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1.
Eur J Neurol ; 28(2): 540-547, 2021 02.
Article in English | MEDLINE | ID: mdl-33043545

ABSTRACT

BACKGROUND AND PURPOSE: B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are well-known surrogates of atrial fibrillation (AF) detection but studies usually present data on either BNP or NT-proBNP. The aim was to determine and directly compare the validity of the two biomarkers as a tool to predict AF and guide prolonged cardiac monitoring in cryptogenic stroke patients. METHODS: Non-lacunar acute ischaemic stroke (<72 h) patients over 55 years of age with cryptogenic stroke after standard evaluation were included in the Crypto-AF study and blood was collected. BNP and NT-proBNP levels were determined by automated immunoassays. AF was assessed by 28 days' monitoring. Highest (optimizing specificity) and lowest (optimizing sensitivity) quartiles were used as biomarker cut-offs to build predictive models adjusted by sex and age. The integrated discrimination improvement index (IDI) and DeLong test were used to compare the performance of the two biomarkers. RESULTS: From 320 patients evaluated, 218 were included in the analysis. AF was detected in 50 patients (22.9%). NT-proBNP (P < 0.001) and BNP (P < 0.001) levels were higher in subjects with AF and their levels correlated (r = 0.495, P < 0.001). BNP showed an increased area under the curve (0.720 vs. 0.669; P = 0.0218) and a better predictive capacity (IDI = 3.63%, 95% confidence interval 1.36%-5.91%) compared to NT-proBNP. BNP performed better than NT-proBNP in a specific model (IDI = 3.7%, 95% confidence interval 0.87%-6.5%), whilst both biomarkers performed similarly in the case of a sensitive model. CONCLUSIONS: Both BNP and NT-proBNP were increased in cryptogenic stroke patients with AF detection. Interestingly, BNP outperforms NT-proBNP, especially in terms of specificity.


Subject(s)
Atrial Fibrillation , Brain Ischemia , Ischemic Stroke , Stroke , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Biomarkers , Humans , Natriuretic Peptide, Brain , Peptide Fragments , Stroke/complications
2.
Eur J Neurol ; 27(8): 1618-1624, 2020 08.
Article in English | MEDLINE | ID: mdl-32347993

ABSTRACT

BACKGROUND AND PURPOSE: Covert paroxysmal atrial fibrillation (pAF) is the most frequent cause of cardiac embolism. Our goal was to discover parameters associated with early pAF detection with intensive cardiac monitoring. METHOD: Crypto-AF was a multicentre prospective study (four Comprehensive Stroke Centres) to detect pAF in non-lacunar cryptogenic stroke continuously monitored within the first 28 days. Stroke severity, infarct pattern, large vessel occlusion (LVO) at baseline, electrocardiography analysis, supraventricular extrasystolia in the Holter examination, left atrial volume index and brain natriuretic peptide level were assessed. The percentage of pAF detection and pAF episodes lasting more than 5 h were registered. RESULTS: Out of 296 patients, 264 patients completed the monitoring period with 23.1% (61/264) of pAF detection. Patients with pAF were older [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01-1.08], they had more haemorrhagic infarction (OR 4.03, 95% CI 1.44-11.22), they were more likely to have LVO (OR 4.29, 95% CI 2.31-7.97) (P < 0.0001), they had a larger left atrial volume index (OR 1.03, 95% CI 1.01-1.1) (P = 0.0002) and they had a higher level of brain natriuretic peptide (OR 1.01, 95% CI 1.0-1.1). Age and LVO were independently associated with pAF detection (OR 1.06, 95% CI 1.00-1.16, and OR 4.58, 95% CI 2.27- 21.38, respectively). Patients with LVO had higher cumulative incidence of pAF (log rank P < 0.001) and more percentage of pAF > 5 h [29.6% (21/71) vs. 8.3% (12/144); OR 4.62, 95% CI 2.11-10.08; P < 0.001]. In a mean follow-up of 26.82 months (SD 10.15) the stroke recurrence rate was 4.6% (12/260). CONCLUSIONS: Large vessel occlusion in cryptogenic stroke emerged as an independent marker of pAF.


Subject(s)
Atrial Fibrillation , Stroke , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Electrocardiography , Electrocardiography, Ambulatory , Humans , Incidence , Prospective Studies
4.
J Intern Med ; 283(5): 461-475, 2018 05.
Article in English | MEDLINE | ID: mdl-29415332

ABSTRACT

BACKGROUND: CCL23 role in the inflammatory response after acute brain injuries remains elusive. Here, we evaluated whether CCL23 blood levels associate with acquired cerebral lesions and determined CCL23 predictive capacity for assessing stroke prognosis. We used preclinical models to study the CCL23 homologous chemokines in rodents, CCL9 and CCL6. METHODS: Baseline CCL23 blood levels were determined on 245 individuals, including ischaemic strokes (IS), stroke mimics and controls. Temporal profile of circulating CCL23 was explored from baseline to 24 h in 20 of the IS. In an independent cohort of 120 IS with a 3-month follow-up, CCL23 blood levels were included in logistic regression models to predict IS outcome. CCL9/CCL6 cerebral expression was evaluated in rodent models of brain damage. Both chemokines were also profiled in circulation and histologically located on brain following ischaemia. RESULTS: Baseline CCL23 blood levels did not discriminate IS, but permitted an accurate discrimination of patients presenting acute brain lesions (P = 0.003). IS exhibited a continuous increase from baseline to 24 h in circulating CCL23 (P < 0.001). Baseline CCL23 blood levels resulted an independent predictor of IS outcome at hospital discharge (ORadj : 19.702 [1.815-213.918], P = 0.014) and mortality after 3 months (ORadj : 21.47 [3.434-134.221], P = 0.001). In preclinics, expression of rodent chemokines in neurons following cerebral lesions was elevated. CCL9 circulating levels decreased early after ischaemia (P < 0.001), whereas CCL6 did not alter within the first 24 h after ischaemia. CONCLUSIONS: Although preclinical models do not seem suitable to characterize CCL23, it might be a novel promising biomarker for the early diagnosis of cerebral lesions and might facilitate the prediction of stroke patient outcome.


