Hepatic Gene Expression of Angiogenic and Regeneration Markers in Cats with Congenital Portosystemic Shunts (CPSS).

Congenital portosystemic shunts (CPSS) are vascular anomalies resulting in liver hypoplasia and hepatic insufficiency. Cats with CPSS typically show signs of hepatic encephalopathy associated with increased ammonia, inflammatory cytokines, and oxidative stress. Surgical attenuation of the CPSS results in improved liver function, resolution of clinical signs, and increased portal blood flow. Hepatic gene expression has not previously been investigated in cats with CPSS. Here, we compared the hepatic expression of genes involved in the urea cycle (CPS1, NAGS), angiogenesis (VEGFR2, NPPA, NPR1, NPPC, NPR2, HIF1a), liver regeneration (SERPINB1, HGF, TGFß), and metabolism (FGF21) from a small series of cats (n = 18) with CPSS to that of control cats (n = 10). The expression of TGFß, VEGFR2, HGF, FGF21, and CPS1 was significantly elevated in liver biopsies from cats with CPSS. Cats that could only tolerate partial closure of their CPSS had increased hepatic expression of SERPINB1, HIF1a, and NPR2 compared with those that could tolerate complete ligation. Furthermore, there were no significant correlations between gene expression and pre-operative plasma ammonia concentrations in cats with CPSS. The changes in hepatic gene expression in cats with CPSS are in direct contrast to those seen in dogs with CPSS, suggesting alternative mechanisms may be involved in mediating hepatic changes in cats with CPSS.

Impact of an educational intervention on public perception of brachycephalic obstructive airway syndrome in brachycephalic dogs.

BACKGROUND: The popularity of brachycephalic dogs continues to increase despite inherent breed health problems. Increased education of current and potential brachycephalic dog owners could reduce the desirability of severely affected dogs. METHODS: Members of the general public were prospectively recruited to assess their understanding and opinions of brachycephalic breed-related health problems, before and after an educational intervention on brachycephalic obstructive airway syndrome (BOAS). RESULTS: A total of 587 people participated. Before the intervention most participants considered characteristics of BOAS to be normal for brachycephalic dogs. Following the intervention this was moderately reduced. Responses highlighted that defining 'normal' for a breed is difficult. Referring to a trait as 'normal', even in a negative context results in normalisation. 99.7% of participants had an improved understanding of BOAS following the intervention. However, only 53.0% of the total participants and 29.3% of brachycephalic dog owning participants had their opinion of brachycephalic dogs changed. 99.5% of participants believed that potential owners should be more aware of BOAS and 57.3% of brachycephalic dog owners would have liked further information about breed health problems before purchasing their dog. CONCLUSION: Educational interventions may be beneficial in improving understanding and awareness of BOAS however, normalisation of clinical signs of BOAS remains prevalent.

Postattenuation neurologic signs after surgical attenuation of congenital portosystemic shunts in dogs: A review.

The development of postattenuation neurologic signs (PANS) is a poorly understood and potentially devastating complication after surgical attenuation of congenital portosystemic shunts in dogs. Postattenuation neurologic signs include seizures but also more subtle neurologic signs such as depression, behavioral changes, tremors, and twitching. They most commonly occur within 7 days postoperatively and are typically unrelated to hyperammonemia, hypoglycemia, or electrolyte disturbances. This narrative review summarizes the findings of 50 publications from 1988-2020 that report occurrence of PANS. While most published reports included only dogs affected by postattenuation seizures (PAS), others included dogs with any form of PANS. Overall, PANS (including PAS) affected 1.6%-27.3% of dogs, whereas incidence of PAS ranged from 0%-18.2%. The etiology of PANS remains unknown; however, several theories have been proposed. Risk factors include preoperative hepatic encephalopathy, increasing age, and possibly certain breeds and extrahepatic shunt morphology. There is increasing evidence that prophylactic antiepileptic drugs do not prevent PANS. Treatment is centered around controlling neurologic signs with antiepileptic drugs and providing supportive intensive care. The 30-day survival rate in studies that included a minimum of four dogs affected by PANS was 0%-100% (median, 50.0%) and 0%-75.0% (median, 37.5%) for those with PAS. Mortality associated with PANS was typically related to occurrence of generalized seizure activity. Prognostic factors positively associated with short-term survival included having a history of preoperative seizures and development of focal seizures only. If affected dogs survived to discharge, survival for several years was possible, and the majority of neurologic signs manifested as part of the phenomenon of PANS appeared to resolve.

