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.

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.

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.

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.

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.

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.

Expression of transforming growth factor-beta1 (TGF-beta1) and urokinase-type plasminogen activator (u-PA) genes during arterial repair in the pig.

OBJECTIVE: The transition from quiescence to proliferation in vitro is accompanied by early expression of proliferation-associated genes encoding products including cytokines and enzymes. We aimed to investigate TGF-beta1, u-PA and PAI-1 gene expressions in relation to proliferation and extracellular matrix (ECM) protein gene expressions in porcine arteries following injury. METHODS: Right iliac arteries of juvenile pigs were de-endothelialised and harvested at fixed times after injury. RNA was then extracted and analysed by Northern blot analysis. RNA transcripts in thickened neointima of arteries were examined by in situ hybridisation using digoxygenin-labelled cDNA probes. RESULTS: TGF-beta1, u-PA and PAI-1 transcripts were rapidly elevated (2-8h) and preceded a peak in histone mRNA at 24h after arterial injury. A second prolonged rise in TGF-beta1 mRNA at 4d coincided with elevated ECM protein gene expression. TGF-beta1 gene expression was detected in neointimal cells lining the arterial lumen at 4wk after injury. CONCLUSIONS: The timings of increases in TGF-beta1, u-PA and PAI-1 mRNAs in injured arteries are consistent with contributions to processes prior to proliferation. The observation of a second protracted elevation in TGF-beta1 expression is supportive of an additional role in stimulation of ECM protein synthesis. Functional specialisation exists within the thickened intima of arteries late in repair.

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.

TP53 gene mutation status in pretreatment biopsies of oesophageal adenocarcinoma has no prognostic value.

Identification of markers which help to predict response to treatment and overall survival at the time of diagnosis would assist in the management of patients with oesophageal adenocarcinoma. In the present study we investigated the prognostic significance of mutations to the TP53 tumour suppressor gene in a large, consecutive series of oesophageal adenocarcinomas. The incidence of TP53 mutation determined by molecular analysis of endoscopic biopsy specimens was 36% (49/135). No statistically significant difference was observed in patient survival according to the TP53 status of the tumour biopsy. The median survival time for patients with mutation was 12 +/- 1 months compared with 14 +/- 2 months for patients with TP53. These results demonstrate that mutation of the TP53 gene is not a useful predictive marker for patient survival in oesophageal adenocarcinoma.

Concordance between p53 protein overexpression and gene mutation in a large series of common human carcinomas.

Immunohistochemical (IHC) detection of p53 protein was compared with the presence of p53 gene mutation in many colorectal (n = 100), breast (n = 92), endometrial (n = 122), and gastric (n = 116) carcinomas. Two commercially available antibodies, DO7 and CM1, were used for IHC analysis of paraffin-embedded tissue sections. Screening for gene mutations in frozen and paraffin-embedded tumor samples was carried out using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP). The frequency of nuclear staining with DO7 or CM1 for each tumor type, respectively, was colorectal (36%, 23%); breast (15%, 19%); endometrial (21%, 33%); and gastric (23%,-). Overall correlation between the two antibodies for nuclear staining was 90% for the 314 tumors analyzed. Cytoplasmic staining was observed with DO7 in 7% of breast and 5% of gastric carcinomas and with CM1 in 17% of breast and 54% of endometrial carcinomas. p53 gene mutation was found in 39% of colorectal, 28% of breast, 13% of endometrial, and 25% of gastric cancers. The concordance between p53 nuclear overexpression and gene mutation (both positive or both negative) was 68% for colorectal, 79% for breast, 76% for endometrial, and 73% for gastric carcinomas. This study provides further evidence that IHC detection of p53 protein accumulation does not always indicate the presence of a gene mutation and vice versa. Discordant results were observed in approximately 20% to 30% of the tumors studied, highlighting the need for careful characterization of both p53 gene and protein alterations when assessing the relationship between p53 status and tumor behavior.

Clonal analysis of colorectal tumors using K-ras and p53 gene mutations as markers.

Mutations to the K-ras oncogene and p53 tumor suppressor gene are two of the most common genetic lesions in human cancers. In the present study we examined the clonality of colorectal tumors with respect to each of these genetic alterations. Screening for mutations was carried out using the polymerase chain reaction-based technique of single-strand conformation polymorphism. Eleven primary colorectal adenocarcinomas and two secondary adenocarcinomas were analyzed at four different sites within the tumor. Involved pericolic lymph nodes were collected from nine of these cases, a metastatic deposit in the liver was obtained in one case, and adjacent adenomatous lesions were collected in two cases. Seven tumors contained mutations in either the K-ras or p53 genes. In all cases, DNA derived from multiple sites within an individual tumor or metastatic deposits arising from that tumor showed the same pattern of gene mutation. Immunohistochemical staining for p53 protein overexpression also showed similar patterns of reactivity within individual tumors and their metastatic deposits. These results suggest that the major clonal expansion of colorectal carcinomas occurs after the acquisition of mutations in these genes. Our results also indicate that sampling errors are unlikely to occur in molecular studies aimed at defining the role of these genes in colorectal cancer progression.

