Maat, A.W.P.M.

Combined TCRG and TCRA TREC analysis reveals increased peripheral T-lymphocyte but constant intra-thymic proliferative history upon ageing (Article)

2013-03-01T00:00:00Z

T-cell receptor (TCR) repertoire diversity, thymic output, clonal size and peripheral T-lymphocyte numbers largely depend on intra-thymic and post-thymic T-lymphocyte proliferation. However, quantitative insight into thymocyte and T-lymphocyte proliferation is still lacking. We developed a new TCRG-based TCR excision circle (TREC) assay, the Vγ-Jγ TREC assay, which we used together with an adjusted δREC-ψJα TREC assay to quantify the proliferative history of human thymocyte and T-lymphocyte subpopulations from children and adults. This revealed that thymocytes undergo ∼6-8 intra-thymic cell divisions from the double negative (DN) 3 developmental stage onwards, which appeared independent of age. Thus thymocyte proliferation after the DN3 developmental stages is stable and therefore not contributing to the reduced thymic output upon ageing. Cord blood naive T lymphocytes had already undergone ∼2-3 post-thymic cell divisions, which increased to ∼6-7 cell divisions in naive T lymphocytes of middle-aged adults, indicating the importance of homeostatic naive T-lymphocyte proliferation from a young age onwards in the maintenance of peripheral T-lymphocyte numbers. In conclusion, our data provide quantitative insight into the proliferative history of thymocyte and T-lymphocyte subpopulations and alterations herein upon ageing. This novel TREC assay approach could prove valuable in immune status monitoring in a variety of conditions.

Validation of a prognostic model to predict survival after non-small-cell lung cancer surgery (Article)

2010-11-01T00:00:00Z

Objective: Surgery is the first choice of treatment for localised non-small-cell lung cancer (NSCLC). When making decisions regarding resection, physicians must balance the potential long-term benefits of surgery with the risk of surgery-related death, particularly among elderly patients with multiple co-morbid conditions. In 2005, a predictive model with a preoperative and a postoperative mode to predict survival of an individual patient after NSCLC surgery was created. This model combines the patient-, tumour- and treatment characteristics and can be used to assist in clinical decision making. Till present, this model has not been validated. The purpose of this study was to validate this model in patients operated on for primary NSCLC. Methods: A total of 126 patients underwent surgery for primary NSCLC between January 2002 and December 2006. Required model variables were collected for all patients and inserted into the model. To evaluate the performance of the two models, we assessed these models in terms of both discrimination (resolution) and calibration (reliability). The discriminative ability was measured using the c-index and calibration was evaluated by the Hosmer-Lemeshow goodness-of-fit test. Results: The median follow-up time was 3.4 years. Hospital mortality was 2.4%. One-, 2- and 3-year survival was 86%, 75% and 72%, respectively. The discriminative ability of the preoperative mode showed a c-statistic for 1-year survival of 0.68, for 2-year of 0.68 and for 3-year of 0.66. The postoperative model showed a discriminative ability for 1-year survival of 0.72, for 2-year of 0.76 and for 3-year of 0.77. Calibration was adequate for the first 2 years. The preoperative mode showed a p-value of 0.62 for 1-year survival and 0.14 for 2-year survival. Calibration was poor for 3-year survival (p= 0.0027). For the postoperative mode, calibration was quite similar with p-values of 0.4 for 1-year survival, 0.14 for 2-year survival and 0.003 for 3-year survival. Conclusions: The model adequately estimates the 1- and 2-year survival. Discrimination was good for 3-year survival. Inclusion of more factors with additional prognostic value could potentially further improve the accuracy of the model.

Stereotactic body radiotherapy using real-time tumor tracking in octogenarians with non-small cell lung cancer (Article)

2010-09-01T00:00:00Z

As the incidence of stage I non-small cell lung cancer (NSCLC) increases among octogenarians and only selected patients are surgical candidates, an alternative treatment is necessary. This manuscript evaluates the overall survival, local tumor control rate, and treatment-related toxicity after stereotactic body radiotherapy (SBRT) in 38 octogenarians with stage I NSCLC. Treatment consisted of 45. Gy (n= 4) or 60. Gy (n= 25) in 3 fractions for patients with peripheral tumors. A risk adaptive schedule of 45-60. Gy in 3-6 fractions was used for central (n= 7) or large peripheral tumors (n= 2).An overall survival rate of 65% at 1 year and 44% at 2 years was achieved in octogenarians after SBRT. The local tumor control rate was excellent (100% at 2 years) and no grade 4 or 5 treatment-related toxicity occurred. Despite the high incidence of comorbidity in these octogenarians (Charlson score ≥5 in 16% of patients), an approach that merely provides supportive care cannot always be justified. SBRT offers octogenarians with stage I NSCLC a good treatment alternative.

