Complications and putative risk factors for cecal or colonic surgery in dogs: 79 cases (2002-2015).

OBJECTIVES: To evaluate the complication rate, mortality rate and putative risk factors for cecal or colonic surgery in dogs. MATERIALS AND METHODS: A multi-institutional retrospective study including dogs that had undergone surgery that involved the cecum or the colon. Medical records from three referral hospitals were reviewed for patient demographics and clinical data. The association between putative risk factors and survival to discharge or complications was assessed using univariable and multivariable analysis. RESULTS: Seventy-nine dogs met the criteria to be included in this study. Fifty-five dogs had full thickness incision surgeries, while 24 dogs had partial thickness surgeries. The complication and mortality rates for full thickness and partial thickness cecal/colonic surgeries were not statistically different. The dehiscence rate of colonic anastomosis in this study was four of 47 (8.5%). On univariate analysis, performing full thickness procedures out of hours had an association with increased complications and mortality. On multivariable analysis, no factors were associated with survival to discharge or complications. There was no association of board-certified surgeon presence in surgery with complications or mortality. CLINICAL SIGNIFICANCE: The performance of full thickness cecal/colonic surgery is not associated with a statistically significant increased risk for complications or mortality compared to partial thickness procedures, with a possible increased risk of complications and mortality in full thickness procedures out of hours.

Adaptation of land treadmill scoring system for underwater treadmill in dogs with thoracolumbar intervertebral disc extrusion.

The underwater treadmill (UWTM) is utilized in dogs recovering from thoracolumbar intervertebral disc extrusion (TL-IVDE). Gait scoring is validated for dogs with TL-IVDE walking on the land treadmill (LT) but has not been reported for the UWTM. Our objective was to investigate if LT gait analysis could be applied to the UWTM and if non-ambulatory dogs walking unassisted on the UWTM, at a standardized water level, would be more likely to generate gait scores compared to on the LT. This was a prospective, observational study in dogs with TL-IVDE managed surigcally. At 0, 2, 4, 8 and 12 weeks post-operatively, paired video footage of dogs walking on the LT and UWTM (water level at the greater trochanter) was used to generate 0-100 stepping (SS) and coordination (regularity index, RI) scores. Scores were compared between treadmill type and over time. Twenty dogs were enrolled and seventy-eight paired recordings were available for review. Median gait scores increased over time but did not differ by treadmill type (P = 0.262 for SS, P = 0.533 for RI). Combining SS and RI, more recordings received scores of 0 for the LT (n = 58/156; 37.2 %) compared to the UWTM (n = 44/156; 28.2 %; P = 0.043). Scores of 0, at visits when there was at least movement present at multiple joints, was more common on the LT (n = 11/108; 10.2 %) compared to the UWTM (n = 2/108, 1.9 %; P = 0.026). In dogs recovering from TL-IVDE, LT-based gait scoring was feasible in dogs walking on the UWTM and might complement other gait analysis methods, especially for non-ambulatory dogs.

Effects of a large-scale, natural sediment deposition event on plant cover in a Massachusetts salt marsh.

In mid-winter 2018, an unprecedented sediment deposition event occurred throughout portions of the Great Marsh in Massachusetts. Evaluation of this event in distinct marsh areas spanning three towns (Essex, Ipswich, and Newbury) revealed deposition covering 29.2 hectares with an average thickness of 30.1±2.1 mm measured shortly after deposition. While sediment deposition helps marshes survive sea level rise by building elevation, effects of such a large-scale deposition on New England marshes are unknown. This natural event provided an opportunity to study effects of large-scale sediment addition on plant cover and soil chemistry, with implications for marsh resilience. Sediment thickness did not differ significantly between winter and summer, indicating sediment is not eroding or compacting. The deposited sediment at each site had similar characteristics to that of the adjacent mudflat (e.g., texture, bivalve shells), suggesting that deposited materials resulted from ice rafting from adjacent flats, a natural phenomenon noted by other authors. Vegetative cover was significantly lower in plots with rafted sediment (75.6±2.3%) than sediment-free controls (93.1±1.6%) after one growing season. When sorted by sediment thickness categories, the low thickness level (1-19 mm) had significantly greater percent cover than medium (20-39 mm) and high (40-90 mm) categories. Given that sediment accretion in the Great Marsh was found to average 2.7 mm per year, the sediment thickness documented herein represents ~11 years of sediment accretion with only a 25% reduction in plant cover, suggesting this natural sediment event will likely increase long-term marsh resilience to sea level rise.

