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Biomedical subjects

Miguel Rivera

Publications and source records attributed to Miguel Rivera.

15 recordsLinked to original sources

Diagnostic and prognostic value of urine NT-proBNP levels in heart failure patients.

BACKGROUND: Plasma NT-proBNP levels are sensitive markers of ventricular dysfunction. However, studies of natriuretic peptides in urine are limited. AIMS: To compare urine and plasma NT-proBNP levels and to investigate the diagnostic and prognostic value of urine levels in heart failure (HF). METHODS: Urinary and plasma NT-proBNP levels were measured in 96 HF patients and 20 control subjects. The patients were functionally classified according to the NYHA criteria. RESULTS: Urine NT-proBNP was higher in HF patients than in control subjects (94+/-31 pg/ml vs. 67+/-6 pg/ml, p<0.0001), correlating with plasma NT-proBNP levels (r=0.78, p<0.0001). Urinary levels were elevated in the more severe functional classes and diminished in obese patients. Urine NT-proBNP was a good tool for diagnosis of HF, the area under the curve (AUC) being 0.96+/-0.02 (p<0.0001), and for predicting 12-month cardiac events (p=0.011). To determine the prognostic power of urinary NT-proBNP in detecting 12-month cardiac mortality, we obtained an AUC of 0.75+/-0.10 (p=0.015). CONCLUSION: Urinary NT-proBNP, a relatively simple non-invasive test, is a new candidate marker for the diagnosis and evaluation of prognosis in HF and for the characterization of functional status in these patients.

Aged↗

Maximum longitudinal relaxation velocity of the left ventricle: its clinical value and relationship with NT-proBNP plasma levels in heart failure.

BACKGROUND: M-mode recordings of the mitral annulus to measure the maximum ascending velocity during early diastole as an expression of maximum longitudinal relaxation velocity of the left ventricle (RVm) can be used as an index of left ventricular (LV) diastolic function. The purpose of this study was to determine the relationship of RVm with LV functional parameters in patients with heart failure, with N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels, and with their functional classification. METHODS AND RESULTS: RVm was recorded in 97 patients by M-mode echocardiography. Patients were classified according to the New York Heart Association (NYHA) and the concentration of NT-proBNP was determined. Patients with ejection fraction (EF)>40 showed a significant correlation between RVm and mitral annulus motion (MAM), mitral flow propagation velocity, E/A, age, deceleration time (DT), and NT-proBNP. In patients with EF 40, though its relationship with NT-proBNP both in patients with EF>or 40 it is influenced only by age. RVm values showed a significant decrease in NYHA class II and III.

Aged↗

[Myocardial remodeling and immunologic activation in patients with heart failure].

INTRODUCTION AND OBJECTIVES: Immune response-mediated regulation of myocardial collagen remains poorly understood. Our objective was to investigate the relationship between ventricular remodeling and immunologic activation in patients with heart failure (HF) by comparing dilated and ischemic cardiomyopathy. METHODS: We studied 94 patients with HF and dilated cardiomyopathy (n=46) or ischemic cardiomyopathy (n=48). We recorded left ventricular (LV) volumes, E/A ratio, and ejection fraction. Plasma concentrations of tumor necrosis factor alpha (TNFalpha), soluble TNFa receptor I (sTNF-RI), sTNF-RII, interleukin-6 (IL-6) and IL-10 were measured. The serum procollagen type-III amino-terminal propeptide (PIIINP) level was also obtained. RESULTS: Ventricular volumes were greater in the dilated cardiomyopathy than in the ischemic cardiomyopathy group (P< .05). However, sTNF-RI, sTNF-RII and PIIINP levels were higher in the ischemic group (P< .05). In this group, there were significant correlations between ventricular volumes and IL-10 and sTNF-RII levels. There was also a significant correlation between PIIINP and sTNF-RII levels (r=0.30; P< .05). In the dilated cardiomyopathy group, there was a significant correlation between ventricular volumes and IL-10 level, and between PIIINP level and IL-6 (r=0.32; P< .05) and sTNF-RII levels (r=0.32; P< .05). Multiple linear regression analysis, which included cytokine levels, age, sex and ventricular function, showed that the sTNF-RII level was an independent predictor of the PIIINP level (adjusted r(2)=0.16; P< .0001) and of ventricular volumes (LV end-systolic volume index, adjusted r(2)=0.034; P< .05; and LV end-diastolic volume index, adjusted r(2)=.048; P< .05) in both groups. CONCLUSIONS: In HF, there is an interaction between proinflammatory cytokines and the extracellular matrix. Immunologic implications vary according to disease etiology. The elevation in proinflammatory cytokine and PIIINP levels is greater in patients with ischemic cardiomyopathy. Multiple regression analysis showed that the sTNF-RII level was an independent predictor of ventricular remodeling.

