Risk Factors for Infection in Patients with Remitted Rheumatic Diseases Treated with Glucocorticoids

It is well known that infection is one of the major causes of morbidity and mortality in rheumatic disease patients treated with high-dose glucocorticoids, especially in the early phase after achievement of disease remission. The aim of this study was to identify the risk factors for infection, with a focus on the dose of glucocorticoids administered, following the achievement of disease remission in rheumatic diseases patients. We retrospectively analyzed the medical records of rheumatic disease patients who had been treated with glucocorticoids. The primary endpoint was the incidence rate of infection during a period from 1 to 2 months after the commencement of treatment. From April 2006 to March 2010, 19 of 92 patients suffered from infection during the observation period. Age≧65 yrs, presence of interstitial pneumonia, diagnosis of systemic vasculitis and serum creatinine level≧2.0mg/dl were found to be univariate predictors for infection. However, only the presence of interstitial pneumonia was an independent risk factor for infection (HR＝4.50, 95%CI＝1.65 to 14.44) by the Cox proportional hazard model. Even after achievement of clinical remission, careful observation is needed for patients with interstitial pneumonia, more so than for those receiving high-dose glucocorticoids

Cause of apical thinning on attenuation-corrected myocardial perfusion SPECT

Objectives: Decreases in apical and apex activities - namely, \u27apical thinning\u27 - are a well-known phenomenon in attenuation-corrected (AC) myocardial perfusion. The aim of this study was to compare actual myocardial thickness derived from a multidetector-row computed tomography with AC myocardial perfusion count from a hybrid single-photon emission computed tomography/computed tomography to investigate the cause of apical thinning. Methods: We enrolled 21 participants with a low likelihood of coronary artery disease (mean age 65±21 years, 13 men) from 185 consecutive patients and 11 healthy volunteers, who independently underwent Tc-sestamibi single-photon emission computed tomography/computed tomography and 64-slice multidetector-row computed tomography scans. AC and non-AC myocardial perfusion counts and thickness were measured on the basis of a 17-segment model and averaged at the apex, apical, mid, and basal walls. Results: Myocardial thickness at the apex was significantly thinner than that at the apical and mid walls (5.1±1.3, 7.3±1.3, and 9.9±2.4 mm, respectively; P<0.005). AC count at the apex was significantly lower than that at the apical and mid regions (76.0±5.5, 82.8±4.7, and 85.6±3.8, respectively; P<0.002). Moderate relationship was observed between myocardial thickness and AC count (y=-10.5+0.22x, r=0.54, P<0.0001. No relationship was found between thickness and non-AC count (r=0.16, P=0.263). Conclusion: The low apex and apical counts were caused by anatomical thinning of the myocardium in AC myocardial perfusion imaging. Attenuation correction provided an accurate relationship between myocardial count and thickness because of the partial volume effect. © 2011 Wolters Kluwer Health | Lippincott Williams and Wilkins

Nuclear myocardial perfusion imaging using thallium-201 with a novel multifocal collimator SPECT/CT: IQ-SPECT versus conventional protocols in normal subjects

Objective A novel multifocal collimator, IQ-SPECT (Siemens) consists of SMARTZOOM, cardio-centric and 3D iterative SPECT reconstruction and makes it possible to perform MPI scans in a short time. The aims are to delineate the normal uptake in thallium-201 (201Tl) SPECT in each acquisition method and to compare the distribution between new and conventional protocol, especially in patients with normal imaging. Methods Forty patients (eight women, mean age of 75 years) who underwent myocardial perfusion imaging were included in the study. All patients underwent one-day protocol perfusion scan after an adenosine-stress test and at rest after administering201Tl and showed normal results. Acquisition was performed on a Symbia T6 equipped with a conventional dual-headed gamma camera system (Siemens ECAM) and with a multifocal SMARTZOOM collimator. Imaging was performed with a conventional system followed by IQ-SPECT/computed tomography (CT). Reconstruction was performed with or without X-ray CT-derived attenuation correction (AC). Two nuclear physicians blinded to clinical information interpreted all myocardial perfusion images. A semi-quantitative myocardial perfusion was analyzed by a 17-segment model with a 5-point visual scoring. The uptake of each segment was measured and left ventricular functions were analyzed by QPS software. Results IQ-SPECT provided good or excellent image quality. The quality of IQ-SPECT images without AC was similar to those of conventional LEHR study. Mid-inferior defect score (0.3 ± 0.5) in the conventional LEHR study was increased significantly in IQ-SPECT with AC (0 ± 0). IQ-SPECT with AC improved the mid-inferior decreased perfusion shown in conventional images. The apical tracer count in IQ-SPECT with AC was decreased compared to that in LEHR (0.1 ± 0.3 vs. 0.5 ± 0.7, p˂0.05). The left ventricular ejection fraction from IQ-SPECT was significantly higher than that from the LEHR collimator (p = 0.0009). Conclusion The images of IQ-SPECT acquired in a short time are equivalent to that of conventional LEHR. The results indicated that the IQ-SPECT system with AC is capable of correcting inferior artifacts with high image quality. © The Japanese Society of Nuclear Medicine 2015

