Publications by authors named "Stephen A Felt"

38 Publications

Biodegradable fluorescent nanoparticles for endoscopic detection of colorectal carcinogenesis.

Adv Funct Mater 2019 Dec 10;29(51). Epub 2019 Oct 10.

Molecular Imaging Program at Stanford University (MIPS), Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Early and comprehensive endoscopic detection of colonic dysplasia - the most clinically significant precursor lesion to colorectal adenocarcinoma - provides an opportunity for timely, minimally-invasive intervention to prevent malignant transformation. Here, the development and evaluation of biodegradable near-infrared fluorescent silica nanoparticles (FSN) is described that have the potential to improve adenoma detection during fluorescence-assisted white-light colonoscopic surveillance in rodent and human-scale models of colorectal carcinogenesis. FSNs are biodegradable (t of 2.7 weeks), well-tolerated, and enable detection and delineation of adenomas as small as 0.5 mm with high tumor-to-background ratios. Furthermore, in the human-scale, porcine model, the clinical feasibility and benefit of using FSN-guided detection of colorectal adenomas using video-rate fluorescence-assisted white-light endoscopy is demonstrated. Since nanoparticles of similar size (., 100-150-nm) or composition (., silica, silica/gold hybrid) have already been successfully translated to the clinic, and, clinical fluorescent/white light endoscopy systems are becoming more readily available, there is a viable path towards clinical translation of the proposed strategy for early colorectal cancer detection and prevention in high-risk patients.
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http://dx.doi.org/10.1002/adfm.201904992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546531PMC
December 2019

The epidemiology of fighting in group-housed laboratory mice.

Sci Rep 2020 10 6;10(1):16649. Epub 2020 Oct 6.

Department of Comparative Medicine, Stanford University, 300 Pasteur Drive, Stanford, CA, 94305-5342, USA.

Injurious home-cage aggression (fighting) in mice affects both animal welfare and scientific validity. It is arguably the most common potentially preventable morbidity in mouse facilities. Existing literature on mouse aggression almost exclusively examines territorial aggression induced by introducing a stimulus mouse into the home-cage of a singly housed mouse (i.e. the resident/intruder test). However, fighting occurring in mice living together in long-term groups under standard laboratory housing conditions has barely been studied. We performed a point-prevalence epidemiological survey of fighting at a research institution with an approximate 60,000 cage census. A subset of cages was sampled over the course of a year and factors potentially influencing home-cage fighting were recorded. Fighting was almost exclusively seen in group-housed male mice. Approximately 14% of group-housed male cages were observed with fighting animals in brief behavioral observations, but only 14% of those cages with fighting had skin injuries observable from cage-side. Thus simple cage-side checks may be missing the majority of fighting mice. Housing system (the combination of cage ventilation and bedding type), genetic background, time of year, cage location on the rack, and rack orientation in the room were significant risk factors predicting fighting. Of these predictors, only bedding type is easily manipulated to mitigate fighting. Cage ventilation and rack orientation often cannot be changed in modern vivaria, as they are baked in by cookie-cutter architectural approaches to facility design. This study emphasizes the need to invest in assessing the welfare costs of new housing and husbandry systems before implementing them.
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http://dx.doi.org/10.1038/s41598-020-73620-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538892PMC
October 2020

The Stability and Efficacy of Tricaine Methanesulfonate (MS222) Solution After Long-Term Storage.

J Am Assoc Lab Anim Sci 2020 Jun 12. Epub 2020 Jun 12.

Tricaine methanesulfonate (MS222) is widely used for the anesthesia and euthanasia of laboratory zebrafish. Fresh solutions have been recommended for each use; however, researchers often mix and store concentrated stock solutions for convenience and to reduce occupational exposure and environmental waste. While this is common practice, published guidelines are often inconsistent. Thus, the objective of this study was to evaluate the stability and anesthetic efficacy of MS222 after long-term storage and to develop specific storage parameters. Stock solutions (100 mg/mL MS222) were mixed and stored in amber jars at 4 °C and -20 °C for 2- and 6-mo. Stability of the solutions was analyzed using liquid chromatography-ion trapmass spectrometry and compared with fresh MS222. Fifty adult (30 male, 20 female) wildtype AB zebrafish (Danio rerio) wererandomly anesthetized with 150 mg/L of one of the following MS222 solutions to evaluate anesthetic efficacy: 1) freshly prepared(0m); 2) 2 mo at 4 °C (2m4); 3) 2 mo at -20 °C (2m-20); 4) 6 mo at 4 °C (6m4); 5) 6 mo at -20 °C (6m-20). Time to cessation of swimming, loss of equilibrium, lack of response to von Frey (VF) stimulation, return of equilibrium, and resumption of swimming were compared between groups. Two fish from each group were euthanized at 24-h and 2-wk after anesthesia, and histopathology was performed. All solutions were determined to be stable under all storage conditions. No clinically significant differences were observed between the fresh and stored stock groups during anesthetic testing. No evidence ofanesthetic-related histologic changes were noted in the gills, skin, kidneys, muscle, and central nervous system. Hepatic megalocytosis and a reduction in hepatic vacuolation were seen to varying degrees across all groups, but did not follow a treatment-related trend. Therefore, 100 mg/mL solutions of MS222 can be stored in amber jars at 4 °C or -20 °C for 6 mo and still used to effectively anesthetize zebrafish.
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http://dx.doi.org/10.30802/AALAS-JAALAS-19-000067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338872PMC
June 2020

Influence of Pain and Analgesia on Orthopedic and Wound-healing Models in Rats and Mice.

Comp Med 2019 12 27;69(6):535-545. Epub 2019 Sep 27.

Department of Comparative Medicine, Stanford University, Stanford, California.

