Clinical features, intestinal histopathology, and outcome in protein-losing enteropathy in Yorkshire Terrier dogs.

BACKGROUND: A poorly understood protein-losing enteropathy (PLE) disorder has been reported in Yorkshire Terrier dogs. OBJECTIVES: To describe clinical features, intestinal histopathology, and outcome in Yorkshire Terrier dogs with PLE, and to identify variables predictive of outcome. ANIMALS: Thirty client-owned Yorkshire Terrier dogs with PLE. METHODS: Retrospective study. Records of dogs with a diagnosis of PLE were reviewed. Intestinal histopathology was interpreted using the World Small Animal Veterinary Association gastrointestinal histopathology classification system. Discriminate analysis techniques were used to identify variables predictive of outcome. RESULTS: Females outnumbered males (20/30). Median age was 7 years (range 1-12). Common clinical signs were diarrhea (20/30), vomiting (11), ascites and abdominal distension (11), and respiratory difficulty (8). Histopathologic abnormalities included villous lymphatic dilatation, crypt lesions, villous stunting, and variable increases in cellularity of the lamina propria. All dogs were treated with glucocorticoids. Of 23 dogs with long-term follow-up, 9 had complete, and 3 had partial, resolution of signs, and 11 failed to respond to treatment. Median survival of responders was 44 months and of nonresponders was 12 months, with 4 dogs experiencing peracute death. Vomiting, monocytosis, severity of hypoalbuminemia, low blood urea nitrogen concentration, and villous blunting were predictive of survival <4 months. CONCLUSIONS: In addition to classic GI signs, Yorkshire Terriers with PLE often show clinical signs associated with hypoalbuminemia and low oncotic pressure. Lymphatic dilatation, crypt lesions, and villous stunting are consistent histopathologic findings. Clinical outcomes are variable, but many dogs experience remission of clinical signs and prolonged survival.

Design of a simplified histopathologic model for gastrointestinal inflammation in dogs.

Significant interobserver variability in the diagnostic interpretation of endoscopic gastrointestinal (GI) specimens exists even with the use of World Small Animal Veterinary Association (WSAVA) standardization criteria. Chi-square analyses compared the extent of pathologists' agreement for microarchitectural features of inflammation in endoscopic specimens obtained from 253 animals of the original WSAVA study. Patterns of agreement between pathologists were classified as broad (3/4 pathologists agreed), dichotomous (2/4 pathologists agreed), or divergent (no agreement between pathologists). The simplified model for GI inflammation was based on those parameters for which the pathologists had either broad or minimally divergent opinions of histopathologic significance. In this model, the parameters chosen were as follows: gastric parameters (intraepithelial lymphocytes [IELs], lamina propria [LP] infiltrates, and mucosal fibrosis), duodenal parameters (villus atrophy, epithelial injury, IELs, crypt changes, and LP infiltrates), and colonic parameters (epithelial injury, crypt dilation, fibrosis, LP infiltrates, and goblet cell depletion). Preliminary data using this simplified model showed excellent correlation between pathologists in defining the presence and extent of GI inflammation in dogs.

Effect of tissue processing on assessment of endoscopic intestinal biopsies in dogs and cats.

BACKGROUND: Prior studies failed to detect significant association between hypoalbuminemia and small intestinal lesions. HYPOTHESIS: Use of pictorial templates will enhance consistency of interpathologist interpretation and identification of intestinal lesions associated with hypoalbuminemia. ANIMALS: Tissues from 62 dogs and 25 cats examined as clinical cases at 7 referral veterinary practices in 4 countries. METHODS: Retrospective, observational study. Histopathology slides from sequential cases undergoing endoscopic biopsy were examined by 4 pathologists by pictorial templates. Changes for 9 microscopic features were recorded as normal, mild, moderate or severe, and 2- and 4-point scales were tested for consistency of interpretation. Logistic regression models determined odds ratios (OR) of histologic lesions being associated with hypoalbuminemia while kappa statistics determined agreement between pathologists on histologic lesions. RESULTS: There was poor agreement (kappa = -0.013 to 0.3) between pathologists, and institution of origin of slides had effect (kappa = 1.0 for 3 of 4 lesions on slides from Institution 5) on agreement between pathologists on selected histologic features. Using 2 point as opposed to 4-point grading scale increased agreement between pathologists (maximum kappa = 0.69 using 4-point scale versus maximum kappa = 1.0 using 2-point scale). Significant association (P = .019- .04; 95% OR = 3.14-10.84) between lacteal dilation and hypoalbuminemia was found by 3 pathologists. CONCLUSIONS AND CLINICAL IMPORTANCE: Substantial inconsistency between pathologists remains despite use of pictorial template because of differences in slide processing. Distinguishing between mild and moderate lesions might be important source of the disagreement among pathologists.

