Anatomical and physiological basis for the allometric scaling of cisplatin clearance in dogs

Cisplatin is a platinum‐containing cytotoxic drug indicated for the treatment of solid tumors in veterinary and human patients. Several of the algorithms used to standardize the doses of cytotoxic drugs utilize allometry, or the nonproportional relationships between anatomical and physiological variables, but the underlying basis for these relationships is poorly understood. The objective of this proof of concept study was to determine whether allometric equations explain the relationships between body weight, kidney weight, renal physiology, and clearance of a model, renally cleared anticancer agent in dogs. Postmortem body, kidney, and heart weights were collected from 364 dogs (127 juveniles and 237 adults, including 51 dogs ≥ 8 years of age). Renal physiological and cisplatin pharmacokinetic studies were conducted in ten intact male dogs including two juvenile and eight adult dogs (4–55 kg). Glomerular filtration rate (GFR), effective renal plasma flow, effective renal blood flow, renal cisplatin clearance, and total cisplatin clearance were allometrically related to body weight with powers of 0.75, 0.59, 0.61, 0.71, and 0.70, respectively. The similar values of these diverse mass exponents suggest a common underlying basis for the allometry of kidney size, renal physiology, and renal drug handling.     

Constitutive expression of types 1 and 2 cytokines by alveolar macrophages from feline immunodeficiency virus-infected cats

Evidence suggests that feline immunodeficiency virus (FIV), causes pulmonary immunodeficiency. The overall objective of this study was to explore FIV-induced alterations in cell counts and cytokine gene expression in the pulmonary compartment during the acute stage infection. Bronchoalveolar lavage (BAL) cells were collected from FIV-infected and control cats at 0, 4, 10, and 16 weeks post-FIV infection for phenotype and cytokine analysis. The major change in BAL cellular populations following FIV-infection was the development of a neutrophilia. Total BAL cell counts and relative numbers of alveolar macrophages (AM), eosinophils, and lymphocytes remained similar in both groups. The RT-qcPCR analyses of AM purified from BAL showed constitutive expression of TNFalpha, IL6 and IL10 mRNAs that peaked during the acute stage of infection then declined. The TNFalpha and IL6 bioactive protein secretion showed a similar response. In contrast, IFNgamma expression increased progressively with time after infection and paralleled a progressive increase in FIV-gag mRNA in AM. The IL12 p40 expression also differed from the other cytokines in that there was a progressive decrease in the number of cats with AM IL12 expression following FIV infection. Infection of AM in vitro with FIV also caused an increase in TNFalpha and IL6 mRNA and bioactive protein suggesting that the increased cytokine response by AM following infection of cats with FIV is an intrinsic characteristic of FIV-infected AM. In summary, pulmonary immune changes seen in FIV-infected cats are similar to those seen in HIV-infected human patients.     

Endotoxn-induced nonthyroidal illness in dogs

OBJECTIVE: To determine the effects of endotoxin administration on thyroid function test results and serum tumor necrosis factor-alpha (TNF-alpha) activity in healthy dogs. ANIMALS: 6 healthy adult male dogs. PROCEDURES: Serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3'5'-triiodothyronine (rT3), free T4 (fT4), and endogenous canine thyroid stimulating hormone (TSH), and TNF-alpha activity were measured before (day-1; baseline), during (days 0 to 3), and after (days 4 to 24) IV administration of endotoxin every 12 hours for 84 hours. RESULTS: Compared with baseline values, serum T3 concentration decreased significantly, whereas rT3 concentration increased significantly 8 hours after initial endotoxin administration. Serum T4 concentration decreased significantly at 8 and 12 hours after initiating endotoxin administration. Serum T4 concentration returned to reference range limits, then decreased significantly on days 6 to 12 and 16 to 20. Serum fT4 concentration increased significantly at 12, 24, and 48 hours after cessation of endotoxin treatment, compared with baseline values. Serum rT3 concentration returned to reference range, then decreased significantly days 5 and 7 after stopping endotoxin treatment. Serum TNF-alpha activity was significantly increased only 4 hours after initial endotoxin treatment, compared with baseline activity. CONCLUSIONS AND CLINICAL RELEVANCE: Endotoxin administration modeled alterations in thyroid function test results found in dogs with spontaneous nonthyroidal illness syndrome. A decrease in serum T4 andT3 concentrations and increase in serum rT3 concentration indicate impaired secretion and metabolism of thyroid hormones. The persistent decrease in serum T4 concentration indicates that caution should be used in interpreting serum T4 concentrations after resolution of an illness in dogs.     

Ameloblastic odontoma in the mandible of a llama

A 4-year-old llama had an aggressive, multiloculated, expansile bone lesion involving the rostral mandible. The mandibular lesion was imaged using radiography and computed tomography. Antemortem diagnosis of an ossifying fibroma was made histologically. Postmortem findings showed the lesion to be limited to the mandible. Final diagnosis was ameloblastic odontoma.     