The surgical stress response and resulting physiologic changes can lead to postoperative complications and negatively impact animal welfare. Although appropriate pain management is crucial to reduce the pain and stress response to surgery, analgesic choice can significantly affect bone and wound healing. This review aims to summarize data from rat and mouse studies and to provide recommendations for integrating analgesia into orthopedic and wound healing models in these species. Data from other species, such as humans, rabbits and other rodents, is included, where available. From these data, we conclude that for orthopedic surgical models, opioids, local anesthetics and dissociative agents have minimal impact on fracture healing; cyclooxygenase 2 (COX2) selective nonsteroidal antiinflammatory drugs (NSAID) may be used in the shortterm; and steroids should be avoided. For wound healing models, short-term systemic or topical opioids have negligible impact on wound healing; NSAID or local anesthetics may be used short-term; and systemic steroids should be avoided. Alternative analgesics such as tramadol, gabapentin, ketamine, and acetaminophen warrant consideration and further evaluation for both orthopedic and wound healing models. In all cases, researchers and veterinarians should work together to determine the appropriate analgesic plan to minimize pain, as well as to minimize unwanted effects on the orthopedic and wound healing models themselves.
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http://dx.doi.org/10.30802/AALAS-CM-19-000013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935707PMC
December 2019

High prevalence of taeniasis and Taenia solium cysticercosis in children in western Sichuan, China.

Acta Trop 2019 Nov 12;199:105133. Epub 2019 Aug 12.

Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.

Data in China on human Taenia infections, including Taenia solium cysticercosis, is largely lacking. We aimed to determine the prevalence of taeniasis with all three human Taenia species as well as T. solium cysticercosis in primary school-aged children in minority areas of western Sichuan, China. During April 2016 to December 2017, we did a cross-sectional study in five western Sichuan Province primary schools in Liangshan (3 schools), Ganzi (1 school) and Aba (1 school) prefectures. Diagnosis of taeniasis was made by stool microscopy for presence of Taenia eggs, as well as recovery of taeniid tapeworms or proglottids by medicinal treatment followed by species identification using multiplex PCR. Diagnosis of T. solium cysticercosis was made serologically using an ELISA with low-molecular-weight antigens purified from T. solium cyst fluid to detect specific IgG antibodies. A total of 1672 children were screened for taeniasis and 1639 were evaluated for cysticercosis antibodies. Overall prevalence of taeniasis was 7.5% but was as high as 15.6% at one school site (e.g., Shuiluo). Of the three known human Taenia species, adult T. solium tapeworms were detected in 42 children from four of the five schools (all three schools in Liangshan and one in Aba), giving a prevalence of T. solium taeniasis of 2.5% (95% confidence interval 0-6.7%). Cysticercosis antibody seropositivity by school varied from 2.3% to 15.6% (overall 7.5%). T. solium taeniasis carriers were more likely to have cysticercosis antibodies than children without T. solium taeniasis (43.6% vs 6.6%). Schools with higher prevalences of T. solium taeniasis were more likely to have children with human cysticercosis IgG antibodies. This study shows a high prevalence of taeniasis and T. solium cysticercosis in primary school-aged children in minority areas of western Sichuan, suggesting an urgent necessity for school-based disease control.
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http://dx.doi.org/10.1016/j.actatropica.2019.105133DOI Listing
November 2019

Ultrasound/microbubble-mediated targeted delivery of anticancer microRNA-loaded nanoparticles to deep tissues in pigs.

J Control Release 2019 09 18;309:1-10. Epub 2019 Jul 18.

Department of Radiology, School of Medicine, Stanford University, Stanford, California, United States of America.

In this study, we designed and validated a platform for ultrasound and microbubble-mediated delivery of FDA-approved pegylated poly lactic-co-glycolic acid (PLGA) nanoparticles loaded with anticancer microRNAs (miRNAs) to deep tissues in a pig model. Small RNAs have been shown to reprogram tumor cells and sensitize them to clinically used chemotherapy. To overcome their short intravascular circulation half-life and achieve controlled and sustained release into tumor cells, anticancer miRNAs need to be encapsulated into nanocarriers. Focused ultrasound combined with gas-filled microbubbles provides a noninvasive way to improve the permeability of tumor vasculature and increase the delivery efficiency of drug-loaded particles. A single handheld, curvilinear ultrasound array was used in this study for image-guided therapy with clinical-grade SonoVue contrast agent. First, we validated the platform on phantoms to optimize the microbubble cavitation dose based on acoustic parameters, including peak negative pressure, pulse length, and pulse repetition frequency. We then tested the system in vivo by delivering PLGA nanoparticles co-loaded with antisense-miRNA-21 and antisense-miRNA-10b to pig liver and kidney. Enhanced miRNA delivery was observed (1.9- to 3.7-fold increase) as a result of the ultrasound treatment compared to untreated control regions. Additionally, we used highly fluorescent semiconducting polymer nanoparticles to visually assess nanoparticle extravasation. Fluorescent microscopy suggested the presence of nanoparticles in the extravascular compartment. Hematoxylin and eosin staining of treated tissues did not reveal tissue damage. The results presented in this manuscript suggest that the proposed platform may be used to safely and noninvasively enhance the delivery of miRNA-loaded nanoparticles to target regions in deep organs in large animal models.
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http://dx.doi.org/10.1016/j.jconrel.2019.07.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815710PMC
September 2019

Structural Equation Modeling (SEM) of Cysticercosis in School-Aged Children in Tibetan Rural Farming Areas of Western China: Implications for Intervention Planning.

Int J Environ Res Public Health 2019 03 4;16(5). Epub 2019 Mar 4.

Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA.

Neurocysticercosis (NCC) significantly contributes to morbidity in developing countries. We recently published a study of prevalence and risk factors in school-aged children in three mountainous areas in Sichuan province of western China. Using structural equation modeling (SEM) on data from that study to guide intervention planning, here we examine risk factors grouped into three broad interventional categories: sociodemographics, human behavior, and sources of pork and pig husbandry. Because neuroimaging is not easily available, using SEM allows for the use of multiple observed variables (serological tests and symptoms) to represent probable NCC cases. Data collected from 2608 students was included in this analysis. Within this group, seroprevalence of cysticercosis IgG antibodies was 5.4%. SEM results showed that sociodemographic factors ( = 0.33, < 0.05), sources of pork and pig husbandry ( = 0.26, < 0.001), and behavioral factors ( = 0.33, < 0.05) were all directly related to probable NCC in school-aged children. Sociodemographic factors affected probable NCC indirectly via sources of pork and pig husbandry factors ( = 0.07, < 0.001) and behavioral variables ( = 0.07, < 0.001). Both sociodemographic factors ( = 0.07, < 0.05) and sources of pork and pig husbandry factors ( = 0.10, < 0.01) affected probable NCC indirectly via behavioral variables. Because behavioral variables not only had a large direct effect but also served as a critical bridge to strengthen the effect of sociodemographics and sources of pork and pig husbandry on probable NCC, our findings suggest that interventions targeting behavioral factors may be the most effective in reducing disease.
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http://dx.doi.org/10.3390/ijerph16050780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427563PMC
March 2019

Multimodality Hyperpolarized C-13 MRS/PET/Multiparametric MR Imaging for Detection and Image-Guided Biopsy of Prostate Cancer: First Experience in a Canine Prostate Cancer Model.

