Improved accuracy in flow mapping of congenital heart disease using stationary phantom technique

<p>Abstract</p> <p>Background</p> <p>Flow mapping by cardiovascular magnetic resonance has become the gold standard for non-invasively defining cardiac output (CO), shunt flow and regurgitation. Previous reports have highlighted the presence of inherent errors in flow mapping that are improved with the use of a stationary phantom control. To our knowledge, these studies have only been performed in healthy volunteers.</p> <p>Results</p> <p>We analyzed the variation in flow measurements made with and without stationary phantom correction in 31 patients with congenital heart disease. Variation in stroke volume (SV) measurements was seen in all vessels across all patient groups. The variation was largest when analyzing the right ventricular outflow tract (RVOT), with a range of absolute differences in SV from 0.2 to 70 ml and in CO from 0.02 to 4.8 L/min. In patients with repaired Tetrology of Fallot (ToF), the average ratio of pulmonary to systemic blood flow (Qp:Qs) was 1.18 without and 1.02 with phantom correction. Without performing phantom correction, 23% of the repaired ToF patients were classified as having a residual shunt as compared to 0% when flow mapping was performed with phantom correction. Similarly, in patients with known atrial level shunting (ASD/PAPVR) 20% of patients had no shunt when flow mapping was performed without phantom correction as compared to 0% with phantom correction. In patients with bicuspid aortic valves (BAV), the differences in the regurgitant fraction between measuring flow with and without phantom correction ranged from 0 to 30%, while the regurgitant fraction in the RVOT of ToF patients varied by as much as 31%.</p> <p>Conclusion</p> <p>The impact of inherent errors in CMR flow mapping should not be underestimated. While the variation across a population may not display a significant trend, for any individual patient it can be quite large. Failure to correct for such variation can lead to clinically significant misinterpretation of flow data. The use of the stationary phantom correction technique appears to improve accuracy both in normal patients as well as those with congenital heart disease.</p

Influenza Virus–induced Dendritic Cell Maturation Is Associated with the Induction of Strong T Cell Immunity to a Coadministered, Normally Nonimmunogenic Protein

We evaluated the proposal that during microbial infection, dendritic cells (DCs) undergo maturation and present a mixture of peptides derived from the microbe as well as harmless environmental antigens. Mice were exposed to an aerosol of endotoxin free ovalbumin (OVA) in the absence or presence of influenza virus. In its absence, OVA failed to induce B and T cell responses and even tolerized, but with influenza, OVA-specific antibodies and CD8+ cytolytic T lymphocytes developed. With or without infection, OVA was presented selectively in the draining mediastinal lymph nodes, as assessed by the comparable proliferation of infused, CD8+ and CD4+, TCR transgenic T cells. In the absence of influenza, these OVA-specific T cells produced little IL-2, IL-4, IL-10, and IFN-γ, but with infection, both CD4+ and CD8+ T cells made high levels of IL-2 and IFN-γ. The OVA plus influenza-treated mice also showed accelerated recovery to a challenge with recombinant vaccinia OVA virus. CD11c+ DCs from the mediastinal lymph nodes of infected mice selectively stimulated both OVA- and influenza-specific T cells and underwent maturation, with higher levels of MHC class II, CD80, and CD86 molecules. The relatively slow (2–3 d) kinetics of maturation correlated closely to the time at which OVA inhalation elicited specific antibodies. Therefore respiratory infection can induce DC maturation and simultaneously B and T cell immunity to an innocuous antigen inhaled concurrently

Granulocyte Colony-Stimulating Factor Protects Mice during Respiratory Virus Infections

A burst in the production of pro-inflammatory molecules characterizes the beginning of the host response to infection. Cytokines, chemokines, and growth factors work in concert to control pathogen replication and activate innate and adaptive immune responses. Granulocyte colony-stimulating factor (G-CSF) mobilizes and activates hematopoietic cells from the bone marrow, and it has been shown to mediate the generation of effective immunity against bacterial and fungal infections. G-CSF is produced at high levels in the lungs during infection with influenza and parainfluenza viruses, but its role during these infections is unknown. Here we show that during infection of mice with a non-lethal dose of influenza or Sendai virus, G-CSF promotes the accumulation of activated Ly6G+ granulocytes that control the extent of the lung pro-inflammatory response. Remarkably, these G-CSF-mediated effects facilitate viral clearance and sustain mouse survival

