Nuclear localization of RelB is associated with effective antigen-presenting cell function

Dendritic cells (DC) are potent APCs that enter resting tissues as precursors and, after Ag exposure, differentiate and migrate to draining lymph nodes. The phenotype of RelB knockout mice implicates this member of the NF kappa B/Rel family in DC differentiation. To further elucidate the role of RelB in DC differentiation, mRNA, intracellular protein expression, and DNA binding activity of RelB were examined in immature and differentiated human DC, as well as other PB mononuclear cell populations. RelB protein and mRNA were detected constitutively in lymphocytes and in activated monocytes, differentiated DC, and monocyte-derived DC. Immunohistochemical staining demonstrated RelB within the differentiated lymph node interdigitating DC and follicular DC, but not undifferentiated DC in normal skin. Active nuclear RelB was detected by supershift assay only in differentiated DC derived from either PB precursors or monocytes and in activated B cells. These RelB+ APC were potent stimulators of the MLR. The data indicate that RelB expression is regulated both transcriptionally and post-translationally in myeloid cells. Within the nucleus, RelB may specifically transactivate genes that are critical for APC function.

Thyroid Function After Unilateral Total Lobectomy

Objective: To evaluate the incidence of postoperative hypothyroidism among patients who underwent unilateral total lobectomy and identify related factors. Design: Retrospective medical record analysis. Setting: Oncological center and private clinic. Patients: From March 1996 to July 2005, 228 euthyroid patients underwent unilateral total lobectomy for benign diseases; 168 had all the information required for inclusion in this study. Main Outcome Measures: Serum levels of thyrotropin and antithyroidal antibodies were assessed, as well as ultrasonographic evaluation of the remaining thyroid lobe and review of all histological specimens, with emphasis on lymphocytic infiltration. Hypothyroidism was defined as thyrotropin level greater than 5.5 mU/L. Results: Most patients were female (88%), with a median (range) age of 45 (16-72) years. Hypothyroidism occurred in 61 cases (32.8%), during a median follow-up period of 29 months (range, 6-108 months). Statistically related factors included higher preoperative thyrotropin levels (2.1 mU/L among hypothyroid patients vs 1.2 mU/L in euthyroid patients; P<.001), smaller thyroid remnant volume (3.9 mL vs; 6.0 mL, respectively; P = .003); right vs left lobectomy (P = .006), and higher thyroperoxidase antibody serum levels (P = .009). Conclusions: Postoperative hypothyroidism appeared in 32.8% of the cases in this series, especially among patients with elevated preoperative thyrotropin and postoperative thyroperoxidase antibody levels, after right lobectomy and when a smaller thyroid remnant was left. After confirmation with larger prospective series, these results may support the indication for early postoperative hormone supplementation in these instances.

Testicular Sertoli cell function in male systemic lupus erythematosus

Objective. To assess the testicular Sertoli cell function in male SLE patients. Methods. Thirty-four consecutive patients were prospectively selected to evaluate serum inhibin B. Clinical features, treatment, semen analysis, urological evaluation, testicular ultrasound, hormones and anti-sperm antibodies were determined. Results. Patients were subdivided into two groups: low serum inhibin B (Group 1, n = 8) and normal levels (Group 2, n 26). The median sperm concentration (P = 0.024), total sperm count (P = 0.023) and total motile sperm count (P = 0.025) were lower in Group 1. Inhibin B levels were positively correlated with sperm concentration (r = 0.343), total motile sperm count (r = 0.357), and negatively correlated with follicule-stimulating hormone (FSH) (r = 0.699) and luteinizing hormone (r = 0.397). The median serum inhibin B was lower in SLE patients treated with intravenous cyclophosphamide (IVCYC) compared with those without this therapy (P = 0.031). Further evaluation of the 26 SLE patients with normal inhibin B and FSH levels revealed that medians of inhibin B/FSH ratio were lower in SLE patients with oligozoospermia compared with normozoospermia (P = 0.004). This ratio was also lower in SLE patients treated with IVCYC than those without this therapy (P = 0.04). In contrast, inhibin B serum level alone did not discriminate the later group of patients (P = 0.12). Conclusions. This is the first study to identify a high frequency of testicular Sertoli cell dysfunction in male SLE associated with semen abnormalities. Further prospective studies are necessary to determine if inhibin levels and inhibin B/FSH ratio will be an earlier and useful marker of IVCYC toxicity in these patients.

