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)

Updated Clinical Classification of Pulmonary Hypertension

The aim of a clinical classification of pulmonary hypertension (PH) is to group together different manifestations of disease sharing similarities in pathophysiologic mechanisms, clinical presentation, and therapeutic approaches. In 2003, during the 3rd World Symposium on Pulmonary Hypertension, the clinical classification of PH initially adopted in 1998 during the 2nd World Symposium was slightly modified. During the 4th World Symposium held in 2008, it was decided to maintain the general architecture and philosophy of the previous clinical classifications. The modifications adopted during this meeting principally concern Group 1, pulmonary arterial hypertension (PAH). This subgroup includes patients with PAH with a family history or patients with idiopathic PAH with germline mutations (e. g., bone morphogenetic protein receptor-2, activin receptor-like kinase type 1, and endoglin). In the new classification, schistosomiasis and chronic hemolytic anemia appear as separate entities in the subgroup of PAH associated with identified diseases. Finally, it was decided to place pulmonary venoocclusive disease and pulmonary capillary hemangiomatosis in a separate group, distinct from but very close to Group 1 (now called Group 1`). Thus, Group 1 of PAH is now more homogeneous. (J Am Coll Cardiol 2009;54:S43-54) (C) 2009 by the American College of Cardiology Foundation

Diagnosis, Assessment, and Treatment of Non-Pulmonary Arterial Hypertension Pulmonary Hypertension

The 4th World Symposium on Pulmonary Hypertension was the first international meeting to focus not only on pulmonary arterial hypertension (PAH) but also on the so-called non-PAH forms of pulmonary hypertension (PH). The term ""non-PAH PH"" summarizes those forms of PH that are found in groups 2 to 5 of the current classification of PH, that is, those forms associated with left heart disease, chronic lung disease, recurrent venous thromboembolism, and other diseases. Many of these forms of PH are much more common than PAH, but all of them have been less well studied, especially in terms of medical therapy. The working group on non-PAH PH focused mainly on 4 conditions: chronic obstructive lung disease, interstitial lung disease, chronic thromboembolic PH, and left heart disease. The medical literature regarding the role of PH in these diseases was reviewed, and recommendations regarding diagnosis and treatment of PH in these conditions are provided. Given the lack of robust clinical trials addressing PH in any of these conditions, it is important to conduct further studies to establish the role of medical therapy in non-PAH PH. (J Am Coll Cardiol 2009;54:S85-96) (C) 2009 by the American College of Cardiology Foundation

Classical and quantum signatures of competing chi((2)) nonlinearities

We report the observation of the quantum effects of competing chi((2)) nonlinearities. We also report classical signatures of competition, namely, clamping of the second-harmonic power and production of nondegenerate frequencies in the visible. Theory is presented that describes the observations as resulting from competition between various chi((2)) up-conversion and down-conversion processes. We show that competition imposes hitherto unsuspected limits to both power generation and squeezing. The observed signatures are expected to be significant effects in practical systems.

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.)

Renal Cell Carcinoma: T1 and T2 Signal Intensity Characteristics of Papillary and Clear Cell Types Correlated with Pathology

