Elevated plasma osteopontin levels were associated with osteopontin expression of CD4+ T cells in patients with unstable angina.

BACKGROUND: Plaque instability in patients with unstable angina (UA) is associated with stimulated CD4+ T cells, so the present study investigated whether there is a relationship among plaque instability, osteopontin and CD4+ T cells. METHODS AND RESULTS: Peripheral blood mononuclear cells were collected from 51 consecutive patients with UA, 60 patients with stable angina (SA), and 39 patients with chest pain syndrome (CPS). Osteopontin-producing CD4+ T cells were quantified by flow cytometry. Plasma osteopontin levels (ng/ml) were measured by ELISA and were higher in patients with UA (792.0 +/- 316.7) than in those with SA (626.0 +/- 195.0, p < 0.005) or CPS (594.7 +/- 239.4, p < 0.005). The frequency (%) of osteopontin-producing CD4+ T cells was higher in patients with UA (26.7 +/- 13.3) than in those with SA (19.5 +/- 11.1, p < 0.05) or CPS (16.6 +/- 9.0, p < 0.005). Furthermore, the plasma osteopontin level correlated with the frequency of osteopontin-producing CD4+ T cells (r = 0.327, p = 0.0004), as did the high-sensitivity C-reactive protein level (r = 0.360, p = 0.0002). CONCLUSIONS: The plasma osteopontin levels are elevated in patients with UA, accompanied by an increase in the number of osteopontin-production of circulating CD4+ T cells. Circulating CD4+ T cells may play a role through osteopontin in the pathophysiology of UA.     

Relation between CD4+ T-cell activation and severity of chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

The percentage of CD4(+) T cells in blood is correlated with left ventricular dysfunction and decreased ejection fraction in heart disease. The aim of this study was to determine the relation between activation of CD4(+) T cells and New York Heart Association functional classes in chronic heart failure (HF) and differences in inflammatory activation between ischemic cardiomyopathy (IC) and idiopathic dilated cardiomyopathy (IDC). Blood samples were obtained from 47 patients with HF and 20 controls. Percentages of interferon-gamma-positive CD4(+) T cells (representative type 1 T-helper cells) and interleukin-4-positive CD4(+) T cells (representative type 2 T-helper cells) were analyzed using 3-color flow cytometry. The proportion of interferon-gamma-positive CD4(+) T cells was higher in patients with HF (28.96 +/- 12.90%) than in controls (18.12 +/- 5.28, p = 0.0006), but there was no difference in percentage of interleukin-4-positive CD4(+) T cells between the 2 groups. The proportion of interferon-gamma-positive CD4(+) T cells and plasma B-type natriuretic peptide levels increased with worsening of New York Heart Association functional class in the IC and IDC groups. The proportion of interferon-gamma-positive CD4(+) T cells in the IC group (33.88 +/- 13.33%) was higher than in the IDC group (22.33 +/- 8.88%, p = 0.002); however, plasma B-type natriuretic peptide levels were higher in the IDC group (358.0 pg/ml, 327.5 to 1,325.7) than in the IC group (82.7 pg/ml, 34.7 to 252.9, p = 0.019). In conclusion, we demonstrated pronounced type 1 T-helper cell activation in patients with HF in proportion to severity of HF and that the specificity of T-cell activation differs between patients with IC and those with IDC.     

Prognostic value of cardiopulmonary exercise testing in children with heart failure secondary to idiopathic dilated cardiomyopathy in a non-beta-blocker therapy setting