Single chromosome defect, partial trisomy 1q, in a colon cancer cell line.

The characterization of a single chromosome defect previously reported in a case of inherited nonpolyposis colorectal cancer is the essence of this communication. The defect, originally described as 13p+, is now being defined and the karyotype designated as 46,XY,-13,+der(13)t(1;13)(q32.1;p11).

Effects of epidermal growth factor and mitogenic pathway inhibitors on rat colon cancer proliferation in vitro.

The proliferative responses of two rat colon cancer cell lines (Per192NR and Per237) to concentrations of epidermal growth factor (EGF) were assessed alone, or in combination with calcium sequestration or inhibitors of protein kinase A, C (PKA and PKC). Up to 160nM of EGF stimulated cell proliferation in Per237 cells, but was ineffective in Per192NR cells. In both cell lines all inhibitors failed to alter basal proliferation. In Per192NR cells the combination of 5 to 20nM EGF and inhibitor resulted in a biphasic reduction in basal proliferation which was lost by 20nM. In the Per237 cells only 10nM EGF and PKA inhibitor reduced proliferation. Tumours derived from the same origin respond differently to EGF-induced mitogenesis.

Hypermethylation of the Myf-3 gene in human colorectal cancer.

Abnormal methylation of DNA is one of the earliest detectable changes in human tumors. We investigated hypermethylation of the Myf-3 gene, the human homolog of the mouse myogenic gene Myo-D1, in colorectal adenomas and adenocarcinomas. Histologically normal gut mucosa from colorectal cancer patients showed moderately higher levels of methylation than in other normal tissues. Varying degrees of Myf-3 hypermethylation were found in all five adenomas and eight adenocarcinomas examined. Carcinomas arising from within adenomas generally showed a decrease in both the heterogeneity and intensity of Myf-3 methylation. Regional hypermethylation of this gene therefore appears to be an early event in human colorectal neoplasia.

The early use of operative lumbar sympathectomy in peripheral vascular disease.

The results of operative lumbar sympathectomy for both intermittent claudication and rest pain in 153 patients have been reviewed. Sympathectomy was performed as an initial procedure to further below the groin reconstructive surgery, should symptoms not be alleviated. Five year post-sympathectomy, 67% of the claudicant and 54% of the rest pain patients had avoided further surgery. Patient mortality from other manifestations of atherosclerosis was notably poor at five years and was significantly greater than the sympathectomy failure rate after the first year. The results in diabetics were not significantly different from those in non-diabetics. The possible value of lumbar sympathectomy in both claudication and rest pain is reviewed and discussed.

Heparinization in aortic surgery.

A prospective study was conducted on 35 patients (25 males and 10 females) undergoing elective reconstructive aortic surgery to examine the heparin activity after a bolus dose of sodium heparin (100 U/kg) given five minutes prior to aortic cross clamping. Recording of heparin activity were made 15 minutes later, on release of the aortic clamp, at abdominal wound closure and hourly thereafter until minimal activity was reached. In 10 patients, protamine was used to reverse anticoagulation. These results were related to clinical parameters of age, renal function, plasma cholesterol, blood pressure, position of the aortic clamp and blood loss. High peak levels of heparin activity were more likely in patients with impaired renal function or high plasma cholesterol concentrations. Heparin activity was prolonged at therapeutic levels in patients with renal impairment, and in this group of patients the use of protamine was significantly increased as was the requirement for blood replacement.

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.

Radiological predictors of response to renovascular reconstructive surgery.

The aim of this study was to identify preoperative angiographic criteria which could be used to predict the response to renovascular reconstruction. A cohort of 49 patients who survived for more than 6 months after renovascular reconstruction was studied. All preoperative angiograms were reviewed independently and the renal size, degree of stenosis and the length of the lesion recorded. The response of blood pressure and renal function to surgery were correlated with the angiographic findings. We found that 58% of patients had long-term improvement in blood pressure control, though the response was significantly better where both kidneys were >12 cm in size (82%) compared with when both kidneys were < 12 cm (25%), P < 0.02. The degree of stenosis, while showing a trend towards a better blood pressure response with increasing stenosis, was not a statistically significant factor. None of the angiographic criteria examined could be used to predict the response in renal function. We have shown that the preoperative renal size is the only angiographic factor that may have some role in predicting the response of blood pressure to renovascular reconstruction.