A prospective, randomized, double-blinded, placebo-controlled study of human intravenous immunoglobulin for the acute management of presumptive primary immune-mediated thrombocytopenia in dogs.

BACKGROUND: Immune-mediated thrombocytopenia (IMT) is a common hematologic disorder in dogs. Human intravenous immunoglobulin (hIVIG) may have a beneficial effect in canine IMT. HYPOTHESIS: A single hIVIG infusion (0.5 g/kg) in dogs with presumed primary IMT (pIMT) is a safe adjunctive emergency treatment to accelerate platelet count recovery and shorten hospitalization time without increasing the cost of patient care. ANIMALS: Eighteen client-owned dogs with a presumptive diagnosis of pIMT. METHODS: Prospective, randomized, double-blinded, placebo-controlled clinical trial. RESULTS: There were no identifiable immediate or delayed adverse reactions associated with hIVIG administration over a 6-month period. The median platelet count recovery time for the hIVIG group was 3.5 days (mean + or - SD: 3.7 + or - 1.3 days; range, 2-7 days) and 7.5 days (mean + or - SD: 7.8 + or - 3.9 days; range, 3-12 days) for the placebo group. The median duration of hospitalization for hIVIG group was 4 days (mean + or - SD: 4.2 + or - 0.4 days; range, 2-8 days) and 8 days (mean + or - SD: 8.3 + or - 0.6 days; range, 4-12 days) for the placebo group. There was no significant difference between groups with respect to expense of initial patient care, whereas significant reduction in platelet count recovery time (P= .018) and duration of hospitalization (P= .027) were detected in the hIVIG group. CONCLUSIONS AND CLINICAL IMPORTANCE: Compared with corticosteroids alone, adjunctive emergency therapy of a single hIVIG infusion was safe and associated with a significant reduction in platelet count recovery time and duration of hospitalization without increasing the expense of medical care in a small group of dogs with presumed pIMT.

Effect of sample quality on the sensitivity of endoscopic biopsy for detecting gastric and duodenal lesions in dogs and cats.

BACKGROUND: The quality of histopathology slides of endoscopic biopsies from different laboratories varies, but the effect of biopsy quality on outcome is unknown. HYPOTHESIS: The ability to demonstrate a histologic lesion in the stomach or duodenum of a dog or cat is affected by the quality of endoscopic biopsy samples submitted. More endoscopic samples are needed to find a lesion in poor-quality tissue specimens. ANIMALS: Tissues from 99 dogs and 51 cats were examined as clinical cases at 8 veterinary institutions or practices in 5 countries. METHODS: Histopathology slides from sequential cases that underwent endoscopic biopsy were submitted by participating institutions. Quality of the histologic section of tissue (inadequate, marginal, adequate), type of lesion (lymphangiectasia, crypt lesion, villus blunting, cellular infiltrate), and severity of lesion (normal, mild, moderate, severe) were determined. Sensitivity of different quality tissue samples for finding different lesions was determined. RESULTS: Fewer samples were required from dogs for diagnosis as the quality of the sample improved from inadequate to marginal to adequate. Duodenal lesions in cats displayed the same trend except for moderate duodenal infiltrates for which quality of tissue sample made no difference. Gastric lesions in dogs and mild gastric lesions in cats had the same trend, whereas the number of tissue samples needed to diagnose moderately severe gastric lesions in cats was not affected by the quality of tissue sample. CONCLUSIONS AND CLINICAL IMPORTANCE: The quality of endoscopically obtained tissue samples has a profound effect on their sensitivity for identifying certain lesions, and there are differences between biopsies of canine and feline tissues.

