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1.
Article in English | MEDLINE | ID: mdl-39143666

ABSTRACT

PURPOSE: The aim of this study was to investigate the utility of native T1 and T2 mapping in the bowel to evaluate disease activity in Crohn disease (CD) using endoscopy as the reference standard. METHODS: This was a prospective study. Magnetic resonance imaging was performed by using a 1.5-T Philips scanner. We used a modified look-locker inversion recovery and a multiecho gradient-spin-echo sequences for single breath-hold native T1 and T2 maps, respectively, for the short-axis image of the intestine, and the measurement at the most severe site was compared with partial Simple Endoscopic Score for Crohn's Disease (pSES-CD, assessed by an expert endoscopist). A pSES-CD ≥ 4 indicated active disease. Statistical analyses were performed using the Student t test, Spearman correlation, and receiver operating characteristic curve analysis. RESULTS: A total of 27 patients (mean age ± standard deviation, 37 ± 18 years; 20 men, 7 women) were included in this study. The native T1 value of active disease was significantly higher than that of inactive disease (1170.8 ± 100.5 milliseconds vs 924.5 ± 95.3 milliseconds; P = 0.018), but the T2 value was not significantly different between active and inactive disease (76.1 ± 7.8 milliseconds vs 69.3 ± 10.9 milliseconds; P = 0.424). A good correlation was found between native T1 value and pSES-CD (ρ = 0.71; P < 0.001) but not between T2 value and pSES-CD (ρ = 0.06; P = 0.790). The area under the receiver operating characteristic curve for differentiating the disease activity was 0.96 (95% confidence interval [CI]: 0.90-1.00) for T1 values and 0.68 (95% confidence interval: 0.41-0.96) for T2 values. CONCLUSIONS: Native T1 mapping could be potentially used as a noninvasive method to differentiate disease activity in patients with CD and may be superior to T2 mapping for this purpose.

2.
J Med Primatol ; 52(6): 374-383, 2023 12.
Article in English | MEDLINE | ID: mdl-37461241

ABSTRACT

BACKGROUND: Diastolic dysfunction in humans is an age-related process with an overrepresentation in women. In rhesus macaques (Macaca mulatta), the incidence and predictors of diastolic dysfunction have yet to be reported. METHODS: Data from routine echocardiographic evaluations on clinically healthy rhesus macaques was obtained and used for univariate, bivariate, hypothesis testing, and linear regression statistical analyses interrogating differences and predictors of diastolic function. RESULTS: Rhesus macaques fully recapitulate previously reported human hemodynamic studies. Female monkeys display impaired diastology and are at an increased risk for developing diastolic dysfunction. Age, sex, and proxies of exercise activity are confirmed predictors for measures of diastolic dysfunction, regardless of specific pathogen-free status. CONCLUSIONS: Rhesus macaques share common sex- and age-related echocardiographic findings as humans, therefore, serve as a valuable translational nonhuman primate model for future studies of diastolic dysfunction. These findings confirm the importance of sex- and age-matching within future rhesus macaque cardiovascular research.


Subject(s)
Echocardiography , Male , Humans , Animals , Female , Macaca mulatta , Echocardiography/veterinary
3.
J Comput Assist Tomogr ; 47(2): 178-185, 2023.
Article in English | MEDLINE | ID: mdl-36729617

ABSTRACT

OBJECTIVE: This study aimed to compare diagnostic performance for tumor detection and for assessment of tumor aggressiveness in prostate cancer (PC) between amide proton transfer magnetic resonance imaging (MRI) with 3-dimensional acquisition (3DAPT) and diffusion-weighted imaging. METHODS: The subjects were 23 patients with 27 pathologically proven PCs who underwent 3T multiparametric MRI. With reference to the pathology findings, 2 readers in consensus identified the location of PC on multiparametric MRI and measured APT signal intensity (APT SI [%]) and mean apparent diffusion coefficient (ADC) of the benign region and each PC lesion. RESULTS: The mean ADC showed a significant difference between benign regions and PC lesions (0.74 ± 0.15 vs 1.37 ± 0.21, P < 0.001), whereas APT SI did not ( P = 0.091). Lesion APT SI was significantly higher and lesion ADC was significantly lower in PCs with Gleason group (GG) ≥3 than in PCs with GG ≤2 (3.37 ± 1.30 vs 1.78 ± 0.67, P < 0.001, and 0.71 ± 0.18 vs 0.79 ± 0.10, P = 0.038, respectively). The APT SI was significantly higher in GG3 than in GG1, in GG3 than in GG2, and in GG4 than in GG2 ( P = 0.009, P = 0.001, and P = 0.006, respectively). The area under the curve for separating tumor lesions and benign regions was 0.601 for 3DAPT and 0.983 for ADC ( P < 0.001). The area under the curve for separating tumors with GG ≤2 from tumors with GG ≥3 was 0.912 for 3DAPT and 0.734 for ADC ( P = 0.172). CONCLUSIONS: In patients with PC, it might be preferable to use ADC to discriminate benign from malignant tissue and use APT SI for assessment of tumor aggressiveness.


