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.

Serum haptoglobin concentrations in dogs with liver disease.

Dogs with liver disease have been shown to have increased serum C-reactive protein (CRP) concentrations. However, it is unclear whether dogs with liver disease also have increased serum haptoglobin concentrations. The aim of the study was to measure serum haptoglobin concentrations in healthy dogs, hospitalised dogs and dogs with liver diseases. Haptoglobin concentrations were measured in 30 healthy dogs, 47 hospitalised dogs with non-hepatic illness, 46 dogs with congenital portosystemic shunt (cPSS) and 11 dogs with primary hepatopathy. Haptoglobin concentrations were not significantly different between cPSS dogs with and without hepatic encephalopathy (HE), thus all cPSS dogs were considered as one group. Haptoglobin concentrations were significantly different between the remaining groups (P<0.0001). Hospitalised ill dogs had significantly higher haptoglobin concentrations than healthy dogs (P<0.001), dogs with cPSS (P<0.001) and dogs with primary hepatopathy (P<0.05). There was no significant difference between haptoglobin concentrations in healthy dogs, dogs with cPSS and dogs with primary hepatopathy. Haptoglobin concentrations were not significantly increased in dogs with liver diseases or in dogs with cPSS and HE. This is in contrast with the previously reported CRP results. This study demonstrates that liver function should be considered when interpreting haptoglobin concentrations in dogs.

Combined Z-plasty and phalangeal fillet for reconstruction of a large carpal defect following ablative oncologic surgery.

A six-year-old Labrador Retriever was presented for management of a 2 x 2 cm cutaneous mass over the dorsal aspect of the carpus. A fine needle aspirate performed by the referring veterinarian was consistent with a mast cell tumour. The ipsilateral prescapular lymph node was enlarged. Preoperative staging did not reveal any evidence of metastasis. Wide excision of the mass and prescapular lymphadenectomy were performed. The large carpal wound was reconstructed using a combination of Z-plasty and phalangeal fillet using the first digit (dewclaw); about 20% of the original defect was allowed to heal by second intention. Histopathology was consistent with a grade II mast cell tumour with metastatic spread to the lymph node. Vinblastine and prednisolone adjuvant chemotherapy was instituted. Functional and cosmetic outcome were good; only a small 1cm area of alopecia persisted. The dog was disease-free 53 months after surgery. A combination of Z-plasty and a phalangeal fillet using the first digit was a successful treatment to reconstruct a large wound over the dorsal aspect of the carpus in this case.

Partial ear canal ablation and lateral bulla osteotomy in rabbits.

Six lop rabbits were presented with clinical signs of otitis media or externa. The presence of disease was confirmed by computerized tomography examination, with two rabbits suffering from bilateral disease. The rabbits were anaesthetized and underwent surgery of the affected bulla. Rabbits with bilateral disease had a minimum of 2 weeks between procedures. A single vertical incision was made over the base of the vertical canal, which was bluntly dissected free from surrounding tissue. The ventral portion of the vertical canal was removed and a lateral bulla osteotomy was performed. The mucosa at the base of the dorsal vertical canal was apposed and the aural cartilage sutured to form a blind-ending pouch open at the pretragic incisure. Histopathological samples taken from the dorsal margin of the vertical canal yielded subtle and non-specific changes in the six samples submitted. All rabbits were discharged within 48 hours of surgery. The cosmetic outcome was excellent with animals retaining visually normal aural anatomy. The partial ear canal ablation/lateral bulla osteotomy procedure is quick and has a good cosmetic result when performed in rabbits.

An unusual morphology of patent ductus arteriosus in a dog.

A 12-week old, entire female Border terrier weighing 3·5 kg was presented for investigation of a continuous left heart base murmur. The clinical presentation and preoperative echocardiogram were consistent with a standard morphology of patent ductus arteriosus (PDA) but a discrete ductal vessel was not identified during surgical dissection. Surgery had to be abandoned due to deterioration of the patient's condition under general anaesthesia which led to cardiorespiratory arrest and death despite attempts at resuscitation. Necropsy identified a recess within the wall of the aorta communicating with the pulmonary artery via an ostium at the heart base which determined this structure as an intramural PDA. This morphology of PDA is previously unreported. This report demonstrates that an intramural PDA is not readily identifiable surgically because of the absence of a discrete ductal vessel and it is important to appreciate that unusual morphologies of PDA may occur.

