Publications by authors named "John M Kruger"

26 Publications

  • Page 1 of 1

Safety and Efficacy of Felid Herpesvirus-1 Deletion Mutants in Cats.

Viruses 2021 01 22;13(2). Epub 2021 Jan 22.

Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, MI 48824, USA.

Felid herpesvirus-1 (FeHV-1) is an important respiratory and ocular pathogen of cats and current vaccines are limited in duration and efficacy because they do not prevent infection, viral nasal shedding and latency. To address these shortcomings, we have constructed FeHV-1 gE-TK- and FeHV-1 PK- deletion mutants (gE-TK- and PK-) using bacterial artificial chromosome (BAC) mutagenesis and shown safety and immunogenicity in vitro. Here, we compare the safety and efficacy of a prime boost FeHV-1 gE-TK- and FeHV-1 PK- vaccination regimen with commercial vaccination in cats. Cats in the vaccination groups were vaccinated at 3-week intervals and all cats were challenge infected 3 weeks after the last vaccination. Evaluations included clinical signs, nasal shedding, virus neutralizing antibodies (VN), cytokine mRNA gene expression, post-mortem histology and detection of latency establishment. Vaccination with gE-TK- and PK- mutants was safe and resulted in significantly reduced clinical disease scores, pathological changes, viral nasal shedding, and viral DNA in the trigeminal ganglia (the site of latency) following infection. Both mutants induced VN antibodies and interferons after immunization. In addition, after challenge infection, we observed a reduction of IL-1β expression, and modulation of TNFα, TGFβ and IL10 expression. In conclusion, this study shows the merits of using FeHV-1 deletion mutants for prevention of FeHV-1 infection in cats.
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http://dx.doi.org/10.3390/v13020163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911815PMC
January 2021

Retrospective analysis of diagnoses and outcomes of 45 cats with micturition disorders presenting as urinary incontinence.

J Vet Intern Med 2020 Jan 20;34(1):216-226. Epub 2019 Dec 20.

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan.

Background: In contrast to dogs, the causes and outcomes of urinary incontinence (UI) in cats are largely unknown.

Objectives: To determine the causes, identify comorbid conditions, and assess outcomes of cats with micturition disorders presenting as UI.

Animals: Forty-five cats with UI.

Methods: Retrospective study. Medical records of cats presented from January 2006 to December 2017 were searched using 45 keywords related to UI. History, presenting complaint, and physical examination findings were used to confirm a diagnosis. Cases were categorized based on functional and anatomic localizations.

Results: Forty-five cats met inclusion criteria. Spinal cord disease was the most common cause of UI (n = 18), followed by urethral (n = 17), bladder (n = 9), and ureteral (n = 1) disorders. Proportions of voiding and storage phase disorders were similar (53% and 47%, respectively). However, voiding-phase disorders were observed more frequently in males and younger-aged cats (P < .03). Urinary tract infection was detected in 11 of 28 (39%) cats. Outcomes were available in 38/45 cases; 16 cats (42%) regained continence, 3 (8%) improved with treatment, and 19 (50%) remained incontinent or were euthanized. Multiple variable logistic regressions indicated that spinal cord disease was significantly more likely to be associated with poor outcomes compared to bladder or urethral disorders (P < .04).

Conclusions And Clinical Importance: Urinary incontinence in cats was associated with a variety of congenital and acquired disorders that affected both phases of micturition with similar frequency. Incontinent cats with spinal cord disorders were common and warrant a more guarded prognosis than do cats with bladder or urethral disorders.
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http://dx.doi.org/10.1111/jvim.15683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979103PMC
January 2020

High-resolution MRI of kidney microstructures at 7.05 T with an endo-colonic Wireless Amplified NMR detector.

J Magn Reson 2019 06 25;303:121-127. Epub 2019 Apr 25.

Department of Radiology, Michigan State University, East Lansing, MI, USA. Electronic address:

To map the hemodynamic responses of kidney microstructures at 7.05 T with improved sensitivity, a Wireless Amplified NMR Detector (WAND) with cylindrical symmetry was fabricated as an endoluminal detector that can convert externally provided wireless signal at 600.71 MHz into amplified MR signals at 300.33 MHz. When this detector was inserted inside colonic lumens to sensitively observe adjacent kidneys, it could clearly identify kidney microstructures in the renal cortex and renal medullary. Owing to the higher achievable spatial resolution, differential hemodynamic responses of kidney microstructures under different breathing conditions could be individually quantified to estimate the underlying correlation between oxygen bearing capability and local levels of oxygen unsaturation. The WAND's ability to map Blood Oxygen Level Dependent (BOLD) signal responses in heterogeneous microstructures will pave way for early-stage diagnosis of kidney diseases, without the use of contrast agents for reduced tissue retention and toxicity.
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http://dx.doi.org/10.1016/j.jmr.2019.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590910PMC
June 2019

Evaluation of Immunomodulatory Properties of Feline Mesenchymal Stem Cells.

Stem Cells Dev 2017 05 28;26(10):776-785. Epub 2017 Mar 28.

1 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University , East Lansing, Michigan.