Mechanical Circulatory Support Devices Improve Tissue Perfusion in Patients With End-Stage Heart Failure or Cardiogenic Shock (Article)

2009-09-01T00:00:00Z

Objectives: This study evaluated the effects of mechanical circulatory support (MCS) on sub-lingual microcirculation as a surrogate for splanchnic microvascular perfusion. Methods: Between May 2008 and April 2009, 10 consecutive patients received an MCS device or extracorporeal membrane oxygenation for end-stage chronic heart failure (n = 6) or cardiogenic shock (n = 4). Microcirculation was investigated using a hand-held Sidestream Dark Field imaging device. Perfused capillary density (PCD) and capillary red blood cell velocity (cRBCv) were assessed before device implantation (T0), immediately after implantation (T1), and 1 day after implantation (T2). Results: Median patient age was 45 years (interquartile range [IQR] 38-52 years) and 70% were men. MCS significantly decreased pulmonary capillary wedge pressure (p = 0.04). Median cardiac power index increased (0.29 [IQR, 0.21-0.34] W/m2at T0 vs 0.48 [IQR, 0.39-0.54] W/m2at T1, p = 0.005) as well as median central venous oxygen saturation (54% [IQR, 46%-61%] at T0 vs 78% [IQR, 67%-85%] at T1, p = 0.007). There was a 3-fold increase in tissue perfusion index (sub-lingual PCD × cRBCv) during mechanical circulatory support (573 [IQR, 407-693] at T0 vs 1909 [IQR, 1771-2835] at T1, p = 0.005). Microcirculatory parameters remained improved at T2. Conclusion: Mechanical circulatory support for severe heart failure is associated with a consistent, significant, and sustained improvement in tissue perfusion, as measured at the bedside by a 2-dimensional microcirculation imaging technique.

Three-dimensional transesophageal echocardiography: Diagnosing the extent of pericarditis constrictiva and intraoperative surgical support (Article)

2009-05-01T00:00:00Z

The traditional two-dimensional transthoracic echocardiography (2DTTE) has limitations in demonstrating the extent of pericardial thickening in constrictive pericarditis (CP) because of poor transmission of ultrasound through the thickened anterior pericardial structures. We describe a case of CP, of unknown etiology, in which transesophageal 3DTEE equalled the accuracy of cardiac magnetic resonance in demonstrating the extent of pericardial thickening in CP.

Inadequate immune regulatory function of CD4+CD25bright+FoxP3+ T cells in heart transplant patients who experience acute cellular rejection (Article)

2009-04-27T00:00:00Z

BACKGROUND.: CD4CD25FoxP3 regulatory T cells are suppressors of antigen-activated immune reactivity. Here, we assessed the clinically relevant role of these cells in the control of immune responses directed to a transplanted heart. METHODS.: We investigated the phenotype and function of peripheral CD4CD25FoxP3 T cells in heart transplant patients free from acute rejections (n=9) and in rejectors (n=12) before and during acute cellular rejection. RESULTS.: Between rejectors and nonrejectors, the proportion of CD4CD25 T cells and of FoxP3 cells within this population was comparable. Yet, CD4CD25FoxP3 T cells of rejectors had a higher CD127 expression than those of nonrejectors (P=0.0001). Depletion of CD4CD25 T cells from peripheral blood mononuclear cells increased the antidonor proliferative response of both nonrejectors (P≤0.0005) and rejectors (P≤0.03). In rejectors, however, only a 2-fold increase was measured, whereas the nonrejectors' response became 14 times higher (P=0.002). Reconstitution of CD4CD25 T cells only suppressed the overall antidonor proliferative response of CD25 responder cells of nonrejectors significantly (P=0.001). Moreover, the percentage inhibition of the response was higher in nonrejectors than in rejectors (P=0.02). Analyses of pretransplant samples revealed that CD4CD25 T cells of rejectors already had a lower suppressive capacity than those of nonrejectors before transplantation (P=0.04). CONCLUSION.: CD4CD25FoxP3 T cells of heart transplant patients who experience acute rejection had an up-regulated CD127 expression and an inadequate regulatory function compared with those of nonrejecting patients. Our observations suggest that the function of circulating CD4CD25FoxP3 regulatory T cells may be pivotal for the prevention of acute cellular rejection after clinical heart transplantation.

