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Rogelio Leira

Publications and source records attributed to Rogelio Leira.

14 recordsLinked to original sources
PubMed2005

Increased plasma levels of 15-deoxyDelta prostaglandin J2 are associated with good outcome in acute atherothrombotic ischemic stroke.

BACKGROUND AND PURPOSE: The 15-deoxyDelta prostaglandin J2 (15-dPGJ2) is an anti-inflammatory prostaglandin that has been proposed to be the endogenous ligand of peroxisome proliferator-activated receptor-gamma (PPARgamma), a nuclear receptor that can exert potent anti-inflammatory actions by repressing inflammatory genes when activated. It has been suggested that 15-dPGJ2 could be beneficial in neurological disorders in which inflammation contributes to cell death such as stroke. METHODS: We investigated the relationship between plasma levels of 15-dPGJ2 and early neurological deterioration (END), infarct volume, and neurologic outcome in 552 patients with an acute stroke admitted within 24 hours after symptoms onset. RESULTS: Median [quartiles] plasma 15-dPGJ2 levels on admission were significantly higher in patients than in controls (60.5 [11.2 to 109.4] versus 5.0 [3.8 to 7.2] pg/mL; P<0.0001). Levels of this prostaglandin were also significantly higher in patients with vascular risk factors (history of hypertension or diabetes) and with atherothrombotic infarcts (113.9 [81.6 to 139.7] pg/mL), than in those with lacunar (58.7 [32.7 to 86.2] pg/mL), cardioembolic (12.1 [6.5 to 39.2] pg/mL), or undetermined origin infarcts (11.4 [5.6 to 24.3] pg/mL) (P<0.0001). In the subgroup of patients with atherothrombotic infarcts, the adjusted odds ratio of END and poor outcome for 1 pg/mL increase in 15-dPGJ2 were 0.95 (95% CI, 0.94 to 0.97) and 0.97 (95% CI, 0.96 to 0.98), respectively. In a generalized linear model, by 1 U increase in 15-dPGJ2, there was a reduction of 0.47 mL (95% CI, 0.32 to 0.63) in the mean estimated infarct volume. CONCLUSIONS: Increased plasma 15-dPGJ2 concentration is associated with good early and late neurological outcome and smaller infarct volume. These findings suggest a neuroprotective effect of 15-dPGJ2 in atherothrombotic ischemic stroke.

Acute Disease↗
PubMed2004

Molecular signatures of vascular injury are associated with early growth of intracerebral hemorrhage.

BACKGROUND AND PURPOSE: To investigate whether molecular markers of inflammation and endothelial injury are associated with early growth of intracerebral hemorrhage (ICH). METHODS: In a multicenter prospective study, we determined concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), matrix metalloproteinase-9 (MMP-9), and cellular fibronectin (c-Fn) in blood samples obtained on admission from 183 patients with primary hemispheric ICH of <12 hours' duration. Patients had a neurological evaluation and a computed tomography (CT) scan performed at baseline and at 48+/-6 hours. Early growth of the ICH was defined as a volume increase >33% between the 2 CT examinations for ICH with a baseline volume <20 mL and >10% for ICH > or =20 mL. Clinical, radiological, and biochemical predictive factors of ICH enlargement were analyzed by logistic regression analysis. RESULTS: Fifty-four (29.5%) patients showed a relevant early growth of ICH. High leukocyte count and fibrinogen levels, low platelet count, and intraventricular bleeding were associated with early ICH growth in bivariate analyses. Plasma concentrations of IL-6 (median [quartiles]: 19.6 [13.6; 29.9] versus 15.9 [11.5; 19.8] pg/mL), TNF-alpha (13.5 [8.4; 30.5] versus 8.7 [4.7; 13.5] pg/mL), MMP-9 (153.3 [117.7; 204.7] versus 70.6 [47.8; 103.8] ng/mL), and c-Fn (8.8 [6.2; 12.5] versus 2.8 [1.6; 4.2] microg/mL) were significantly higher in patients with early growth of ICH (all P<0.001). C-Fn levels >6 microg/mL (OR, 92; 95%CI, 22 to 381; P<0.0001) and IL-6>24 pg/mL (OR, 16; 95%CI, 2.3 to 119; P=0.005) were independently associated with ICH enlargement in the logistic regression analysis. CONCLUSIONS: Molecular signatures of vascular injury and inflammatory markers in the early acute phase of ICH are associated with subsequent enlargement of the hematoma.