Mesenchymal stem cells (MSC) offer a novel approach to treatment of inflammatory disorders in humans and companion animals. Cats spontaneously develop a wide variety of inflammatory disorders and may potentially benefit from MSC-based therapies. Multiple genes are involved in immunomodulation by MSC and interspecies differences between expressions of these genes exist. The goals of the study were to characterize the expression of genes known to be involved in MSC-based immunomodulation and determine the effect of MSC on proliferation of T cells in coculture experiments with peripheral blood mononuclear cells (PBMC). Unstimulated MSC expressed all immunomodulatory genes studied except for IL-10. Levels of iNOS and FASL were low or undetectable at the RNA level. INFγ stimulation resulted in significant dose-dependent upregulation of IDO1, PD-L1, IL-6, COX2, and HGF. Levels of kynurenine were increased after 3-day incubation with INFγ. TNFα stimulation increased expression of IL-6 at both RNA and protein level as well as upregulated COX2 gene expression and PTGES1.Stimulation with both INFγ and TNFα resulted in significant increase in PGE2 levels in cell culture medium. MSC significantly decreased proliferation of ConA-stimulated PBMC in coculture experiments at 1:5 ratio. Our results suggest that feline MSC have similar immunomodulatory gene expression and react to inflammatory cytokines in a manner similar to human MSC. Thus, MSC may play an important role in treatment of feline disease as well as serve as an important translational species to evaluate MSC-based therapies of diseases common to both humans and cats.
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http://dx.doi.org/10.1089/scd.2016.0041DOI Listing
May 2017

The authors respond.

J Am Vet Med Assoc 2015 Dec;247(11):1227-8

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December 2015

Comparison of foods with differing nutritional profiles for long-term management of acute nonobstructive idiopathic cystitis in cats.

J Am Vet Med Assoc 2015 Sep;247(5):508-17

Objective: To evaluate the effect of nutrition on recurrent clinical signs of lower urinary tract (LUT) disease in cats with idiopathic cystitis.

Design: Randomized, controlled, masked clinical trial.

Animals: 31 cats with acute nonobstructive idiopathic cystitis.

Procedures: Cats were assigned to receive 1 of 2 foods (a cystitis prevention or control food) that differed in mineral (calcium, phosphorous, and magnesium), antioxidant, and fatty acid profiles. Owners documented LUT signs daily for up to 1 year. The primary endpoint was the number of recurrent episodes in which a cat had multiple (≥ 2 concurrent) LUT signs within a day (defined as multiple-sign day). Consecutive days in which a cat had multiple LUT signs were considered as a single episode.

Results: 4 cats fed prevention food and 2 cats fed control food were excluded from analysis because of noncompliance, gastrointestinal signs, food refusal, or owner voluntary withdrawal. The proportion of cats fed prevention food that had ≥ 1 recurrent episode of multiple-sign days (4/11) was not significantly lower than that of cats fed control food (9/14). However, cats fed prevention food had significantly lower mean incidence rates for recurrent episodes of multiple-sign days (0.7 episodes/1,000 cat-days) and episodes of hematuria (0.3 episodes/1,000 cat-days), dysuria (0.2 episodes/1,000 cat-days), and stranguria (0.2 episodes/1,000 cat-days) as single LUT signs, compared with cats fed control food (5.4, 3.4, 3.1, and 3.8 episodes/1,000 cat-days, respectively). Significantly fewer cats fed prevention food required analgesics (4/11), compared with cats fed control food (12/14).

Conclusions And Clinical Relevance: Foods with differing nutritional profiles appeared to impact mean incidence rates of recurrent feline idiopathic cystitis-associated signs.
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http://dx.doi.org/10.2460/javma.247.5.508DOI Listing
September 2015

Efficacy of two commercially available, low-magnesium, urine-acidifying dry foods for the dissolution of struvite uroliths in cats.

J Am Vet Med Assoc 2013 Oct;243(8):1147-53

Minnesota Urolith Center, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55105.

Objective: To compare the efficacy and safety of using 2 commercially available, low-magnesium, urine-acidifying dry foods to dissolve sterile struvite uroliths in cats.

Design: Prospective, multicenter, randomized clinical trial .

Sample: 37 cats with presumed struvite uroliths.

Procedures: Cats were randomly assigned to be fed 1 of 2 low-magnesium, urine-acidifying dry foods (food A or B). For each cat, physical examination, urinalysis, and abdominal radiography were performed weekly to assess treatment response.

Results: 32 cats had complete urolith dissolution. Mean ± SD times for a 50% reduction in urolith size (0.69 ± 0.1 weeks) and complete urolith dissolution (13.0 ± 2.6 days) were significantly shorter for cats fed food A, compared with those (1.75 ± 0.27 weeks and 27.0 ± 2.6 days, respectively) for cats fed food B. At study termination, mean ± SD urine pH (6.083 ± 0.105) for cats fed food A was lower than that (6.431 ± 0.109) for cats fed food B. In 5 cats, uroliths did not dissolve and were subsequently determined to be composed of 100% ammonium urate (n = 4) or 100% calcium oxalate (1). Adverse events associated with diet were not observed in any of the cats.

