmacological or intervening therapy is likely to improve the outcome of the patient with a stroke.

Animals↗
PubMed2000

European Stroke Initiative (EUSI) recommendations for stroke management. The European Stroke Initiative Writing Committee.

The European Stroke Initiative (EUSI) is the common body of stroke-related activities within the European Federation of Neurological Societies (EFNS), the European Neurological Society (ENS) and the European Stroke Council (ESC). The Executive committee of the EUSI has authorized the writing committee of the EUSI to create recommendations for stroke management covering all areas of stroke treatment. The recommendations are listed according to levels of evidence pre-specified and modified according to several proposals in the literature. The recommendations have been approved by the executive committees of the EUSI, the ESC, the EFNS and the ENS. They are called recommendations rather than guidelines in order to underline the large amount of individual decision making due to the fact that for many important questions, no data of high evidence level is available. The EUSI plans to review and update the recommendations on a regular basis.

Anticoagulants↗
PubMed2000

Lubeluzole in acute ischemic stroke treatment: A double-blind study with an 8-hour inclusion window comparing a 10-mg daily dose of lubeluzole with placebo.

BACKGROUND AND PURPOSE: This trial was a double-blind, placebo-controlled, phase III trial with an 8-hour inclusion window to assess the efficacy and safety of an intravenous loading dose of 7.5 mg followed by a daily intravenous dose of 10 mg lubeluzole for 5 days in acute ischemic stroke patients. METHODS: A total of 1786 patients were randomized: 901 to lubeluzole and 885 to placebo. Overall, 212 patients (23.5%) from the lubeluzole group and 213 (24.1%) from the placebo group discontinued the trial prematurely. In the lubeluzole group 201 patients (22.3%) discontinued because of adverse events compared with 193 patients (21.8%) in the placebo group. RESULTS: The primary population for the efficacy analysis comprised the core stroke patients (exclusion of older patients aged >75 years with severe stroke) in the 0- to 6-hour inclusion time window. The primary efficacy parameter was a 3-category functional status (Barthel Index 70 to 100/0 to 70/vegetative, dead) at week 12. In the lubeluzole group 207 patients (47.8%) were classified as mildly dependent/independent at week 12, 131 (30.3%) were moderately/severely dependent, and 95 (21.9%) were vegetative/dead. In the placebo group these numbers were 221 (54.4%), 112 (27.6%), and 73 (18.0%), respectively. Logistic regression analysis showed no statistically significant difference between the treatment groups (P:=0.162). Additionally, for none of the secondary efficacy parameters (mortality at week 12, modified Rankin score, total Barthel score) was a statistically significant difference between the lubeluzole and placebo groups obtained. There were no statistically significant differences between the 2 treatments for all treated patients, patients included within the 6- to 8-hour window, and patients with severe strokes aged >75 years. Overall, of all treated patients, 401 (22.5%) died: 203 (22.5%) in the lubeluzole group and 198 (22.4%) with placebo. Of all subjects treated, 853 (95%) on lubeluzole and 826 (93%) on placebo reported an adverse event during their treatment period or within the next 2 days after discontinuation of treatment. The most frequently observed adverse events were fever (25.9% lubeluzole; 23.4% placebo), constipation (20.2%; 19.7%), and headache (17.6%; 21.2%). Imbalances were found for atrial fibrillation (1.8% lubeluzole; 1.1% placebo) and QT prolongation (0.9%; 0.2%). CONCLUSIONS: This study failed to show an efficacy of lubeluzole in the treatment of acute stroke. On the other hand, lubeluzole treatment by the current dosage schedule was not associated with a significant safety problem.

Acute Disease↗
PubMed2000

Comparison of different clinical criteria (DSM-III, ADDTC, ICD-10, NINDS-AIREN, DSM-IV) for the diagnosis of vascular dementia. National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences.

BACKGROUND AND PURPOSE: The criteria for vascular dementia (VaD) include definition of the cognitive syndrome and the vascular cause. Different criteria for dementia identify different frequencies and clusters of patients. In addition, variation in defining the cause and etiology may have an effect. We compared different clinical criteria for VaD in series of patients with poststroke dementia. METHODS: The study group comprised 107 patients fulfilling the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) definition for dementia from a cohort of consecutive patients with ischemic stroke who completed a comprehensive neuropsychological test battery and MRI. The mean age (SD) of the patients was 71.4 (7.6) years. The definitions of vascular cause of VaD were those of the DSM-III (1980), Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC; 1992), International Statistical Classification of Diseases, 10th Revision (ICD-10; 1992), National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN; 1993), and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; 1994). RESULTS: The number of cases that could be classified as VaD according to the different criteria varied considerably: 36.4% (n=39) by DSM-III, 86.9% (n=93) by ADDTC, 32.7% (n=35) by NINDS-AIREN, 36.4% (n=39) by ICD-10, and 91.6% (n=98) by DSM-IV criteria. The concordance between DSM-III/ICD-10 was perfect (100%; kappa=1.0), between ICD-10/NINDS-AIREN and ADDTC/DSM-IV good to moderate (85.0% and 87. 3%; kappa=0.87 and 0.37, respectively), but otherwise poor between the other criteria. Only 31 patients fulfilled all the criteria for VaD applied. Major discriminating factors between the criteria were requirement of (1) focal neurological signs, (2) unequal distribution of deficits in higher cortical functions, and (3) evidence of relevant CVD based on brain imaging findings. CONCLUSIONS: Current criteria of VaD identify different frequencies and clusters of patients and are not interchangeable. Optimally, prospective studies with clinicopathological correlation could identify new criteria. Meanwhile, focus on more homogeneous subtypes (eg, small-vessel subcortical VaD) and detailed neuroimaging criteria could improve the diagnostics.