Aged↗
PubMed2004

Plasma cellular-fibronectin concentration predicts hemorrhagic transformation after thrombolytic therapy in acute ischemic stroke.

BACKGROUND AND PURPOSE: Elevated plasma levels of cellular fibronectin (c-Fn) reflect vascular damage, so c-Fn might be a marker of secondary bleeding risk in cerebral ischemia. We investigated whether high plasma levels of c-Fn were associated with hemorrhagic transformation (HT) after treatment with tissue plasminogen activator (tPA) in patients with acute stroke. METHODS: Eighty-seven patients (mean age: 67+/-12) received tPA after the ECASS II criteria (mean time to infusion: 160+/-46 minutes; median NIHSS: 12). HT and hypodensity volume were studied on computed tomography (CT) performed 24 to 36 hours after treatment. HT was classified according to the ECASS II definitions. c-Fn and matrix metalloproteinase 9 (MMP-9) levels were determined by ELISA in blood samples obtained before treatment and in 30 healthy subjects. RESULTS: HT was found in 26 patients (30%); 15 patients had hemorrhagic infarction type 1 (HI-1), 7 had HI-2, and 4 had parenchymal hemorrhage (PH). Median c-Fn concentrations were 1.3, 1.7, 4.2, 5.4, and 7.3 microg/mL in controls, non-HT, HI-1, HI-2, and PH groups, respectively (P<0.001); median MMP-9 values were 54, 87, 154, 176, and 225 ng/mL (P<0.001). Logistic regression analysis showed that only c-Fn plasma levels remained independently associated with HT after adjusting for potential confounders (OR, 2.1; 95% CI, 1.3 to 3.4; P=0.002). Similar results were obtained in the 71 patients treated within 3 hours. CONCLUSIONS: High plasma c-Fn levels are significantly associated with subsequent HT in stroke patients treated with tPA, so plasma c-Fn determinations might be useful in clinical practice to improve the risk/benefit ratio of thrombolytic treatment.

Aged↗
PubMed2004

Blood pressure decrease during the acute phase of ischemic stroke is associated with brain injury and poor stroke outcome.

BACKGROUND AND PURPOSE: Studies on the relation between blood pressure (BP) and stroke outcome have shown contradictory results. We explored the association of systolic (SBP) and diastolic (DBP) BP during acute stroke with early neurological deterioration, infarct volume, neurological outcome, and mortality at 3 months. METHODS: We included 304 patients with acute ischemic stroke. SBP and DBP on admission and on the first day were the average values of all readings obtained in the emergency department and during a 24-hour period after patient allocation in the stroke unit. RESULTS: A U-shaped effect was observed: for every 10 mm Hg 180 mm Hg, the risk of early neurological deterioration increased by 40% and the risk of poor outcome increased by 23%, with no effect on mortality. Mean infarct volume increased 7.3 and 5.5 cm(3) for every 10 mm Hg 180 mm Hg. A similar pattern was found in patients with DBP 100 mm Hg. These effects disappeared after adjustment for the use of antihypertensive drugs and BP drop >20 mm Hg within the first day, with the latter being the more important prognostic factor of poor outcome. CONCLUSIONS: High and low SBP and DBP, as well as a relevant drop in BP, are associated with poor prognosis in patients with ischemic stroke.

Acute Disease↗
PubMed2004

Cerebral hemodynamic reserve and early neurologic deterioration in acute ischemic stroke.