Subject(s)
Chemokines, CC/blood , Stroke/blood , Stroke/mortality , Aged , Aged, 80 and over , Animals , Biomarkers/blood , Case-Control Studies , Chemokines/metabolism , Disease Models, Animal , Early Diagnosis , Female , Follow-Up Studies , Humans , Macrophage Inflammatory Proteins/blood , Male , Mice, Inbred C57BL , Neurons/metabolism , Neutrophils/metabolism , Prognosis , Rats, Wistar , Stroke/diagnosis , Up-Regulation
6.
Rev. nefrol. diál. traspl ; 34(1): 13-20, mar 2014. ilus, tab
Article in Spanish | LILACS | ID: lil-749979

ABSTRACT

La paratiroidectomía (PTx) es el tratamiento de elección en pacientes con HPT 2º severo, refractario al tratamiento médico. Se cuenta con muy poca información en Argentina de este procedimiento, por lo cual se realizó este estudio. Material y Métodos: Se incluyeron 255 pacientes con PTx entre el año 2003 al 2007 de un registro voluntario. Se evaluaron los estudios de localización prequirúrgicos, de laboratorio de metabolismo fosfocálcico previo y posterior a la cirugía y el tipo de técnica quirúrgica utilizada. Se analizó la persistencia y recidiva del HPT postcirugía. Resultados: La tasa de PTx fue de 2,7/1000 pacientes año. 83% de los pacientes tuvieron ecografía de cuello y 59% Sesta Mibi con Tc 99. Hubo una correlación positiva (p<0.001) entre el número de glándulas detectadas por ecografía y Sesta Mibi. La paratiroidectomía realizada fue: subtotal en 77%, total con autoimplante en 14% y total sin autoimplante en 9%. Hubo descensos significativos de Ca y P, fosfatasa alcalina y PTH (1744 ± 788 pg/ml a 247 ±450 pg/ml; p<0.0001) postcirugía. A los 2,4 ±2,5 meses de la PTx, el 72% de los pacientes tenía PTH <250 pg/ml, 19,8% tenía persistencia y 8,3% había recidivado. De acuerdo al tipo de cirugía la persistencia y recidiva fueron para PTx subtotal 22% y 8,3%, PTx total con implante 11% y 11% y PTx total sin autoimplante 13% y 4% respectivamente. La realización de Sesta Mibi no influyó en los resultados de la PTx. No se observaron diferencias entre los centros en relación con persistencia y recidiva. Conclusiones: La tasa de PTx fue muy baja, la ecografía fue el método de localización prequirúrgico preferido y la PTX subtotal la técnica quirúrgica más utilizada. La PTx fue exitosa en la mayoría de los pacientes y la persistencia y recidiva no estuvieron relacionadas con la técnica.


Parathyroidectomy (PTx) is the selecte treatment for patients with severe secondary hyperparathyroidism, refractory to medical treatment. There is not enough information about this procedure in Argentina, that is the reason why we performed this study. Material and Methods: 255 patients with PTx were included from the year 2003 to 2007 on a voluntary register. Studies of pre-surgical localization, phosphocalcic metabolism laboratories before and after surgery were evaluated, and the type of surgical technique used. The persistence and recurrence of post-surgical hyperparathyroidism was analyzed. Results: The PTx rate was 2,7/1000 patients year. 83% of the patients had neck echography and 59% Sestamibi scans with Tc 99. There was a positive correlation (p<0,001) between the number of detected glands by echography and Sestamibi. The parathyroidectomy performed was: subtotal in 77%, total with self-implant in 14% and total without self-implant in 9%. There were significant falls of Ca and P, Alkaline Phosphatase and PTH (1744±788 pg/ml to 247±450 pg/ml; p<0.0001) post-surgical. 2.4 ±2,5 months after the PTx, 72% of patients had PTH <250 pg/ml, 19,8% had persistence and 8,3% had recurrence. According to the type of surgery, the persistence and recurrence were for subtotal PTx 22% and 8,3%, total PTx with implant 11% and 11%, and total PTx without selfimplant 13% and 4% respectively. The performance of the Sestamibi scan did not affect the PTx results. No noticeable differences were observed among the centers for persistence and recurrence. Conclusions: The PTx rate was very low, echography was the preferred method of pre-surgical localization, and subtotal PTx was the most used surgical technique. PTx was successful in most of the patients, and persistence and recurrence were not related to the technique.


Subject(s)
Humans , Male , Female , Kidney Failure, Chronic , Parathyroidectomy/trends , General Surgery , Surgical Procedures, Operative , Recurrence
7.
Atherosclerosis ; 233(1): 186-9, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24529142

ABSTRACT

BACKGROUND AND PURPOSE: We prospectively examine the single and combined predictive value of biological and clinical markers in recurrent strokes related to intracranial atherosclerotic disease (ICAD). METHODS: In 73 ICAD first-ever stroke patients, ankle-brachial index (ABI) was assessed three months after TIA or stroke together with CRP, Lp-PLA2, ICAM-1, E-selectin and PAI-1 measurements. Appearance of new TIA/stroke was assessed every 6 months. RESULTS: After a median follow-up of 22.4 months, 13 patients (17.8%) suffered a new stroke or TIA. Risk of new cerebrovascular events (CVEs) was associated with lowered ABI (p=0.011), baseline PAI-1>22.52 ng/ml (<0.001), E-selectin>24.75 ng/ml (p = 0.008) and ICAM-1>205 ng/ml (p = 0.029). The combination of PAI-1 with ABI or ESRS reclassified 55.4% (p<0.005) and 48.3% (p<0.05) of patients between low, high and very high-risk categories. CONCLUSIONS: This tentative study shows that ABI and PAI-1 are associated with the risk of new CVEs in symptomatic ICAD patients, and their combination might improve identification of patients at higher risk.