Intraoperative transesophageal echocardiography is beneficial for hemodynamic stabilization during left ventricular assist device implantation in children (Article)

2009-04-01T00:00:00Z

Background: Mechanical circulatory support, with a left ventricular assist device (LVAD) is used in an increasing number of children for treatment of advanced heart failure as bridge-to-transplant. To date no data are available and no studies have defined the role of intraoperative transesophageal echocardiography (TEE) for hemodynamic stabilization during Centrimag Levitronix centrifugal pump implantation in children. Methods: Children with therapy resistant heart failure, undergoing LVAD implantation using Berlin Heart Excor pediatric cannula connected to a Levitronix Centrifumag pump, are intraoperatively monitored using an Oldelft micromultiplane TEE. Intraoperative TEE is specially used to monitor right ventricular (RV) and left ventricular (LV) function, correct position of the cannulas and response to pharmacological treatment. Results: In five consecutive patients RV function was assessed by TEE after starting LVAD Levitronix centrifugal pump. Initial RV failure presents with RV dilation and LV collapse. After titration of vasopressor and inotropic agents, RV contractility improved and thereby the filling of the LV. In one child, despite those measures the RV showed no improvement by TEE and a Levitronix right ventricular assist device to support the RV function was implanted as well. All patients could hemodynamically be stabilized before transport to the intensive care unit. Conclusion: The complex interaction of the RV and LV function and correct positioning of the cannula, during LVAD implantation in children with end-stage cardiac failure is improved by simultaneous visualization of cardiac performance of both ventricles and cannula positioning by means of intraoperative multiplane TEE.

Donor-specific immune regulation by CD8+ lymphocytes expanded from rejecting human cardiac allografts (Article)

2009-02-01T00:00:00Z

To assess whether regulatory T cells are present in rejecting human cardiac allografts, we performed functional analyses of graft lymphocytes (GLs) expanded from endomyocardial biopsies (EMB; n = 5) with histological signs of acute cellular rejection. The GL cultures were tested for their proliferative capacity and regulatory activity on allogeneic-stimulated peripheral blood mononuclear cells (PBMC) of the patient (ratio PBMC:GLs = 5:1). Three of these GL cultures were hyporesponsive to donor antigens and suppressed the antidonor proliferative T-cell response of PBMC, but not the anti-third-party response. Interestingly, it was the CD8+GL subset of these cultures that inhibited the antidonor response (65-91% inhibition of the proportion of proliferating cells); the CD4+GLs of the expanded GL cultures were not suppressive. In conclusion, CD8+GLs expanded from rejecting human cardiac allografts can exhibit donor-specific immune regulatory activities in vitro. We suggest that during acute cellular rejection, GLs may not only consist of graft-destructing effector T cells, but also of cells of the CD8+type with the potential to specifically inhibit antidonor immune reactivity.

Pseudomediastinal fibrosis caused by massive lymphadenopathy in domestically acquired particulate lung disease (Article)

2008-04-01T00:00:00Z

In this report, we describe a case of domestically acquired particulate lung disease (DAPLD) or "hut lung" in a 59-year-old woman of Moroccan descent who emigrated to the Netherlands, having lived in an rural area for most her life. She presented with obstructive lung disease and with signs of mediastinal fibrosis which were shown to be caused by massive enlargement of mediastinal lymph nodes. To the best of our knowledge, this is the first case of DAPLD from Morocco and the first report of a case of DAPLD mimicking mediastinal fibrosis.

Inclusion of the transcervical approach in the video-assisted thoracoscopic extended thymectomy (BATET) for myasthenia gravis: A prospective trial [7] (Article)

2008-01-01T00:00:00Z

FOXP3 mRNA expression analysis in the peripheral blood and allograft of heart transplant patients (Article)

2008-01-01T00:00:00Z

Previously, we demonstrated in heart transplant patients that FOXP3, a gene required for the development and function of regulatory T cells, was highly expressed in the graft during an acute cellular rejection. In this study, we analyzed whether the FOXP3 gene expression in the peripheral blood also reflects anti-donor immune responses, and therefore may provide clues for non-invasive detection of non-responsiveness or acute rejection. We examined the FOXP3 expression patterns of peripheral blood mononuclear cells (PBMC; n = 69) of 19 heart transplant patients during quiescence and rejection in comparison with those of endomyocardial biopsies (EMB; n = 75) of 24 heart transplant patients. While the FOXP3 mRNA levels were abundantly expressed in rejecting EMB (ISHLT rejection grade > 1R) compared with EMB without histological evidence of myocardial damage (ISHLT rejection grade 0R-1R; p = 0.003), no association with rejection or non-responsiveness was found for the FOXP3 mRNA levels in the peripheral blood. Thus, in contrast to intragraft FOXP3 gene expression, the peripheral FOXP3 mRNA levels lack correlation with anti-donor immune responses in the graft, and, consequently, FOXP3 does not appear to be a potential candidate gene for non-invasive diagnosis of non-responsiveness or rejection.