Early neurological deterioration (END) is associated with increased mortality and morbidity. Although several predictive factors have been reported, there are little data about the hemodynamic factors. Our aim was to determine the capacity of cerebral hemodynamic reserve (CHR) to predict END. We studied 100 hospitalized patients with a first ever ischemic stroke of the middle cerebral artery (MCA) within the first 24 hours of symptoms onset. END was defined as a drop of at least one point in the Canadian Stroke Scale between admission and 72 hours. The mean flow velocity (mV) in the MCA and the CHR were measured by means of transcranial Doppler within the first 24 hours of admission. The CHR was expressed as the percentage increase in the MCA mV divided by the absolute increase in the end-tidal CO2 pressure in mm Hg after carbogen inhalation. END was observed in 23 patients. Reduced values of the mV in the symptomatic MCA (P = 0.043) and of the CHR in the symptomatic hemisphere (P < 0.001) were significantly associated with END. A CHR of less than 2%/1 mm Hg was independently associated with END (OR 8.45, 95% CI 1.82-39.2) after adjusting for potential confounders. CHR impairment within the first 24 hours of acute ischemic stroke is associated with a higher risk of END. This technique may be useful in selecting patients requiring a more intensive management.

Aged↗
PubMed2004

The impact of migraine on work, family, and leisure among young women -- a multinational study.

OBJECTIVE: To assess the impact of migraine on work, family, and leisure among young women who were employed full or part time, or as a full-time student. RESEARCH DESIGN AND METHODS: This cross-sectional telephone survey with 6-month recall was conducted in Israel and eight European countries (Finland, Germany, Greece, Italy, Norway, Spain, Sweden, and The Netherlands). Random-digit dialing was used to identify study participants: women 18-35 years of age with migraine, who used medication to treat their migraine, and who were employed or full-time students. RESULTS: Of 1810 participants, 42% self-reported having a physician diagnosis of migraine. During the prior 6 months, 46% of participants missed at least 1 day of work or school and 74% were prevented from functioning fully at work or school because of migraine. Mean work/school absenteeism due to migraine was 1.9 days over 6 months (range, 0.8 days in Sweden to 2.8 days in Norway). Over half of participants reported one or more occurrences of being unable to spend time with family or friends (62%) or being unable to enjoy recreational or leisure activities (67%) because of migraine. The percentage of study participants using triptans was lowest in southern Europe and highest in the Nordic countries, ranging from 1% in Greece to 50% in Sweden. Country, age, marital status, physician diagnosis of migraine, and number of migraines or severe headaches in the prior year were independent predictors of the mean number of days of migraine-related work loss. Migraine-related work loss was lowest in Sweden and greatest in Greece, Israel, and The Netherlands. Higher work loss was recorded for those 18-24 years of age; those who were separated, widowed, or divorced; those with migraine diagnosed by a physician; and those with more frequent migraines or severe headaches (> or =24/year). The 6-month recall period used when estimating patient-reported work loss, and identifying participants with migraine based on self-reported migraine or severe headache, were the most important limitations of the study. CONCLUSIONS: We found substantial migraine-related impairment of productivity at work and school as well as of family and leisure time among young women in Israel and eight European countries.

Adolescent↗
PubMed2003

Neuroprotective effects of aspirin in patients with acute cerebral infarction.

Aspirin may reduce ischemic brain injury. The aim of this study was to explore the effect of aspirin on glutamate release after acute stroke. We studied 238 patients with a first episode of hemispheric ischemic stroke of less than 24 h duration. Early neurological deterioration was diagnosed when the Canadian Stroke Scale dropped 1 or more points between admission and 48 h. Glutamate was determined on cerebrospinal fluid (CSF) samples obtained at admission. Sixty-three patients were undergoing treatment with 75-500 mg/day of aspirin at the time of stroke onset. CSF glutamate concentrations were higher in the group of patients not taking aspirin (8.9+/-5.2 vs. 4.9+/-3.1 microM/l, P< 0.0001). Aspirin treatment at stroke onset had a 97% risk reduction of early neurological deterioration, and this effect remained unchanged after a further adjustment for glutamate concentrations. These findings suggest that low doses of aspirin may be useful in the management of patients with cerebral ischemia, not only for its antithrombotic properties, but also by direct neuroprotective effects.