BACKGROUND: Peak oxygen consumption and resting left ventricular ejection fraction (LVEF) are independent predictors of survival in adult heart failure (HF) patients. Aim: To evaluate these factors in children. METHODS: We prospectively studied 31 children with NYHA class I to III HF (mean LVEF 26+/-10%; mean age 8.6+/-1.9 years). All had dilated cardiomyopathy and were awaiting heart transplantation. A cardiopulmonary treadmill exercise test was performed and LVEF determined by radionuclide ventriculography. RESULTS: During a median follow-up of 1282 days, 20 children reached at least one end-point (death or heart transplantation). Clinical data from the 11 children without events and the 20 children with events are as follows: NYHA class 1+/-0 vs. 2+/-0.9 (p<0.01); SBP 118+/-17 vs. 102+/-16 (p=0.01); DBP 70+/-10 vs. 61+/-10 (p=0.02); heart rate 165+/-22 vs. 148+/-22 (NS); double-product 19+/-4 vs. 15+/-4 (p=0.01); end-tidal carbon dioxide tension (PetCO2) 35+/-5 vs. 30+/-6 (NS); oxygen consumption (VO2) 22+/-5.4 vs. 18.3+/-5.7 (NS); exercise time 19+/-4 vs. 13+/-6 (p<0.003), and LVEF 31+/-8 vs. 22+/-10 (p=0.02). These variables all correlated with prognosis on univariate analysis. In multivariate analysis, only decreasing exercise time and LVEF were predictive of events during follow-up (p<0.001 and 0.04). CONCLUSION: These findings suggest that reduction in LVEF and exercise tolerance in children with heart failure is predictive of functional status.     

Increased productivity of tumor necrosis factor-alpha in helper T cells in patients with systolic heart failure

BACKGROUND AND AIMS: Whereas increased circulating proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), play an important role in heart failure, where and how TNF-alpha production is upregulated remains largely unknown. We studied the productivity of TNF-alpha in peripheral lymphocytes and underlying mechanisms in patients with heart failure. METHODS: Symptomatic NYHA II-IV patients with chronic heart failure with systolic dysfunction (n=39, aged 74+/-11, ejection fraction [EF]<==50%) were compared with asymptomatic NYHA I patients (n=18, aged 72+/-10, EF>50%) and normal subjects (n=15, aged 67+/-11). Lymphocyte subsets (CD3, CD4, and CD8) and intracellular production of TNF-alpha in peripheral leukocytes were quantified by immunofluorescent flow cytometry, and relationships between these parameters and circulating proinflammatory cytokines were analyzed. RESULTS: Subpopulation of TNF-alpha-producing CD4 was larger in NYHA II-IV patients (23.7% [18.0-28.6]) than in normal subjects (17.1% [6.5-19.5], p<0.05) and was correlated with plasma TNF-alpha levels (r=0.26, p<0.05), EF (r=-0.26, p<0.05), CD4/CD8 ratios (r=0.42, p<0.001), and subpopulation of TNF-alpha-producing monocytes (r=0.47, p<0.0001). Plasma levels of soluble CD14 and interleukin-12 (IL-12) were significantly higher in NYHA II-IV patients than in normal subjects (1971 ng/mL [1740-2375] vs. 1607 ng/mL [1530-1930], p<0.01; and 121 pg/mL [62-230] vs. 62 pg/mL [54-99], p<0.05, respectively), and plasma IL-12 levels were correlated with plasma TNF-alpha levels (r=0.41, p<0.001). CONCLUSIONS: Increased productivity of TNF-alpha in helper T cells, associated with their dominance over cytotoxic T cells, may partially contribute to an increase in circulating TNF-alpha levels in heart failure.     

Decreased recent thymus emigrant number is associated with disease activity in systemic lupus erythematosus