Clinical usefulness of novel cardiac MDCT/SPECT fusion image

金沢大学附属病院核医学診療科Background: We evaluated the relationship between computed tomography angiography (CTA) and SPECT, and assessed to determine the clinical usefulness of the fusion image using CTA and myocardial perfusion imaging (MPI). Methods: Forty-one consecutive patients [after coronary artery bypass operation (n = 13) and suspected stenosis (n = 28)] underwent MPI and CTA. SPECT/CTA fused images were generated. Results: In total, 687 segments including bypass graft in 164 coronary arteries were analyzed. Myocardial ischemia on MPI was observed in 11 patients among 28 with CTA abnormalities, one had both ischemia and infarction, and 7 had only infarction. Segment-based analysis showed that ischemia was found in 14 segments (24%) among 59 stenoses on CTA. Forty stenotic segments (69%) were not associated with perfusion abnormality. The rest 5 stenotic segments were considered equivocal (8%). A fusion image made it possible to associate perfusion defects with its corresponding coronary artery in 4 out of 5 equivocal lesions on side-by-side analysis. Patients with incremental diagnostic information on SPECT/CTA fusion (n = 4) had significant smaller coronary diameter than that of not-improved coronary vessels (2.0 ± 0.4 vs. 3.9 ± 0.4 mm, p = 0.001). Conclusion: Cardiac fusion imaging accurately diagnosed functionally relevant coronary stenosis. SPECT/CTA fusion images in coronary artery disease may provide added diagnostic information on functional relevance of coronary artery disease. © 2009 The Japanese Society of Nuclear Medicine

Lipopolysaccharide Interaction with Cell Surface Toll-like Receptor 4-MD-2: Higher Affinity than That with MD-2 or CD14

Toll-like receptors (TLRs) are innate recognition molecules for microbial products, but their direct interactions with corresponding ligands remain unclarified. LPS, a membrane constituent of gram-negative bacteria, is the best-studied TLR ligand and is recognized by TLR4 and MD-2, a molecule associated with the extracellular domain of TLR4. Although TLR4-MD-2 recognizes LPS, little is known about the physical interaction between LPS and TLR4-MD-2. Here, we demonstrate cell surface LPS–TLR4-MD-2 complexes. CD14 greatly enhances the formation of LPS–TLR4-MD-2 complexes, but is not coprecipitated with LPS–TLR4-MD-2 complexes, suggesting a role for CD14 in LPS loading onto TLR4-MD-2 but not in the interaction itself between LPS and TLR4-MD-2. A tentative dissociation constant (Kd) for LPS–TLR4-MD-2 complexes was ∼3 nM, which is ∼10–20 times lower than the reported Kd for LPS–MD-2 or LPS–CD14. The presence of detergent disrupts LPS interaction with CD14 but not with TLR4-MD-2. E5531, a lipid A antagonist developed for therapeutic intervention of endotoxin shock, blocks LPS interaction with TLR4-MD-2 at a concentration 100 times lower than that required for blocking LPS interaction with CD14. These results reveal direct LPS interaction with cell surface TLR4-MD-2 that is distinct from that with MD-2 or CD14

Multicenter cross-calibration of I-123 metaiodobenzylguanidine heart-tomediastinum ratios to overcome camera-collimator variations

Background The heart-to-mediastinum ratio (HMR) of 123I-metaiodobenzylguanidine (MIBG) showed variations among institutions and needs to be standardized among various scinticamera-collimator combinations. Methods A total of 225 phantom experiments were performed in 84 institutions to calculate cross-calibration coefficients of HMR. Based on phantom studies, a conversion coefficient for each camera-collimator system was created, including low-energy (LE, n = 125) and a medium-energy (ME, n = 100) collimators. An average conversion coefficient from the most common ME group was used to calculate the standard HMR. In clinical MIBG studies (n = 52) from three institutions, HMRs were standardized from both LE- and ME-type collimators and classified into risk groups of <1.60, 1.60-2.19, and ≥2.20. Results The average conversion coefficients from the individual camera-collimator condition to the mathematically calculated reference HMR ranged from 0.55 to 0.75 for LE groups and from 0.83 to 0.95 for ME groups. The conversion coefficient of 0.88 was used to unify HMRs from all acquisition conditions. Using the standardized HMR, clinical studies (n = 52) showed good agreement between LE and ME types regarding three risk groups (κ = 0.83, P < .0001, complete agreement in 90%, 42% of the patients reclassified into the same risk group). Conclusion By using the reference HMR and conversion coefficients for the system, HMRs with various conditions can be converted to the standard HMRs in a range of normal to low HMRs