Long-term outcome and quality of life of dogs that developed neurologic signs after surgical treatment of a congenital portosystemic shunt: 50 cases (2005-2020).

OBJECTIVE: To determine survival time and quality of life of dogs that developed postattenuation neurologic signs (PANS) after surgical treatment of a single congenital portosystemic shunt and survived at least 30 days and identify whether neurologic signs present at the time of discharge would resolve or reoccur. ANIMALS: 50 client-owned dogs. PROCEDURES: Medical records were retrospectively reviewed, and follow-up data relating to neurologic signs and seizure activity were obtained. Owners were asked to complete a questionnaire related to the presence of neurologic signs, including seizures, and their dog's quality of life. RESULTS: Thirty of the 50 (60%) dogs had postattenuation seizures with or without other nonseizure neurologic signs, and 20 (40%) had neurologic signs other than seizures. Neurologic signs had fully resolved by the time of discharge in 24 (48%) dogs. Signs resolved in 18 of the remaining 26 (69%) dogs that still had PANS other than seizures at the time of discharge. Seizures reoccurred in 15 of the 30 dogs that had postattenuation seizures. Twenty-seven of 33 (82%) owners graded their dog's long-term (> 30 days after surgery) quality-of-life as high. Forty-five (90%) dogs survived > 6 months. Most (29/43 [67%]) neurologic signs (other than seizures) present at the time of hospital discharge resolved. CLINICAL RELEVANCE: Findings highlighted that survival times of > 6 months and a high QOL can be achieved in most dogs with PANS that survive at least 30 days. Most neurologic signs other than seizures resolved within 1 month postoperatively. Half of the dogs with postattenuation seizures had a reoccurrence.

Owner reported breathing scores, accelerometry and sleep disturbances in brachycephalic and control dogs: A pilot study.

OBJECTIVES: To compare physical activity and length and quality of sleep between brachycephalic dogs and a control population. METHODS: Brachycephalic and control dogs were prospectively enrolled. Length of activity and sleep were determined via accelerometer use. Owners completed a questionnaire regarding typical daily activity, sleep patterns and an 'owner reported breathing score (ORBS)'. One hour of normal home sleep was recorded for each dog, and a veterinary observer subjectively scored the dogs' sleep quality. RESULTS: Twenty brachycephalic and 15 control dogs were included. There were no differences between age and weight. Owners reported brachycephalic dogs to be less active (p = 0.022) and have higher ORBS (p < 0.001) compared to control dogs. Brachycephalic dogs had increased sleep disturbances compared to control dogs (p = 0.001), and video sleep score was positively correlated with increased sleep disturbances (r2 = 0.47, p = 0.007). There were no differences in active and sleep times based on accelerometry between groups. CONCLUSION: Brachycephalic dogs have more disturbed sleep, which may have negative implications on welfare, but there were no differences in activity or length of sleep between groups. There is evidence that signs suggestive of brachycephalic obstructive airway syndrome (BOAS) as assessed by ORBS is correlated with poorer sleep quality, indicating that reduced sleep quality is part of BOAS. Owners may underestimate disturbed sleep or may perceive disturbed sleep to be normal.

Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells.

