Interstitial cystitis-an imbalance of risk and protective factors?

Interstitial cystitis (IC) presents as a chronic pain condition with variable combinations of symptoms depending on the species and individual patient. It is diagnosed by the presence of lower urinary tract signs and symptoms in combination with a variety of comorbid health problems, a history of life adversities, and the absence of other conditions that could cause the lower urinary tract signs. IC occurs naturally in humans and cats as a dimensional condition, with patients presenting with mild, moderate, and severe symptoms. Most patients appear to recover without specific treatment. A number of rodent models of IC have been used to study its causes and treatments. Unfortunately, current therapies generally fail to ameliorate IC symptoms long-term. The recent classification of IC as a chronic primary pain disorder calls for a rethinking of current clinical and research approaches to it. Beginning when a patient encounters a clinician, precipitating, perpetuating, and palliating risk factors can be addressed until a cause or reliably effective therapy is identified, and identifying predisposing and preventive factors can inform epidemiological studies and health promotion interventions. Predisposing, precipitating, and perpetuating risk factors, including environmental, psychological, and biological, increase the activity of the central threat response system (CTRS), which plays a clinically important role in IC symptoms. Studies in cats and rodent models have revealed that environmental enrichment (EE), in the absence of bladder-directed therapies, leads to amelioration of IC symptoms, implying a central role for the CTRS in symptom precipitation and perpetuation. Conceptually moving the source of IC pain to the brain as a motivational state rather than one resulting from peripheral nociceptive input offers both clinicians and researchers novel opportunities to improve care for patients with IC and for researchers to use more ecologically valid rodent models. It may even be that IC results from an excess of risk to protective factors, making this imbalance a targetable cause rather than a consequence of IC.

ACVIM consensus statement on diagnosis and management of urinary incontinence in dogs.

Urinary incontinence (UI) is a disorder of micturition that can occur in dogs of any age, sex, and breed depending on the underlying cause and time of onset. Diagnosis and treatment for various causes of UI in dogs have been described by multiple comprehensive single author review articles, but large prospective clinical trials comparing treatment outcomes in veterinary medicine are lacking. The objectives of this consensus statement therefore are to provide guidelines on both recommended diagnostic testing and treatment for various causes of UI in dogs. Specifically, pathophysiology directly related to the canine urinary system will be reviewed and diagnostic and therapeutic challenges will be addressed. A panel of 12 experts in the field (8 small animal internists [L. Adams, J. Bartges, A. Berent, J. Byron, J. Foster, A. Kendall, S. Vaden, J. Westropp], 2 neurologists [J. Coates, N. Olby], 1 radiologist [G. Oetelaar], and 1 surgeon [C. Adin]) was formed to assess and summarize evidence in the peer-reviewed literature and to complement it with consensus recommendations using the Delphi method. Some statements were not voted on by all panelists. This consensus statement aims to provide guidance for management of both male and female dogs with underlying storage or voiding disorders resulting in UI.

Idiopathic functional urinary outflow tract obstruction in dogs, a retrospective case series (2010-2021): 31 cases.

BACKGROUND: Idiopathic functional urinary outflow tract obstruction (iFUOTO) is an uncommon but life-limiting disease whose etiology and clinical course of disease remain poorly understood. OBJECTIVE: Characterize signalment, clinical signs, clinicopathologic findings, treatments, and propose a standardized response score for dogs with iFUOTO. ANIMALS: Thirty-one client-owned dogs diagnosed with iFUOTO. METHODS: Retrospective case series. Medical records from 2010 to 2021 were reviewed and findings recorded. Dogs were categorized based on the presence or absence of overt signs of neurological disease. Response to treatment was scored. RESULTS: Thirty-one dogs were included. All dogs had stranguria and 14 (45%) had overflow urinary incontinence. Mean age of onset for signs was 6.9 years±8 months. Twenty-four dogs (77%) were castrated males, 5 (16%) intact males, and 2 (6%) spayed females. Eight (26%) of dogs had overt neurological deficits. Follow-up data were available for 29 dogs (median 38 days, range: 2-1277). Final outcome scores were not significantly different among dogs with overt signs of neurological disease (median score 2.5; range: 0-3) and those without (median score 1; range; 0-3; P = .35). Treatments included alpha antagonists, skeletal muscle relaxants, parasympathomimetics, anti-inflammatories, castration, temporary placement of a urethral catheter, or a combination of these. CONCLUSIONS AND CLINICAL RELEVANCE: Multimodal treatment was frequently prescribed, but a standard outcome score is needed to evaluate the effectiveness of these therapies. Serial neurological examinations and monitoring of the dogs' dysuria are warranted.