Conclusions And Clinical Relevance: Results indicated that dietary dissolution is safe and effective for eradication of sterile struvite uroliths in cats. Cats fed food A had faster urolith dissolution than did cats fed food B. Lack of a reduction in urolith size at 2 weeks after diet initiation was indicative of misdiagnosis or noncompliance.
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http://dx.doi.org/10.2460/javma.243.8.1147DOI Listing
October 2013

Acquisition and persistence of antimicrobial-resistant bacteria isolated from dogs and cats admitted to a veterinary teaching hospital.

J Am Vet Med Assoc 2013 Oct;243(7):990-1000

Center for Comparative Epidemiology, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824.

Objective: To assess antimicrobial resistance among bacteria isolated from dogs and cats admitted to a veterinary teaching hospital (VTH), determine the incidence of acquisition of and frequency of persistent colonization by antimicrobial-resistant organisms among these animals, and identify risk factors associated with these variables.

Design: Prospective longitudinal study.

Animals: 622 dogs and 92 cats admitted to a VTH and expected to stay ≥ 48 hours.

Procedures: Samples were collected with rectal and nasal or oropharyngeal swabs at admission and discharge. Isolates of enterococci, staphylococci, and Escherichia coli were tested for antimicrobial resistance via microbroth dilution methods. A subset of isolates was analyzed with pulsed-field gel electrophoresis and multilocus sequence typing. Significant trends in proportions of organisms with antimicrobial resistance over the 3-year study period were assessed.

Results: The proportion of staphylococci with antimicrobial resistance increased, whereas the proportion of E coli with resistance decreased, over time; resistance among enterococci was more variable. For 506 dogs with paired admission and discharge samples, multidrug-resistant (MDR) E coli was acquired by 40 (8%) and methicillin-resistant Staphylococcus aureus (MRSA) was acquired by 7 (1.4%); hospitalization for > 3 days was significantly associated with both variables. Most (5/7 isolates) acquired MRSA was of sequence type (ST) 5.

Conclusions And Clinical Relevance: Extended hospitalization was associated with increased risk of acquiring MDR E coli or MRSA, although few animals acquired MRSA. It is unclear whether associations were confounded by illness severity or use of infection control measures. Additionally, MRSA of ST5, which has been associated with small animal medicine, was the most commonly acquired MRSA in this study.
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http://dx.doi.org/10.2460/javma.243.7.990DOI Listing
October 2013

Successful treatment of intracardiac and intraocular blastomycosis in a dog with combination azole therapy.

J Am Anim Hosp Assoc 2013 Jul-Aug;49(4):273-80. Epub 2013 May 20.

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.

A 4 yr old spayed female Labrador retriever with clinical signs of blindness, cutaneous lesions, coughing, inappetence, and lethargy was diagnosed with disseminated blastomycosis based on cytologic (skin and lymph node aspirates) and histopathologic (skin biopsy) examinations of tissue samples. The dog deteriorated clinically during hospitalization and developed sustained ventricular tachycardia. Echocardiography revealed pericardial effusion, a nodule associated with the left ventricular papillary muscle, and a right atrial mural lesion. Therapy for myocardial performance and glaucoma was initiated. A combination of itraconazole and fluconazole successfully treated the dog. The dog regained vision in the left eye (oculus sinister [OS]) and had no residual cardiac disease detectable by either electrocardiography or echocardiography. This report is unique in documenting survival from intracardiac blastomycosis and in the use of combination azole therapy for treating disseminated disease with intraocular involvement.
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http://dx.doi.org/10.5326/JAAHA-MS-5874DOI Listing
June 2014

Clinical features and risk factors for development of urinary tract infections in cats.

J Feline Med Surg 2012 Oct 18;14(10):729-40. Epub 2012 Jun 18.

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.

The clinical and diagnostic features of 155 cats with urinary tract infection (UTI) and 186 controls with negative urine culture/s were characterized retrospectively (signalment, clinical signs, urinalysis, urine culture, concurrent diseases, lower urinary tract diagnostic/therapeutic procedures). Multivariable logistic regression was used to identify risk factors associated with UTI. Cats of all ages were affected by UTI with no sex/breed predisposition. Lower urinary tract signs were absent in 35.5% of cats with UTI. Pyuria and bacteriuria had sensitivities of 52.9% and 72.9%, and specificities of 85.5% and 67.7% for detection of UTI, respectively. Risk factors significantly associated with increased odds of UTI were urinary incontinence [odds ratio (OR)=10.78, P=0.0331], transurethral procedures (OR=8.37, P<0.0001), urogenital surgery (OR=6.03, P=0.0385), gastrointestinal disease (OR=2.62, P=0.0331), decreased body weight (OR=0.81, P=0.0259) and decreased urine specific gravity (OR=0.78, P=0.0055). Whilst not independently significant, renal disease and lower urinary tract anatomic abnormalities improved statistical model performance and contributed to UTI.
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http://dx.doi.org/10.1177/1098612X12451372DOI Listing
October 2012

Prevalence and antimicrobial resistance of Enterococcus spp and Staphylococcus spp isolated from surfaces in a veterinary teaching hospital.

J Am Vet Med Assoc 2012 Jun;240(12):1463-73

Center for Comparative Epidemiology, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.

Objective: To determine the prevalence and antimicrobial resistance of enterococci and staphylococci collected from environmental surfaces at a veterinary teaching hospital (VTH).

Design: Longitudinal study.