Aged↗

[8-hydroxy-2'-deoxyguanosine and lipid peroxidation in patients with heart failure].

INTRODUCTION AND OBJECTIVES: Heart failure is associated with increased free radical production, which leads to a state of oxidative stress. Known markers of oxidative stress include 8-hydroxy-2'-deoxyguanosine, which reflects oxidative damage to DNA, and lipid peroxidation, which can be used to quantify damage to lipid-rich structures. The aims of this study were to compare 8-hydroxy-2'-deoxyguanosine and lipid peroxidation levels in heart failure patients and healthy subjects and to assess how these levels are influenced by heart failure etiology. METHODS: The study included 78 patients (57 male, age 64 [14] years) with heart failure and 12 control subjects. Patients completed a questionnaire and were graded according to the New York Heart Association classification. Doppler echocardiography was performed and blood samples were obtained. 8-hydroxy-2'-deoxyguanosine and lipid peroxidation levels were determined. RESULTS: Significant differences were observed between patients and control subjects in 8-hydroxy-2'-deoxyguanosine and lipid peroxidation levels, at 0.34 (0.54) ng/mL vs 0.04 (0.07) ng/mL (P<.05), and 18 (10) microM vs 8 (3) microM (P<.01), respectively. Subsequent analysis showed that heart failure etiology had a significant effect on the levels of the two markers (P<.05), which were highest in patients with hypertensive cardiomyopathy. CONCLUSIONS: Levels of 8-hydroxy-2'-deoxyguanosine and lipid peroxidation were higher in heart failure patients than in control subjects. The most significant increases were found in patients with hypertensive cardiomyopathy.

8-Hydroxy-2'-Deoxyguanosine↗

Obese subjects with heart failure have lower N-terminal pro-brain natriuretic peptide plasma levels irrespective of aetiology.

N-terminal pro-brain natriuretic peptide (NT-proBNP) may be useful in the diagnosis of heart failure and ventricular dysfunction. Obesity is an independent cardiovascular risk factor. The purpose of this study was to measure NT-proBNP plasma levels in obese and non-obese subjects with heart failure and to compare levels in subjects with ischaemic and dilated aetiology. In this study, obese subjects had 63% lower NT-proBNP plasma levels than non-obese subjects (p < 0.01). In multivariate analysis, BMI was inversely associated with NT-proBNP plasma levels (p < 0.05) and a 17% decrease in natriuretic peptide levels was attributed to obesity (p < 0.036). When we analyzed data according to the aetiology of heart failure, we found that both groups (ischaemic and dilated) had a 65% decrease in NT-proBNP plasma levels in obese subjects compared to non-obese subjects.

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[Plasma concentration of big endothelin-1 and its relation with plasma NT-proBNP and ventricular function in heart failure patients].

