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A potential approach for assessing the quality of human and nonhuman adenoviral vector preparations
2020
Sayedahmed, Ekramy E. | Mittal, Suresh K.
Various types of human and nonhuman adenoviral (AdV) vectors are being used as gene delivery vectors in preclinical and clinical investigations. The objective of this study was to determine the ratio between the 2 best assays that would effectively address the variability in the titration of various AdV vectors in different cell lines and help obtain consistent results in preclinical and clinical studies using different AdV vectors. Here, we compared plaque-forming units, tissue culture infectious dose 50, focus-forming units (FFU), virus particle (VP) count, and genome copy number (GCN) of purified preparations of human AdV type C5, bovine AdV type 3, and porcine AdV type 3 to determine a correlation between infectious and noninfectious virus particles. Our results suggest that a VP:FFU or a VP:GCN ratio could accurately reflect the quality of an AdV preparation and could serve as an indicator to control batch-to-batch variability.
显示更多 [+] 显示较少 [-]Clinical significance of Proteus mirabilis bacteriuria in dogs, risk factors and antimicrobial susceptibility
2020
Decome, Magali | Cuq, Benoit | Fairbrother, Julie-Helene | Gatel, Laure | Conversy, Berenice
The objectives of this study were to describe the in vitro antimicrobial susceptibility and clinical significance of Proteus mirabilis in canine bacteriuria and to identify the risk factors associated with P. mirabilis urinary tract infections. This is a retrospective observational study of 48 P. mirabilis-positive canine urinary cultures. Only 22 of the 48 P. mirabilis isolates (45.8%) were non-susceptible to at least one tested antimicrobial. Most P. mirabilis isolates (98%) were susceptible to enrofloxacin, 93.7% to amoxicillin/clavulanic acid, and 85.4% to ampicillin, cephalothin, and trimethoprim-sulfamethoxazole. Five multidrug-resistant isolates were detected (10.4%). A significant increase in antimicrobial resistance was observed over the study period. Positive P. mirabilis cultures were associated with bacterial cystitis in 36 of 39 dogs (92.3%), pyelonephritis in 2 of 39 dogs (5.1%), and one dog had both bacterial cystitis and pyelonephritis (2.5%). There was no subclinical bacteriuria. Most urinary tract infections were complicated as risk factors were identified in 37 of 39 dogs (94.8%). The most commonly identified risk factors were the presence of a contaminated peri-vulvar area with urine/feces or a hypoplastic vulva. To conclude, P. mirabilis bacteriuria was associated with upper and lower urinary tract infections in this study and was found more frequently in complicated bacterial cystitis. Multidrug-resistant isolates and increased P. mirabilis antimicrobial resistance have been identified over the last 10 years, but most isolates remain susceptible to first-line antimicrobials such as amoxicillin and trimethoprim-sulfamethoxazole.
显示更多 [+] 显示较少 [-]Accuracy of tidal volume delivery by five different models of large-animal ventilators
2020
Floriano, Dario | Hopster, Klaus | Driessen, Bernd
OBJECTIVE To determine the accuracy of tidal volume (VT) delivery among 5 different models of large-animal ventilators when tested at various settings for VT delivery, peak inspiratory flow (PIF) rate, and fresh gas flow (FGF) rate. SAMPLE 4 different models of pneumatically powered ventilators and 1 electrically powered piston-driven ventilator. PROCEDURES After a leak flow check, each ventilator was tested 10 times for each experimental setting combination of 5 levels of preset VT, 3 PIF rates, and 4 FGF rates. A thermal mass flow and volume meter was used as the gold-standard method to measure delivered VT. In addition, circuit systems of rubber versus polyvinyl chloride breathing hoses were evaluated with the piston-driven ventilator. Differences between preset and delivered VT (volume error [ΔVT]) were calculated as a percentage of preset VT, and ANOVA was used to compare results across devices. Pearson correlation coefficient analyses and the coefficient of determination (r2) were used to assess potential associations between the ΔVT and the preset VT, PIF rate, and FGF rate. RESULTS For each combination of experimental settings, ventilators had ΔVT values that ranged from 1.2% to 22.2%. Mean ± SD ΔVT was 4.8 ± 2.5% for the piston-driven ventilator, compared with 6.6 ± 3.2%, 10.6 ± 2.9%, 13.8 ± 2.97%, and 15.2 ± 2.6% for the 4 pneumatic ventilators. The ΔVT increased with higher PIF rates (r2 = 0.69), decreased with higher FGF rates (r2 = 0.62), and decreased with higher preset VT (r2 = 0.58). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the tested ventilators all had ΔVT but that the extent of each of ΔVT varied among ventilators. Close monitoring of delivered VT with external flow and volume meters is warranted, particularly when pneumatic ventilators are used or when very precise VT delivery is required.