Subject(s)
Prostatic Neoplasms , Protons , Male , Humans , Magnetic Resonance Imaging/methods , Diffusion Magnetic Resonance Imaging/methods , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Amides , Retrospective Studies
4.
MAGMA ; 35(4): 533-547, 2022 Aug.
Article in English | MEDLINE | ID: mdl-34491467

ABSTRACT

Diffusion-weighted imaging (DWI), a key component in multiparametric MRI (mpMRI), is useful for tumor detection and localization in clinically significant prostate cancer (csPCa). The Prostate Imaging Reporting and Data System versions 2 and 2.1 (PI-RADS v2 and PI-RADS v2.1) emphasize the role of DWI in determining PIRADS Assessment Category in each of the transition and peripheral zones. In addition, several recent studies have demonstrated comparable performance of abbreviated biparametric MRI (bpMRI), which incorporates only T2-weighted imaging and DWI, compared with mpMRI with dynamic contrast-enhanced MRI. Therefore, further optimization of DWI is essential to achieve clinical application of bpMRI for efficient detection of csPC in patients with elevated PSA levels. Although DWI acquisition is routinely performed using single-shot echo-planar imaging, this method suffers from such as susceptibility artifact and anatomic distortion, which remain to be solved. In this review article, we will outline existing problems in standard DWI using the single-shot echo-planar imaging sequence; discuss solutions that employ newly developed imaging techniques, state-of-the-art technologies, and sequences in DWI; and evaluate the current status of quantitative DWI for assessment of tumor aggressiveness in PC.


Subject(s)
Multiparametric Magnetic Resonance Imaging , Prostatic Neoplasms , Humans , Magnetic Resonance Imaging/methods , Male , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Retrospective Studies , Sensitivity and Specificity
5.
MAGMA ; 35(4): 549-556, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35403993

ABSTRACT

OBJECTIVES: Image quality (IQ) of diffusion-weighted imaging (DWI) with single-shot echo-planar imaging (ssEPI) suffers from low signal-to-noise ratio (SNR) in high b-value acquisitions. Compressed SENSE (C-SENSE), which combines SENSE with compressed sensing, enables SNR to be improved by reducing noise. The aim of this study was to compare IQ and prostate cancer (PC) detectability between DWI with ssEPI using SENSE (EPIS) and using C-SENSE (EPICS). MATERIALS AND METHODS: Twenty-five patients with pathologically proven PC underwent multi-parametric magnetic resonance imaging at 3T. DW images acquired with EPIS and EPICS were assessed for the following: lesion conspicuity (LC), SNR, contrast-to-noise ratio (CNR), mean and standard deviation (SD) of apparent diffusion coefficient (ADC) of lesion (lADCm and lADCsd), coefficient of variation of lesion ADC (lADCcv), and mean ADC of benign prostate (bADCm). RESULTS: LC were comparable between EPIS and EPICS (p > 0.050), and SNR and CNR were significantly higher in EPICS than EPIS (p = 0.001 and p < 0.001). In both EPIS and EPICS, lADCm was significantly lower than bADCm (p < 0.001). In addition, lADCcv was significantly lower in EPICS than in EPIS (p < 0.001). CONCLUSION: Compared with EPIS, EPICS has improved IQ and comparable diagnostic performance in PC.