OBJECTIVE: T cell receptor excision circle (TREC) is produced during T cell maturation within the thymus, and the number of TREC-bearing cells reflects the proportion of recent thymic emigrants in the peripheral lymphocyte pool. We studied TREC levels in peripheral CD4+ and CD8+ lymphocytes in patients with systemic lupus erythematosus (SLE) with quiescent and with active disease and in age- and sex-matched healthy volunteers. METHODS: TREC levels in peripheral CD4+ and CD8+ lymphocytes were determined in 29 patients with quiescent SLE, in 22 with active disease, and in 31 age- and sex-matched healthy volunteers. The number of TREC/microg DNA was determined by real-time polymerase chain reaction gauged by a standard curve with known number of TREC-containing plasmids. RESULTS: TREC levels in CD4+ and CD8+ cells were lower in patients with active SLE (2.27 +/- 2.05 x 10(4) and 4.14 +/- 4.06 x 10(4) TREC/microg DNA, respectively) compared to quiescent SLE (5.83 +/- 7.41 x 10(4) and 11.24 +/- 15.06 x 10(4) TREC/microg DNA; p = 0.03, p = 0.02, respectively). Patients with active SLE had lower TREC levels in CD4+ T cells than controls (2.27 +/- 2.05 x 10(4) vs 5.64 +/- 4.99 x 10(4) TREC/microg DNA; p = 0.03), but this difference did not reach statistical significance for CD8+ cells (4.14 +/- 4.06 x 10(4) vs 8.77 +/- 8.78 x 10(4) TREC/microg DNA; p = 0.1). Patients with quiescent SLE presented TREC levels similar to controls in CD4+ and CD8+ cells (p = 0.49, p = 0.3, respectively). CONCLUSION: Our results reveal decreased TREC levels in the peripheral blood of patients with active but not in patients with quiescent SLE. These data suggest that TREC levels are affected by disease activity in SLE.     

Granulocyte-colony stimulating factor or granulocyte-colony stimulating factor associated to stem cell intracoronary infusion effects in non ischemic refractory heart failure

We prospectively studied bone marrow stem cell (BMSC) therapy in 23 patients with non ischemic refractory heart failure(HF) in comparison with a HF control group with 17 patients. BMSC patients randomly underwent granulocyte-colony stimulating factor (G-CSF) administration (14 patients) or G-CSF associated to BMSC intracoronary infusion (eight patients). After the first month all BMSC patients received G-CSF with one-month interval between each one. CD34+ cell peaks (per mm(3)) in BMSC patients were 19+/-12 and in normal control 60+/-20 (p=0.003). In BMSC patients after the 1st G-CSF left ventricular(LV) ejection fraction (EF) increased from 21.4+/-4.7% to 23.6+/-7.7%(p=.048), peak VO(2) (ml/kg/min) from 9.9+/-2.4 to 11.6+/-3 (p=.04), functional class and quality of life improved whereas in the HF control group LVEF, RFEF and functional class were unchanged. Both BMSC subgroups presented improvement of LV function evaluated by DTI velocities. Evaluations after the first month in BMSC patients showed improvements in LVEF (p=.001), right VEF (p=0.01), DTI velocities (p=.009), peak VO(2) (p=0.04), functional class (p<0.001) and quality of life (p<0.001). In conclusion, CD34+ mobilization is impaired in HF. Stem cell therapy can improve HF. Randomized trials should be developed to confirm our results.     

CTLA-4 upregulation during HIV infection: association with anergy and possible target for therapeutic intervention