Effect of clinical signs, endocrinopathies, timing of surgery, hyperlipidemia, and hyperbilirubinemia on outcome in dogs with gallbladder mucocele.

Gallbladder mucocele (GBM) is a common extra-hepatic biliary syndrome in dogs with death rates ranging from 7 to 45%. Therefore, the aim of this study was to identify the association of survival with variables that could be utilized to improve clinical decisions. A total of 1194 dogs with a gross and histopathological diagnosis of GBM were included from 41 veterinary referral hospitals in this retrospective study. Dogs with GBM that demonstrated abnormal clinical signs had significantly greater odds of death than subclinical dogs in a univariable analysis (OR, 4.2; 95% CI, 2.14-8.23; P<0.001). The multivariable model indicated that categorical variables including owner recognition of jaundice (OR, 2.12; 95% CI, 1.19-3.77; P=0.011), concurrent hyperadrenocorticism (OR 1.94; 95% CI, 1.08-3.47; P=0.026), and Pomeranian breed (OR, 2.46; 95% CI 1.10-5.50; P=0.029) were associated with increased odds of death, and vomiting was associated with decreased odds of death (OR, 0.48; 95% CI, 0.30-0.72; P=0.001). Continuous variables in the multivariable model, total serum/plasma bilirubin concentration (OR, 1.03; 95% CI, 1.01-1.04; P<0.001) and age (OR, 1.17; 95% CI, 1.08-1.26; P<0.001), were associated with increased odds of death. The clinical utility of total serum/plasma bilirubin concentration as a biomarker to predict death was poor with a sensitivity of 0.61 (95% CI, 0.54-0.69) and a specificity of 0.63 (95% CI, 0.59-0.66). This study identified several prognostic variables in dogs with GBM including total serum/plasma bilirubin concentration, age, clinical signs, concurrent hyperadrenocorticism, and the Pomeranian breed. The presence of hypothyroidism or diabetes mellitus did not impact outcome in this study.

Disruption of FOXF2 as a Likely Cause of Absent Uvula in an Egyptian Family.

This study investigated the genetic basis of an unusual autosomal dominant phenotype characterized by familial absent uvula, with a short posterior border of the soft palate, abnormal tonsillar pillars, and velopharyngeal insufficiency. Cytogenetic analysis and single-nucleotide polymorphism-based linkage analysis were investigated in a 4-generation family with 8 affected individuals. Whole exome sequencing data were overlaid, and segregation analysis identified a single missense variant, p.Q433P in the FOXF2 transcription factor, that fully segregated with the phenotype. This was found to be in linkage disequilibrium with a small 6p25.3 tandem duplication affecting FOXC1 and GMDS. Notably, the copy number imbalances of this region are commonly associated with pathologies that are not present in this family. Bioinformatic predictions with luciferase reporter studies of the FOXF2 missense variant indicated a negative impact, affecting both protein stability and transcriptional activation. Foxf 2 is expressed in the posterior mouse palate, and knockout animals develop an overt cleft palate. Since mice naturally lack the structural equivalent of the uvula, we demonstrated FOXF2 expression in the developing human uvula. Decipher also records 2 individuals with hypoplastic or bifid uvulae with copy number variants affecting FOXF2. Nevertheless, given cosegregation with the 6p25.3 duplications, we cannot rule out a combined effect of these gains and the missense variant on FOXF2 function, which may account for the rare palate phenotype observed.

A targeted sequencing panel identifies rare damaging variants in multiple genes in the cranial neural tube defect, anencephaly.

Neural tube defects (NTDs) affecting the brain (anencephaly) are lethal before or at birth, whereas lower spinal defects (spina bifida) may lead to lifelong neurological handicap. Collectively, NTDs rank among the most common birth defects worldwide. This study focuses on anencephaly, which despite having a similar frequency to spina bifida and being the most common type of NTD observed in mouse models, has had more limited inclusion in genetic studies. A genetic influence is strongly implicated in determining risk of NTDs and a molecular diagnosis is of fundamental importance to families both in terms of understanding the origin of the condition and for managing future pregnancies. Here we used a custom panel of 191 NTD candidate genes to screen 90 patients with cranial NTDs (n = 85 anencephaly and n = 5 craniorachischisis) with a targeted exome sequencing platform. After filtering and comparing to our in-house control exome database (N = 509), we identified 397 rare variants (minor allele frequency, MAF < 1%), 21 of which were previously unreported and predicted damaging. This included 1 frameshift (PDGFRA), 2 stop-gained (MAT1A; NOS2) and 18 missense variations. Together with evidence for oligogenic inheritance, this study provides new information on the possible genetic causation of anencephaly.

