Whole blood manganese concentrations in dogs with primary hepatitis.

OBJECTIVES: Increased whole blood manganese concentrations have been reported in humans with primary liver disease. Due to the neurotoxic effects of manganese, altered manganese homeostasis has been linked to the development of hepatic encephalopathy. Whole blood manganese concentrations are increased in cases of canine congenital portosystemic shunts, but it remains unclear whether dogs with primary hepatopathies also have altered manganese homeostasis. METHODS: Whole blood manganese concentrations were measured by graphite furnace atomic absorption spectrometry in 21 dogs with primary hepatitis, 65 dogs with a congenital portosystemic shunt, 31 dogs with non-hepatic illnesses and 18 healthy dogs. RESULTS: The whole blood manganese concentrations were significantly different between dogs with primary hepatitis, dogs with non-hepatic illnesses and healthy dogs (P=0·002). Dogs with primary hepatitis had significantly increased whole blood manganese concentrations compared with healthy dogs (P<0·05) and dogs with non-hepatic illnesses (P<0·01). Dogs with primary hepatitis had significantly lower whole blood manganese concentration compared with dogs with congenital portosystemic shunts (P=0·0005). CLINICAL SIGNIFICANCE: Dogs with primary hepatopathies have increased concentrations of whole blood manganese although these concentrations are not as high as those in dogs with congenital portosystemic shunts. The role of altered manganese homeostasis in canine hepatic encephalopathy is worthy of further study.

A comparison of factors that influence survival in dogs with adrenal-dependent hyperadrenocorticism treated with mitotane or trilostane.

BACKGROUND: Trilostane is a recognized treatment for canine pituitary-dependent hyperadrenocorticism (PDH); however, its efficacy in dogs with adrenal-dependent hyperadrenocorticism (ADH) is unknown. OBJECTIVES: To examine factors that might influence survival in the medical management of ADH, with particular emphasis on treatment selection. ANIMALS: Thirty-seven animals referred to 4 centers over a period of 12 years that had been diagnosed with ADH and treated with either trilostane (22/37), mitotane (13/37), or both (2/37). METHODS: Retrospective analysis of clinical records. RESULTS: There was no statistically significant difference between the survival times of 13 dogs treated only with mitotane when compared with 22 dogs treated only with trilostane. The median survival time for animals treated with trilostane was 353 days (95% confidence interval [CI] 95-528 days), whereas it was 102 days (95% CI 43-277 days) for mitotane. Metastatic disease was detected in 8 of 37 dogs. There was a significantly lower probability of survival for dogs with metastatic disease when compared with those without metastatic disease (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: The choice of medical treatment for ADH may not have a major effect on survival times. However, the presence of metastatic disease considerably decreases survival time regardless of the choice of medical treatment.

Caecal impaction and chronic intestinal pseudo-obstruction in a dog.

A 10-year-old female neutered cross-breed dog presented with a 4-month history of chronic intermittent diarrhoea and vomiting. Abdominal ultrasound showed dilated loops of small intestine and a suspected faecolith. Exploratory surgery revealed a caecal impaction and a typhlectomy was performed. Histopathological examination of caecal and full thickness small intestine sections demonstrated atrophy of smooth muscle fibres as well as an influx of plasma cells, lymphocytes and macrophages, and mild lymphoplasmacytic and eosinophilic enteritis. This combination of caecal impaction and chronic intestinal pseudo-obstruction has not been reported previously in the dog.

Traumatic partial hypopituitarism in a cat.

Traumatic hypopituitarism was diagnosed in an 11-month-old male neutered cat. The presenting complaints were polydipsia, polyuria and lethargy of three months' duration. Craniocerebral trauma, as a result of a road traffic accident, had preceded the onset of clinical signs by six weeks. Neurological examination revealed right-sided mydriasis, reduced visual and tactile left forelimb placing reflexes and decreased proprioception in both the left fore- and hindlimb. Initial laboratory findings included hypernatraemia, hyperchloraemia, mild azotaemia, eosinophilia and isosthenuria. Low basal cortisol, thyroxine, thyroid-stimulating hormone and insulin growth factor-1 were noted. Subsequent to treatment with prednisolone, a water deprivation test confirmed the presence of central diabetes insipidus and therapy with synthetic antidiuretic hormone successfully ameliorated the polydipsia.

A potential causal association between gastrointestinal disease and primary polydipsia in three dogs.

