European Stroke Prevention Study 2: Baseline data.
Explore the source record for details and available documents.
Cerebrovascular Disorders↗
Biomedical subjects
A Lowenthal
Publications and source records attributed to A Lowenthal.
Defective measles virus in human subacute sclerosing panencephalitis brain.
Evidence is presented showing that the brain cells of patients with subacute sclerosing panencephalitis (SSPE) contain mutant measles (MV) genomes having the characteristics of 5' copy-back defective interfering (DI) RNAs. Using a polymerase chain reaction-based amplification specific for copy-back DIs, abundant, discrete cDNAs representing different-sized MV defective RNA species were generated from each SSPE brain. The defective genomes were cloned in two portions. The most common of these defective species were sequenced, confirming their MV genome origin and 5' copy-back nature. We deduced that the minimum DI stem length of these species was 95 nucleotides, further delimiting the prerequisite 5' regulatory region sequences specifying MV genomic replication/encapsidation functions. This calculation assumes a precise copy-back mechanism and complete complementarity of the panhandle structure. Since the SSPE-derived viral genome encodes dysfunctional viral envelope proteins, we hypothesize that SSPE brains may lack the high degree of selective pressure encountered in tissue culture MV infections. This allows for the coexistence of numerous replication-competent defective particles in each SSPE brain. A role for viral defective particles as modulators of this persistent measles virus infection of humans is proposed.
Base Sequence↗
The value of studying the cerebrospinal fluid in slow viral and related diseases.
Explore the source record for details and available documents.
Animals↗
Cerebrospinal fluid in multiple sclerosis.
The diagnosis of multiple sclerosis (MS) is a clinical one which should be made by a neurologist. Examination of the cerebrospinal fluid (CSF) [Lowenthal (1991): Neurol Neurosurg 4:914-918], the results of evoked potential studies, and magnetic resonance imaging serve as confirmatory tests. CSF is a window which permits a glimpse into the metabolism of the nervous system. The detailed investigation of the CSF proteins has provided important clues about our understanding of the pathogenesis of MS.
Evoked Potentials↗
Secondary prevention of stroke: does dipyridamole add to aspirin?
BACKGROUND AND PURPOSE: The purpose of this paper is to evaluate, in the light of all available evidence, the place of aspirin alone and of aspirin combined with dipyridamole in the secondary prevention of cerebrovascular accidents. METHODS: We performed a meta-analysis of all identified double blind, controlled, studies in secondary prevention of cerebrovascular accidents for the following categories: studies comparing aspirin with placebo; studies comparing aspirin plus dipyridamole with placebo; studies comparing aspirin plus dipyridamole with aspirin alone. An indirect comparison was carried out to compare the results obtained with aspirin alone and those obtained with aspirin combined with dipyridamole. RESULTS: The meta-analysis of trials involving aspirin alone against placebo showed a risk reduction on strokes (17% reduction, p = 0.02), "important vascular events", i.e. a combination of vascular deaths, non-fatal strokes and non-fatal myocardial infarction (18% reduction, p = 0.003). Fatal vascular events (vascular deaths and fatal strokes) did not seem to be reduced at all. The overall mortality was reduced by 10%, but this reduction failed to reach statistical significance (p = 0.23). The meta-analysis of trials involving aspirin combined with dipyridamole showed more important risk reductions on every outcome whether fatal or not. Strokes were reduced by 42% (p < 0.001), fatal strokes by 43% (p = 0.02) and vascular deaths by 24% (p = 0.07, not significant). The overall mortality was reduced by 30% (p = 0.004). Direct comparisons of aspirin with aspirin plus dipyridamole did not indicate differences between the two treatment regimens. However the sample sizes involved in these comparisons were far too small to be informative. Indirect comparisons yielded statistically significant results in favour of the combination in terms of "important vascular events" (p = 0.007), all strokes (p = 0.007) and fatal strokes (p = 0.03). The results were also in favour of the combination but not statistically significant in terms of all deaths (p = 0.10) and vascular deaths (p = 0.08). CONCLUSIONS: Aspirin used alone reduces secondary occurrence of vascular events in cerebrovascular patients. There is no evidence, however, of a reduction of fatal events (vascular deaths and fatal strokes). In contrast, aspirin in combination with dipyridamole reduces non-fatal as well as fatal events. These results as well as the indirect comparisons of the risk reductions suggest that the combination of aspirin with dipyridamole may be superior to aspirin alone; this hypothesis is presently tested in a large randomized trial.