INTRODUCTION AND OBJECTIVES: Elevated plasma concentrations of big endothelin-1 (big ET-1) are related with severity and prognosis in patients with heart failure, and N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of ventricular remodeling. The purpose of this study was to investigate the relationship between plasma levels of big ET-1 and NT-proBNP, and between the former and ventricular function. PATIENTS AND METHOD: We studied 103 patients with heart failure (75 men, mean age 63 [13] years). Each participant completed a questionnaire and underwent Doppler echocardiographic study to measure ejection fraction (EF), mitral flow propagation velocity (Vp) and atrioventricular plane displacement (AVPD). Blood samples were also taken to determine plasma levels of big ET-1, aldosterone and NT-proBNP. RESULTS: For the whole population big ET-1 concentration was 1.03 [0.75] fmol/m, NT-proBNP 619 (307-1328) pg/mL, aldosterone 168 [102] pg/mL, EF 37 [10], Vp 37 [11] cm/s, and AVPD 8.0 [1.7] mm. Plasma big ET-1 correlated positively with plasma NT-proBNP (r=0.50, P<.0001). However, a negative correlation was found between big ET-1 and EF (r=-0.30, P<.01), Vp, (r=-0.30, P<.01) and AVPD (r=-0.21, P<.05). When ET-1 levels were divided into quartiles and the corresponding NT-proBNP, EF, Vp and AVPD values were compared, we found significant differences (ANOVA P<.0001, P<.01, P<.05 and P<.05, respectively). CONCLUSIONS: Plasma levels of big ET-1 correlated positively with NT-proBNP levels and inversely with EF, Vp and AVPD. These findings help clarify the relationships between ventricular function and the neurohormonal activation involved in heart failure, and may aid the search for therapeutic interventions.

Endothelin-1↗

Soluble TNF-alpha and interleukin-6 receptors in the urine of heart failure patients. Their clinical value and relationship with plasma levels.

BACKGROUND: Proinflammatory cytokines are important mediators in heart failure (HF). Recently, urinary levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) have been determined. AIMS: The purpose of this study was to measure the urinary levels of TNF-alpha and IL-6 receptors, sTNF-RI, sTNF-RII, sIL-6R, and the relationship with plasma levels and NYHA classes in HF. METHODS: Plasma and urine were collected from 114 HF patients and sTNF-RI, sTNF-RII and sIL-6R (ng/ml) were analyzed. RESULTS: For the whole population, plasma levels of sTNF-RI were 2.1+/-0.1, of sTNF-RII were 5.0+/-0.3 and of sIL-6R were 49.8+/-2.5. Urinary levels were: sTNF-RI, 2.8+/-0.5, r=0.5, p<0.001; sTNF-RII, 12.6+/-2.1, r=0.4, p<0.001; and sIL-6R, 4.2+/-0.4, NS. In NYHA III subjects, we found sTNF-RI, r=0.6, p<0.01, sTNF-RII, r=0.5, p<0.05, and sILR-6, r=0.5, p<0.05. Both plasma TNF receptors and urinary levels of sTNF-RII were higher in patients in a more severe NYHA class (p<0.05). CONCLUSIONS: Urine is a good environment to study sTNF-RI and sTNF-RII, and this fact has diagnostic and prognostic implications. Plasma and urinary levels of TNF receptors showed a fair correlation, which was increased in higher NYHA classes. Plasma and urinary levels of sIL6R showed a good correlation in NYHA III. The TNF receptor levels in urine increased in patients with more severe HF.

Aged↗

[NT-proBNP levels and hypertension. Their importance in the diagnosis of heart failure].

INTRODUCTION: N-terminal pro-brain natriuretic peptide (NT-proBNP) is useful in the diagnosis of heart failure. We compared NT-proBNP levels in patients with and without a diagnosis of arterial hypertension. PATIENTS AND METHOD: Participants were recruited from a random sample of 999 inhabitants from the Community of Valencia (eastern Spain). Of these patients, 432 said they suffered from dyspnea and were referred to their hospital (10 hospitals involved), where blood samples were taken, an echo-Doppler study was performed, and the patients completed a questionnaire. Of the 432 participants with dyspnea, 215 gave informed consent for their inclusion in the study, and 202 completed the study. Hypertension was diagnosed in 72 participants and 130 were normotensive. RESULTS: For the whole population, NT-proBNP, expressed as the median and range, was 88 (0-2586) pg/mL. When we compared hypertensive with normotensive participants, we found higher NT-proBNP levels in the former group: median 123, range 0-2184 pg/mL, versus median 77, range 0-2586 pg/mL (P<.01). When we excluded subjects with systolic left ventricular dysfunction, we found higher levels in participants with hypertension: 119 (0-2184 pg/mL) vs 72 (0-997 pg/mL) (P<.01). When we also excluded subjects with diastolic dysfunction, we found (median 85, range 0-430 pg/mL) and (median 66, range 0-997 pg/mL), respectively (p = NS). CONCLUSION: In a population study of subjects with dyspnea, hypertensive patients have higher NT-proBNP levels than subjects with normal blood pressure. This difference disappeared when patients with diastolic dysfunction were excluded from the analysis. Hypertension can thus be a confounding factor that potentially decreases the specificity of NT-proBNP levels for the diagnosis of heart failure. These findings should be taken into account when conducting clinical and epidemiological studies in which patients with both heart failure and hypertension are included.

