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A Dávalos

Publications and source records attributed to A Dávalos.

At least 37 records · Page 2Linked to original sources
PubMed2000

Body iron stores and early neurologic deterioration in acute cerebral infarction.

BACKGROUND: Iron-dependent free radicals formation has been related to greater damage in cerebral ischemia. The authors analyzed whether increased body iron stores were associated with early neurologic worsening and excitatory amino acid release in patients with acute ischemic stroke. METHODS: Ferritin, total iron, and glutamate concentrations in plasma and CSF were measured on admission in 100 consecutive patients with a cerebral infarction of <24 hours' duration. The authors diagnosed progressing stroke when the Canadian Stroke Scale score decreased one or more points between admission and 48 hours. Cranial CT was performed on admission and repeated on days 4 to 7 of hospitalization. RESULTS: Ferritin concentrations in plasma (median 391, range 119 to 500 versus 148, 21 to 399 ng/mL) and in CSF (17.4, 6.8 to 82, versus 4.8, 0.6 to 14 ng/mL) were significantly higher in the 45 patients with subsequent progressing stroke than in those with nonprogressing stroke (p < 0.001). There was a positive correlation between ferritin and glutamate concentrations in plasma (r = 0.81, p < 0.001) and CSF (r = 0.64, p < 0.001). Plasma ferritin concentrations >275 ng/mL in plasma (OR, 33.5; 95% CI, 4.7 to 235) and >11 ng/mL in CSF (OR, 11.4; 95% CI, 3. 1 to 41) were independently and significantly related to early neurologic worsening. The effect was reduced by >60% after controlling for glutamate concentrations, but remained significant. CONCLUSIONS: High plasma and CSF ferritin concentrations within the first 24 hours from the onset of ischemic stroke are associated with early neurologic deterioration. Increased body iron stores may contribute to stroke progression by enhancing the cytotoxic mechanisms in cerebral ischemia.

Acute Disease↗
PubMed2000

Cerebral embolism in a patient with polycythemia rubra vera.

Polycythemia rubra vera (PRV) is a rare haematological disorder that has a high risk of stroke, although the pathophysiological origin of the cerebral ischaemia in this disease is not well known. We report a case of a stroke patient with PRV in whom bilateral embolic signals were detected by transcranial Doppler (TCD). Cerebral computed tomography showed a cortical middle cerebral artery infarction, echocardiography was normal, duplex-scan showed moderate left carotid stenosis and digital angiography disclosed right siphon stenosis. TCD examinations in the acute phase repeatedly showed a great number of bilateral microembolic signals (MESs). Four months later magnetic resonance angiography showed no flow signal in the right siphon and a severe stenosis of the proximal right MCA. The detection of bilateral MESs in the absence of cardiac sources of embolism observed in this patient suggests that ischaemic cerebral events in PRV may have an embolic origin favoured by a prothrombotic state.

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PubMed2000

Differential regulation of fixN-reiterated genes in Rhizobium etli by a novel fixL-fixK cascade.

Among the complexities in the regulation of nitrogen fixation in the Rhizobiaceae are reiteration of regulatory components as well as variant roles for each component between species. For Rhizobium etli CFN42, we reported that the symbiotic plasmid (pCFN42d) contains a key regulatory gene (fixKd) and genes for a symbiotic cytochrome oxidase (fixNOQPd). Here we discuss the occurrence of reiteration of these genes (fixKf and fixNOQPf) and the finding of an unusual fixL homolog on a plasmid previously considered cryptic (pCFN42f). The structure of the deduced FixL polypeptide is suggestive of a fusion of the receiver and transmitter modules of a two-component regulatory system as described in R. leguminosarum bv. viciae VF39. Gene fusion analysis, coupled with mutation of each regulatory element, revealed that free-living expression of FixKf was dependent fully on FixL. In contrast, synthesis of FixKd was not detected under the conditions tested. The FixKf protein is needed for microaerobic expression of both fixN reiterations, whereas the FixKd protein appears to be dispensable. Interestingly, expression of the fixN reiterations exhibits a differential dependence for FixL, where transcription of fixNf was suppressed in the absence of FixL but expression of fixNd still showed significant levels. This suggests the existence of a FixL-independent mechanism for expression of the fixNd reiteration. Surprisingly, mutations in fixL, fixKd, or fixKf (either singly or in combination) did not alter symbiotic effectiveness. A mutation in fixNd (but not in fixNf) was, however, severely affected, indicating a differential role for these reiterations in nitrogen fixation.