OBJECTIVE: To study the role of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) during HIV infection. METHODS: Intracellular CTLA-4 expression, determined by flow-cytometry, and proliferative responses to HIV antigens, were studied in peripheral blood mononuclear cells (PBMC) from 93 HIV-1-infected [HIV(+)] patients and 40 HIV-1 seronegative controls. RESULTS: The proportions of CTLA-4 expressing CD4+ T cells were: (1) significantly higher in HIV(+) patients, 10.95 +/- 0.66%, than in controls, 6 +/- 0.45% (P < 0.0001); (2) inversely correlated to CD4+ counts (r = -0.67, P < 0.005, n = 16, drug-naive patients; r = -0.57, P < 0.0001, n = 77, HAART-treated patients); and (3) positively correlated to proportion of activated (HLA-DR+CD3+) (r = 0.53, P < 0.0001) and memory (CD45RO+CD4+) T cells (r = 0.46, P < 0.001). CD28 median fluorescence intensity in CTLA-4- cells was twice that in CTLA-4+ cells (140 +/- 5.3 versus 70 +/- 2.28, P < 0.00001), whereas cells low in CD28 and CD4, expressed more CTLA-4 (P < 0.0001). Higher proportion of CTLA-4+CD4+ cells expressed CCR5 and Ki-67, in comparison with CTLA-4-CD4+ cells, (65 +/- 11.9 and 25 +/- 7.5% versus 27 +/- 8.9 and 3.7 +/- 2%, P < 0.0001 and P < 0.01, respectively). Among HAART-treated patients, with viral load below detectable levels, CD4+ cells increase was inversely correlated to %CTLA-4+CD4+ cells (r = -0.5, P = 0.003, n = 39). Proliferation of PBMC to anti-CD3, gp-120 depleted HIV-1 antigen or HIV-1 p24 stimulation was inversely correlated with CTLA-4 levels (r = -0.68, P = 0.0035; r = -0.38,P = 0.04; and r = -0.43, P = 0.028, respectively). CONCLUSIONS: (1) CTLA-4 is upregulated during HIV infection and may therefore account for CD4 T-cell decline and anergy in HIV-1 infection. (2) Increased levels of CTLA-4 may undermine immune responses and in the HAART-treated patient-immune reconstitution. (3) Blocking of CTLA-4 may offer a novel approach for immune-based therapy in HIV infection.     

Osteopontin is released from the heart into the coronary circulation in patients with a previous anterior wall myocardial infarction.

The present study was designed to clarify whether osteopontin, an extracellular matrix protein, is released from the heart into the coronary circulation in patients with a previous (>3 months) anterior wall myocardial infarction (MI). Using a commercially available enzyme immunoassay kit, plasma concentrations of osteopontin were measured in 30 patients (26 men, 4 women; mean age, 61+/-12 years). Blood samples were obtained from the aortic root and coronary sinus. The difference in the plasma concentrations of osteopontin in the aortic root and coronary sinus, which reflects the cardiac production of osteopontin released into the coronary circulation, was compared with the left ventricular ejection fraction (LVEF) and volumes obtained from contrast left ventriculography. Plasma osteopontin concentrations were significantly higher in the coronary sinus than in the aortic root (672+/-446 vs 610+/-398 ng/ml, p=0.02). The transcardiac gradient of plasma osteopontin concentration correlated negatively with LVEF (r=-0.55, p=0.0005) and positively with left ventricular (LV) end-diastolic (r=0.63, p=0.0001) and end-systolic volume indexes (r=0.79, p<0.0001). This is the first study to show that in patients with a previous anterior wall MI osteopontin is released from the heart into the coronary circulation in proportion to the LV systolic function and volumes, suggesting that this extramatrix protein is associated with post-MI LV remodeling.     

哈萨克族心力衰竭患者血浆生长分化因子15和B型利钠肽的临床意义

目的:研究血浆生长分化因子15(GDF-15)、B型利钠肽(BNP)对新疆哈萨克族(哈族)心力衰竭(HF)的意义及与其严重程度之间的关系。方法:选取新疆哈族HF患者90例(NYHAⅡ～IV级)及哈族NYHAⅠ级患者30例为研究对象,均采取空腹静脉血,测定血浆BNP及GDF-15水平,同时超声心动图测定各项心功能指标。结果:哈族HF组患者血浆GDF-15和BNP水平明显高于对照组[GDF-15(132.14±56.36)ng/L∶(34.08±10.80)ng/L;BNP(273.78±93.37)ng/ml∶(82.80±15.18)ng/ml,P<0.01],并随NYHA心功能分级的增加而升高,各组间差异均有统计学意义(均P<0.01)。哈族HF患者血浆GDF-15水平与血肌酐(Cr)、左心房前后径(LAD)、左心室舒张末期内径(LVEDd)、NYHA、BNP呈正相关(r=0.266、0.423、0.668、0.925、0.845,P<0.05);与左心室射血分数(LVEF)、左心室短轴缩短率(FS)呈显著负相关(r=-0.807、-0.733,P<0.01)。结论:哈族HF患者血浆GDF-15、BNP水平明显升高,与哈族HF程度密切相关,血浆GDF-15水平是判断哈族HF严重程度有价值的指标。     