Histopathological standards for the diagnosis of gastrointestinal inflammation in endoscopic biopsy samples from the dog and cat: a report from the World Small Animal Veterinary Association Gastrointestinal Standardization Group.

The characterization of inflammatory change in endoscopic biopsy samples of the gastrointestinal mucosa is an increasingly important component in the diagnosis and management of canine and feline gastrointestinal disease. Interpretation has hitherto been limited by the lack of standard criteria that define morphological and inflammatory features, and the absence of such standardization has made it difficult, if not impossible, to compare results of retrospective or prospective studies. The World Small Animal Veterinary Association (WSAVA) Gastrointestinal Standardization Group was established, in part, to develop endoscopic and microscopical standards in small animal gastroenterology. This monograph presents a standardized pictorial and textual template of the major histopathological changes that occur in inflammatory disease of the canine and feline gastric body, gastric antrum, duodenum and colon. Additionally, a series of standard histopathological reporting forms is proposed, to encourage evaluation of biopsy samples in a systematic fashion. The Standardization Group believes that the international acceptance of these standard templates will advance the study of gastrointestinal disease in individual small companion animals as well as investigations that compare populations of animals.

Pathogenesis and outcome of extrahepatic biliary obstruction in cats.

Extrahepatic biliary obstruction (EHBO) was confirmed at surgery or necropsy in 22 cats. Biliary or pancreatic adenocarcinoma was diagnosed by histopathology in six cats and one cat had an undiagnosed mass in the common bile duct. The remaining 15 cats had at least one of a complex of inflammatory diseases including pancreatitis, cholangiohepatitis, cholelithiasis and cholecystitis. The most common clinical signs were jaundice, anorexia, lethargy, weight loss and vomiting. Hyperbilirubinaemia was present in all cases. Distension of the common bile duct and gall bladder was the most commonly observed finding on abdominal ultrasound. Nineteen cats underwent exploratory laparotomy for biliary decompression and diversion. Mortality in cats with underlying neoplasia was 100 per cent and, in those with non-neoplastic lesions, was 40 per cent. Long-term complications, in those that survived, included recurrence of cholangiohepatitis, chronic weight loss and recurrence of obstruction. Based on these findings, the prognosis for EHBO in cats must be considered guarded.

Incidence and prognostic value of low plasma ionized calcium concentration in cats with acute pancreatitis: 46 cases (1996-1998).

OBJECTIVE: To determine the incidence and prognostic significance of low plasma ionized calcium concentration in cats with clinical signs of acute pancreatitis (AP). DESIGN: Retrospective study. ANIMALS: 46 cats with AP and 92 control cats with nonpancreatic diseases. PROCEDURE: Medical records were reviewed, and results of clinicopathologic testing, including plasma ionized and total calcium concentrations, acid-base values, and electrolyte concentrations, were recorded. Cats with AP were grouped on the basis of outcome (survived vs died or were euthanatized), and plasma ionized calcium concentrations, acid-base values, and electrolyte concentrations were compared between groups. RESULTS: Serum total calcium concentration was low in 19 (41%) cats with AP, and plasma ionized calcium concentration was low in 28 (61%). Cats with AP had a significantly lower median plasma ionized calcium concentration (1.07 mmol/L) than did control cats (1.12 mmol/L). Nineteen (41%) cats with AP died or were euthanatized; these cats had a significantly lower median plasma ionized calcium concentration (1.00 mmol/L) than did cats that survived (1.12 mmol/L). Ten of the 13 cats with AP that had plasma ionized calcium concentrations < or = 1.00 mmol/L died or were euthanatized. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that low plasma ionized calcium concentration is common in cats with AP and is associated with a poorer outcome. A grave prognosis and aggressive medical treatment are warranted for cats with AP that have a plasma ionized calcium concentration < or = 1.00 mmol/L.

Clinical, clinicopathologic, radiographic, and ultrasonographic characteristics of intestinal lymphangiectasia in dogs: 17 cases (1996-1998).