Evaluation of a rapid immunoassay for bacteriuria in dogs.

BACKGROUND: The ability to detect bacteriuria in dogs with a point-of-care test might improve medical care and antimicrobial stewardship. HYPOTHESIS AND OBJECTIVE: A rapid immunoassay (RIA; RapidBac) will provide acceptable sensitivity and specificity for diagnosis of bacteriuria. ANIMALS: Forty-four client-owned dogs with a clinical indication for urinalysis and aerobic bacterial urine culture. METHODS: Prospective study. Urine, collected by cystocentesis, was submitted for urinalysis and culture at a diagnostic laboratory. Owners completed an enrollment questionnaire regarding their dogs' clinical signs. The RIA was performed according to the manufacturer's guidelines. Results were compared to culture. RESULTS: Forty-four urine specimens were evaluated from 44 dogs. The sensitivity and specificity of the RIA test to detect bacteriuria compared to urine culture were 81.8% (95% CI, 65.7%-97.9%) and 95.5% (95% CI, 86.8%-99.9%), respectively. For cultures yielding ≥103  CFU/mL, sensitivity increased to 90.0% (95% CI, 76.9%-100%) and specificity was similar at 95.2% (95% CI, 86.1%-99.9%). Malodorous urine, bacteriuria, and pyuria were more likely to be present in dogs with positive RIA or urine culture results compared to dogs with negative results. CONCLUSIONS AND CLINICAL IMPORTANCE: The RIA was easy to perform and had good sensitivity and excellent specificity in this group of dogs. The RIA might be a useful screening test for decision-making regarding antimicrobial therapy in dogs with a clinical indication for urine culture. Consideration could be given to amending the International Society for Companion Animal Infectious Disease definition of bacterial cystitis as the presence of signs of lower urinary tract disease together with positive culture or a positive RIA.

Antimicrobial susceptibility patterns from urinary isolates obtained from cats (2013-2020).

BACKGROUND: Bacterial urinary tract infections have been associated with comorbidities and increased antimicrobial resistance over time. OBJECTIVE: To identify bacterial species, antimicrobial susceptibility patterns and risk factors associated with antimicrobial resistance. ANIMALS: Three hundred sixty-three positive urine cultures from 308 cats. METHODS: Bacterial species and antimicrobial susceptibility data from positive aerobic bacterial urine cultures from cats with growth of ≥103 colony forming units per milliliter (cfu/ml) were included. Medical records were reviewed, and bacteriuria was classified as sporadic bacterial cystitis, recurrent bacterial cystitis or subclinical bacteriuria (SBU). Multivariable logistic regression analysis was used to evaluate antimicrobial resistance risk factors. RESULTS: A total of 444 bacterial isolates from 363 bacteriuric episodes were identified. Escherichia coli (52%) and SBU (59%) were the most common organism and classification, respectively. When compared to other classifications of bacteriuria, Enterococcus spp. were more likely to be isolated from SBU episodes (P < .001), whereas E. coli was more likely to be isolated from sporadic bacterial cystitis episodes (P < .001). Recurrent bacterial cystitis was associated with an increased risk of antimicrobial resistance to amoxicillin/clavulanic acid (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.3-11.3). The percent susceptibilities of all bacterial isolates to commonly prescribed antimicrobials were amoxicillin/clavulanic acid (72%), cefazolin (49%), enrofloxacin (61%), and trimethoprim/sulfamethoxazole (75%). Multidrug resistance was highest for Enterococcus faecium isolates (65%). CONCLUSIONS AND CLINICAL IMPORTANCE: No antimicrobial achieved >90% susceptible designation to all bacteria isolated highlighting the importance of performing urine culture and susceptibility testing, particularly for cats with recurrent bacterial cystitis.

Diagnostic yield of uroendoscopy compared to ultrasonography for evaluating lower urinary tract disorders in dogs.