Polydipsia, defined as a water intake of over 100 ml/kg/day, is a common presenting medical complaint in dogs. Polydipsia can be secondary (eg, to central or nephrogenic diabetes insipidus) or primary in origin, where increased water intake cannot be explained as a response to obligatory water loss. Primary polydipsia is confirmed by ruling out other known causes of polydipsia and demonstrating that renal concentrating ability is intact. The causes and associations of primary polydipsia in dogs are poorly defined. This report describes three dogs presented with signs of gastrointestinal disease with concurrent polydipsia. Investigations (including water deprivation testing) showed normal renal urinary concentrating ability and indicated primary polydipsia. Treatment of the gastrointestinal signs resulted in resolution of the polydipsia in each case. This is the first description of a possible association between gastrointestinal disease and primary polydipsia in the dog, the pathophysiology of which remains obscure.

Assessment of an ECG event recorder in healthy dogs in a hospital environment.

Ambulatory electrocardiography techniques are superior to standard electrocardiography in evaluating rhythm disturbances in dogs with episodic weakness or collapse. Disadvantages include cumbersome equipment, short recording periods and an inherent delay in trace analysis. A small programmable cardiac event recorder with combined automatic and owner-triggered recording capability was evaluated in 13 healthy dogs in a hospital environment. The unit was well tolerated and produced diagnostic recordings directly to a personal computer, with useful information about continuous heart rate. It detects premature complexes, pauses and bradycardias according to programmed detection thresholds. These events were counted frequently but trace review revealed concerns regarding specificity. Recordings were often triggered by sinus arrhythmia, sinus tachycardia and unclassifiable rate changes rather than by clinically significant arrhythmias. Correct detection of ventricular ectopic complexes, a single supraventricular premature complex, sinus arrest and second-degree atrioventricular block occurred in individual dogs. Visual review of all automatically recorded events was essential and significantly increased the time required for event recording analysis. Manual recordings might be more useful and the overall results suggest that further studies are warranted to evaluate the system in clinical cases in the home environment.

Trilostane treatment of a dog with functional adrenocortical neoplasia.

A 13-year-old, crossbreed dog presented with a history of recent onset polydipsia, progressive lethargy, weakness and reduced appetite. Blood tests showed raised concentrations of alkaline phosphatase and alanine aminotransferase with marginally low serum potassium. There was a leucocytosis with a mature neutrophilia and no eosinophils. Endocrine tests showed a normal aldosterone concentration and an exaggerated adrenocorticotropic hormone (ACTH) stimulation test, consistent with a diagnosis of hyperadrenocorticism (HAC). A diagnosis of adrenal-dependent HAC was made, based on the presence of a calcified mass involving the left adrenal gland, and hepatomegaly, on radiography and ultrasonography. The owners declined surgical adrenalectomy. Medical management with trilostane rapidly improved the clinical signs and normalised the serum chemistry. ACTH stimulation tests showed an improvement in post-ACTH cortisol concentrations and were used to make dose adjustments where necessary. At the time of writing, no adverse side effects had been seen and the dog remained well after 80 weeks of treatment.

Cholelithiasis and hyperthyroidism in a cat.

A 14-year-old domestic short-hair cat presented with a history of intermittent malaise and increased drinking. A diagnosis of hyperthyroidism and cholelithiasis was made by a combination of blood testing, radiography and ultrasonography. After medical management of hyperthyroidism, thyroidectomy and cholecystectomy were successfully performed. Removed choleliths were comprised of calcium carbonate and bilirubinate. Histopathological analysis of tissue suggested low grade pancreatic and hepatobiliary disease, as well as hyperthyroidism, might have contributed to stone formation.

In situ hybridization as a technique for the immunological investigation of canine intestine: jejunal expression of IFNgamma and IL10 in Irish setters and beagles.

In situ hybridization (ISH) has found numerous applications in biology and medicine. However, its use to demonstrate expression of cytokines within the canine small intestine has not been described. Digoxigenin-labelled riboprobes complementary to mRNA encoding canine IFNgamma and IL10 were used to demonstrate expression of these cytokines within formalin-fixed, paraffin-embedded sections of jejunum obtained from healthy control Irish setter (IS) dogs (n = 4), gluten-sensitive IS in remission (n = 7), and beagles with high enteric bacterial populations (n = 5). Proportional areas of cells within the lamina propria showing one of three mutually exclusive staining intensities were measured, as well as the total stained area. Intensity categories were chosen arbitrarily to represent cells showing weak, moderate or dense staining (grades 1-3 respectively), reflecting increasing expression of mRNA. Control and gluten-sensitive IS showed similar total and grade-by-grade areas of expression of IFNgamma and IL10 in the lamina propria (p>0.05), in contrast to beagles, which showed greater total and grade 1 areas of expression of IFNgamma, and greater total, grade 1 and grade 2 areas of expression of IL10, than both groups of IS (p<0.05). Epithelial expression of both cytokines was demonstrated in beagles and IS, but differences between groups for each cytokine were not apparent (p>0.05). This study has validated the use of in situ hybridization for the detection of IFNgamma and IL10 mRNA within canine intestinal biopsies, andhas shown heightened jejunal expression of both cytokines in beagles with high enteric bacterial populations.

