Short-term and long-term outcomes for overweight dogs with cranial cruciate ligament rupture treated surgically or nonsurgically.

OBJECTIVE: To determine short- and long-term rates of successful outcomes of surgical and nonsurgical treatments for overweight dogs with cranial cruciate ligament rupture (CCLR). DESIGN: Prospective, randomized, clinical trial. Animals-40 client-owned overweight dogs with unilateral CCLR. PROCEDURES: Dogs were randomly assigned to nonsurgical (physical therapy, weight loss, and NSAID administration) or surgical (tibial plateau leveling osteotomy) treatment groups; dogs in both groups received the same nonsurgical treatments. Dogs were evaluated immediately before and 6, 12, 24, and 52 weeks after initiation of treatments via owner questionnaires, gait analysis, and dual-energy x-ray absorptiometry. A successful outcome was defined as an affected limb net ground reaction force > 85% of the value for healthy dogs and a ≥ 10% improvement in values of questionnaire variables. RESULTS: Owner questionnaire responses indicated dogs in both groups improved during the study, but dogs in the surgical treatment group seemed to have greater improvement. Body fat percentages for dogs in both treatment groups significantly decreased during the study. Surgical treatment group dogs had significantly higher peak vertical force for affected limbs versus nonsurgical treatment group dogs at the 24- and 52-week evaluation times. Surgical treatment group dogs had a higher probability of a successful outcome (67.7%, 92.6%, and 75.0% for 12-, 24-, and 52-week evaluations, respectively) versus nonsurgical treatment group dogs (47.1%, 33.3%, and 63.6% for 12-, 24-, and 52-week evaluations, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Overweight dogs with CCLR treated via surgical and nonsurgical methods had better outcomes than dogs treated via nonsurgical methods alone. However, almost two-thirds of the dogs in the nonsurgical treatment group had a successful outcome at the 52-week evaluation time.

Gene expression in intestinal mucosal biopsy specimens obtained from dogs with chronic enteropathy.

OBJECTIVE: To characterize mucosal gene expression in dogs with chronic enteropathy (CE). ANIMALS: 18 dogs with CE and 6 healthy control dogs. PROCEDURES: Small intestinal mucosal biopsy specimens were endoscopically obtained from dogs. Disease severity in dogs with CE was determined via inflammatory bowel index scores and histologic grading of biopsy specimens. Total RNA was extracted from biopsy specimens and microchip array analysis (approx 43,000 probe sets) and quantitative reverse transcriptase PCR assays were performed. RESULTS: 1,875 genes were differentially expressed between dogs with CE and healthy control dogs; 1,582 (85%) genes were downregulated in dogs with CE, including neurotensin, fatty acid-binding protein 6, fatty acid synthase, aldehyde dehydrogenase 1 family member B1, metallothionein, and claudin 8, whereas few genes were upregulated in dogs with CE, including genes encoding products involved in extracellular matrix degradation (matrix metallopeptidases 1, 3, and 13), inflammation (tumor necrosis factor, interleukin-8, peroxisome proliferator-activated receptor γ, and S100 calcium-binding protein G), iron transport (solute carrier family 40 member 1), and immunity (CD96 and carcinoembryonic antigen-related cell adhesion molecule [CEACAM] 18). Dogs with CE and protein-losing enteropathy had the greatest number of differentially expressed genes. Results of quantitative reverse transcriptase PCR assay for select genes were similar to those for microchip array analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Expression of genes encoding products regulating mucosal inflammation was altered in dogs with CE and varied with disease severity. Impact for Human Medicine-Molecular pathogenesis of CE in dogs may be similar to that in humans with inflammatory bowel disease.

Inflammation, apoptosis, and necrosis induced by neoadjuvant fas ligand gene therapy improves survival of dogs with spontaneous bone cancer.

Fas ligand (FasL) gene therapy for cancer has shown promise in rodents; however, its efficacy in higher mammals remains unknown. Here, we used intratumoral FasL gene therapy delivered in an adenovirus vector (Ad-FasL) as neoadjuvant to standard of care in 56 dogs with osteosarcoma. Tumors from treated dogs had greater inflammation, necrosis, apoptosis, and fibrosis at day 10 (amputation) compared to pretreatment biopsies or to tumors from dogs that did not receive Ad-FasL. Survival improvement was apparent in dogs with inflammation or lymphocyte-infiltration scores >1 (in a 3-point scale), as well as in dogs that had apoptosis scores in the top 50th percentile (determined by cleaved caspase-3). Survival was no different than that expected from standard of care alone in dogs with inflammation scores ≤1 or apoptosis scores in the bottom 50th percentile. Reduced Fas expression by tumor cells was associated with prognostically advantageous inflammation, and this was seen only in dogs that received Ad-FasL. Together, the data suggest that Ad-FasL gene therapy improves survival in a subset of large animals with naturally occurring tumors, and that at least in some tumor types like osteosarcoma, it is most effective when tumor cells fail to express Fas.