Aged↗
PubMed2000

Decreased severity of brain infarct can in part explain the decreasing case fatality rate of stroke.

BACKGROUND AND PURPOSE: Case fatality rates for stroke has declined in most Western industrialized countries during recent decades. One possible explanation for this is a decrease in the severity of stroke symptoms. We therefore sought evidence for a change in stroke severity and its relationship with case fatality rates. METHODS: We compared the severity of symptoms among first-ever stroke patients in 2 population-based prospective stroke registers maintained during 1972 to 1973 and 1989 to 1991 in Finland. Patients who were evaluated by study assistants or the investigator during the first week after the onset of symptoms were included in the study, and their severity of symptoms was assessed with the use of comparable scales modified from the Scandinavian Stroke Scale. RESULTS: A total of 244 and 594 patients were registered, and a portion of them (155 [63.5%] and 360 [60.6%]) were included in the analyses in the registers for Espoo-Kauniainen from 1972 to 1973 and for 4 separate districts in Finland from 1989 to 1991, respectively. The death rates during the first week among those who were not included did not differ between the registers. The severity of symptoms decreased significantly between the registers in both patients with brain infarct or intracerebral hemorrhage but not in those with subarachnoid hemorrhage. The severity of symptoms was an independent factor of case fatality at 1 month. CONCLUSIONS: The severity of symptoms of brain infarcts has decreased and can in part explain the decreased case fatality rate of stroke in Finland. However, the change in patients with intracerebral hemorrhage may be overestimated due to undiagnosed intracerebral hemorrhages in the first register resulting from the lack of brain CT.

Aged↗
PubMed2000

MRI pontine hyperintensity after supratentorial ischemic stroke relates to poor clinical outcome.

BACKGROUND AND PURPOSE: MRI studies in patients with atherosclerosis often reveal ill-defined hyperintensity in the pons on T2-weighted images. This pontine hyperintensity (PHI) does not fulfill the criteria of a brain infarct, and its clinical relevance is not established. We examined the frequency, as well as the radiological and clinical correlates, of PHI in poststroke patients. METHODS: Three hundred nineteen patients were studied 3 months after supratentorial ischemic stroke with the use of 1.0-T MRI. Brain infarcts, atrophy, white matter hyperintensities, and PHI were registered. The clinical outcome was assessed 3 and 15 months after the stroke. RESULTS: Of the patients, 152 (47.6%) had PHI. The risk factors for stroke did not differ in patients without or with PHI. PHI was related to a higher frequency (P=0.002) and larger volume (P<0.001) of supratentorial brain infarcts, to parietal (P=0.020) and temporal (P=0.002) atrophy, to central atrophy (P< or =0.040), and to white matter hyperintensity grade (P<0.001). Brain infarcts that affected the corpus striatum (putamen, caudate, and pallidum) (P< or =0. 011) or pyramidal tract (P<0.001) were more frequent in patients with PHI. The 3- and 15-month outcomes were worse in patients with PHI (P< or =0.004). The total volume of brain infarcts (OR 1.22), mean atrophy (OR 3.59), and PHI (OR 3.76) were independent correlates of a poor 15-month outcome. CONCLUSIONS: PHI after supratentorial ischemic stroke deserves attention because it relates to poor clinical outcome.

Activities of Daily Living↗
PubMed2000

Plasma endothelin-1 levels neither increase nor correlate with neurological scores, stroke risk factors, or outcome in patients with ischemic stroke.

BACKGROUND AND PURPOSE: Endothelins (ETs) are potent vasoconstrictors and may play a role in the pathophysiology of several diseases. Limited and controversial data exist on their role in human ischemic stroke. We planned a prospective, observational, and longitudinal clinical study to test whether ET-1 levels increase in various phases of ischemic stroke and whether the ET-1 levels correlate with neurological scores, stroke etiology, stroke risk factors, or final outcome. METHODS: We measured plasma ET-1 levels with a sandwich-enzyme immunoassay method in 101 consecutive patients with ischemic stroke on admission and 1 week, 1 month, and 3 months after stroke and in 101 sex- and age-matched control subjects. At each sampling, the patients underwent a complete neurological evaluation. All stroke risk factors were recorded, an array of laboratory tests were performed, and the subtype of ischemic stroke was determined. The patients were contacted 3 years later for prognostic determination. RESULTS: ET-1 levels in patients (2.4+/-1.3 pg/mL on admission, 2.2+/-1.4 pg/mL at 1 week, 2.1+/-1.4 pg/mL at 1 month, and 2.1+/-1.2 pg/mL at 3 months) were not different from those of the control subjects (2.2+/-0.9 pg/mL) at any time point. No correlation was found between the ET-1 levels and stroke etiology, stroke risk factors, stroke recurrence risk, age, sex, or neurological scores, except that ET-1 levels correlated with the use of warfarin and with body mass index. CONCLUSIONS: Plasma ET-1 levels were normal in patients with ischemic stroke. Our findings cannot exclude a role of ETs in the pathophysiology of ischemic stroke because plasma levels might not accurately reflect intracerebral concentrations, but they also do not support the occurrence of a major plasma ET-1 level increase at any phase of stroke. Our patient population is the largest ever reported in whom ET-1 levels were measured, but it consisted of mild and moderately ill patients with stroke due to the study design, of which the aim was long-term observation, which excludes severely ill patients.