Gastrointestinal immunity in health and disease.

The gastrointestinal lymphoid tissue (GALT) is under constant antigenic challenge from bacteria and food and must be able to distinguish between benign and pathogenic organisms. Recent advances in understanding the organization and function of GALT reveal how it is able to direct appropriate immune responses according to the nature of the antigen and how inappropriate immune responses can lead to local and systemic immunopathology and/or infection. The interaction of the normal bowel flora and GALT is critical to normal local and systemic immune function and plays a major role in the pathogenesis of some immune-related diseases. This review draws upon information from veterinary, human, and laboratory animal studies to provide an update of mechanisms and consequences of function and dysfunction in the gastrointestinal immune system.

Humoral and cell-mediated responses to Malassezia pachydermatis in healthy dogs and dogs with Malassezia dermatitis.

The in vitro proliferative responses of peripheral blood mononuclear cells from seven healthy basset hounds exposed to Malassezia pachydermatis antigen (500 micrograms/ml) exceeded (P < 0.05) those of seborrhoeic basset hounds with high populations of M pachydermatis and eight Irish setters with gluten-sensitive enteropathy. The stimulation indices in the latter two groups and in eight healthy beagles were comparable. The stimulation indices of the four groups after exposure to phytohaemaglutinin did not differ significantly. The serum titres of M pachydermatis-specific IgG and IgA measured by enzyme-linked immunosorbent assays (ELISA) in 21 seborrhoeic basset hounds and 11 affected dogs of various breeds exceeded those of 14 healthy basset hounds and eight healthy beagles (P < 0.01 for IgG, P < 0.05 for IgA). Total serum IgA concentrations measured by ELISA in the affected dogs were not lower than those of healthy dogs.

Insulin-like growth factor axis of gluten-sensitive dogs during a gluten challenge.

Eight gluten-sensitive Irish setters underwent a gluten challenge to investigate changes in the insulin-like growth factor (IGF) axis. In the first study, they were challenged with an acute intraduodenal administration of tryptic-peptic gluten digest and then maintained on dietary gluten for three months. In the second study, the challenge came solely from dietary gluten fed for three months. After the acute intraduodenal administration of gluten, serum IGF-I levels decreased significantly by 21.8 per cent, (P = 0.01) on day 3 after challenge and then returned to normal. There was also a decrease (52.5 per cent, P < 0.03) in the levels of serum IGF-binding protein-3 (IGFBP-3) until day 14 after challenge but they had returned to normal by day 28. In two dogs IGFBP-3 levels decreased through specific serum protease activity. There were no changes in serum IGF-I or IGFBP levels during the second study after the dietary gluten challenge alone, or in four non-gluten-sensitive beagles studied as controls during the acute intraduodenal/dietary gluten challenge.

Risk factors for gastric dilatation in Irish setter dogs.

Questionnaires were used to obtain data about Irish setters with gastric dilatation (GD) and control Irish setters. The risk of GD increased with age (P < 0.01) but was not associated with gender. Age and gender-matched controls were compared with cases (n = 74). Predisposing risks were aerophagia (unadjusted odds ratio 12.44, P < 0.001), a single food type (adjusted odds ratio 3.15, P < 0.01) and feeding once daily (adjusted odds ratio 2.90, P < 0.02). Apparent risk from a dry food diet and a condition score of less than 2 was not confirmed by logistic regression. Precipitating risks were recent kennelling (unadjusted odds ratio 100, P < 0.005) or a car journey (unadjusted odds ratio 3.29, P < 0.025). No risk was attributed to intensity or duration of exercise, temperament, appetite, speed of eating, vomiting or diarrhoea.

Canine major histocompatibility complex genes DQA and DQB in Irish setter dogs.