Aspirin↗
Antiplatelet therapy is effective in primary prevention of myocardial infarction in patients with a previous cerebrovascular ischemic event.
OBJECTIVE: A secondary subgroup analysis of the European Stroke Prevention Study of the effect of antiplatelet medication on the risk of myocardial infarction. DESIGN AND SETTING: A randomized, double-blind placebo-controlled study with two parallel treatment groups (dipyridamole plus aspirin and placebo). Sixteen centers from six countries participated in the study. PATIENTS: A total of 2500 patients who had had one or more transient ischemic attacks or cerebral infarctions participated. INTERVENTION: Combination therapy with dipyridamole (75 mg three times a day) and aspirin (330 mg three times a day) was compared with placebo during 24 months' follow-up. OUTCOME MEASURES: Prevention of fatal and nonfatal myocardial infarction. RESULTS: A total of 105 myocardial infarctions occurred in the intention-to-treat analysis and 76 occurred in the explanatory analysis. The overall risk reduction of myocardial infarction with the study drugs was approximately 40% in both statistical analyses, but the result was statistically significant only in the intention-to-treat analysis. Therapeutic efficacy was better among male patients, patients younger than 65 years, and patients with hypertension. CONCLUSION: Combination therapy with dipyridamole and aspirin reduces not only the risk of cerebrovascular ischemic events but also the risk of myocardial infarction.
Aged↗
European Stroke Prevention Study (ESPS): antithrombotic therapy is also effective in the elderly.
The ESPS was a multicenter study comparing the effect of the combination of dipyridamole 75 mg and acetylsalicylic acid 330 mg t.i.d. to placebo in 2500 patients (intention-to-treat analysis) and 1861 patients (explanatory analysis) in the secondary prevention of stroke or death after one or more attacks of TIA, RIND or stroke of atherothrombotic origin. End-point reduction was evaluated in two age groups, those not older than 65 years (1358 patients) and those who were older than 65 years (1142 patients). End-point reduction was significantly greater in patients with active therapy than in the placebo group in both age groups. Subgroup analyses with stroke as an end-point indicated that younger patients with TIA (< or = 65 years) had lower risk of stroke than those > 65 years or patients with stroke. The overall risk reduction was best in TIA patients > 65 years of age. The risk reduction with study medication was 40-50% in both sexes and in both age groups. Thus, age of the patient does not influence the efficacy of antithrombotic therapy. However, since these results are obtained from a secondary analysis of a subgroup of patients, the results may need confirmation by further studies.
Actuarial Analysis↗
European stroke prevention study: effectiveness of antiplatelet therapy in diabetic patients in secondary prevention of stroke.
BACKGROUND AND PURPOSE: The European Stroke Prevention Study was a multicenter trial comparing the effect of a combination of 75 mg dipyridamole and 330 mg acetylsalicylic acid three times a day with the effect of a placebo in the prevention of stroke or death in 1,861 patients after one or more episodes of recent transient ischemic attack or cerebral infarction. METHODS: The present study represents a secondary analysis of the efficacy of study medication in diabetic (n = 216) and nondiabetic (n = 1,645) patients. RESULTS: The risk of end point events was greater in diabetic than in nondiabetic subjects. Total end point reduction in individuals receiving the combination of dipyridamole and acetylsalicylic acid was 39% in nondiabetic subjects and 23% in diabetic subjects in the explanatory analysis, and the reduction in the risk of stroke was 48% and 32%, respectively. However, a statistically significant reduction of risk was obtained only in nondiabetic subjects. CONCLUSIONS: The combination of dipyridamole and acetylsalicylic acid appeared to be more effective in nondiabetic subjects than in diabetic subjects in the prevention of death and stroke although the low number of diabetic patients may at least in part explain this result.
Aged↗
GABAA receptor complex function in frontal cortex membranes from control and neurological patients.