Exhaled nitric oxide for monitoring childhood asthma inflammation compared to sputum analysis, serum interleukins and pulmonary function

The level of fractional exhaled nitric oxide (FENO) is significantly elevated in uncontrolled asthma and decreases after anti-inflammatory therapy The aim of this prospective study was to analyze the behavior of FENO in the follow-up and management of the inflammation in asthmatic pediatric patients treated with inhaled corticosteroids (ICS), compared to sputum cellularity, serum interleukins (IL), and pulmonary function. Twenty-six clinically stable asthmatic children aged from 6 to 18 years, previously treated or not with ICS were included. Following an international consensus (GINA), the patients were submitted to standard treatment with inhaled fluticasone for 3 months according to the severity of the disease. During this period, each patient underwent three assessments at intervals of approximately 6 weeks: Each evaluation consisted of the measurement of FENO, determination of serum interleukins IL-5, IL-10, IL-13, and interferon gamma (INF-gamma), spirometry and cytological analysis of spontaneous or induced sputum. A significant reduction in mean FENO and IL-5, without concomitant changes in FEV1, was observed along the study. There was no significant correlation between FeNO and FEV1 in the three assessments. A significant correlation between FeNO and IL-5 levels was only observed in the third assessment (r = 0.499, P=0.025). In most patients, serum IL-10, IL-13, and INF-gamma concentrations were undetectable throughout the study Sputum samples were obtained spontaneously in 11 occasions and in 56 by induction with 3% hypertonic saline solution (success rate: 50.8%), with 39 (69.9%) of them adequate for analysis. Only two of the 26 patients produced adequate samples in the three consecutive evaluations, which impaired the determination of a potential association between sputum cellularity and FeNO levels throughout the study. In conclusion, among the parameters of this study, it was difficult to perform and to interpret the serial analysis of spontaneous or induced sputum. Serum interleukins, which remained at very low or undetectable levels in most patients, were not found to be useful for therapeutic monitoring, except for IL-5 that seems to present some correlation with levels of FeNO exhaled. Monitoring of the mean FEV1 indicated no significant variations during the treatment, demonstrating that functional stability or the absence of obstruction may not reflect the adequate management of asthma. Serial measurement of FeNO seemed to best reflect the progressive anti-inflammatory action of ICS in asthma.

Creatine supplementation does not impair kidney function in type 2 diabetic patients: a randomized, double-blind, placebo-controlled, clinical trial

Creatine supplementation may have a therapeutic role in diabetes, but it is uncertain whether this supplement is safe for kidney function. The aim of this study was to investigate the effects of creatine supplementation on kidney function in type 2 diabetic patients. A randomized, double-blind, placebo-controlled trial was performed. The patients were randomly allocated to receive either creatine or placebo for 12 weeks. All the patients underwent exercise training throughout the trial. Subjects were assessed at baseline and after the intervention. Blood samples and 24-h urine samples were obtained for kidney function assessments. Additionally, (51)Cr-EDTA clearance was performed. To ensure the compliance with creatine intake, we also assessed muscle phosphorylcreatine content. The creatine group presented higher muscle phosphorylcreatine content when compared to placebo group (CR Pre 44 +/- A 10, Post 70 +/- A 18 mmol/kg/wt; PL Pre 52 +/- A 13, Post 46 +/- A 13 mmol/kg/wt; p = 0.03; estimated difference between means 23.6; 95% confidence interval 1.42-45.8). No significant differences were observed for (51)Cr-EDTA clearance (CR Pre 90.4 +/- A 16.9, Post 96.1 +/- A 15.0 mL/min/1.73 m(2); PL Pre 97.9 +/- A 21.6, Post 96.4 +/- A 26.8 mL/min/1.73 m(2); p = 0.58; estimated difference between means -0.3; 95% confidence interval -24.9 to 24.2). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria were unchanged. CR supplementation does not affect kidney function in type 2 diabetic patients, opening a window of opportunities to explore its promising therapeutic role in this population. ClinicalTrials.gov registration number: NCT00992043.