Subject(s)
Intracranial Arteriosclerosis/diagnosis , Stroke/etiology , 1-Alkyl-2-acetylglycerophosphocholine Esterase/blood , Aged , Ankle Brachial Index , E-Selectin/blood , Female , Humans , Intercellular Adhesion Molecule-1/blood , Ischemic Attack, Transient , Longitudinal Studies , Male , Middle Aged , Plasminogen Activator Inhibitor 1/blood , Predictive Value of Tests , Recurrence , Risk Factors
8.
Cerebrovasc Dis ; 35(1): 81-8, 2013.
Article in English | MEDLINE | ID: mdl-23429001

ABSTRACT

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is an important cause of ischemic stroke (IS) and endothelial dysfunction plays a critical role in its onset and progression. Endothelial progenitor cells (EPCs) and endothelial production of angiogenic growth factors (AGFs) may play an essential role in this process. This study investigated the association of EPCs and AGFs with ICAD severity. METHODS: A total of 42 patients who had experienced a transient ischemic attack (TIA) or IS attributable to symptomatic ICAD were included. Clinical and neurosonological evaluations were conducted between 2.4 and 8.7 years after the initial cerebrovascular event. Severe ICAD was defined as the presence of at least 1 severe intracranial stenosis, and extensive ICAD as 3 or more intracranial stenoses. Blood samples were obtained to determine EPC levels using flow cytometry (CD34+KDR+ cells), and the plasma levels of several growth factors were assessed with a protein array (Searchlight(®)). Twenty-two individuals without cerebrovascular disease and with normal ultrasonographic examination were also included. RESULTS: No difference in the count of circulating EPCs was found between patients and controls, and a moderate increase in the number of EPCs/ml was noted in patients with extensive ICAD (p = 0.05). Patients presented decreased levels of fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-BB) compared with controls (p = 0.002, p = 0.079 and p = 0.061, respectively). Higher levels of FGF, VEGF and PDGF-BB were found in patients with severe ICAD (p = 0.007, p = 0.07 and p = 0.07, respectively), but there was no correlation between any AGFs and EPCs. CONCLUSIONS: Symptomatic ICAD patients have decreased levels of AGFs with no correlation to the number of circulating EPCs, while patients with severe ICAD have higher levels of EPCs, FGF, VEGF and PDGF-BBs. This suggests that reduced EPC and proangiogenic factor production capacity is implicated in ICAD pathogenesis, while the more severe forms of chronic brain hypoperfusion in ICAD patients might stimulate EPC mobilization and AGF production.


Subject(s)
Angiogenic Proteins/blood , Endothelial Cells/metabolism , Intracranial Arteriosclerosis/diagnosis , Stem Cells/metabolism , Aged , Analysis of Variance , Biomarkers/blood , Case-Control Studies , Cell Count , Down-Regulation , Endothelial Cells/pathology , Female , Flow Cytometry , Humans , Intracranial Arteriosclerosis/blood , Intracranial Arteriosclerosis/complications , Intracranial Arteriosclerosis/pathology , Ischemic Attack, Transient/etiology , Male , Middle Aged , Predictive Value of Tests , Protein Array Analysis , Risk Factors , Severity of Illness Index , Stem Cells/pathology , Stroke/etiology , Time Factors , Ultrasonography, Doppler, Transcranial
9.
J Neurol ; 259(12): 2538-45, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22592287

ABSTRACT

The risk of recurrent stroke is likely related to etiology. Therefore it is important to identify which patients are at highest early risk. We evaluated whether selected blood biomarkers may aid in the diagnosis of stroke etiology. We studied consecutive non-lacunar stroke patients between November 2006 and January 2007, and selected undetermined origin strokes. Blood samples were drawn at arrival to test brain natriuretic peptide (BNP), D-dimer, CK-MB, myoglobin, and troponin. Second harmonic transthoracic echocardiography (SHTTE) and ECG-24 h monitoring were also performed within the first 24 h. We evaluated 294 patients with ischemic stroke; 89 had an initial undetermined origin. After a cardiological work-up, 49 were diagnosed as embolic including atrial fibrillation (4), severe aortic arch atheromatosis (24), severe wall abnormalities (12), valve disease (3), dilated cardiomyopathy (1), and patent foramen (5). Higher levels of CK-MB, BNP, and myoglobin were found in patients with embolic source in SHTTE, but only CK-MB >1.5 ng/ml and BNP >64 pg/ml remained as independent predictors: BNP (OR 8.86; CI 95 % 2.79-28.09), CK-MB (OR 6.28; CI 95 % 1.66-23.69). BNP showed specificity of 75 %, sensitivity of 63.4 %, and positive predictive value (PPV) of 75.6 %. CK-MB had specificity of 85 %, sensitivity of 47.9 %, and PPV of 79.3 %. Measuring both biomarkers improves the finding of embolic source, increasing specificity to 95 % and PPV to 88.2 %. High-level CK-MB and BNP during the acute phase of ischemic stroke are associated with an embolic source. Measurement of both biomarkers may improve the diagnosis, guiding the need to perform a heart exploration.