Adult↗
PubMed2000

The effect of acute ingestion of a large dose of alcohol on the hemostatic system and its circadian variation.

BACKGROUND AND PURPOSE: Heavy binge drinking may trigger the onset of embolic stroke and acute myocardial infarction, but the underlying mechanisms are unclear. The effects of binge drinking on the hemostatic system and its circadian variation have not been investigated. We investigated the effects of an acute intake of a large dose of alcohol (1.5 g/kg). METHODS: Twelve healthy, nonsmoking men participated in sessions where they were served ethanol in fruit juice or served fruit juice alone and, lying in a supine position, were followed up for 12 to 24 hours. The treatments were randomized and separated from each other by a 1-week washout period. Blood and urine were collected for hemostatic measurements. RESULTS: The urinary excretion of the platelet thromboxane A(2) metabolite 2, 3-dinor-thromboxane B(2) was significantly (P<0.05) greater during the night after an evening intake of alcohol than during the control night. A smaller increase was observed during the daytime after an intake of alcohol in the morning. The effects on the endothelial prostacyclin metabolite 2,3-dinor-6-ketoprostaglandin F(1alpha) excretion were negligible. A 7-fold increase in plasminogen activator inhibitor 1 activity was observed after both morning (P<0. 05) and evening (P<0.01) intakes of alcohol. CONCLUSIONS: This is the first study to suggest that acute ingestion of a relatively large but tolerable dose of alcohol transiently enhances thromboxane-mediated platelet activation. The observations also demonstrate alcohol-induced changes in the normal circadian periodicity of the hemostatic system in subjects not accustomed to consumption of alcohol.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Anti-ICAM-1 monoclonal antibody R6.5 (Enlimomab) promotes activation of neutrophils in whole blood.

R6.5 (BIRR-1, Enlimomab), a murine IgG2a mAb to the human ICAM-1, inhibits leukocyte adhesion to the vascular endothelium, thereby decreasing leukocyte extravasation and inflammatory tissue injury. In initial clinical trials, R6.5 proved to be beneficial in reducing both disease activity in refractory rheumatoid arthritis and the incidence of acute rejection after kidney and liver allograft transplantations. However, adverse effects such as fever, leukopenia, or cutaneous reactions were not infrequent. We studied the effects of R6.5 on neutrophil function in whole blood samples ex vivo. Surprisingly, at the concentrations achieved in clinical trials, R6. 5 activated neutrophilic granulocytes, as indicated by a significant increase in expression of the adhesion molecule beta2-integrin CD11b, a concurrent decrease in L-selectin expression, and an enhancement of the oxidative burst activity. Neutrophil activation was not exerted by an anti-ICAM-1 mAb of the IgG1 isotype, by isotype-matched, irrelevant anti-2-phenyloxazolone mAb, or by F(ab')2 fragments of R6.5. Neutrophil activation was completely inhibited by soluble complement receptor type 1. We conclude that in whole blood, R6.5 activates resting neutrophils in a complement-dependent manner. This finding can explain, at least in part, the side effects associated with R6.5 therapy.

Animals↗
PubMed1999

Post-stroke depression and functional recovery in a population-based stroke register. The Finnstroke study.

Post-stroke depression and functional outcome were examined in a population-based stroke register active in four different districts (total population, 134 804) in Finland. Five hundred and ninety four first time strokes were registered. Beck's depression inventory (BDI), with ten as the cutoff point for depression, was applied to 321 of 423 survivors after three months and to 311 of 390 survivors after 12 months. Functional outcome was measured with the Barthel Index (BI) and the Rankin Scale (RS). One hundred and fifty one of 321 (47.0%) and 147 of 311 (47.3%) patients were depressed after three and 12 months, respectively. Depression at three months was associated with poor functional outcome at the one-year follow-up (P = 0.001 for the BI and the RS). On the other hand, poor functional outcome at three months was associated with depression after one year (P = 0.004 and 0.002 for the BI and the RS, respectively). Patients who were depressed at three months were more often in institutional care between three and 12 months later than non-depressed patients (P = 0.005). Post-stroke depression is associated with poor functional recovery of patients. If depression were diagnosed and treated early, it might help patients to recover more completely and/or faster, which could save community healthcare resources by avoiding or shortening the time of institutional care or reducing the need for home care.

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