Artificial Gene Fusion↗
PubMed2000

Proinflammatory cytokines and early neurological worsening in ischemic stroke.

BACKGROUND AND PURPOSE: The mechanisms for clinical deterioration in patients with ischemic stroke are not completely understood. Several proinflammatory cytokines are released early after the onset of brain ischemia, but it is unknown whether inflammation predisposes to neurological deterioration. We assessed the implication of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in early neurological worsening in ischemic stroke. METHODS: Two hundred thirty-one patients consecutively admitted with first-ever ischemic cerebral infarction within the first 24 hours from onset were included. Neurological worsening was defined when the Canadian Stroke Scale (CSS) score fell at least 1 point during the first 48 hours after admission. IL-6 and TNF-alpha were determined in plasma and cerebrospinal fluid (CSF; n=81) obtained on admission. RESULTS: Eighty-three patients (35.9%) deteriorated within the first 48 hours. IL-6 in plasma (>21.5 pg/mL; OR 37.7, CI 11.9 to 118.8) or in CSF (>6.3 pg/mL; OR 13.1, CI 2.2 to 77.3) were independent factors for early clinical worsening, with multiple logistic regression. The association was statistically significant in all ischemic stroke subtypes as well as in subjects with cortical or subcortical infarctions. IL-6 in plasma was highly correlated with body temperature, glucose, fibrinogen, and infarct volume. CSF and plasma concentrations of TNF-alpha were also higher in patients who deteriorated, but the differences observed did not remain significant on multivariate analysis. CONCLUSIONS: In addition to participating in the acute-phase response that follows focal cerebral ischemia, IL-6 levels on admission are associated with early clinical deterioration. The association between IL-6 and early neurological worsening prevails without regard to the initial size, topography, or mechanism of the ischemic infarction.

Aged↗
PubMed2000

Nitric oxide-related brain damage in acute ischemic stroke.

BACKGROUND AND PURPOSE: The neurotoxic and neuroprotective role of nitric oxide (NO) in experimental cerebral ischemia has generated considerable debate. The aim of this study was to analyze the relationship between NO metabolite (NO-m) concentrations in cerebrospinal fluid (CSF) and clinical and neuroimaging parameters of brain injury in patients with acute ischemic stroke. METHODS: We studied 102 patients and 24 control subjects who were included in a larger previous study conducted to analyze risk factors of progressing stroke. NO generation was calculated by quantifying nitrates and nitrites with a colorimetric assay in CSF samples obtained within the first 24 hours from symptoms onset. Early neurological deterioration was defined as a fall of 1 or more points in Canadian Stroke Scale score between admission and 48 hours after inclusion. Infarct volume was measured on days 4 to 7 by cranial CT. RESULTS: Median NO-m concentrations [quartiles] were 2.1 [1.0, 4.5] micromol/mL in patients and 1.0 [1.0, 1.0] micromol/mL in control subjects (P<0.0001). In 45 patients with subsequent early neurological deterioration, NO-m levels in CSF were significantly higher than in those with stable stroke (4.0 [1.7, 7.8] versus in 1. 6 [1.0, 2.5] micromol/mL, P<0.0001). There was a moderate correlation between NO-m and infarct volume (coefficient 0.39, P<0. 001). NO-m concentrations >5.0 micromol/mL were significantly associated with early neurological worsening (OR 5.7, 95% CI 1.2 to 27.4; P=0.030) independent of other important factors related to progressing stroke, such as CSF glutamate levels. CONCLUSIONS: Our clinical findings suggest an important role of NO generation in acute ischemic stroke. Increased NO-m in CSF are associated with a greater brain injury and early neurological deterioration.

Acute Disease↗
PubMed1999

Neurological deterioration in acute ischemic stroke: potential predictors and associated factors in the European cooperative acute stroke study (ECASS) I.