Mandibular Function is Severely Impaired in Systemic Sclerosis Patients

Aims: To evaluate the presence of temporomandibular disorders (TMD) in systemic sclerosis (SSc) patients and its possible association with the severity of skin involvement. Methods: The presence of TMD was evaluated in 35 SSc women and 30 age- and sex-matched healthy controls by means of the anamnestic (A(i)) and clinical (D(i)) Helkimo indices; the jaw mobility was further analyzed (M(I)). Skin involvement was scored by the Modified Rodnan Skin Score (MRSS). Results: Signs and symptoms of TMD were more frequent in SSc patients than in controls, the frequency distribution of the different clinical dysfunction indices differing significantly (P < .001) between patients (D(i)0 8.6%, D(i)I 48.6%, D(i)II 22.8%, and D(i)III 20%) and controls (D(i)0 50%, D(i)I 33.3%, and D(i)II 16.7%). Cyclophosphamide for severe and rapidly progressive cutaneous fibrosis was prescribed in six out of seven patients with severe signs (D(i)III), in contrast this treatment was indicated for only two out of 25 patients with mild to moderate signs (D(i)I and D(i)II, P <. 001). Impaired jaw mobility was more frequent in SSc patients than controls (P < .001). It was severe in 77.1% (M(I)II) and mild in 22.9% (M(1)I) of the cases, in contrast to controls (M(I)0 33.4%, M(I)I 53.3%, and M(I)II 13.3%; P < .001). Approximately half of SSc patients with severe (M(I)II) but none of those with mild impairment were on cyclophosphamide treatment for severe cutaneous fibrosis (P = .02). Conclusion: Severe signs of TMD according to the anamnestic and clinical Helkimo indices were very frequent in SSc patients. J OROFAC PAIN 2010;24:197-202

Clinical Approaches to Preserve beta-Cell Function in Diabetes

In type 2 diabetes (DM2) there is progressive deterioration in beta-cell function and mass. It was found that islet function was about 50% of normal at the time of diagnosis and reduction in beta-cell mass of about 60% at necropsy (accelerated apoptosis). Among the interventions to preserve the beta-cells, those to lead to short-term improvement of beta-cell secretion are weight loss, metformin, sulfonylureas, and insulin. The long-term improvement was demonstrated with short-term intensive insulin therapy of newly diagnosed DM2, the use of antiapoptotic drugs such as glitazones, and the use of glucagon-like peptide-1 receptor agonists (GLP-1 mimetics), not inactivated by the enzyme dipeptidyl peptidase 4 and/or to inhibit that enzyme (GLP-1 enhancers). The incretin hormones are released from the gastrointestinal tract in response to nutrient ingestion to enhance glucose-dependent insulin secretion from the pancreas and overall maintenance of glucose homeostasis. From the two major incretins, GLP-1 and GIP (glucose-dependent insulinotropic polypeptide), only the first one or its mimetics or enhancers can be used for treatment. The GLP-1 mimetics exenatide and liraglutide as well as the DPP4 inhibitors (sitagliptin and vildagliptin) were approved for treatment of DM2.

Qualitative and Quantitative Real Time Myocardial Contrast Echocardiography for Detecting Hibernating Myocardium

Background: Real time myocardial contrast echocardiography (RTMCE) is an emerging imaging modality for assessing myocardial perfusion that allows for noninvasive quantification of regional myocardial blood flow (MBF). Aim: We sought to assess the value of qualitative analysis of myocardial perfusion and quantitative assessment of myocardial blood flow (MBF) by RTMCE for predicting regional function recovery in patients with ischemic heart disease who underwent coronary artery bypass grafting (CABG). Methods: Twenty-four patients with coronary disease and left ventricular systolic dysfunction (ejection fraction < 45%) underwent RTMCE before and 3 months after CABG. RTMCE was performed using continuous intravenous infusion of commercially available contrast agent with low mechanical index power modulation imaging. Viability was defined by qualitative assessment of myocardial perfusion as homogenous opacification at rest in >= 2 segments of anterior or >= 1 segment of posterior territory. Viability by quantitative assessment of MBF was determined by receiver-operating characteristics curve analysis. Results: Regional function recovery was observed in 74% of territories considered viable by qualitative analysis of myocardial perfusion and 40% of nonviable (P = 0.03). Sensitivity, specificity, positive and negative predictive values of qualitative RTMCE for detecting regional function recovery were 74%, 60%, 77%, and 56%, respectively. Cutoff value of MBF for predicting regional function recovery was 1.76 (AUC = 0.77; 95% CI = 0.62-0.92). MBF obtained by RTMCE had sensitivity of 91%, specificity of 50%, positive predictive value of 75%, and negative predictive value of 78%. Conclusion: Qualitative and quantitative RTMCE provide good accuracy for predicting regional function recovery after CABG. Determination of MBF increases the sensitivity for detecting hibernating myocardium. (Echocardiography 2011;28:342-349).

