Evaluation of serum ferritin as a tumor marker for canine histiocytic sarcoma.

BACKGROUND: Canine histiocytic sarcoma (HS) is an aggressive malignancy. Hyperferritinemia has been documented in dogs with HS and could serve as a tumor marker aiding in diagnosis and treatment. In people, hyperferritinemia is found in inflammatory diseases, liver disease, and hemolysis, and thus may occur in dogs with these conditions. OBJECTIVE: To determine if serum ferritin concentration is a tumor marker for canine HS. ANIMALS: Dogs with HS (18), inflammatory diseases (20), liver disease (24), immune-mediated hemolytic anemia (IMHA) (15), and lymphoma (23). METHODS: Prospective, observational, cohort study: Serum ferritin concentration was measured at initial diagnosis. Parametric methods were used to compare mean log ferritin concentrations among disease categories. Receiver-operating characteristic curves and likelihood ratios were used to evaluate serum ferritin concentration as a tumor marker. RESULTS: Varying proportions of dogs with IMHA (94%), HS (89%), liver disease (79%), lymphoma (65%), and inflammatory diseases (40%) had hyperferritinemia. Dogs with IMHA had significantly higher mean ferritin concentration than dogs in all other categories. Dogs with HS had significantly higher mean ferritin concentration than those in the inflammatory disease and lymphoma categories. Mean serum ferritin concentration was not significantly different between dogs with HS and those with liver disease. Decision thresholds were determined to distinguish IMHA and HS from the other diseases associated with hyperferritinemia. CONCLUSION: Hyperferritinemia is common in dogs with HS and, after IMHA is ruled out, the degree of hyperferritinemia may be useful in differentiating dogs with HS from dogs with inflammatory diseases, liver disease, and lymphoma.

Juvenile pancreatic atrophy in Greyhounds: 12 cases (1995-2000).

BACKGROUND: This study describes compound failure of the endocrine and exocrine pancreas in Greyhounds, a condition that has not been reported in the veterinary literature. OBJECTIVE: To describe the clinical and pathologic findings in 12 Greyhounds with juvenile pancreatic atrophy. ANIMALS: Ten Greyhounds presented for necropsy examination and 2 sibling Greyhounds presented for clinical evaluation before necropsy, all with a history of small-bowel diarrhea. PROCEDURES: Retrospective study of laboratory and pathologic findings in 12 Greyhounds, including serum trypsin-like immunoreactivity assays, oral glucose tolerance testing, and serum anti-insulin antibody concentrations. RESULTS: Gross pancreatic atrophy was found in all 12 dogs. Histopathologic lesions were found in both the endocrine and exocrine pancreas and included acinar cell apoptosis, zymogen granule loss, cytoplasmic clearing or vacuolar change, lobular atrophy, islet loss, and lymphocytic or lymphoplasmacytic pancreatitis. Antemortem test results on the 2 Greyhound puppies indicated concurrent exocrine pancreatic insufficiency (EPI) and insulin-dependent diabetes mellitus (IDDM). CONCLUSIONS AND CLINICAL IMPORTANCE: Compound failure of the exocrine and endocrine pancreas is rarely reported in dogs and neither disease is well recognized in the Greyhound. This condition is of potential economic importance to the Greyhound racing industry.

Fibrosarcoma over the tarsal groove of a 14-month-old Quarter horse.

A 14-month-old male Quarter horse was presented for evaluation of a grade 3 out of 5 (grade 0 = sound; grade 5 = non-weight bearing) right rear lameness. A firm, 8 x 16 cm mass was palpable at the caudal medial aspect of the distal tibia and proximal tarsal region of the right hind limb. A percutaneous needle aspirate contained mesenchymal cells that were moderate to large in size with single, oblong nuclei. Differential diagnoses included fibrous hyperplasia, fibroma, or well-differentiated fibrosarcoma. Excisional biopsy for both definitive diagnosis and treatment was offered and selected by the owner. A fibrosarcoma was confirmed by histological examination of the mass. One and a half years after resection signs of lameness or evidence of regrowth of the mass were not evident.

Ga-67 citrate imaging in tumors of the genito-urinary tract: report of cooperative study.

Whole-body imaging with Ga-67 citrate in 127 tumors of the genito-urinary tract has been evaluated by a cooperative group using a uniform protocol. Primary sites of tumor were not detectable by imaging, except for one bladder and one kidney tumor. Proven and apparent metastases yielded positive scans, however, in 51% of prostatic, 50% of bladder, 72% of kidney, and 53% of testicular neoplasms. In bladder and kidneys metastases, if bone sites are excluded, detection of soft tissue metastases was 61% and 75%, respectively. In embryonal-cell carcinoma of the testicle, 74% of metastatic foci were detected.

Ga-67 citrate imaging in malignant lymphoma: final report of cooperative group.

