Virus-Negative Necrotizing Coronary Vasculitis with Aneurysm Formation in Human SARS-CoV-2 Infection

We report a case of myopericarditis associated to SARS-CoV-2 infection with necrotizing coronary vasculitis of intramural vessels, giving rise to biventricular apical microaneurysms and to electrical instability. Negativity of myocardial polymerase chain reaction for the most common cardiotropic viruses and for SARS-CoV-2 suggested an immune-mediated myocardial and pericardial inflammatory disease. High dose (1 mg/Kg daily) prednisone and anti-viral (Remdesivir, IDA Business, Carrigtohill, County Cork, T45 DP77, Ireland) therapy led to resolution of cardiac inflammation and ventricular arrhythmias. Morpho-molecular characterization of endomyocardial tissue may improve the outcome in subjects with SARS-CoV-2-associated myopericarditis and coronary vasculitis.

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Myocarditis-associated necrotizing coronary vasculitis: incidence, cause and outcome

European Heart Journal ◽

10.1093/ehjci/ehaa946.1199 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Frustaci ◽

R Verardo ◽

M Alfarano ◽

C Agrati ◽

R Casetti ◽

...

Keyword(s):

Hospital Mortality ◽

Large Population ◽

Hypereosinophilic Syndrome ◽

Left Ventricular ◽

Response To Therapy ◽

Control Group ◽

High Dose ◽

Funding Source ◽

Immune Mediated ◽

Coronary Vasculitis

Abstract Background Necrotizing coronary vasculitis (NCV) is a rare entity usually associated to myocarditis (M), which incidence, cause and responsiveness to therapy is unreported. Purpose We set out a retrospective study to report our experience in the diagnosis and management of myocarditis-associated necrotizing coronary vasculitis (M-NCV) and patients' outcome. Methods Among 5180 patients undergoing endomyocardial biopsy in our institution, 1916 received a histological diagnosis of myocarditis with associated NCV in 30 (12F, 18M, mean age 47.7 years±15). NVC endomyocardial samples were retrospectively evaluated with, immunohistochemistry for Toll like Receptor 4 (TLR4) and real-time PCR for viral genomes. Serum samples were processed for anti-heart autoantibodies and inflammatory cytokine profile (ELLA assay).Identification of an immunologic pathway (virus-, TLR4+, anti-heart abs +) was followed by immunosuppression including steroids, azathioprine, cyclophosphamide, high dose immunoglobulins and anakinra. M-NCV patients were followed for 6-months with resting ECG, Holter monitoring, 2D-echo and in 45% of cases with cardiac magnetic resonance. Increase of ≥10% in left ventricular EF was classified as response to therapy. M-NCV patients were compared to a control group of 60 consecutive patients with virus + and − lymphocithic myocarditis and a control group of 30 patients with mitral stenosis and normal LV size and function, undergoing surgical repair. Results 26 M-NCV patients presented with heart failure or cardiogenic shock; 3 with electrical instability; 1 with infarct-like symptoms. Cause of M-NCV included infectious agents (PVB19, HHV2, EBV and co-infection of Toxoplasma gondii and PVB19) in 4 patients; chest trauma in 1; drug-hypersensitivity in 2; hypereosinophilic syndrome in 1; primary autoimmune disease in 7; giant cells in 3; while it was idiopathic in the remaining cases. CMR imaging did not detect any qualitative difference between M-NVC and M patients. Anti-heart autoantibodies were positive in immune-mediated M-NCV and virus- M; in M-NCV patients in which anti-heart autoantibodies were positive, we found a cross-reaction with vessel walls. Myocardial expression of TLR4 was high in the immune-mediated forms and negative in the viral. Interleukins 1-beta was more elevated (p<0.001) in patients with M-NCV in comparison with virus-M patients. M-NCV patients presented a more severe clinical profile with 24% in-hospital mortality compared with 1.5% of the M group. Immunosuppression resulted in an improvement of cardiac function in 86% of M-NCV and 88% of virus-M cohort. Conclusion NCV can be histologically detected in up to 1.5% of a large population with myocarditis. Major causes include viral, autoreactive and autoimmune processes. Intra-hospital mortality is high (24%). Presence of an immunologic pathway is associated with a beneficial response to immunosuppression. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Project ERA-CVD