显示更多 [+] 显示较少 [-]Effects of a priming dose of alfaxalone on the total anesthetic induction dose for and cardiorespiratory function of sedated healthy cats
2020
Lagos-Carvajal, Angie | Queiroz-Williams, Patricia | Cremer, Jeannette | Ricco-Pereira, Carolina H. | Nevarez, Javier | Da Cunha, Anderson F. | Liu, Qinqi
OBJECTIVE To investigate the effects of a priming dose of alfaxalone on the total anesthetic induction dose for and cardiorespiratory function of sedated healthy cats. ANIMALS 8 healthy adult cats. PROCEDURES For this crossover study, cats were sedated with dexmedetomidine and methadone administered IM. Cats next received a priming induction dose of alfaxalone (0.25 mg/kg, IV) or saline (0.9% NaCl) solution (0.025 mL/kg, IV) over 60 seconds and then an induction dose of alfaxalone (0.5 mg/kg/min, IV) until orotracheal intubation was achieved. Cardiorespiratory variables were recorded at baseline (immediately prior to priming agent administration), immediately after priming agent administration, after orotracheal intubation, and every 2 minutes until extubation. The total induction dose of alfaxalone was compared between the 2 priming agents. RESULTS Mean ± SD total anesthetic induction dose of alfaxalone was significantly lower when cats received a priming dose of alfaxalone (0.98 ± 0.28 mg/kg), compared with when cats received a priming dose of saline solution (1.41 ± 0.17 mg/kg). Mean arterial blood pressure was significantly higher when alfaxalone was used as the priming dose. No cats became apneic or had a hemoglobin oxygen saturation of < 90%. Expired volume per minute was not significantly different between the 2 priming agents. CONCLUSIONS AND CLINICAL RELEVANCE Administration of a priming dose of alfaxalone to healthy sedated cats reduced the total dose of alfaxalone needed to achieve orotracheal intubation, maintained mean arterial blood pressure, and did not adversely impact the measured respiratory variables.
显示更多 [+] 显示较少 [-]Novel use of an activity monitor to model jumping behaviors in cats
2020
Sharon, Kate P. | Thompson, Caryn M. | Lascelles, B. Duncan X. | Parrish, Rudolph S.
OBJECTIVE To develop methods to identify and characterize activity monitor (AM) data signatures for jumps performed by cats. ANIMALS 13 healthy, client-owned cats without evidence of osteoarthritis or degenerative joint disease. PROCEDURES Each cat was fitted with the same AM, individually placed in an observation room, then simultaneously recorded by 3 video cameras during the observation period (5 to 8 hours). Each cat was encouraged to jump up (JU), jump down (JD), and jump across (JA) during the observation period. Output from the AM was manually annotated for jumping events, each of which was characterized by functional data analysis yielding relevant coefficients. The coefficients were then used in linear discriminant analysis to differentiate recorded jumps as JUs, JDs, or JAs. To assess the model's ability to distinguish among the 3 jump types, a leave-one-out cross-validation method was used, and the misclassification error rate of the overall categorization of the model was calculated. RESULTS Of 731 jumping events, 29 were misclassified. Overall, the mean misclassification error rate per cat was 5.4% (range, 0% to 12.5%), conversely indicating a correct classification rate per cat of 94.6%. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the model was successful in correctly identifying JUs, JDs, and JAs in healthy cats. With advancements in AM technology and data processing, there is potential for the model to be applied in clinical settings as a means to obtain objective outcome measures.