Subject(s)
Echo-Planar Imaging , Prostatic Neoplasms , Diffusion Magnetic Resonance Imaging/methods , Echo-Planar Imaging/methods , Humans , Magnetic Resonance Imaging , Male , Prostate/diagnostic imaging , Prostate/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Reproducibility of Results , Signal-To-Noise Ratio
6.
Acta Radiol ; 63(11): 1489-1496, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34558315

ABSTRACT

BACKGROUND: Ligaments and tendons are difficult to differentiate on conventional magnetic resonance imaging (MRI). Ligaments and tendons are different histologically, and tendon graft ligamentization is known to occur after anterior cruciate ligament (ACL) reconstruction. PURPOSE: To quantify and differentiate the ultrashort echo time T2* (UTE-T2*) values of normal knee ligaments and tendons using a 1.5-T MRI scanner. MATERIAL AND METHODS: The right knees of 12 healthy volunteers (6 men, 6 women; mean age = 30.8 ± 9.6 years) were scanned using a UTE-T2* sequence and the UTE-T2* values of the proximal, middle, and distal portions of the ACL, posterior cruciate ligament (PCL), and patellar tendon (PT) were evaluated. Two doctors manually drew the regions of interest four times and intra- and inter-observer reliability were evaluated by intraclass correlation coefficients. RESULTS: The UTE-T2* values of ACL at the proximal, middle, distal, and mean were 12.0 ± 2.3, 11.3 ± 2.3, 12.3 ± 2.6, and 11.9 ± 2.4 ms, respectively. The UTE-T2* values of the PCL at each site were 6.9 ± 1.5, 9.0 ± 1.8, 8.8 ± 2.4, and 8.3 ± 2.1 ms, respectively. The UTE-T2* values of the PT at each site were 7.1 ± 1.7, 4.3 ± 1.7, 4.3 ± 1.8, and 5.2 ± 2.1 ms, respectively. Both intra- and inter-observer reliability showed high agreement rates. There were significant differences among the ACL mean, PCL mean, and PT mean, with a P value <0.01 in all cases. CONCLUSION: This study confirms that UTE-T2* mapping can quantify the ACL, PCL, and PT, and tendons and ligaments can be differentiated using the UTE-T2* values in normal volunteer knee joints.


Subject(s)
Knee Joint , Posterior Cruciate Ligament , Adult , Female , Humans , Knee Joint/diagnostic imaging , Knee Joint/surgery , Magnetic Resonance Imaging/methods , Male , Reproducibility of Results , Tendons/diagnostic imaging , Young Adult
7.
BMC Vet Res ; 17(1): 89, 2021 Feb 23.
Article in English | MEDLINE | ID: mdl-33622315

ABSTRACT

BACKGROUND: Prior studies have suggested that pimobendan is associated with several positive effects in cats, including improved survival in cats with congestive heart failure and improved left atrial function in research colony cats with hypertrophic cardiomyopathy (HCM) and normal cats. However, there is still a paucity of pharmacodynamic data refuting or supporting the use of pimobendan in a clinical cat population. This clinical trial aimed to evaluate the pharmacodynamic effects and tolerability of a single dose of pimobendan in cats with HCM. Echocardiograms and Doppler-derived systolic blood pressures were performed in 21 client-owned cats with subclinical HCM at baseline and 90-min after oral administration of 1.25 mg of pimobendan (Vetmedin). Seven additional cats were evaluated post-placebo administration to account for intra-day variability. RESULTS: Heart rate, systolic blood pressure, and murmur grade were not significantly different between baseline and post-pimobendan evaluations. Left auricular blood flow velocity, left atrial size, and left ventricular fractional shortening were not significantly different between baseline and post-pimobendan evaluations. Mean (± standard deviation) tissue Doppler peak systolic velocity of the mitral annulus was significantly higher following pimobendan (7.4 cm/s ± 1.5 vs 8.5 ± 1.6; p = 0.02). Median (min, max) left-ventricular outflow tract maximum velocity was significantly higher following pimobendan [1.9 m/sec (1.5, 3.4) vs 2.6 m/sec (2.0, 4.0); p = 0.01]. Mean right-ventricular outflow tract maximum velocity was also significantly higher following pimobendan (1.5 m/s ± 0.51 vs 2.0 ± 0.53; p = 0.004). Mean left atrial fractional shortening was significantly higher following pimobendan (28% ± 6 vs 32% ± 7; p = 0.02). No adverse events were observed following pimobendan administration. Right ventricular outflow tract velocity was significantly higher following placebo in control cats (1.02 ± 0.21 versus 1.31 ± 0.31; p = 0.01). No other significant differences were detected. CONCLUSIONS: In client-owned cats with HCM, pimobendan acutely increased left atrial function and mildly increased left ventricular systolic function. Left ventricular outflow tract velocity was increased after pimobendan. Pimobendan was well tolerated in the acute setting in cats with HCM. The findings of this prospective, acute-dosing study confirm previous findings in research animals and retrospective analyses and suggest that chronic dosing studies are safe and warranted.


