Perinuclear antineutrophilic cytoplasmic antibody and response to treatment in diarrheic dogs with food responsive disease or inflammatory bowel disease

The goal of this study was to investigate the correlation between perinuclear antineutrophilic cytoplasmic antibody (pANCA) and clinical scores before and after treatment in diarrheic dogs with food-responsive disease (FRD) or inflammatory bowel disease (IBD). pANCA serology was evaluated prospectively by indirect immunofluorescence in 65 dogs with signs of gastrointestinal disease, and if positive, pANCA antibody titers were determined. Thirty-nine dogs with FRD responded to a novel diet, and 26 dogs with IBD were treated with corticosteroids. The severity of clinical signs was scored by means of a canine IBD activity index (CIBDAI). At initial examination, a significantly (P = .002) higher percentage of dogs were pANCA-positive in the FRD group (62%) compared with the IBD group (23%). pANCA titers were significantly higher (P = .003) before treatment in the FRD group (median titer 100) compared with the IBD group (median titer 1). However, there was no difference in pANCA titers between the groups after respective treatments because dogs in the IBD group had a significant increase in pANCA titer after treatment. The CIBDAI score decreased significantly (P < .001) after treatment in both groups (74% moderate to severe in FRD dogs before versus 8% after treatment; 85% moderate to severe in IBD dogs before versus 32% after treatment). There was no correlation between pANCA status in FRD or IBD dogs before treatment and scores for CIBDAI, endoscopy, or histopathology before or after treatment, except for the endoscopic duodenal score in dogs with FRD after treatment (P = .03). A positive pANCA test before therapy may aid in the diagnosis of FRD.     

Immune cell populations in the duodenal mucosa of cats with inflammatory bowel disease

The aim of this study was to characterize the phenotype of leukocytes infiltrating the duodenal mucosa of cats with inflammatory bowel disease (IBD) by using immunohistochemistry and computer-aided morphometry to assess whether immunologic markers would aid in characterization of IBD. Frozen and formalin-fixed duodenal biopsies were collected from cats referred for investigation of chronic vomiting, diarrhea, or both (n = 34). Reference ranges were previously established by using duodenal samples from healthy cats (n = 16). No significant difference was found in the number of immunoglobulin G+ (IgG+) or IgA+ in either the villous lamina propria or the crypt lamina propria between cats with IBD and control cats. T cells (CD3+) increased in number from crypt to the tip of the villi in biopsies from both diseased (mean +/- SD for each group was 18.8 +/- 6.6 and 17.7 +/- 4.2 cells/ 10,000 m2 in cryptal areas to 25.2 +/- 9.5 and 29.1 +/- 13.3 cells/10,000m2 in villous areas) and healthy animals (17.9 +/- 3.9 cells/10,000 microm2 in cryptal areas to 24.1 +/- 9.3 cells/10,000 microm2 in villous areas) and no significant difference was found between diseased and control cats. By contrast, major histocompatibility complex (MHC) class II expression by leukocytes with dendritic cell or macrophage morphology in the lamina propria was significantly greater in cats with IBD (13.3 +/- 4.2 cells/10,000 microm2 in cryptal area; P = .016) than in healthy cats (11.9 +/- 3.0 cells/10,000 microm2) and MHC class II expression by enterocytes also was more pronounced in these cats showing an overall intensity of expression of 7.1 +/- 4.0 cells/10,000 microm2 in cats with IBD as opposed to 0.0 +/- 0.0 cells/10,000 microm2 to 0.3 +/- 0.7 cells/10,000 microm2 in healthy cats. These findings suggest that a subtle immunologic dysregulation occurs in spontaneously arising feline IBD.     