Circulating CD4+CD25+ T cells in rheumatic mitral stenosis

BACKGROUND AND AIM OF THE STUDY: Autoimmunity plays an essential role in the pathogenesis of rheumatic heart disease. Although the ongoing rheumatic process has been demonstrated with high levels of inflammatory markers, the cellular mechanism(s) of autoimmunity have not yet been investigated. The study aim was to examine levels of circulating CD4+CD25+ T cells in patients with rheumatic mitral stenosis, and to evaluate the relationship between regulatory CD4+CD25+ T-cell count and clinical and echocardiographic measures. METHODS: A total of 42 patients with mitral stenosis was enrolled into the study, and 27 normal age- and gender-matched healthy subjects served as controls. All patients and controls underwent clinical, electrocardiographic, echocardiographic and laboratory evaluation. T-cell levels were determined with flow cytometry using monoclonal fluorescein isothiocyanate-labeled anti-CD4 and phycoerythrin-labeled anti-CD25 antibodies. RESULTS: The circulating CD4+CD25+ T-cell count was significantly lower in patients with mitral stenosis than in controls (231 +/- 120 versus 372 +/- 180 per mm3; p = 0.001). The percentage ratio of CD4+CD25+ T cells to total leukocytes and lymphocytes was significantly lower in patients with mitral stenosis than in controls (2.9 +/- 1.5 versus 5.2 +/- 2.1; p < 0.001, and 11.2 +/- 5.6 versus 14.8 +/- 5.6; p = 0.011, respectively). In addition, a significant negative correlation was identified between the erythrocyte sedimentation rate and circulating CD4+CD25+ T-cell count (Spearman rho = -0.414; p = 0.006). No correlation was found between CD4+CD25+ T-cell count and clinical and echocardiographic parameters in patients with mitral stenosis. CONCLUSION: A decrease in CD4+CD25+ T cell numbers in mitral stenosis patients might suggest a role for cellular autoimmunity in a smoldering rheumatic process.     

Diminished CD4+CD25+ T-lymphocytes in peripheral blood of patients with systemic lupus erythematosus

The exact aetio-pathogenesis of systemic lupus erythematosus (SLE) is still speculative, where dysregulation or depletion of CD4+CD25+ T lymphocytes is among the supposed mechanisms. In this study, we thought to investigate patients with SLE for percentages of CD4+CD25+ T cells in their peripheral blood and to correlate this with their disease activity scores. Twenty-five patients with SLE who fulfilled, at least, four of the revised Criteria of the American College of Rheumatology (ACR) and twenty healthy volunteers participated in this study. Activity of SLE was assessed by SLE disease activity index (SLEDAI) score. Percentages of CD4+CD25+ T-cells were determined by a flowcytometric technique, while recently activated T-cells were analysed by assaying the expression of the T-cell activation marker, CD69. A statistically significant (p = 0.003) reduction of percentage of CD4+CD25+ T cells was observed among patients (mean 7.16+/-4.53 %) when compared with control subjects (mean 11.36+/-4.50 %), while a non-significant (p = 0.475) low expression of CD69 on CD4+ T cells was observed between patients (mean 0.32+/-0.28 %) and control subjects (mean 0.32+/-0.38 %). In addition, no correlation could be detected between percentages of CD4+CD25+ T cells and SLEDAI scores among SLE patients (p=0.079). In conclusion, this study adds some evidence for the role of CD4+CD25+ T cells in the pathogenesis of SLE that may have some future therapeutic applications.     

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.     