Subject(s)
Brain Ischemia/blood , Creatine Kinase, MB Form/blood , Natriuretic Peptide, Brain/blood , Stroke/blood , Aged , Aged, 80 and over , Biomarkers/blood , Brain Ischemia/diagnostic imaging , Echocardiography , Embolism/blood , Embolism/diagnostic imaging , Female , Humans , Male , Middle Aged , Risk Factors , Stroke/diagnostic imaging
10.
J Intern Med ; 270(2): 166-74, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21198992

ABSTRACT

BACKGROUND AND AIMS: At present, a rapid and widely available diagnostic test for stroke remains elusive. The aim of this study was to examine the predictive value of a panel of blood-borne biochemical markers for stroke diagnosis. DESIGN: Consecutive patients with strokes or stroke-mimicking conditions (mimics) were evaluated within 24 h from symptom onset (915 strokes and 90 mimics). Blood samples were analysed by enzyme-linked immunosorbent assay for C-reactive protein, d-dimer, soluble receptor for advanced glycation end products (sRAGE), metalloproteinase 9 (MMP-9), S100B, brain natriuretic peptide, caspase-3, neurotrophin-3, chimerin and secretagogin. RESULTS: The main independent predictors of stroke versus mimics were caspase-3 >1.96 ng mL(-1) [odds ratio (OR) = 3.32; 95% confidence interval (CI) 1.88-5.88, P < 0.0001], d-dimer >0.27 µg mL(-1) (OR = 2.97; 95% CI 1.72-5.16, P = 0.0001), sRAGE >0.91 ng mL(-1) (OR = 2.19; 95% CI 1.26-3.83, P = 0.006), chimerin <1.11 ng mL(-1) (OR = 0.4; 95% CI 0.19-0.81, P = 0.011), secretagogin <0.24 ng mL(-1) (OR = 0.51; 95% CI 0.27-0.97, P = 0.041) and MMP-9 > 199 ng mL(-1) (OR = 1.66; 95% CI 1.01-2.73, P = 0.046). The model's predictive probability of stroke when the six biomarkers are above/below these cut-off levels was 99.01%. The best combination of biomarkers in the model was caspase-3 and d-dimer. Moreover, a model developed for samples obtained within the first 3 h showed high sensitivity (Se) and specificity (Sp) (threshold at 25th percentile: Se 0.87, Sp 0.55; threshold at 75th percentile: Se 0.28, Sp 0.99). CONCLUSIONS: A combination of biomarkers including caspase-3 and d-dimer appears to be the most promising to achieve a rapid biochemical diagnosis of stroke. If replicated, this approach could be used as a tool for urgent referral of stroke patients to hospitals in which acute treatments are available.


Subject(s)
Caspase 3/blood , Fibrin Fibrinogen Degradation Products/analysis , Stroke/diagnosis , Acute Disease , Aged , Aged, 80 and over , Biomarkers/blood , C-Reactive Protein/analysis , Chimerin Proteins/blood , Diagnosis, Differential , Female , Humans , Male , Matrix Metalloproteinase 9/blood , Middle Aged , Natriuretic Peptide, Brain/blood , Nerve Growth Factors/blood , Neurotrophin 3/blood , Predictive Value of Tests , Receptor for Advanced Glycation End Products , Receptors, Immunologic/blood , S100 Calcium Binding Protein beta Subunit , S100 Proteins/blood , Stroke/blood
11.
J Neurol ; 258(3): 486-93, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20967551

ABSTRACT

Osteopontin (OPN) is a multifunctional protein which has shown neuroprotective properties in animal models of cerebral ischemia. Nevertheless, its role in acute human stroke has not yet been established. Therefore, we aimed to determine human serum OPN level during acute ischemic stroke and its relationship with patient outcome. We measured OPN levels in 178 consecutive patients with a middle cerebral artery (MCA) occlusion who received fibrinolytic therapy and in 40 control subjects. OPN level was determined by an enzyme-linked immunosorbent assay (ELISA). Bad functional outcome was defined by modified Rankin Scale (mRS) score >2 at 3 months after stroke onset. A logistic regression analysis was performed to determine factors that could be independently associated with poor prognosis. OPN levels among stroke patients did not differ from the controls' OPN levels (16.65 vs. 17.83 ng/mL, p = 0.404). Interestingly, OPN level was increased among those patients who showed worse prognosis at 3 months (19.96 vs. 15.48 ng/mL, p = 0.040). In a logistic regression model, an OPN level >27.22 ng/mL was found to be an independent factor for a bad outcome (OR 5.01, 95% CI 1.60-15.72, p = 0.006) after adjusting for potential confounders. Those patients showing higher OPN levels before tPA administration displayed a worse prognosis compared to those with lower OPN levels. Further research is necessary to elucidate the role of OPN in ischemic stroke pathophysiology and validate OPN as a useful tool to predict long-term stroke outcome.


Subject(s)
Brain Ischemia/blood , Brain Ischemia/diagnosis , Osteopontin/blood , Recovery of Function/physiology , Stroke/blood , Stroke/diagnosis , Aged , Aged, 80 and over , Biomarkers/blood , Brain Ischemia/physiopathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Predictive Value of Tests , Stroke/physiopathology , Time Factors , Treatment Outcome
12.
Rev. argent. reumatol ; 21(2): 46-53, 2010. graf
Article in Spanish | LILACS | ID: lil-576277