Assessment of disease severity and outcome of dietary, antibiotic, and immunosuppressive interventions by use of the canine IBD activity index in 21 dogs with chronic inflammatory bowel disease

Recently, the canine IBD activity index (CIBDAI) was developed for evaluation of the severity of illness, therapeutic strategies, and efficacy of therapy.The aim of the present study was to assess the severity of illness and the therapeutic strategy in dogs with IBD by the use of CIBDAI, serum albumin concentration, and histologic score (HPEG). Furthermore the use of CIBDAI and the efficacy of therapy in a prospective study during a 3 month treatment period were evaluated. Twentyone dogs with inflammatory bowel disease (lymphocytic-plasmacytic enteritis and enterocolitis) were examined in this study. In 11 dogs with IBD the severity of illness was assessed as low, according to CIBDAI and HPEG (CIBDAI score 4 or between 5 and 10 with HPEG score between 1 and 1.5). Six dogs were treated with hypoallergenic diet (Group D), five dogs were treated with hypoallergenic diet and metronidazole (15.6-22,3 mg/kg/day) (Group M). In 10 dogs with IBD the severity of illness was assessed as high (CIBDAI <10, or CIBDAI between 5 and 10 with HPEG score between 2 and 3 or hypoalbuminemia (< or = 2.5 g/dl)). This group (Group I) was treated with immunosuppressive therapy.Treatment consisted of prednisolone (n=10; 0.9-2 mg/kg/day), azathioprine (n=5; 0.9-2.3 mg/kg/day), sulfasalazine (n=4; 18.2-25 mg/kg/day) and hypoallergenic diet (n=10). Efficacy of therapy was evaluated prospectively 3 times in a 12 weeks treatment period. Remission (CIBDAI score < 4) indicated good therapeutic response, chronic or recurrent disease (CIBDAI score persistent or recurrent > or =4) indicated poor therapeutic response. Age, CIBDAI score and HPEG score were significantly different in IBD dogs with low severity of illness (age: median 60 months; CIBDAI score: median 5; HPEG score: median (1) and IBD dogs with high severity of illness (age: median 90 months; CIBDAI score: median 9.5; HPEG score: median 2.25) (p = 0.0101 and p = 0.0099, respectively). The presence of hypoalbuminemia was not significantly different between these two groups (p = 0.3108). There was no significant correlation between CIBDAI score and serum albumin concentration (r = 0.0394; p = 0.0802) or between CIBDAI score and HPEG score (r = 0.2587; p = 0.2574). In the treatment groups, HPEG score was only significantly different between D-group and group I (p < 0.01). The CIBDAI score decreased significantly in group I after 4 weeks of treatment (median 4th week: 3; p < 0.05), and in the D-group after 8 weeks of treatment (median 8" week 1; p < 0.05). No significant decrease of CIBDAI score was seen in the M-group (median 12th week: 1.75; p > 0.05). All dogs in group D, four of five dogs in group M, and six from ten dogs in group I went into remission. Poor therapeutic response (1 dog in group M and 5 dogs in group I; one dog died) was seen in 6 dogs, where as 15 dogs showed good therapeutic response. There was no significant association between efficacy of therapy and age (p = 0.8455), CIBDAI score (p = 0.3293), or serum albumin concentraton (p = 0.8455). Poor therapeutic response was weekly associated with HPEG score > or =2 (p = 0.0635). Using CIBDAI in dogs with IBD as a single parameter to assess the severity of illness and the therapeutic response, misinterpretations are possible.The assessment of the severity of illness by the combination of CIBAI, HPEG, and serum albumin concentration is leading to adaequate therapeutic results. Dogs with low grade IBD benefit from hypoallergenic diet, whereas dogs with high grade IBD benefit from immunosuppressive therapy. The effect of antibiotic treatment is questionable.     

Evaluation of lymphocyte apoptosis in dogs with inflammatory bowel disease

Objective-To determine whether lymphocyte apoptosis in intestinal mucosae is more common in healthy dogs than dogs with inflammatory bowel disease (IBD) and whether numbers of apoptotic cells increase after successful treatment of affected dogs. Animals-8 dogs with IBD (IBD dogs) and 8 healthy control dogs. Procedures-Biopsy specimens of the duodenum and colon were obtained via endoscopy from dogs with IBD before and after 10 weeks of standard treatment and compared with specimens obtained from control dogs. Expression of activated caspase 3 (Casp3), caspase-cleaved fragment p85 from poly-ADP-ribose polymerase (PARP), and B-cell leukemia/lymphoma 2 (Bcl-2) was measured in the duodenal (villous tip and base) and colonic mucosae. Results-Expression of Casp3 was greater in the duodenal villous tips of control dogs, compared with expression in similar tissues from dogs with IBD before or after treatment. Despite clinical improvement of dogs with IBD, expression of Casp3 did not increase after treatment. Expression of PARP did not differ between groups at any time point. Expression of Bcl-2 was greater at all 3 tissue sites in control dogs, compared with expression at the same sites in dogs with IBD. Furthermore, Bcl-2 expression in duodenal villous tips was higher in dogs with IBD after treatment but was not higher elsewhere. In control dogs, expression patterns for all 3 markers were similar between sites (villous tip > villous base > colon). Conclusions and Clinical Relevance-Expression of Casp3 in lymphocytes in duodenal villous tips was significantly reduced in dogs with IBD, compared with expression in healthy dogs, but no increase was detected following successful treatment of IBD. Increased expression of Bcl-2 may be a potential marker of the success of treatment.     