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Clinical Characterization of High-Dose Gamma-Hydroxybutyric Acid (GHB) Intoxication

PsycEXTRA Dataset ◽

10.1037/e510612007-001 ◽

2006 ◽

Author(s):

Matthew W. Johnson ◽

Lawrence P. Carter ◽

Annie Umbricht ◽

Roland R. Griffiths

Keyword(s):

High Dose ◽

Hydroxybutyric Acid

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Characterization of a cDNA for Rhesus Monkey Protein C Inhibitor – Evidence for N-Terminal Involvement in Heparin Stimulation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649885 ◽

1995 ◽

Vol 74 (04) ◽

pp. 1079-1087 ◽

Cited By ~ 8

Author(s):

Klaus-P Radtke ◽

José A Fernández ◽

Bruno O Villoutreix ◽

Judith S Greengard ◽

John H Griffin

Keyword(s):

Rhesus Monkey ◽

Protein C ◽

Activated Protein C ◽

Pcr Amplification ◽

Amino Acid Sequences ◽

Heparin Binding ◽

Reactive Center ◽

Protein C Inhibitor ◽

Polymerase Chain

SummarycDNAs for protein C inhibitor (PCI) were cloned from human and rhesus monkey 1 liver RNAs by reverse transcription and polymerase chain reaction (PCR) amplification. Sequencing showed that rhesus monkey and human PCI cDNAs were 93% identical. Predicted amino acid sequences differed at 26 of 387 residues. Pour of these differences (T352M, N359S, R362K, L3631) were in the reactive center loop that is important for inhibitory specificity, and two were in the N-terminal helix (M8T, E13K) that is implicated in glycosaminoglycan binding. PCI in human or rhesus monkey plasma showed comparable inhibitory activity towards human activated protein C in the presence of 10 U/ml heparin. However, maximal acceleration of the inhibition of activated protein C required 5-fold lower heparin concentration for rhesus monkey than for human plasma, consistent with the interpretation that the additional positive charge (E13K) in a putative-heparin binding region increased the affinity for heparin.

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Characterization of the Original Christmas Disease Mutation (Cysteine 206 → Serine): From Clinical Recognition to Molecular Pathogenesis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648381 ◽

1992 ◽

Vol 67 (01) ◽

pp. 063-065 ◽

Cited By ~ 6

Author(s):

Sherryl A M Taylor ◽

Jacalyn Duffin ◽

Cherie Cameron ◽

Jerome Teitel ◽

Bernadette Garvey ◽

...

Keyword(s):

Nucleotide Substitution ◽

Novel Mutation ◽

Factor Ix ◽

Causative Mutation ◽

Coding Region ◽

Body Of Knowledge ◽

Polymerase Chain ◽

Splice Junctions

SummaryChristmas disease was first reported as a distinct clinical entity in two manuscripts published in 1952 (1, 2). The eponym associated with this disorder, is the surname of the first patient examined in detail and reported by Biggs and colleagues in a paper describing the clinical and laboratory features of seven affected individuals (3). This patient has severe factor IX coagulant deficiency (less than 0.01 units/ml) and no detectable circulating factor IX antigen (less than 0.01 units/ml). Coding sequence and splice junctions of the factor IX gene from this patient have been amplified in vitro through the polymerase chain reaction (PCR). One nucleotide substitution was identified at nucleotide 30,070 where a guanine was replaced by a cytosine. This mutation alters the amino acid encoded at position 206 in the factor IX protein from cysteine to serine. The non conservative nature of this substitution, the absence of this change in more than 200 previously sequenced factor IX genes and the fact that the remainder of the coding region of this gene was normal, all provide strong circumstantial evidence in favour of this change being the causative mutation in this patient. The molecular characterization of this novel mutation in the index case of Christmas disease, contributes to the rapidly expanding body of knowledge pertaining to Christmas disease pathogenesis.