BACKGROUND AND PURPOSE: The present study was undertaken to identify potential predictors of and factors associated with early and late progression in acute stroke. We performed secondary analysis of the clinical, biochemical, and radiological data recorded in the acute phase of stroke patients enrolled in the European Cooperative Acute Stroke Study (ECASS) I. METHODS: Early progressing stroke (EPS) was diagnosed when there was a decrease of > or = 2 points in consciousness or motor power or a decrease of > or = 3 points in speech scores in the Scandinavian Neurological Stroke Scale from baseline to the 24-hour evaluation, and late progressing stroke (LPS) was diagnosed when 1 of these decreases occurred between the 24-hour evaluation and the evaluation at day 7. Using logistic regression analyses, we looked for baseline variables that predicted EPS and LPS and for factors measured after the early or late acute phase and associated with the 2 clinical courses. RESULTS: Of the 615 patients studied, 231 (37.5%) worsened during the first 24 hours after inclusion. The overall incidence of EPS was 37% in the placebo group and 38% in the recombinant tissue plasminogen activator group (P=0.68, Fisher's Exact Test). Focal hypodensity (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.3 to 2.9) and hyperdensity of the middle cerebral artery sign (OR, 1.8; 95% CI, 1.1 to 3.1) on baseline computed tomography, longer delay until treatment (OR, 1.2; 95% CI, 1.1 to 1. 4) and history of coronary heart disease (OR, 1.7; 95% CI, 1.1 to 2. 8) and diabetes (OR, 1.8; 95% CI, 1.0 to 3.1) were independent prognostic factors for EPS. Extent of hypodensity >33% in the middle cerebral artery territory (OR, 2.5; 95% CI, 1.6 to 4.0) and brain swelling (OR, 1.8; 95% CI, 1.1 to 3.2) on CT at 24 hours but not hemorrhagic transformation of cerebral infarct nor decrease in systolic blood pressure within the first 24 hours after treatment were associated with EPS in multivariate analyses. LPS was observed in 20.3% of patients. Older age, a low neurological score, and brain swelling at admission independently predicted late worsening. CONCLUSION: In the setting of a multicenter trial, EPS and LPS are mainly related to computed tomographic signs of cerebral edema. Treatment with recombinant tissue plasminogen activator, hemorrhagic transformation, and moderate changes in systolic blood pressure did not influence the early clinical course.

Aged↗
PubMed1999

[Thrombolysis in cerebral ischemia].

Thrombolytic treatment with rt-PA is the first effective step in the therapeutic management of acute ischemic infarction. The benefit of rt-PA was clearly demonstrated in the NINDS study which showed a reduction in mortality or dependence in 13% of the cases. However, a reduction of only 3-5% as observed in the ECASS-II study is clinically relevant. In both the individual analysis and metaanalysis, the rt-PA studies indicate that despite a high frequency of symptomatic hemorrhages, mortality or morbidity do not increase and the clinical evolution improves. We believe that, at present, the question is not whether thrombolysis is effective in acute infarction, but whether we have well trained physicians in well equipped centers to provide this treatment adequately and safely. The patients admitted to stroke units within the first six hours should be considered for thrombolysis with rt-PA after careful evaluation of the inclusion and exclusion criteria. In Spain, however, rt-PA should be exclusively administered in accredited centers which have obtained authorization to perform its compassive use. In these cases, treatment with rt-PA should be carefully adjusted to the recommendations published by the AHA, it should be indicated by neurologists who are experts in the management of ictus, and administered in patients who may be closely monitored in stroke units. Hospitals without these possibilities should promote a radical change in stroke management. In these centers, neurologists, in collaboration with radiologists, internists and emergency physicians, should develop protocols of clinical performance, reorganize the priorities of the emergency departments, and familiarize themselves with CT findings and with the treatment criteria. The results of the metaanalysis of the finalized studies will allow better definition of the groups of patients at high risk of developing cerebral hemorrhage, and those in whom rt-PA may be more effective. The potential risks and benefits of rt-PA should be individually evaluated and discussed with the patient and relatives before initiation of treatment. However, the existence of severe potential complications should not invalidate the benefit of thrombolytic treatment, similar to the fact that the severe surgical complications of carotid endarterectomy (5%) have not obscured the clear benefits of this intervention on the long term prognosis of the patients.

Brain↗
PubMed1999

[Normal values for transcranial doppler studies in our medium].

OBJECTIVE: Transcranial Doppler is a technique which is being used ever more frequently in the study of intracranial arteries and is very useful in the study of cerebrovascular disease. The typical values of a healthy population in our country are unknown. The aim of this study was determine mean velocity and pulsatility index reference values in a healthy population. PATIENTS AND METHOD: Transcranial Doppler basal examination was carried out on 118 healthy volunteers without prior haematological or cerebrovascular conditions. Those found to have extracranial arterial stenoses were excluded as were those in whom bilateral temporal bone hyperostosis did not permit insonation in either middle cerebral arteries. The nine intracranial arteries were sounded systematically at fixed depths. The mean and standard deviations of each variable were calculated for side, age group and sex. RESULTS: 49% were males and average age was of 56 years (range, 21-87 years). A sufficient signal to determine the parameters of the study was obtained in 89% of middle cerebral arteries. Statistically significant differences in mean velocity and pulsatility index were found between age groups and sexes. CONCLUSIONS: Sex and age must be taken into account in establishing typical patterns in transcranial Doppler examination. Our results enable parameters of typical values to be established for the adult population in Spain.