Mol Imaging Biol 2019 10;21(5):861-870

Department of Radiology, Stanford University, Stanford, CA, USA.

Purpose: To assess whether simultaneous hyperpolarized C-13 magnetic resonance spectroscopy (MRS)/positron emission tomography (PET)/multiparametric magnetic resonance (mpMR) imaging is feasible in an orthotopic canine prostate cancer (PCa) model using a clinical PET/MR system and whether the combined imaging datasets can be fused with transrectal ultrasound (TRUS) in real time for multimodal image fusion-guided targeted biopsy of PCa.

Procedures: Institutional Animal Care and Use Committee approval was obtained for this study. Canine prostate adenocarcinoma (Ace-1) cells were orthotopically injected into the prostate of four dogs. Once tumor engraftment was confirmed by TRUS, simultaneous hyperpolarized C-13 MRS of [1-C]pyruvate, PET (2-deoxy-2-[F]fluoro-D-glucose ([F]FDG), [Ga]NODAGA-SCH1), and mpMR (T2W, DWI) imaging was performed using a clinical PET/MR system. Multimodality imaging data sets were then fused with TRUS and image-guided targeted biopsy was performed. Imaging results were then correlated with histological findings.

Results: Successful tumor engraftment was histologically confirmed in three of the four dogs (dogs 2, 3, and 4) and simultaneous C-13 MRS/PET/mpMR was feasible in all three. In dog 2, C-13 MRS showed increased lactate signal in the tumor (lactate/totalC = 0.47) whereas mpMR did not show any signal changes. In dog 3, [F]FDG-PET (SUV = 1.90) and C-13 MRS (lactate/totalC = 0.59) showed elevated metabolic activity in the tumor. In dog 4, [F]FDG (SUV = 2.43), [Ga]NODAGA-SCH1 (SUV = 0.75), and C-13 MRS (Lac/totalC = 0.53) showed elevated uptake in tumor compared to control tissue and multimodal image fusion-guided biopsy of the tumor was successfully performed.

Conclusion: Simultaneous C-13 MRS/PET/mpMR imaging and multimodal image fusion-guided biopsy is feasible in a canine PCa model.
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http://dx.doi.org/10.1007/s11307-018-1235-6DOI Listing
October 2019

A Bird's-Eye View of Regulatory, Animal Care, and Training Considerations Regarding Avian Flight Research.

Comp Med 2019 05 14;69(3):169-178. Epub 2019 Feb 14.

Comparative Medicine.

A thorough understanding of how animals fly is a central goal of many scientific disciplines. Birds are a commonly used model organism for flight research. The success of this model requires studying healthy and naturally flying birds in a laboratory setting. This use of a nontraditional laboratory animal species presents unique challenges to animal care staff and researchers alike. Here we review regulatory, animal care, and training considerations associated with avian flight research.
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http://dx.doi.org/10.30802/AALAS-CM-18-000033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591680PMC
May 2019

Safety Considerations When Working with Humanized Animals.

ILAR J 2018 12;59(2):150-160

Unit for Laboratory Animal Medicine, University of Michigan Medical School in Ann Arbor, Michigan.

Research using laboratory animals has been revolutionized by the creation of humanized animal models, which are immunodeficient animals engrafted with human cells, tissues, or organs. These animal models provide the research community a unique and promising opportunity to mimic a wide variety of disease conditions in humans, from infectious disease to cancer. A vast majority of these models are humanized mice like those injected with human CD34+ hematopoietic stem cells and patient-derived xenografts. With this technology comes the need for the animal research enterprise to understand the inherent and potential risks, such as exposure to bloodborne pathogens, associated with the model development and research applications. Here, we review existing humanized animal models and provide recommendations for their safe use based on regulatory framework and literature. A risk assessment program-from handling the human material to its administration to animals and animal housing-is a necessary initial step in mitigating risks associated with the use of humanized animals in research. Ultimately, establishing institutional policies and guidelines to ensure personnel safety is a legal and ethical responsibility of the research institution as part of the occupational health and safety program and overall animal care and use program.
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http://dx.doi.org/10.1093/ilar/ily012DOI Listing
December 2018

US Molecular Imaging of Acute Ileitis: Anti-Inflammatory Treatment Response Monitored with Targeted Microbubbles in a Preclinical Model.

Radiology 2018 10 24;289(1):90-100. Epub 2018 Jul 24.

From the Department of Radiology, Stanford University School of Medicine, 300 Pasteur Dr, Grant SO62B, Stanford, CA 94305-5105 (H.W., A.M.L., J.K.W.); Bracco Suisse SA, Geneva, Switzerland (J.M.H., S.C., T.B.); Departments of Comparative Medicine (S.A.F., J.G.V.) and Health, Research & Policy (L.T.), Stanford University, Stanford, Calif; and Ultrasound Business Unit, Siemens Healthcare, Mountain View, Calif (I.G.).