C-type natriuretic peptide (CNP) is the major natriuretic peptide of the central nervous system and acts via its selective guanylyl cyclase-B (GC-B) receptor to regulate cGMP production in neurons, astrocytes and endothelial cells. CNP is implicated in the regulation of neurogenesis, axonal bifurcation, as well as learning and memory. Several neurological disorders result in toxic concentrations of ammonia (hyperammonaemia), which can adversely affect astrocyte function. However, the relationship between CNP and hyperammonaemia is poorly understood. Here, we examine the molecular and pharmacological control of CNP in rat C6 glioma cells and rat GPNT brain endothelial cells, under conditions of hyperammonaemia. Concentration-dependent inhibition of C6 glioma cell proliferation by hyperammonaemia was unaffected by CNP co-treatment. Furthermore, hyperammonaemia pre-treatment (for 1 h and 24 h) caused a significant inhibition in subsequent CNP-stimulated cGMP accumulation in both C6 and GPNT cells, whereas nitric-oxide-dependent cGMP accumulation was not affected. CNP-stimulated cGMP efflux from C6 glioma cells was significantly reduced under conditions of hyperammonaemia, potentially via a mechanism involving changed in phosphodiesterase expression. Hyperammonaemia-stimulated ROS production was unaffected by CNP but enhanced by a nitric oxide donor in C6 cells. Extracellular vesicle production from C6 cells was enhanced by hyperammonaemia, and these vesicles caused impaired CNP-stimulated cGMP signalling in GPNT cells. Collectively, these data demonstrate functional interaction between CNP signalling and hyperammonaemia in C6 glioma and GPNT cells, but the exact mechanisms remain to be established.

Incidence and risk factors for neurological signs after attenuation of a single congenital portosystemic shunt in 50 cats.

OBJECTIVE: To determine the incidence, outcome, and risk factors for postattenuation neurological signs (PANS) in cats treated for single congenital portosystemic shunts (CPSS). STUDY DESIGN: Retrospective cohort study. ANIMALS: Cats (n = 50) with a single CPSS. METHODS: Medical records of cats treated by surgical attenuation of a single CPSS between 2003 and 2017 were reviewed for signalment, surgical technique, preoperative management and postoperative clinical outcomes. Binary logistic regression was performed to investigate risk factors for occurrence of PANS and seizures. RESULTS: Congenital portosystemic shunts in 50 cats included 40 extrahepatic and 10 intrahepatic shunts. Postattenuation neurological signs were recorded in 31 (62%) cats and graded as 1 in 10 cats, 2 in nine cats, and 3 in 12 cats. Postattenuation neurological signs included seizures in 11 cats. Five of 31 cats with PANS did not survive to discharge. No association was detected between PANS or seizures and the type of CPSS (intrahepatic or extrahepatic), degree of attenuation, age, or the use of perioperative levetiracetam or hepatic encephalopathy immediately preoperatively. Osmolality at a median 24 hours postoperatively was lower in cats with PANS (P < .049, Wald 3.867, odds ratio [Exp(B)] 0.855, CI 0.732-0.999). CONCLUSION: Postattenuation neurological signs are common complications in cats treated for CPSS. Preoperative levetiracetam did not prevent the occurrence of PANS or seizures. The only risk factor for PANS detected was lower postoperative Osmolality in cats with PANS at 24 hours. CLINICAL SIGNIFICANCE: Postattenuation neurological signs including seizures occur frequently in cats undergoing surgical attenuation of a CPSS. Preoperative levetiracetam did not protect against the development of PANS.

Prognostic factors for short-term survival of dogs that experience postattenuation seizures after surgical correction of single congenital extrahepatic portosystemic shunts: 93 cases (2005-2018).

OBJECTIVE: To identify prognostic factors for short-term survival of dogs that experience seizures within 7 days after surgical correction of single congenital extrahepatic portosystemic shunts (cEHPSS). STUDY DESIGN: Multi-institutional retrospective study. SAMPLE POPULATION: Ninety-three client-owned dogs. METHODS: Medical records at 14 veterinary institutions were reviewed to identify dogs that underwent surgical attenuation of a single cEHPSS from January 1, 2005 through February 28, 2018 and experienced postattenuation seizures (PAS) within 7 days postoperatively. Logistic regression analysis was performed to identify factors associated with 1-month survival. Factors investigated included participating institution, signalment, shunt morphology, concurrent/historical conditions, presence of preoperative neurologic signs, presence of preoperative seizures, aspects of preoperative medical management, surgical details including method and degree of shunt attenuation, type of PAS (focal only or generalized ± focal), drugs administered as part of the treatment of PAS, and development of complications during treatment of PAS. RESULTS: Thirty (32.3%) dogs survived to 30 days. Seventy-six (81.7%) dogs experienced generalized PAS. Factors positively associated with short-term survival included having a history of preoperative seizures (P = .004) and development of focal PAS only (P = .0003). Most nonsurvivors were humanely euthanized because of uncontrolled or recurrent seizures. CONCLUSION: Dogs that experienced PAS that had a history of preoperative seizures and those that experienced focal PAS only had significantly improved short-term survival. CLINICAL SIGNIFICANCE: The results of this study provide information that will help in the counseling of owners who seek treatment for PAS after surgical correction of cEHPSS. © 2020 The American College of Veterinary Surgeons.