Sample: Samples collected from surfaces in 5 areas (emergency and critical care, soft tissue and internal medicine, and orthopedic wards; surgery preparation and recovery rooms; and surgery office and operating rooms) of a VTH.

Procedures: Selected surfaces were swabbed every 3 months during the 3-year study period (2007 to 2009). Isolates of enterococci and staphylococci were identified via biochemical tests, and antimicrobial susceptibility was evaluated with a microbroth dilution technique. A subset of isolates was analyzed to assess clonality by use of pulsed-field gel electrophoresis.

Results: 430 samples were collected, and isolates of enterococci (n = 75) and staphylococci (110) were identified. Surfaces significantly associated with isolation of Enterococcus spp and Staphylococcus spp included cages and a weight scale. Fourteen Enterococcus spp isolates and 17 Staphylococcus spp isolates were resistant to ≥ 5 antimicrobials. Samples collected from the scale throughout the study suggested an overall increase in antimicrobial resistance of Enterococcus faecium over time. Clonality was detected for E faecium isolates collected from 2 different surfaces on the same day.

Conclusions And Clinical Relevance: Although not surprising, the apparent increase in antimicrobial resistance of E faecium was of concern because of the organism's ability to transmit antimicrobial resistance genes to other pathogens. Results reported here may aid in identification of critical control points to help prevent the spread of pathogens in VTHs.
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http://dx.doi.org/10.2460/javma.240.12.1463DOI Listing
June 2012

Evaluation of modified Wright-staining of dried urinary sediment as a method for accurate detection of bacteriuria in cats.

Vet Clin Pathol 2011 Jun 9;40(2):256-64. Epub 2011 May 9.

Department of Pathobiology and Diagnostic Investigation and Diagnostic Center for Population and Animal Health, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.

Background: Urinary sediment examination and quantitative urinary culture results are frequently discordant.

Objectives: The aims of this study were to compare accuracy of light microscopic examination of wet-mounted unstained (wet-unstained) and air-dried modified Wright-stained (dry-stained) sedimented preparations of urine with results of quantitative aerobic bacterial culture for detection and characterization of bacteriuria in cats. In addition, the presence of pyuria detected by urinalysis and potential risk factors were assessed.

Methods: A blinded prospective study was conducted on 472 urinary samples collected from 410 cats by cystocentesis. The age and sex of each cat were recorded. Complete urinalyses were performed and included quantification of WBCs. Quantity and morphology of bacteria in each specimen were determined by light microscopic examination of wet-unstained (performed by certified medical technologists) and dry-stained (performed by a veterinary clinical pathologist) sedimented preparations of urine and compared with results of quantitative bacterial cultures.

Results: Of 472 urinary specimens, 29 were positive for bacteriuria by culture and considered true positives and 443 were considered true negatives. Compared with these results, examination of wet-unstained and dry-stained urines had sensitivities of 75.9% and 82.8%, specificities of 56.7% and 98.7%, and test efficiencies of 57.8% and 97.7%, respectively. Positive likelihood ratios were 1.8 and 63.7 and negative likelihood ratios were 0.42 and 0.17 for wet-unstained and dry-stained examinations, respectively. Compared with 29 culture-positive samples, the wet-unstained method had morphologic concordance and misclassification rates of 37.9% and 62.1%, respectively, whereas the dry-stained method had morphologic concordance and misclassification rates of 65.5% and 34.5%, respectively. Only 34% of samples with bacteriuria had pyuria. Frequency of bacteriuria was not significantly different based on age and sex of the cats, but there was a tendency for increased frequency in female cats and in cats >10 years old.

Conclusions: Staining dried urinary sediment with a modified Wright-stain significantly improved sensitivity, specificity, and test efficiency of microscopic detection and classification of bacteriuria compared with the wet-unstained method. Pyuria should not be a criterion for determining the presence or absence of bacteriuria.
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http://dx.doi.org/10.1111/j.1939-165X.2011.00314.xDOI Listing
June 2011

Comparison of three immunodiagnostic assays for antemortem detection of Mycobacterium bovis stimulation in domestic cats.

J Vet Diagn Invest 2010 Sep;22(5):724-9

Diagnostic Center for Population and Animal Health, College of Veterinary Medicine, Michigan State University, Lansing, MI 48910-8104, USA.

Mycobacterium bovis causes disease in numerous mammalian species including humans, thus making research, surveillance, and control important in the eradication of tuberculosis. Domestic cats are susceptible to multiple mycobacterial species including Mycobacterium bovis; however, their role in the epidemiology of bovine tuberculosis is not fully documented. The current study was an evaluation of the immune response in specific pathogen-free (SPF) cats stimulated with sensitinogen, a heat-killed M. bovis product, using the rapid test, multiple antigen print immunoassay (MAPIA), and bovine-purified protein derivative (bPPD) single skin test. Six cats were inoculated with sensitinogen subcutaneously on days 0 and 24; 2 noninoculated cats and 49 non-SPF cats were controls. Serial serum samples were collected during 135 days and assayed for M. bovis antibodies by rapid test and MAPIA. On day 123, bPPD skin test was performed and read at 48 and 72 hr. The bPPD test at 72 hr had a mean skin thickness of 0.3 mm for stimulated cats and 0.1 mm for controls. Rapid test identified 4 of 6 stimulated cats after bPPD injection. The MAPIA detected antibody against MPB83, 16/83, 16 kDa, and M. bovis culture filtrate (MBCF) antigens. All assays differentiated between stimulated and control cats; however, 7 of 49 non-SPF control cats had a reaction for either antigen MBCF or 16/83. These preliminary studies show potential for antemortem detection of M. bovis among domestic cats. Additional studies to better characterize virulent M. bovis infection in cats would be of value.
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http://dx.doi.org/10.1177/104063871002200509DOI Listing
September 2010

Complete genomic sequence and an infectious BAC clone of feline herpesvirus-1 (FHV-1).