Purpose To evaluate whether dual-selectin-targeted US molecular imaging allows longitudinal monitoring of anti-inflammatory treatment effects in an acute terminal ileitis model in swine. Materials and Methods The Institutional Animal Care and Use Committee approved all animal studies. Fourteen swine with chemically induced acute terminal ileitis (day 0) were randomized into the following groups: (a) an anti-inflammatory treatment group (n = 8; meloxicam, 0.25 mg per kilogram of body weight; prednisone, 0.5 mg/kg) and (b) a control group (n = 6; saline). US molecular imaging was performed with a clinical US machine after intravenous injection of clinically translatable dual P- and E-selectin-targeted microbubbles (5 × 10/kg). Three inflamed bowel segments per swine were imaged at baseline, as well as on days 1, 3, and 6 after treatment initiation. At day 6, bowel segments were analyzed ex vivo for selectin expression levels by using quantitative immunofluorescence. Results After induction of inflammation, US molecular imaging signal increased at day 1 in both animal groups (P < .001). At day 3, signal in the treatment group decreased (P < .001 vs day 1), while signal in control animals did not significantly change (P = .18 vs day 1) and was higher (P = .001) compared with that in the treatment group. At day 6, signal in the treatment group further decreased and remained lower (P = .02) compared with that in the control group. Immunofluorescence confirmed significant (P ≤ .04) downregulation of both P- and E-selectin expression levels in treated versus control bowel segments. Conclusion Dual-selectin-targeted US molecular imaging allows longitudinal monitoring of anti-inflammatory treatment effects in a large-animal model of acute ileitis. This supports further clinical development of this quantitative and radiation-free technique for monitoring inflammatory bowel disease. © RSNA, 2018 Online supplemental material is available for this article.
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http://dx.doi.org/10.1148/radiol.2018172600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6190483PMC
October 2018

Prevalence and risk factors for Taenia solium cysticercosis in school-aged children: A school based study in western Sichuan, People's Republic of China.

PLoS Negl Trop Dis 2018 05 8;12(5):e0006465. Epub 2018 May 8.

Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA, United States of America.

Background: Taenia solium cysticercosis affects millions of impoverished people worldwide and can cause neurocysticercosis, an infection of the central nervous system which is potentially fatal. Children may represent an especially vulnerable population to neurocysticercosis, due to the risk of cognitive impairment during formative school years. While previous epidemiologic studies have suggested high prevalence in rural China, the prevalence in children as well as risk factors and impact of disease in low-resource areas remain poorly characterized.

Methodology/principal Findings: Utilizing school based sampling, we conducted a cross-sectional study, administering a questionnaire and collecting blood for T. solium cysticercosis antibodies in 2867 fifth and sixth grade students across 27 schools in west Sichuan. We used mixed-effects logistic regression models controlling for school-level clustering to study associations between risk factors and to characterize factors influencing the administration of deworming medication. Overall prevalence of cysticercosis antibodies was 6%, but prevalence was significantly higher in three schools which all had prevalences of 15% or higher. Students from households owning pigs (adjusted odds ratio [OR] 1.81, 95% CI 1.08-3.03), from households reporting feeding their pigs human feces (adjusted OR 1.49, 95% CI 1.03-2.16), and self-reporting worms in their feces (adjusted OR 1.85, 95% CI 1.18-2.91) were more likely to have cysticercosis IgG antibodies. Students attending high prevalence schools were more likely to come from households allowing pigs to freely forage for food (OR 2.26, 95% CI 1.72-2.98) and lacking a toilet (OR 1.84, 95% CI 1.38-2.46). Children who were boarding at school were less likely to have received treatment for gastrointestinal worms (adjusted OR 0.58, 95% CI 0.42-0.80).

Conclusions/significance: Our study indicates high prevalences of cysticercosis antibodies in young school aged children in rural China. While further studies to assess potential for school-based transmission are needed, school-based disease control may be an important intervention to ensure the health of vulnerable pediatric populations in T. solium endemic areas.
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http://dx.doi.org/10.1371/journal.pntd.0006465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959190PMC
May 2018

A mm-Sized Wireless Implantable Device for Electrical Stimulation of Peripheral Nerves.

IEEE Trans Biomed Circuits Syst 2018 04;12(2):257-270

A wireless electrical stimulation implant for peripheral nerves, achieving >10× improvement over state of the art in the depth/volume figure of merit, is presented. The fully integrated implant measures just 2 mm × 3 mm × 6.5 mm (39 mm, 78 mg), and operates at a large depth of 10.5 cm in a tissue phantom. The implant is powered using ultrasound and includes a miniaturized piezoelectric receiver (piezo), an IC designed in 180 nm HV BCD process, an off-chip energy storage capacitor, and platinum stimulation electrodes. The package also includes an optional blue light-emitting diode for potential applications in optogenetic stimulation in the future. A system-level design strategy for complete operation of the implant during the charging transient of the storage capacitor, as well as a unique downlink command/data transfer protocol, is presented. The implant enables externally programmable current-controlled stimulation of peripheral nerves, with a wide range of stimulation parameters, both for electrical (22 to 5000 μA amplitude, ∼14 to 470 μs pulse-width, 0 to 60 Hz repetition rate) and optical (up to 23 mW/mm optical intensity) stimulation. Additionally, the implant achieves 15 V compliance voltage for chronic applications. Full integration of the implant components, end-to-end in vitro system characterizations, and results for the electrical stimulation of a sciatic nerve, demonstrate the feasibility and efficacy of the proposed stimulator for peripheral nerves.
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http://dx.doi.org/10.1109/TBCAS.2018.2799623DOI Listing
April 2018

Anatomical Road Mapping Using CT and MR Enterography for Ultrasound Molecular Imaging of Small Bowel Inflammation in Swine.

Eur Radiol 2018 May 23;28(5):2068-2076. Epub 2017 Nov 23.

Department of Radiology, Stanford University, School of Medicine, 300 Pasteur Drive, Room H1307, Stanford, CA, 94305-5621, USA.

Objectives: To evaluate the feasibility and time saving of fusing CT and MR enterography with ultrasound for ultrasound molecular imaging (USMI) of inflammation in an acute small bowel inflammation of swine.

Methods: Nine swine with ileitis were scanned with either CT (n = 3) or MR (n = 6) enterography. Imaging times to load CT/MR images onto a clinical ultrasound machine, fuse them to ultrasound with an anatomical landmark-based approach, and identify ileitis were compared to the imaging times without anatomical road mapping. Inflammation was then assessed by USMI using dual selectin-targeted (MB) and control (MB) contrast agents in diseased and healthy control bowel segments, followed by ex vivo histology.

