Complications and postoperative non-steroidal anti-inflammatory use of three extracapsular cruciate ligament repair techniques performed in a general practice clinic environment.

OBJECTIVE: To report complications and postoperative non-steroidal anti-inflammatory use associated with fabellotibial suture, Tightrope and Ligafiba Isotoggle procedures performed on dogs of varying weights within a general practice setting. MATERIALS AND METHODS: Clinical records of eligible patients from 2009 to 2018 were retrospectively extracted from five general practice clinics. Data for signalment, patient weight, surgery performed, complications, postoperative use of non-steroidal anti-inflammatory drugs, and timing thereof were extracted and analysed using multinomial logistic regression. Predicted probability tables were generated for complications and non-steroidal anti-inflammatory drug use. RESULTS: The study included 370 surgeries, with 97 fabellotibial suture, 158 Tightrope and 42 Ligafiba Isotoggle procedures in patients less than 15 kg, and 43 fabellotibial suture, 16 Tightrope and 30 Ligafiba Isotoggle procedures in patients at least 15 kg. The proportion of patients that can be expected to have no complications was greatest for older dogs (9 years) weighing less than 15 kg (fabellotibial suture, 91%; Tightrope/Ligafiba Isotoggle, 88%), and the highest major medical and surgical complication risks were expected in young dogs (1 year) weighing over 15 kg (fabellotibial suture, 28%; Tightrope/Ligafiba Isotoggle, 59%). The predicted risk of requiring repeated non-steroidal anti-inflammatory drug prescriptions in the 18-month postoperative period for an 15 kg patient was 37% to 39%. CONCLUSION: Weight and age were significant factors influencing complications and postoperative non-steroidal anti-inflammatory drug use in fabellotibial suture, Tightrope and Ligafiba Isotoggle surgical patients in a general practice setting. CLINICAL SIGNIFICANCE: Clinicians should consider the possibility of complications and requirement for ongoing non-steroidal anti-inflammatory drug use before performing extracapsular procedures in patients weighing more than 15 kg.

Treatment of sacro-coccygeal intervertebral disc extrusion causing tail paresis and faecal incontinence in a dog.

A 4-year 9-month-old beagle was presented for a 2-week history of acute onset of lowered tail carriage and faecal incontinence. Neurological examination was unremarkable except for an absent perineal reflex, there was no history of trauma. Blood work was unremarkable. Lumbosacral and coccygeal CT pre- and post-intravenous contrast revealed a large sacrococcygeal disc extrusion with mineralised material extending from the level of S2 and to midbody of Cd1. A dorsal laminectomy was performed from the cranial margin of S2 to the caudal margin of Cd1. A large volume of mineralised disc material was removed. The material was confirmed on histopathology to be consistent with extruded nucleus pulposus. The patient regained faecal continence within 3 days of hospital discharge. Based on a literature search this is the first report of a sacrococcygeal disc extrusion resulting in faecal incontinence, with successful surgical management.

Lipopolysaccharide and toll-like receptor 4 in dogs with congenital portosystemic shunts.

Surgical attenuation of a congenital portosystemic shunt (CPSS) results in increased portal vein perfusion, liver growth and clinical improvement. Portal lipopolysaccharide (LPS) is implicated in liver regeneration via toll-like receptor (TLR) 4 mediated cytokine activation. The aim of this study was to investigate factors associated with LPS in dogs with CPSS. Plasma LPS concentrations were measured in the peripheral and portal blood using a limulus amoebocyte lysate (LAL) assay. LPS concentration was significantly greater in the portal blood compared to peripheral blood in dogs with CPSS (P = 0.046) and control dogs (P = 0.002). LPS concentrations in the peripheral (P = 0.012) and portal (P = 0.005) blood of dogs with CPSS were significantly greater than those of control dogs. The relative mRNA expression of cytokines and TLRs was measured in liver biopsies from dogs with CPSS using quantitative PCR. TLR4 expression significantly increased following partial CPSS attenuation (P = 0.020). TLR4 expression was significantly greater in dogs that tolerated complete CPSS attenuation (P = 0.011) and those with good portal blood flow on pre-attenuation (P = 0.004) and post-attenuation (P = 0.015) portovenography. Serum interleukin (IL)-6 concentration was measured using a canine specific ELISA and significantly increased 24 h following CPSS attenuation (P < 0.001). Portal LPS was increased in dogs with CPSS, consistent with decreased hepatic clearance. TLR4 mRNA expression was significantly associated with portal blood flow and increased following surgery. These findings support the concept that portal LPS delivery is important in the hepatic response to surgical attenuation. Serum IL-6 significantly increased following surgery, consistent with LPS stimulation via TLR4, although this increase might be non-specific.