老年心力衰竭患者血浆脑钠素含量与心功能的关系

目的:探讨老年心力衰竭患者血浆脑纳素(BNP)水平与心力衰竭严重程度,左室功能的关系。方法:采用免疫荧光法测定63例心力衰竭患者和30例对照组血浆BNP浓度,用心脏彩色多普勒超声诊断仪测定并比较各组左室射血分数(LVEF)。结果:心力衰竭患者BNP浓度显著高于对照组(P<0.01);BNP水平随着心功能NY-HA分级程度的加重而显著增高,其与LVEF呈负相关(r=-0.58,P<0.001)。结论:老年心力衰竭患者血浆BNP水平随着心力衰竭严重程度的增加而升高,可反映左室功能状态。     

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.     

Association of hyperadiponectinemia with severity of ventricular dysfunction in congestive heart failure.

BACKGROUND: Adiponectin, which is a collagen-like plasma protein produced by adipose tissue, has anti-atherogenic and anti-inflammatory effects. Plasma adiponectin levels in patients with congestive heart failure (CHF) were determined, as well as relationships between the plasma levels of adiponectin and other hormones. METHODS AND RESULTS: The study group comprised 90 patients with CHF and 20 control subjects, who were divided into 4 subgroups according to New York Heart Association (NYHA) functional class. Plasma levels of adiponectin, tumor necrosis factor (TNF)-alpha and brain natriuretic peptide (BNP) and cardiac hemodynamics were determined. Plasma adiponectin levels were significantly increased according to the severity of NYHA class in the patients with CHF; control: 6.2+/-1.0; NYHA I: 8.5+/-1.9, NYHA II: 12.0+/-2.2, NYHA III: 13.0+/-2.7, NYHA IV: 14.9+/-2.7 microg/ml (p=0.0008). Similarly, plasma BNP levels were significantly increased in accordance with the NYHA class. Plasma adiponectin levels correlated positively with BNP (r=0.40, p=0.0002) and TNF-alpha (r=0.49, p=0.0001), and correlated negatively with cardiac index (r=-0.27, p=0.05). In 24 of 46 patients in the NYHA III and IV subgroups, according to the prompt improvement in cardiac function, levels of both plasma adiponectin and BNP were significantly reduced (p<0.0001). CONCLUSION: Plasma adiponectin levels increased according to the severity of CHF and, moreover, they correlated with the plasma levels of BNP and TNF-alpha. These results indicate that augmented release of adiponectin is involved in the pathogenesis of CHF and further study is needed to elucidate its exact role.     

A randomized, placebo-controlled trial assessing the effects of rosiglitazone on echocardiographic function and cardiac status in type 2 diabetic patients with New York Heart Association Functional Class I or II Heart Failure.

OBJECTIVES: This study investigated the effects of rosiglitazone (RSG) on left ventricular ejection fraction (LVEF) in subjects with type 2 diabetes (T2DM) and pre-existing chronic heart failure (CHF) (New York Heart Association [NYHA] functional class I to II). BACKGROUND: Fluid retention is an important consideration in the use of thiazolidinediones in T2DM patients because it could exacerbate symptoms or precipitate decompensation in those with previously stable CHF. METHODS: A total of 224 patients with T2DM and NYHA functional class I to II CHF with LVEF < or =45% were randomized to a 52-week treatment with RSG (4 to 8 mg daily, n = 110) or placebo (PLB) (n = 114) in addition to background antidiabetes therapy. Treatment was uptitrated to achieve target fasting plasma glucose <126 mg/dl; CHF medications were adjusted as appropriate. RESULTS: The LVEF was similar in both groups at baseline (RSG 35.3 +/- 6.2%, PLB 35.7 +/- 7.8%) and after 52 weeks of treatment (mean difference 1.49%, p = 0.1). Glycemic control was significantly better in the RSG group (mean difference in hemoglobin A1c -0.65%, p < 0.0001). There were significantly more adjudicated events in the RSG group of new or worsening edema (RSG n = 28 [25.5%]; PLB n = 10 [8.8%]; p = 0.005) and increased CHF medication (RSG n = 36 [32.7%], PLB n = 20 [17.5%]; p = 0.037), but no significant difference between groups for other adjudicated end points. A similar proportion of patients withdrew from each treatment group because of adverse events. CONCLUSIONS: After 52 weeks of treatment, RSG improved glycemic control but did not adversely affect LVEF in patients with T2DM and NYHA functional class I to II CHF. More fluid-related events occurred with RSG, although these generally did not lead to withdrawal from the study.     