Results: Cross-sectional image fusion with ultrasound was feasible with an alignment error of 13.9 ± 9.7 mm. Anatomical road mapping significantly reduced (P < 0.001) scanning times by 40%. Localising ileitis was achieved within 1.0 min. Subsequently performed USMI demonstrated significantly (P < 0.001) higher imaging signal using MB compared to MB and histology confirmed a significantly higher inflammation score (P = 0.006) and P- and E-selectin expression (P ≤ 0.02) in inflamed vs. healthy bowel.

Conclusions: Fusion of CT and MR enterography data sets with ultrasound in real time is feasible and allows rapid anatomical localisation of ileitis for subsequent quantification of inflammation using USMI.

Key Points: • Real-time fusion of CT/MRI with ultrasound to localise ileitis is feasible. • Anatomical road mapping using CT/MRI significantly decreases the scanning time for USMI. • USMI allows quantification of inflammation in swine, verified with ex vivo histology.
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http://dx.doi.org/10.1007/s00330-017-5148-6DOI Listing
May 2018

Use of Liposomal Bupivacaine for Postoperative Analgesia in an Incisional Pain Model in Rats ().

J Am Assoc Lab Anim Sci 2017 Jan;56(1):63-68

Department of Comparative Medicine, Stanford University, Stanford, California.

The local anesthetic bupivacaine is valuable for perioperative analgesia, but its use in the postoperative period is limited by its short duration of action. Here, we evaluated the application of a slow-release liposomal formulation of bupivacaine for postoperative analgesia. The aim was to assess whether liposomal bupivacaine effectively attenuates postoperative mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats (n = 36) were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC every 12 h for 2 d; buprenorphine HCl, 0.05 mg/kg SC every 12 h for 2 d (Bup HCl); 0.5% bupivacaine, 2 mg/kg SC local infiltration once (Bupi); liposomal bupivacaine, 1 mg/kg SC local infiltration once (Exp1); and liposomal bupivacaine, 6 mg/kg SC local infiltration once (Exp6). Mechanical and thermal hypersensitivity were evaluated daily on days -1, 0, 1, 2, 3, and 4. The saline group exhibited both hypersensitivities through all 4 evaluated postoperative days. Bup HCl attenuated mechanical hypersensitivity for 2 d and thermal hypersensitivity for 1 d. Bupi attenuated only thermal hypersensitivity for 4 d. Rats in the Exp1 group showed attenuation of both mechanical and thermal hypersensitivity for 4 d, and those in the Exp6 group had attenuation of mechanical hypersensitivity on day 0 and thermal hypersensitivity for 4 d. These data suggest that a single local infiltration of liposomal bupivacaine at a dose of 1 mg/kg SC effectively attenuates postoperative mechanical and thermal hypersensitivity for 4 d in a rat model of incisional pain.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5250497PMC
January 2017

Acute and Chronic Outcomes of Gas-Bubble Disease in a Colony of African Clawed Frogs ().

Comp Med 2017 02;67(1):4-10

Department of Comparative Medicine, Stanford University School of Medicine, Stanford, California;, Email:

Gas-bubble disease occurs in aquatic species that are exposed to water that is supersaturated with gases. In February 2007, municipal water supersaturated with gas was inadvertently pumped into the vivarium's aquatic housing systems and affected approximately 450 adult female Xenopus laevis. The inflow of supersaturated water was stopped immediately, the holding tanks aggressively aerated, and all experimental manipulations and feeding ceased. Within the first 6 h after the event, morbidity approached 90%, and mortality reached 3.5%. Acutely affected frogs showed clinical signs of gas-bubble disease: buoyancy problems, micro- and macroscopic bubbles in the foot webbing, hyperemia in foot webbing and leg skin, and loss of the mucous slime coat. All of the frogs that died or were euthanized had areas of mesenteric infarction, which resulted in intestinal epithelial necrosis and degeneration of the muscular tunic. Over the subsequent 2 wk, as gas saturation levels returned to normal, the clinical symptoms resolved completely in the remaining frogs. However, 3 mo later, 85% of them failed to lay eggs or produce oocytes, and the remaining 15% produced oocytes of low number and poor quality, yielding cytosolic extracts with poor to no enzymatic activity. Histology of the egg mass from a single 2- to 3-y-old frog at 3 mo after disease resolution revealed irregularly shaped oocytes, few large mature oocytes, and numerous small, degenerating oocytes. At 6 mo after the incident, the remaining frogs continued to fail to produce eggs of sufficient quantity or quality after hormonal priming. The researchers consequently opted to cull the remainder of the colony and repopulate with new frogs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310619PMC
February 2017

Postoperative Analgesia Due to Sustained-Release Buprenorphine, Sustained-Release Meloxicam, and Carprofen Gel in a Model of Incisional Pain in Rats (Rattus norvegicus).

J Am Assoc Lab Anim Sci 2016 ;55(3):300-5

Departments of Comparative Medicine, Stanford University, Stanford, California, USA.

Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day-1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity-but not thermal hypersensitivity-on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR-but not Melox-SR or CG-effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865691PMC
February 2017

A "Pedi" Cures All: Toenail Trimming and the Treatment of Ulcerative Dermatitis in Mice.

PLoS One 2016 6;11(1):e0144871. Epub 2016 Jan 6.

Department of Comparative Medicine, Stanford University, Stanford, California, United States of America.