OBJECTIVE: To characterize the clinical, clinicopathologic, and imaging findings in dogs with intestinal lymphangiectasia and to compare the histologic grade of lymphangiectasia with clinicopathologic and imaging abnormalities. DESIGN: Retrospective study. ANIMALS: 17 dogs with a histologic diagnosis of intestinal lymphangiectasia. PROCEDURE: Medical records of dogs with a histologic diagnosis of intestinal lymphangiectasia were reviewed for signalment, history, clinical signs, results of exploratory laparotomy, and clinicopathologic, radiographic, ultrasonographic, and histologic findings. RESULTS: Mean age of dogs was 8.3 years; the most common clinical signs were diarrhea, anorexia, lethargy, vomiting, and weight loss. Abnormal physical examination findings included dehydration, ascites, and signs of pain on palpation of the abdomen. The most notable clinicopathologic findings were low serum ionized calcium concentration and hypoalbuminemia. Abdominal ultrasonography was performed in 12 dogs and revealed intestinal abnormalities in 8 dogs and peritoneal effusion in 7 dogs. Exploratory laparotomy revealed abnormalities in 9 of 16 dogs including thickened small intestine, dilated lacteals, lymphadenopathy, and adhesions. On histologic examination of the small intestine, concurrent inflammation was observed in 15 of 17 dogs, crypt ectasia in 5 of 17, and lipogranulomas in 2 of 17. CONCLUSIONS AND CLINICAL RELEVANCE: Intestinal lymphangiectasia in dogs appears to be a heterogeneous disorder characterized by various degrees of panhypoproteinemia, hypocholesterolemia, lymphocytopenia, and imaging abnormalities. In most dogs, the severity of hypoalbuminemia appears to offer the best correlation with severity of histologic lesions of lymphangiectasia. Imaging abnormalities are common in dogs with intestinal lymphangiectasia but are not specific enough to differentiate this disorder from other gastrointestinal disorders, nor are they predictive of histologic severity.

Radiographic, ultrasonographic, and endoscopic findings in cats with inflammatory bowel disease of the stomach and small intestine: 33 cases (1990-1997).

OBJECTIVE: To characterize imaging findings in cats with confirmed inflammatory bowel disease (IBD) of the upper gastrointestinal tract (i.e., stomach and small intestine) and relate these findings to clinical signs and histologic changes. DESIGN: Retrospective study. ANIMALS: 32 cats with clinical and histopathologic diagnoses of IBD. PROCEDURE: Medical records were reviewed for signalment, clinical signs, clinicopathologic findings, radiographic and ultrasonographic findings, and results of endoscopic examination. Histologic findings were reviewed and characterized by severity and type of inflammatory infiltrate. RESULTS: All cats had 1 or more clinical signs (e.g., vomiting, diarrhea, weight loss, and anorexia) consistent with IBD. Lymphocytic and plasmacytic infiltrates were observed in histologic sections of gastrointestinal tissue. Crypt distortion, villous blunting and fusion, and fibrosis were most commonly seen in cats with moderate or severe IBD. Clinicopathologic findings of some cats included anemia, leukocytosis or leukopenia, hypocholesterolemia, and hyper- or hypoproteinemia. Abnormalities were not found on abdominal radiographic views in 9 of 9 cats. However, contrast studies using barium revealed radiographic abnormalities in 1 of 3 cats. In 13 of 17 cats, abdominal ultrasonography revealed several intestinal abnormalities (e.g., poor intestinal wall layer definition, focal thickening) and large mesenteric lymph nodes with hypoechoic changes consistent with IBD. Endoscopic observation revealed findings (e.g., erythema, plaques, mucosal friability) consistent with inflammation in 9 of 18 cats. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with endoscopy of the gastrointestinal tract or abdominal radiography, clinical signs and ultrasonographic findings appear to have the best association with histologic grade of IBD in cats.

Copper associated acute hepatic failure in a dog.

A 1.5-year-old Dalmatian was examined because of vomiting, weight loss, and high serum activities of alanine aminotransferase and aspartate aminotransferase. Abdominal ultrasonography revealed normal appearing hepatic structure with echogenicity, but histologic examination of hepatic biopsy specimens revealed extensive necrosis of hepatocytes involving the centrilobular areas. Macrophages and remaining hepatocytes contained pigments that were positive for copper by rubeanic acid-staining and hepatic copper concentration was high. The dog was treated with crystalloid fluids, antibiotics, and a low copper diet; its condition deteriorated, and the dog was euthanatized. Primary copper storage disease was suspected on the basis of histologic findings and high copper concentration in the liver.