In a large cooperative study of Ga-67 uptake in non-Hodgkin's malignant lymphoma, 76% of untreated patients showed positive uptake in one or more lesions. The percentage of known individual lesions seen on scan was significantly lower; thus, negative findings at any one site may have much less significance than positive findings. After treatment, the number of lesions seen decreases sharply, but the role of Ga-67 in evaluating response to therapy is uncertain, especially in view of the fairly large number of lesions undetectable before therapy. Histologic type plays a role in Ga-67 uptake. Large lesions are much more effectively detected than small ones. In spite of numerous false-negative results, Ga-67 scanning is a useful method in evaluating the extent of untreated disease and the presence of lesions posttherapy.

Tumor location with 1-aminocyclopentane [11C] carboxylic acid: preliminary clinical trials with single-photon detection.

High specific activity [11C] Carboxyl-labeled 1-aminocyclopentane-carboxylic acid ([11C] ACPC) was tested as a tumor-scanning agent in thirty-eight patients. This artificial amino acid clears the blood to a level of less than 12% within 45 min; thus, imaging is possible within the useful life of C-11. [11C] ACPC can be produced in amounts adequate for clinical scanning. Doses between 12 and 45 mCi were given by i.v. injection, and scans obtained only in the single-photon mode gave clinical information on the sites of tumors. There was no evidence of any toxic effects from [11C] ACPC, and the radiation doses as extrapolated from animal data are approximately 0.01 rad per mCi for the whole body and less than 0.06 rad per mCi for the pancreas. In all but five of the 38 patients [11C] ACPC scans were compared with those obtained with Ga-67 citrate. There were 19 positive [11C] ACPC scans and 24 positive Ga-67 scans. The results indicate that [11C] ACPC is likely to be of diagnostic value for cancer patients if used in conjunction with positron tomography instrumentation.

Carbon-11-labeled amino acids for the rectilinear and positron tomographic imaging of the human pancreas.

Modification of the Bücherer-Strecker amino acid synthesis facilitated the production of DL-[11C]tryptophan and DL-[11C]valine for clinical trials in patients with proven or suspected pancreatic disease. Examples of rectilinear scans and tomographic images of the pancreas are presented in this initial paper. Positron computed tomography was done with the ORTEC ECAT system. Rapid localization of these C-11-labeled amino acids and fast clearance from the plasma permit almost immediate examination following i.v. injection. Illustrative images include the normal pancreas, pancreatitis, and pancreatic carcinoma. The use of positron tomobraphy with C-11-labeled DL-tryptophan and DL-valine appears to offer a new and promising diagnostic modality for the detection and study of pancreatic diseases.

Gallium-67 citrate imaging in Hodgkin's disease: final report of cooperative group.

A large cooperative study of Ga-67 uptake in Hodgkin's disease showed that 88% of untreated patients had a positive uptake in one or more lesions. The percent of individual lesions seen on scan, however, was significantly lower; this indicated that negative findings at any one site do not argue strongly against the possiblilty of a lesion there. After treatment, the number of visualized lesions decreased sharply, but the exact role of Ga-67 in evaluating therapy is still not clear. Of the various histologic types of Hodgkin's disease, there was a high incidence of localization in all except the lymphocyte-predominance type, which showed a slightly lower uptake. No lesions less than 1 cm in diameter were successfully imaged and the size most easily detected was 4 cm in diameter. As expected, the imaging technique was much less successful for abdominal lesions than for those at other sites because of interfering concentration in bowel and liver. Both radiotherpy and chemotherapy tend to reverse the abnormalities seen on scan. The finding of a significant number of unsuspected positive lesions in asymptomatic patients returning for routine followup suggests that this is a distinctly valuable use of Ga-67, allowing early therpy for recurrences.

Reactivity of lichen lectins with blood typed canine erythrocytes.

Extracts from 69 species of lichens were tested for their ability to agglutinate untreated and enzyme-modified erythrocytes from a panel of blood typed dogs. Forty-three lichen species reacted positively with either untreated or enzyme-modified cells. Many extracts exhibited differential agglutination among red cells tested. The patterns of differential agglutination observed with the lichen extracts did not correspond to known canine blood groups present on the test red cell panel.

Chromogranin A plasma concentration and expression in pancreatic islet cell tumors of dogs and cats.

OBJECTIVES: To describe expression of the neuroendocrine marker chromogranin A (CgA) in canine and feline pancreatic islet cell tumors and their metastases, and to evaluate plasma CgA concentration in dogs and cats with insulinoma. SAMPLE POPULATION: Paraffin-embedded tissues from 25 canine and 2 feline pancreatic islet cell tumors, 5 canine and 6 feline exocrine pancreatic tumors, and normal pancreatic tissue from 2 dogs and 2 cats. Heparinized plasma samples from 3 dogs and 2 cats diagnosed with insulinoma, and 10 control plasma samples from each species. PROCEDURE: Immunohistochemical analysis was performed on the 42 tissue specimens, using antisera against CgA, neuron-specific enolase, insulin, somatostatin, glucagon, and pancreatic polypeptide. The 25 plasma samples were evaluated, using a soluble-phase, double-antibody, equilibrium radioimmunoassay directed against the amino- and carboxy-terminal peptides of bovine CgA. RESULTS: Chromogranin A expression was found in 76% of canine and 2 of 2 feline pancreatic islet cell tumors. Of 7 animals with CgA immunoreactivity in primary tumors, 6 also had CgA immunostaining of metastatic lesions. Plasma CgA concentration in 2 dogs with insulinoma (0.9, 1.0 ng/ml) exceeded the reference range established for 10 clinically normal control dogs (0.50 +/- 0.16 ng/ml). Feline plasma CgA samples had extensive nonspecific background immunoreactivity. CONCLUSIONS: Chromogranin A is a useful immunohistochemical marker for pancreatic tumors of neuroendocrine origin and their metastases. Plasma CgA concentration determined by radioimmunoassay was high in 2 dogs with insulinoma. CLINICAL RELEVANCE: Immunohistochemical staining of tissues or cytologic specimens for CgA and/or neuron-specific enolase may help distinguish masses of unknown origin as neuroendocrine in nature. Increase in plasma CgA concentration may be useful diagnostically for animals with suspected neuroendocrine tumors.