Successful Endoscopic Injection Sclerotherapy of High-Risk Gastroesophageal Varices in a Cirrhotic Patient with Hemophilia A

A 68-year-old man with hemophilia A and liver cirrhosis caused by hepatitis C virus was referred to our hospital to receive prophylactic endoscopic treatment for gastroesophageal varices (GOV). He had large, tense, and winding esophageal varices (EV) with cherry red spots extending down to lesser curve, predicting the likelihood of bleeding. Esophageal endoscopic injection sclerotherapy (EIS) was performed with a total 15 mL of 5% ethanolamine oleate with iopamidol (EOI). Radiographic imaging during EIS demonstrated that 5% EOI reached the afferent vein of the varices. He was administered sufficient factor VIII concentrate before and after EIS to prevent massive bleeding from the varices. Seven days after EIS, upper gastrointestinal endoscopy (UGIE) showed that the varices were eradicated almost completely. Eighteen months after EIS, the varices continued to diminish. We report a successful case of safe and effective EIS for GOV in a high-risk cirrhotic patient with hemophilia A

Axon terminal hypertrophy of striatal projection neurons with levodopa-induced dyskinesia priming

BackgroundA rat model of levodopa-induced dyskinesia (LID) showed enlarged axon terminals of striatal direct pathway neurons in the internal segment of the globus pallidus (GPi) with excessive gamma-aminobutyric acid (GABA) storage in them. Massive GABA release to GPi upon levodopa administration determines the emergence of LID.ObjectivesWe examined whether LID and axon terminal hypertrophy gradually develop with repeated levodopa treatment in Parkinsonian rats to examine if the hypertrophy reflects dyskinesia priming.Methods6-hydroxydopamine-lesioned hemiparkinsonian rats were randomly allocated to receive saline injections (placebo group, 14 days; n = 4), injections of 6 mg/kg levodopa methyl ester combined with 12.5 mg/kg benserazide (levodopa-treated groups, 3-day-treatment; n = 4, 7-day-treatment; n = 4, 14-day-treatment; n = 4), or injections of 6 mg/kg levodopa methyl ester with 12.5 mg/kg benserazide and 1 mg/kg 8-hydroxy-2-(di-n-propylamino)tetralin for 14 days (8-OH-DPAT-treated group; n = 4). We evaluated abnormal involuntary movement (AIM) scores and axon terminals in the GPi.ResultsThe AIM score increased with levodopa treatment, as did the hypertrophy of axon terminals in the GPi, showing an increased number of synaptic vesicles in hypertrophied terminals.ConclusionIncreased GABA storage in axon terminals of the direct pathway neurons represents the priming process of LID

Ribosome binding protein GCN1 regulates the cell cycle and cell proliferation and is essential for the embryonic development of mice.

Amino acids exert many biological functions, serving as allosteric regulators and neurotransmitters, as constituents in proteins and as nutrients. GCN2-mediated phosphorylation of eukaryotic initiation factor 2 alpha (elF2α) restores homeostasis in response to amino acid starvation (AAS) through the inhibition of the general translation and upregulation of amino acid biosynthetic enzymes and transporters by activating the translation of Gcn4 and ATF4 in yeast and mammals, respectively. GCN1 is a GCN2-binding protein that possesses an RWD binding domain (RWDBD) in its C-terminus. In yeast, Gcn1 is essential for Gcn2 activation by AAS; however, the roles of GCN1 in mammals need to be established. Here, we revealed a novel role of GCN1 that does not depend on AAS by generating two Gcn1 mutant mouse lines: Gcn1-knockout mice (Gcn1 KO mice (Gcn1-/-)) and RWDBD-deleted mutant mice (Gcn1ΔRWDBD mice). Both mutant mice showed growth retardation, which was not observed in the Gcn2 KO mice, such that the Gcn1 KO mice died at the intermediate stage of embryonic development because of severe growth retardation, while the Gcn1ΔRWDBD embryos showed mild growth retardation and died soon after birth, most likely due to respiratory failure. Extension of pregnancy by 24 h through the administration of progesterone to the pregnant mothers rescued the expression of differentiation markers in the lungs and prevented lethality of the Gcn1ΔRWDBD pups, indicating that perinatal lethality of the Gcn1ΔRWDBD embryos was due to simple growth retardation. Similar to the yeast Gcn2/Gcn1 system, AAS- or UV irradiation-induced elF2α phosphorylation was diminished in the Gcn1ΔRWDBD mouse embryonic fibroblasts (MEFs), suggesting that GCN1 RWDBD is responsible for GCN2 activity. In addition, we found reduced cell proliferation and G2/M arrest accompanying a decrease in Cdk1 and Cyclin B1 in the Gcn1ΔRWDBD MEFs. Our results demonstrated, for the first time, that GCN1 is essential for both GCN2-dependent stress response and GCN2-independent cell cycle regulation