Identification of tumour initiating cells in feline head and neck squamous cell carcinoma and evidence for gefitinib induced epithelial to mesenchymal transition.

Feline oral squamous cell carcinoma is considered a highly invasive cancer that carries a high level of morbidity. Despite aggressive surgery, patients often succumb to disease, the tumour having inherent insensitivity to radiation and chemotherapy. In this study we sought to identify cells within the feline SCC1 line that have stem cell properties, including inherent resistance mechanisms. When feline cells were subjected to harsh growth conditions, they formed sphere colonies consistent with a stem cell phenotype. Utilising CD133, we were able to identify a small fraction of cells within the population that had enhanced sphere-forming ability, reduced sensitivity to radiation and conventional chemotherapy and demonstrated resistance to the EGFR-targeting drug, gefitinib. In addition, long-term culture of feline SSC1 cells in gefitinib caused a change in cell morphology and gene expression reminiscent of an epithelial to mesenchymal transition. Taken together, these results suggest that feline SCC may be driven by small subset of cancer stem cells.

Dogs with congenital porto-systemic shunting (cPSS) and hepatic encephalopathy have higher serum concentrations of C-reactive protein than asymptomatic dogs with cPSS.

Hepatic encephalopathy (HE) is a cause of significant morbidity and mortality in patients with liver disorders and a wide range of rodent models of HE have been described to facilitate studies into the pathogenesis and treatment of HE. However, it is widely acknowledged that no individual model perfectly mimics human HE and there is a particular need for spontaneous, larger animal models. One common congenital abnormality in dogs is the portosystemic shunt (cPSS) which causes clinical signs that are similar to human HE such as ataxia, disorientation, lethargy and occasionally coma. As inflammation has recently been shown to be associated with HE in humans, we hypothesised that inflammation would similarly be associated with HE in dogs with cPSS. To examine this hypothesis we measured C-reactive protein (CRP) in 30 healthy dogs, 19 dogs with a cPSS and no HE and 27 dogs with a cPSS and overt HE. There was a significant difference in CRP concentration between healthy dogs and dogs with HE (p < 0.001) and between dogs with HE and without HE (p < 0.05). The novel finding that there is an association between inflammation and canine HE strengthens the concept that HE in dogs with cPSS shares a similar pathogenesis to humans with HE. Consequently, dogs with a cPSS may be a good spontaneous model of human HE in which to further examine the role of inflammation and development of HE.

Chronic gastric instability and presumed incomplete volvulus in dogs.

Chronic gastric volvulus in dogs results in long-standing gastrointestinal signs unlike those of acute gastric dilatation and volvulus. This report describes chronic gastric volvulus in seven dogs. The majority of dogs presented with weight loss, chronic vomiting, lethargy and abdominal pain. A combination of radiographic, ultrasonographic and endoscopic imaging indicated altered positioning of gastric landmarks. Dynamic changes were identified in some cases. Exploratory coeliotomy and surgical gastropexy were performed in all dogs. Clinical signs improved or resolved in six of seven dogs postoperatively. Chronic gastric volvulus is an uncommon condition in dogs, but should be considered as a differential in cases presenting with the above clinical signs.

Retained surgical swabs in 13 dogs.

To report the signalment, history, clinical signs, diagnostic and surgical findings and outcome in dogs and cats with retained swabs, medical records of dogs and cats that were referred to four referral centres were reviewed. Cases in which a retained surgical swab was identified during surgery at the referral hospital were selected for further study. The signalment, history, clinical signs, diagnostic and surgical findings and outcome in these cases were reviewed. Thirteen dogs with retained surgical swabs were included in the study. Bodyweight ranged from 9 to 45 kg. The initial surgery was a 'non-routine' abdominal procedure in seven dogs, ovariohysterectomy in five dogs and perineal hernia repair in one dog. Time from initial surgery to presentation at the referral centre ranged from four days to seven years. Treatment involved major surgery in eight of the 13 dogs. Outcome was excellent in 12 of 13 cases, one dog was euthanased.

Epidermal growth factor receptor as a therapeutic target in veterinary oncology.

Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor that stimulates cell proliferation and survival and becomes dysregulated in a range of solid tumours in man. It is recognized as a key oncogenic driver and has become a favoured therapeutic target and a prognostic and predictive marker of cancer in man. In animals, EGFR dysregulation is emerging as a potential factor in the development of a number of naturally occurring tumours including mammary, lung, glial and epithelial cancers. Comparative analyses suggest that these diseases share many features with equivalent diseases in man and EGFR may have value as a prognostic or a biological marker of animal disease. There is still little direct evidence that EGFR is a critical oncogenic driver in naturally occurring animal disease and there are no veterinary trials of EGFR-targeted therapy. These will be critical steps in establishing a role for EGFR in veterinary oncology.

Expression of epidermal growth factor receptor (EGFR) and Ki67 in feline oral squamous cell carcinomas (FOSCC).

The aims of this study were to establish expression of epidermal growth factor receptor (EGFR) and Ki67 in 67 archived biopsy samples of feline oral squamous cell carcinomas (FOSCCs) and to establish if the expression of either markers was predictive of survival. Samples were immunohistochemically labelled for the two proteins and scored. Statistical analyses of data, including Kaplan-Meier survival curves, were performed. All samples expressed both markers although levels differed between samples. Median overall survival was 46 days and 1-year survival was 5%. There was no correlation between Ki67 and EGFR scores (Pearson's correlation coefficient, P = 0.861). Low cellular proliferation (low Ki67 score) was positively correlated with an overall longer survival (Log Rank, P = 0.02) and a trend towards better survival for the high EGFR group was observed (Log Rank, P = 0.076). Ki67 and EGFR immunostaining in FOSCC may be of value as biochemical markers for screening of biopsies from cases of FOSCC.

Delayed-onset urinary incontinence in five female dogs with ectopic ureters.

This case series describes five female dogs with congenital ectopic ureter presenting with delayed-onset urinary incontinence out of 22 female dogs diagnosed with ectopic ureter over a 102-month period at a veterinary teaching hospital. All five dogs improved following surgical treatment of ectopic ureter, but only three remained continent long-term without further intervention. Delayed-onset urinary incontinence in female dogs with ectopic ureters may be more common than the current literature suggests. Congenital ectopic ureter should be considered and investigated as a possible contributing factor in female dogs presenting with delayed-onset urinary incontinence.

Assessment of the incidence of GDV following splenectomy in dogs.

OBJECTIVE: To establish if splenectomy increases the incidence of gastric dilatation and volvulus (GDV) in dogs. METHODS: Two case-series studies of cases and controls were performed. Records of dogs that had undergone splenectomy (37 cases) were compared with records of dogs that had undergone other abdominal surgery (43 cases). Records of dogs that presented for non-elective gastropexy (33 cases) were compared with records of dogs presented to the hospital for unrelated reasons (39 cases). Survival following splenectomy and development of GDV in the first 12 months following surgery were retrieved from the clinical records and by questionnaire-based canvassing of the referring clinician. The incidence of GDV following splenectomy was established and the association between a current episode of GDV and previous splenectomy was assessed. RESULTS: There was no evidence that splenectomy was associated with an increased incidence of subsequent GDV (P=0.469). No association between a current episode of GDV and previous splenectomy was found. CLINICAL SIGNIFICANCE: Splenectomy is not associated with an increase in the incidence of GDV.

Whole blood manganese concentrations in dogs with congenital portosystemic shunts.

BACKGROUND: Manganese (Mn) is an essential mineral that is a cofactor for many enzymes required in the synthesis of proteins, carbohydrates, and lipids. Because hepatic clearance is essential in Mn homeostasis, conditions in humans resulting in hepatic insufficiency including cirrhosis and both acquired and congenital portosystemic shunting have been reported to result in increased blood Mn concentrations and increased Mn content in the central nervous system. Because Mn toxicity causes neurologic disturbances, increased Mn concentrations have been implicated in the pathogenesis of hepatic encephalopathy. HYPOTHESES: Dogs with congenital portosystemic shunts (cPSS) have significantly higher whole blood Mn concentrations than do healthy dogs or those with nonhepatic illnesses. ANIMALS: Eighteen dogs with cPSS, 26 dogs with nonhepatic illnesses, and 14 healthy dogs. METHODS: Whole blood Mn was measured by graphite furnace atomic absorption spectrometry. The diagnosis of cPSS was made by ultrasonography or during celiotomy either by visual inspection of a shunting vessel or portovenography. RESULTS: Dogs with a cPSS had significantly higher whole blood Mn concentrations than did healthy dogs and dogs with nonhepatic illnesses. Whole blood Mn concentrations were not significantly different between healthy dogs and dogs with non-hepatic illnesses. CONCLUSION AND CLINICAL IMPORTANCE: Dogs with a cPSS have significantly increased whole blood Mn concentrations. Additional studies are warranted to investigate the role of Mn in cPSS-associated hepatic encephalopathy.