Subject(s)
Cardiomyopathy, Hypertrophic/veterinary , Cardiotonic Agents/pharmacokinetics , Cat Diseases/drug therapy , Pyridazines/pharmacokinetics , Animals , Blood Flow Velocity/drug effects , Blood Flow Velocity/veterinary , Blood Pressure , Cardiomyopathy, Hypertrophic/drug therapy , Cardiotonic Agents/pharmacology , Cats , Echocardiography/veterinary , Female , Heart Rate/drug effects , Male , Prospective Studies , Pyridazines/pharmacology , Ventricular Function, Left
8.
BMC Vet Res ; 16(1): 348, 2020 Sep 22.
Article in English | MEDLINE | ID: mdl-32962713

ABSTRACT

BACKGROUND: Echocardiography is commonly used for assessing cardiac structure and function in various species including non-human primates. A few previous studies reported normal echocardiographic reference intervals of clinically healthy rhesus macaques under sedation. However, these studies were under-powered, and the techniques were not standardized. In addition, body weight, age, and sex matched reference intervals should be established as echocardiographic measurements are commonly influenced by these variables. The purpose of this study was to establish reference intervals for complete echocardiographic parameters based on a large cohort of clinically healthy rhesus macaques with wide ranges of weight and age distributions using allometric scaling. RESULTS: A total of 823 rhesus macaques (ages 6 months to 31 years old; body weights 1.4 to 22.6 kg) were enrolled. Of these rhesus macaques, 421 were males and 402 were females. They were assessed with a complete echocardiographic examination including structural and functional evaluation under sedation with ketamine hydrochloride. The reference intervals of the key echocardiographic parameters were indexed to weight, age, and sex by calculating the coefficients of the allometric eq. Y = aMb. On correlation matrix, body weight, age, sex, and heart rate were significantly correlated with various echocardiographic parameters and some of the parameters were strongly correlated with body weight and age. Multiple regression analysis revealed that heart rate and body weight statistically significantly predicted several echocardiographic parameters. Valve regurgitation including tricuspid, aortic, pulmonic, and mitral regurgitations without other cardiac structural and functional abnormalities are common in clinically healthy rhesus macaques under ketamine sedation. CONCLUSIONS: In this study, the reference intervals of echocardiographic parameters were established by performing complete echocardiographic examinations on a large number of clinical healthy rhesus macaques. In addition, allometric scaling was performed based on their weight, and further indexed to age and sex. These allometrically scaled reference intervals can be used to accurately evaluate echocardiographic data in rhesus macaques and diagnose structural and functional evidence of cardiac disease.


Subject(s)
Echocardiography/veterinary , Macaca mulatta/physiology , Age Factors , Animals , Body Weight , Female , Heart Rate , Hypnotics and Sedatives/administration & dosage , Ketamine/administration & dosage , Male , Reference Values
9.
Pflugers Arch ; 471(5): 745-753, 2019 05.
Article in English | MEDLINE | ID: mdl-30284024

ABSTRACT

Comparative and translation medicine is of particular value within the field of inherited cardiomyopathies. Despite massive advances in understanding the functional role of mutations in human cardiomyopathies, these advances have frequently failed to translate into medical discoveries that alter patient care. One potential explanation for this failure lies in the lack of suitable translational models that adequately recapitulate human cardiovascular physiology and disease expression. The vast genetic heterogeneity that complicates human cardiomyopathy research is potentially alleviated through the study of naturally occurring large animal models of disease, where incredibly homogenous populations, like those seen in a single breed of dog or cat, may exist (Kol et al., Sci Transl Med 7:308-321, 2015; Ueda and Stern, Yale J Biol Med 90:433-448, 2017). Veterinary medicine is in a unique position to provide research resources and information that may be readily applied to human disease (Kol et al., Sci Transl Med 7:308-321, 2015). Many inherited cardiomyopathies of humans are phenotypically and genotypically similar in veterinary species and ongoing research holds promise for aiding veterinary and human patients alike (Basso et al., Circulation 109:1180-1185, 2004; Fox et al., Cardiovasc Pathol 23:28-34, 2014; Fox et al., Circulation 102:1863-1870, 2000; Kittleson et al., J Vet Cardiol 17 Suppl 1:S53-73, 2015; Ueda and Stern, Yale J Biol Med 90:433-448, 2017). This article presents the current knowledge of inherited cardiomyopathies in dogs, cats, and non-human primates, with a goal of identifying areas of translational research and future directions.