BACKGROUND: Cystourethroscopy and vaginoscopy (uroendoscopy) is often used in the diagnostic evaluation of dogs with lower urinary tract disorders (LUTD). OBJECTIVE/HYPOTHESIS: To evaluate if uroendoscopy is warranted in dogs with various LUTD, the agreement between uroendoscopic and ultrasonographic diagnoses were compared. Dogs with recurrent urinary tract infections (rUTI) will have the highest diagnostic agreement between uroendoscopy and ultrasonography (US) compared to dogs presenting for other LUTD. ANIMALS: Two hundred thirty-seven dogs presenting between 2014 and 2019 with lower urinary tract signs (LUTS) that had US within 60 days preceding uroendoscopy. METHODS: Retrospective study. Dogs were categorized by primary indication for ultrasound. Pertinent uroendoscopic findings were recorded and agreements (κ analysis) between the final uroendoscopic diagnosis were compared with the final ultrasonographic diagnosis. RESULTS: Pertinent uroendoscopic findings were recorded for 69/237 (29%) cases. For dogs presenting primarily for urinary incontinence (UI), agreement between uroendoscopy and US was 71% (46/65; κ = 0.47, 95% CI 0.28-0.66), for dogs with stranguria, 58% (29/50; κ = 0.47, 95% CI 0.31-0.62) and for dogs with rUTI the agreement was substantial at 87% (26/30; κ = 0.70, 95% CI 0.43-0.98). Urethral strictures were the majority (14/21; 67%) of pertinent uroendoscopic findings for dogs with stranguria, of which 12 were male dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Agreement between uroendoscopy and US was moderate for all dogs. Based on these data, recommendation for uroendoscopy should be tailored to individual clinical presentation and signalment; transabdominal US is not the preferred modality for urethral lesions.

Urolithiasis in dogs: Evaluation of trends in urolith composition and risk factors (2006-2018).

BACKGROUND: Urolithiasis is a common and often recurrent problem in dogs. OBJECTIVE: To evaluate trends in urolith composition in dogs and to assess risk factors for urolithiasis, including age, breed, sex, neuter status, urolith location, and bacterial urolith cultures. SAMPLE POPULATION: A total of 10 444 uroliths and the dogs from which they were obtained. METHODS: The laboratory database at the UC Davis Gerald V. Ling Urinary Stone Analysis Laboratory was searched for all urolith submissions from dogs between January 2006 and December 2018. Mineral type, age, breed, sex, neuter status, urolith location, and urolith culture were recorded. Trends were evaluated and variables compared to evaluate risk factors. RESULTS: Calcium oxalate (CaOx) and struvite-containing uroliths comprised the majority of all submissions from dogs, representing 47.0% and 43.6%, respectively. The proportion of CaOx-containing uroliths significantly decreased from 49.5% in 2006 to 41.8% in 2018 (P = .006), with no change in the proportion of struvite-containing urolith submissions. Cystine-containing uroliths comprised 2.7% of all submissions between 2006 and 2018 and a significant nonlinear increase in this mineral type occurred over time (1.4% of all submissions in 2006 to 8.7% in 2018; P < .001). Of all cystine-containing uroliths, 70.3% were from intact male dogs. Age, breed, and sex predispositions for uroliths were similar to those previously identified. CONCLUSIONS AND CLINICAL IMPORTANCE: Although calcium oxalate- and struvite-containing uroliths continue to be the most common uroliths submitted from dogs, a decrease in the proportion of CaOx-containing uroliths and an increase in the proportion of cystine-containing uroliths occurred during the time period evaluated.

Urolithiasis in cats: Evaluation of trends in urolith composition and risk factors (2005-2018).