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

BACKGROUND: Dogs with congenital portosystemic shunts (CPSS) have hypoplasia of the intrahepatic portal veins. Surgical CPSS attenuation results in the development of the intrahepatic portal vasculature, the precise mechanism for which is unknown, although new vessel formation by angiogenesis is suspected. HYPOTHESIS: That the degree of portal vascular development and the increase in portal vascularization after CPSS attenuation is significantly associated with hepatic vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) gene expression and serum VEGF concentration. ANIMALS: Client-owned dogs with CPSS undergoing surgical treatment. Forty-nine dogs were included in the gene expression data and 35 in the serum VEGF data. MATERIALS AND METHODS: Dogs surgically treated by partial or complete CPSS attenuation were prospectively recruited. Relative gene expression of VEGF and VEGFR2 was measured in liver biopsy samples taken at initial and follow-up surgery using quantitative polymerase chain reaction. Serum VEGF concentration was measured before and after CPSS attenuation using a canine specific ELISA. Statistical significance was set at the 5% level (P ≤ .05). RESULTS: There was a significant increase in the mRNA expression of VEGFR2 after partial attenuation (P = .006). Dogs that could tolerate complete attenuation had significantly greater VEGFR2 mRNA expression than those that only tolerated partial attenuation (P = .037). Serum VEGF concentration was significantly increased at 24 (P < .001) and 48 (P = .003) hours after attenuation. CONCLUSIONS AND CLINICAL IMPORTANCE: These findings suggest that intrahepatic angiogenesis is likely to occur after the surgical attenuation of CPSS in dogs, and contributes to the development of the intrahepatic vasculature postoperatively.

Hepatic hepcidin gene expression in dogs with a congenital portosystemic shunt.

BACKGROUND: Microcytic anemia is common in dogs with a congenital portosystemic shunt (cPSS) and typically resolves after surgical attenuation of the anomalous vessel. However, the pathophysiology of the microcytic anemia remains poorly understood. Hepcidin has been a key role in controlling iron transport in both humans and animals and in mediating anemia of inflammatory disease in humans. The role of hepcidin in the development of microcytic anemia in dogs with a cPSS has not been examined. HYPOTHESIS: To determine whether hepatic hepcidin mRNA expression decreases, while red blood cell count (RBC) and mean corpuscular volume (MCV) increase in dogs after surgical attenuation of a cPSS. ANIMALS: Eighteen client-owned dogs with confirmed cPSS undergoing surgical attenuation. METHOD: Prospective study. Red blood cell count (RBC) and mean corpuscular volume (MCV), together with hepatic gene expression of hepcidin, were measured in dogs before and after partial attenuation of a cPSS. RESULTS: There was a significant increase in both RBC (median pre 6.17 × 10(12) /L, median post 7.08 × 10(12) /L, P < .001) and MCV (median pre 61.5fl, median post 65.5fl, P = .006) after partial surgical attenuation of the cPSS. Despite the increase in both measured red blood cell parameters, hepatic gene expression of hepcidin remained unchanged. CONCLUSIONS AND CLINICAL IMPORTANCE: This study found no evidence that dysregulated production of hepcidin was associated with anemia in dogs with a cPSS.