The use of porcine small-intestinal submucosa for abdominal wall reconstruction--a clinical case.

A seven-year-old miniature dachshund was presented with a large contaminated bite wound centred on the left costal arch. Survey radiographs revealed a pneumomediastinum, a mid-body fracture of the left 11th rib and luxation of the xiphisternum. The compromised skin, ribs, xiphisternum, diaphragm and abdominal wall were surgically debrided. This resulted in a large combined thoracic and abdominal wall defect. The thoracic cavity was closed by diaphragmatic advancement. The abdominal wall defect was partially closed by advancing local abdominal musculature. A cranial abdominal mid-line defect remained and was repaired using two sheets of lyophilised porcine small-intestinal submucosa. Dehiscence of the skin exposing the SIS graft was seen but the abdominal repair remained intact. Eighteen months after the initial injury, the dog remained clinically well and no associated complications were reported.

Neurological dysfunction in three dogs and one cat following attenuation of intrahepatic portosystemic shunts.

Neurological dysfunction is an uncommon complication following extrahepatic portosystemic shunt ligation. Three dogs and one cat are described that developed neurological signs within 21 to 42 hours of attenuation of intrahepatic portosystemic shunts. None of these cases had biochemical evidence of hepatic encephalopathy postoperatively. Two dogs died during management of status epilepticus following aspiration of food. One dog died six months postoperatively. The cat had persistent neurological dysfunction at discharge, but was alive and had recovered most of its neurological function at the time of writing, 37 months after surgery. This report demonstrates the potential for animals with intrahepatic portosystemic shunts to develop postoperative neurological signs and highlights the difficulty of managing such cases. Two dogs had both intrahepatic and extrahepatic portosystemic shunts. Large intestinal malrotation (partial situs inversus) may have been linked to the development of a portosystemic shunt in the remaining dog.

Myelin proteolipid proteins promote the interaction of oligodendrocytes and axons.

Although proteolipid protein (PLP) and its DM20 isoform are the major membrane proteins of CNS myelin, their absence causes surprisingly few developmental defects. In comparison, missense mutations of the X-linked Plp gene cause severe dysmyelination. Previous studies have established roles for PLP/DM20 in the formation of the intraperiod line and in maintaining axonal integrity. We now show that a normal number of oligodendrocytes are present in mice lacking PLP/DM20. However, in heterozygous females, which are natural chimeras for X-linked genes, oligodendrocytes lacking PLP/DM20 are in direct competition with wild-type oligodendrocytes that have a distinct advantage. PLP+ oligodendrocytes and PLP+ myelin sheaths make up the greater majority, and this feature is generalised in the CNS throughout life. Moreover, in the absence of PLP/DM20, a proportion of small-diameter axons fails to myelinate, remaining ensheathed but lacking a compact sheath, or show delayed myelination. These findings suggest that PLP/DM20 is also involved in the early stages of axon-oligodendrocyte interaction and wrapping of the axon.

The proteolipid protein gene and myelin disorders in man and animal models.

The two proteins, proteolipid protein and DM20, which are encoded by alternative transcripts from the proteolipid protein ( PLP ) gene, are major components of central nervous system myelin. In man, mutations of these proteins cause Pelizaeus-Merzbacher disease (PMD), an X-linked dysmyelinating neuropathy. The mutations found are very varied, ranging from deletions, loss-of-function and missense mutations to additional copies of the gene. This same range of known genetic defects has been observed in animal models with spontaneous and engineered Plp gene mutations. The relationship between genotype and phenotype is remarkably close in the animal models and the PMD cases, making them useful models for studying the mechanisms of PLP gene-related disease. As a result, it has become clear that the PLP gene plays a wider role in neural development in addition to its function as a structural component of myelin. It has also emerged that duplications of the PLP gene are the commonest mutation in PMD. Genetic disorders arising from a dosage effect may be more common than previously recognized. The study of the PLP gene in this rare disorder is, therefore, contributing both to our understanding of neural development and maintenance and to the mechanisms of human genetic disorders.