Aged↗

[NT-proBNP and atrioventricular plane displacement. Relationship and diagnostic implications].

INTRODUCTION AND OBJECTIVES: NT-proBNP is useful in the diagnosis of heart failure and ventricular dysfunction. Left atrioventricular plane displacement (AVPD) is a consolidated index of ventricular function. Our objective was to carry out a multicenter population-based study to establish the relationship between plasma NT-proBNP levels with AVPD values. PATIENTS AND METHOD: We studied 215 subjects (age 66 9 years; 57.7% women) chosen from a random sample of 432 people from the Community of Valencia, who previously reported suffering from some degree of dyspnea. Doppler echocardiography was done, AVPD was calculated and plasma NT-proBNP concentrations were determined. All studies were completed in 194 patients. RESULTS: For the whole population NT-proBNP was 88 (0-2,586) pg/ml and AVPD was 11.9 1.6 mm. NT-proBNP concentration correlated well with AVPD (r = 0.44; p < 0.00001), and higher peptide levels were obtained in AVPD quartiles that indicated less displacement (p < 0.05). When NT-proBNP values were grouped according to their association with AVPD lower or higher than the 50th percentile AVPD, the difference was significant at p < 0.01. When AVPD values lower and higher than 10 mm were compared, NT-proBNP values were higher in persons with AVPD lower than 10 mm (p < 0.05). CONCLUSIONS: This population study found higher NT-proBNP concentrations in subjects with lower AVPD, and illustrates the potential diagnostic usefulness of NT-proBNP in clinical practice.

Aged↗

Quantification of proinflammatory cytokines in the urine of congestive heart failure patients. Its relationship with plasma levels.

AIMS: Proinflammatory cytokines are important mediators for the development of heart failure and increased plasma levels of these cytokines have been reported in patients with this condition. The purpose of the study was to investigate whether urine, a non-invasively obtained biological sample, was an appropriate medium in which to measure the concentration of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in patients in the advanced stages of the disease. METHODS AND RESULTS: Thirty consecutive patients who had severe congestive heart failure (NYHA classes III and IV) and 30 matched healthy control subjects were enrolled. Plasma and the first urine of the day were collected and TNF-alpha and IL-6 were quantitatively analyzed by enzyme-linked immunosorbent assays. For every subject there were no differences in the amount of cytokine determined in plasma and urine. Both urine and plasma levels of IL-6 and TNF-alpha were greater in heart failure patients than in controls. CONCLUSION: Our results show that plasmatic and urinary levels of proinflammatory cytokines did not differ significantly. Thus, urine may be a good milieu in which to study these cytokines and may have diagnostic, prognostic and therapeutic implications.

Aged↗

Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance.