ABSTRACT

Objetivo: Describir los eventos adversos (EA) asociados a ciclofosfamiday su relación con la dosis acumulada. Material y método: Se revisaron las historias clínicas de pacientes con LES (Criterios ACR) de 6 centros de Reumatología de la Argentina. Se incluyeron 81 pacientes (72 mujeres y 9 hombres) que habían recibido tratamiento con pulsos mensuales de CIC (0,5-1g/m2). Se estudiaron los EA asociados a CIC, dosis acumulada, dosis de corticosteroides y actividad de la enfermedad al momento del evento. Se excluyeron los pacientes con otro tratamiento inmunosupresor. Resultados: La edad de diagnóstico del LES fue x¯ 26 años (DS 11,3); tiempo de evolución de la enfermedad x¯ 6,2 años (DS 5,9). La edad al inicio de CIC fue x¯ 30 años (DS 12,4). Se encontraron 105 eventos adversos asociados a CIC en 53 pacientes (65,4%). Infección (45%) fue el efecto más frecuente, fatal en 6 pacientes; intolerancia gástrica (náuseas y vómitos) en 21% y las citopenias 14,3%. Tres pacientes (2,8%) presentaron amenorrea y sólo una cistitis hemorrágica. No se detectaron neoplasias. La mediana de dosis acumulada al momento del EA fue 2600 mg. Al comparar los pacientes con y sin EA, no se encontraron diferencias significativas en el SLEDAI ni en la dosis de prednisona recibida. No se encontró asociación entre dosis acumulada de CIC y náuseas, vómitos, convulsiones y citopenias (p NS). Al aplicar el modelo de riesgo proporcional para eventos múltiples, el riesgo de infecciones aumentaba a mayor dosis de CIC. Los pacientes que fallecieron por sepsis recibieron una dosis mediana de CIC de 4000 mg. Conclusiones: 1) La dosis acumulada de CIC se asoció a infecciones: mayor dosis, mayor número de infecciones. 2) Náuseas, vómitos, convulsiones y citopenias fueron eventos independientes de la dosis de CIC.


Subject(s)
Cyclophosphamide , Lupus Erythematosus, Systemic
13.
Rev. argent. reumatol ; 21(2): 46-53, 2010. graf
Article in Spanish | BINACIS | ID: bin-125430

ABSTRACT

Objetivo: Describir los eventos adversos (EA) asociados a ciclofosfamiday su relación con la dosis acumulada. Material y método: Se revisaron las historias clínicas de pacientes con LES (Criterios ACR) de 6 centros de Reumatología de la Argentina. Se incluyeron 81 pacientes (72 mujeres y 9 hombres) que habían recibido tratamiento con pulsos mensuales de CIC (0,5-1g/m2). Se estudiaron los EA asociados a CIC, dosis acumulada, dosis de corticosteroides y actividad de la enfermedad al momento del evento. Se excluyeron los pacientes con otro tratamiento inmunosupresor. Resultados: La edad de diagnóstico del LES fue x¯ 26 años (DS 11,3); tiempo de evolución de la enfermedad x¯ 6,2 años (DS 5,9). La edad al inicio de CIC fue x¯ 30 años (DS 12,4). Se encontraron 105 eventos adversos asociados a CIC en 53 pacientes (65,4%). Infección (45%) fue el efecto más frecuente, fatal en 6 pacientes; intolerancia gástrica (náuseas y vómitos) en 21% y las citopenias 14,3%. Tres pacientes (2,8%) presentaron amenorrea y sólo una cistitis hemorrágica. No se detectaron neoplasias. La mediana de dosis acumulada al momento del EA fue 2600 mg. Al comparar los pacientes con y sin EA, no se encontraron diferencias significativas en el SLEDAI ni en la dosis de prednisona recibida. No se encontró asociación entre dosis acumulada de CIC y náuseas, vómitos, convulsiones y citopenias (p NS). Al aplicar el modelo de riesgo proporcional para eventos múltiples, el riesgo de infecciones aumentaba a mayor dosis de CIC. Los pacientes que fallecieron por sepsis recibieron una dosis mediana de CIC de 4000 mg. Conclusiones: 1) La dosis acumulada de CIC se asoció a infecciones: mayor dosis, mayor número de infecciones. 2) Náuseas, vómitos, convulsiones y citopenias fueron eventos independientes de la dosis de CIC.(AU)


Subject(s)
Cyclophosphamide , Lupus Erythematosus, Systemic
14.
Theriogenology ; 72(8): 1017-22, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19747718

ABSTRACT

The aim of this work was to study the effects of dilution and centrifugation (i.e., two methods of reducing the influence of the seminal plasma) on the survival of spermatozoa and the structure of motile sperm cell subpopulations in refrigerated Catalonian donkey (Equus asinus) semen. Fifty ejaculates from nine Catalonian jackasses were collected. Gel-free semen was diluted 1:1, 1:5 or 1:10 with Kenney extender. Another sample of semen was diluted 1:5, centrifuged, and then resuspended with Kenney extender until a final dilution of 25x10(6) sperm/ml was achieved (C). After 24 h, 48 h or 72 h of refrigerated storage at 5 degrees C, aliquots of these semen samples were incubated at 37 degrees C for 5 min. The percentage of viable sperm was determined by staining with eosin-nigrosin. The motility characteristics of the spermatozoa were examined using the CASA system (Microptic, Barcelona, Spain). At 24h, more surviving spermatozoa were seen in the more diluted and in the centrifuged semen samples (1:1 48.71%; 1:5 56.58%, 1:10 62.65%; C 72.40%). These differences were maintained at 48 h (1:1 34.31%, 1:5 40.56%, 1:10 48.52%, C 66.30%). After 72 h, only the C samples showed a survival rate of above 25%. The four known donkey motile sperm subpopulations were maintained by refrigeration. However, the percentage of motile sperms in each subpopulation changed with dilution. Only the centrifuged samples, and only at 24h, showed exactly the same motile sperm subpopulation proportions as recorded for fresh sperm. However, the 1:10 dilutions at 24 and 48 h, and the centrifuged semen at 48 h, showed few variations compared to fresh sperm. These results show that the elimination of seminal plasma increases the survival of spermatozoa and the maintenance of motility patterns. The initial sperm concentration had a significant (P<0.05) influence on centrifugation efficacy, but did not influence the number of spermatozoa damaged by centrifugation. In contrast, the percentage of live spermatozoa in the fresh semen significantly influenced the number of spermatozoa damaged by centrifugation, but not centrifugation efficacy.