Early and long-term outcome of mitral valve repair with a Cosgrove band combined with coronary revascularization in patients with ischemic cardiomyopathy and moderate-severe mitral regurgitation

BACKGROUND AND AIM OF THE STUDY: Clinical and echocardiographic results were investigated to evaluate mitral valve repair in patients undergoing coronary artery bypass grafting (CABG) for ischemic cardiomyopathy (ICM) with moderately severe mitral regurgitation (MR). METHODS: A total of 78 patients (21 women, 57 men; mean age 69.5 +/- 7.8 years) with ischemic mitral regurgitation underwent mitral valve repair and CABG. The mean left ventricular ejection fraction (LVEF) was 42.4 +/- 12.4%. Among the patients, 19 (24.4%) had preoperative congestive heart failure (CHF). This surgery constituted a second such operation in five patients (6.4%). The MR was grade 3+ in 28 patients (35.9%) and 4+ in 50 (64.1%). The mean number of grafts was 3.6 per patient. RESULTS: Hospital mortality was 11.5% (n = 9). Risk factors for early mortality were preoperative NYHA class > or = III (p = 0.014), preoperative heart failure (p <0.001) and reoperation (p = 0.002). The five-year survival was 82.6 +/- 5.9%, and freedom from grade > or =2+ MR was 93.1 +/- 4.1%. Postoperatively, 66 patients (89.6%) were in NYHA class I and seven (9.4%) in class II, demonstrating a statistically significant improvement (p = 0.03). Late echocardiography showed a significant improvement in LVEF (from 42.4 +/- 12.4% to 51.7 +/- 10.9%; p = 0.01) and a reduction in pulmonary artery pressure (from 37.6 +/- 11.9 mmHg to 29.3 +/- 7.4 mmHg; p = 0.004). CONCLUSION: It is concluded that in patients with ICM, mitral valve repair combined with CABG provides a dramatic improvement in ejection fraction and in CHF, with excellent long-term survival, even in patients with a low LVEF.     

Crohn's disease intestinal CD4+ T cells have impaired interleukin-10 production which is not restored by probiotic bacteria

OBJECTIVE: Crohn's disease (CD) has been associated with low mucosal interleukin (IL)-10 production, but the mechanism behind this deficiency remains unclear. The aim of this study was to investigate IL-10 and interferon (IFN)-gamma production in intestinal CD4+ T cells from CD patients and healthy volunteers (HV) and to examine how this was affected by bacterial products and the presence or absence of autologous dendritic cells. MATERIAL AND METHODS: We cultured intestinal CD4+ T cells from CD patients (n=9) and HV (n=6) and differentiated dendritic cells from their peripheral monocytes. Intestinal T cells were stimulated with Lactobacillus strains or autologous intestinal bacteria in the presence or absence of dendritic cells. IL-10 and IFN-gamma were measured on day 4. RESULTS: When there were autologous dendritic cells present, CD intestinal T cells produced high levels of IFN-gamma (mean 6.4 ng/ml+/-standard error of the mean 1.1 ng/ml) but low levels of IL-10 (0.7 ng/ml+/-0.1 ng/ml). In contrast, HV intestinal T cells produced less IFN-gamma (3.9 ng/ml+/-0.8 ng/ml, p=0.06) and more IL-10 (4.6 ng/ml+/-0.9 ng/ml, p=0.0001) than CD intestinal T cells. Co-culture with Lactobacilli failed to revert this imbalance in CD, but tended to do so in HV. When there were no dendritic cells, CD intestinal T cells responded to autologous bacteria with an increased IFN-gamma production (2.3+/-1.3 ng/ml) compared with HV intestinal T cells (0.3+/-0.2 ng/ml). CONCLUSIONS: Crohn's disease intestinal CD4+ T cells display a pro-inflammatory cytokine profile with impaired production of the regulatory cytokine IL-10. Tolerogenic bacteria (Lactobacilli) failed to restore this regulatory defect.     