Ciclosporin modulates the responses of canine progenitor epidermal keratinocytes (CPEK) to toll-like receptor agonists.

Toll-like receptor (TLR) 2 dependent pathways have an important role in the antimicrobial defense of human keratinocytes, and various factors and compounds have been shown to affect those pathways. Investigating Toll-like receptor function in canine keratinocytes and the potential for their modulation is of similar relevance in dogs due to the frequency of staphylococcal skin infections in this species, particularly in the context of canine atopic dermatitis. This pilot study hypothesized that ciclosporin would have a modulatory effect on the cytokine and TLR mRNA expression of canine progenitor epidermal keratinocytes in response to TLR2 agonists. No detectable up-regulation of TLR2, TLR4, IL-8 and TNF-α mRNA was detected following exposure to FSL-1, Pam3CSK4 and staphylococcal peptidoglycan (PGN). Ciclosporin alone did not alter the expression levels of these transcripts but in the presence of ciclosporin, TNF-α mRNA expression was upregulated in response to all three agonists and both TNF-α and IL-8 transcript abundance was increased in response to Pam3CSK4. The enhanced responsiveness of canine keratinocytes to TLR2 agonists in response to ciclosporin may imply that administration of this drug might enhance the innate immune barrier of skin.

Development and validation of a tissue cage model of acute inflammation in the cat.

Four cylindrical silicon tissue cages (TC, internal volume: 6.7 ± 0.11 cm(3)) were inserted subcutaneously in 29 young healthy cats. A mild inflammatory reaction was induced by intracaveal injection of 1 mL of a 2%λ-carrageenan solution. TC exudate was subsequently sampled at predetermined times (up to 120 h) to measure exudate leucocyte counts and the concentrations of protein and eicosanoids. TC remained in situ for 9-10 months and were well tolerated. Leucocyte counts peaked at 34 h (50.1 ± 57.6 × 10(3) cells/mm(3) ) and returned towards baseline after 72 h. Protein concentration increased from 26.2 ± 2.7 g/L to a peak of 35.9 ± 6.0 g/L at 12 h before returning to baseline at 48 h. Exudate prostaglandin (PG)E(2) concentration peaked at 24 h (11.7 ± 13.7 ng/mL) and returned to baseline by 120 h. Repeated collection of fluid from noninjected cages did not increase transudate PGE(2). Ketoprofen (2 mg/kg, subcutaneously) suppressed exudate PGE(2) at 24 h. The carrageenan-stimulated TC model is an ethical and novel means of investigating soft tissue inflammation in the cat, in which exudate PGE(2) acts as surrogate marker of cyclooxygenase-2 activity. This model will facilitate the investigation of in vivo pharmacokinetics and pharmacodynamics of anti-inflammatory drugs in this species.

Vascular endothelial growth factor (VEGF) and VEGF receptor expression in biopsy samples of liver from dogs with congenital portosystemic shunts.

Surgical attenuation of a congenital portosystemic shunt (CPSS) results in increased liver mass, development of intrahepatic portal vasculature and improved liver function. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. The aim of this study was to investigate the role of VEGF and its receptor in the hepatic response to CPSS surgery. The study included 99 dogs with CPSS treated with either partial or complete suture attenuation. Forty-four dogs with partial attenuation underwent a second surgery for complete attenuation. The expression of VEGF and VEGF receptor 2 (VEGFR2) in biopsy samples of liver was assessed by immunohistochemistry with rabbit anti-human VEGF polyclonal antibody and mouse anti-human VEGFR2 monoclonal antibody. Expression of these molecules was graded. The proportion of samples expressing VEGF was significantly greater in samples from dogs with CPSS compared with control samples (P=0.04) and the proportion of samples expressing VEGFR2 was significantly greater in control samples compared with samples from dogs with CPSS (P=0.04). VEGF labelling grade decreased significantly (P=0.038) and VEGFR2 increased significantly (P=0.046) between first and second surgery. The decrease in VEGF may reflect transient expression, preferential expression of other factors, reperfusion of existing vessels and/or increased angiogenesis before surgery in the form of arterialization and subsequent reduction due to improved portal blood flow. Partial suture attenuation was associated with a degree of 'normalization' of VEGF and VEGFR2 expression when compared with the control samples. Further investigation is needed to provide more information on the hepatic response to CPSS surgery.