Abundance of mRNA of growth hormone receptor and insulin-like growth factors-1 and -2 in duodenal and colonic biopsies of dogs with chronic enteropathies*

Repair processes of the inflamed intestine are very important for dissolution of chronic enteropathies (CE). Therefore, we examined the mRNA abundance of growth hormone receptor (GHR), insulin-like growth factors (IGF)-1 and -2 in duodenal and colonic biopsies of dogs with CE such as food-responsive diarrhoea (FRD) and inflammatory bowel disease (IBD) before and after treatment as compared with each other and healthy dogs. A clinical score (Canine IBD Activity Index = CIBDAI) was applied to judge the severity of CE. Biopsies of duodenum and colon from client-owned dogs with CE were sampled before (FRD(bef), n = 5; IBD(bef), n = 5) and after treatment (FRD(aft), n = 5; IBD(aft), n = 5). Intestinal control samples were available from a homogenous control population (n = 15; C). Intestinal samples were homogenized, total RNA was extracted, reverse transcribed and analysed by real-time polymerase chain reaction to measure mRNA levels of GHR, IGF-1 and IGF-2. Results were normalized with glyceraldehyde phosphate dehydrogenase as housekeeping gene. The CIBDAI decreased during the treatment period in FRD and IBD (P < 0.01). In duodenum, GHR mRNA levels were higher in all groups than in C (P < 0.001). Duodenal IGF-1 mRNA levels in FRD(aft) and IBD(aft) tended to be higher than in C (P < 0.1). The IGF-2 mRNA abundance in FRD(aft) was higher than in C (P < 0.05) in duodenum. In colon, mRNA levels of IGF-1 in IBD(aft) were higher than in FRD(aft) (P < 0.05) and levels differed between IBD(aft) and C (P < 0.05). In conclusion, mRNA levels of GHR, IGF-1 and IGF-2 in the gastrointestinal tract were increased during CE when compared with gastrointestinally healthy dogs. The data suggest that GHR, IGF-1 and IGF-2 are involved in gastrointestinal repair processes.     

Upregulation of toll-like receptors in chronic enteropathies in dogs

BACKGROUND: Inflammatory bowel disease (IBD) is thought to result from a dysregulated interaction between the host immune system and commensal microflora. Toll-like receptors (TLRs) recognize microbe-associated molecular patterns (MAMPs), but their role in enteropathies in dogs is unknown. HYPOTHESIS: That there is a dysregulation of TLRs recognizing bacterial MAMPs in dogs with IBD. ANIMALS: Sixteen healthy beagles and 12 dogs with steroid-treated (ST) and 23 dogs with food-responsive (FR) diarrhea. METHODS: Prospective, observational study. mRNA expression of canine TLR2, 4, and 9 was evaluated by quantitative real-time RT-PCR in duodenal and colonic biopsies obtained before and after standard therapy. Samples from control dogs were taken at necropsy, with additional biopsies of stomach, jejunum, ileum, and mesenteric lymph node in 6 dogs. RESULTS: There were significant differences (P< or = .017) in expression of TLR2, 4, and 9 between the 6 sampled locations in healthy control dogs (lymph node > small intestine > or = colon). Before therapy, ST expressed more mRNA than control dogs for all 3 receptors (P < .05). There were no significant differences between pretreatment and posttreatment values, even though 32/35 dogs improved clinically. No associations were found when comparing receptor mRNA expression with either histology or clinical activity scores. CONCLUSIONS AND CLINICAL IMPORTANCE: Bacteria-responsive TLR2, 4, and 9 are upregulated in duodenal and colonic mucosa in IBD. This might lead to increased inflammation through interaction with the commensal flora. The absence of significant changes after therapy despite clinical improvement might point toward the existence of a genetic predisposition to IBD as described in human IBD.     