OBJECTIVE. The objective of our study was to describe the T1 and T2 signal intensity characteristics of papillary renal cell carcinoma (RCC) and clear cell RCC with pathologic correlation. MATERIALS AND METHODS. Of 539 RCCs, 49 tumors (21 papillary RCCs and 28 clear cell RCCs) in 45 patients were examined with MRI. Two radiologists retrospectively and independently assessed each tumor`s T1 and T2 signal intensity qualitatively and quantitatively (i.e., the signal intensity [SI] ratio [tumor SI/renal cortex SI]). Of the 49 tumors, 37 (76%) were assessed for pathology features including tumor architecture and the presence of hemosiderin, ferritin, necrosis, and fibrosis. MRI findings and pathology features were correlated. Statistical methods included summary statistics and Wilcoxon`s rank sum test for signal intensity, contingency tables for assessing reader agreement, concordance rate between the two readers with 95% CIs, and Fisher`s exact test for independence, all stratified by RCC type. RESULTS. Papillary RCCs and clear cell RCCs had a similar appearance and signal intensity ratio on T1-weighted images. On T2-weighted images, most papillary RCCs were hypointense (reader 1, 13/21; reader 2, 14/21), with an average mean signal intensity ratio for both readers of 0.67 +/- 0.2, and none was hyperintense, whereas most clear cell RCCs were hyperintense (reader 1, 21/28; reader 2, 17/28), with an average mean signal intensity ratio for both readers of 1.41 +/- 0.4 (p < 0.05). A tumor T2 signal intensity ratio of <= 0.66 had a specificity of 100% and sensitivity of 54% for papillary RCC. Most T2 hypointense tumors exhibited predominant papillary architecture; most T2 hyperintense tumors had a predominant nested architecture (p < 0.05). CONCLUSION. On T2-weighted images, most papillary RCCs are hypointense and clear cell RCCs, hyperintense. The T2 hypointense appearance of papillary RCCs correlated with a predominant papillary architecture at pathology.

Ligaments of the Posterior and Lateral Talar Processes: MRI and MR Arthrography of the Ankle and Posterior Subtalar Joint with Anatomic and Histologic Correlation

OBJECTIVE. MRI and combined ankle and posterior subtalar MR arthrography in cadavers were used to evaluate the ligaments of the posterior and lateral talar processes. Subsequent anatomic and histologic correlation was performed. MATERIALS AND METHODS. Ten cadaveric ankles were used. Routine radiography and MRI were initially performed. Ankle and posterior subtalar MR arthrography, followed by anatomic and histologic analysis, was then performed to allow better assessment of the ligaments of the lateral and posterior talar process. RESULTS. In all subjects, MR arthrography provided superior delineation of the articular and periarticular structures, as well as the ligaments. The lateral talocalcaneal and medial talocalcaneal ligaments were best seen in the axial and coronal planes, respectively. The axial plane was best for visualizing the fibulotalocalcaneal ligament, and the sagittal plane was best for evaluating the posterior talocalcaneal ligament. The anterior and posterior talofibular ligaments and the posterior tibiotalar ligament (superficial and deep portions) were best seen in the axial plane. Histologic analysis was correlated to anatomic sectioning and showed the attachment sites of these ligaments. CONCLUSION. Combined ankle and posterior subtalar MR arthrography enhances visualization of the ligaments attaching to the posterior and lateral talar processes, including the posterior, lateral, and medial talocalcaneal and fibulotalocalcaneal ligaments.

Expression of activated mutants of the human interleukin-3/interleukin-5 granulocyte-macrophage colony-stimulating factor receptor common beta subunit in primary hematopoietic cells induces factor-independent proliferation and differentiation

To date, several activating mutations have been discovered in the common signal-transducing subunit (h beta c) of the receptors for human granulocyte-macrophage colony-stimulating factor, interleukin-3, and interleukin-5. Two of these, Fl Delta and 1374N, result in a 37 amino acid duplication and a single amino acid substitution in the extracellular domain of h beta c, respectively. A third, V449E, results in a single amino acid substitution in the transmembrane domain, Previous studies comparing the activity of these mutants in different hematopoietic cell lines imply that the transmembrane and extracellular mutations act by different mechanisms and suggest the requirement for cell type-specific molecules in signalling. To characterize the ability of these mutant hpc subunits to mediate growth and differentiation of primary cells and hence investigate their oncogenic potential, we have expressed all three mutants in primary murine hematopoietic cells using retroviral transduction. It is shown that, whereas expression of either extracellular hpc mutant confers factor-independent proliferation and differentiation on cells of the neutrophil and monocyte lineages only, expression of the transmembrane mutant does so on these lineages as well as the eosinophil, basophil, megakaryocyte, and erythroid lineages, Factor-independent myeloid precursors expressing the transmembrane mutant display extended proliferation in liquid culture and in some cases yielded immortalized cell lines. (C) 1997 by The American Society of Hematology.