Effect of prophylactic treatment with levetiracetam on the incidence of postattenuation seizures in dogs undergoing surgical management of single congenital extrahepatic portosystemic shunts.

OBJECTIVE: To report the incidence of postattenuation seizures (PAS) in dogs that underwent single congenital extrahepatic portosystemic shunt (cEHPSS) attenuation and to compare incidence of PAS in dogs that either did or did not receive prophylactic treatment with levetiracetam (LEV). STUDY DESIGN: Multi-institutional retrospective study. POPULATION: Nine hundred forty dogs. METHODS: Medical records were reviewed to identify dogs that underwent surgical attenuation of a single cEHPSS from January 2005 through July 2017 and developed PAS within 7 days postoperatively. Dogs were divided into 3 groups: no LEV (LEV-); LEV at ≥15 mg/kg every 8 hours for ≥24 hours preoperatively or a 60 mg/kg intravenous loading dose perioperatively, followed by ≥15 mg/kg every 8 hours postoperatively (LEV1); and LEV at <15 mg/kg every 8 hours, for <24 hours preoperatively, or continued at <15 mg/kg every 8 hours postoperatively (LEV2). RESULTS: Seventy-five (8.0%) dogs developed PAS. Incidence of PAS was 35 of 523 (6.7%), 21 of 188 (11.2%), and 19 of 228 (8.3%) in groups LEV-, LEV1, and LEV2, respectively. This difference was not statistically significant (P = .14). No differences between groups of dogs that seized with respect to investigated variables were identified. CONCLUSION: The overall incidence of PAS was low (8%). Prophylactic treatment with LEV according to the protocols that were investigated in our study was not associated with a reduced incidence of PAS. CLINICAL SIGNIFICANCE: Prophylactic treatment with LEV does not afford protection against development of PAS. Surgically treated dogs should continue to be monitored closely during the first 7 days postoperatively for seizures.

Incidence and risk factors for neurological signs after attenuation of single congenital portosystemic shunts in 253 dogs.

OBJECTIVE: To determine the incidence, outcome, and risk factors for postattenuation neurological signs (PANS) and seizures after attenuation of single congenital portosystemic shunts (CPSS) in dogs. STUDY DESIGN: Retrospective cohort study. SAMPLE POPULATION: Dogs (N = 253) with single CPSS. METHODS: Medical records of dogs treated by surgical attenuation of a single CPSS between February 2000 and July 2015 were reviewed for signalment and preoperative and postoperative clinical outcomes, including the occurrence of PANS. Univariable and multivariable binary logistic regression was used to assess risk factors for PANS and for seizures. RESULTS: Twenty-eight (11.1%) dogs developed PANS, including 12 (4.7%) dogs with seizures. Five (17.9%) dogs with PANS did not survive to discharge. Risk factors for PANS included the presence of hepatic encephalopathy (HE) immediately preoperatively (P = .038, odds ratio [OR] 2.704, CI 1.057-6.922) and increasing age (P < .001, OR 1.476, CI 1.223-1.780). Risk factors for seizures included the presence of HE immediately preoperatively (P = .048, OR 3.538, CI 1.013-12.363) and increasing age (P = .009, OR 1.364, CI 1.082-1.720). No association was found between the location of portosystemic shunts (extrahepatic and intrahepatic) and post-operative PANS (P = .532) or seizures (P = .620). Similarly, preemptive administration of levetiracetam did not influence the risk of PANS (P = .991) or seizures (P = .752). CONCLUSION: Preoperative HE and older age in dogs with a CPSS increased the odds of developing PANS and seizures in our population. Preemptive administration of levetiracetam did not protect dogs against the development of PANS or seizures. CLINICAL SIGNIFICANCE: Surgical attenuation of a single CPSS should not be excessively delayed, and surgeons should stabilize the clinical signs of HE before surgery to prevent postoperative PANS and seizures.