BACKGROUND: Urolithiasis is an important upper and lower urinary tract disease in cats that results in morbidity and mortality. OBJECTIVE: To describe trends in composition of uroliths in cats and evaluate risk factors related to age, breed, sex, urolith location, and bacterial urolith cultures. SAMPLE POPULATION: A total of 3940 uroliths and the cats from which they were obtained. METHODS: The database of the UC Davis Gerald V. Ling Urinary Stone Analysis Laboratory was searched for all urolith submissions from cats between January 2005 and December 2018. Mineral type, age, breed, sex, and urolith location and culture results were recorded. Trends were evaluated and variables compared to evaluate risk factors. RESULTS: A significant decrease in the proportion of calcium oxalate (CaOx)-containing uroliths occurred over time (P = .02), from 50.1% (204/407) of all submissions in 2005 to 37.7% (58/154) in 2018. In contrast, the proportion of struvite-containing uroliths increased significantly (P = .002), from 41.8% (170/407) in 2005 to 54.5% (84/154) in 2018. The proportion of CaOx-containing uroliths in the upper urinary tract was significantly higher compared to the proportion of other urolith types in the upper urinary tract. Urate-containing uroliths were the third most common type (361/3940, 9.2%). Overall, sex and age predispositions were similar to those reported previously. CONCLUSIONS AND CLINICAL IMPORTANCE: The decrease in the proportion of CaOx-containing uroliths and increase in the proportion of struvite-containing uroliths warrants investigation. Further education regarding the efficacy of medical dissolution of struvite-containing uroliths is recommended.

Ultrasonographic Evaluation of Uterine Stump Size in Ovariohysterectomized Dogs Receiving Estriol Compared to Control Dogs.

In ovariohysterectomized dogs, the uterine stump rarely causes clinical disease. However, changes could occur in this anatomic structure due to exposure to estrogen therapy. Ultrasonographic examination of the uterine stump has not been reported in dogs receiving estriol and normal dimensions for this area have not been reported for ovariohysterectomized dogs. Therefore, the aims of this study were to retrospectively evaluate records and ultrasound images from dogs receiving and not receiving (controls) estriol as well as defining a standard method to measure the uterine stump. Clinical features of dogs administered estriol were also reported. Fourteen dogs receiving estriol and 14 control dogs were included in the study. Seven dogs receiving estriol had changes associated with the external vulva, 5 were noted to be "hooded" and 3 were "prominent/swollen." Ultrasonographic transverse maximum uterine stump measurements were available for 4 dogs receiving estriol (median 0.81 cm, range 0.53-1.4). The maximum uterine height/aorta ratio was available for only 2 dogs receiving estriol (0.9 and 0.6). The median transverse maximum height of the uterine stump noted in the control group was 0.43 cm (range 0.28-0.52 cm); The maximal uterine height/aorta ratio was a median of 0.48 in the control group (range 0.32-1.1). Normal values for the uterine stump measurements can be standardized to the distal aorta for consistency. Vulvar enlargement was the most common physical examination change in our dogs receiving estriol. Routine screening, including ultrasonography is not usually indicated for dogs receiving estriol, but can be tailored to the individual patient.

Evaluation of a dry therapeutic urinary diet and concurrent administration of antimicrobials for struvite cystolith dissolution in dogs.

BACKGROUND: Struvite urolithiasis with bacterial urinary tract infection (UTI) is commonly reported in dogs; few data exist to describe successful dissolution protocols in dogs with naturally occurring disease. We hypothesized that a dry therapeutic urinary diet combined with targeted antimicrobial therapy can effectively dissolve presumptive struvite cystolithiasis in dogs with naturally occurring urease-producing bacterial UTI. RESULTS: Ten dogs with presumed infection-induced struvite cystolithiasis based on lower urinary tract signs (LUTS), radiodense cystoliths, and urease-producing bacterial UTI were enrolled. At enrollment, antimicrobials and dry therapeutic urinary diet were dispensed. In addition to lack of radiographic resolution of urolithiasis, dogs with persistent clinical signs were considered non-responders. There was no significant difference in pH between responders and non-responders; USG was significantly higher in the responder group. Recheck visits continued until radiographic dissolution or failure was documented. Five of the 10 dogs achieved radiographic dissolution of cystolithiasis within a median of 31 days (range 19-103). In the other 5 dogs, surgical urolith removal was necessary due to persistent LUTS (3 dogs within 2 weeks) or lack of continued dissolution noted radiographically (1 dog with numerous cystoliths failed at day 91; 1 dog failed by day 57 with questionable owner compliance). CONCLUSIONS: Dissolution of urinary tract infection induced struvite cystoliths can be accomplished in some dogs fed this dry therapeutic urinary diet in conjunction with antimicrobial therapy. Case selection could increase the likelihood of successful dissolution; however, if calcium phosphate is present, this could also prevent stone dissolution. If clinical signs persist despite diet and antimicrobials, stone removal is advised.