In vitro anti-LPS dose determination of ketorolac tromethamine and in vivo safety of repeated dosing in healthy horses.

Flunixin meglumine (FM) is a commonly used Nonsteroidal anti-inflammatory drug (NSAID) in horses, but clinical efficacy is often unsatisfactory. Ketorolac tromethamine (KT) demonstrates superior efficacy compared to other NSAIDs in humans, but its anti-inflammatory effects have not been investigated in the horse. Safety of repeated dosing of KT has not been evaluated. The first objective was to conduct a dose determination study to verify that a previously described dosage of KT would inhibit Lipopolysaccharide (LPS)-induced eicosanoid production in vitro, and to compare KT effects of this inhibition to those of FM. Then, a randomized crossover study was performed using nine healthy horses to evaluate plasma concentrations of KT and FM following IV administration. Administered dosages of KT and FM were 0.5 mg/kg and 1.1 mg/kg, respectively. Safety following six repeated doses of KT was assessed. Ketorolac tromethamine and FM suppressed LPS-induced Thromboxane B2 (TXB2 ) and Prostaglandin E2 (PGE2 ) production in vitro for up to 12 hr. Intravenous administration produced plasma concentrations of KT and FM similar to previous reports. No adverse effects were observed. A KT dosage of 0.5 mg/kg IV inhibited LPS-induced eicosanoids in vitro, and repeated dosing for up to 3 days appears safe in healthy horses. Investigation of in vivo anti-inflammatory and analgesic effects of KT is warranted.

Glutathione Peroxidase Activity, Plasma Total Antioxidant Capacity, and Urinary F2- Isoprostanes as Markers of Oxidative Stress in Anemic Dogs.

BACKGROUND: Oxidative stress plays a role in the pathophysiology of several diseases and has been documented as a contributor to disease in both the human and veterinary literature. One at-risk cell is the erythrocyte, however, the role of oxidative stress in anemia in dogs has not been widely investigated. HYPOTHESIS/OBJECTIVE: Anemic dogs will have an alteration in the activity of glutathione peroxidase (GPx), a decrease in of total antioxidant capacity (TAC), and an increased concentration of urinary 15-F2 -isoprostanes (F2 -IsoP) when compared to healthy dogs. ANIMALS: 40 client-owned dogs with anemia (PCV <30%) age-matched to 40 client-owned healthy control dogs. METHODS: Prospective, cross-sectional study. Whole blood GPx activity, plasma TAC, and urinary F2 -isoprostane concentrations were evaluated in each dog and compared between groups. RESULTS: Anemic dogs had significantly lower GPx activity (43.1 × 103 +/- 1.6 × 103 U/L) than did dogs in the control group (75.8 × 103 +/- 2.0 × 103 U/L; P < 0.0001). The GPx activity in dogs with hemolysis (103 +/- 0.8 × 103 U/L) was not significantly different (P = 0.57) than in dogs with nonhemolytic anemia (43.5 × 103 +/- 1.1 × 103 U/L). The TAC concentrations (P = 0.15) and urinary F2 -isoprostanes (P = 0.73) did not significantly differ between groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Glutathione peroxidase activity was significantly decreased in anemic dogs indicating oxidative stress. Additional studies are warranted to determine if antioxidant supplementation would improve survival and overall outcome as part of a therapeutic regimen for anemic dogs.

Neonatal Encephalopathy in Calves Presented to a University Hospital.