Troponin, B-type natriuretic peptides and outcomes in severe heart failure: differences between ischemic and dilated cardiomyopathies

BACKGROUND: Ischemic (ISCM) and idiopathic dilated (IDCM) cardiomyopathies have different responses to therapy and outcomes. Both may demonstrate elevations in troponin and B-type natriuretic peptides, but biomarker levels have not been reported to differ as a function of the etiology of heart failure (HF). Accordingly, we compared these biomarkers in patients with chronic HF. HYPOTHESIS: Biomarker levels of troponin T, troponin I, B-type natriuretic peptide (BNP), and N-terminal prohormone brain natriuretic peptide (NT-proBNP) are quantitatively different between ischemic and idiopathic dilated etiologies of chronic HF. METHODS: Forty patients (27 male, 68 +/- 2 years; LVEF 25 +/- 1%; NYHA Class III-IV) admitted to hospital for acute HF were studied. Biomarkers were drawn at admission prior to treatment intervention. RESULTS: Of the 40 patients, 27 had ISCM and 13 IDCM. Baseline clinical characteristics were similar with the exception of GFR. cTnT, cTnI, and BNP levels were higher in ISCM patients (cTnT: 0.373 +/- 0.145 vs. 0.064 +/- 0.016 ng/mL, p < 0.05; cTnI: 2.02 +/- 0.76 vs. 0.21 +/- 0.11 ng/mL, p < 0.05; BNP: 776 +/- 91 vs. 532 +/- 85 pg/mL, p < 0.05). Cardiovascular mortality during follow up (10 +/- 1 months) was 48% in patients with ISCM and 23% with IDCM (p < 0.05). CONCLUSIONS: Patients with acutely decompensated chronic HF have elevations in troponin and BNP. These elevations, as well as mortality are significantly higher in patients with ISCM compared to IDCM. The differential levels in biomarkers may be due to differences in disease pathogenesis, and fit with the adverse prognosis in these patients.     

西宁地区老年心力衰竭患者血浆脑钠肽和炎性因子水平变化的分析

目的探讨西宁地区(海拔2 260米以上)老年心力衰竭患者血浆脑钠肽(BNP)、C反应蛋白(CRP)、TNF-α水平变化的临床意义。方法将65例心力衰竭患者分为心衰组,同期选择34例健康体检者为对照组。采用美国博适Triage干式快速定量心力衰竭诊断仪检测血浆BNP水平、放射免疫法测定TNFα-水平、ELISA法测定CRP水平,同时行心脏超声检查。20例NYHAⅡ~Ⅳ级患者,常规抗心力衰竭治疗平均3个月后再次接受上述检查并留取血标本。结果(1)心衰组患者血浆BNP、CRP、TNF-α水平明显高于对照组,差异显著(P<0.01);(2)NYHAⅡ~Ⅳ级患者血浆BNP水平较治疗前明显下降;(3)心衰组患者血浆BNP水平在NYHA不同级别之间差异显著,与NYHA呈正相关(r=0.458,P<0.01),与LVEF呈负相关(F=-0.715,P<0.01)。结论血浆BNP、CRP、TNF-α参与了心力衰竭的发病过程,监测上述指标,可预测心力衰竭患者远期NYHA恢复情况,也可作为疗效观察及判定的重要参数。