International Society for Companion Animal Infectious Diseases (ISCAID) guidelines for the diagnosis and management of bacterial urinary tract infections in dogs and cats.

Urinary tract disease is a common clinical presentation in dogs and cats, and a common reason for antimicrobial prescription. This document is a revision and expansion on the 2011 Antimicrobial Use Guidelines for Treatment of Urinary Tract Disease in Dogs and Cats, providing recommendations for diagnosis and management of sporadic bacterial cystitis, recurrent bacterial cystitis, pyelonephritis, bacterial prostatitis, and subclinical bacteriuria. Issues pertaining to urinary catheters, medical dissolution of uroliths and prophylaxis for urological procedures are also addressed.

Chronic Lower Urinary Tract Signs in Cats: Current Understanding of Pathophysiology and Management.

Cats that present with chronic lower urinary tract signs are often diagnosed with feline idiopathic/interstitial cystitis, a disease syndrome that is more than just a bladder disease and can be associated wtih a myriad of other co-morbidities. Further, gaining a better understanding of FIC (including the most accurate descriptive terminology) may help researchers, veterinarians, pet food companies, and clients develop and tailor the best possible approaches to management of these cat's unique health and welfare needs.

Clinical, histopathologic, cystoscopic, and fluorescence in situ hybridization analysis of proliferative urethritis in 22 dogs.

BACKGROUND: Proliferative urethritis (PU) is a lower urinary tract disease of dogs characterized by frond-like lesions in the urethra. The etiology of PU is unknown, although an association with bacterial cystitis is reported. OBJECTIVES: Deep-seated bacterial cystitis is associated with PU, particularly in dogs with neutrophilic or granulomatous inflammation. ANIMALS: Twenty-two client-owned dogs with PU and 5 control dogs euthanized for non-urinary disease. METHODS: In retrospective analysis, medical records of dogs with PU from 1986 to 2016 were reviewed. Signalment, clinical signs, cystoscopic findings, antimicrobial use, and results of urine, bladder, or urethral tissue cultures, if available, were recorded. Histopathology was reviewed and classified as lymphocytic-plasmacytic (LP), neutrophilic, LP-neutrophilic (LPN), granulomatous, or pleocellular. Eubacterial fluorescence in situ hybridization (FISH) was performed on 18 tissue samples (13 cases, 5 controls), with subsequent evaluation of bacterial species. RESULTS: Of the 22 dogs, 9 had LP urethritis, 6 had LPN, 4 had pleocellular, and 3 had neutrophilic urethritis. Of note, 7 of 13 PU samples were FISH+ for adherent or invasive bacteria; 1 of 5 controls were FISH+ for adherent bacteria. Five dogs had negative urine and tissue cultures when FISH was positive. There was no association detected between the type of urethral inflammation and the results of urine and tissue culture or FISH. CONCLUSIONS AND CLINICAL IMPORTANCE: The type of inflammation varied widely in these 22 PU cases. Deep-seated bacterial urethritis could be contributing to the inflammatory process in some dogs, regardless of the inflammation type. Urine and tissue cultures likely underestimate bacterial colonization of the urethra in dogs.

Correction: DNA Sequence Variants in the Five Prime Untranslated Region of the Cyclooxygenase-2 Gene Are Commonly Found in Healthy Dogs and Gray Wolves.

[This corrects the article DOI: 10.1371/journal.pone.0133127.].

MicroRNA profiling of dogs with transitional cell carcinoma of the bladder using blood and urine samples.