Connecting the Centrimag Levitronix Pump to Berlin Heart Excor Cannulae; A New Approach to Bridge to Bridge (Article)

2008-01-01T00:00:00Z

Background: An increasing number of children are requiring circulatory suport. Hospitals offering pediatric Ventricular Assist Device (VAD) should have devices of different sizes available to cover the full range of patient sizes incurring considerable expense. As in adults, post-operative bleeding often complicates VAD implantation. The use of a Levitronix Centrimag centrifugal pump, connected to Berlin Heart Excor cannulae, seems an attractive and logic combination, both in terms of patient safety and of hospital economics. Methods: We describe 3 children with therapy resistant cardiac failure who underwent extracorporeal membrane oxygenation (ECMO) as a rescue before proceeding to placement of the Berlin Heart Excor paracorporeal assist device. The Levitronix Centrimag pump was used as an intermediate device to allow the patients to be stabilised. Therefore, only Berlin Heart cannulae of different sizes have to be readily available; if successful stabilization can be achieved, the Berlin Heart Excor ventricles and the drive unit can then be ordered to replace the Levitronix pump. Results: Two patients were successfully stabilised with the Levitronix pump and were switched to the definitive Berlin Heart Excor ventricles after 6 days of support. The third child succumbed due to intractable pulmonary hemorrhage in severely damaged lungs. No device related complications, especially no thrombo-embolic events, occurred during Levitronix support. Conclusion: The Levitronix Centrimag pump was easy to handle and gave effective circulatory support, the patients were only switched to the Berlin Heart Excor system after stabilization. In patients with a high risk of failure, it is a relatively cheap but safe and effective support system.

Intragraft FOXP3 mRNA expression reflects antidonor immune reactivity in cardiac allograft patients (Article)

2007-06-01T00:00:00Z

BACKGROUND. Regulatory FOXP3+ T cells control immune responses of effector T cells. However, whether these cells regulate antidonor responses in the graft of cardiac allograft patients is unknown. Therefore, we analyzed the gene expression profiles of regulatory and effector T-cell markers during immunological quiescence and acute rejection. METHODS. Quantitative real-time polymerase chain reaction was used to analyze mRNA expression levels in time-zero specimens (n=24) and endomyocardial biopsies (EMB; n=72) of cardiac allograft patients who remained free from rejection (nonrejectors; n=12) and patients with at least one histologically proven acute rejection episode (rejectors; International Society for Heart and Lung Transplantation [ISHLT] rejection grade >2; n=12). RESULTS. For all analyzed regulatory and effector T-cell markers, mRNA expression levels were increased in biopsies taken after heart transplantation compared with those in time-zero specimens. Posttransplantation, the FOXP3 mRNA levels were higher in EMB assigned to a higher ISHLT rejection grade than the biopsies with grade 0: the highest mRNA levels were detected in the rejection biopsies (rejection grade >2; P=0.003). In addition, the mRNA levels of CD25, glucocorticoid-induced TNF receptor family-related gene, cytotoxic T lymphocyte-associated antigen 4, interleukin-2, and granzyme B were also significantly higher in rejecting EMB than in nonrejecting EMB (rejection grade ≤2). This increase in expression levels in relation to the histological rejection grade was only observed in patients who developed an acute rejection episode; the mRNA levels of nonrejectors remained stable irrespective of ISHLT rejection grade. CONCLUSIONS. These observations suggest that, after clinical heart transplantation, FOXP3+ T cells do not prevent acute rejection, but rather are a response to antidonor effector T-cell activity.