显示更多 [+] 显示较少 [-]Histologic changes and gene expression patterns in biopsy specimens from bacteria-inoculated and noninoculated excisional body and limb wounds in horses healing by second intention
2020
Jorgensen, Elin | Hjerpe, Freja B. | Hougen, Hans P. | Bjarnsholt, Thomas | Berg, Lise C. | Jacobsen, Stine
OBJECTIVE To evaluate histologic changes and gene expression patterns in body and limb wounds in horses in response to bacterial inoculation. SAMPLE Wound biopsy specimens from 6 horses collected on days 7, 14, 21, and 27 after excisional wounds (20 wounds/horse) were created over the metacarpal and metatarsal region and lateral thoracic region (body) and then inoculated or not inoculated on day 4 with Staphylococcus aureus and Pseudomonas aeruginosa. PROCEDURES Specimens were histologically scored for the amount of inflammation, edema, angiogenesis, fibrosis organization, and epithelialization. Quantitative PCR assays were performed to quantify gene expression of 10 inflammatory, proteolytic, fibrotic, and hypoxia-related markers involved in wound healing. RESULTS Except for gene expression of interleukin-6 on day 27 and tumor necrosis factor-α on day 14, bacterial inoculation had no significant effect on histologic scores and gene expression. Gene expression of interleukin-1β and -6, serum amyloid A, and matrix metalloproteinase-9 was higher in limb wounds versus body wounds by day 27. Gene expression of cellular communication network factor 1 was higher in limb wounds versus body wounds throughout the observation period. CONCLUSIONS AND CLINICAL RELEVANCE The lack of clear markers of wound infection in this study reflected well-known difficulties in detecting wound infections in horses. Changes consistent with protracted inflammation were evident in limb wounds, and gene expression patterns of limb wounds shared similarities with those of chronic wounds in humans. Cellular communication network factor warrants further investigation and may be useful in elucidating the mechanisms underlying poor limb wound healing in horses.
显示更多 [+] 显示较少 [-]Effects of refrigerated storage on hemostatic stability of four canine plasma products
2020
Edward, Thomas H. | Meledeo, Michael A. | Peltier, Grantham C. | Ruiz, Daikor D. | Henderson, Alice F. | Travieso, Stephanie | Pusateri, Anthony E.
OBJECTIVE To assess clotting times, coagulation factor activities, sterility, and thromboelastographic parameters of liquid plasma (LP), thawed fresh frozen plasma (FFP-T), and 2 novel formulations of freeze-dried plasma (FDP) stored refrigerated over 35 days. SAMPLE 6 units of canine LP and FFP-T from a commercial animal blood bank and 5 units each of 2 formulations of canine FDP. PROCEDURES Prothrombin time; activated partial thromboplastin time; activities of coagulation factors II, V, VII, VIII, IX, X, XI, and XII; and thromboelastographic parameters were determined for each product on days 0 (baseline), 3, 7, 14, 21, 28, and 35. For each day, a sample of each product was also submitted for aerobic bacterial culture. RESULTS Small changes in coagulation factor activities and mild increased time to initial clot formation in LP and FFP-T were noted over the 35-day storage period. Activities of factor VIII in FDP1 and factor XII in FDP2 were < 50% at baseline but varied throughout. Compared with FFP-T, time to initial clot formation was increased and clot strength was preserved or increased for the FDPs throughout the study. One FDP had decreased pH, compared with other products. No plasma product yielded bacterial growth. CONCLUSIONS AND CLINICAL RELEVANCE Liquid plasma and FFP-T would be reasonable to use when stored refrigerated for up to 35 days. Both FDP products showed variability in coagulation factor activities. Studies investigating the usefulness of these plasma products (FDPs) in dogs and the variable days of refrigerated storage (all products) are warranted.
显示更多 [+] 显示较少 [-]Effects of kernel and window setting combinations on assessments of small and complicated vasculature in computed tomography angiographic images of dogs with and without tumors
2020
Yoon, Sooa A. | Park, Seungjo J. | Choi, Jihye H.
OBJECTIVE To evaluate the effect of kernel and window settings on the assessment of small and complicated vasculature in CT angiographic (CTA) images of kidneys, jejunum with mesentery, and tumors in dogs. ANIMALS 20 healthy dogs and 20 dogs with tumors. PROCEDURES Images from CTA performed previously in dogs were reconstructed with 3 different combinations of kernel and window settings (soft kernel with soft tissue window, soft kernel with bone window, and sharp kernel with bone window), and reconstructed images of the left kidney and the jejunum with the mesentery in healthy dogs and tumors in affected dogs were evaluated by reviewers blinded to the settings. RESULTS For images of kidney and jejunum with mesentery, reviewers’ scores for the conspicuity of vascularity in the arterial phase and the differentiation of the organs from the adjacent structures were significantly higher when viewed in bone window (vs soft tissue window) regardless of kernel setting. For images of head and gastrointestinal tumors, reviewers’ scores for differentiation of intratumoral vasculature were higher when viewed in sharp kernel with bone window versus other setting combinations. However, the conspicuity of gastrointestinal, hepatic, or splenic tumoral vessels from the adjacent structures had higher reviewer scores for images in soft kernel with soft tissue window, compared with other setting combinations. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that reconstruction of CTA images with sharp kernel combined with bone window settings might have clinical utility in evaluating and planning treatments for dogs with various tumors; however, additional research is warranted to further identify effects of various kernel and window setting combinations on assessments of small and complicated vasculature in larger and more diverse populations of dogs with and without tumors.