BACKGROUND: While studies have examined bovine dystocia in relation to calf survival, little has been published regarding perinatal morbidity and treatment of newborn calves beyond failure of transfer of passive immunity (FTPI). Neonatal encephalopathy (NE) is a clinical syndrome commonly diagnosed in infants and foals but is poorly described in calves. HYPOTHESIS/OBJECTIVES: To identify risk factors for development of NE in calves and factors predictive of survival. ANIMALS: Neonatal calves presented to a University hospital over a 10-year period. METHODS: Retrospective cohort study (2005-2015). Medical records of all neonatal calves presented to the hospital were examined, and cases of NE were identified. Data pertaining to demographics, dam parity, labor, treatment, and outcome were collected and analyzed with univariate and multivariate statistics. RESULTS: Of 200 calves in the final analysis, 58 (29%; 95% CI: 22.8-35.8%) were classified as NE and 142 calves as non-NE. In univariate analysis, factors significantly associated with diagnosis of NE included male sex, presence of dystocia, abnormal position in the birth canal, and prolonged labor. In the multivariate model, only orientation of the calf in the birth canal remained significant (OR 2.14; 95% CI: 1.02-4.49; P = 0.044). Overall survival of calves with NE was good (45/58; 77.6%; 95% CI: 64.7-87.5); dam parity and being a twin was significantly associated with nonsurvival. CONCLUSIONS: Calves born after dystocia, especially if malpresented, should be closely monitored for nursing behavior within the first 24 hours of life. Prognosis for survival is good, but supportive care might be required for several days.

Thrombocytosis in 715 Dogs (2011-2015).

BACKGROUND: Thrombocytosis is a hematologic abnormality in dogs that has been associated with various neoplastic, metabolic, and inflammatory conditions. OBJECTIVE: To classify thrombocytosis in dogs based on severity and evaluate whether there are associations between severity and underlying disease processes. ANIMALS: Seven hundred and fifteen dogs with thrombocytosis and 1,430 dogs with normal numbers of platelets. METHODS: Retrospective study. Medical records of dogs with increased (>500 × 103 /µL; thrombocytosis group) and normal (300-500 × 103 /µL; control group) platelet counts between 2011 and 2015 were reviewed. Dogs were characterized by severity of platelet increase and diagnosis. Diagnostic categories included neoplasia, endocrine disease, inflammatory disease, or miscellaneous. RESULTS: A total of 1,254 complete blood counts with thrombocytosis from 715 dogs were included in the study. Median platelet count in this population was 582 × 103 /µL (500-1,810 × 103 /µL). No correlation between severity of thrombocytosis and diagnosis was identified. Causes of secondary thrombocytosis included neoplasia (55.7%), endocrine disease (12.0%), and inflammatory disease (46.6%). Immune-mediated disease was common (22.2%), associated with frequent glucocorticoid administration, and had a significantly higher median platelet count (636 × 103 /µL [500-1,262 × 103 /µL] versus 565 × 103 /µL [500-1,810 × 103 /µL]) when compared to the other inflammatory processes (P < 0.001). The diagnoses in the thrombocytosis dogs differed significantly from the control population (P < 0.001). CONCLUSIONS AND CLINICAL IMPORTANCE: Thrombocytosis is commonly associated with carcinoma and immune-mediated disease in dogs.

Factors Associated with Survival in 97 Horses with Septic Pleuropneumonia.

BACKGROUND: Septic pleuropneumonia is a common cause of morbidity and mortality in horses, but there is limited data available regarding factors associated with survival. HYPOTHESIS/OBJECTIVES: To identify factors predictive of survival in horses with septic pleuropneumonia. ANIMALS: A total of 97 horses with septic pleuropneumonia at 2 referral institutions. METHODS: A retrospective study was performed. A diagnosis of septic pleuropneumonia was based on the presence of sepsis, pleural effusion, and positive bacterial culture from tracheal aspiration (TA) or pleural fluid (PF). RESULTS: Thirty-one percent of horses had a recent history of travel. Clinical signs included lethargy (78%), tachycardia (75%), tachypnea (60%), fever (43%), prolonged capillary refill time (22%), and ventral edema (14%). The most common clinicopathologic abnormality was hyperfibrinogenemia (79%). Increased serum creatinine concentration at presentation was negatively associated with survival (OR, 5.13; CI, 1.88-14.01; P = .001) and return to work (OR, 6.46; CI, 1.10-37.92; P = .034). Eighty-four TA and 67 PF samples were submitted for culture, 98 and 84% of which were positive, respectively. The most common isolate was Streptococcus equi subsp zooepidemicus. Tracheal aspirates were more sensitive than PF for bacterial growth, but some organisms isolated from PF were not isolated from TA. Thoracotomy was positively associated with survival (OR, 0.13; CI, 0.01-0.83; P = .028). CONCLUSIONS AND CLINICAL IMPORTANCE: Increased serum creatinine concentration is a negative prognostic indicator and is likely a reflection of dehydration. Submission of TA and PF is recommended. Thoracotomy should be considered as a treatment for pleuropneumonia.