Acute Disease↗
PubMed2003

The release of tumor necrosis factor-alpha is associated with ischemic tolerance in human stroke.

Tumor necrosis factor (TNF)-alpha overexpression has been related to experimental ischemic tolerance when transient ischemia precedes cerebral infarction. We investigated TNF-alpha and interleukin (IL)-6 plasma concentrations in 283 patients with an acute stroke within 24 hours after symptom onset. An ipsilateral transient ischemic attack (TIA) within 72 hours before stroke was recorded in 38 patients. The infarct volume measured on computed tomography on days 4 to 7 and the frequency of poor outcome (Barthel Index score < 85) at 3 months were significantly lower in patients with prior TIA. Plasma concentrations of TNF-alpha were higher (42.5 +/- 9.9 vs 13.1 +/- 6.4pg/ml, p < 0.0001) and IL-6 levels were lower (10.1 +/- 6.2 vs 28.3 +/- 17.3pg/ml, p < 0.0001) in patients with prior TIA. A new variable termed TNF-alpha/IL-6 index was considered positive when TNF-alpha was greater than 30pg/ml and IL-6 was less than 30pg/ml. Positive TNF-alpha/IL-6 index was found in 92% of patients with prior TIA and in 1% of those without. TNF-alpha/IL-6 index (p = 0.0003) and TIA (p = 0.0001) were associated with good outcome in logistic regression analysis after adjusting for potential confounding factors. Ischemic tolerance in acute stroke is associated with increased plasma levels of TNF-alpha in the presence of reduced concentrations of IL-6.

Aged↗
PubMed2003

L-arginine levels in blood as a marker of nitric oxide-mediated brain damage in acute stroke: a clinical and experimental study.

There are no useful markers in blood of nitric oxide (NO)-mediated brain damage. Because l-arginine (l-arg) is the only known substrate for NO generation, the authors investigated the plasma profile of l-arg after cerebral ischemia, and the relationship of L-arg concentrations in blood with stroke outcome and infarct volume in a clinical and experimental study. l-Arg levels were determined with high-performance liquid chromatography in blood and CSF samples obtained on admission, and in blood 48 hours after inclusion, in 268 patients admitted with a hemispheric ischemic stroke lasting 8.2 +/- 5.9 hours. Infarct volume was measured by days 4 to 7 using computed tomography. Plasma l-arg profiles were analyzed in a separate group of 29 patients seen within 8 hours of onset (median, 4.5 hours) and in 24 male Fischer rats treated with subcutaneous vehicle or 20-mg/kg 1400W (a specific inducible NO synthase inhibitor) every 8 hours for 3 days after performing sham or permanent middle cerebral artery occlusion. Plasma l-arg concentrations decreased after the ischemic event, both in patients and rats, and peaked between 6 and 24 hours. In patients, there was a highly correlation between l-arg levels in CSF and plasma at 48 hours (r = 0.85, P<0.001). CSF and plasma l-arg concentrations negatively correlated with infarct volume (r = -0.40 and r = -0.35, respectively, P<0.001), and were significantly lower in patients with early neurologic deterioration and in those with poor outcome (Barthel index <85) at 90 days (P<0.001). In rats, the administration of 1400W resulted in a 55% significant reduction of infarct volume measured 72 hours after permanent middle cerebral artery occlusion, an effect that correlated with the inhibition caused by 1400W on the ischemia-induced decrease of plasma l-arg concentrations at 6 to 24 hours after the onset of the ischemia. Taken together, these data indicate that determination of l-arg levels in blood might be useful to evaluate the neurotoxic effects of NO generation. These findings might be helpful to guide future neuroprotective strategies in patients with ischemic stroke.

Acute Disease↗
PubMed2003

Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke.