A Clinical Randomized Trial to Evaluate the Safety of a Noninvasive Approach in High-Risk Patients Undergoing Major Vascular Surgery. The DECREASE-V Pilot Study (Article)

2007-05-01T00:00:00Z

Objectives: The purpose of this research was to perform a feasibility study of prophylactic coronary revascularization in patients with preoperative extensive stress-induced ischemia. Background: Prophylactic coronary revascularization in vascular surgery patients with coronary artery disease does not improve postoperative outcome. If a beneficial effect is to be expected, then at least those with extensive coronary artery disease should benefit from this strategy. Methods: One thousand eight hundred eighty patients were screened, and those with ≥3 risk factors underwent cardiac testing using dobutamine echocardiography (17-segment model) or stress nuclear imaging (6-wall model). Those with extensive stress-induced ischemia (≥5 segments or ≥3 walls) were randomly assigned for additional revascularization. All received beta-blockers aiming at a heart rate of 60 to 65 beats/min, and antiplatelet therapy was continued during surgery. The end points were the composite of all-cause death or myocardial infarction at 30 days and during 1-year follow-up. Results: Of 430 high-risk patients, 101 (23%) showed extensive ischemia and were randomly assigned to revascularization (n = 49) or no revascularization. Coronary angiography showed 2-vessel disease in 12 (24%), 3-vessel disease in 33 (67%), and left main in 4 (8%). Two patients died after revascularization, but before operation, because of a ruptured aneurysm. Revascularization did not improve 30-day outcome; the incidence of the composite end point was 43% versus 33% (odds ratio 1.4, 95% confidence interval 0.7 to 2.8; p = 0.30). Also, no benefit during 1-year follow-up was observed after coronary revascularization (49% vs. 44%, odds ratio 1.2, 95% confidence interval 0.7 to 2.3; p = 0.48). Conclusions: In this randomized pilot study, designed to obtain efficacy and safety estimates, preoperative coronary revascularization in high-risk patients was not associated with an improved outcome.

Outcome after redo coronary artery bypass grafting in patients with ischaemic cardiomyopathy and viable myocardium (Article)

2007-02-01T00:00:00Z

Background: Repeat coronary artery bypass grafting (redo-CABG) in patients with ischaemic cardiomyopathy is associated with high perioperative risk and worse long-term outcome compared with patients undergoing their first CABG. Objective: To assess whether patients with viable myocardium undergoing redo-CABG have a better outcome. Methods: 18 patients with ischaemic cardiomyopathy underwent redo-CABG and 34 underwent their first CABG; all had substantial viability (≥25% of the left ventricle) on dobutamine stress echocardiography (DSE). Left ventricular ejection fraction (LVEF) and heart failure symptoms were assessed before and 9-12 months after revascularisation. Cardiac event rate was assessed during the follow-up period (median 4 years, 25-75th centile 2.8-4.9 years). Results: The extent of viable myocardium on DSE was comparable in the two groups (11.3 (3.9) segments in patients who underwent redo-CABG v 12.8 (3.0) in patients who underwent their first CABG; p = NS). LVEF improved from 32% (9%) to 39% (12%); p = 0.01, in patients who underwent redo-CABG and from 30% (7%) to 36% (7%); p<0.01, in those who underwent their first CABG; New York Heart Association class improved from 2.5 (1.1) to 1.9 (0.8); p = 0.03, and from 2.7 (1.0) to 1.8 (0.70); p<0.01, respectively. In patients who underwent redo-CABG, the perioperative mortality was 0, post-surgery inotropic support was needed in 11% of the patients and mid-term (4-year) survival was 100%, with a total event rate of 28%. All these variables were not statistically different from patients who underwent their first CABG (p = 0.50, 0.90, 0.08 and 0.81, respectively). Conclusion: Patients with ischaemic cardiomyopathy and substantial viability undergoing redo-CABG benefit from revascularisation in terms of improvement in LVEF, heart failure symptoms, angina and mid-term prognosis.

Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up. (Article)

2003-12-17T00:00:00Z

Objectives We report on the procedural and six-month results of the first percutaneous and stand-alone study on myocardial repair with autologous skeletal myoblasts. Background Preclinical studies have shown that skeletal myoblast transplantation to injured myocardium can partially restore left ventricular (LV) function. Methods In a pilot safety and feasibility study of five patients with symptomatic heart failure (HF) after an anterior wall infarction, autologous skeletal myoblasts were obtained from the quadriceps muscle and cultured in vitro for cell expansion. After a culturing process, 296 ± 199 million cells were harvested (positive desmin staining 55 ± 30%). With a NOGA-guided catheter system (Biosense-Webster, Waterloo, Belgium), 196 ± 105 million cells were transendocardially injected into the infarcted area. Electrocardiographic and LV function assessment was done by Holter monitoring, LV angiography, nuclear radiography, dobutamine stress echocardiography, and magnetic resonance imaging (MRI). Results All cell transplantation procedures were uneventful, and no serious adverse events occurred during follow-up. One patient received an implantable cardioverter-defibrillator after transplantation because of asymptomatic runs of nonsustained ventricular tachycardia. Compared with baseline, the LV ejection fraction increased from 36 ± 11% to 41 ± 9% (3 months, P = 0.009) and 45 ± 8% (6 months, P = 0.23). Regional wall analysis by MRI showed significantly increased wall thickening at the target areas and less wall thickening in remote areas (wall thickening at target areas vs. 3 months follow-up: 0.9 ± 2.3 mm vs. 1.8 ± 2.4 mm, P = 0.008). Conclusions This pilot study is the first to demonstrate the potential and feasibility of percutaneous skeletal myoblast delivery as a stand-alone procedure for myocardial repair in patients with post-infarction HF. More data are needed to confirm its safety.