Long-Term Pulmonary Vascular Reactivity After Orthotopic Heart Transplantation by the Biatrial Versus the Bicaval Technique

Introduction. Advantages of the bicaval versus the biatrial technique have been reported, emphasizing atrial electrical stability and less tricuspid regurgitation. Objective. To analyze the impact of the surgical technique on long-term pulmonary pressures, contractility, and graft valvular behavior after heart transplantation. Methods. Among 400 orthotopic heart transplantation recipients from 1985 to 2010, we selected 30 consecutive patients who had survived beyond 3 years. The biatrial versus bicaval surgical technique groups included 15 patients each. Their preoperative clinical characteristics were similar. None of the patients displayed a pulmonary vascular resistance or pulmonary artery pressure over 6U Wood or 60 mm Hg, respectively. We evaluated invasive hemodynamic parameters during routine endomyocardial biopsies. Two-dimensional echocardiographic parameters were obtained from routine examinations. Results. There were no significant differences regarding right atrial pressure, systolic pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, cardiac index, systolic blood pressure, left ventricular ejection fraction, and mitral regurgitation (P > .05). Tricuspid regurgitation increased significantly over the 3 years of observation only among the biatrial group (P = .0212). In both groups, the right atrial pressure, pulmonary wedge capillary pressure, transpulmonary gradient, and pulmonary vascular resistance decreased significantly (P < .05) from the pre- to the postoperative examination. In both groups cardiac index and systemic blood pressure increased significantly after transplantation (P < .05). Comparative analysis of the groups only showed significant differences regarding right atrial pressure and degree of tricuspid regurgitation; the bicaval group showing the best performance. Conclusions. Both surgical techniques ensure adequate left ventricular function in the long term; however, the bicaval technique provided better trends in hemodynamic performance, as well as a lower incidence and severity of tricuspid valve dysfunction.

Reference Values of Tissue Doppler Imaging and Pulsed Doppler Echocardiography for Analysis of Left Ventricular Diastolic Function in Healthy Adults

To determine reference values for tissue Doppler imaging (TDI) and pulsed Doppler echocardiography for left ventricular diastolic function analysis in a healthy Brazilian adult population. Observations were based on a randomly selected healthy population from the city of Vitoria, Espirito Santo, Brazil. Healthy volunteers (n = 275, 61.7% women) without prior histories of cardiovascular disease underwent transthoracic echocardiography. We analyzed 175 individuals by TDI and evaluated mitral annulus E`- and A`-waves from the septum (S) and lateral wall (L) to calculate E`/A` ratios. Using pulsed Doppler echocardiography, we further analyzed the mitral E- and A-waves, E/A ratios, isovolumetric relaxation times (IRTs), and deceleration times (DTs) of 275 individuals. Pulsed Doppler mitral inflow mean values for men were as follows: E-wave: 71 +/- 16 cm/sec, A-wave: 68 +/- 15 cm/sec, IRT: 74.8 +/- 9.2 ms, DT: 206 +/- 32.3 ms, E/A ratio: 1.1 +/- 0.3. Pulsed Doppler mitral inflow mean values for women were as follows: E-wave: 76 +/- 17, A-wave: 69 +/- 14 cm/sec, IRT: 71.2 +/- 10.5 ms, DT: 197 +/- 33.3 ms, E/A ratio: 1.1 +/- 0.3. IRT and DT values were higher in men than in women (P = 0.04 and P = 0.007, respectively). TDI values in men were as follows: E`S: 11 +/- 3 cm/sec, A`S: 13 +/- 2 cm/sec, E`S/A`S: 0.89 +/- 0.2, E`L: 14 +/- 3 cm/sec, A`L: 14 +/- 2 cm/sec, E`L/A`L: 1.1 +/- 0.4. E-wave/ E`S ratio: 6.9 +/- 2.2; E-wave / E`L ratio: 4.9 +/- 1.7. In this study, we determined pulsed Doppler and TDI derived parameters for left ventricular diastolic function in a large sample of healthy Brazilian adults. (Echocardiography 2010;27:777-782).