Impact of rare variants in ARHGAP29 to the etiology of oral clefts: role of loss-of-function vs missense variants.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a prevalent, complex congenital malformation. Genome-wide association studies (GWAS) on NSCL/P have consistently identified association for the 1p22 region, in which ARHGAP29 has emerged as the main candidate gene. ARHGAP29 re-sequencing studies in NSCL/P patients have identified rare variants; however, their clinical impact is still unclear. In this study we identified 10 rare variants in ARHGAP29, including five missense, one in-frame deletion, and four loss-of-function (LoF) variants, in a cohort of 188 familial NSCL/P cases. A significant mutational burden was found for LoF (Sequence Kernel Association Test, p = 0.0005) but not for missense variants in ARHGAP29, suggesting that only LoF variants contribute to the etiology of NSCL/P. Penetrance was estimated as 59%, indicating that heterozygous LoF variants in ARHGAP29 confer a moderate risk to NSCL/P. The GWAS hits in IRF6 (rs642961) and 1p22 (rs560426 and rs4147811) do not seem to contribute to the penetrance of the phenotype, based on co-segregation analysis. Our data show that rare variants leading to haploinsufficiency of ARHGAP29 represent an important etiological clefting mechanism, and genetic testing for this gene might be taken into consideration in genetic counseling of familial cases.

Risk factors for treatment-related adverse events in cancer-bearing dogs receiving piroxicam.

Piroxicam has antitumour effects in dogs with cancer, although side effects may limit its use. The purpose of this study was to retrospectively identify factors predisposing cancer-bearing dogs to adverse events (AEs) following piroxicam therapy. Medical records of dogs presented to the Purdue Veterinary Teaching Hospital between 2005 and 2015 were reviewed, and 137 dogs met the criteria for study inclusion. Toxic effects of piroxicam in these dogs were graded according to an established system. Multivariate logistic regression was used to estimate the extent to which certain factors affected the risk for AEs. Age [odds ratio (OR) 1.250, P = 0.009; 95% confidence interval (CI) 1.057-1.479] and concurrent use of gastroprotectant medications (OR 2.612, P = 0.025; 95% CI 1.127-6.056) significantly increased the risk for gastrointestinal AEs. The results of this study may help inform the risk versus benefit calculation for clinicians considering the use of piroxicam to treat dogs with cancer.

What's New in Old Horses? Postmortem Diagnoses in Mature and Aged Equids.

Postmortem findings in 241 equids admitted to a teaching hospital that were at least 15 years old at autopsy were reviewed (1) to determine disease prevalence, (2) to compare the cause of death (or euthanasia) in equids 15 to 19 years of age (n = 116) with that in equids ≥20 years of age (n = 125), and (3) to catalog coexisting lesions in equids with pituitary pars intermedia dysfunction (PPID). Breed and sex were evenly distributed between the age groups. Death or euthanasia was attributed to disease of the digestive system (41.5%), pituitary gland (12.9%), locomotor system (10.0%), nervous system (7.9%), cardiovascular system (4.6%), urinary system (4.6%), reproductive system (4.2%), respiratory system (4.2%), integumentary system (4.2%), lymphoid system (2.5%), liver (2.5%), or systemic neoplasia (1.2%). Nervous system disease was more common in the 15- to 19-year group; urinary tract disease was more common in the ≥20-year group. Neoplastic disease, regardless of systemic location, was the basis for death or euthanasia in 18.7% of all equids. Squamous cell carcinoma, lymphoma, and melanoma were the most common malignant neoplasms. PPID was the most common specific diagnosis, based on the postmortem presence of hyperplasia or adenoma, and was the reason for euthanasia in 47.7% of 65 equids with PPID. The most common nonpituitary causes for death or euthanasia in equids with PPID were colic, lameness, cancer, and spinal cord disease. Coexisting conditions in equids with PPID that were not considered the basis for euthanasia included neoplasms, infections, lameness, and recurrent airway obstruction.

Effect of Feeding an Iodine-Restricted Diet in Cats with Spontaneous Hyperthyroidism.