Comparison of core needle biopsy and fine-needle aspiration of enlarged peripheral lymph nodes for antemortem diagnosis of enzootic bovine lymphosarcoma in cattle

OBJECTIVE: To determine whether antemortem core needle biopsy and fine-needle aspiration of enlarged peripheral lymph nodes could be used to distinguish between inflammation and lymphosarcoma in cattle. DESIGN: Prospective study. ANIMALS: 25 cattle with enlarged peripheral lymph nodes. PROCEDURES: Antemortem biopsies of the selected lymph nodes were performed with an 18-gauge, 12-cm core needle biopsy instrument. Fine-needle aspirates were performed with a 20-gauge, 4-cm needle. Specimens were analyzed by pathologists who were unaware of clinical findings and final necropsy findings, and specimens were categorized as reactive, neoplastic, or nondiagnostic for comparison with necropsy results. RESULTS: Sensitivity and specificity of core needle biopsy ranged from 38% to 67% and from 80% to 25%, respectively. Sensitivity of fine-needle aspiration ranged from 41% to 53%, and specificity was 100%. Predictive values for positive test results ranged from 77% to 89% for core needle biopsy and were 100% for fine-needle aspiration. Predictive values for negative test results were low for both core needle biopsy and fine-needle aspiration. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that core needle biopsy and fine-needle aspiration can aid in the antemortem diagnosis of bovine enzootic lymphosarcoma. Results of fine-needle aspiration of enlarged peripheral lymph nodes were more specific and more predictive for a positive test result than were results of core needle biopsy.     

AN INTRATHORACIC MALIGNANT PERIPHERAL NERVE SHEATH TUMOR IN A DOG

A 7-year-old, neutered male Labrador Retriever presented for a persistent, productive cough and regurgitation. Radiography, ultrasonography, and computed tomography confirmed a large, smoothly marginated intrathoracic mass causing tracheal compression. The mass was removed via a thoracotomy, and a malignant peripheral nerve sheath tumor, most likely originating from the ventral spinal nerve roots, was confirmed using immunohistochemistry.     

Hairy vetch (Vicia villosa Roth) poisoning in cattle: update and experimental induction of disease.

Hairy vetch poisoning (vetch-associated disease) of cattle is a generalized disease characterized pathologically by infiltration of skin and many internal organs by monocytes, lymphocytes, plasma cells, and often eosinophils and multinucleated giant cells and clinically by dermatitis, pruritis, often diarrhea, wasting, and high mortality. The disease was experimentally reproduced in an adult Angus female that had recovered from the natural disease 1 year earlier. She developed dermatitis on the 11th day of vetch feeding, and despite withdrawal from the vetch diet on the 12th day, death occurred 24 days after first day of vetch feeding. The cow developed lymphocytosis and hyperproteinemia. The results of other hematologic evaluations, blood chemical profiles, urinalysis, and cutaneous hypersensitivity tests using vetch lectin were normal. Lymphocyte blastogenesis studies with vetch lectin were not interpretable. Necropsy revealed gross lesions characteristic of the disease in the skin, heart, kidney, adrenal, and lymphoid tissues. Microscopically there was typical cellular infiltration in those organs and in the thyroid, liver, pancreas, salivary and mammary glands, urinary bladder, corpus luteum, and cerebral meninges. Cutaneous apocrine gland necrosis was present. The inflammatory reaction has qualities of a type-IV hypersensitivity reaction. Hypersensitivity may occur when constituents of the ingested plant are absorbed and act as antigens that sensitize lymphocytes and evoke the multisystemic granulomatous inflammatory response that characterizes the disease. Alternatively, vetch lectin may directly activate T lymphocytes to initiate the cellular response. Vetch-like diseases have been associated with a variety of diets that did not contain hairy vetch.(ABSTRACT TRUNCATED AT 250 WORDS)     

Juvenile nephropathy in two related Pembroke Welsh corgi puppies

Juvenile nephropathy has been documented in many breeds. Two related Pembroke Welsh corgi puppies presented at three and five months of age, respectively, for evaluation of lethargy, diarrhoea, poor body condition, polyuria and proteinuria. Based upon the clinical presentation, urinalysis and serum biochemistry, chronic renal failure was diagnosed. Renal histopathology was consistent with juvenile nephropathy, revealing lesions similar to the juvenile renal disease of dobermann dogs. To the authors' knowledge, this is the first report of juvenile nephropathy in related Pembroke Welsh corgi dogs. Familial nephropathy should now be considered as a differential diagnosis in cases of young Pembroke Welsh corgi dogs presenting with clinical signs indicating renal failure.