BACKGROUND: Early signs of canine transitional cell carcinoma (TCC) are frequently assumed to be caused by other lower urinary tract diseases (LUTD) such as urinary tract infections, resulting in late diagnosis of TCC which could be fatal. The development of a non-invasive clinical test for TCC could dramatically reduce mortality. To determine whether microRNAs (miRNAs) can be used as non-invasive diagnostic biomarkers, we assessed miRNA expression in blood and/or urine from dogs with clinically normal bladders (n = 28), LUTD (n = 25), and TCC (n = 17). Expression levels of 5 miRNA associated with TCC pathophysiology (miR-34a, let-7c, miR-16, miR-103b, and miR-106b) were assessed by quantitative real-time PCR. RESULTS: Statistical analyses using ranked ANOVA identified significant differences in miR-103b and miR-16 levels between urine samples from LUTD and TCC patients (miR-103b, p = 0.002; and miR-16, p = 0.016). No statistically significant differences in miRNA levels were observed between blood samples from LUTD versus TCC patients. Expression levels of miR-34a trended with miR-16, let-7c, and miR-103b levels in individual normal urine samples, however, this coordination was completely lost in TCC urine samples. In contrast, co-ordination of miR-34a, miR-16, let-7c, and miR-103b expression levels was maintained in blood samples from TCC patients. CONCLUSIONS: Our combined data indicate a potential role for miR-103b and miR-16 as diagnostic urine biomarkers for TCC, and that further investigation of miR-103b and miR-16 in the dysregulation of coordinated miRNA expression in bladder carcinogenesis is warranted.

Evaluation of dogs with genetic hyperuricosuria and urate urolithiasis consuming a purine restricted diet: a pilot study.

BACKGROUND: Urate urolithiasis is a common problem in breed homozygous for the mutation that results in hyperuricosuria. Low purine diets have been recommended to reduce purine intake in these dogs. METHODS: A higher protein, purine restricted diet with water added was evaluated in dogs with genetic hyperuricosuria and a history of clinical urate urolithiasis over a one year time period. Dogs were evaluated at baseline and 2, 6, and 12 months after initiating the test diet. Bloodwork, urinalysis, abdominal ultrasound, body composition, and 24-h urinary purine metabolite analyses were performed. RESULTS: Transient, mild, self-limited lower urinary tract signs were noted in only one dog on a single day, despite variable but usually mild and occasionally moderate amounts of echogenic bladder stones (<2-3 mm in size) in almost every dog at each visit. No significant differences were noted in urine specific gravity, urine pH, lean body condition score or body composition. Urinary uric acid concentration was lower on the test diet (p = 0.008), but 24-h uric acid excretions were similar (p = 0.220) compared to baseline. Significant differences between least squares mean plasma amino acid concentrations measured at the 0 and 12-month visits were found only for valine (p = 0.0119) and leucine (p = 0.0017). CONCLUSION: This study suggests the use of a low purine, higher protein diet with added water may be beneficial as part of the management of dogs with genetic hyperuricosuria and history of clinical urate urolithiasis.

Diagnosis and treatment of urolithiasis in client-owned chelonians: 40 cases (1987-2012).

OBJECTIVE: To calculate the prevalence of urolithiasis in client-owned chelonians examined at a veterinary teaching hospital and to describe the clinical signs, diagnosis, and treatment of urolithiasis in chelonians. DESIGN: Retrospective case series. ANIMALS: 40 client-owned turtles and tortoises with urolithiasis. PROCEDURES: The medical record database of a veterinary teaching hospital was searched from 1987 through 2012 for records of client-owned chelonians with urolithiasis. The prevalence of urolithiasis was calculated for client-owned chelonians examined at the hospital. Signalment and physical examination, hematologic, biochemical, urinalysis, diagnostic imaging, treatment, and necropsy results were described. RESULTS: The mean prevalence of urolithiasis in client-owned chelonians for the study period was 5.1 cases/100 client-owned chelonians examined. Thirty-one of the 40 chelonians were desert tortoises. Only 5 of 40 chelonians had physical examination abnormalities associated with the urogenital tract. Surgery was performed on 17 chelonians; 5 developed postoperative complications, and 4 of those died. Necropsy was performed on 18 chelonians, and urolithiasis contributed to the decision to euthanize or was the cause of death for 9. Uroliths from 13 chelonians were analyzed, and all were composed of 100% urate. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated chelonians with urolithiasis have various clinical signs and physical examination findings that may or may not be associated with the urinary tract. Hematologic, biochemical, and urinalysis findings were nonspecific for diagnosis of urolithiasis. Many chelonians died or were euthanized as a consequence of urolithiasis, which suggested the disease should be identified early and appropriately treated.