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Molecular Characterization of hobo-Mediated Inversions in Drosophila melanogaster

Genetics ◽

10.1093/genetics/144.2.647 ◽

1996 ◽

Vol 144 (2) ◽

pp. 647-656

Author(s):

William B Eggleston ◽

Nac R Rim ◽

Johng K Lim

Keyword(s):

X Chromosome ◽

Polymerase Chain Reaction Amplification ◽

Polytene Chromosomes ◽

Chromosomal Inversions ◽

Hobo Element ◽

Reaction Amplification ◽

Notch Locus ◽

Polymerase Chain

Abstract The structure of chromosomal inversions mediated by hobo transposable elements in the Uc-1 X chromosome was investigated using cytogenetic and molecular methods. Uc-1 contains a phenotypically silent hobo element inserted in an intron of the Notch locus. Cytological screening identified six independent Notch mutations resulting from chromosomal inversions with one breakpoint at cytological position 3C7, the location of Notch. In situ hybridization to salivary gland polytene chromosomes determined that both ends of each inversion contained hobo and Notch sequences. Southern blot analyses showed that both breakpoints in each inversion had hobo-Notch junction fragments indistinguishable in structure from those present in the Uc-1 X chromosome prior to the rearrangements. Polymerase chain reaction amplification of the 12 hobo-Notch junction fragments in the six inversions, followed by DNA sequence analysis, determined that each was identical to one of the two hobo-Notch junctions present in Uc-1. These results are consistent with a model in which hobo-mediated inversions result from homologous pairing and recombination between a pair of hobo elements in reverse orientation.

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Bilateral dysthyroid compressive optic neuropathy responsive to teprotumumab

European Journal of Ophthalmology ◽

10.1177/1120672121991042 ◽

2021 ◽

pp. 112067212199104

Author(s):

Catherine J Hwang ◽

Erin E Nichols ◽

Brian H Chon ◽

Julian D Perry

Keyword(s):

Side Effects ◽

Optic Neuropathy ◽

Surgical Decompression ◽

Thyroid Eye Disease ◽

Eye Disease ◽

High Dose ◽

Compressive Optic Neuropathy ◽

Traditional Management ◽

Immune Mediated ◽

Orbital Radiation

Thyroid eye disease is an auto-immune mediated orbitopathy which can cause dysthyroid compressive optic neuropathy. Traditional management of active thyroid eye disease includes temporizing high-dose steroids, orbital radiation and surgical decompression, which each possess significant limitations and/or side effects. Teprotumumab is an IGF-IR inhibitor recently FDA-approved for active thyroid eye disease. The authors report reversal of bilateral dysthyroid compressive optic neuropathy managed medically utilizing teprotumumab.

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Myocarditis-associated necrotizing coronary vasculitis: incidence, cause, and outcome

European Heart Journal ◽

10.1093/eurheartj/ehaa973 ◽

2020 ◽

Author(s):

Andrea Frustaci ◽

Maria Alfarano ◽

Romina Verardo ◽

Chiara Agrati ◽

Rita Casetti ◽

...

Keyword(s):

Hospital Mortality ◽

Hypereosinophilic Syndrome ◽

Left Ventricular ◽

Response To Therapy ◽

Left Ventricular Ejection ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Ventricular Ejection Fraction ◽