显示更多 [+] 显示较少 [-]Respiratory and hemodynamic effects of 2 protocols of low-dose infusion of dexmedetomidine in dogs under isoflurane anesthesia
2020
Di Bella, Caterina | Skouopoulou, Despoina | Staffieri, Francesco | Muresan, Cosmin | Grasso, Salvatore | Lacitignola, Luca
The aim of this study was to evaluate the respiratory and hemodynamic effects of a low-dose dexmedetomidine infusion [1mg/kg body weight (BW) per hour], with or without a loading dose (1 mg/kg BW), in dogs under isoflurane anesthesia. Thirty dogs were premedicated with methadone [0.3 mg/kg BW intramuscular (IM)], induced with propofol intravenous (IV) and maintained with isoflurane (1.3% to 1.4%) under mechanical ventilation. Animals were randomly assigned to 3 intravenous (IV) treatments (n = 10): 1 mg/kg BW dexmedetomidine, followed by 1 mg/kg BW per hour (group BI); or saline solution bolus, followed by either an infusion of 1 mg/kg BW per hour dexmedetomidine (group I) or saline solution (group C). The infusions were interrupted after 30 minutes. Respiratory system static compliance (Cstat) and respiratory system resistance (Rrs), partial pressure of oxygen/fractional inspired oxygen ratio (PaO(2)/FIO(2)), intrapulmonary shunt (Fshunt), and cardiac output (CO) were determined 5 minutes before the bolus (BASELINE), at the end of the bolus (BOLUS), and at 15 (T15), 30 (T3(0)), and 45 minutes (T45) intervals. In group BI, Cstat and PaO(2)/FiO(2) were higher at T15 and T3(0) than at BASELINE in the same group and than group C at the same times. In group I, the same parameters at T30 were higher than at BASELINE and than group C at the same time. In group BI, Rrs and Fshunt were lower than at BASELINE and than group C at the same time. In group I, the same parameters at T30 were lower than at BASELINE and those of group C at the same time. Cardiac output (CO) at T30 was higher in groups BI and I than in group C. The results of this study showed that low-dose dexmedetomidine infusion improves oxygenation and respiratory system mechanics and has a stabilizing hemodynamic effect in dogs anesthetized with isoflurane and mechanically ventilated.
显示更多 [+] 显示较少 [-]Effect of slice thickness on computed tomographic perfusion analysis of the pancreas in healthy dogs
2020
Park, Seungjo | Jung, Jin-Woo | Je, Hyejin | Jang, Youjung | Choi, Jihye
OBJECTIVE To evaluate the effect of slice thickness on CT perfusion analysis of the pancreas in healthy dogs. ANIMALS 12 healthy Beagles. PROCEDURES After precontrast CT scans, CT perfusion scans of the pancreatic body were performed every second for 30 seconds by sequential CT scanning after injection of contrast medium (iohexol; 300 mg of 1/kg) at a rate of 3 mL/s. Each dog underwent CT perfusion scans twice in a crossover-design study with 2 different slice thicknesses (2.4 and 4.8 mm). Computed tomographic pancreatic perfusion variables, including blood flow, blood volume determined with the maximum slope model, times to the start of enhancement and peak enhancement, permeability, and blood volume determined by Patlak plot analysis, were measured independently by 2 reviewers. The CT perfusion variables were compared between slice thicknesses. Interoperator reproducibility was determined by ICC calculation. RESULTS Interoperator reproducibility of CT perfusion variable measurements was excellent on 2.4-mm (mean ± SD ICC, 0.81 ± 0.17) and 4.8-mm (0.90 ± 0.07) slice thicknesses, except for time to peak pancreatic enhancement on 2.4-mm-thick slices, which had moderate reproducibility (intraclass correlation coefficient, 0.473). There was no significant difference in measurements of blood flow, blood volume by either method, times to the start and peak of pancreatic enhancement, or permeability between slice thicknesses. CONCLUSIONS AND CLINICAL RELEVANCE Results supported that a thin slice thickness of 2.4 mm can be used for assessment of pancreatic perfusion variables in healthy dogs.
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