Ulcerative Dermatitis (UD) is the most common cause of unplanned euthanasia in mice used in research, with prevalence rates reported between 4 and 21%. UD is characterized by a deep, ulcerative lesion that appears most commonly over the dorsal neck and is attendant with an intense pruritus. The underlying cause of UD is currently unknown, and as a consequence, there are no directed therapies that resolve lesions reliably. However, there is a growing body of evidence that suggests a behavioral component to the onset, maintenance, and progression of UD lesions. Scratching behavior in response to the intense pruritus associated with UD lesions may be an effective target for interventional therapies. We hypothesized that interfering with scratching behavior by trimming the toenails of mice with UD, would resolve UD lesions. To test this hypothesis, we first evaluated the efficacy of toenail trims with a single application of Vetericyn at the time of treatment versus our previous standard of care, topical Tresaderm applied daily. We found that toenail trims were significantly more effective at resolving lesions (n = 39 toenail trims, n = 100 Tresaderm, p<0.0001) with 93.3% of animals healing by 14 days (median time to lesion resolution). Furthermore, dorsal neck lesions did not recur by 42 days after a single toenail trim (n = 54); however, flank lesions did not resolve and the outcome of the two lesion distributions following treatment were significantly different (p<0.0001). Finally, we implemented toenail trims at an institutional level and found similar efficacies (approximately 90%) for toenail trims regardless of one-time topical supplement used (triple antibiotic ointment, Tresaderm, and Vetericyn, n = 55, 58, 18, p = 0.63). This is the first report of a highly effective treatment for one of the most serious welfare issues in laboratory mice.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144871PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703297PMC
July 2016

Quantitative Assessment of Inflammation in a Porcine Acute Terminal Ileitis Model: US with a Molecularly Targeted Contrast Agent.

Radiology 2015 Sep 12;276(3):809-17. Epub 2015 May 12.

From the Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, 300 Pasteur Dr, Room H1307; Stanford, CA 94305-5621 (H.W., S.M., A.M.L., J.K.W.); Department of Comparative Medicine (S.A.F., R.L.) and Department of Health, Research and Policy (L.T.), Stanford University, Stanford, Calif; Ultrasound Business Unit, Siemens Healthcare, Mountain View, Calif (I.G.); and Bracco Suisse, Geneva, Switzerland (T.B.).

Purpose: To evaluate the feasibility and reproducibility of ultrasonography (US) performed with dual-selectin-targeted contrast agent microbubbles (MBs) for assessment of inflammation in a porcine acute terminal ileitis model, with histologic findings as a reference standard.

Materials And Methods: The study had institutional Animal Care and Use Committee approval. Acute terminal ileitis was established in 19 pigs; four pigs served as control pigs. The ileum was imaged with clinical-grade dual P- and E-selectin-targeted MBs (MBSelectin) at increasing doses (0.5, 1.0, 2.5, 5.0, 10, and 20 × 10(8) MB per kilogram of body weight) and with control nontargeted MBs (MBControl). For reproducibility testing, examinations were repeated twice after the MBSelectin and MBControl injections. After imaging, scanned ileal segments were analyzed ex vivo both for inflammation grade (by using hematoxylin-eosin staining) and for expression of selectins (by using quantitative immunofluorescence analysis). Statistical analysis was performed by using the t test, intraclass correlation coefficients (ICCs), and Spearman correlation analysis.

Results: Imaging signal increased linearly (P < .001) between a dose of 0.5 and a dose of 5.0 × 10(8) MB/kg and plateaued between a dose of 10 and a dose of 20 × 10(8) MB/kg. Imaging signals were reproducible (ICC = 0.70), and administration of MBSelectin in acute ileitis resulted in a significantly higher (P < .001) imaging signal compared with that in control ileum and MBControl. Ex vivo histologic grades of inflammation correlated well with in vivo US signal (ρ = 0.79), and expression levels of both P-selectin (37.4% ± 14.7 [standard deviation] of vessels positive; P < .001) and E-selectin (31.2% ± 25.7) in vessels in the bowel wall of segments with ileitis were higher than in control ileum (5.1% ± 3.7 for P-selectin and 4.8% ± 2.3 for E-selectin).

Conclusion: Quantitative measurements of inflammation obtained by using dual-selectin-targeted US are reproducible and correlate well with the extent of inflammation at histologic examination in a porcine acute ileitis model as a next step toward clinical translation.
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http://dx.doi.org/10.1148/radiol.2015142478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557395PMC
September 2015

A real-time clinical endoscopic system for intraluminal, multiplexed imaging of surface-enhanced Raman scattering nanoparticles.

PLoS One 2015 29;10(4):e0123185. Epub 2015 Apr 29.

Department of Radiology, Stanford University, Stanford, California, United States of America; Department of Pediatrics, Stanford University, Stanford, California, United States of America; Department of Microbiology & Immunology, Stanford University, Stanford, California, United States of America; Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California, United States of America.

The detection of biomarker-targeting surface-enhanced Raman scattering (SERS) nanoparticles (NPs) in the human gastrointestinal tract has the potential to improve early cancer detection; however, a clinically relevant device with rapid Raman-imaging capability has not been described. Here we report the design and in vivo demonstration of a miniature, non-contact, opto-electro-mechanical Raman device as an accessory to clinical endoscopes that can provide multiplexed molecular data via a panel of SERS NPs. This device enables rapid circumferential scanning of topologically complex luminal surfaces of hollow organs (e.g., colon and esophagus) and produces quantitative images of the relative concentrations of SERS NPs that are present. Human and swine studies have demonstrated the speed and simplicity of this technique. This approach also offers unparalleled multiplexing capabilities by simultaneously detecting the unique spectral fingerprints of multiple SERS NPs. Therefore, this new screening strategy has the potential to improve diagnosis and to guide therapy by enabling sensitive quantitative molecular detection of small and otherwise hard-to-detect lesions in the context of white-light endoscopy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123185PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414592PMC
February 2016

Antinociceptive effects of sustained-release buprenorphine in a model of incisional pain in rats (Rattus norvegicus).

J Am Assoc Lab Anim Sci 2014 Mar;53(2):193-7

Department of Comparative Medicine, Stanford University, Stanford, California, USA.