The functional integrity of the GABAA receptor-benzodiazepine (BZ) recognition site-Cl- ionophore complex was assessed by means of [35S]TBPS (t-butylbicyclophosphorothionate) binding to frontal cortex membranes prepared from frozen postmortem brain tissue taken from control (n = 4), Alzheimer (n = 7), Parkinson (n = 3) and Huntington's chorea (n = 2) patients. Specific [35S]TBPS binding was similar in control, Parkinson's disease and Huntington's chorea brains, but was significantly reduced (78% control, P less than 0.01) in frontal cortex membranes from Alzheimer's patients. The linkage between the BZ recognition sites and the GABAA receptor-linked Cl- ionophore was functionally intact in these membranes as BZ site agonists (zolpidem, alpidem, flunitrazepam and clonazepam) enhanced [35S]TBPS binding under the conditions used (well-washed membranes in the presence of 1.0 M NaCl). Zolpidem (BZ1 selective) exhibited a biphasic enhancement in control membranes whereas the other compounds induced a bell-shaped concentration-response curve. The enhancement of [35S]TBPS binding by alpidem, flunitrazepam and clonazepam was greater in frontal cortex membranes from Alzheimer's patients than in controls whereas it tended to be reduced in membranes from the brains of Huntington's chorea patients. These studies demonstrate the functional integrity of the GABAA receptor macromolecular complex and also the usefulness of [35S]TBPS binding in the study of human postmortem tissue.
Adult↗
The European Stroke Prevention Study (ESPS): results by arterial distribution.
The European Stroke Prevention Study was a multicenter study comparing the effect of the combination of dipyridamole, 75 mg, and acetylsalicylic acid, 330 mg, three times a day, to that of placebo in 2,500 patients in the secondary prevention of stroke or death after one or more transient ischemic attacks, reversible ischemic neurological deficits, or strokes of atherothrombotic origin. The patients with vertebrobasilar events at entry comprised one-third of the whole patient population. The overall total incidence of stroke or death (the end points) during the 2-year follow-up in the placebo group was lower in the vertebrobasilar group compared to the carotid group (14% versus 24%, respectively). The combination therapy of dipyridamole and acetylsalicylic acid caused a marked reduction in the incidence of stroke or death in patients with vertebrobasilar (51%) and carotid (30%) events. When only stroke was considered as the end point, dipyridamole and acetylsalicylic acid seemed to be more effective in reducing the risk of transient ischemic attacks than stroke, and more effective in men than in women.
Aspirin↗
Ticlopidine, a new anti-thrombotic drug.
Explore the source record for details and available documents.
Aspirin↗
Slow progressive bilateral posterior artery infarction presenting as agitated delirium, complicated with Anton's syndrome.
Three patients presented with an acute agitated delirium as the earliest sign of bilateral posterior cerebral artery infarction. All patients showed a unique slow progressive deterioration with a remarkably long interval between the first neuropsychological and subsequent visual and neurological symptoms, ranging from 3 to 30 days. Repeated CT scans demonstrated hypodensities in the posterior artery territory only after a long interval of 9-12 days, in case 3, and between 33 and 48 days in case 2. In the latter case MRI was still negative 33 days after onset. In 2 patients the cortical blindness was complicated with anosognosia for blindness. Clinical condition worsened progressively in all patients, leading to death, probably due to brainstem infarction. In all 3, the combination of clinical and radiological findings indicated a 'top of the basilar' distribution, which could be confirmed in two by autopsy.
Aged↗
The European Stroke Prevention Study: results according to sex.
The European Stroke Prevention Study was a multicenter trial comparing the effect of a combination of 75 mg dipyridamole and 330 mg acetylsalicylic acid tid with placebo in the prevention of stroke or death after one or more attacks of recent transient ischemic attacks or stroke of atherothrombotic origin. From the 2,500 patients in the intention-to-treat analysis, the proportion of women was 42%, and from the 1,861 patients in the explanatory analysis it was 44%. The endpoint incidence was significantly higher in men than in women. The endpoint reduction was statistically significant only in the intention-to-treat analysis with total endpoints. However, there was a marked percentage reduction of endpoints in both men and women in explanatory analysis. The risk reduction of strokes was 49% for men and 41% for women, and the reduction of total endpoints was 39% in men and 30% in women. Thus, antiplatelet therapy is effective in the prevention of stroke or death in both sexes.
Aspirin↗
Detection of neuron specific enolase concentrations in cerebrospinal fluid from patients with neurological disorders by means of a sensitive enzyme immunoassay.