Buying Time—The Immune System Determinants of the Incubation Period to Respiratory Viruses

Respiratory viruses cause disease in humans characterized by an abrupt onset of symptoms. Studies in humans and animal models have shown that symptoms are not immediate and appear days or even weeks after infection. Since the initial symptoms are a manifestation of virus recognition by elements of the innate immune response, early virus replication must go largely undetected. The interval between infection and the emergence of symptoms is called the incubation period and is widely used as a clinical score. While incubation periods have been described for many virus infections the underlying mechanism for this asymptomatic phase has not been comprehensively documented. Here we review studies of the interaction between human pathogenic respiratory RNA viruses and the host with a particular emphasis on the mechanisms used by viruses to inhibit immunity. We discuss the concept of the “stealth phase”, defined as the time between infection and the earliest detectable inflammatory response. We propose that the “stealth phase” phenomenon is primarily responsible for the suppression of symptoms during the incubation period and results from viral antagonism that inhibits major pathways of the innate immune system allowing an extended time of unhindered virus replication

Hepatic fibrogenesis requires sympathetic neurotransmitters

Background and aims: Hepatic stellate cells (HSC) are activated by liver injury to become proliferative fibrogenic myofibroblasts. This process may be regulated by the sympathetic nervous system (SNS) but the mechanisms involved are unclear. Methods: We studied cultured HSC and intact mice with liver injury to test the hypothesis that HSC respond to and produce SNS neurotransmitters to promote fibrogenesis. Results: HSC expressed adrenoceptors, catecholamine biosynthetic enzymes, released norepinephrine (NE), and were growth inhibited by α- and β-adrenoceptor antagonists. HSC from dopamine β-hydroxylase deficient (Dbh(−/−)) mice, which cannot make NE, grew poorly in culture and were rescued by NE. Inhibitor studies demonstrated that this effect was mediated via G protein coupled adrenoceptors, mitogen activated kinases, and phosphatidylinositol 3-kinase. Injury related fibrogenic responses were inhibited in Dbh(−/−) mice, as evidenced by reduced hepatic accumulation of α-smooth muscle actin(+ve) HSC and decreased induction of transforming growth factor β1 (TGF-β1) and collagen. Treatment with isoprenaline rescued HSC activation. HSC were also reduced in leptin deficient ob/ob mice which have reduced NE levels and are resistant to hepatic fibrosis. Treating ob/ob mice with NE induced HSC proliferation, upregulated hepatic TGF-β1 and collagen, and increased liver fibrosis. Conclusions: HSC are hepatic neuroglia that produce and respond to SNS neurotransmitters to promote hepatic fibrosis

Broadband acoustic measurement of an agar-based tissue mimicking material - a longitudinal study

Commercially available ultrasound quality assurance test phantoms rely upon the long-term acoustic stability of tissue-mimicking-materials (TMMs). The measurement of the acoustic properties can be technically challenging and it is important to ensure its stability. The standard technique is to film-wrap samples of TMM and to measure the acoustic properties in a water bath. In this study, a modified technique is proposed whereby the samples of TMM are measured in a preserving fluid that is intended to maintain their characteristics. The acoustic properties were evaluated using a broadband pulse-echo substitution technique over the frequency range of 4.5 – 50 MHz at 0, 6 and 12 months using both techniques. For both techniques, the measured mean values for the speed of sound and the attenuation were very similar and within the IEC recommended value. However, the results obtained using the proposed modified technique demonstrated greater stability over the 1-year period when compared with the results acquired using the standard technique