Effective management of postoperative pain is an essential component of the care and welfare of laboratory animals. A sustained-release formulation of buprenorphine (Bup-SR) has recently been introduced to the veterinary market and has been reported to provide analgesia for as long as 72 h. Using evoked mechanical and thermal hypersensitivity tests, we here evaluated the antinociceptive effects of Bup-SR in a model of incisional pain in rats. Paw withdrawal responses were obtained before and 1 through 4 d after surgery. Rats are assigned to receive Bup-SR (0.3, 1.2, or 4.5 mg/kg SC once) or buprenorphine HCl (Bup HCl, 0.05 mg/kg SC twice daily for 3 d). Responses to mechanical and thermal stimuli in the 1.2 and 4.5 Bup-SR groups did not differ from those of rats in the Bup HCl group. Thermal latency on day 3 in rats that received 0.3 mg/kg Bup-SR was significantly different from baseline, indicating that this dose effectively decreased thermal hypersensitivity for at least 48 h. Marked sedation occurred in rats in the 4.5 Bup-SR group. Our findings indicate that Bup-SR at 0.3 or 1.2 mg/kg SC is effective in minimizing hypersensitivity with minimal sedation for at least 48 h (thermal hypersensitivity) and 72 h, respectively, in the incisional pain model in rats.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3966277PMC
March 2014

Effect of intratonsillar injection of steroids on the palatine tonsils of rabbits.

Laryngoscope 2014 Dec 27;124(12):2811-7. Epub 2014 Sep 27.

Department of Otolaryngology-Head and Neck Surgery, Stanford University, School of Medicine, Stanford, California.

Objectives/hypothesis: Nasal steroids may significantly improve nasal obstructive symptoms with a reduction of adenoid size in children, but they do not consistently yield the same concurrent effect on enlarged palatine tonsils. Failure of nasal steroids to decrease the size of palatine tonsils is believed to be attributable to location and washout by saliva. The purpose of this study was to determine if direct application of steroid via intratonsillar injection would reduce the size of palatine tonsils in the rabbit model.

Study Design: Prospective animal study.

Methods: Eight rabbits (16 tonsils) were administered intratonsillar injections of fluticasone (n = 8, 1 mg/ml) or saline (n = 8, 0.1 ml) on days 0, 3, 7, 10, 14, and 17. Two rabbits (4 tonsils) received a single steroid injection to compare single versus multiple steroid injections. The rabbit's tonsil size was measured before each injection. After the fifty injections, the tonsils were harvested for histologic analysis.

Results: A total of 16 tonsils were analyzed. After five steroid injections, the reduction (-7.7 mm(2)  ± 4.27) in size was statistically significant when compared to reduction (6.12 mm(2)  ± 6.57) in the saline injected group (P = 0.001). Repeated steroid injection was more potent than a single injection (-3.00 mm(2)  ± 3.08) in reducing the size (P = 0.006). In histologic analysis, tonsils after repeated steroid injections were significantly smaller than saline-injected tonsils (P = 0.014), without obvious lymphoid follicles.

Conclusion: Repeated focal tonsillar injections of corticosteroids significantly reduced the size of palatine tonsils as compared to saline-injected controls. A single injection of corticosteroids appears to be effective, but not as effective, as multiple injections.

Level Of Evidence: N/A.
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http://dx.doi.org/10.1002/lary.24396DOI Listing
December 2014

Maternal antibodies or nonproductive infections confound the need for rederivation.

J Am Assoc Lab Anim Sci 2013 Jul;52(4):495-8

Department of Comparative Medicine, Stanford University School of Medicine, Stanford, CA, USA.

After rederivation of a mouse parvovirus (MPV)-contaminated transgenic mouse strain, serology and PCR testing of the surrogate dam showed it to be infected with mouse parvovirus strain 1 (MPV-1). The rederived pups (n = 3) also were MPV-positive, according to serology. Despite MPV seropositivity, fecal PCR tests of the pups were negative, as were serologic results from direct-contact sentinels. Only one rederived pup survived, and this male was bred successfully. None of its mates or progeny seroconverted to MPV. At 14.5 mo of age, the rederived male mouse was euthanized; tissues were collected and submitted for MPV testing; both serologic tests and PCR analysis of mesenteric lymph nodes were MPV-negative. One explanation for the rederived pups' MPV seropostivity is passive transfer of maternal antibodies or a nonproductive MPV infection. This case illustrates that although routine serological testing of surrogate mothers and pups is appropriate, any positive results should be further investigated by using transmissibility testing (fecal PCR or contact sentinels or both) prior to repeat rederivation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725937PMC
July 2013

Prevalence of Batrachochytrium dendrobatidis in Xenopus collected in Africa (1871-2000) and in California (2001-2010).

PLoS One 2013 15;8(5):e63791. Epub 2013 May 15.

Department of Biology, San Francisco State University, San Francisco, California, United States of America.

International trade of the invasive South African clawed frog (Xenopus laevis), a subclinical carrier of the fungal pathogen Batrachochytrium dendrobatis (Bd) has been proposed as a major means of introduction of Bd into naïve, susceptible amphibian populations. The historical presence of Bd in the indigenous African population of Xenopus is well documented. However, there are no reports documenting the presence of Bd in wild Xenopus populations in the US, particularly in California where introduced populations are well-established after intentional or accidental release. In this report, a survey was conducted on 178 archived specimens of 6 species of Xenopus collected in Africa from 1871-2000 and on 23 archived specimens (all wild-caught Xenopus laevis) collected in California, USA between 2001 and 2010. The overall prevalence rate of Bd in the tested Xenopus was 2.8%. The earliest positive specimen was X. borealis collected in Kenya in 1934. The overall prevalence of Bd in the X. laevis collected in California was 13% with 2 positive specimens from 2001 and one positive specimen from 2003. The positive Xenopus (3/23) collected in California were collected in 2001 (2/3) and 2003 (1/3). These data document the presence of Bd-infected wild Xenopus laevis in California. The findings reported here support the prevailing hypothesis that Bd was present as a stable, endemic infection in Xenopus populations in Africa prior to their worldwide distribution likely via international live-amphibian trade.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0063791PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655066PMC
January 2014

Mortality and morbidity in African clawed frogs (Xenopus laevis) associated with construction noise and vibrations.

J Am Assoc Lab Anim Sci 2012 Mar;51(2):253-6

Department of Comparative Medicine, Stanford University School of Medicine, Stanford, California, USA.