Virology 2010 Jun 21;401(2):215-27. Epub 2010 Mar 21.

Graduate Program in Comparative Medicine and Integrative Biology, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.

Infection with feline herpesvirus-1 (FHV-1) is a major cause of upper respiratory and ocular diseases in Felidae. We report the first complete genomic sequence of FHV-1, as well as the construction and characterization of a bacterial artificial chromosome (BAC) clone of FHV-1, which contains the entire FHV-1 genome and has the BAC vector inserted at the left end of U(L). Complete genomic sequences were derived from both the FHV-1 BAC clone and purified virion DNA. The FHV-1 genome is 135,797bp in size with an overall G+C content of 45%. A total of 78 open reading frames were predicted, encoding 74 distinct proteins. The gene arrangement is collinear with that of most sequenced varicelloviruses. The virus regenerated from the BAC was very similar to the parental C-27 strain in vitro in terms of plaque morphology and growth characteristics and highly virulent in cats in a preliminary in vivo study.
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http://dx.doi.org/10.1016/j.virol.2010.02.021DOI Listing
June 2010

In vitro comparison of plain radiography, double-contrast cystography, ultrasonography, and computed tomography for estimation of cystolith size.

Am J Vet Res 2010 Mar;71(3):374-80

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.

Objective: To compare accuracy of estimates of cystolith size obtained by means of plain radiography, double-contrast cystography, ultrasonography, and computed tomography.

Sample Population: 30 canine cystoliths ranging from 1 to 11 mm in diameter with various mineral compositions.

Procedures: A bladder phantom model was created by filling a rubber balloon with saline (1% NaCl) solution and positioning it on top of a 2% gelatin cushion at the bottom of a water-filled 4-quart container. Cystoliths were individually placed in the bladder phantom and imaged by each of the 4 techniques. For each image, cystolith size was measured by 2 radiologists with computerized calipers, and size estimates were compared with actual cystolith size.

Results: Mean cystolith size estimates obtained by means of radiography, cystography, and computed tomography did not differ significantly from each other. However, for ultrasonographic images, mean +/- SD difference between actual and estimated cystolith size (2.95 +/- 0.73 mm) was significantly higher than mean difference for radiographic, cystographic, and computed tomographic images. For ultrasonography, mean +/- SD percentage overestimation in cystolith size was 68.4 +/- 51.5%.

Conclusions And Clinical Relevance: Results indicated that measurements of cystolith size obtained by means of ultrasonography may overestimate the true size. This suggests that cystolith size estimates obtained by means of ultrasonography should be interpreted with caution whenever cystolith size may influence patient management.
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http://dx.doi.org/10.2460/ajvr.71.3.374DOI Listing
March 2010

Analysis of 451,891 canine uroliths, feline uroliths, and feline urethral plugs from 1981 to 2007: perspectives from the Minnesota Urolith Center.

Vet Clin North Am Small Anim Pract 2009 Jan;39(1):183-97

Veterinary Clinical Sciences Department, Minnesota Urolith Center, College of Veterinary Medicine, University of Minnesota, 1352 Boyd Avenue, St. Paul, MN 55108, USA.

Urolithiasis is a general term referring to the causes and effects of stones anywhere in the urinary tract. Urolithiasis should not be viewed conceptually as a single disease with a single cause, but rather as a sequela of multiple interacting underlying abnormalities. Thus, the syndrome of urolithiasis may be defined as the occurrence of familial, congenital, or acquired pathophysiologic factors that, in combination, progressively increase the risk of precipitation of excretory metabolites in urine to form stones (ie, uroliths). The following epidemiologic discussion is based on quantitative analysis of 350,803 canine uroliths, 94,778 feline uroliths, and 6310 feline urethral plugs submitted to the Minnesota Urolith Center from 1981 to 2007.
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http://dx.doi.org/10.1016/j.cvsm.2008.09.011DOI Listing
January 2009

Changing paradigms of feline idiopathic cystitis.

Vet Clin North Am Small Anim Pract 2009 Jan;39(1):15-40

Department of Small Animal Clinical Sciences, Michigan State University College of Veterinary Medicine, Room D208, Veterinary Teaching Hospital, East Lansing, MI 48824-1314, USA.

Since 1996, when the authors assembled the existing body of knowledge about lower urinary tract disease in cats, the understanding of the biological behavior and pathologic features of naturally occurring feline idiopathic cystitis has increased. No single model explains all the biological variability observed in cats with idiopathic cystitis. The authors' experience and available evidence indicate that feline idiopathic cystitis represents a syndrome resulting from a number of separate underlying but potentially interrelated mechanisms rather than a disease with a single cause. Identification of safe and effective treatment and prevention strategies of feline idiopathic cystitis will likely vary, depending on the underlying causes.
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http://dx.doi.org/10.1016/j.cvsm.2008.09.008DOI Listing
January 2009

Prevalence of serum antibodies against six Leptospira serovars in healthy dogs.