Subject(s)
Equidae , Refrigeration , Semen Preservation , Semen/cytology , Spermatozoa/cytology , Animals , Cell Culture Techniques , Centrifugation , Male , Semen Analysis
15.
Neurosci Lett ; 430(1): 1-6, 2008 Jan 03.
Article in English | MEDLINE | ID: mdl-18055116

ABSTRACT

Our aim was to investigate caspase-3 plasma levels after stroke, its correlation with infarct expansion and neurological outcome. Caspase-3 plasma levels were determined by ELISA at different time points after stroke in 116 t-PA-treated patients and a control group of 40 healthy controls. Neurological status was evaluated by NIHSS scores and functional outcome by modified Rankin Scale. To assess brain infarct growth, serial brain magnetic resonance imaging scans including diffusion- (DWI) and perfusion-weighted (PWI) images were performed in a subgroup of 58 patients. Plasma caspase-3 levels were higher in stroke patients versus the control group throughout the acute phase of stroke. Furthermore, caspase-3 level at 24h was associated with poorer short- and long-term neurological outcome and positively correlated with infarct growth assessed by diffusion-weighted images. Our data suggest that caspase-3 could be involved in recruitment of ischemic brain tissue being a marker of infarct growth.


Subject(s)
Biomarkers/blood , Brain Infarction/enzymology , Caspase 3/blood , Stroke/enzymology , Aged , Brain/enzymology , Brain/pathology , Brain Infarction/blood , Brain Infarction/pathology , Diffusion Magnetic Resonance Imaging , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Stroke/blood , Stroke/pathology
16.
Neurologia ; 21(4): 176-80, 2006 May.
Article in Spanish | MEDLINE | ID: mdl-16832771

ABSTRACT

INTRODUCTION: Apolipoprotein E has been associated with intracerebral hemorrhages and with neurological outcome of ischemic stroke patients treated with rt-PA. Therefore, we hypothesized that ApoE genotype might influence the appearance of post-tPA hemorrhagic transformation and that the favorable outcome of E2 patients might be due to better rates of recanalization. PATIENTS AND METHODS: We analyzed the ApoE genotype of 77 patients with ischemic stroke involving the territory of the middle cerebral artery who received rt- PA within 3 h of symptoms onset. The hemorrhagic events were evaluated by computed tomography and the arterial recanalization by transcraneal doppler. RESULTS: We did not observe any association between ApoE genotypes and the rates of hemorrhagic transformation following rt-PA treatment (E2 = 33.3 %, E3 = 32.7%, E4=11.8%; p=0.241). Rates of artery recanalization following thrombolysis were similar regarding ApoE genotypes at 1 hour post-tPA administration (E2=40%, E3+E4=45.9%; p=0.799), at 6 hours post-tPA (E2=80%, E3+E4=62.3 %; p=0.43) or at 24 hours post-tPA (E2= 100%, E3+E4=75%, p=0.203). No association was observed between ApoE genotypes and NIHSS scores at 48 hours (E2=8, E3+E4=12; p=0.811) nor with the modified ranking scale at 3 months (E2=1.5, E3+E4=4; p=0.350). CONCLUSIONS: In our group of stroke patients, ApoE genotypes are not related with the presence of hemorrhagic transformations neither with the rates of recanalization following thrombolytic treatment.


Subject(s)
Apolipoproteins E/genetics , Fibrinolytic Agents/therapeutic use , Stroke/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/therapeutic use , Aged , Female , Genotype , Humans , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/pathology , Stroke/pathology
17.
Neurología (Barc., Ed. impr.) ; 21(4): 176-180, mayo 2006. tab, graf
Article in Es | IBECS | ID: ibc-048784

ABSTRACT

Introducción. Estudios previos relacionaban la apolipoproteína E (ApoE) con la aparición de hemorragias intracerebrales y con el pronóstico de pacientes con ictus isquémicos tratados con rt-PA. Por ello hipotetizamos que el genotipo ApoE podría influir en la aparición de transformaciones hemorragicas (TH) post-tPA y que el pronóstico favorable de los pacientes E2 podía ser debido a una mejor recanalización de la arteria en este grupo de pacientes. Pacientes y métodos. Analizamos el genotipo ApoE en una serie de 77 pacientes con ictus isquémicos del territorio de la arteria cerebral media a los que se les había administrado rt-PA <3 h desde el inicio de los síntomas. Las TH fueron evaluadas mediante tomografía computarizada y la recanalización arterial mediante doppler transcraneal. Resultados. No se observó asociación entre el genotipo ApoE y las TH post-tPA (E2 = 33.3 %, E3 = 32.7%, E4=11.8%; p=0.241). Tampoco observamos ninguna asociación respecto a la recanalización de la arteria a la hora de la infusión del rt-PA (E2=40%, E3+E4=45.9%; p=0.799), ni a las 6 h (E2=80%, E3+E4=62.3 %; p=0.43) ni a las 24 h (E2= 100%, E3+E4=75%, p=0.203). No se observó tampoco relación con la NIHSS a las 48 h (E2=8, E3+E4=12; p=0.811) o con la escala Ranking modificada. a los 3 meses (E2=1.5, E3+E4=4; p=0.350). Conclusiones. En nuestro grupo de pacientes con ictus ninguno de los genotipos ApoE predice la aparición de complicaciones hemorragicas ni se relaciona con unos mayores índices de recanalización tras el tratamiento trombolítico