Adult↗
PubMed1999

[Neuroprotective agents].

In the last decade, a huge number of drugs have been developed in order to block the different molecular reactions of the ischemic cascade. Most of neuroprotective compounds decrease infarct volume in experimental stroke models, but none of them has reduced stroke mortality and morbidity in clinical trials. This article comments those factors that justify discrepancies between the laboratory and clinical findings, and reviews the neuroprotective drugs studied in patients with acute ischemic stroke. Although the clinical investigation of many of them has been abandoned because safety concerns, preliminary observations suggest a beneficial effect of ebselen, a compound with antioxidant activity, and citicoline, a stabiliser of cell membranes. Other neuroprotective drugs like trafermin and glycine antagonists are in advanced clinical investigation, thus the neuroprotection scenario may favourably change in the near future.

Acute Disease↗
PubMed1999

[New treatments in cerebrovascular diseases].

Acute stroke is a neurologic emergency which should be preferentially treated in a Stroke Unit. The applications of general therapeutic measures in these units decreases the mortality or dependence in 29% of the cases. Thrombolytic treatment with rt-PA in the first 3 hours of cerebral ischemia reduces the risk of mortality or dependence at 3 months by 51%. This treatment should be used in centers with an adequate organization and experience in the management of stroke. Careful patient selection allows a favorable conscious risk/benefit when rt-PA is used in clinical practice. In the last decade numerous neuroprotector drugs have been developed which, despite decreasing the volume of the infarction in animal models, have not currently achieved a reduction in the mortality and morbidity of cerebral infarction in clinical trials. Ebselen, citicoline, piracetam and clomethiazol have shown beneficial effects in preliminary studies or in some subgroups of patients, but their use based on evidence is not recommendable. Anticoagulants and antiplatelet drugs have not been shown to be effective in the acute phase of cerebral infarction. The neuroprotector effect of unfractionated heparin and glycoprotein IIb IIIa antagonists is still under study. Clopidogrel and the association of aspirin and dipiridamol are new alternatives to aspirin in the secondary prevention of cerebral infarction. Both options provide a lower risk of recurrence, and clopidogrel also shows better tolerance. The preventive effect of low intensity anticoagulation and statins is being analyzed in clinical studies.

Humans↗
PubMed1998

Timing for fever-related brain damage in acute ischemic stroke.

BACKGROUND AND PURPOSE: The association between hyperthermia and early neurological deterioration, increased morbidity, and mortality in acute ischemic stroke is well known. However, the timing at which the cerebral lesion may be aggravated by high temperature has not been firmly established. The aim of this study was to determine the prognostic value of body temperature measured at different times after onset of stroke. METHODS: Axillary temperature was recorded every 2 hour hours for 72 hours in 260 patients with a hemispheric cerebral infarction of <24 hours' duration. A potential infectious focus was examined in all patients with hyperthermia (temperature >37.5 degreesC in any of the assessments). Stroke severity was quantified with the Canadian Stroke Scale on admission. The relationship between the highest temperature recorded in each 6-hour interval from stroke onset and stroke outcome (Canadian Stroke Scale and Barthel Index at 3 months) or infarct volume was evaluated by correlation analyses. The importance of the time at which hyperthermia was first detected was assessed by logistic regression analysis. RESULTS: During the first 72 hours, 158 patients (60.8%) had hyperthermia, and in 57.6% of them an infectious cause was identified. Mortality rate at 3 months was 1% in normothermic patients and 15.8% in hyperthermic patients (P<0.001). The correlation coefficients between the final infarct volume, Canadian Stroke Scale and Barthel Index scores at 3 months, and each temperature recording decreased progressively over time from symptom onset. Hyperthermia initiated within the first 24 hours from stroke onset, but not afterward, was independently related to larger infarct volume (odds ratio [OR]=3.23, 95% CI=1.63 to 6.43; P<0.001) and higher neurological deficit (OR=3.06, 95% CI=1.70 to 5.53; P<0. 001) and dependency (OR=3.41, 95% CI=1.69 to 6.88; P=0.002) at 3 months. The infectious origin of hyperthermia was not associated with poorer outcome or greater infarct volume. CONCLUSIONS: The relationship between brain damage and high temperature is greater the earlier the increase in temperature occurs. However, only body temperature within the first 24 hours from stroke onset is associated with poor outcome and large cerebral infarcts.

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