Subject(s)
Cardiomyopathy, Dilated/veterinary , Cardiomyopathy, Hypertrophic/veterinary , Animals , Cardiomyopathy, Dilated/diagnostic imaging , Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Dilated/pathology , Cardiomyopathy, Hypertrophic/diagnostic imaging , Cardiomyopathy, Hypertrophic/genetics , Cardiomyopathy, Hypertrophic/pathology , Cats , Dogs , Macaca mulatta , Mutation
10.
Yale J Biol Med ; 90(3): 433-448, 2017 09.
Article in English | MEDLINE | ID: mdl-28955182

ABSTRACT

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease in humans and results in significant morbidity and mortality. Research over the past 25 years has contributed enormous insight into this inherited disease particularly in the areas of genetics, molecular mechanisms, and pathophysiology. Our understanding continues to be limited by the heterogeneity of clinical presentations with various genetic mutations associated with HCM. Transgenic mouse models have been utilized especially studying the genotypic and phenotypic interactions. However, mice possess intrinsic cardiac and hemodynamic differences compared to humans and have limitations preventing their direct translation. Other animal models of HCM have been studied or generated in part to overcome these limitations. HCM in cats shows strikingly similar molecular, histopathological, and genetic similarities to human HCM, and offers an important translational opportunity for the study of this disease. Recently, inherited left ventricular hypertrophy in rhesus macaques was identified and collaborative investigations have been conducted to begin to develop a non-human primate HCM model. These naturally-occurring large-animal models may aid in advancing our understanding of HCM and developing novel therapeutic approaches to this disease. This review will highlight the features of HCM in humans and the relevant available and developing animal models of this condition.


Subject(s)
Cardiomyopathy, Hypertrophic/genetics , Cardiomyopathy, Hypertrophic/physiopathology , Animals , Cardiomyopathies/genetics , Cardiomyopathies/metabolism , Cardiomyopathies/physiopathology , Cardiomyopathy, Hypertrophic/metabolism , Disease Models, Animal , Genetic Predisposition to Disease/genetics , Hemodynamics/genetics , Hemodynamics/physiology , Humans , Hypertrophy, Left Ventricular/genetics , Hypertrophy, Left Ventricular/metabolism , Hypertrophy, Left Ventricular/physiopathology , Macaca mulatta
11.
J Magn Reson Imaging ; 43(1): 138-48, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26119033

ABSTRACT

BACKGROUND: To evaluate more detailed information noninvasively through on diffusion and perfusion in prostate cancer (PCa) using triexponential analysis of diffusion-weighted imaging (DWI). METHODS: Sixty-three prostate cancer patients underwent preoperative 3.0 Tesla MRI including eight b-values DWI. Triexponential analysis was performed to obtain three diffusion coefficients (Dp , Df , Ds ), as well as fractions (Fp , Ff , Fs ). Each diffusion parameter for cancerous lesions and normal tissues was compared and the relationship between diffusion parameters and Gleason score (GS) was assessed. K(trans) , Ve , and the ratios of intracellular components measured in histopathological specimens were compared with diffusion parameters. RESULTS: Dp was significantly greater for cancerous lesions than normal peripheral zone (PZ) (P < 0.001), whereas Dp in transition zone (TZ) showed no significant difference (P = 0.74, 95% confidence interval (CI) = -4.69-6.48). Ds was significantly smaller for each cancerous lesions in PZ and TZ (P < 0.001, respectively). There was no significant difference in Df between cancerous lesions and normal tissues in PZ and TZ (P = 0.07, 95% CI = -0.29-0.12 and P = 0.53, 95% CI = -3.51-2.29, respectively). D obtained with biexponential analysis were significantly smaller in cancerous lesions than in normal tissue in PZ and TZ (P < 0.001 for both), while D* in PZ and TZ showed no significant difference (P = 0.14, 95% CI = -1.60-0.24 and P = 0.31, 95% CI = -3.43-1.16, respectively). Dp in PZ and TZ showed significant correlation with K(trans) (R = 0.85, P < 0.001; R = 0.81, P < 0.001, respectively), while D(*) in PZ obtained with biexponential analysis showed no such correlation (P = 0.08, 95% CI = -0.14-0.30). Fs was significantly correlated with intracellular space fraction evaluated in histopathological specimens in PZ and TZ cancer (R = 0.41, P < 0.05; R = 0.59, P < 0.001, respectively). Ff and Fs correlated significantly with GS in PZ and TZ cancer (PZ: R = -0.44, P < 0.05; R = 0.37, P < 0.05, TZ: R = -0.59, P < 0.05; R = 0.57, P < 0.05, respectively). CONCLUSION: Triexponential analysis is a noninvasive approach that can provide more detailed information regarding diffusion and perfusion of PCa than biexponential analysis.


