Response of dogs with functional pituitary macroadenomas and macrocarcinomas to radiation

A prospective study was conducted to assess the use of radiation therapy for treatment of dogs with large, functional pituitary tumours and pituitary-dependent hyperadrenocorticism. Four dogs received only pituitary irradiation, whereas two dogs received irradiation and concurrent mitotane treatment. Effects of radiation therapy on tumour size and function were assessed by sequential CT scans, ACTH assays and ACTH stimulation tests. Reduction in tumour size and resolution of neurological abnormalities occurred in all dogs. The mean and median survival time following irradiation for dogs in this report was 740 days and 743 days, respectively. Atnecropsy, a pituitary chromophobe adenoma was detected in three dogs, and a pituitary carcinoma in one dog; necropsy was not carried out on two dogs. Pituitary hypersecretion of ACTH persisted for at     

Potassium depletion in cats: hypokalemic polymyopathy

Generalized weakness of acute onset, apparent muscular pain, and persistent ventroflexion of the neck were observed in 6 cats. These clinical signs were associated with a low serum potassium concentration and high serum creatine kinase activity. Generalized electromyographic abnormalities, together with normal motor nerve conduction velocity determinations, were detected in all cats. Muscle biopsy specimens from 4 of 5 cats were not abnormal on light microscopic examination. Mild necrosis and infrequent macrophages were evident in a muscle biopsy specimen from one cat. Signs of polymyopathy resolved in all cats, and creatine kinase activities returned to the normal range after parenteral and oral administration of potassium. Polymyopathy and hypokalemia recurred in 3 cats in which dietary potassium supplementation was not maintained after initial recovery from hypokalemic polymyopathy.     

Continuous low-dose oral chemotherapy for adjuvant therapy of splenic hemangiosarcoma in dogs

BACKGROUND: Hemangiosarcoma (HSA) is a highly metastatic and often rapidly fatal tumor in dogs. At present, conventional adjuvant chemotherapy provides only a modest survival benefit for treated dogs. Continuous oral administration of low-dose chemotherapy (LDC) has been suggested as an alternative to conventional chemotherapy protocols. Therefore, we evaluated the safety and effectiveness of LDC using a combination of cyclophosphamide, etoposide, and piroxicam as adjuvant therapy for dogs with stage II HSA. HYPOTHESIS: We hypothesized that oral adjuvant therapy with LDC could be safely administered to dogs with HSA and that survival times would be comparable to those attained with conventional doxorubicin (DOX) chemotherapy. ANIMALS: Nine dogs with stage II splenic HSA were enrolled in the LDC study. Treatment outcomes were also evaluated retrospectively for 24 dogs with stage II splenic HSA treated with DOX chemotherapy. METHODS: Nine dogs with stage II splenic HSA were treated with LDC over a 6-month period. Adverse effects and treatment outcomes were determined. The pharmacokinetics of orally administered etoposide were determined in 3 dogs. Overall survival times and disease-free intervals were compared between the 9 LDC-treated dogs and 24 DOX-treated dogs. RESULTS: Dogs treated with LDC did not develop severe adverse effects, and long-term treatment over 6 months was well-tolerated. Oral administration of etoposide resulted in detectable plasma concentrations that peaked between 30 and 60 minutes after dosing. Both the median overall survival time and the median disease-free interval in dogs treated with LDC were 178 days. By comparison, the overall survival time and disease-free interval in dogs treated with DOX were 133 and 126 days, respectively. CONCLUSIONS: Continuous orally administered LDC may be an effective alternative to conventional high-dose chemotherapy for adjuvant therapy of dogs with HSA.     

Immune regulation of canine tumour and macrophage PD‐L1 expression

Expression of programmed cell death receptor ligand 1 (PD‐L1) on tumor cells has been associated with immune escape in human and murine cancers, but little is known regarding the immune regulation of PD‐L1 expression by tumor cells and tumor‐infiltrating macrophages in dogs. Therefore, 14 canine tumor cell lines, as well as primary cultures of canine monocytes and macrophages, were evaluated for constitutive PD‐L1 expression and for responsiveness to immune stimuli. We found that PD‐L1 was expressed constitutively on all canine tumor cell lines evaluated, although the levels of basal expression were very variable. Significant upregulation of PD‐L1 expression by all tumor cell lines was observed following IFN‐γ exposure and by exposure to a TLR3 ligand. Canine monocytes and monocyte‐derived macrophages did not express PD‐L1 constitutively, but did significantly upregulate expression following treatment with IFN‐γ. These findings suggest that most canine tumors express PD‐L1 constitutively and that both innate and adaptive immune stimuli can further upregulate PD‐L1 expression. Therefore the upregulation of PD‐L1 expression by tumor cells and by tumor‐infiltrating macrophages in response to cytokines such as IFN‐γ may represent an important mechanism of tumor‐mediated T‐cell suppression in dogs as well as in humans.     