INTRODUCTION: Apolipoprotein E has been associated with intracerebral hemorrhages and with neurological outcome of ischemic stroke patients treated with rt-PA. Therefore, we hypothesized that ApoE genotype might influence the appearance of post-tPA hemorrhagic transformation and that the favorable outcome of E2 patients might be due to better rates of recanalization. PATIENTS AND METHODS: We analyzed the ApoE genotype of 77 patients with ischemic stroke involving the territory of the middle cerebral artery who received rt- PA within 3 h of symptoms onset. The hemorrhagic events were evaluated by computed tomography and the arterial recanalization by transcraneal doppler. RESULTS: We did not observe any association between ApoE genotypes and the rates of hemorrhagic transformation following rt-PA treatment (E2 = 33.3 %, E3 = 32.7%, E4=11.8%; p=0.241). Rates of artery recanalization following thrombolysis were similar regarding ApoE genotypes at 1 hour post-tPA administration (E2=40%, E3+E4=45.9%; p=0.799), at 6 hours post-tPA (E2=80%, E3+E4=62.3 %; p=0.43) or at 24 hours post-tPA (E2= 100%, E3+E4=75%, p=0.203). No association was observed between ApoE genotypes and NIHSS scores at 48 hours (E2=8, E3+E4=12; p=0.811) nor with the modified ranking scale at 3 months (E2=1.5, E3+E4=4; p=0.350). CONCLUSIONS: In our group of stroke patients, ApoE genotypes are not related with the presence of hemorrhagic transformations neither with the rates of recanalization following thrombolytic treatment


Subject(s)
Female , Aged , Humans , Apolipoproteins E/genetics , Stroke/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/therapeutic use , Fibrinolytic Agents/therapeutic use , Stroke/pathology , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/pathology , Genotype
18.
Nefrologia ; 23 Suppl 2: 95-9, 2003.
Article in Spanish | MEDLINE | ID: mdl-12778863

ABSTRACT

Hyperphosphatemia is an important risk factor of secondary hyperparathyroidism and extraosseous calcifications in chronic renal failure patients. In this study our hypothesis is that physicians misconception of adequate phosphatemia is a risk factor for hyperphosphatemia. In 1999 GEMOR sent a renal osteodystrophy inquiry to different hemodialysis centers in Argentina. It included 80 dialysis centers in 17 Argentinian provinces. The enquire had 33 questions about renal osteodystrophy. Here we report the section related to phosphorous metabolism. We obtained responses from 80 dialysis centers (4,512 dialysis patients), which represents about 24% of Argentinian dialysis centers. Physicians considered phosphorous levels between 4.5 to 5.5 mg/dl in 83.5% of centers as adequate, and between 5.5 to 6.5 mg/dl in 10.1%. Five out of 77 centers reported that they had no patients with hyperphosphatemia. The percentage of hemodialysis patients that had more than 6 mg/dl in each center was 28.8 +/- 15.9%. Those centers that aimed for phosphatemia between 5.5 and 6.5 mg/dl, had a higher percentage of patients with phosphatemia above 6 mg/dl than those aiming for between 4.5 and 5.5 mg/dl (42.8 +/- 16.7 vs 27.1 +/- 15.2% respectively, p = 0.007), and had higher mean of phosphatemia (6.4 +/- 0.7 vs 5.3 +/- 0.7 mg/dl respectively, p = 0.0001), than the last group. In conclusion, a higher mean phosphate level was obtained in hemodialysis centers where physicians considered higher pre-dialysis target levels. Some centers had no patients with hyperphosphatemia (neglect or good control?).


Subject(s)
Attitude of Health Personnel , Chronic Kidney Disease-Mineral and Bone Disorder/prevention & control , Phosphates/blood , Physicians/psychology , Argentina , Blood Chemical Analysis/statistics & numerical data , Calcinosis/blood , Calcinosis/etiology , Calcium/blood , Chelation Therapy/statistics & numerical data , Chronic Kidney Disease-Mineral and Bone Disorder/blood , Chronic Kidney Disease-Mineral and Bone Disorder/etiology , Culture , Diagnostic Tests, Routine/statistics & numerical data , Health Surveys , Hemodialysis Units, Hospital/statistics & numerical data , Humans , Hyperparathyroidism, Secondary/blood , Hyperparathyroidism, Secondary/drug therapy , Hyperparathyroidism, Secondary/etiology , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Phosphorus/blood , Practice Patterns, Physicians'/statistics & numerical data , Reference Values , Renal Dialysis/adverse effects , Risk Factors , Vitamin D/therapeutic use
19.
Nefrologia ; 23 Suppl 2: 112-6, 2003.
Article in Spanish | MEDLINE | ID: mdl-12778866

ABSTRACT

The present paper aims to assess radiographic vascular and soft parts calcifications occurrence and its correlation with biochemical profiles. The study was performed in 47 patients (ten diabetic patients), 49 years old, who had been on dialysis for a period of 51 months. Vascular calcifications (VCs) were classified as proximal, distal and soft tissues. In addition, Ca, P, CaxP values in the six months prior to the recruitment period, PTH, FAL and calcium carbonate, calcium acetate, and vitamin D3 intake were determined. A higher frequency of VCs was observed in diabetics, yielding a significant association with proximal 60% (p = 0.05) and almost significant with distal calcifications 70% (p = 0.07). Likewise, a lower CaxP was noted for diabetic VCs in comparison to that seen in non-diabetic VCs (p < 0.05). Proximal and distal VCs in the non-diabetics population were 25% and 20%, respectively; and tissue calcifications were 24%. Age was correlated with proximal and distal VCs (p < 0.01). A higher CaxP was observed in patients with VCs and it yielded an even higher value for tissue calcifications. Lastly, calcium acetate and overall calcium intake was higher in patients with tissue calcifications (p = 0.05). VCs were more frequent in diabetics and they also showed a lower CaxP. VCs in non-diabetics were correlated with CaxP values, whereas tissue calcifications were associated with calcium intake. Therefore, the management of renal osteodystrophy should be changed in order to prevent calcifications as well as to decrease morbidity in hemodialysis patients.