Immune Mediated ◽

Coronary Vasculitis

Abstract Aims Necrotizing coronary vasculitis (NCV) is a rare entity usually associated to myocarditis which incidence, cause, and response to therapy is unreported. Methods and results Among 1916 patients with biopsy-proven myocarditis, 30 had NCV. Endomyocardial samples were retrospectively investigated with immunohistochemistry for toll-like receptor 4 (TLR4) and real-time polymerase chain reaction (PCR) for viral genomes. Serum samples were processed for anti-heart autoantibodies (Abs), IL-1β, IL-6, IL-8, tumour necrosis factor (TNF)-α. Identification of an immunologic pathway (including virus-negativity, TLR4-, and Ab-positivity) was followed by immunosuppression. Myocarditis-NCV cohort was followed for 6 months with 2D-echo and/or cardiac magnetic resonance and compared with 60 Myocarditis patients and 30 controls. Increase in left ventricular ejection fraction ≥10% was classified as response to therapy. Control endomyocardial biopsy followed the end of treatment. Twenty-six Myocarditis-NCV patients presented with heart failure; four with electrical instability. Cause of Myocarditis-NCV included infectious agents (10%) and immune-mediated causes (chest trauma 3%; drug hypersensitivity 7%; hypereosinophilic syndrome 3%; primary autoimmune diseases 33%, idiopathic 44%). Abs were positive in immune-mediated Myocarditis-NCV and virus-negative Myocarditis; Myocarditis-NCV patients with Ab+ presented autoreactivity in vessel walls. Toll-like receptor 4 was overexpressed in immune-mediated forms and poorly detectable in viral. Interleukin-1β was significantly higher in Myocarditis-NCV than Myocarditis, the former presenting 24% in-hospital mortality compared with 1.5% of Myocarditis cohort. Immunosuppression induced improvement of cardiac function in 88% of Myocarditis-NCV and 86% of virus-negative Myocarditis patients. Conclusion Necrotizing coronary vasculitis is histologically detectable in 1.5% of Myocarditis. Necrotizing coronary vasculitis includes viral and immune-mediated causes. Intra-hospital mortality is 24%. The immunologic pathway is associated with beneficial response to immunosuppression.

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Electrochemical Investigation of Curcumin–DNA Interaction by Using Hydroxyapatite Nanoparticles–Ionic Liquids Based Composite Electrodes

Materials ◽

10.3390/ma14154344 ◽

2021 ◽

Vol 14 (15) ◽

pp. 4344

Author(s):

Merve Uca ◽

Ece Eksin ◽

Yasemin Erac ◽

Arzum Erdem

Keyword(s):

Electrochemical Impedance ◽

Differential Pulse ◽

Dna Interaction ◽

Composite Electrodes ◽

Hydroxyapatite Nanoparticles ◽

Graphite Electrodes ◽

X Ray ◽

Pulse Voltammetry ◽

Polymerase Chain

Hydroxyapatite nanoparticles (HaP) and ionic liquid (IL) modified pencil graphite electrodes (PGEs) are newly developed in this assay. Electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and cyclic voltammetry (CV) were applied to examine the microscopic and electrochemical characterization of HaP and IL-modified biosensors. The interaction of curcumin with nucleic acids and polymerase chain reaction (PCR) samples was investigated by measuring the changes at the oxidation signals of both curcumin and guanine by differential pulse voltammetry (DPV) technique. The optimization of curcumin concentration, DNA concentration, and the interaction time was performed. The interaction of curcumin with PCR samples was also investigated by gel electrophoresis.

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Nonepileptic Myoclonus in COVID-19: Case Report

The Neurohospitalist ◽

10.1177/19418744211004315 ◽

2021 ◽

pp. 194187442110043

Author(s):

Henly Hewan ◽

Annie Yang ◽

Aparna Vaddiparti ◽

Benison Keung

Keyword(s):

Case Report ◽

Critically Ill ◽

Recovery Phase ◽

Critically Ill Patient ◽

High Dose ◽

The Novel ◽

Neurological Manifestations ◽

Immune Mediated ◽

Novel Coronavirus ◽

Post Infectious

In late 2019, the novel coronavirus, SARS-CoV-2, and the disease it causes, COVID-19, was identified. Since then many different neurological manifestations of COVID-19 have been well reported. Movement abnormalities have been rarely described. We report here a critically ill patient with COVID-19 who developed generalized myoclonus during the recovery phase of the infection. Myoclonus was associated with cyclical fevers and decreased alertness. Movements were refractory to conventional anti-epileptic therapies. There was concern that myoclonus could be part of a post-infectious immune-mediated syndrome. The patient improved fully with a 4-day course of high-dose steroids. Our experience highlights a rare, generalized myoclonus syndrome associated with COVID-19 that may be immune-mediated and is responsive to treatment.

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