Haematology and coagulation profiles in cats with congenital portosystemic shunts.

Objectives The objectives of this study were, first, to report the haematological parameters and coagulation times for cats with a congenital portosystemic shunt (CPSS) and the influence of surgical shunt attenuation on these parameters; and, second, to identify any association between prolongation in coagulation profiles and incidence of perioperative haemorrhage. Methods This was a retrospective clinical study using client-owned cats with a CPSS. Signalment, shunt type (extra- or intrahepatic), degree of shunt attenuation (complete or partial), haematological parameters, prothrombin time (PT) and activated partial thromboplastin time (aPTT) test results, and occurrence of any perioperative clinical bleeding complications were recorded for cats undergoing surgical treatment of a CPSS at the Royal Veterinary College, UK, between 1994 and 2011. Results Forty-two cats were included. Thirty-six (85.7%) had an extrahepatic CPSS and six (14.3%) had an intrahepatic CPSS. Preoperatively, mean cell volume (MCV) and mean cell haemoglobin (MCH) were below the reference interval (RI) in 32 (76.2%) and 31 (73.8%) cats, respectively. Red blood cell count and mean cell haemoglobin concentration (MCHC) were above the RI in 10 (23.8%) and eight (19.1%) cats, respectively. Postoperatively, there were significant increases in haematocrit ( P = 0.044), MCV ( P = 0.008) and MCH ( P = 0.002). Despite the significant increase in MCV postoperatively, the median MCV postoperatively was below the RI, indicating persistence of microcytosis. Preoperatively, PT was above the upper RI in 14 cats (87.5%), and aPTT was above the upper RI in 11 cats (68.8%). No cat demonstrated a perioperative clinical bleeding complication. Conclusions and relevance Cats with a CPSS are likely to present with a microcytosis, but rarely present with anaemia, leukocytosis or thrombocytopenia. Surgical attenuation of the CPSS results in a significant increase in the HCT and MCV. Coagulation profiles in cats with a CPSS are likely to be prolonged, irrespective of shunt type, but do not appear to be associated with an increased risk of clinical bleeding.

Electrosurgery reduces blood loss and immediate postoperative inflammation compared to cold instruments for midline celiotomy in dogs: A randomized controlled trial.

OBJECTIVES: To compare the use of an electrosurgical device with traditional cold instruments (scalpel and scissors) for midline celiotomy incision. STUDY DESIGN: Prospective randomized controlled clinical trial. SAMPLE POPULATION: One hundred and twenty client-owned dogs undergoing abdominal surgery. METHODS: Dogs were prospectively recruited and randomized to receive electroincision or cold instrument incision. For cold incision, surgeons used basic surgical instruments including scalpel and scissors. For electroincision, surgeons only used the electrosurgical device in cutting mode. Time for the approach, blood loss, and the incision length were recorded. A blinded observer assessed pain and incision redness, swelling, and discharge at 24 and 48 hours postoperative (graded 0-3). Owner assessment of incision healing was recorded by telephone interview. RESULTS: Blood loss during surgery was significantly lower for electroincision (mean 0.7, SD 1.7 mL) than cold incision (mean 3.0, SD 4.3 mL, P < .0001) with no significant difference in incision length or time for approach. Electroincision was associated with significantly less incision redness (cold median 1, range 0-3; electroincision median 0, range 0-2, P = .02) and less incision discharge (cold median 0.5 range 0-3; electroincision median 0, range 0-1, P = .006) at 24 hours postoperative. There was no significant difference in pain scores or incision healing in dogs receiving the two techniques. No incisional hernias were reported. A surgical site infection occurred in 1 dog (cold incision). CONCLUSIONS: Electroincision for a celiotomy approach in the dog reduces blood loss, and incision redness and discharge in the immediate postoperative period without affecting the occurrence of wound complications such as infection and dehiscence (including linea alba).