Treatment of extrahepatic congenital portosystemic shunts in dogs - what is the evidence base?

A variety of surgical treatments and medical therapies are recommended for dogs with extrahepatic congenital portosystemic shunts (CPSS). The objective of this review was to assess the evidence base for the management of extrahepatic CPSS in dogs. An online bibliographic search was performed in November 2010 to identify articles relating to the question "Which of the treatment options for extrahepatic CPSS in dogs offers the best short- and long-term outcomes?" Articles were assigned a level of evidence based on a modified grading system. Thirty-eight articles were included in the review. Thirty-six articles were classified as grade 4 and two as grade 5. The timings and methods of assessment of short- and long-term outcomes varied widely between studies. One prospective study (grade 4a) showed that surgically treated dogs survived significantly longer than medically treated dogs. Four retrospective studies (grade 4b) compared the outcome of two surgical techniques but there were no statistically significant differences between treatment groups in terms of complications or outcome. The review found that the evidence base for the treatment of extrahepatic CPSS is weak. There is a lack of evidence of short- and long-term outcomes to recommend one treatment over another.

Expression of Toll-like receptor 2 in duodenal biopsies from dogs with inflammatory bowel disease is associated with severity of disease.

There is growing evidence that aberrant innate immune responses towards the bacterial flora of the gut play a role in the pathogenesis of canine inflammatory bowel disease (IBD). Toll-like receptors (TLR) play an important role as primary sensors of invading pathogens and have gained significant attention in human IBD as differential expression and polymorphisms of certain TLR have been shown to occur in ulcerative colitis (UC) and Crohn's disease (CD). The aim of the current study was to evaluate the expression of two TLR important for recognition of commensals in the gut. TLR2 and TLR4 mRNA expression in duodenal biopsies from dogs with IBD was measured and correlated with clinical and histological disease severity. Endoscopic duodenal biopsies from 20 clinical cases and 7 healthy control dogs were used to extract mRNA. TLR2 and TLR4 mRNA expression was assessed using quantitative real-time PCR. TLR2 mRNA expression was significantly increased in the IBD dogs compared to controls, whereas TLR4 mRNA expression was similar in IBD and control cases. In addition, TLR2 mRNA expression was mildly correlated with clinical severity of disease, however, there was no correlation between TLR2 expression and histological severity of disease.

Preliminary experiences of the triple tibial osteotomy procedure: tibial morphology and complications.

OBJECTIVE: To document the effect of variable tibial morphology on the planning and execution of the triple tibial osteotomy (TTO) procedure in dogs and complications encountered while becoming familiar with the technique. METHODS: The records of 21 consecutive cases that had a TTO performed were reviewed. Preoperative tibial morphology was assessed. Modifications in the described technique and complications were documented. Postoperative outcome was evaluated using a client-based questionnaire. RESULTS: The size of the tibial wedge ostectomy was modified because of variable tibial morphology in four dogs (19 per cent) to avoid over or under correction of the tibial plateau angle (TPA). Intraoperatively, fracture through the caudal tibial cortex occurred in nine cases (41 percent) and through the distal tibial crest cortex in four cases (18 percent). Major complications occurred in five (23 per cent) of cases with four (18 per cent) requiring further surgery. The client questionnaire results demonstrated significant improvements in all parameters and no significant difference from the preinjury status. CLINICAL SIGNIFICANCE: TPA measurement is recommended when planning a TTO to avoid over or under correction of the TPA. Despite frequent minor complications, it appears that the TTO is an effective procedure for management of cranial cruciate ligament rupture in the dog.

Analysis of NOD1, NOD2, TLR1, TLR2, TLR4, TLR5, TLR6 and TLR9 genes in anal furunculosis of German shepherd dogs.