J Am Vet Med Assoc 2007 Jun;230(11):1657-64

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824-1314, USA.

Objective: To determine the prevalence of antibodies against 6 Leptospira serovars and determine risk factors associated with positive Leptospira titers in healthy client-owned dogs in Michigan.

Design: Cross-sectional study.

Animals: 1,241 healthy dogs at least 4 months of age.

Procedures: Dogs were examined by veterinarians at private practices. Vaccinated and unvaccinated dogs were enrolled in the study, which occurred prior to the availability of a 4-serovar (Canicola, Grippotyphosa, Icterohaemorrhagiae, and Pomona) Leptospira vaccine. Sera were tested by use of the microscopic agglutination test to determine antibody titers against Leptospira serovars Bratislava, Canicola, Grippotyphosa, Hardjo, Icterohaemorrhagiae, and Pomona. A questionnaire was used to collect demographic information about each dog to identify risk factors associated with seropositive status.

Results: 309 of 1,241 (24.9%) dogs had antibody titers against at least 1 of the 6 Leptospira serovars, which suggested exposure to Leptospira spp. Prevalence of antibodies was highest to serovar Grippotyphosa, followed by Bratislava, Canicola, Icterohaemorrhagiae, and Pomona. Age, travel outside Michigan, exercise outside fenced yards, and exposure to livestock and wildlife were significant risk factors for positive titers.

Conclusions And Clinical Relevance: Among healthy dogs from the lower peninsula of Michigan, > 20% have antibodies against leptospiral serovars historically considered uncommon but more recently incriminated as causing clinical canine leptospirosis. Wildlife and livestock may be of increasing importance as reservoirs for canine leptospirosis as urbanization continues to occur. Expanded vaccination strategies may partially mitigate these trends.
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http://dx.doi.org/10.2460/javma.230.11.1657DOI Listing
June 2007

Evaluation of the effects of nephrotomy on renal function in clinically normal cats.

Am J Vet Res 2005 Aug;66(8):1400-7

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.

Objective: To evaluate the effects of nephrotomy on renal function in clinically normal cats.

Animals: 20 specific-pathogen-free, 9- to 11-month-old female mixed-breed cats.

Procedure: Serum chemistry analyses, CBC determinations, urinalyses, microbiologic urine cultures, renal ultrasonography, abdominal radiography, and single-kidney and total glomerular filtration rate (GFR) determinations by use of renal scintigraphy and measurements of plasma disappearance of technetium 99m-diethylenetriaminepentaacetic acid were performed before surgery and at 3, 12, 26, 52, and 78 weeks after surgery in 10 cats that underwent unilateral nephrotomy and in 10 control cats that underwent a sham surgical procedure.

Results: Two cats (1 from each group) did not complete the study, and their data were eliminated from analyses. Unilateral nephrotomy resulted in a 10% to 20% reduction in mean single-kidney GFR, compared with that of nephrotomy contralateral control kidneys. However, mean total GFR in nephrotomy-group cats was not significantly different from that of sham-group cats. Over the 78 weeks of study, mean total GFR declined 34% and 40% in nephrotomy- and sham-group cats, respectively. Adverse events associated with nephrotomy included persistent microscopic hematuria, renal pelvis hyperechogenicity with distant shadowing on ultrasonographic evaluation, dilatation of renal pelves, and hydronephrosis.

Conclusions And Clinical Relevance: Nephrotomy in normal functioning feline kidneys results in a modest relative reduction in renal function, compared with contralateral kidney controls, but has minimal effect on total GFR when compared with sham-operated control cats. However, any detrimental effects of nephrotomy may be magnified in cats with diseased kidneys, which may have little or no capacity for repair or compensation.
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http://dx.doi.org/10.2460/ajvr.2005.66.1400DOI Listing
August 2005

In vitro comparison of RNA preparation methods for detection of feline calicivirus in urine of cats by use of a reverse transcriptase-polymerase chain reaction assay.

Am J Vet Res 2005 May;66(5):915-20

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.

Objective: To compare 5 methods of preparation of RNA from feline urine samples for use in a feline calicivirus (FCV), p30 gene-based, real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay.

Sample Population: Urine and blood samples from 6 specific-pathogen-free cats.

Procedures: Aliquots of each urine sample (unmodified, centrifuged, or mixed with whole or hemolyzed blood) were spiked with FCV and serially diluted in urine. Serial dilutions of FCV in tissue culture medium were used as positive controls. Viral RNA was prepared via dilution and thermal inactivation (DT method), polyethylene glycol precipitation (PEG method), isolation with oligo(dT)25-coated magnetic beads (dTMB method), or extraction by use of 2 silica gel-based columns (RN or QA method). Lower detection limits and mean RT-PCR threshold cycle (Ct) values associated with each RNA preparation method and sample type were compared.