An enzyme linked immunosorbent assay (ELISA) for the detection of neuron specific enolase (NSE) in cerebrospinal fluid (CSF) was developed. The sensitivity of the ELISA was less than 1 microgram/ml. This sensitivity is comparable with radioimmunoassays which have the disadvantage that radiolabelled products are used. The developed assay was used to measure cerebrospinal fluid neuron specific enolase (CSF-NSE) levels in 1178 patients with neurological disorders to establish its potential usefulness and clinical application. CSF-NSE levels in this group of patients were independent of sex and no correlation with age was found. CSF-NSE was significantly increased in Creutzfeldt-Jacob disease, meningeal hemorrhage, thrombosis, Guillain-Barré syndrome and in schizophrenia.
Animals↗
Familial Creutzfeldt-Jakob disease with temporal and spatial separation of affected members.
Familial occurrence of three definitive and two possible cases of Creutzfeldt-Jakob disease (CJD) with temporal and spatial separation in the area of focal CJD accumulation in Slovakia is reported. Incubation period is 51 and 53 years respectively, if spatial and temporal separation of affected siblings is considered, and 51 years when the time interval between the death of the affected mother and the clinical onset in the first affected child is determined. Affected children tend to die at the same time (mean difference 3.3 years) and not at the same age (mean difference 6 years). Due to separation of the affected children, a possible common exposure to CJD infection was limited to approximately seven years during their childhood. Potential endo- and exogenous risk factors and a possible mode of CJD transmission in the described family, as well as in the CJD focus, is discussed.
Aged↗
Secondary prevention of myocardial infarction in the first European Stroke Prevention Study.
The first European Stroke Prevention Study (ESPS 1) showed that a statistically significant degree of secondary ischemic lesions could be prevented by combined therapy with aspirin (330 mg) and dipyridamole (75 mg) t.i.d. The risk of both central and myocardial secondary ischemic lesions was reduced by more than 30%. Similar results were seen after both transient ischemic attacks and stroke, and in both men and women.
Aspirin↗
Serum guanidino compound levels and clearances in uremic patients treated with continuous ambulatory peritoneal dialysis.
Guanidino compounds are increased in uremia and have been implicated as uremic toxins. The serum concentrations of 13 guanidino compounds and the clearances of 10 guanidino compounds were determined in 15 steady-state uremic patients treated with continuous ambulatory peritoneal dialysis. Guanidino compounds were determined using liquid cation-exchange chromatography with a sensitive fluorescence detection method. Standardized dialysis procedures were performed, including an overnight and a 3-hour dwell period. Guanidino compound levels did not significantly differ at the end of an overnight or a 3-hour exchange, indicating a steady-state blood chemistry for these substances in chronic ambulatory peritoneal dialysis. High levels were found for guanidinosuccinic acid, creatinine, guanidine and methylguanidine, while creatine and homoarginine levels were lower than in controls. Guanidinosuccinic acid, creatinine and methylguanidine reached levels associated with toxic effects in vitro. Significantly different clearances were found ranging from 4.02 +/- 1.08 ml/min for arginine to 7.94 +/- 2.76 ml/min for creatine during a 3-hour exchange.
Adult↗
Guanidino compound analysis as a complementary diagnostic parameter for hyperargininemia: follow-up of guanidino compound levels during therapy.
The aim of this collaborative study was to investigate whether guanidino compound analyses in the biologic fluids can be used as a complementary diagnostic parameter for hyperargininemia. Guanidino compounds were determined in the biologic fluids of all known living hyperargininemic patients using a cation exchange chromatographic system with a fluorescence detection method. The serum arginine, homoarginine, alpha-keto-delta-guanidino-valeric acid, argininic acid, and N-alpha-acetylarginine levels of all the hyperargininemic patients are higher than the normal range. Similar increases were seen for the urinary excretion of alpha-keto-delta-guanidinovaleric acid and argininic acid. Untreated hyperargininemic patients have the highest guanidino compound levels in cerebrospinal fluid. However, even under therapy, the arginine, homoarginine, alpha-keto-delta-guanidinovaleric acid, and argininic acid levels in cerebrospinal fluid are still increased. Protein restriction alone is not sufficient to normalize the hyperargininemia, but protein restriction together with supplementation of essential amino acids with or without sodium benzoate decreases further the arginine levels. However, whereas the argininemia can be normalized, the catabolites of arginine are still increased. We conclude that the urinary amino acid levels may remain normal in hyperargininemia, whereas consistent increases of the guanidino compounds are observed. Thus, guanidino compound analyses can be used as a complementary biochemical diagnostic parameter for hyperargininemia. Although the argininemia can be normalized by therapy, the levels of the catabolites of arginine are still elevated.
Adolescent↗