Clinical signs, histology, and CD3-positive cells before and after treatment of dogs with chronic enteropathies

Background: Histopathology is widely used for the diagnosis of inflammatory bowel disease in dogs. Variations in lesions and unavailability of uniform grading systems limit the usefulness of histologic examination.
Hypothesis: CD3 cell numbers in chronic enteropathies of dogs correlate with clinical activity of the disease and with severity of histopathologic changes.
Animals: Nineteen client-owned dogs examined because of chronic diarrhea, vomiting, or both.
Methods: Samples of duodenal and colonic mucosa were collected endoscopically before and after treatment. Dogs that responded to a hypoallergenic diet were grouped as food-responsive diarrhea dogs (FRD, n = 10). Dogs with no clinical improvement after 10 days of treatment then received prednisolone (immunosuppressive doses) and were grouped as steroid-responsive diarrhea dogs (SRD, n = 9). Histopathologic assessment with a standardized grading system was performed retrospectively on the intestinal samples. Histologic score, total number of infiltrating cells, and CD3-positive cells were counted and compared with the clinical scoring.
Results: No statistically significant difference was detected among histologic grading, total number of cells in the lamina propria, and T-cell numbers in biopsies before and after treatment in either group (FRD and SRD).
Conclusions and Clinical Importance: Currently used histopathologic grading scores, total numbers of cells, and numbers of CD3-positive cells did not allow differentiation between FRD and SRD and did not correlate with clinical response to therapy. Based on these results, new grading scores assessing other criteria than total cell numbers and CD3-positive cells should be evaluated in the future.     

Evaluation of clinical, macroscopic, and histopathologic response to treatment in nonhypoproteinemic dogs with lymphocytic-plasmacytic enteritis

BACKGROUND: Lymphocytic-plasmacytic enteritis (LPE) is a common cause of chronic vomiting and diarrhea in dogs. However, little information is available about endoscopic or histopathologic improvement after therapy in dogs with LPE. HYPOTHESIS: The objective was to study the clinical, endoscopic, and histopathologic evolution of LPE during and after immunosuppressive treatment with prednisone and metronidazole. Most dogs also were treated symptomatically with metoclopramide and cimetidine. ANIMALS: Sixteen dogs with LPE and normal serum protein concentrations diagnosed at the Veterinary Medical Teaching Hospital of the Complutense University of Madrid were monitored during and after drug treatment. The control group consisted of 9 dogs that had no gastrointestinal signs for the preceding 12 months. METHODS: In this prospective clinical treatment trial, clinical, endoscopic, and histopathologic scores were evaluated to describe disease evolution during conventional therapy. Dogs with LPE were monitored for 120 days from the start of treatment. Re-evaluation was performed on post-treatment days 30, 60, 90 (end of treatment), and 120. RESULTS: The average disease activity index observed in our study fell progressively from its initial value, and the decrease between consecutive re-evaluations was statistically significant until day 60 (P = .04). Our results indicate that 75% of the animals revealed improvement of endoscopic gastric lesions (defined as a reduction of the endoscopic score) after treatment, and 75% exhibited improvement of endoscopic duodenal lesions. Statistical analysis of the data revealed significant differences between pre- and post-treatment gastric and duodenal macroscopic endoscopic lesions (P < .05). On the other hand, treatment did not lead to any significant changes in the severity of the gastric and duodenal histopathologic lesions of the affected dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Treatment of nonhypoproteinemic dogs with LPE led to clinical and endoscopic improvement, but histopathologic lesions were unchanged during therapy.     