Subject(s)
Algorithms , Diffusion Magnetic Resonance Imaging/methods , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Prostatic Neoplasms/pathology , Aged , Humans , Male , Numerical Analysis, Computer-Assisted , Reproducibility of Results , Sensitivity and Specificity
12.
Sci Technol Adv Mater ; 17(1): 753-759, 2016.
Article in English | MEDLINE | ID: mdl-27933115

ABSTRACT

We systematically investigated effects of molecular crowding with trimethylamine N-oxide (TMAO) as a zwitterionic and protective osmolyte and urea as a nonionic denaturing osmolyte on conformation and thermodynamics of the canonical DNA duplex and the non-canonical DNA G-quadruplex. It was found that TMAO and urea stabilized and destabilized, respectively, the G-quadruplex. On the other hand, these osmolytes generally destabilize the duplex; however, it was observed that osmolytes having the trimethylamine group stabilized the duplex at the lower concentrations because of a direct binding to a groove of the duplex. These results are useful not only to predict DNA structures and their thermodynamics under physiological environments in living cells, but also design of polymers and materials to regulate structure and stability of DNA sequences.

13.
J Vet Intern Med ; 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39122666

ABSTRACT

An 8-year-old American Quarter Horse gelding was treated with extracorporeal hemoperfusion (HP) therapy for treatment of Clostridioides difficile (C. difficile) colitis-induced systemic inflammatory response syndrome (SIRS). The gelding developed C. difficile associated peracute colitis and severe SIRS as evidenced by a positive fecal C. difficile PCR and tachypnea, tachycardia, fever, neutropenia, altered mucous membrane color, and hyperlactatemia. Concurrent acute kidney injury in the horse limited the use of routine anti-inflammatory and anti-lipopolysaccharide treatments, including flunixin meglumine and polymyxin B, because of potential for nephrosis. Extracorporeal HP therapy was performed twice within 48 hours of the onset of severe SIRS during which the horse's physical examination variables stabilized. The horse was euthanized after 4 days because of laminitis. These findings support further investigation of extracorporeal HP therapy as an adjunctive treatment for severe SIRS/sepsis in horses.

14.
Am J Vet Res ; 85(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38484466

ABSTRACT

OBJECTIVE: Plasma cytokine adsorption has shown benefit as an adjunctive therapy in human sepsis but has yet to be investigated in horses. We hypothesized that ex vivo filtration of equine plasma with a novel cytokine adsorption device would significantly reduce concentrations of lipopolysaccharide-stimulated cytokines. We also hypothesized that the device would adsorb medications commonly used to treat sepsis. ANIMALS: 8 horses owned by North Carolina State University. METHODS: Four liters of heparinized whole blood was collected from healthy adult horses (n = 8) and stimulated with lipopolysaccharide (100 ng/mL) for 6 hours (37 °C.) from June 4, 2023, to December 15, 2023. Plasma was filtered through a cytokine adsorption device or sham circuit. Samples were collected at 11 time points for multiplex cytokine analysis. Chemistry analysis was performed before and after filtration. To investigate the impact of the device on medication concentrations, equine plasma containing potassium penicillin, gentamicin, and flunixin meglumine was filtered through the cytokine adsorption device or sham for 6 hours. Drug concentrations before and after filtration were determined by ultra-high-performance liquid chromatography. Prefiltration versus postfiltration sample concentrations were analyzed by Student paired t test using GraphPad Prism 9.0 (P < .05). RESULTS: Filtration of lipopolysaccharide-stimulated equine plasma (n = 8) for 6 hours resulted in significant mean reductions in the cytokines IL-10, IL-5, IL-8, tumor necrosis factor-α (TNF-α), and IL-1ß, as well as albumin. Drug concentrations of potassium penicillin, gentamicin, and flunixin meglumine were also significantly reduced by filtration. CLINICAL RELEVANCE: This work provides proof of concept for further investigation of extracorporeal cytokine adsorption as a potential adjunct treatment for equine sepsis.


