Pathological findings and diagnostic implications of a rhesus macaque (Macaca mulatta) model of aerosol-exposure melioidosis (Burkholderia pseudomallei)

2014 ◽  
Vol 63 (1) ◽  
pp. 118-128 ◽  
Author(s):  
Samuel L. Yingst ◽  
Paul Facemire ◽  
Lara Chuvala ◽  
David Norwood ◽  
Mark Wolcott ◽  
...  

Aerosolized Burkholderia pseudomallei, the causative agent of melioidosis, can infect many species of mammals (including humans), causing rapid, severe pneumonia with high mortality. Diagnosis in humans is challenging, as few organisms can be detected in blood or other non-invasive samples. Although it cannot be said that the model is established, studies to date indicate that rhesus macaques may represent a good model of human melioidosis. This is supported by the results of this study. The early progression of meliodosis in the rhesus macaque was studied in an effort to better understand the disease and the application of rapid diagnostic methods. Results indicate that a PCR analysis of key diagnostic samples such as nasal swabs, throat swabs, tracheo bronchial lymph node aspirates and broncho-alveolar lavage may be a useful component of a rapid diagnostic algorithm in case of aerosol exposure.

Author(s):  
Brandi N. Williamson ◽  
Friederike Feldmann ◽  
Benjamin Schwarz ◽  
Kimberly Meade-White ◽  
Danielle P. Porter ◽  
...  

AbstractBackgroundEffective therapeutics to treat COVID-19 are urgently needed. Remdesivir is a nucleotide prodrug with in vitro and in vivo efficacy against coronaviruses. Here, we tested the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection.MethodsTo evaluate the effect of remdesivir treatment on SARS-CoV-2 disease outcome, we used the recently established rhesus macaque model of SARS-CoV-2 infection that results in transient lower respiratory tract disease. Two groups of six rhesus macaques were infected with SARS-CoV-2 and treated with intravenous remdesivir or an equal volume of vehicle solution once daily. Clinical, virological and histological parameters were assessed regularly during the study and at necropsy to determine treatment efficacy.ResultsIn contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs. Virus titers in bronchoalveolar lavages were significantly reduced as early as 12hrs after the first treatment was administered. At necropsy on day 7 after inoculation, lung viral loads of remdesivir-treated animals were significantly lower and there was a clear reduction in damage to the lung tissue.ConclusionsTherapeutic remdesivir treatment initiated early during infection has a clear clinical benefit in SARS-CoV-2-infected rhesus macaques. These data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to severe pneumonia.


2010 ◽  
Vol 59 (6) ◽  
pp. 724-730 ◽  
Author(s):  
Samuel L. Yingst ◽  
Louis M. Huzella ◽  
Lara Chuvala ◽  
Mark Wolcott

The US Centers for Disease Control and Prevention lists Brucella as a potential bioterrorism threat requiring enhanced diagnostic capacity and surveillance (http://emergency.cdc.gov/bioterrorism/). Successful treatment and management of patients after exposure to biological threat agents depends on accurate and timely diagnosis, but many biothreat agents present with similar, vague clinical signs – commonly referred to as ‘flu-like illness’. Diagnosis of brucellosis is notoriously challenging, especially early in infection, and definitive diagnosis may require invasive methods, e.g. bone marrow biopsy. We studied the pathogenesis of Brucella suis aerosol infection in rhesus macaques in an effort to guide the diagnostic algorithm in case of possible intentional exposure of humans. Rhesus proved to be an excellent model for human brucellosis; the data showed that PCR DNA amplification testing of non-invasive diagnostic samples has the potential to definitively detect a point-source outbreak immediately and for several days after exposure.


2019 ◽  
Vol 178 (1) ◽  
pp. 34-38
Author(s):  
B. N. Kotiv ◽  
I. M. Samokhvalov ◽  
V. Ju. Markevich ◽  
I. I. Dzidzava ◽  
O. V. Barinov ◽  
...  

Theobjectivewas to determine the optimal therapeutic and diagnostic algorithm for thoracoabdominal injury.Material and methods. The results of the examination and treatment of 389 injured patients with combined stab wounds of chest and abdomen were analyzed. The injuries were thoracoabdominal in 54 (13.9 %) cases.Results. We analyzed instrumental invasive and non-invasive diagnostic methods. The sequence of surgical interventions was determined.Conclusion. We revealed that the correct sequence and volume of surgical intervention ensured the success of treating the injured patients, while in cases of competing sources of bleeding, priority should be given in favor of performing thoracotomy.