Effects of Exercise Training on Myocardial Blood Flow Reserve in Patients With Heart Failure and Left Ventricular Systolic Dysfunction

Exercise training has been shown to be effective in improving exercise capacity and quality of life in patients with heart failure and left ventricular (LV) systolic dysfunction. Real-time myocardial contrast echocardiography (RTMCE) is a new technique that allows quantitative analysis of myocardial blood flow (MBF). The aim of this study was to determine the effects of exercise training on MBF in patients with LV dysfunction. We studied 23 patients with LV dysfunction who underwent RTMCE and cardiopulmonary exercise testing at baseline and 4 months after medical treatment (control group, n = 10) or medical treatment plus exercise training (trained group, n = 13). Replenishment velocity (0) and MBF reserves were derived from quantitative RTMCE. The 4-month exercise training consisted of 3 60-minute exercise sessions/week at an intensity corresponding to anaerobic threshold, 10% below the respiratory compensation point. Aerobic exercise training did not change LV diameters, volumes, or ejection fraction. At baseline, no difference was observed in MBF reserve between the control and trained groups (1.89, 1.67 to 1.98, vs 1.81, 1.28 to 2.38, p = 0.38). Four-month exercise training resulted in a significant increase in beta reserve from 1.72 (1.45 to 1.48) to 2.20 (1.69 to 2.77, p <0.001) and an MBF reserve from 1.81 (1.28 to 2.38) to 3.05 (2.07 to 3.93, p <0.001). In the control group, 13 reserve decreased from 1.51 (1.10 to 1.85) to 1.46 (1.14 to 2.33, p = 0.03) and MBF reserve from 1.89 (1.67 to 1.98) to 1.55 (1.11 to 2.27, p <0.001). Peak oxygen consumption increased by 13.8% after 4 months of exercise training and decreased by 1.9% in the control group. In conclusion, exercise training resulted in significant improvement of MBF reserve in patients with heart failure and LV dysfunction. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:243-248)

Subclinical Regional Left Ventricular Dysfunction in Obese Patients With and Without Hypertension or Hypertrophy

We investigated the impact of obesity on the abnormalities of systolic and diastolic regional left ventricular (LV) function in patients with or without hypertension or hypertrophy, and without heart failure. We studied 120 individuals divided into 6 groups of 20 patients (42 +/- 6 years, 60 females) using standard and pulsed-wave tissue Doppler imaging (TDI) echocardiography, and heterogeneity index (HI): nonobese (I: no hypertension, no hypertrophy, control group; II: hypertension, no hypertrophy; III: hypertension and hypertrophy) and obese (IV: no hypertension, no hypertrophy; V: hypertension, no hypertrophy; VI: hypertension and hypertrophy). The criterion for obesity was BMI >= 30 kg/m(2), for hypertension was blood pressure >= 140/90 mm Hg, for hypertrophy in nonobese was LV mass/body surface area (BSA) >134 g/m(2) (men) and >110 mg/m(2) (women), and in obese was LV mass/height((2.7)) >50 (men) and >40 (women). Obese groups had normal LV ejection fraction compared with nonobese groups, but decreased longitudinal and radial systolic myocardial peak velocities (S`), and early diastolic myocardial peak velocity (E`). Also, a great variability of E` and late diastolic myocardial peak velocity (A`) from the longitudinal basal region was observed in obese groups (E` basal nonobese: 11 +/- 7 vs. obese 19 +/- 11, P < 0.001, A` basal nonobese: 7 +/- 4 vs. obese 11 +/- 7, P < 0.001). Our findings were more evident when comparing groups IV with V and VI, with the latter having concentric hypertrophy and obvious segmental systolic and diastolic dysfunctions. Subclinical myocardial alterations and increased variability of the velocities were observed in obese groups, especially with hypertension and hypertrophy, reflecting impaired regional LV relaxation, segmental atrial, and systolic dysfunctions.