Diagnosis and treatment of gastric motility disorders.

A disorder of gastric motility should be suspected in patients with chronic vomiting. Imaging studies are used to confirm delayed gastric emptying, the most common form of a gastric motility disorder. Other causes of chronic vomiting, for example, metabolic or endocrine disorders, other abdominal disorders, mechanical causes of gastric obstruction, and lower gastrointestinal tract disease, are then ruled out. If no underlying cause is determined, a functional disorder of gastric emptying is presumptively diagnosed. Treatment consists of dietary management and gastric prokinetic agents. Cisapride is the drug of choice for treating delayed gastric emptying followed by erythromycin and ranitidine or nizatidine.

Pathogenesis, diagnosis, and therapy of feline idiopathic megacolon.

Many cats have one or two episodes of constipation without further recurrence, although others progress to complete colonic failure. Middle-aged male cats are particularly at risk for the clinical continuum of constipation, obstipation, and dilated megacolon. Pelvic canal stenosis and nerve injury are minor causes in the development of this syndrome. In most affected cats, the underlying pathogenesis appears to involve colonic smooth muscle dysfunction. In this group of cats, it is not yet clear whether this disorder represents a primary or secondary (resulting from long-standing constipation and colonic distension) abnormality. Many cats with mild to moderate constipation respond to conservative medical management (e.g., dietary fiber supplementation, emollient or hyperosmotic laxatives, colonic prokinetic agents). Indeed, early use of colonic prokinetic agents is likely to prevent the progression of constipation of obstipation and dilated megacolon in many cats. Some cats may become refractory to these therapies, however, as they progress through moderate or recurrent constipation to obstipation and dilated megacolon. These cats eventually require colectomy. Cats have a generally favorable prognosis for recovery following colectomy, although mild to moderate diarrhea may persist for 4 to 6 weeks postoperatively in some cases.

Evaluation of risk factors for fatal acute pancreatitis in dogs.

OBJECTIVE: To identify risk factors associated with fatal acute pancreatitis in dogs. DESIGN: Case-control study. ANIMALS: 70 case dogs with clinical evidence and histopathologic confirmation of fatal acute pancreatitis and 104 control dogs that had trauma, underwent necropsy, and did not have histologic evidence of acute pancreatitis. PROCEDURE: Information on signalment, weight, body condition, medical history, concurrent disease, and results of histopathologic examination was obtained by reviewing medical records. Logistic regression analysis included calculation of univariate and multivariate (adjusted) odds ratios and 95% confidence intervals. RESULTS AND CLINICAL IMPLICATIONS: Dogs with fatal acute pancreatitis were largely middle- to older-aged dogs. Risk of developing fatal acute pancreatitis was increased by overweight body condition, diabetes mellitus, hyperadrenocorticism, hypothyroidism, prior gastrointestinal tract disease, and epilepsy. Additionally, Yorkshire Terriers were at increased risk, and Labrador Retrievers and Miniature Poodles were at decreased risk, of developing fatal acute pancreatitis. Males and neutered females appeared to have an increased risk of developing fatal acute pancreatitis, compared with sexually intact females. Thrombus formation was more likely in dogs that developed fatal acute pancreatitis than in control dogs.

Correlation between longitudinal bone growth, growth hormone, and insulin-like growth factor-I in prepubertal dogs.

OBJECTIVE: To determine the association between longitudinal bone growth and concentrations of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in serum from prepubertal dogs. Animals-6 male 14-week-old German Shepherd Dogs. PROCEDURE: Blood was obtained every 30 minutes for 14 consecutive days. Concentrations of GH and IGF-I in serum were determined, using a canine-specific radioimmunoassay and conventional radioimmunoassay after acid-ethanol extraction, respectively. Simultaneous biplanar radiography was performed daily to measure bone growth. Spectral analysis was used to estimate specific features of GH secretion during an extended period. Multiple linear regression with different lag times between independent and dependent variables was used to determine the strongest predictors of bone growth. RESULTS: The power spectra of GH concentrations in serum had a primary peak at a frequency of 0.02 cycles/h or a periodicity of 50 h/cycle. A significant determinant of longitudinal bone growth was a lag time of 1 day in concentration of GH in serum. The relationship between IGF-I concentration in serum and bone growth was not significant. CONCLUSIONS: The primary frequency of GH secretion is outside the time frame of a single day and the concentration of GH in serum is a primary determinant of bone growth. CLINICAL RELEVANCE: A better understanding of the components of bone growth provide discernment to improved diagnosis and treatment of abnormal bone growth.