Clinical End Points and Response Criteria in Mycosis Fungoides and Sezary Syndrome: A Consensus Statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer

Mycosis fungoides (MF) and Sezary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin`s lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS. J Clin Oncol 29:2598-2607. (C) 2011 by American Society of Clinical Oncology

An Insight into the Sialotranscriptome of Simulium nigrimanum, a Black Fly Associated with Fogo Selvagem in South America

Pemphigus foliaceus is a life threatening skin disease that is associated with autoimmunity to desmoglein, a skin protein involved in the adhesion of keratinocytes. This disease is endemic in certain areas of South America, suggesting the mediation of environmental factors triggering autoimmunity. Among the possible environmental factors, exposure to bites of black flies, in particular Simulittm nigrimanum has been suggested. In this work, we describe the sialotranscriptome of adult female S. nigrimanum flies. It reveals the complexity of the salivary potion of this insect, comprised by over 70 distinct genes within over 30 protein families, including several novel families, even when compared with the previously described sialotranscriptome of the autogenous black fly, S. vitiation. The uncovering of this sialotranscriptome provides a platform for testing pemphigus patient sera against recombinant salivary proteins from S. nigrimanum and for the discovery of novel pharmacologically active compounds.

Prevalence of fibromyalgia and chronic widespread pain in community-dwelling elderly subjects living in Sao Paulo, Brazil

Objectives: To estimate the prevalence of fibromyalgia (FM) and chronic widespread pain (CWP) in community-dwelling elderly individuals living in Sao Paulo, to assess the spectrum of problems related to these diseases using the Fibromyalgia Impact Questionnaire (FIQ) and to correlate the FIQ with the number of tender points and with pain threshold. Methods: Our sample consisted of 361 individuals (64% women, 36% men, mean age of 73.3 +/- 5.7 years). Individuals were classified into four groups: FM (according to American College of Rheumatology criteria), CWP, regional pain (RP) and no pain (NP). Pain characteristics and dolorimetry for 18 tender points and the FIQ were assessed. Results: The prevalence of FM was 5.5% [95% confidence interval (CI) = 5.4-5.7], and the prevalence of CWP was 14.1% (95% Cl: 10.5-17.7%). The frequency of RP was 52.6% and the prevalence of NP was 27.7%. FIQ scores were higher in people with FM (44.5), followed by CWP (31.4), RP (18.1) and NP (5.5) (p < 0.001). There was a positive correlation between the domains of the FIQ and the number of tender Points (p < 0.05), and a negative correlation between FIQ score and pain threshold (p < 0.05). Conclusion: In our elderly subjects, the prevalence of FM was slightly higher compared to previously reported studies, and CWP was around 14%. The spectrum of problems related to chronic pain was more severe in FM followed by CWP, strongly suggesting that these conditions should be diagnosed and adequately treated in older individuals. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

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.

Expression of constitutively activated human c-Kit in myb transformed early myeloid cells leads to factor independence, histiocytic differentiation, and tumorigenicity