BACKGROUND AND PURPOSE: Matrix metalloproteinase-9 (MMP-9) activity has been associated with hemorrhagic transformation (HT) in experimental models of cerebral ischemia. Our aim was to investigate the relationship between MMP-9 concentrations in blood within 24 hours of stroke onset and subsequent HT of cerebral infarction. METHODS: We studied 250 patients with a hemispheric ischemic stroke of 7.8+/-4.5 hours' duration. Early CT signs of cerebral infarction were evaluated on admission. The HT and infarct volume were analyzed from the CT performed on days 4 through 7. MMP-9 levels were determined by enzyme-linked immunosorbent assay in blood samples obtained on admission. RESULTS: HT was observed in 38 patients (15.2%): 24 (63.2%) had a hemorrhagic infarction, and 14 (36.8%) had a parenchymal hematoma. A total of 108 patients (43%) received anticoagulants before the second CT scan. Systolic and diastolic blood pressures, body temperature, frequency of early CT signs of ischemia (92% versus 22%), and treatment with anticoagulants (79% versus 37%) were significantly higher in the group with HT (P<0.001). Mean infarct volume was 126+/-60 cm(3) in the HT group and 90+/-68 cm3 in the group without HT (P=0.003). Median (quartiles) plasma MMP-9 concentrations were higher in the HT group (193 [163, 213] versus 62 [40, 93] ng/mL, P<0.001), even in the 24 patients seen within 3 hours of symptom onset (P=0.014). MMP-9 levels > or =140 ng/mL had a positive and negative predictive value of HT of 61% and 97%, respectively. MMP-9 > or =140 ng/mL was associated with HT (odds ratio, 12; 95% confidence interval, 3 to 51; P<0.001) after adjustment for potential confounders and final infarct volume. CONCLUSIONS: High plasma MMP-9 concentration in the acute phase of a cerebral infarct is an independent biochemical predictor of HT in all stroke subtypes.

Biomarkers↗
PubMed2002

Inflammation-mediated damage in progressing lacunar infarctions: a potential therapeutic target.

BACKGROUND AND PURPOSE: The mechanisms underlying neurological deterioration in patients with lacunar infarction are not completely understood. In this study, we sought to investigate the role of proinflammatory molecules in the early worsening and outcome of acute lacunar stroke. METHODS: We performed a secondary analysis of 113 consecutive patients with lacunar infarction included within the first 24 hours of the onset of symptoms in a previous study aimed at investigating clinical and biochemical factors of early neurological deterioration (END). END was defined as a fall of > or =1 points in the motor items of Canadian Stroke Scale between inclusion and 48 hours. Poor outcome at 3 months was considered death or Barthel Index <85. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and intercellular adhesion molecule-1 (ICAM-1) were determined by enzyme-linked immunoabsorbent assay in blood samples obtained on admission. RESULTS: END was recorded in 27 patients (23.9%); poor outcome was noted in 26 (23%). Median (quartiles) concentrations in plasma of TNF-alpha [16.5 pg/mL (13.7 and 21.2 pg/mL) versus 7.5 pg/mL (6.2 and 9.0 pg/mL)], IL-6 [28.8 pg/mL (22.5 and 35.7 pg/mL) versus 11.5 pg/mL (8.5 and 16.2 pg/mL)], and ICAM-1 [285 pg/mL (219 and 315 pg/mL) versus 158 pg/mL (137 and 187 pg/mL)] were significantly higher in patients who had END than in those with nonprogressing strokes (P< 0.001). Significant differences were also observed between patients with poor and good outcome at 3 months. Logistic regression analysis after adjustment for potential confounders showed that TNF-alpha >14 pg/mL and ICAM-1 >208 pg/mL were independently associated with both END (OR, 511; 95% CI, 17 to 4937; P<0.001; and OR, 315; 95% CI, 17 to 5748; P< 0.001, respectively) and poor outcome at 3 months (OR, 3.0; 95% CI, 1.0 to 8.5; P=0.042; and OR, 4.2; 95% CI, 1.3 to 13.6; P<0.015, respectively). CONCLUSIONS: High concentrations of inflammatory markers in blood are associated with END and poor functional outcome in lacunar infarctions. These findings suggest that inflammation contributes to brain injury in lacunar stroke.