Results: Because DT-prepared samples yielded negative results via RT-PCR assay, this method was not evaluated. Lower detection limits (TCID50/sample) for the assay in urine were 1950, 104, 11, and 7 for PEG-, dTMB-, RN-, and QA-prepared samples, respectively. For RN and QA preparations, Ct values were similar and significantly lower than those for dTMB and PEG preparations. Overall, urine modifications did not affect FCV RNA detection in dTMB-, QA-, and RN-prepared samples.

Conclusions And Clinical Relevance: Of the methods evaluated, the RN and QA methods of RNA preparation were most appropriate for the FCV RT-PCR assay. An RT-PCR assay optimized for detection of FCV in feline urine may aid investigations of FCV-induced urinary tract diseases in cats.
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http://dx.doi.org/10.2460/ajvr.2005.66.915DOI Listing
May 2005

Evaluation of modified Wright-staining of urine sediment as a method for accurate detection of bacteriuria in dogs.

J Am Vet Med Assoc 2004 Apr;224(8):1282-9

Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.

Objective: To compare the findings of light microscopic evaluation of routine unstained wet-mounted preparations and air-dried, modified Wright-stained preparations of urine sediment with results of quantitative aerobic bacteriologic culture of urine.

Design: Masked prospective study.

Sample Population: 459 urine samples collected by cystocentesis from 441 dogs.

Procedure: Urinalyses and quantitative bacteriologic cultures of urine were performed. Unstained wet-mounted preparations and air-dried, modified Wright-stained urine sediment preparations were examined by light microscopy for the presence of bacteria.

Results: Compared with results of quantitative bacteriologic culture, routine unstained preparations and modified Wright-stained preparations had sensitivities of 82.4% and 93.2%, specificities of 76.4% and 99.0%, positive predictive values of 40.1% and 94.5%, negative predictive values of 95.8% and 98.7%, and test efficiencies of 77.3% and 98.0%, respectively. Compared with 74 samples that yielded growth on bacteriologic culture, the routine unstained method had concordance and misclassification rates of 39.2% and 60.8%, respectively, whereas the Wright-stained method had concordance and misclassification rates of 78.4% and 21.6%, respectively. Significant associations between each of occult blood in urine, pyuria, female sex, and lower urine specific gravity with bacteriuria detected by Wright-stained sediment examination and quantitative bacteriologic culture of urine were identified.

Conclusions And Clinical Relevance: Examination of modified Wright-stained preparations of urine sediment appeared to be a rapid, cost effective method that significantly improved the sensitivity, specificity, positive predictive value, and test efficiency of light microscopic detection of bacteriuria, compared with that of the routine unstained method.
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http://dx.doi.org/10.2460/javma.2004.224.1282DOI Listing
April 2004

Evaluation of a p30 gene-based real-time reverse transcriptase polymerase chain reaction assay for detection of feline caliciviruses.

J Vet Intern Med 2004 Jan-Feb;18(1):135-8

Department of Small Animal Clinical Sciences, Michigan State University, College of Veterinary Medicine, East Lansing, MI 48824-1314, USA.

This report describes a feline calicivirus (FCV) p30 gene-based real-time SYBR Green I reverse transcriptase polymerase chain reaction (RT-PCR) assay that is capable of detecting low virus concentrations and a broad range of FCV isolates. The assay consisted of a 1-step RT-PCR reaction with primers delineating a 126-base-pair (bp) region of the FCV p30 gene. Sensitivity of the RT-PCR assay was determined to be equivalent to a FCV titer of 1.2 x 10(1) to 1.2 x 10(2) TCID50/mL. The assay was linear over a wide range of template concentrations and had a reaction efficiency of 95%. Specific FCV amplification products were detected from 51 wild-type FCV isolates, whereas specific products were not detected from a canine calicivirus, a rabbit calicivirus, and a bovine calicivirus. The primers used in this study amplified a large number of North American FCV isolates and further confirm the diagnostic utility of p30 gene-based real-time RT-PCR for detection of FCV.
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http://dx.doi.org/10.1892/0891-6640(2004)18<135:eoapgr>2.0.co;2DOI Listing
February 2004

Transfusion-associated Babesia gibsoni infection in a dog.

J Am Vet Med Assoc 2003 Apr;222(7):959-63, 952

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.

A 2.5-year-old spayed female German Shepherd Dog was referred for evaluation of progressive anemia, lethargy, and weight loss. Seventeen days earlier, the dog had received a whole blood transfusion to manage hemorrhage after ovariohysterectomy. Mild fever, splenomegaly, and thrombocytopenia were also identified. Von Willebrand disease and Babesia gibsoni infection were diagnosed. Because of the serologic cross-reactivity of B gibsoni and B canis in the immunofluorescent antibody assay for IgG antibodies against these organisms, polymerase chain reaction amplification of parasite DNA was required to identify the infecting Babesia sp. The source of the B gibsoni infection was traced to an apparently healthy American Pit Bull Terrier blood donor. Despite resolution of clinical signs in the dog of this report, a series of antiparasitic treatments failed to eliminate the B gibsoni infection. Screening of potential blood donor dogs for Babesia spp is becoming increasingly important in the United States.
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http://dx.doi.org/10.2460/javma.2003.222.959DOI Listing
April 2003

Randomized controlled trial of the efficacy of short-term amitriptyline administration for treatment of acute, nonobstructive, idiopathic lower urinary tract disease in cats.