Two cases of paraprostatic cysts in castrated male dogs.

Two castrated male dogs presented for evaluation of tenesmus. Presurgical evaluations included complete physical examinations, serum biochemistry, abdominal ultrasonography, and MRI (case 2 only). Paraprostatic cysts were diagnosed in both cases based on the results of abdominal ultrasonography, MRI, and histopathology of tissue samples obtained during exploratory laparotomy. To the authors' knowledge, the two cases presented herein are the first documented cases of paraprostatic cysts that developed after castration in male dogs. Paraprostatic cysts should be considered in the differential diagnoses for castrated male dogs with prostatic disease.

Serum cortisol concentration and force plate analysis in the assessment of pain associated with sodium urate-induced acute synovitis in dogs.

OBJECTIVE: To determine the relationship between serum cortisol concentration and pain severity as measured by force platform gait analysis in dogs with experimentally induced synovitis of the stifle joint. ANIMALS: 10 healthy hound-type dogs. PROCEDURES: Dogs underwent 2 study phases. In the first phase, serum cortisol concentration, systolic arterial blood pressure, heart rate, and gait data were obtained at 0 (first sample), 2.5, 5, 7.5, and 10 hours. In the second phase, the same data were gathered immediately before (0 hours) and 2.5, 5, 7.5, and 10 hours after induction of acute urate synovitis in the left stifle joint. Data were statistically evaluated to compare changes in variable values over time and to determine the accuracy of serum cortisol measurements for diagnosis of acute orthopedic pain. RESULTS: Following induction of synovitis, ground reaction forces were significantly decreased relative to preinduction values at 2.5, 5.0, 7.5, and 10.0 hours and serum cortisol concentration was significantly increased at 2.5 hours. A cortisol concentration of >or= 1.6 microg/dL indicated pain with a 91% sensitivity and 35% specificity. CONCLUSIONS AND CLINICAL RELEVANCE: In this model, cortisol concentration may be useful for diagnosing pain in dogs. Although, with a cutoff of >or= 1.6 microg/dL, pain would be detected in most dogs with pain, some pain-free dogs would also be identified as having pain. Conversely, dogs with a serum cortisol of < 1.6 microg/dL would be unlikely to have pain. Validation of this diagnostic test in a large, heterogeneous group of clinical patients is necessary.

Nasal rhinosporidiosis in two dogs native to the upper Mississippi river valley region.

Two dogs, 4 and 7 years of age, were presented for evaluation and treatment of excessive sneezing. Physical examinations in both cases were within acceptable limits except for the presence of a single mass in the left nasal passage in the first case and left-sided nasal discharge in the second case. Rhinoscopy was used to visualize the nasal masses, and in both cases a single mass was surgically removed. Impression smears and histopathology submitted from each mass revealed lymphoplasmacytic and neutrophilic inflammation with spores typical of Rhinosporidium seeberi. These are the first reported cases of nasal rhinosporidiosis in two dogs native to the Upper Mississippi River Valley area with no travel history outside the region.

Identification of chromosomal regions associated with cranial cruciate ligament rupture in a population of Newfoundlands.

OBJECTIVE: To identify chromosomal regions associated with cranial cruciate ligament rupture (CCLR) in a population of Newfoundlands. ANIMALS: 90 client-owned Newfoundlands. PROCEDURES: A pedigree was constructed for dogs that did or did not have CCLR (determined on the basis of physical examination and radiographic findings). From this pedigree, affected and unaffected dogs were selected for genotyping on the basis of their predicted statistical likelihood of being homozygous CCLR-unaffected (n = 53) or homozygous CCLR-affected (37) dogs. Genotyping was performed for 532 microsatellite markers (MSATs). Comparisons of genotypes and allele frequencies were made between CCLR-affected and CCLR-unaffected dogs. RESULTS: In the selected population, 495 MSATs were informative with a mean interval between markers of 5.5 centimorgans. Eighty-six MSATs were significantly associated with the CCLR trait, whereas 4 markers (located on 4 chromosomes) were significantly associated with the trait when false discovery rate (q value) was controlled at the 0.05 level. Subsequent initial validation confirmed significant trait association for 3 of the 4 MSATs. CONCLUSIONS AND CLINICAL RELEVANCE: In the population of Newfoundlands, 4 MSATs that were located on 4 chromosomes were significantly associated with the CCLR trait. Three of those markers were validated in part via genotyping additional closely located markers. The MSATs that were associated with the CCLR trait were identified in all regions (except for those on chromosome 24). Newfoundlands with CCLR could be used to study the disease process associated with anterior cruciate ligament injuries that occur in young female human athletes.