Information about genetic variation within the canine major histocompatibility complex (MHC) class II genes is limited. In common with most other vertebrate species the canine MHC, or DLA, includes genes which are homologous to human DR, DQ, and DP. Recently, at least one functional DLA DQ gene-pair has been characterized, but so far systematic screening efforts have been lacking. In the present study, we sequenced both cDNA and genomic clones derived from DLA DQ genes of Irish setter dogs. This breed was of interest, since it shows a high prevalence of gluten sensitive enteropathy (GSE), which may be a useful animal model for celiac disease (CD) of man. Interestingly, few of the alleles found in Irish setters were identical to those previously detected in other breeds. Three novel DLA DQA and four novel DLA DQB alleles were discovered in 19 unrelated dogs. Strong association between certain HLA DQ alleles and CD of man prompted us to screen the DQ alleles of members of a family of gluten-sensitive Irish setter dogs. No haplotypes or alleles were shared by all affected dogs, but one frequent haplotype in this family was also detected in an unrelated gluten-sensitive Irish setter; this haplotype was absent in the healthy dogs. This observation warrants further investigation by screening the DQ alleles of a large population of unrelated gluten-sensitive Irish setters.

Quantitative and qualitative immunohistochemistry of T cell subsets and MHC class II expression in the canine small intestine.

In man and rodents, cells of the gastrointestinal immune system include B and T lymphocytes, granulocytes, macrophages and dendritic cells. Abnormalities in leucocyte numbers and function have been described in diseases of humans, such as coeliac disease and inflammatory bowel disease. The purpose of this study is to describe the normal distribution of T cells and MHC Class II expression in the small intestine of clinically normal dogs, to allow subsequent comparison with disease states. Full-thickness sections of duodenum, jejunum and ileum from seven young adult beagle dogs were immediately snap-frozen following euthanasia. Avidin-biotin-enhanced immunocytochemistry was used to detect expression of canine CD3, CD4, CD8 and MHC Class II antigens. Positively stained lamina propria cells were quantified using an eyepiece graticule, and positively stained intraepithelial cells by counts per 100 epithelial cells. In the lamina propria, the density of all leucocyte subsets was significantly increased towards the villus tip for all regions (p < 0.05). There was no apparent difference in the distribution of CD3+, CD4+ and CD8+ leucocytes between the three portions of the small intestine. The ratios of CD4+ cells to CD8+ cells in the lamina propria and epithelium were 59:41 and 15:85, respectively. Subtractive analysis suggested that 50-55% of CD3+ intraepithelial cells were CD4-CD8-. MHC Class II expression was apparent upon lamina propria cells with a dendritic morphology, as well as round cells. Epithelial MHC Class II expression was apparent in 7/7 ileal sections, compared with only 1/7 duodenal and 1/7 jejunal sections. This study shows that the small intestinal mucosa of the dog contains similar leucocyte populations to those found in other species, and suggests that these cells may play similar roles in gastrointestinal immunity.

Intestinal permeability and function in dogs with small intestinal bacterial overgrowth.

Small intestinal bacterial overgrowth (SIBO) has been reported to occur commonly in dogs with signs of chronic intestinal disease. There are usually few intestinal histological changes, and it is uncertain to what extent bacteria cause mucosal damage. The aim of this study was to apply a differential sugar absorption test for intestinal permeability and function to the objective assessment of intestinal damage in dogs with SIBO. Studies were performed on 63 dogs with signs of chronic small and, or, large bowel disease, in which SIBO (greater than 10(5) total or greater than 10(4) anaerobic colony forming units/ml) was diagnosed by quantitative culture of duodenal juice obtained endoscopically. None of the dogs had evidence of intestinal pathogens, parasites, systemic disease or pancreatic insufficiency. differential sugar absorption was performed by determining the ratios of urinary recoveries of lactulose/rhamnose (L/R ratio, which reflects permeability) and D-xylose/3-O-methylglucose (X/G ratio, which reflects intestinal absorptive function) following oral administration. Dogs with SIBO comprised 28 different breeds, including 13 German shepherd dogs. SIBO was aerobic in 18/63 dogs (29 per cent), and anaerobic in 45/63 (71 per cent). Histological examination of duodenal biopsies showed no abnormalities in 75 per cent, and mild to moderate lymphocytic infiltrates in 25 per cent of the dogs. The L/R ratio was increased (greater than 0.12) in 52 per cent, and the X/G ratio reduced (less than 0.60) in 33 per cent of the dogs. Differential sugar absorption was repeated in 11 dogs after their four weeks of oral antibiotic therapy. The L/R ratio declined in all 11 dogs (mean +/- SD pre: 0.24 +/- 0.14; post: 0.16 +/- 0.11; P < 0.05), but changes in the X/G ratio were more variable. These findings show that SIBO is commonly associated with mucosal damage not detected on histological examination of intestinal biopsies, and that changes in intestinal permeability following oral antibiotics may be used to monitor response to treatment.