Primary lymphoma of the heart: three-dimensional reconstruction

Primary cardiac lymphoma is defined as a lymphoma of the heart and pericardium with little or no extracardiac or local involvement such as mediastinal lymph nodes or pleural effusion. Most cases are diagnosed only post mortem (1). If this disease could be diagnosed earlier, therapy with chlorpropamide, doxorubicin, vincristine and prednisone (CHOP) could bring about a remission (2,3,4). Transoesophageal echocardiography with three-dimensional acquisition is a new technique which can allow earlier diagnosis, and facilitate guided transvenous biopsy (5,6). We here report an example of the pre-mortem diagnosis of cardiac lymphoma by these techniques.     

High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification

Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures.     

Ebola Risk Perception in Germany, 2014

Ebola virus disease (EVD) outbreaks have occurred during the past 5 decades, but none has affected European countries like the 2014 epidemic in West Africa. We used an online questionnaire to investigate risk perceptions in Germany during this epidemic peak. Our questionnaire covered risk perceptions, knowledge about transmission routes, media use, reactions to the outbreak, attitudes toward measures to prevent the spread of EVD and vaccination against EVD, and willingness to volunteer for aid missions. Of 974 participants, 29% indicated that they worried about EVD, 4% correctly stated virus transmission routes, and 75% incorrectly rated airborne transmission and transmission by asymptomatic patients as possible. Many indicated that if a patient were flown to Germany for treatment in a nearby hospital, they would adapt preventive behavior. Although most participants were not worried about EVD at the current stage of the epidemic, misperceptions regarding transmission were common and could trigger inappropriate behavior changes.     

Increased SR Ca2+ cycling contributes to improved contractile performance in SERCA2a-overexpressing transgenic rats

OBJECTIVE: Heart failure is associated with reduced function of sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) but increased function of sarcolemmal Na+/Ca2+ exchanger (NCX), leading to decreased SR Ca2+ content and loss of frequency-potentiation of contractile force. We reported that SERCA2a-overexpression in transgenic rat hearts (TG) results in improved contractility. However, it was not clear whether TG have improved contractility due to frequency-dependent improved SR Ca2+ handling. METHODS: Therefore, we characterized TG (n=35) vs. wild-type (WT) control rats (n=39) under physiological conditions (37 degrees C, stimulation rate <8 Hz). Twitch force, intracellular Ca2+ transients ([Ca2+]i), and SR Ca2+ content were measured in isolated muscles. The contribution of transsarcolemmal Ca2+ influx (I(Ca)) through L-type Ca2+ channels (LTCC) and reverse mode NCX (I(Na/Ca)) to Ca2+ cycling were studied in isolated myocytes. RESULTS: With increasing frequency, force increased in TG muscles by 168+/-35% (8 Hz; P<0.05) and SR Ca2+ content increased by maximally 118+/-31% (4 Hz; P<0.05). In WT, there was a flat force-frequency response without changes in SR Ca2+ content. Relaxation parameters of force and [Ca2+]i decay were accelerated at each frequency in TG vs. WT by approximately 10%. At prolonged rest intervals (<240 s), force and SR Ca2+ content increased significantly more in TG. Consequently, absolute SR Ca2+ content measured in myocytes was increased approximately 2-fold in TG. Transsarcolemmal Ca2+ fluxes estimated by I(Ca) (at 0 mV -10.2+/-1.1 vs. -16.9+/-1.3 pA/pF) and I(Na/Ca) (0.17+/-0.02 vs. 0.46+/-0.05 pA/pF) were decreased in TG vs. WT (P<0.05), whereas NCX and LTCC protein expression was only slightly reduced (P=n.s.). CONCLUSION: In summary, SERCA2a-overexpression improved contractility in a frequency-dependent way due to increased SR Ca2+ loading whereas transsarcolemmal Ca2+ fluxes were decreased.     

Effects of 5-hydroxytryptamine uptake blockers on the concentration in brain of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in male rats, pro-oestrous rats and ovariectomized rats treated with oestrogen and progesterone