1995 ◽  
Vol 73 (04) ◽  
pp. 592-596 ◽  
Author(s):  
Sabina Villalta ◽  
Paolo Prandoni ◽  
Alberto Cogo ◽  
Paola Bagatella ◽  
Andrea Piccioli ◽  
...  

SummaryBackground. Despite the availability of several diagnostic methods for the detection of deep-vein thrombosis (DVT), the identification of previous episodes of DVT remains a diagnostic challenge.Study objective. To assess the reliability of a combination of a standardized clinical score with three non-invasive tests: compression ultrasonography (CUS), Doppler ultrasound (DUS), and photoplethysmography (PPG), in determining the presence or the absence of previous proximal DVT.Methods. One hundred consecutive unselected outpatients were identified, who had undergone contrast venography six to nine years previously because of the clinical suspicion of DVT (confirmed in 43). They were blindly reinvestigated by a panel of trained operators unaware of venography results. They underwent a clinical evaluation of the lower limb, by applying a standardized score to five symptoms and six signs (grading each item from 0 to 3); a PPG test to determine the venous refilling time; a DUS test to determine the venous reflux separately in the common femoral and the popliteal vein; and a CUS test to determine vein compressibility in the same regions.Results. An abnormal CUS test and/or the demonstration of venous reflux in the popliteal region and/or a high clinical score (≥ 8) identified twenty-four of the 43 (56%) DVT + patients with a specificity of 89%. The combination of normal CUS with the absence of venous reflux in both the common femoral and popliteal vein and a low clinical score excluded previous thrombosis in 45 (79%) of the 57 DVT- patients (negative predictive value, 78%). Abnormal venous reflux in the isolated common femoral vein did not reliably predict the presence or absence of previous DVT. However, this occurred in only 13 (13%) patients. The PPG determination of venous refilling time did not improve the results obtained with the other tests.Conclusions. The combination of a standardized clinical evaluation with the results of CUS and DUS can reliably diagnose or exclude previous proximal-vein thrombosis in almost 90% of patients with previous episodes of suspected DVT.


2020 ◽  
pp. 54-59
Author(s):  
A. S. Molostova ◽  
N. S. Gladyshev ◽  
A. V. Svarval ◽  
R. S. Ferman ◽  
A. B. Karasyova ◽  
...  

(HP) infection was performed using invasive and non-invasive methods. The study group consisted of 95 patients with dyspepsia. HP infection was detected in 47 patients (49.4 %). The expediency of using a set of diagnostic methods for detecting HP (PCR, immunochromatographic, bacteriological and method for determining urease activity) is proved. Most often (100 %) in patients HP infection was detected in biopsies using the PCR method. Somewhat less frequently it was detected when examining biopsies with an invasive biochemical method (AMA RUT Reader) (82 %) and fecal immunochromatographic method (83 %). Despite the fact that helicobacteriosis was detected bacteriologically in a small number of patients (24 %), this method is of particular value, since it allows you to assess the sensitivity to antimicrobial drugs and probiotics, and does not give false positive results.


2015 ◽  
Vol 24 (2) ◽  
pp. 197-201 ◽  
Author(s):  
Ramesh P. Arasaradnam ◽  
Michael McFarlane ◽  
Emma Daulton ◽  
Erik Westenbrink ◽  
Nicola O’Connell ◽  
...  