Gene expression of selected signature cytokines of T cell subsets in duodenal tissues of dogs with and without inflammatory bowel disease

Inflammatory bowel disease (IBD) is a common cause of chronic diarrhoea in dogs. In people, specific cytokine patterns attributed to T cell subsets, especially T helper cell [Th]1, Th17 and regulatory T(reg) cells have emerged in IBD. In contrast, no specific involvement of a distinct T cell subset has been described so far in canine IBD. Thus, the aim of the present study was to assess gene expression of signature cytokines in duodenal tissues from 18 German shepherd dogs with IBD (group 1), 33 dogs of other breeds with IBD (group 2) and 15 control dogs (group 3). Relative quantification of IL-17A, IL-22, IL-10, IFNy and TGFβ was performed. Expression of IL-17A was significantly lower in groups 1 and 2 compared to group 3 (p=0.014), but no difference in the expression of IL-22 (p=0.839), IFNγ (p=0.359), IL-10 (p=0.085) or TGFβ (p=0.551) across groups was detected. Thus, no clear evidence for the involvement of Th-17 signature cytokines in canine IBD at the mRNA level could be shown. The contribution of specific T cell subsets to the pathogenesis of canine IBD warrants further investigation.     

Canine inflammatory bowel disease: retrospective analysis of diagnosis and outcome in 80 cases (1995-2002)

The case records of 80 dogs in which idiopathic inflammatory bowel disease (IBD) had been diagnosed were reviewed, and owners were contacted for follow-up information using a telephone questionnaire. The types of IBD encountered were lymphocytic (n=6), lymphocytic-plasmacytic (n=38), eosinophilic (n=6) and mixed inflammation (n=30). Prednisolone, sulphasalazine, metronidazole and tylosin were the most frequently prescribed medications. At follow-up, 21 dogs (26 per cent) were classified as being in remission (for a median of 14 months), 40 dogs (50 per cent) had intermittent clinical signs (for a median of 17 months) and three dogs (4 per cent) had uncontrolled disease (for a median of 19 months). Ten dogs (13 per cent) had been euthanased due to refractory IBD and four of these had entered remission for a median of 21 months prior to developing severe relapse and refractoriness to further treatment. Six dogs (8 per cent) had been euthanased or had died for reasons unrelated to IBD. Hypoalbuminaemia at the time of diagnosis was significantly associated with a negative outcome (P=0.0007). No association was found between the site (P=0.75), type (P=0.44) and severity (P=0.75) of disease. Dietary change to single protein and carbohydrate commercial diets had no association with outcome (P=0.12). Owner assessment of quality of life at follow-up was significantly associated with outcome (P=0.006).     

Efficacy of omeprazole for the prevention of exercise-induced gastritis in racing Alaskan sled dogs

Exercise-induced gastritis and gastric ulcers are common in humans and horses, and recently have been described in racing sled dogs. The cause of exercise-induced gastric disease is not completely understood in any species, but pharmacologic suppression of acid secretion is an effective treatment in humans and horses. Thus, we tested the hypothesis that omeprazole, a proton-pump inhibitor shown to reduce gastric acid secretion in dogs, would reduce the severity of exercise-induced gastric disease. Three teams of 16 dogs each competing in the 2002 Iditarod Sled Dog Race were recruited for participation. Within each team, dogs were randomly assigned to either treatment (20 mg omeprazole PO q24h) or placebo. Treatments were administered until either completion of the race or withdrawal of an individual dog from competition. Gastric endoscopy was performed in all dogs 24 hours after completion or withdrawal, and the gastric mucosa was scored by using a subjective severity score (0 = normal, 3 = numerous bleeding ulcers). Treatment with omeprazole significantly reduced mean gastricseverity score compared to placebo (omeprazole: 0.65 +/- 0.17, placebo: 1.09 +/- 0.18; P = .028), but also was associated with increased frequency of diarrhea during the race (omeprazole 54%, placebo 21%; P = .017). Examination of our data suggests that omeprazole may be an effective treatment for exercise-induced gastric disease in racing sled dogs. However, further investigation regarding the cause and clinical relevance of diarrhea associated with omeprazole treatment must be conducted before omeprazole can be recommended for routine prophylactic treatment in these athletes.     