Clinical, clinicopathologic, radiographic, and ultrasonographic abnormalities in dogs with fatal acute pancreatitis: 70 cases (1986-1995).

OBJECTIVE: To determine clinical, clinicopathologic, radiographic, ultrasonographic, and coagulation abnormalities in dogs in which acute pancreatitis was fatal. DESIGN: Retrospective study. ANIMALS: 70 dogs. PROCEDURE: History, clinical signs, and physical examination findings at the time of initial evaluation at the veterinary teaching hospital; results of pretreatment laboratory tests, abdominal radiography, and ultrasonography; and histologic abnormalities were obtained from medical records. RESULTS: Clinical signs included anorexia, vomiting, Weakness, diarrhea, polyuria and polydipsia, neurologic abnormalities, melena, weight loss, hematemesis, and passage of frank blood in feces. At the time of initial examination at the veterinary teaching hospital, 68 (97%) dogs were dehydrated, 18 (26%) were icteric, 22 (32%) were febrile, 40 (58%) had signs of abdominal pain, and 30 (43%) were classified as overweight or obese. Most dogs had leukocytosis, neutrophilia with a left shift, and thrombocytopenia. Various serum biochemical abnormalities were identified, including hypoglycemia, azotemia, hypercalcemia and other electrolyte abnormalities, hypoalbuminemia, high hepatic and pancreatic enzyme activities, hypercholesterolemia, and lipemia. For 17 of 28 (61%) dogs, results of coagulation function tests were abnormal. Results of abdominal ultrasonography and radiography were consistent with a diagnosis of acute pancreatitis in 23 of 34 (68%) and 10 of 41 (24%) dogs, respectively. For 2 dogs, results of abdominal ultrasonography were not suggestive of acute pancreatitis, but results of abdominal radiography were. CLINICAL IMPLICATIONS: Clinical signs and results of clinicopathologic tests are inconsistent. Abdominal ultrasonography may be valuable in the diagnostic evaluation of dogs suspected to have acute pancreatitis.

Risk factors for acquired megaesophagus in dogs.

OBJECTIVE: To identify risk factors associated with acquired megaesophagus in dogs. DESIGN: Case-control study. ANIMALS: 136 dogs with acquired megaesophagus (case dogs); 272 dogs from the general hospital population and 151 dogs that underwent thyroid-stimulating hormone response tests (control dogs). All dogs were more than 6 months old. PROCEDURE: Medical records of dogs in which megaesophagus was diagnosed during a 10-year period were reviewed. Inclusion criteria included regurgitation or vomiting, onset of clinical signs at more than 6 months of age, and radiographic evidence of generalized esophageal dilatation. Dogs with intra- or extraesophageal obstructive disease, brain stem disease, or neck trauma were excluded from analyses. Statistical analyses included odds ratios, 95% confidence intervals, and two-tailed t-tests. Control dogs were frequency matched to case dogs on the basis of year of diagnosis. RESULTS: Dogs with megaesophagus ranged from 0.75 to 18 years old (mean, 8.1 years) and were significantly older and heavier than control dogs. More males than females were affected, but sex and reproductive status were not associated with megaesophagus. German Shepherd Dogs, Golden Retrievers, and Irish Setters were at increased risk for developing megaesophagus. Peripheral neuropathies, laryngeal paralysis, acquired myasthenia gravis, esophagitis, and chronic or recurrent gastric dilatation with or without volvulus were associated with an increased risk of developing megaesophagus. Hypothyroidism was not associated with megaesophagus. CLINICAL IMPLICATIONS: Dogs with acquired megaesophagus should be evaluated for peripheral neuropathies, laryngeal paralysis, acquired myasthenia gravis, esophagitis, and chronic or recurrent gastric dilatation with or without volvulus. These dogs may be evaluated for hypothyroidism; however, this study did not reveal a clear association between hypothyroidism and acquired megaesophagus.