The aim of this study was to determine the effect of 5-hydroxytryptamine (5-HT) uptake blockade on 5-HT turnover by measuring the concentrations of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in brain with the aid of high performance liquid chromatography and electrochemical detection. The indoleamines were measured in the anterior hypothalamus (AH), posterior hypothalamus (PH) and raphe nuclei 30 min after the i.v. injection of either alaproclate (30 mg/kg) or zimelidine (20 mg/kg). The effect of alaproclate was studied in male rats, pro-oestrous female rats, rats ovariectomized and injected s.c. with 20 micrograms oestradiol benzoate (OB) on dioestrus and at 12.00 h of the next day (presumptive pro-oestrus) with 2 mg progesterone (model 1) and rats ovariectomized 3-4 weeks before an s.c. injection of 20 micrograms OB followed 72 h later by an s.c. injection of 2 mg progesterone (model 2). Alaproclate caused a significant decrease in the 5-HIAA/5-HT ratio in the AH and PH of the brain of male rats, in the PH and raphe nuclei in pro-oestrous rats and model 1, and in the raphe nuclei alone in model 2. Zimelidine had no effect on the 5-HIAA/5-HT ratio in any area in model 2. In male rats the injection of parachlorophenylalanine produced a marked reduction in the brain concentrations of 5-HT and 5-HIAA, but the 5-HIAA/5-HT ratio was unchanged by a subsequent injection of alaproclate. None of the pharmacological agents affected significantly the brain concentrations of noradrenaline, dopamine or dihydroxyphenylacetic acid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mycobacteria Induces Pleural Mesothelial Permeability by Down-Regulating β-Catenin Expression

Patients with pulmonary tuberculosis develop pleural effusions with a high protein content. Pleural mesothelial adherens junctions promote mesothelial cell-cell adhesion and contribute to pleural integrity. In the present study we have investigated the effect of mycobacterium (BCG) on mesothelial cell adherens junction proteins and pleural permeability. BCG enhanced pleural mesothelial cell (PMC) release of vascular endothelial growth factor (VEGF), and decreased electrical resistance across the PMC monolayer. Neutralizing antibodies to VEGF significantly restored the drop in PMC electrical resistance caused by BCG. BCG infection down regulated -catenin (adherens junction protein) expression and caused increased permeability across confluent mesothelial monolayer. Our results suggest that in TB pleurisy, mycobacteria cause VEGF release from mesothelial cells and leads to protein exudation by altering mesothelial adherens junction proteins.     

45/47 kilodalton (APA) antigen capture and antibody detection assays for the diagnosis of tuberculosis.

SETTING: APA complex (45/47 kDa) is an antigen specifically excreted by Mycobacterium tuberculosis and could therefore be a good candidate for diagnosis. OBJECTIVES: To develop three APA immunocapture ELISA assays using monoclonal antibodies (Mabs) and one IgG anti-APA ELISA test, and to determine their usefulness for the diagnosis of tuberculosis in Madagascar. DESIGN: For the Ag assays, 23 negative sputum and serum samples and 64 pairs of sputum and serum from active smear-positive patients (PTM+) were tested. For antibody assay, 116 negative controls, 143 PTM+ and 54 extra-pulmonary tuberculosis patients were tested. RESULTS: The sensitivities of the APA antigen detection assays were low (less than 40%) for a specificity of 95.6%, using either monoclonal antibodies or clinical specimens. The anti-APA serology was more sensitive (76.9% for PTM+ patients) but less specific (73.2%). Due to their poor predictive values, these tests cannot be recommended for the routine diagnosis of tuberculosis in Madagascar.     

Acute myocardial infarction during streptokinase therapy

A 45-year-old man developed sequential inferolateral and anterior myocardial infarctions within 10 hours of a possible allergic reaction to oral penicillin. The anterior myocardial infarction occurred during apparently successful streptokinase therapy for the initial inferolateral infarction. Subsequent coronary arteriography confirmed a subtotal stenosis of the left circumflex coronary artery and a complete thrombotic occlusion of the left anterior descending artery. This case documents the occurrence of three rare clinical phenomena; first, the occurrence of sequential acute myocardial infarctions in close temporal proximity; second, the occurrence of myocardial infarction during thrombolytic therapy; and third, the association of myocardial infarction with a possible allergic reaction.     

Sodium channel mutations in paramyotonia congenita exhibit similar biophysical phenotypes in vitro.

Mutations in the skeletal muscle voltage-gated Na+ channel alpha-subunit have been found in patients with two distinct hereditary disorders of sarcolemmal excitation: hyperkalemic periodic paralysis (HYPP) and paramyotonia congenita (PC). Six of these mutations have been functionally expressed in a heterologous cell line (tsA201 cells) using the recombinant human skeletal muscle Na+ channel alpha-subunit cDNA hSkM1. PC mutants from diverse locations in this subunit (T1313M, L1433R, R1448H, R1448C, A1156T) all exhibit a similar disturbance in channel inactivation characterized by reduced macroscopic rate, accelerated recovery, and altered voltage dependence. PC mutants had no significant abnormality in activation. In contrast, one HYPP mutation studied (T704M) has a normal inactivation rate but exhibits shifts in the midpoints of steady-state activation and inactivation along the voltage axis. These findings help to explain the phenotypic differences between HYPP and PC at the molecular and biophysical level and contribute to our understanding of Na+ channel structure and function.