BACKGROUND: Exclusive feeding of an iodine-restricted diet has been proposed as a method for controlling clinical manifestations of hyperthyroidism in hyperthyroid cats. OBJECTIVES: To determine the effect of feeding an iodine-restricted diet on TT4 concentrations and clinical signs in cats with spontaneous hyperthyroidism. ANIMALS: Forty-nine client-owned cats with spontaneous hyperthyroidism. METHODS: Retrospective case series. Hyperthyroid cats were exclusively fed a commercially available iodine-restricted diet. Clinical response was assessed by change in weight and heart rate and serum TT4, blood urea nitrogen (BUN), and creatinine concentrations at various times during dietary management (21-60 days, 60-180 days). RESULTS: Serum TT4 normalized in 20/48 cats (42%) and 39/47 cats (83%) at 21-60 days and 61-180 days, respectively. Cats in which the TT4 concentrations were still above reference range at 21-60 days had a significantly higher starting TT4 than those that normalized their TT4 levels during the same time period (P = .038). Body weight did not significantly increase (P = .34) nor heart rate decrease (P = .64) during the study. There was a significant decrease in serum creatinine (P = .028). Cats in the low reference range for serum TT4 concentrations did not have a significant increase in body weight (P = .41) nor creatinine (P = .54) when compared to those with high reference range. CONCLUSIONS AND CLINICAL IMPORTANCE: Restricted-iodine diets were effective at maintaining serum TT4 concentrations within reference ranges for a majority of cats with spontaneous hyperthyroidism over 1 year, although not all clinical signs of hyperthyroidism improved.

Ex vivo biomechanical comparison of barbed suture and standard polypropylene suture for acute tendon laceration in a canine model.

OBJECTIVES: Evaluate performance and resistance to gap formation of a non-absorbable, barbed, monofilament suture, in comparison with a non-absorbable, smooth, monofilament polypropylene suture, in two different suture patterns: three-loop pulley (3LP) and modified Bunnell-Mayer (BM). SAMPLE SIZE: Seventy-two medium-sized cadaveric superficial digital flexor muscle tendon units. METHODS: After manual transection and suture repair, individual specimens were placed in an electromechanical tensile testing machine and tested to monotonic failure using tensile ramp loading. Video data acquisition allowed evaluation of failure mode and quantification of gap formation. RESULTS: Incidence of gap formation between tendon ends was significantly greater in tenorrhaphies repaired with barbed suture compared to those repaired with smooth polypropylene. Use of a 3LP suture pattern caused significantly less gapping between tendon ends when compared to the BM pattern. CONCLUSION: Smooth polypropylene suture was consistently superior in load performance than a unidirectional barbed suture. The 3LP pattern was more resistant than a BM pattern at preventing gap formation. CLINICAL SIGNIFICANCE: Smooth polypropylene should be recommended over barbed unidirectional suture for use in canine tendinous repair to provide increased resistance to gap formation. The 3LP is superior to the BM suture pattern, requiring significantly more force to cause tenorrhaphy gap formation and failure, which may translate to increased accrual of repair site strength and tendinous healing in clinical situations.

Genome-wide methylation analysis in Silver-Russell syndrome patients.

Silver-Russell syndrome (SRS) is a clinically heterogeneous disorder characterised by severe in utero growth restriction and poor postnatal growth, body asymmetry, irregular craniofacial features and several additional minor malformations. The aetiology of SRS is complex and current evidence strongly implicates imprinted genes. Approximately, half of all patients exhibit DNA hypomethylation at the H19/IGF2 imprinted domain, and around 10% have maternal uniparental disomy of chromosome 7. We measured DNA methylation in 18 SRS patients at >485,000 CpG sites using DNA methylation microarrays. Using a novel bioinformatics methodology specifically designed to identify subsets of patients with a shared epimutation, we analysed methylation changes genome-wide as well as at known imprinted regions to identify SRS-associated epimutations. Our analysis identifies epimutations at the previously characterised domains of H19/IGF2 and at imprinted regions on chromosome 7, providing proof of principle that our methodology can detect DNA methylation changes at imprinted loci. In addition, we discovered two novel epimutations associated with SRS and located at imprinted loci previously linked to relevant mouse and human phenotypes. We identify RB1 as an additional imprinted locus associated with SRS, with a region near the RB1 differentially methylated region hypermethylated in 13/18 (~70%) patients. We also report 6/18 (~33%) patients were hypermethylated at a CpG island near the ANKRD11 gene. We do not observe consistent co-occurrence of epimutations at multiple imprinted loci in single SRS individuals. SRS is clinically heterogeneous and the absence of multiple imprinted loci epimutations reflects the heterogeneity at the molecular level. Further stratification of SRS patients by molecular phenotypes might aid the identification of disease causes.