The cDNAs encoding wild type (WT) human receptor tyrosine kinase c-Kit and a constitutively activated mutant, V816Kit, were introduced into granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent early murine hemopoietic cells, which had been transformed with activated Myb, WTKit cells were able to grow in the presence of the human ligand for Kit, stem cell factor (SCF), but displayed reduced growth and clonogenic potential in either SCF or GM-CSF compared with the parental cells in GM-CSF. In contrast, V816Kit cells grew without factor at a higher rate than the parental cells in GM-CSF and displayed increased clonogenicity. Dissection of the growth characteristics in liquid culture showed that in the presence of appropriate factors, the different populations had similar proliferation rates, but that V816Kit profoundly increased cell survival compared with WTKit or parental cells, This suggests that the signals transduced by WTKit activated with SCF, and by V816Kit, were not identical. Also, WTKit and V816Kit-expressing cells both varied from the early myeloid progenitor phenotype of the parental cells and gave rise to a small number of large to giant adherent cells that expressed macrophage (alpha-naphthyl acetate) esterase and neutrophil (naphtol-AS-D-chloroacetate) esterase, were highly phagocytic and phenotypically resembled histiocytes. Thus, WTKit activated by SCF and V816Kit were able to induce differentiation in a proportion of Myb-transformed myeloid cells. The factor independent V816Kit cells, unlike the parental and WTKit expressing cells, were shown to produce tumors of highly mitotic, invasive cells at various stages of differentiation in syngeneic mice. These results imply that constitutively activated Kit can promote the development of differentiated myeloid tumors and that its oncogenic effects are not restricted to lineages (mast cell and B-cell acute lymphoblastic leukemia), which have been reported previously. Furthermore, the mixed populations of cells in culture and in the tumors phenotypically resembled the leukemic cells from patients with monocytic leukemia with histiocytic differentiation (acute myeloid leukemia-M5c), a newly proposed subtype of myeloid leukemia. (C) 1997 by The American Society of Hematology.

Evaluation of interventions to reduce catheter-associated bloodstream infection: Continuous tailored education versus one basic lecture

Background: This study evaluated the impact of 2 models of educational intervention on rates of central venous catheter-associated bloodstream infections (CVC-BSIs). Methods: This was a prospective observational study conducted between January 2005 and June 2007 in 2 medical intensive care units (designated ICU A and ICU B) in a large teaching hospital. The study was divided into in 3 periods: baseline (only rates were evaluated), preintervention (questionnaire to evaluate knowledge of health care workers [HCWs] and observation of CVC care in both ICUs), and intervention (in ICU A, tailored, continuous intervention; in ICU B, a single lecture). The preintervention and intervention periods for each ICU were compared. Results: During the preintervention period, 940 CVC-days were evaluated in ICUA and 843 CVC-days were evaluated in ICU B. During the intervention period, 2175 CVC-days were evaluated in ICUA and 1694 CVC-days were evaluated in ICU B. Questions regarding CVC insertion, disinfection during catheter manipulation, and use of an alcohol-based product during dressing application were answered correctly by 70%-100% HCWs. Nevertheless, HCWs` adherence to these practices in the preintervention period was low for CVC handling and dressing, hand hygiene (6%-35%), and catheter hub disinfection (45%-68%). During the intervention period, HCWs` adherence to hand hygiene was 48%-98%, and adherence to hub disinfection was 82%-97%. CVC-BSI rates declined in both units. In ICUA, this decrease was progressive and sustained, from 12CVC-BSIs/1000 CVC-days at baseline to 0 after 9 months. In ICU B, the rate initially dropped from 16.2 to 0 CVC-BSIs/1000 CVC-days, but then increased to 13.7 CVC-BSIs/1000 CVC-days. Conclusion: Personal customized, continuous intervention seems to develop a ""culture of prevention"" and is more effective than single intervention, leading to a sustained reduction of infection rates.

Outbreak of vancomycin-resistant enterococci in a tertiary hospital: The lack of effect of measures directed mainly by surveillance cultures and differences in response between Enterococcus faecium and Enterococcus faecalis

To describe the effect of active surveillance to control vancomycin-resistant enterococci (VRE) after an outbreak, 549 surveillance rectal cultures were performed in 308 patients (35% positive). An educational intervention to prevent transmission was implemented. Infection and colonization by VR-Enterococcus faecalis decreased, but Enterococcus faecium persisted despite control measures. Infections by VR-E faecalis fell to zero in 2008. We observed difficulties in controlling colonization with measures directed mainly by surveillance cultures and differences between responses of E faecium and E faecalis.