Anal furunculosis (AF) primarily affects German shepherd dogs (GSD) and is characterised by inflammation and ulceration of the perianal tissues with development of cutaneous sinuses or rectocutaneous fistulae. Investigation of pattern recognition receptor (PRR) function has suggested that defective responses might occur in AF-affected GSD. The aim of the current study was to investigate whether canine PRR genes are involved in determining susceptibility to AF in this breed. Chromosomal location and coding sequences for NOD1, NOD2, TLR1, TLR2, TLR4, TLR5, TLR6 and TLR9 were determined and microsatellite markers identified for each gene. Microsatellite genotyping of 100 control GSD and 47 AF-affected GSD showed restricted allelic variation for AHT H91 (associated with TLR5) and REN216 NO5 (associated with both TLR1 and TLR6) compared with non-GSD dogs. Genotyping of single nucleotide polymorphisms identified in canine TLR1, TLR5, TLR6 and NOD2 genes failed to show any significant associations between PRR polymorphisms and AF. The highly restricted PRR genotypes seen in GSD are likely to have resulted from selective breeding and might influence innate immune responses in this breed.

Matrix metalloproteinase mRNA expression in canine anal furunculosis lesions.

Although the aetiology of anal furunculosis (AF) in dogs is poorly understood, there is evidence for an underlying immune dysfunction. This is illustrated by the presence of a T helper type 1 cytokine mRNA profile in AF lesions and the clinical response to ciclosporin therapy. Expression of MMPs 2, 9 and 13 were evaluated in AF lesional biopsies by real-time quantitative RT-PCR. There was significantly increased expression of both MMP-9 and MMP-13 mRNA in AF biopsies compared to controls (p<0.001) but no significant difference in MMP-2 mRNA expression. Since MMP-9 and MMP-13 are primarily produced by macrophages, these data suggest that ulceration could be the result of aberrant activation of this cell type in the tissues. It is feasible that such pathological macrophage activity occurs in response to interferon-gamma secreted by T helper type 1 cells. This could explain why the lesions resolve following treatment with the immunosuppressive drug ciclosporin.

Unusual vascular ring anomaly associated with a persistent right aortic arch in two dogs.

An unusual vascular ring anomaly consisting of a persistent right aortic arch and a left ligamentum arteriosum extending from the main pulmonary artery to an aberrant left subclavian artery and left aortic arch remnant complex was identified in a German shepherd dog and a great Dane. The left subclavian artery and left aortic arch remnant complex originated at the junction between the right distal aortic arch and the descending aorta and coursed dorsal to the oesophagus in a cranial direction. The attachment of the ligamentum arteriosum to the aberrant left subclavian artery was approximately 5 cm cranial to the point of origin of the aberrant left subclavian artery and left aortic arch remnant complex from the descending aorta in both dogs. This anomaly observed in both dogs is similar to an anomaly reported in humans, in which a persistent right aortic arch is found in conjunction with an aberrant left subclavian artery and a left aortic arch remnant (Kommerell's diverticulum). Surgical ligation and division of the left ligamentum arteriosum in both dogs, along with division of the left subclavian artery in the great Dane, resulted in resolution of clinical signs in both of the dogs in this report.

Localised mid-jejunal volvulus following intussusception and enteroplication in a dog.

Ileocolic intussusception was successfully treated surgically by partial enterectomy and enteroplication in an 11-month-old, male neutered German shepherd dog. Segmental intestinal volvulus was identified in the same dog two months later and was managed successfully by a second partial enterectomy. The dog made an uneventful recovery and was free of clinical disease six months after the second surgery. Both conditions are reviewed in this case report and a possible relationship between these two episodes in this dog is discussed.

Aciclovir or ganciclovir universal prophylaxis of cytomegalovirus infection in liver transplantation: an economic analysis.

