Department of clinical research established · Atrial fibrillation and the circus movement · Mechanism and Graphic Registration of the Heart Beat · Experimental and clinical studies with quinidine

1997 ◽  
pp. 84-94
Author(s):  
Arthur Hollman
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Research ◽  
Clinical Studies ◽  
Heart Beat ◽  
Circus Movement ◽  
Movement Mechanism

Redox State in Atrial Fibrillation Pathogenesis and Relevant Therapeutic Approaches

2019 ◽  
Vol 26 (5) ◽  
pp. 765-779 ◽  
Author(s):  
Alexios S. Antonopoulos ◽  
Athina Goliopoulou ◽  
Evangelos Oikonomou ◽  
Sotiris Tsalamandris ◽  
Georgios-Angelos Papamikroulis ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Studies ◽  
Redox State ◽  
Redox Balance ◽  
Therapeutic Approaches ◽  
Critical Determinant ◽  
Electrophysiological Properties ◽  
Antioxidant Agents ◽  
Clinical Benefits

Background: Myocardial redox state is a critical determinant of atrial biology, regulating cardiomyocyte apoptosis, ion channel function, and cardiac hypertrophy/fibrosis and function. Nevertheless, it remains unclear whether the targeting of atrial redox state is a rational therapeutic strategy for atrial fibrillation prevention. Objective: To review the role of atrial redox state and anti-oxidant therapies in atrial fibrillation. Method: Published literature in Medline was searched for experimental and clinical evidence linking myocardial redox state with atrial fibrillation pathogenesis as well as studies looking into the role of redoxtargeting therapies in the prevention of atrial fibrillation. Results: Data from animal models have shown that altered myocardial nitroso-redox balance and NADPH oxidases activity are causally involved in the pathogenesis of atrial fibrillation. Similarly experimental animal data supports that increased reactive oxygen / nitrogen species formation in the atrial tissue is associated with altered electrophysiological properties of atrial myocytes and electrical remodeling, favoring atrial fibrillation development. In humans, randomized clinical studies using redox-related therapeutic approaches (e.g. statins or antioxidant agents) have not documented any benefits in the prevention of atrial fibrillation development (mainly post-operative atrial fibrillation risk). Conclusion: Despite strong experimental and translational data supporting the role of atrial redox state in atrial fibrillation pathogenesis, such mechanistic evidence has not been translated to clinical benefits in atrial fibrillation risk in randomized clinical studies using redox-related therapies.

scholarly journals In Vitro,In Vivo, and Clinical Studies of Tedizolid To Assess the Potential for Peripheral or Central Monoamine Oxidase Interactions

2013 ◽  
Vol 57 (7) ◽  
pp. 3060-3066 ◽  
Author(s):  
S. Flanagan ◽  
K. Bartizal ◽  
S. L. Minassian ◽  
E. Fang ◽  
P. Prokocimer
Keyword(s):  
Blood Pressure ◽  
Monoamine Oxidase ◽  
Clinical Research ◽  
Systolic Blood Pressure ◽  
Clinical Studies ◽  
Geometric Mean ◽  
Interaction Study ◽  
Mao B ◽  
Mao A

ABSTRACTTedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions.In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-Bin vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered atwww.clinicaltrials.govas NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459 (pseudoephedrine interaction study conducted at Vince and Associates Clinical Research, Overland Park, KS).

scholarly journals Remdesivir: Critical Clinical Appraisal for COVID 19 Treatment

Drug Research ◽  
2020 ◽  
Author(s):  
Saptarshi Chatterjee
Keyword(s):  
Clinical Trials ◽  
Clinical Research ◽  
Clinical Studies ◽  
Promising Result ◽  
Drug Repurposing ◽  
In Vitro Studies ◽  
Therapeutic Molecules ◽  
Regulatory Aspect ◽  
Plausible Mechanism

AbstractRemdesivir is presently been considered as ‘molecule of hope’ to curb the menace of COVID19. Non-availability of any USFDA approved drug has led to several attempt of drug-repurposing and development of new therapeutic molecules. However, Remdesivir has been found to be effective against a broad range of virus including SARS, MERS and COVID 19 through in-vitro studies. Several clinical research attempt are presently being conducted showing promising result yet not conclusive. This review summarized all such clinical trials to critically appraise the usage of Remdesivir against COVID 19 along with the publications related to the results of the clinical studies. The present regulatory aspect i. e. Emergency Use Authorization (EYA) and information of molecule and plausible mechanism is also dealt.

P2438Deep learning model for atrial fibrillation detection based on single beat morphology

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S W E Baalman ◽  
F E Schroevers ◽  
A Oakley ◽  
L A Ramos ◽  
R R Lopes ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Deep Learning ◽  
Sinus Rhythm ◽  
Learning Model ◽  
Heart Beat ◽  
Fourier Cosine ◽  
Cosine Series ◽  
Specificity And Sensitivity ◽  
Fourier Cosine Series ◽  
Data Points

Abstract Background The electrocardiogram (ECG) is commonly used, but most recent rhythm discrimination algorithms still lack both specificity and sensitivity. Deep learning techniques have shown promising results in the classification of physiological signals like ECGs. Purpose To develop and test a deep learning (DL) model to discriminate between atrial fibrillation (AF) and sinus rhythm (SR). Methods For the development of the DL model we used 1499 ECGs sampled at 500 Hz of patients diagnosed with AF. All ECGs were labeled by two experienced investigators. Only ECGs labeled as SR or AF were included in the dataset. To simplify the learning process, solely the first ECG channel was used. The ECG waveforms were preprocessed using the Fourier cosine series to correct for baseline wander. Input data was generated by normalizing and scaling all different heartbeats by centralizing the R peak, leading to 15744 single heart beat samples of 80 data points (figure A). Multiple feedforward architectures were tested with different numbers of layers, filters and activation functions. The models were trained by equally splitting the data (50%SR, 50%AF) in a training (65%), validation (25%) and test set (15%). The best performing model was chosen based on the accuracy. Results A total of 1469 ECGs (1061 (72%)SR, 408 (28%)AF) were included. The model with the best performance was a feedforward model consisting three dense layers with ReLU activation and four dense layers with Linear activation. Training of the model was performed in 32 epochs. Validation of the model resulted in an accuracy of 96% (figure B), precision of 95% and recall of 96%. Conclusions The morphology based deep learning model developed in this study was able to discriminate atrial fibrillation from sinus rhythm with a fairly high accuracy using a limited size dataset and only one lead.

Animal Models of Osteomyelitis

1988 ◽  
Vol 97 (2_suppl) ◽  
pp. 18-20
Author(s):  
Carl W. Norden
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Clinical Research ◽  
Clinical Studies ◽  
Disease Process ◽  
Controlled Experiments ◽  
Ideal Model ◽  
Treatment Protocols ◽  
Multiple Variables ◽  
The Ideal

Clinical studies of osteomyelitis are difficult because of the multiple variables found in this disease. Reproducible animal models in rabbits, rats, and dogs have been introduced and have been useful. Each animal model has certain advantages and limitations, and the ideal model is not yet available. However, the models have provided us with a clearer understanding of the disease and its treatment. Clinical research into osteomyelitis is difficult because of the multiple variables involved in the disease process and because of the difficulty of standardizing treatment protocols. To perform controlled experiments in the field of osteomyelitis, it is clear that reliable animal models are needed. Most studies have been performed with S aureus (the major pathogen isolated from patients with osteomyelitis), but other organisms have also been tested more recently.

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