Retrospective evaluation of recurrent secondary septic peritonitis in dogs (2000-2011): 41 cases.

OBJECTIVE: To describe the clinical characteristics of recurrent septic peritonitis in dogs. DESIGN: Multicenter retrospective observational study. ANIMALS: Client-owned dogs with recurrent septic peritonitis. SETTING: Three university emergency and referral hospitals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records from 3 veterinary university teaching hospitals were reviewed and data were collected using a standardized data collection sheet for all cases of septic peritonitis during the study period (2000-2011). Forty one dogs met the inclusion criteria for recurrent peritonitis. All dogs underwent relaparotomy. The original cause of septic peritonitis in these cases included previous surgery for gastrointestinal foreign body removal (n = 26), gastrointestinal neoplasia (n = 3), gastric or duodenal ulceration (n = 3), biliary tract leakage (n = 2), and single instance for each of the following: penetrating foreign body, hernia strangulation, intussusception, mesenteric volvulus, infection of the laparotomy incision, prostatic abscess, and trauma. Eighteen animals survived to discharge. There was no difference detected between survivors and nonsurvivors with recurrent peritonitis in terms of inciting cause, serum albumin concentration, surgical management, or provision of appropriate initial antimicrobials. The survival rate for dogs having recurrent peritonitis was 43.9% (18/41 dogs). CONCLUSIONS: This retrospective study did not identify any significant prognostic indicators for dogs with recurrent peritonitis and that the mortality rate for dogs having more than one surgery for septic peritonitis is similar to that reported for a single surgery for septic peritonitis.

Impact of Facial Conformation on Canine Health: Brachycephalic Obstructive Airway Syndrome.

The domestic dog may be the most morphologically diverse terrestrial mammalian species known to man; pedigree dogs are artificially selected for extreme aesthetics dictated by formal Breed Standards, and breed-related disorders linked to conformation are ubiquitous and diverse. Brachycephaly--foreshortening of the facial skeleton--is a discrete mutation that has been selected for in many popular dog breeds e.g. the Bulldog, Pug, and French Bulldog. A chronic, debilitating respiratory syndrome, whereby soft tissue blocks the airways, predominantly affects dogs with this conformation, and thus is labelled Brachycephalic Obstructive Airway Syndrome (BOAS). Despite the name of the syndrome, scientific evidence quantitatively linking brachycephaly with BOAS is lacking, but it could aid efforts to select for healthier conformations. Here we show, in (1) an exploratory study of 700 dogs of diverse breeds and conformations, and (2) a confirmatory study of 154 brachycephalic dogs, that BOAS risk increases sharply in a non-linear manner as relative muzzle length shortens. BOAS only occurred in dogs whose muzzles comprised less than half their cranial lengths. Thicker neck girths also increased BOAS risk in both populations: a risk factor for human sleep apnoea and not previously realised in dogs; and obesity was found to further increase BOAS risk. This study provides evidence that breeding for brachycephaly leads to an increased risk of BOAS in dogs, with risk increasing as the morphology becomes more exaggerated. As such, dog breeders and buyers should be aware of this risk when selecting dogs, and breeding organisations should actively discourage exaggeration of this high-risk conformation in breed standards and the show ring.

Attenuation of congenital portosystemic shunt reduces inflammation in dogs.

Liver disease is a major cause of morbidity and mortality. One of the most significant complications in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incompletely understood, which has resulted in the development of a wide range of experimental models. Congenital portosystemic shunt is one of the most common congenital disorders diagnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiology of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a congenital portosystemic shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have demonstrated an important role for ammonia and inflammation in the development of hepatic encephalopathy in dogs with a congenital portosystemic shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil, lymphocyte and monocyte concentrations together with C-reactive protein concentrations, would decrease following successful treatment of congenital portosystemic shunts in dogs. One hundred and forty dogs with a congenital portosystemic shunt were enrolled into the study. We found that the proportion of dogs with a monocyte concentration above the reference range was significantly greater in dogs with hepatic encephalopathy at time of initial diagnosis. Importantly, neutrophil and monocyte concentrations significantly decreased following surgical congenital portosystemic shunt attenuation. We also found a significant decrease in C-reactive protein concentrations following surgical attenuation of congenital portosystemic shunts. Our study demonstrates that haematological and biochemical indices of inflammation reduce following successful treatment of the underlying liver disorder.