Chronic enteropathies in dogs: evaluation of risk factors for negative outcome

HYPOTHESIS: Certain variables that are routinely measured during the diagnostic evaluation of dogs with chronic enteropathies will be predictive for outcome and a new clinical disease activity index incorporating these variables can be applied to predict outcome of disease. ANIMALS: Seventy dogs were entered into a sequential treatment trial with elimination diet (FR, food-responsive group) followed by immunosuppressive treatment with steroids if no response was seen with the dietary trial alone (ST, steroid-treatment group). A 3rd group consisted of dogs with panhypoproteinemia and ascites (PLE, protein-losing enteropathy) that were treated with immunosuppressive doses of steroids. METHODS: Three years of follow-up information was available for all dogs. Clinicopathologic variables were tested for their ability to predict negative outcome, defined as euthanasia due to refractoriness to treatment. Different scoring systems including different combinations of these variables were evaluated using receiver operating characteristic (ROC) curves. RESULTS: Thirteen of 70 (18%) dogs were euthanized because of intractable disease. Univariate analysis identified a high clinical activity index, high endoscopic score in the duodenum, hypocobalaminemia (<200 ng/L) and hypoalbuminemia (<20 g/L) as risk factors for negative outcome. CONCLUSIONS AND CLINICAL IMPORTANCE: Based on the factors identified by logistic regression and ROC curve analysis, a new clinical scoring index (CCECAI) was defined that predicts negative outcome in dogs suffering from chronic enteropathies.     

Effects of deracoxib and aspirin on serum concentrations of thyroxine, 3,5,3'-triiodothyronine, free thyroxine, and thyroid-stimulating hormone in healthy dogs

OBJECTIVE: To evaluate the effects of deracoxib and aspirin on serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) in healthy dogs. ANIMALS: 24 dogs. PROCEDURE: Dogs were allocated to 1 of 3 groups of 8 dogs each. Dogs received the vehicle used for deracoxib tablets (PO, q 8 h; placebo), aspirin (23 to 25 mg/kg, PO, q 8 h), or deracoxib (1.25 to 1.8 mg/kg, PO, q 24 h) and placebo (PO, q 8 h) for 28 days. Measurement of serum concentrations of T4, T3, fT4, and TSH were performed 7 days before treatment (day -7), on days 14 and 28 of treatment, and 14 days after treatment was discontinued. Plasma total protein, albumin, and globulin concentrations were measured on days -7 and 28. RESULTS: Mean serum T4, fT4, and T3 concentrations decreased significantly from baseline on days 14 and 28 of treatment in dogs receiving aspirin, compared with those receiving placebo. Mean plasma total protein, albumin, and globulin concentrations on day 28 decreased significantly in dogs receiving aspirin, compared with those receiving placebo. Fourteen days after administration of aspirin was stopped, differences in hormone concentrations were no longer significant. Differences in serum TSH or the free fraction of T4 were not detected at any time. No significant difference in any of the analytes was detected at any time in dogs treated with deracoxib. CONCLUSIONS AND CLINICAL RELEVANCE: Aspirin had substantial suppressive effects on thyroid hormone concentrations in dogs. Treatment with high dosages of aspirin, but not deracoxib, should be discontinued prior to evaluation of thyroid function.     

Immunohistochemical investigation of Foxp3 expression in the intestine in healthy and diseased dogs

ABSTRACT: Intestinal immune regulation including development of oral tolerance is of great importance for the maintenance of intestinal homeostasis. Concerning this, regulatory T cells (Tregs) occupy a pivotal role in cell-mediated immunosuppression. Dysregulation of mucosal immunology leading to an abnormal interaction with commensal bacteria is suggested to play a key role in the pathogenesis of Inflammatory Bowel Disease (IBD) in men and dogs. The aim of this study was to characterise the expression of Foxp3 in the normal canine gut of 18 dogs (mean age: 6.03 years), in 16 dogs suffering from IBD (mean age: 5.05 years), and of 6 dogs with intestinal nematode infection (mean age: 0.87 years) using immunohistochemistry. In the duodenum, Tregs in healthy dogs declined from villi (median: 10.67/62 500 μm2) to crypts (median: 1.89/62 500 μm2). Tregs were further increased in the villi of middle-aged dogs (median: 18.92/62 500 μm2) in contrast to juvenile (median: 3.50/62 500 μm2) and old (median: 9.56/62 500 μm2) individuals. Compared to healthy controls, animals suffering from IBD revealed reduced numbers of Tregs in duodenal villi (median: 4.13/62 500 μm2). Dogs with intestinal nematode infection displayed increased numbers of Tregs (median: 21.06/62 500 μm2) compared to healthy animals.Age-related changes indicate a progressive establishment of oral tolerance and immunosenescence in the canine elderly. The results further suggest that a defect in Treg homeostasis may be involved in the pathogenesis of canine IBD. In contrast, increased numbers of Tregs in the duodenum may be due to nematode infection.     