Inheritance of rupture of the cranial cruciate ligament in Newfoundlands.

OBJECTIVE: To determine prevalence, level of inbreeding, heritability, and mode of inheritance for rupture of the cranial cruciate ligament (RCCL) in Newfoundlands. DESIGN: Retrospective and recruitment study. ANIMALS: 574 client-owned Newfoundlands. PROCEDURE: Medical records from January 1, 1996, to December 31, 2002, were evaluated for prevalence of RCCL. A pedigree was constructed by use of recruited Newfoundlands with RCCL status based on results of veterinary examination; level of inbreeding, heritability, and mode of inheritance were calculated. RESULTS: Hospital prevalence for RCCL was 22%; dogs in the pedigree from the recruitment study had a mean level of inbreeding of 1.19 x 10(4), heritability of 0.27, and a possible recessive mode of inheritance with 51% penetrance for RCCL. CONCLUSIONS AND CLINICAL RELEVANCE: Identification of a genetic basis for RCCL in Newfoundlands provided evidence that investigators can now focus on developing methods to identify carriers to reduce the prevalence of RCCL.

Estimate of the annual economic impact of treatment of cranial cruciate ligament injury in dogs in the United States.

OBJECTIVE: To estimate the economic impact to veterinary clients for the medical and surgical treatment of rupture of the cranial cruciate ligament (RCCL) in dogs for the year 2003. DESIGN: Economic impact survey. SAMPLE POPULATION: 501 diplomates of the American College of Veterinary Surgeons (ACVS) indicating that their area of surgical emphasis was small animal orthopedic surgery or small animal general and orthopedic surgery and 4,000 veterinarians indicating to the AVMA that their professional area was small animal practice exclusive or mixed animal practice (at least 80% small animal). PROCEDURE: Veterinarians were surveyed concerning the cost for medical and surgical treatment of RCCL for 2003. The economic impact was calculated by multiplying the number of RCCL surgeries performed by the mean cost of surgery. This was added to the number of RCCL cases managed medically multiplied by the mean cost of medical management. This estimate for survey responders was extrapolated to the total number of veterinarians in the study population for the ACVS or AVMA. RESULTS: Estimates for the total cost of surgery were $171,730,134.72 and $1,020,167,907 for veterinarians in the ACVS and AVMA populations, respectively. The cost of medical management was $2,885,687.86 and $126,558,155.16 for veterinarians in the ACVS and AVMA populations, respectively. After combining the ACVS and AVMA populations, we estimated that owners spent $1.32 billion for the treatment of RCCL in the United States in 2003. CONCLUSIONS AND CLINICAL RELEVANCE: RCCL is a prevalent, costly injury. Results may motivate veterinary and consumer agencies to prioritize funding for a better understanding of the injury.

Comparison of tibial plateau angle between clinically normal Greyhounds and Labrador Retrievers with and without rupture of the cranial cruciate ligament.

OBJECTIVE: To compare tibial plateau angle (TPA) between Greyhounds without damage to the cranial cruciate ligaments and Labrador Retrievers with and without damage to the cranial cruciate ligaments. DESIGN: Clinical study. ANIMALS: 87 client-owned dogs and 15 research colony Greyhounds. PROCEDURE: Standing position, horizontal-beam radiography was performed on Greyhounds and unaffected Labrador Retrievers to determine standing TPA. Lateral radiography of the stifle joint was performed on all dogs to determine traditional TPA. Age and body weight were recorded for unaffected and affected Labrador Retrievers. RESULTS: Greyhounds had mean standing TPA of 1.56 degrees and mean traditional TPA of 22.50 degrees. Unaffected Labrador Retrievers had mean standing TPA of 3.52 degrees and traditional TPA of 27.97 degrees. Affected Labrador Retrievers had mean traditional TPA of 25.55 degrees. No significant difference was found in mean standing TPA between Greyhounds and unaffected Labrador Retrievers. Standing TPAs in Greyhounds and unaffected Labrador Retrievers were not significantly different from a plane drawn parallel to the ground. Significant differences in traditional TPAs were detected among all 3 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Greyhounds had mean traditional TPA of 22.50 degrees; similar angles should be considered normal for dogs. Although affected Labrador Retrievers had mean traditional TPA that was significantly greater than that of Greyhounds, the steepest TPA was found in unaffected Labrador Retrievers. Because Greyhounds and unaffected Labrador Retrievers had similar standing TPAs, we conclude that although TPA may be associated with damage to the cruciate ligaments, many dogs with a steep TPA do not develop cruciate ligament disease.