Strategies for the management and prevention of conformation-related respiratory disorders in brachycephalic dogs.

Brachycephalic (short-muzzled) dogs are increasingly popular pets worldwide, with marked increases in registrations of breeds such as the Pug and French Bulldog over the past decade in the UK. Despite their popularity, many brachycephalic breeds are affected by an early-onset, lifelong respiratory disorder, brachycephalic obstructive airway syndrome (BOAS). This disorder arises due to a mismatch in the proportions of the skull and the soft tissues held within the nose and pharynx, resulting in obstruction of the airway during respiration. Increased airway resistance encourages secondary changes such as eversion of the laryngeal saccules and collapse of the larynx. Clinical signs of BOAS are often early onset and chronic, including dyspnea, exercise intolerance, heat intolerance, and abnormal and increased respiratory noise. Episodes of severe dyspnea can also occur, leading to cyanosis, syncope, and death. BOAS may have a severe impact upon the welfare of affected dogs, compromising their ability to exercise, play, eat, and sleep. Although a well-described condition, with surgical treatments for the palliation of this disorder published since the 1920s, many dogs still experience airway restrictions postsurgically and a compromised quality of life. In addition, the prevalence of this disorder does not appear to have substantially reduced in this time, and may have increased. Ultimately, strategies to improve the breeding of these dogs to prevent BOAS are required to improve brachycephalic health and welfare. Recent studies have revealed conformational risk factors associated with BOAS, such as short muzzles and thick necks, which should be discouraged to avoid perpetuating this serious disorder. Positive changes to brachycephalic health may be impeded by a perception of BOAS being "normal for the breed". This perception must be avoided by owners, breeders, and vets alike to prevent undertreatment of individuals and the perpetuation of this serious disorder to future generations of dogs.

Markers of hepatic regeneration associated with surgical attenuation of congenital portosystemic shunts in dogs.

Dogs with congenital portosystemic shunts (CPSS) have liver hypoplasia and hepatic insufficiency. Surgical CPSS attenuation results in liver growth associated with clinical improvement. The mechanism of this hepatic response is unknown, although liver regeneration is suspected. This study investigated whether markers of liver regeneration were associated with CPSS attenuation. Dogs treated with CPSS attenuation were prospectively recruited. Residual liver tissue was collected for gene expression analysis (seven genes) from 24 CPSS dogs that tolerated complete attenuation, 25 dogs that tolerated partial attenuation and seven control dogs. Relative gene expression was measured using quantitative polymerase chain reaction (qPCR). Blood samples were collected before, 24 h and 48 h post-surgery from 36 CPSS dogs and from 10 control dogs. Serum hepatocyte growth factor (HGF) concentration was measured using a canine specific enzyme-linked immunosorbent assay (ELISA). HGF mRNA expression was significantly decreased in CPSS compared with control dogs (P = 0.046). There were significant increases in HGF (P = 0.050) and methionine adenosyltransferase 2 A (MAT2A; P = 0.002) mRNA expression following partial CPSS attenuation. Dogs with complete attenuation had significantly greater MAT2A (P = 0.024) mRNA expression compared with dogs with partial attenuation. Serum HGF concentration significantly increased 24 h following CPSS attenuation (P < 0.001). Hepatic mRNA expression of two markers of hepatocyte proliferation (HGF and MAT2A) was associated with the response to surgery in dogs with CPSS, and serum HGF significantly increased following surgery, suggesting hepatocyte proliferation. These findings support the concept that hepatic regeneration is important in the hepatic response to CPSS surgery.

Vaginourethroplasty as a salvage procedure for management of traumatic urethral rupture in a cat.