J Am Vet Med Assoc 2003 Mar;222(6):749-58

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.

Objective: To determine whether short-term amitriptyline administration would be efficacious in the treatment of acute, nonobstructive, idiopathic lower urinary tract disease in cats.

Design: Randomized controlled trial.

Animals: 31 untreated male and female cats with acute, nonobstructive, idiopathic lower urinary tract disease.

Procedures: Cats were treated with amitriptyline (5 mg/d; n = 16) or a placebo (15) for 7 days and monitored for pollakiuria, hematuria, and adverse events. Cats were reexamined 1 month after treatment, and owners were interviewed by telephone 6, 12, and 24 months after treatment.

Results: 2 amitriptyline-treated cats were excluded from analyses because of acquired urinary tract infection. Clinical signs resolved by day 8 in 8 amitriptyline-treated and 10 control cats. There were no apparent differences in likelihood or rate of recovery from pollakiuria or hematuria between groups. Overall, clinical signs recurred significantly faster and more frequently in amitriptyline-treated than control cats. However, after excluding recurrences within 21 days of treatment, risk of recurrence was similar in both groups. Increasing age was significantly associated with increased likelihood and rate of recovery from hematuria and with decreased risk of recurrence of signs.

Conclusions And Clinical Relevance: Results suggest that short-term amitriptyline treatment has no benefit in terms of resolution of pollakiuria and hematuria in cats with idiopathic lower urinary tract disease and may be associated with an increased risk of recurrence.
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http://dx.doi.org/10.2460/javma.2003.222.749DOI Listing
March 2003

Genetic characterization of 2 novel feline caliciviruses isolated from cats with idiopathic lower urinary tract disease.

J Vet Intern Med 2002 May-Jun;16(3):293-302

Department of Small Animal Clinical Sciences, Michigan State University College of Veterinary Medicine, East Lansing, 48824-1314, USA.

Feline caliciviruses (FCVs) are potential etiologic agents in feline idiopathic lower urinary tract disease (I-LUTD). By means of a modified virus isolation method, we examined urine obtained from 28 male and female cats with nonobstructive I-LUTD, 12 male cats with obstructive I-LUTD, and 18 clinically healthy male and female cats. All cats had been routinely vaccinated for FCV. Two FCVs were isolated; I (FCV-U1) from a female cat with nonobstructive I-LUTD, and another (FCV-U2) from a male cat with obstructive I-LUTD. To determine the genetic relationship of FCV-U1 and FCV-U2 to other FCVs. capsid protein gene RNA was reverse transcribed into cDNA, amplified, and sequenced. Multiple amino acid sequence alignments and phylogenetic trees were constructed for the entire capsid protein, hypervariable region E, and the more conserved (nonhypervariable) regions A, B, D, and F. When compared to 23 other FCV isolates with known biotypes, the overall amino acid sequence identity of the capsid protein of FCV-U1 and FCV-U2 ranged from 83 to 96%; identity of hypervariable regions C and E ranged from 58 to 85%. Phylogenetically, FCV-U1 clearly separated from other FCV strains in phenograms based on nonhypervariable regions. In contrast, FCV-U2 consistently segregated with the Urbana strain in all phenograms. Clustering of isolates by geographic origin was most apparent in phenograms based on nonhypervariable regions. No clustering of isolates by biotype was apparent in any phenograms. Our results indicate that FCV-UI and FCV-U2 are genetically distinct from other known vaccine and field strains of FCV.
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http://dx.doi.org/10.1892/0891-6640(2002)016<0293:gconfc>2.3.co;2DOI Listing
November 2002

Clinical evaluation of a leukocyte esterase test-strip for detection of feline pyuria.

Vet Clin Pathol 1997 ;26(3):126-131

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824.

Commercial macroscopic test-strips (dipsticks) that indirectly detect urine leukocytes by quantifying leukocyte esterase (LE) activity have been advocated as a simple, rapid, and inexpensive alternative to microscopic examination for detection of significant pyuria in urine specimens. The purpose of this study was to evaluate the diagnostic performance of a commercial LE test-strip for detection of feline pyuria. Two hundred and thirteen consecutive urine specimens were collected from 188 different feline patients and analyzed for LE activity with a LE test-strip (Multistix 2 Reagent Strips:Ames Division, Bayer Corp., Elkhart, IN). Results of the LE test-strip were compared with those of standard urine biochemical and microscopic sediment evaluations. Compared with urine sediment leukocyte counts, the LE test-strip had a sensitivity of 77%, a specificity of 34%, positive and negative predictive values of 14 and 91 % respectively, and an overall test efficiency of 39%. Multivariable logistic regression analysis did not reveal significant associations between pyuria (>5 WBC/hpf) and a positive LE test- strip reaction; however, hematuria, lipiduria, increasing age, and decreasing urine specific gravity were associated with a significantly increased risk for positive LE test-strip reactions. We conclude that the LE test-strip evaluated in this study is highly nonspecific for detection of significant pyuria in feline urine specimens and should not replace routine microscopic urine sediment examination in this species.
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http://dx.doi.org/10.1111/j.1939-165x.1997.tb00723.xDOI Listing
January 1997