Predictive value of ex vivo biodynamic imaging in determining response to chemotherapy in dogs with spontaneous non-Hodgkin's lymphomas: a preliminary study.

Biodynamic imaging (BDI) is a novel phenotypic cancer profiling technology which optically characterizes changes in subcellular motion within living tumor tissue samples in response to ex vivo treatment with cancer chemotherapy drugs. The purpose of this preliminary study was to assess the ability of ex vivo BDI to predict in vivo clinical response to chemotherapy in ten dogs with naturally-occurring non-Hodgkin's lymphomas. Pre-treatment tumor biopsy samples were obtained from all dogs and treated ex vivo with doxorubicin (10 µM). BDI measured six dynamic biomarkers of subcellular motion from all biopsy samples at baseline and at regular intervals for 9 h following drug application. All dogs subsequently received doxorubicin to treat their lymphomas. Best overall response to and progression-free survival time following chemotherapy were recorded for all dogs. Receiver operating characteristic (ROC) curves were used to determine accuracy and identify possible cut-off values for the BDI-measured biomarkers which could accurately predict those dogs' cancers that would and would not respond to doxorubicin chemotherapy. One biomarker (designated 'MEM') showed 100% discriminative capability for predicting clinical response to doxorubicin (area under the ROC curve = 1.00, 95% CI 0.692-1.000), while other biomarkers also showed promising predictive capability. These preliminary findings suggest that ex vivo BDI can accurately predict treatment outcome following doxorubicin chemotherapy in a spontaneous animal cancer model, and is worthy of further investigation as a technology for personalized cancer medicine.

Diagnostic accuracy of a urine reagent strip to identify bacterial peritonitis in dogs with ascites.

The leukocyte esterase test pad on a urine dipstick has been used as a preliminary test for bacterial peritonitis in humans but has not previously been evaluated in dogs. Here, free abdominal fluid from 60 dogs was tested on the leukocyte esterase test pad and results were compared with culture and microscopic analysis. Depending on the 'gold standard' comparator, the dipstick had sensitivity of ~60-75%, specificity of ~91-92%, positive predictive value of ~69%, and negative predictive value of ~87-94%. Based on these data, it appears that the leukocyte esterase test pad is most useful for tentative identification of cases in which bacterial infection is unlikely. Therefore a negative test may aid in re-directing clinician attention to alternative diagnoses in dogs with free abdominal effusion, whereas a positive result implies the necessity for further diagnostic tests.

Environmental exposures and airway inflammation in young thoroughbred horses.

BACKGROUND: Inflammatory airway disease (IAD) in horses is a widespread, performance-limiting syndrome believed to develop in response to inhaled irritants in the barn environment. OBJECTIVES: To evaluate changes in bronchoalveolar lavage fluid (BALF) cytology and exposure to particulates, endotoxin, and ammonia during horses' first month in training. ANIMALS: Forty-nine client-owned 12- to 36-month-old Thoroughbred horses entering race training. METHODS: In this prospective cohort study, a convenience sample of horses was assigned to be fed hay from a net (n = 16), whereas the remaining horses were fed hay from the ground (n = 33). BALF was collected at enrollment and after 14 and 28 days in training. Respirable particulate, inhalable particulate, respirable endotoxin, and ammonia concentrations were measured at the breathing zone of each horse weekly. RESULTS: Median respirable particulates were significantly higher when horses were fed from hay nets than when fed hay from the ground (hay net 0.28 mg/m(3) , no hay net 0.055 mg/m(3) , P < .001). Likewise, inhalable particulate (hay net 8.3 mg/m(3) , no hay net 3.3 mg/m(3) , P = .0064) and respirable endotoxin (hay net 173.4 EU/m(3) , no hay net 59.2 EU/m(3) , P = .018) exposures were significantly higher when horses were fed from hay nets. Feeding hay from a net resulted in significantly higher BALF eosinophil proportions over time (P < .001). BALF eosinophils were significantly related to respirable particulate exposure (14 days in training rs = 0.37, P = .012, 28 days in training, rs = 0.38, P = .017). CONCLUSIONS AND CLINICAL IMPORTANCE: Pulmonary eosinophilic inflammation develops in response to respirable particulate exposure in young Thoroughbreds, indicating a potential hypersensitivity to inhaled particulate allergens.