This report describes a cat that suffered pelvic urethral rupture associated with multiple pelvic fractures. A vaginourethroplasty was performed as a salvage procedure, via intrapelvic anastomosis of the proximal urethra to the caudal vagina, following failure of a primary urethral anastomosis. Urinary diversion was achieved via tube cystostomy and a vagino-urethral catheter was maintained for 3 days postoperatively. Anterograde cystourethrography was performed at 7 days and 14 days postoperatively. Absence of contrast leakage from the vagino-urethral anastomosis was documented at 14 days postoperatively and the tube cystostomy was removed. An Escherichia coli urinary tract infection was treated following removal of the tube cystostomy and subsequent urine culture revealed no evidence of urinary tract infection. The cat retained normal urinary continence and elimination behaviour during the 7-month follow-up period. Vaginourethroplasty could be considered as a salvage option for management of traumatic pelvic urethral rupture in the neutered female cat.

Separation of the auricular and annular ear cartilages: surgical repair technique and clinical use in dogs and cats.

OBJECTIVE: To report a surgical technique for primary repair of separation of the annular and auricular cartilages of the ear and long-term outcome. STUDY DESIGN: Case series. ANIMALS: Cats (3) and dogs (2) with ear canal separation. METHODS: Medical records (1998-2007) of dogs and cats with ear canal separation were reviewed. Long-term outcome was obtained by telephone interview of owners or referring veterinarians. RESULTS: Three cats and 1 dog had ear canal separation after being hit by a car; there was no history of trauma in 1 dog. Successful repair was achieved by a caudal approach to the ear canal, identifying and debriding separated cartilage edges and using primary repair. A patent ear canal was confirmed in all animals by otoscopy 4-12 weeks later and by ear canalography in 3 animals. Long-term outcome was excellent with no reported complications 10-90 months later (median 24 months). CONCLUSIONS: Both acute and chronic separation between the annular and auricular cartilages, in the absence of middle ear disease, can be successfully treated using primary repair via a caudal approach to the ear canal, with excellent long-term outcome. CLINICAL RELEVANCE: Primary repair should be considered in animals with separation of the annular and auricular cartilages.

Interleukin-2 and interferon-gamma mRNA expression in canine anal furunculosis lesions and the effect of ciclosporin therapy.

German Shepherd Dogs have an increased incidence of anal furunculosis (AF), which is a disease characterised by inflammation and ulceration of the perianal tissues. Ciclosporin, an immunosuppressive drug, has been successfully used to treat AF, suggesting that the pathogenesis of disease is likely to have an immune-mediated component. Previous research has shown that the cytokine mRNA profile in AF lesions is consistent with T cell-mediated inflammation. The aims of the current study were to quantify IL-2 and IFNgamma mRNA expression in AF biopsies taken before and after treatment with ciclosporin and to compare cytokine expression with lesion severity. Twenty-two dogs with AF were recruited into the study and lesional biopsies were taken prior to ciclosporin therapy. Lesion severity was graded using a visual analogue scale. All dogs were evaluated after 4 weeks of ciclosporin therapy and, in 10 dogs with persistent disease, residual lesions were resected. RNA was extracted from AF-lesional tissue and control perianal tissue samples (n=10), which was used as the template for RT-PCR. Analysis of IL-2 and IFNgamma mRNA expression was performed using real-time PCR. IL-2 and IFNgamma mRNA was consistently detected in pre-treatment AF biopsies and, when quantified, this was significantly increased compared to control tissue (P<0.05). However, no correlation was seen between lesion severity and pre-treatment cytokine mRNA expression. In the ten paired pre- and post-treatment samples, IL-2 mRNA expression was significantly reduced in residual disease tissue following ciclosporin therapy (P=0.013). Treatment with ciclosporin seemed to result in decreased expression of IFNgamma mRNA in AF lesions but this was not statistically significant. In six of the 10 dogs with persistent disease, T cell cytokine mRNA could still be detected in the tissues, suggesting that there was inadequate immunosuppression. The absence of a correlation between T cell cytokine expression and the severity of disease suggests that tissue destruction observed in AF might be a consequence of other inflammatory mediators or downstream effects of T cell activation.