Inhibition of equine complement activity by polysulfated glycosaminoglycans.

The ability of polysulfated glycosaminoglycans (PSGAG) to inhibit the complement cascade was evaluated. The role of complement in inflammation and infection has been well documented. Inhibition of the complement cascade by PSGAG could explain why intra-articularly administered PSGAG diminish diarthrodial joint inflammation and potentiate septic arthritis in horses. Hemolytic complement testing was performed to evaluate the effect of PSGAG on the equine classical and alternate pathways of complement, using rabbit erythrocytes as the target cells. Concentration of PSGAG between 0.2 mg/ml and 0.6 mg/ml significantly (P less than 0.05) inhibited equine complement in dose-related fashion. Further increase in complement inhibition was not observed at PSGAG concentration greater than 0.6 mg/ml. Difference was not apparent in the extent of inhibition of complement from each of the 4 horses tested. Polysulfated glycosaminoglycans appeared to inhibit the classical and alternate complement pathways equally, indicating possible effect on complement components common to both pathways. Heat inactivation of complement function completely inhibited (P less than 0.01) the hemolytic activity of the serum from all horses.

Unintentional intra-arterial injection of a bone-imaging agent.

The inadvertent intra-arterial injection of a dose of Tc-99m-MDP is reported. Limited quantitative studies were done on the distribution pattern. More extensive investigations of cases of this type may yield useful data on the behavior of radiopharmaceuticals.

Production, characterization, and applications of a murine monoclonal antibody to dog erythrocyte antigen 1.1.

A murine IgM monoclonal antibody, which recognizes dog erythrocyte antigen (DEA) 1.1, has been produced. The antibody correctly identified canine RBC possessing DEA 1.1 in a panel of RBC typed by an independent laboratory. Reactivity of the monoclonal antibody was compared with canine anti-DEA 1.1 antiserum with 163 RBC samples from 145 dogs. Results of agglutination tests with the 2 reagents were in agreement for all samples. A card agglutination test that uses the monoclonal antibody with blood is described. A monoclonal antibody-based test should facilitate blood typing for DEA 1.1 in clinical practice.

Hepatotoxicity of stanozolol in cats.

OBJECTIVE: To determine hepatotoxicity of stanozolol in cats and to identify clinicopathologic and histopathologic abnormalities in cats with stanozolol-induced hepatotoxicosis. DESIGN: Clinical trial and case series. ANIMALS: 12 healthy cats, 6 cats with chronic renal failure, and 3 cats with gingivitis and stomatitis. PROCEDURES: Healthy cats and cats with renal failure were treated with stanozolol (25 mg, i.m., on the first day, then 2 mg, p.o., q 12 h) for 4 weeks. Cats with gingivitis were treated with stanozolol at a dosage of 1 mg, p.o., every 24 hours. RESULTS: Most healthy cats and cats with renal failure developed marked inappetence, groomed less, and were less active within 7 to 10 days after initiation of stanozolol administration. Serum alanine transaminase (ALT) activity was significantly increased in 14 of 18 cats after stanozolol administration, but serum alkaline phosphatase activity was mildly increased in only 3. Four cats with serum ALT activity > 1,000 U/L after only 2 weeks of stanozolol administration had coagulopathies; administration of vitamin K resolved the coagulopathy in 3 of the 4 within 48 hours. All 18 cats survived, and hepatic enzyme activities were normal in all cats tested more than 4 weeks after stanozolol administration was discontinued. Two of the 3 cats with gingivitis developed evidence of severe hepatic failure 2 to 3 months after initiation of stanozolol treatment; both cats developed coagulopathies. Histologic evaluation of hepatic biopsy specimens from 5 cats revealed diffuse hepatic lipidosis and cholestasis without evidence of hepatocellular necrosis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that stanozolol is hepatotoxic in cats.

Respiratory diagnostic pathology.

Effective treatment and control of bovine respiratory disease is dependent upon an accurate diagnosis. This article discusses the approach to diagnosis of bovine respiratory disease from the perspective of respiratory pathology. Topics covered include necropsy examination of the respiratory system, sample collection and submission, and the gross, and histopathologic lesions of the upper and lower bovine respiratory system.