Background & Aims: Non-Alcoholic Fatty Liver Disease (NAFLD) is the commonest cause of chronic liver disease in the western world. Current diagnostic methods including Fibroscan have limitations, thus there is a need for more robust non-invasive screening methods. The gut microbiome is altered in several gastrointestinal and hepatic disorders resulting in altered, unique gut fermentation patterns, detectable by analysis of volatile organic compounds (VOCs) in urine, breath and faeces. We performed a proof of principle pilot study to determine if progressive fatty liver disease produced an altered urinary VOC pattern; specifically NAFLD and Non-Alcoholic Steatohepatitis (NASH).Methods: 34 patients were recruited: 8 NASH cirrhotics (NASH-C); 7 non-cirrhotic NASH; 4 NAFLD and 15 controls. Urine was collected and stored frozen. For assay, the samples were defrosted and aliquoted into vials, which were heated to 40±0.1°C and the headspace analyzed by FAIMS (Field Asymmetric Ion Mobility Spectroscopy). A previously used data processing pipeline employing a Random Forrest classification algorithm and using a 10 fold cross validation method was applied.Results: Urinary VOC results demonstrated sensitivity of 0.58 (0.33 - 0.88), but specificity of 0.93 (0.68 - 1.00) and an Area Under Curve (AUC) 0.73 (0.55 -0.90) to distinguish between liver disease and controls. However, NASH/NASH-C was separated from the NAFLD/controls with a sensitivity of 0.73 (0.45 - 0.92), specificity of 0.79 (0.54 - 0.94) and AUC of 0.79 (0.64 - 0.95), respectively.Conclusions: This pilot study suggests that urinary VOCs detection may offer the potential for early non-invasive characterisation of liver disease using 'smell prints' to distinguish between NASH and NAFLD.


2019 ◽  
Vol 19 (2) ◽  
pp. 105-111
Author(s):  
Nadia Shafei ◽  
Mohammad Saeed Hakhamaneshi ◽  
Massoud Houshmand ◽  
Siavash Gerayeshnejad ◽  
Fardin Fathi ◽  
...  

Background: Beta thalassemia is a common disorder with autosomal recessive inheritance. The most prenatal diagnostic methods are the invasive techniques that have the risk of miscarriage. Now the non-invasive methods will be gradually alternative for these invasive techniques. Objective: The aim of this study is to evaluate and compare the diagnostic value of two non-invasive diagnostic methods for fetal thalassemia using cell free fetal DNA (cff-DNA) and nucleated RBC (NRBC) in one sampling community. Methods: 10 ml of blood was taken in two k3EDTA tube from 32 pregnant women (mean of gestational age = 11 weeks), who themselves and their husbands had minor thalassemia. One tube was used to enrich NRBC and other was used for cff-DNA extraction. NRBCs were isolated by MACS method and immunohistochemistry; the genome of stained cells was amplified by multiple displacement amplification (MDA) procedure. These products were used as template in b-globin segments PCR. cff-DNA was extracted by THP method and 300 bp areas were recovered from the agarose gel as fetus DNA. These DNA were used as template in touch down PCR to amplify b-globin gen. The amplified b-globin segments were sequenced and the results compared with CVS resul. Results: The data showed that sensitivity and specificity of thalassemia diagnosis by NRBC were 100% and 92% respectively and sensitivity and specificity of thalassemia diagnosis by cff-DNA were 100% and 84% respectively. Conclusion: These methods with high sensitivity can be used as screening test but due to their lower specificity than CVS, they cannot be used as diagnostic test.


Author(s):  
Jian Liu ◽  
Yong Yu ◽  
Chenqi Zhu ◽  
Yu Zhang

The finite volume method (FVM)-based computational fluid dynamics (CFD) technology has been applied in the non-invasive diagnosis of coronary artery stenosis. Nonetheless, FVM is a time-consuming process. In addition to FVM, the lattice Boltzmann method (LBM) is used in fluid flow simulation. Unlike FVM solving the Navier–Stokes equations, LBM directly solves the simplified Boltzmann equation, thus saving computational time. In this study, 12 patients with left anterior descending (LAD) stenosis, diagnosed by CTA, are analysed using FVM and LBM. The velocities, pressures, and wall shear stress (WSS) predicted using FVM and LBM for each patient is compared. In particular, the ratio of the average and maximum speed at the stenotic part characterising the degree of stenosis is compared. Finally, the golden standard of LAD stenosis, invasive fractional flow reserve (FFR), is applied to justify the simulation results. Our results show that LBM and FVM are consistent in blood flow simulation. In the region with a high degree of stenosis, the local flow patterns in those two solvers are slightly different, resulting in minor differences in local WSS estimation and blood speed ratio estimation. Notably, these differences do not result in an inconsistent estimation. Comparison with invasive FFR shows that, in most cases, the non-invasive diagnosis is consistent with FFR measurements. However, in some cases, the non-invasive diagnosis either underestimates or overestimates the degree of stenosis. This deviation is caused by the difference between physiological and simulation conditions that remains the biggest challenge faced by all CFD-based non-invasive diagnostic methods.


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