Aged↗
PubMedDate not supplied

Almotriptan versus rizatriptan in patients with migraine in Spain.

OBJECTIVES: To compare patient-reported use of rizatriptan 10 mg with that of almotriptan 12.5 mg per migraine attack (24 hours) in a Spanish population. METHODS: One hundred twenty Spanish community pharmacies recruited patients with migraine to whom they had dispensed almotriptan and rizatriptan. No other selection criteria were used. Patients kept diaries for baseline pain intensity, the number of triptan tablets used, additional medication taken per attack, and their degree of satisfaction with the medication 2 hours after the initial dose. Patients recorded details for a maximum of 3 attacks. Analysis of variance or the Student t test and chi-squared or Fisher exact tests were used for univariate comparisons. A generalized estimating equation method was used to correct for within-subject variability. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: One hundred twenty-six patients (85% women) recorded data for 318 migraine attacks. Rizatriptan was used to treat 122 attacks, almotriptan was used to treat 110 attacks, and a nontriptan medication was used in the initial treatment of 86 attacks. Triptan use (adjusted mean, 95% CI) per attack in this study was lower for rizatriptan (1.19 tablets; 95% CI, 1.06 to 1.32) than for almotriptan (1.43 tablets; 95% CI, 1.30 to 1.56; P=.003). The use of a triptan and additional medication per attack increased with baseline pain severity. Rizatriptan was used to treat more attacks with only one tablet (78%) than almotriptan (58%). Treatment of attacks with almotriptan was more than twice as likely to involve the use of more than one tablet per attack (24 hours) than those treated with rizatriptan (adjusted OR, 2.42; 95% CI, 1.37 to 4.30; P=.003). Patient satisfaction with treatment response at 2 hours was more than 2-fold greater for rizatriptan (85%) than for almotriptan (68%) (adjusted OR, 2.55; 95% CI, 1.11 to 5.87; P=.03). CONCLUSIONS: In this prescription-selected Spanish population, a significantly lower number of rizatriptan tablets were required to treat migraine attacks compared with almotriptan. Further, patients were more than twice as likely to use more than one tablet or additional medication (or both) for attacks treated with almotriptan than for those treated with rizatriptan. Although these data suggest that rizatriptan may be a more effective treatment for migraine than almotriptan, further randomized studies are required to confirm this conclusion.

Adult↗
PubMedDate not supplied

Preventing disturbing migraine aura with lamotrigine: an open study.

BACKGROUND: Lamotrigine has been suggested as possibly effective for preventing migraine aura. OBJECTIVE: To describe our experience with a series of patients with disturbing migraine aura treated with lamotrigine. METHODS: The members of the Headache Group of the Spanish Society of Neurology were sent an ad hoc questionnaire to collect patients treated with lamotrigine due to disturbing migraine aura. The main outcome parameter ("response") was a >50% reduction in the mean frequency of migraine auras at 3 to 6 months of treatment. RESULTS: A total of 47 patients had been treated with lamotrigine due to severe migraine aura. Three could not complete the protocol as a result of developing skin rashes. Thirty (68%) patients responded. These were 21 females and 9 males whose ages ranged from 19 to 71 years. Eight suffered from migraine with "prolonged" aura, 8 typical aura with migraine headache (but had frequent episodes including speech symptoms), 6 basilar-type migraine, 6 typical aura without headache, and 2 hemiplegic migraine. Fifteen had been previously treated, without response, with other preventatives. The mean monthly frequency of migraine auras in these 30 patients changed from 4.2 (range: 1 to 15) to 0.7 (range: 0 to 6). Response was considered as excellent (>75% reduction) in 21 cases (70% of responders). Auras reappeared in 2 months in 9 out of 13 patients where lamotrigine was stopped, and ceased as soon as this drug was reintroduced. CONCLUSIONS: Lamotrigine should be considered in clinical practice for the preventive treatment of selected patients with disturbing migraine auras. Lamotrigine seems worthy of a controlled trial as prophylaxis of migraine aura.

Adult↗