Long-Term Efficacy of a Percutaneously Adjustable Hydraulic Urethral Sphincter for Treatment of Urinary Incontinence in Four Dogs

Objective— To evaluate the efficacy of a surgically placed, static hydraulic urethral sphincter (SHUS) for treatment of urethral sphincter mechanism incompetency (USMI).
Study Design— Prospective study.
Animals— Spayed female dogs (n=4) with acquired USMI.
Methods— Urinary incontinence was assessed using a subjective continence score before and after implantation of an SHUS on the proximal urethra via ventral median celiotomy. Dogs were assessed for urinary continence, urinary tract infections, and implant-associated complications for 30 months. Residual incontinence was treated with percutaneous inflation of the SHUS with sterile saline solution through a biocompatible subcutaneous administration port.
Results— At last follow-up (26–30 months after surgery), continence scores improved from a median preoperative score of 3/10 to a median postoperative score of 10. One dog developed wound drainage over the subcutaneously placed administration port but remained continent after port removal. Three occluders were percutaneously filled with additional saline (median, 0.18 mL; mean, 0.16 mL) to improve continence after surgery.
Conclusions— Application and adjustment of an SHUS provided sustained improvements in continence score in all dogs.
Clinical Relevance— In this pilot study, 3 of 4 dogs with hydraulic urethral sphincter implantation had successful percutaneous adjustment and maintained improved continence scores for 2 years after surgery. Continence was maintained in the 4th dog even after administration port removal. Based on this pilot study, the SHUS warrants further clinical evaluation for treatment of dogs with USMI unresponsive to medical management.     

Combination of CCNU and DTIC chemotherapy for treatment of resistant lymphoma in dogs

BACKGROUND: Pleotropic-glycoprotein (P-gp)-mediated resistance is the usual cause of relapse in dogs with lymphoma. 1-(2-chloroethyl)3-cyclohexyl-1-nitrosurea (CCNU) and 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) are alkylating agents that are not affected by P-gp and lack cross-resistance to each other. A combination protocol offers the advantage of improved summation dose and synergistic activity. HYPOTHESIS: A combination of CCNU and DTIC that is well tolerated can be used to treat dogs with lymphoma that developed resistance or failed to respond to previously administered chemotherapy. ANIMALS: Fifty-seven dogs with lymphoma that were resistant to treatment with standard chemotherapy (L-CHOP; L-asparaginase, cyclophosphamide, doxorubicin, vincristine, prednisone). METHODS: Prospective phase I and II trials were performed. CCNU was given PO immediately before a 5-h IV infusion of DTIC. Concurrent antiemetics and prophylactic antibiotics were used. Treatments were administered every 4 weeks. RESULTS: Based on the results of 8 dogs in the phase I study, CCNU at 40 mg/m(2) PO combined with DTIC at 600 mg/m(2) IV was used to treat 57 dogs with resistant lymphoma. Thirteen (23%) dogs had a complete response (CR) for a median of 83 days and 7 (12%) had a partial response for a median of 25 days. The median L-CHOP CR duration of the dogs that did not respond to CCNU-DTIC was significantly longer than that of the dogs that did achieve remission with CCNU-DTIC (225 days versus 92 days, P= .02). The principal toxic event was neutropenia; the median neutrophil count 7 days after treatment was 1,275 cells/microL. Increases in alanine transaminase activity, possibly associated with hepatotoxicity, were detected in 7 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: A combination of CCNU and DTIC can be an effective option to rescue dogs with resistant lymphoma.     