Subject(s)
Calcinosis/etiology , Chronic Kidney Disease-Mineral and Bone Disorder/etiology , Kidney Failure, Chronic/complications , Renal Dialysis/adverse effects , Vascular Diseases/etiology , Acetates/administration & dosage , Acetates/analysis , Adult , Aged , Argentina/epidemiology , Calcinosis/blood , Calcinosis/diagnostic imaging , Calcium/blood , Calcium Compounds , Calcium, Dietary/adverse effects , Chronic Kidney Disease-Mineral and Bone Disorder/prevention & control , Diabetic Nephropathies/complications , Diabetic Nephropathies/therapy , Female , Hemodialysis Solutions/adverse effects , Hemodialysis Solutions/chemistry , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/therapy , Male , Middle Aged , Organ Specificity , Phosphorus/blood , Radiography , Vascular Diseases/blood , Vascular Diseases/diagnostic imaging
20.
Nefrología (Madr.) ; 23(supl.2): 95-99, 2003. graf
Article in Spanish | IBECS | ID: ibc-148534

ABSTRACT

En 1999 GEMOR realizó una encuesta entre centros de diálisis de Argentina para conocer la realidad de dicha patología en el país. Presentamos los resultados relacionados al fósforo. Participaron 80 centros de diálisis (24% de los centros nacionales), donde dializaban 4.512 pacientes (34% del país). El 95% determinaban Calcio y Fósforo sérico en forma mensual. El 83,5% pretendía en sus pacientes una fosfatemia entre 4,5 y 5,5 mg/dl, mientras que en el 10,1% el objetivo estaba entre 5,5 y 6,5 mg/dl. La media porcentual de fosfatemia superior a 6 mg/dl fue del 28,8 ± 15,9%. Cinco de 77 centros reportaron que no tenían pacientes hiperfosfatémicos en la última determinación mensual. Los que pretendían una fosfatemia entre 5,5 y 6,5 mg/dl, tenían un porcentaje de pacientes con fosfatemia mayor de 6 mg/dl superior a aquellos que pretendían entre 4,5 y 5,5 mg/dl (42,8 ± 16,7 vs 27,1 ± 15,2% respectivamente, p = 0,007). Mientras que la media de fosfatemia también fue superior (6,4 ± 0,7 vs 5,3 ± 0,7 mg/dl respectivamente, p = 0,0001). Esto sugiere que los centros donde se pretendía mayor fosfatemia tenían más casos de hiperfosfatemia. Existen centros sin pacientes hiperfosfatémicos. Esto supone o un buen control de la fosfatemia o resultados de laboratorio «falsos negativos» (AU)


Hyperphosphatemia is an important risk factor of secondary hyperparathyroidism and extraosseous calcifications in chronic renal failure patients. In this study our hypothesis is that physicians misconception of adequate phosphatemia is a risk factor for hyperphosphatemia. In 1999 GEMOR sent a renal osteodystrophy inquiry to different hemodialysis centers in Argentina. It included 80 dialysis centers in 17 Argentinian provinces. The enquire had 33 questions about renal osteodystrophy. Here we report the section related to phosphorous metabolism. We obtained responses from 80 dialysis centers (4,512 dialysis patients), which represents about 24% of Argentinian dialysis centers. Physicians considered phosphorous levels between 4.5 to 5.5 mg/dl in 83.5% of centers as adequate, and between 5.5 to 6.5 mg/dl in 10.1%. Five out of 77 centers reported that they had no patients with hyperphosphatemia. The percentage of hemodialysis patients that had more than 6 mg/dl in each center was 28.8 ± 15.9%. Those centers that aimed for phosphatemia between 5.5 and 6.5 mg/dl, had a higher percentage of patients with phosphatemia above 6 mg/dl than those aiming for between 4.5 and 5.5 mg/dl (42.8 ± 16.7 vs 27.1 ± 15.2% respectively, p = 0.007), and had higher mean of phosphatemia (6.4 ± 0.7 vs 5.3 ± 0.7 mg/dl respectively, p = 0.0001), than the last group. In conclusion, a higher mean phosphate level was obtained in hemodialysis centers where physicians considered higher pre-dialysis target levels. Some centers had no patients with hyperphosphatemia (neglect or good control?) (AU)


Subject(s)
Humans , Physicians/psychology , Phosphates/blood , Chronic Kidney Disease-Mineral and Bone Disorder/prevention & control , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Hyperparathyroidism, Secondary/blood , Hyperparathyroidism, Secondary/drug therapy , Hyperparathyroidism, Secondary/etiology , Attitude of Health Personnel , Argentina , Calcinosis/blood , Calcinosis/etiology , Calcium/blood , Chelation Therapy , Culture , Chronic Kidney Disease-Mineral and Bone Disorder/blood , Chronic Kidney Disease-Mineral and Bone Disorder/etiology , Vitamin D/therapeutic use , Risk Factors , Reference Values , Renal Dialysis/adverse effects , Phosphorus/blood , Blood Chemical Analysis , Diagnostic Tests, Routine , /statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Health Surveys
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