Subject(s)
Cytokines , Lipopolysaccharides , Animals , Horses , Cytokines/metabolism , Cytokines/blood , Horse Diseases/therapy , Sepsis/veterinary , Sepsis/therapy , Adsorption , Male , Female , Anti-Bacterial Agents
15.
Front Vet Sci ; 11: 1362730, 2024.
Article in English | MEDLINE | ID: mdl-38686029

ABSTRACT

Introduction: Dosing recommendations for hydromorphone intravenous constant rate infusion (IV CRI) are derived from simulations following IV bolus administration. While this extrapolated dose regimen has been described clinically, pharmacokinetics (PK) of hydromorphone infusions in dogs are not yet described. The study objective was to describe the PK of hydromorphone in healthy dogs receiving an IV bolus followed by an IV CRI for 48 h. Methods: A prospective, experimental study was performed involving the administration of hydromorphone (0.1 mg/kg IV bolus then IV CRI 0.01 mg/kg/h over a 48 h period) to 6 healthy Beagle dogs. Blood samples were collected at 16 time points between 0 and 58 h relative to the initial bolus. Plasma hydromorphone concentrations were analyzed by high pressure liquid chromatography with tandem mass spectrometry detection. Pharmacokinetic parameter estimates were obtained with compartmental methods using commercially available software. Results: A two-compartment model with first order elimination was used. At the end of the infusion, median (range) plasma hydromorphone concentrations were 6.8 (5.5-19.6) ng/mL. The median total body clearance was 30.4 (19.8-36.7) mL/min/kg; volume of distribution at steady state was 4.5 (3.2-7.8) L/kg; and terminal elimination half-life was 11.2 (7.6-24.3) h. Conclusion: Hydromorphone (0.1 mg/kg IV bolus then IV CRI of 0.01 mg/kg/h) maintained steady-state plasma concentrations above the minimum human analgesic target in healthy Beagle dogs with minimal side effects. Further studies are needed to determine the effective plasma concentrations of hydromorphone in painful dogs.

16.
Front Vet Sci ; 11: 1414426, 2024.
Article in English | MEDLINE | ID: mdl-38803798

ABSTRACT

Objective: Develop, implement, and monitor for adverse effects of, a novel hemoperfusion therapy in adult horses. Methods: A prospective, observational feasibility study using three healthy adult horses from the North Carolina State University teaching herd. Health status was determined by physical exam, complete blood count, coagulation panel, and serum biochemistry. Each horse was instrumented with a 14 Fr × 25 cm double-lumen temporary hemodialysis catheter and underwent a 240 min polymer-based hemoperfusion session. Horses were administered unfractionated heparin to maintain anti-coagulation during the session. Given the novelty of this therapy in horses, each horse was treated as a learning opportunity that informed an iterative process of protocol development and modification. Measurements and main results: Our long-term goal is to investigate potential clinical applications of hemoperfusion in horses, including cytokine reduction in horses with severe SIRS/sepsis. Horses were monitored for changes in clinical exam, biochemistry and hematology parameters. Additionally, cytokines were quantified to determine whether extracorporeal hemadsorption therapy alone caused an inflammatory response. Our results show that hemoperfusion therapy was associated with decreased platelet counts and serum albumin concentration. There was no significant change in plasma cytokine concentrations with hemoperfusion therapy. In one horse, the cytokine concentrations decreased, as previously reported with hemoperfusion therapy in humans. Hypothesis: We hypothesized that hemoperfusion therapy could be performed in healthy adult horses without significant adverse effects. Conclusion: Polymer-based hemoperfusion is a feasible extracorporeal therapy (ECT) modality for adult horses. Additional studies are needed to further establish clinical protocols, as well as establish efficacy of polymer-based hemoperfusion for treatment of various conditions in horses, including intoxications, immune-mediated conditions, and sepsis.