To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal alphaDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c- cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When alphaDEC-205:OVA was injected subcutaneously, OVA protein was identified over a 4-48 h period in DCs, primarily in the lymph nodes draining the injection site. In vivo, the OVA protein was selectively presented by DCs to TCR transgenic CD8+ cells, again at least 400 times more effectively than soluble OVA and in a TAP-dependent fashion. Targeting of alphaDEC-205:OVA to DCs in the steady state initially induced 4-7 cycles of T cell division, but the T cells were then deleted and the mice became specifically unresponsive to rechallenge with OVA in complete Freund's adjuvant. In contrast, simultaneous delivery of a DC maturation stimulus via CD40, together with alphaDEC-205:OVA, induced strong immunity. The CD8+ T cells responding in the presence of agonistic alphaCD40 antibody produced large amounts of interleukin 2 and interferon gamma, acquired cytolytic function in vivo, emigrated in large numbers to the lung, and responded vigorously to OVA rechallenge. Therefore, DEC-205 provides an efficient receptor-based mechanism for DCs to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation.

Animals↗

Analysis of genomic and proteomic data using advanced literature mining.

High-throughput technologies, such as proteomic screening and DNA micro-arrays, produce vast amounts of data requiring comprehensive analytical methods to decipher the biologically relevant results. One approach would be to manually search the biomedical literature; however, this would be an arduous task. We developed an automated literature-mining tool, termed MedGene, which comprehensively summarizes and estimates the relative strengths of all human gene-disease relationships in Medline. Using MedGene, we analyzed a novel micro-array expression dataset comparing breast cancer and normal breast tissue in the context of existing knowledge. We found no correlation between the strength of the literature association and the magnitude of the difference in expression level when considering changes as high as 5-fold; however, a significant correlation was observed (r = 0.41; p = 0.05) among genes showing an expression difference of 10-fold or more. Interestingly, this only held true for estrogen receptor (ER) positive tumors, not ER negative. MedGene identified a set of relatively understudied, yet highly expressed genes in ER negative tumors worthy of further examination.

Abstracting and Indexing↗

The flutter device and expiratory pressures.

PURPOSE: Flutter therapy uses a handheld instrument that consists of a pipe-like device with a ball in the central core that oscillates during exhalation, providing oscillating positive expiratory pressure. The purpose of this study was to determine the effect of airflow and the incline of the device at the mouth on expiratory pressure and oscillation frequency. METHODS: A Flutter device was attached to a circuit that consisted of a pneumotachograph and a ventilator. The ventilator generated different flows and expiratory pressure was measured with a pressure transducer. The angles considered were +40 degrees to -40 degrees in increments of 10 degrees , with the reference for incline being the horizontal line. Expiratory pressure, airflow, angle of incline, and oscillation frequency were measured. RESULTS: There was a strong and significant correlation between flow and expiratory pressure at each level of incline (P < or =006; r > 0.93). There also was a significant and strong correlation between expiratory pressure and oscillation frequency (P <.05; r = 0.81-0.97). There was a significant reduction in expiratory pressure at a negative incline of -40 degrees. CONCLUSIONS: The results of this study indicate that a positive incline and a large airflow result in an increase in expiratory pressure. This information will assist clinicians to better understand the effects of the Flutter device.

Analysis of Variance↗

Malignant tumors of the anterior skull base.

BACKGROUND: Cancers of the paranasal sinuses or nasal cavity are the most common malignant tumors of the anterior skull base. Several types of tumors occur in this location, including cancers of endodermal, mesodermal, and epidermal origins. Although anterior skull base surgery is a relatively recent approach in treating these tumors, widespread changes have already occurred in procedural methods and treatment goals. METHODS: We review the tumor types that occur in the anterior skull base and discuss the current treatment options, including multimodal therapy and the team approach to surgery. Surgical techniques are also described. RESULTS: Management of anterior skull base cancer is complex due to the anatomic detail of the region and the variety of cancers that occur in this area. Currently, the "gold standard" for surgery is the anterior craniofacial approach. Combined with adjuvant radiation therapy, 5-year disease-free survival rates have increased to 50%, with some tumors such as adenocarcinomas and esthesioneuroblastomas reaching up to 80% 5-year survival rates. Potential complications include cerebrospinal fluid leakage, meningitis, abscess formation, and pneumocephalus. CONCLUSIONS: Treatment of anterior skull base cancer is complex due to the significant anatomic detail of the region and the variety of cancers that occur in this area. Multimodal therapy through a team approach is the optimal management approach for these tumors.

Adenocarcinoma↗