Association of Blood Monocyte and Lymphocyte Count and Disease‐Free Interval in Dogs with Osteosarcoma

Background: Identification of biomarkers that predict outcomes in dogs with osteosarcoma (OSA) would be valuable to veterinarians and owners. Leukocyte numbers in peripheral blood are associated with outcomes in some types of cancer in humans. Hypothesis/Objectives: We hypothesized that increased numbers of monocytes would be associated with reduced disease‐free interval (DFI) in dogs with OSA. Animals: Medical data from 69 dogs with appendicular OSA treated with amputation and chemotherapy were selected for study. Methods: Retrospective study. Statistical associations were assessed by univariate and multivariate analysis. Information about DFI and leukogram values, tumor location, and serum alkaline phosphatase was abstracted from the medical record. Results: Higher numbers of circulating monocytes (>0.4 × 10³ cells/μL) and lymphocytes (>1.0 × 10³ cells/μL) before treatment were found to be significantly (P < .05) associated with shorter DFI in dogs with OSA. Other parameters associated with poor outcomes were increased alkaline phosphatase, primary tumor location, and age. Conclusion and Clinical Importance: These results indicated that pretreatment evaluation of monocyte and lymphocyte counts provided prognostic information for dogs with appendicular OSA. Notably, most animals in this study had monocyte counts within the normal reference range, indicating that variations within the reference range of leukocyte values might also have prognostic significance.     

Hypodipsic hypernatremia and associated myopathy in a hydrocephalic cat with transient hypopituitarism

Hypodipsic hypernatremia developed in association with hypopituitarism and hydrocephalus in a 7-month-old cat. Initial clinical signs (generalized weakness, cervical ventroflexion) were related to a hypernatremia-induced polymyopathy. Forced water intake and dietary sodium restriction corrected the hypernatremia and signs of muscle dysfunction. After restoration of eunatremia, secretion of pituitary hormones normalized. It was speculated that hypothalamic dysfunction, possibly related to hydrocephalus, induced both hypodipsia and transient hypopituitarism.     

Central nervous system toxicosis associated with metronidazole treatment of dogs: five cases (1984-1987)

Metronidazole, administered to 5 dogs for periods ranging from 3 to 14 days, was associated with acute development of CNS dysfunction. Metronidazole dosage ranged from 67.3 to 129.0 mg/kg of body weight/d. Clinical signs of toxicosis began with anorexia and intermittent vomiting and progressed rapidly to include pronounced, generalized ataxia and vertical, positional nystagmus. These signs were consistent with lesions of the vestibular nuclei and/or cerebellum. High CSF protein content was detected in 2 of 3 dogs from which CSF was collected. Two dogs were euthanatized because of severe neurologic dysfunction. Three dogs improved slowly and recovered completely over several months. These findings suggest that currently recommended dosages of metronidazole may be too high for some dogs.     

Helpers: effects of experimental removal on reproductive success

Experimental removal of helpers from a communal bird population decreased the reproductive success of the reduced units. By controlling for variables that are potentially correlated with both reproductive success and unit size, this experiment establishes that helpers-contribute significantly to their indirect fitness.     

Checkpoint molecule expression by B and T cell lymphomas in dogs

Immunotherapies targeting checkpoint molecule programmed cell death 1 (PD‐1) protein were shown to be effective for treatment of non‐Hodgkin lymphoma in people, but little is known about the expression of PD‐1 or its ligand PD‐L1 by canine lymphoma. Therefore, flow cytometry was used to analyse expression of PD‐1 and PD‐L1 in canine lymphoma, using fine‐needle aspirates of lymph nodes from 34 dogs with B cell lymphoma (BCL), 6 dogs with T cell lymphoma (TCL) and 11 dogs that had relapsed. Furthermore, fine‐needle aspirates were obtained from 17 healthy dogs for comparison. Lastly, the impact of chemotherapy resistance on expression of PD‐1 and PD‐L1 was assessed in vitro. These studies revealed increased expression of PD‐L1 by malignant B cells compared to normal B cells. In the case of TCL, tumour cells and normal T cells both showed low to negative expression of PD‐1 and PD‐L1. In addition, tumour infiltrating lymphocytes from both BCL and TCL had increased expression of both PD‐1 and PD‐L1 expression compared to B and T cells from lymph nodes of healthy animals. In vitro, chemotherapy‐resistant BCL and TCL cell lines exhibited increases in both PD‐1 and PD‐L1 expression, compared to non‐chemotherapy selected tumour cells. These findings indicate that canine lymphomas exhibit upregulated checkpoint molecule expression, though the impact of checkpoint molecule expression on tumour biological behaviour remains unclear.