Elevated canine pancreatic lipase immunoreactivity concentration in dogs with inflammatory bowel disease is associated with a negative outcome

O bjectives : To investigate whether elevated canine pancreatic lipase immunoreactivity (CPLI) concentrations in dogs with inflammatory bowel disease (IBD) is associated with a worse clinical outcome.
M ethods : Serum CPLI assays were performed on serum stored from cases diagnosed with IBD. Thirty-two dogs with CPLI results within the reference range were designated as the control group and 15 dogs had CPLI above the reference range. Clinical signs, age, serum lipase and amylase activities, serum albumin and cobalamin concentrations, abdominal ultrasound examination, histopathology on small intestinal biopsies, management of IBD and outcome were compared between the two groups.
R esults : No significant differences were found in clinical activity score (P=0·54), number of antibiotic-responsive disease cases (P=0·480), number of steroid-responsive disease cases (P=0·491), serum amylase activity (P=0·058), serum cobalamin concentration (P=0·61), serum albumin concentration (P=0·052), abdominal ultrasound score (P=0·23) and histopathology scores for IBD (P=0·74) between the two groups. Dogs with increased CPLI concentration were significantly older and had a higher serum lipase activity than dogs with a CPLI concentration within the normal reference range (P=0·001, P=0·001, respectively). Moreover, dogs with increased CPLI concentration responded poorly to steroid treatment (P=0·01) and were significantly more likely to be euthanased at follow-up (P=0·02).
C linical S ignificance : CPLI should be measured in cases of canine IBD as elevated CPLI was associated with a worse outcome.     

Ultrasonographic evaluation of the thickness of the small intestinal wall in dogs with inflammatory bowel disease

OBJECTIVES: To establish whether the intestinal wall thickness, as measured ultrasonographically, is significantly increased in dogs with inflammatory bowel disease (IBD). The results would provide the information necessary to decide whether measurement of ultrasonographic wall thickness can predict IBD in dogs. METHODS: The intestinal wall thickness of 75 dogs with idiopathic IBD, as measured by ultrasonography, was compared with recently published normal values. IBD was either confirmed histologically (n = 54) or suspected (n = 21). In all cases there was a positive response to immunosuppressive treatment. RESULTS: A positive association between intestinal wall thickness in dogs and either the histological diagnosis or the response to treatment was not found. Ultrasonographic intestinal wall measurements do not appear to be able to establish a diagnosis of intestinal inflammation and may result in a false negative diagnosis in cases of IBD. CLINICAL SIGNIFICANCE: The same 'grey zone' of between 4 and 6 mm used in humans can be used in the canine duodenum to distinguish the normal range, reserving the term 'abnormal' for an intestinal measurement greater than 6 mm in the duodenum and greater than 4.7 mm in the jejunum.     

Clinical characteristics and outcome in dogs with small cell T‐cell intestinal lymphoma

Small cell intestinal lymphoma has not been well characterized in dogs. The objective of this study was to describe clinical characteristics and outcome in dogs with small cell intestinal lymphoma. We hypothesized that affected dogs would have prolonged survival compared with high‐grade gastrointestinal (GI) lymphoma. Pathology records were searched for dogs with histologically confirmed small cell GI lymphoma. Seventeen dogs with confirmed small cell intestinal lymphoma were identified, and clinical and outcome data were retrospectively collected. Histopathology was reviewed by a board‐certified pathologist, and tissue sections were subjected to immunophenotyping and molecular clonality assessment. All dogs had small cell, T‐cell, lymphoma confirmed within various regions of small intestine, with 1 dog also having disease in abdominal lymph nodes. All dogs had clinical signs attributable to GI disease; diarrhoea (n = 13) was most common. Ultrasonographic abnormalities were present in 8 of 13 dogs with abnormal wall layering (n = 7) and hyperechoic mucosal striations (n = 7) representing the most common findings. In total, 14 dogs received some form of treatment. The median survival time (MST) for all dogs was 279 days and the MST for the 14 dogs that received any treatment was 628 days. Dogs with anaemia and weight loss at presentation had significantly shorter survival times and dogs that received a combination of steroids and an alkylating agent had significantly longer survival times. Small cell, T‐cell, intestinal lymphoma is a distinct disease process in dogs, and those undergoing treatment may experience prolonged survival.