In Spring 2008, 175 adult female Xenopus laevis were exposed to construction-related vibrations that caused overt water rippling in the frog tanks. The 3 affected tanks were custom-built static, 300-gal 'pond-style' tanks that sat on the floor of the housing room. The water in the tank developed visible ripples as a result of the vibrations transmitted through the floor during jack-hammering in an adjacent room that was approximately 10 ftaway. All frogs in the tanks displayed buoyancy problems, excessive air gulping, and skin sloughing; ultimately 7 frogs died. In addition, these 7 animals were bloated, and 5 of these 7 had regurgitated and everted their stomach and distal esophagus into the oral cavity, resulting in airway obstruction and death. Gross pathologic findings included regurgitation and eversion of the stomach of the distal portion of the esophagus into the oral cavity, obstruction of the airway, and lung overinflation. No significant histologic lesions were observed. Construction vibrations transmitted through the water appeared to have disrupted the mechanoreceptive function of the lateral line system, resulting in overstimulation of the noxious feeding response, regurgitation, and eversion of the stomach and distal esophagus into the oral cavity and subsequent suffocation due to airway obstruction. After immediate cessation of the jack-hammering and relocation of the remaining frogs, no additional morbidities or mortalities occurred.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314530PMC
March 2012

Carbon dioxide and oxygen levels in disposable individually ventilated cages after removal from mechanical ventilation.

J Am Assoc Lab Anim Sci 2012 Mar;51(2):155-61

Department of Comparative Medicine, Stanford University School of Medicine, Stanford, California, USA.

Disposable individually ventilated cages have lids that restrict air exchange when the cage is not mechanically ventilated. This design feature may cause intracage CO2 to increase and O2 to decrease (hypercapnic and hypoxic conditions, respectively) when the electrical supply to the ventilated rack fails, the ventilated rack malfunctions, cages are docked in the rack incorrectly, or cages are removed from the ventilated rack for extended periods of time. We investigated how quickly hypercapnic and hypoxic conditions developed within disposable individually ventilated cages after removal from mechanical ventilation and compared the data with nondisposable static cages, disposable static cages, and unventilated nondisposable individually ventilated cages. When disposable individually ventilated cages with 5 adult mice per cage were removed from mechanical ventilation, CO2 concentrations increased from less than 1% at 0 h to approximately 5% at 3 h and O2 levels dropped from more than 20% at 0 h to 11.7% at 6 h. The breathing pattern of the mice showed a prominent abdominal component (hyperventilation). Changes were similar for 4 adult mice per cage, reaching at least 5% CO2 at 4 h and 13.0% O2 at 6 h. For 3 or 2 mice per cage, values were 4.6% CO2 and 14.7% O2 and 3.04% CO2 and 17.1% O2, respectively, at 6 h. These results document that within disposable individually ventilated cages, a hypercapnic and hypoxic microenvironment develops within hours in the absence of mechanical ventilation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314517PMC
March 2012

A far-reaching career.

Authors:
Stephen A Felt

Lab Anim (NY) 2011 May;40(5):162-3

Laboratory Animal Medicine Residency Program, Stanford University, Stanford, CA, USA.

An interview with Stephen A. Felt, DVM, MPH, DACLAM, DACVPM, Attending Veterinarian, Assistant Professor, Department of Comparative Medicine, Associate Director, Veterinary Service Center, Director, Laboratory Animal Medicine Residency Program, Stanford University, Stanford, CA.
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http://dx.doi.org/10.1038/laban0511-162DOI Listing
May 2011

Analgesic effects of tramadol, tramadol-gabapentin, and buprenorphine in an incisional model of pain in rats (Rattus norvegicus).

J Am Assoc Lab Anim Sci 2011 Mar;50(2):192-7

Department of Comparative Medicine, Stanford University School of Medicine, Stanford, California, USA.

Postoperative pain management in laboratory animals relies heavily on a limited number of drug classes, such as opioids and nonsteroidal antiinflammatory drugs. Here we evaluated the effects of saline, tramadol, tramadol with gabapentin, and buprenorphine (n = 6 per group) in a rat model of incisional pain by examining thermal hyperalgesia and weight-bearing daily for 6 d after surgery. All drugs were administered preemptively and continued for 2 consecutive days after surgery. Rats treated with saline or with tramadol only showed thermal hyperalgesia on days 1 through 4 and 1 through 3 after surgery, respectively. In contrast, buprenorphine-treated rats showed no thermal hyperalgesia on days 1 and 2 after surgery, and rats given tramadol with gabapentin showed reduced thermal hyperalgesia on days 2 and 4. For tests of weight-bearing, rats treated with saline or with tramadol only showed significantly less ipsilateral weight-bearing on day 1 after surgery, whereas rats given either buprenorphine or tramadol with gabapentin showed no significant change in ipsilateral weight-bearing after surgery. These data suggest that tramadol alone provides insufficient analgesia in this model of incisional pain; buprenorphine and, to a lesser extent, tramadol with gabapentin provide relief of thermal hyperalgesia and normalize weight-bearing.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061419PMC
March 2011

Cross-species surveillance of Leptospira in domestic and peri-domestic animals in Mahalla City, Gharbeya Governorate, Egypt.

Am J Trop Med Hyg 2011 Mar;84(3):420-5

Laboratory Unit, United States Naval Medical Research Unit-3, Imtidad Ramses Street, Abbassia, Cairo, Egypt.

A survey of 179 animals (black rats, dogs, sheep, buffaloes, cattle, donkeys, weasels, and cats) for Leptospira infection was conducted in Mahalla City (Lower Egypt). Blood, urine, and kidney were collected and tested by culture, microscopic agglutination test (MAT), and/or polymerase chain reaction (PCR). Among rats, 26% were positive by PCR, including 7% that were also positive by culture for L. interrogans serovars Grippotyphosa, Pyrogenes, and Icterohaemorrhagiae. L. borpetersenii serovar Polonica was isolated for the first time in Egypt in three rats. MAT titers ≥ 1:800 were observed in 11% of rats and 12% of dogs. L. interrogans serovar Grippotyphosa was detected in one cat. Sheep and donkeys were negative for leptospirosis by all methods. Buffaloes and cattle were seropositive in 20% and 44% of animals, respectively. Data indicate that several pathogenic serovars are circulating in the animals, which may pose exposure risks and account for high rates of acute febrile illness.
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http://dx.doi.org/10.4269/ajtmh.2011.10-0393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042818PMC
March 2011