Alpha-defensins 1-3 release by dendritic cells is reduced by estrogen

<p>Abstract</p> <p>Background</p> <p>During pregnancy the immune system of the mother must protect any activation that may negatively affect the fetus. Changes in susceptibility to infection as well as resolution of some autoimmune disorders represent empirical evidence for pregnancy related alterations in immunity. Sex hormones reach extremely high levels during pregnancy and have been shown to have direct effects on many immune functions including the antiviral response of dendritic cells. Among the immunologically active proteins secreted by monocyte derived DCs (MDDC) are the alpha-defensins 1-3. This family of cationic antimicrobial peptides has a broad spectrum of microbicidal activity and has also been shown to link innate to adaptive immunity by attracting T cells and immature DCs, which are essential for initiating and polarizing the immune response.</p> <p>Methods</p> <p>We compare culture-generated monocyte derived DCs (MDDCs) with directly isolated myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) and measure their alpha-defensins 1-3 secretion by ELISA both, in basal situations and after hormone (E2 or PG) treatments. Moreover, using a cohort of pregnant women we isolated mDCs from blood and also measure the levels of these anti-microbial peptides along pregnancy.</p> <p>Results</p> <p>We show that mDCs and pDCs constitutively produce alpha-defensins 1-3 and at much higher levels than MDDCs. Alpha-defensins 1-3 production from mDCs and MDDCs but not pDCs is inhibited by E2. PG does not affect alpha-defensins 1-3 in any of the populations. Moreover, alpha-defensins 1-3 production by mDCs was reduced in the later stages of pregnancy in 40% of the patients.</p> <p>Conclusions</p> <p>Here, we demonstrate that mDCs and pDCs secrete alpha-defensins 1-3 and present a novel effect of E2 on the secretion of alpha-defensins 1-3 by dendritic cells.</p

Orbital inflammatory complications of Crohn’s disease: a rare case series

Orbital inflammatory disease is a rare ophthalmic manifestation of Crohn’s disease. Inflammation is characteristically non-specific, involving one or multiple structures of the orbit. Mechanisms of disease and optimal methods of treatment are poorly understood. The aim of this report is to present three cases of orbital involvement in Crohn’s disease. A retrospective case note review of patients with orbital inflammatory disease and Crohn’s disease was performed at our academic centre to determine the clinical, imaging and histopathological features of this condition and its relationship to intestinal Crohn’s disease. Three patients were identified with orbital inflammatory manifestations complicating Crohn’s disease. All patients described were female with active intestinal disease and had a history of treatment with immunosuppressive therapies. Similarities were observed in clinical presentations with variance noted in radiological and histopathological findings. In all cases, symptoms improved with oral corticosteroids or non-steroidal drugs in combination with anti-tumour necrosis factor (anti-TNF) agents. Inflammatory bowel disease-related orbital complications are rare but potentially vision-threatening. It is important to consider mimics of orbital inflammatory disease such as systemic inflammatory disease, malignancy, congenital malformations, infection and trauma when formulating a comprehensive differential diagnosis. Therapeutic intervention is directed towards preservation of vision and orbital function and reducing the acute inflammatory process. Corticosteroids are typically the initial treatment of choice for moderate-to-severe disease, although several classes of immunomodulatory agents have been variably useful in treating this condition. Heightened awareness and close cooperation between gastroenterologists and ophthalmologists is mandatory

Solar Magnetic Field Studies Using the 12-Micron Emission Lines. IV. Observations of a Delta-Region Solar Flare

We have recently developed the capability to make solar vector (Stokes IQUV) magnetograms using the infrared line of MgI at 12.32 microns. On 24 April 2001, we obtained a vector magnetic map of solar active region NOAA 9433, fortuitously just prior to the occurrence of an M2 flare. Examination of a sequence of SOHO/MDI magnetograms, and comparison with ground-based H-alpha images, shows that the flare was produced by the cancellation of newly emergent magnetic flux outside of the main sunspot. The very high Zeeman-sensitivity of the 12-micron data allowed us to measure field strengths on a spatial scale which was not directly resolvable. At the flare trigger site, opposite polarity fields of 2700 and 1000 Gauss occurred within a single 2 arc-sec resolution element, as revealed by two resolved Zeeman splittings in a single spectrum. Our results imply an extremely high horizontal field strength gradient (5 G/km) prior to the flare, significantly greater than seen in previous studies. We also find that the magnetic energy of the cancelling fields was more than sufficient to account for the flare's X-ray luminosity.Comment: 14 pages, 5 figures, accepted for Ap.