Effects of Exercise Training in Patients with Chronic Heart Failure and Sleep Apnea

Study Objectives: To test the effects of exercise training on sleep and neurovascular control in patients with systolic heart failure with and without sleep disordered breathing. Design: Prospective interventional study. Setting: Cardiac rehabilitation and exercise physiology unit and sleep laboratory. Patients: Twenty-five patients with heart failure, aged 42 to 70 years, and New York Heart Association Functional Class I-III were divided into 1 of 3 groups: obstructive sleep apnea (n = 8), central sleep apnea (n 9) and no sleep apnea (n = 7). Interventions: Four months of no-training (control) followed by 4 months of an exercise training program (three 60-minute, supervised, exercise sessions per week). Measures and Results: Sleep (polysomnography), microneurography, forearm blood flow (plethysmography), peak VO(2). and quality of life were evaluated at baseline and at the end of the control and trained periods. No significant changes occurred in the control period. Exercise training reduced muscle sympathetic nerve activity (P < 0.001) and increased forearm blood flow (P < 0.01), peak VO(2) (P < 0.01), and quality of life (P < 0.01) in all groups, independent of the presence of sleep apnea. Exercise training improved the apnea-hypopnea index, minimum O(2) saturation, and amount stage 3-4 sleep (P < 0.05) in patients with obstructive sleep apnea but had no significant effects in patients with central sleep apnea. Conclusions. The beneficial effects of exercise training on neurovascular function, functional capacity, and quality of life in patients with systolic dysfunction and heart failure occurs independently of sleep disordered breathing. Exercise training lessens the severity of obstructive sleep apnea but does not affect central sleep apnea in patients with heart failure and sleep disordered breathing.

Quantification of Regional Left and Right Ventricular Deformation Indices in Healthy Neonates by Using Strain Rate and Strain Imaging

Background: Color Doppler myocardial imaging (CDMI) allows the calculation of local longitudinal or radial strain rate (SR) and strain (epsilon). The aims of this study were to determine the feasibility and reproducibility of longitudinal and radial SR and epsilon in neonates during the first hours of life and to establish reference values. Methods: Data were obtained from 55 healthy neonates (29 male; mean age, 20 +/- 14 hours; mean birth weight, 3,174 +/- 374 g). Apical and parasternal views quantified regional longitudinal and radial SR and epsilon in differing ventricular wall segments. Values at peak systole, early diastole, and late diastole were calculated from the extracted curves. CDMI data acquired at 300 +/- 50 frames/s were analyzed offline. Three consecutive cardiac cycles were measured during normal respiration. The timing of specific systolic or diastolic regional events was determined. Multiple comparisons between walls and segments were made. Results: Left ventricular (LV) longitudinal deformation showed basal differences compared with apical segments within one specific wall. Right ventricular (RV) longitudinal deformation was not homogeneous, with significant differences between basal and apical segments. Longitudinal 3 values were higher in the RV free basal and middle wall segments compared with the left ventricle. In the RV free wall apical segment, longitudinal SR and 3 were maximal. LV systolic SR and epsilon values were higher radially compared with longitudinally (radial peak systolic SR midportion, 2.9 +/- 0.6 s(-1); radial peak systolic epsilon 53.8 +/- 19%; longitudinal peak systolic SR midportion, -1.8 +/- 0.5 s(-1); longitudinal peak systolic epsilon, -24.8 +/- 3%; P < .01). Longitudinal systolic epsilon and SR interobserver variability values were 1.2% and 0.7%, respectively. Conclusion: Ultrasound-based SR and 3 imaging is a practical and reproducible clinical technique in neonates, allowing the calculation of regional longitudinal and radial deformation in RV and LV segments. These regional SR and epsilon indices represent new, noninvasive parameters that can quantify normal neonate regional cardiac function. Independent from visual interpretation, they can be used as reference values for diagnosis in ill neonates. (J Am Soc Echocardiogr 2009;22:369-375.)