DNA Sequence Variants in the Five Prime Untranslated Region of the Cyclooxygenase-2 Gene Are Commonly Found in Healthy Dogs and Gray Wolves.

The aim of this study was to investigate the frequency of regional DNA variants upstream to the translation initiation site of the canine Cyclooxygenase-2 (Cox-2) gene in healthy dogs. Cox-2 plays a role in various disease conditions such as acute and chronic inflammation, osteoarthritis and malignancy. A role for Cox-2 DNA variants in genetic predisposition to canine renal dysplasia has been proposed and dog breeders have been encouraged to select against these DNA variants. We sequenced 272-422 bases in 152 dogs unaffected by renal dysplasia and found 19 different haplotypes including 11 genetic variants which had not been described previously. We genotyped 7 gray wolves to ascertain the wildtype variant and found that the wolves we analyzed had predominantly the second most common DNA variant found in dogs. Our results demonstrate an elevated level of regional polymorphism that appears to be a feature of healthy domesticated dogs.

Elemental Content of Calcium Oxalate Stones from a Canine Model of Urinary Stone Disease.

One of the most common types of urinary stones formed in humans and some other mammals is composed of calcium oxalate in ordered hydrated crystals. Many studies have reported a range of metals other than calcium in human stones, but few have looked at stones from animal models such as the dog. Therefore, we determined the elemental profile of canine calcium oxalate urinary stones and compared it to reported values from human stones. The content of 19 elements spanning 7-orders of magnitude was quantified in calcium oxalate stones from 53 dogs. The elemental profile of the canine stones was highly overlapping with human stones, indicating similar inorganic composition. Correlation and cluster analysis was then performed on the elemental profile from canine stones to evaluate associations between the elements and test for potential subgrouping based on elemental content. No correlations were observed with the most abundant metal calcium. However, magnesium and sulfur content correlated with the mineral hydration form, while phosphorous and zinc content correlated with the neuter status of the dog. Inter-elemental correlation analysis indicated strong associations between barium, phosphorous, and zinc content. Additionally, cluster analysis revealed subgroups within the stones that were also based primarily on barium, phosphorous, and zinc. These data support the use of the dog as a model to study the effects of trace metal homeostasis in urinary stone disease.

Changes in blood pressure following escalating doses of phenylpropanolamine and a suggested protocol for monitoring.

This prospective, cross-over, blinded study evaluated the effect of various doses of phenylpropanolamine (PPA) on blood pressure in dogs. Dogs were randomized to receive a placebo or 1 of 3 dosages of immediate release PPA, q12h for 7 days [1 mg/kg body weight (BW), 2 mg/kg BW, or 4 mg/kg BW] in a cross-over design. Blood pressure was recorded every 2 h, for 12 h, on days 1 and 7. There were significant increases in systolic, diastolic, and mean blood pressure following administration of PPA at 2 mg/kg BW and 4 mg/kg BW. A significant decrease in heart rate was also noted at all PPA dosages, but not in the placebo. Administration of PPA was associated with a dose response increase in blood pressure. Dosages of up to 2 mg/kg BW should be considered safe in healthy dogs.

Changements de la pression artérielle après des doses progressives de phénylpropanolamine et suggestion d'un protocole de surveillance. Cette étude prospective à l'insu et à plan d'étude croisée a évalué l'effet de diverses doses de phénylpropanolamine (PPA) sur la pression artérielle des chiens. Les chiens ont reçu au hasard un placebo ou 1 de 3 doses de PPA à action immédiate, q12h pendant 7 jours (1 mg/kg de poids corporel [PC], 2 mg/kg PC ou 4 mg/kg PC) dans un plan d'étude croisé. La pression artérielle a été consignée toutes les 2 h, pendant 12 h, aux jours 1 et 7. Il n'y a pas eu de hausses significatives de la pression artérielle systolique et diastolique ni de la pression artérielle moyenne après l'administration de PPA à 2 mg/kg PC et à 4 mg/kg PC. Une baisse significative de la fréquence cardiaque a aussi été notée dans toutes les doses de PPA, mais non avec le placebo. L'administration de PPA a été associée à une hausse de la pression artérielle en fonction de la dose. Des doses jusqu'à 2 mg/kg PC devraient être considérées sûres chez des chiens en santé.(Traduit par Isabelle Vallières).