17.
Eur J Radiol ; 175: 111445, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38537605

ABSTRACT

PURPOSE: To evaluate the feasibility of a free-breathing sequence (4D FreeBreathing) combined with Compressed SENSE in dynamic contrast-enhanced pancreatic MRI and compare it with a breath-holding sequence (eTHRIVE). METHOD: Patients who underwent pancreatic MRI, either eTHRIVE or 4D FreeBreathing, from April 2022 to November 2023 were included in this retrospective study. Two radiologists, who were unaware of the scan sequence, independently and randomly reviewed the images at the precontrast, pancreatic, portal venous, and equilibrium phases and assigned confidence scores for motion and streaking artifacts, pancreatic sharpness, and overall image quality using a 5-point scale. Furthermore, the radiologists assessed the appropriateness of the scan timing of the pancreatic phase. Mann-Whitney U and Fisher's exact tests were conducted to compare the confidence scores and adequacy of the pancreatic phase scan timing between eTHRIVE and 4D FreeBreathing. RESULTS: Overall, 48 patients (median age, 71 years; interquartile range, 64-77 years; 24 women) were included. Among them, 20 patients (42%) were scanned using 4D FreeBreathing. The 4D FreeBreathing showed moderate streaking artifact but improved motion artifact (P <.001-.17) at all phases. Pancreatic sharpness and overall image quality were almost comparable between two sequences (P = .17-.96). All 20 examinations in 4D FreeBreathing showed appropriate pancreatic phase images, but only 16 (57%; P <.001 for reviewer 1) and 18 (64%; P = .003 for reviewer 2) examinations showed it in eTHRIVE. CONCLUSION: The use of 4D FreeBreathing combined with Compressed SENSE was feasible in pancreatic MRI and provided appropriate pancreatic phase images in all examinations.


Subject(s)
Contrast Media , Feasibility Studies , Magnetic Resonance Imaging , Humans , Female , Male , Middle Aged , Aged , Retrospective Studies , Magnetic Resonance Imaging/methods , Artifacts , Respiration , Image Enhancement/methods , Breath Holding , Data Compression/methods , Pancreatic Neoplasms/diagnostic imaging , Pancreas/diagnostic imaging , Pancreatic Diseases/diagnostic imaging
19.
Vet Clin North Am Small Anim Pract ; 53(6): 1255-1276, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37423841

ABSTRACT

Cardiomyopathies remain one of the most common inherited cardiac diseases in both human and veterinary patients. To date, well over 100 mutated genes are known to cause cardiomyopathies in humans with only a handful known in cats and dogs. This review highlights the need and use of personalized one-health approaches to cardiovascular case management and advancement in pharmacogenetic-based therapy in veterinary medicine. Personalized medicine holds promise in understanding the molecular basis of disease and ultimately will unlock the next generation of targeted novel pharmaceuticals and aid in the reversal of detrimental effects at a molecular level.


Subject(s)
Cardiology , Cardiomyopathies , Cat Diseases , Dog Diseases , Veterinary Drugs , Humans , Animals , Cats , Dogs , Pets , Precision Medicine/veterinary , Cardiomyopathies/genetics , Cardiomyopathies/therapy , Cardiomyopathies/veterinary , Cat Diseases/drug therapy , Cat Diseases/genetics , Dog Diseases/drug therapy , Dog Diseases/genetics
20.
Magn Reson Med Sci ; 22(2): 191-208, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-36928124

ABSTRACT

Since its first observation in the 18th century, the diffusion phenomenon has been actively studied by many researchers. Diffusion-weighted imaging (DWI) is a technique to probe the diffusion of water molecules and create a MR image with contrast based on the local diffusion properties. The DWI pixel intensity is modulated by the hindrance the diffusing water molecules experience. This hindrance is caused by structures in the tissue and reflects the state of the tissue. This characteristic makes DWI a unique and effective tool to gain more insight into the tissue's pathophysiological condition. In the past decades, DWI has made dramatic technical progress, leading to greater acceptance in clinical practice. In the abdominal region, however, acquiring DWI with good quality is challenging because of several reasons, such as large imaging volume, respiratory and other types of motion, and difficulty in achieving homogeneous fat suppression. In this review, we discuss technical advancements from the past decades that help mitigate these problems common in abdominal imaging. We describe the use of scan acceleration techniques such as parallel imaging and compressed sensing to reduce image distortion in echo planar imaging. Then we compare techniques developed to mitigate issues due to respiratory motion, such as free-breathing, respiratory-triggering, and navigator-based approaches. Commonly used fat suppression techniques are also introduced, and their effectiveness is discussed. Additionally, the influence of the abovementioned techniques on image quality is demonstrated. Finally, we discuss the current and future clinical applications of abdominal DWI, such as whole-body DWI, simultaneous multiple-slice excitation, intravoxel incoherent motion, and the use of artificial intelligence. Abdominal DWI has the potential to develop further in the future, thanks to scan acceleration and image quality improvement driven by technological advancements. The accumulation of clinical proof will further drive clinical acceptance.


Subject(s)
Abdomen , Artificial Intelligence , Abdomen/diagnostic imaging , Image Enhancement/methods , Respiration , Motion , Diffusion Magnetic Resonance Imaging/methods , Echo-Planar Imaging/methods , Reproducibility of Results
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