BACKGROUND: Cytomegalovirus (CMV) following orthotopic liver transplantation can result in significant morbidity and mortality. Prophylaxis with oral aciclovir (ACV) or ganciclovir (GCV) for all transplant recipients (universal prophylaxis) may be beneficial, but which agent is more cost-effective is unknown. METHODS: A single centre, retrospective study of all patients who had OLT at the Western Australian Liver Transplantation Service was performed. Patients received ACV from 1992 to 1998, and GCV from 1999 to 2001. A comparative cost-effectiveness analysis for the two groups was performed based on the mean total cost of the number of cases of CMV infection and disease as the clinical end-point. RESULTS: The ACV group comprised of 55 patients and there were 24 in the GCV group. The incidence of CMV disease was 7% and 4% for the ACV and GCV groups, respectively (P > 0.05). For CMV infection it was 16% and 8%, respectively (P > 0.05). GCV prevented more cases of CMV infection and disease than ACV but at an incremental cost of dollars A20,000 (dollars US10,172) per case prevented. Overall, ACV was more cost-effective than GCV by dollars A2200 (dollars US1119) per person. The cost benefit of ACV was derived principally through a reduced pharmaceutical cost. Both agents were well tolerated without development of antiviral resistance. CONCLUSIONS: Universal prophylaxis of CMV infection-following liver transplantation with aciclovir is more cost-effective than with ganciclovir.

Rural residents' utilisation of health and visiting specialist health services.

INTRODUCTION AND OBJECTIVES: The purpose of the study was to identify the demographic and health service characteristics impacting on rural residents' utilisation of health and visiting specialist services in Western Australia. METHOD: Focus group discussions were held with an age-stratified, randomly selected group of forty-eight residents in four rural Western Australian towns between May and June 2000. RESULTS: Discussions revealed a preference to use local health services for basic care and to travel for the treatment of major or severe illnesses. The focus group participants supported visiting specialist services, indicating a willingness to use them for consultations, diagnostic and minor procedures. Utilisation of visiting services was conditional on the provision of information on specialist reputation, service outcomes, integration of the service into local facilities, and recommendation by the local general practitioner. CONCLUSION: Numerous factors influence the service-seeking behaviour of rural patients. These factors need to be recognised and considered in the design and promotion of resident and visiting specialist services if the migration for health care is to be rationalised.

Adult-to-adult living donor liver transplantation for fulminant hepatic failure.

The outcome of fulminant hepatic failure without timely liver transplantation is poor. We describe a 19-year-old woman with fulminant hepatic failure due to acute hepatitis B infection who received a living donor liver transplant from her sister. The donor's recovery was uneventful, allowing hospital discharge on Day 6. Two months after transplantation the recipient developed a biliary stricture requiring surgery. One year after transplantation, her liver function was normal.

Costs of accessing surgical specialists by rural and remote residents.

INTRODUCTION: Access to surgical specialist services by rural and remote residents in Australia is limited. Little information is available on the cost to rural residents of accessing specialist treatment. The aim of the present study was to define the personal costs incurred by country patients in Western Australia when accessing specialist surgical services in a rural or metropolitan setting. METHODS: A random sample of 50 patients who attended a visiting rural surgical service between December 1998 and February 1999 inclusive was recruited. In a structured telephone interview patients were asked 40 non-clinical questions relating to their recent specialist consultation. The cost of accessing these services was determined from time lost from work, distance and travel expenses. The same formula was then applied to estimate the cost of attending a base metropolitan hospital. The need for an accompanying person was determined from a subset of 16 patients who had transferred to metropolitan specialist consultation in the previous 12 months. Average waiting list times for consultations and common surgical procedures for the visiting service were compared with those for a metropolitan-based service. RESULTS: An estimated saving of AU$1,077 was made per specialist consultation when accessing a local rather than a metropolitan service. Savings were observed in travel time, distance travelled, lost income, provision of an escort and waiting time. CONCLUSION: The present study shows that the personal costs and difficulties incurred by rural and remote residents when accessing specialist treatment can be reduced if a visiting specialist service is available.