Intragraft interleukin 2 mRNA expression during acute cellular rejection and left ventricular total wall thickness after heart transplantation (Article)

2002-01-01T00:00:00Z

OBJECTIVE: To assess whether diastolic graft function is influenced by intragraft interleukin 2 (IL-2) messenger RNA (mRNA) expression in rejecting cardiac allografts. DESIGN: 16 recipients of cardiac allografts were monitored during the first three months after transplantation. The presence of IL-2 mRNA in endomyocardial biopsies (n = 123) was measured by reverse transcriptase polymerase chain reaction. To determine heart function, concurrent M mode and two dimensional Doppler echocardiograms were analysed. RESULTS: Histological signs of acute rejection (International Society for Heart and Lung Transplantation (ISHLT) rejection grade > 2) were strongly associated with IL-2 mRNA expression (IL-2 mRNA was present in 12 of 20 endomyocardial biopsies (60%) with acute rejection and in 24 of 103 endomyocardial biopsies (23%) without acute rejection, p = 0.002). No significant relation was found between either histology or IL-2 mRNA expression alone and the studied echocardiographic parameters. However, stratification of the echocardiographic data into those of patients with and those without acute rejection showed that during acute rejection IL-2 mRNA expression was significantly associated with increased left ventricular total wall thickness (mean change in total wall thickness was +0.22 cm in patients with IL-2 mRNA expression versus -0.18 cm in patients without IL-2 mRNA expression, p = 0.048). CONCLUSIONS: An increase in left ventricular total wall thickness precedes IL-2 positive acute rejection after heart transplantation. Thus, cardiac allograft rejection accompanied by intragraft IL-2 mRNA expression may be indicative of more severe rejection episodes.

The TNF-alpha system in heart failure and after heart transplantation: plasma protein levels, mRNA expression, soluble receptors and plasma buffer capacity (Article)

1999-01-01T00:00:00Z

BACKGROUND: The two soluble tumour necrosis factor (TNF) receptors (sTNF-R1, sTNF-R2) can bind TNF-alpha, which is a cytokine with cardiodepressant properties. In heart failure and after heart transplantation, the TNF-alpha system is unbalanced, due to elevated levels of sTNF receptors. AIM: To assess the activity of the TNF-alpha system in patients with heart failure and after heart transplantation. METHODS: We measured TNF-alpha mRNA expression of peripheral blood mononuclear cells, plasma levels of TNF-alpha and sTNF reverse transcriptase receptors, using polymerase chain reaction and ELISA and performed a TNF-alpha binding capacity analysis, quantitating the buffer capacity of patients' plasma. RESULTS: In 11 patients with heart failure and in 15 cardiac allograft recipients, the TNF-alpha mRNA expression was comparable to controls. This level of mRNA was not accompanied by detectable TNF-alpha plasma levels. Significantly higher sTNF receptors levels were found in patients: ( P <0.001; ANOVA). The TNF-alpha binding capacity of patients' plasma was significantly increased, which led to decreased TNF-alpha recovery ( P<0.05). Both sTNF receptors showed a linear correlation with serum creatinine (sTNF-RI: r=0.92; sTNF-R2: r=0.82, P<0.001). CONCLUSIONS:The TNF-alpha mRNA expression and plasma levels show that the 'peripheral' TNF-alpha system is not activated. The high sTNF-receptors levels and their elevated TNF-alpha binding capacity, resulting in decreased TNF-alpha bioavailability, may contribute to an immunosuppressed state in these patients.

Nasal Carriage of Staphylococcus Aureus as a Major Risk Factor for Wound Infections after Cardiac Surgery (Article)

1995-01-01T00:00:00Z