Influence of antibody infusion on pathogenesis of experimental feline leukemia virus infection.

For examination of the influence of antibody on the pathogenesis of feline leukemia virus (FeLV) infection, 12 weanling specific-pathogen-free cats were inoculated with isolates of FeLV and were treated beginning at 7, 19, 21, 24, 34, or 49 days post inoculation (DPI) with feline anti-FeLV hyperimmune serum (10 infusions, 37 mg globulin/kg each at 48-hr intervals). Anti-FeLV serum infusion initiated at 7 DPI prevented the onset of hematopoietic cell infection and viremia. Antibody treatment initiated at 19 or 24 DPI abrogated recently established FeLV viremia and extinguished p27 expression in bone marrow and blood cells. Viremia established for longer periods was refractory to antibody infusion despite establishment of enzyme-linked immunosorbent assay antibody titers of 1:80 to 1:320 in the treated cats. Latent FeLV infection was a sequel to antibody-induced curtailment of viral replication in bone marrow cells and was able to reactivate spontaneously in vivo as well as in vitro.

Physiological studies of whole-body hyperthermia of dogs.

Whole body hyperthermia to 42 degrees C was induced in five normal beagles, using a humidity- and temperature-controlled chamber. Core temperatures of 41.2-43.0 degrees C were achieved in 50 min and maintained for 60 min. Cardiopulmonary responses included marked tachypnea and tachycardia. Blood gases underwent progressive drops in both PO2 (mean, 117 torr) and PCO2 (mean, 22 torr), suggesting the possibility of the development of a diffusion barrier during heating. Increased anion gaps in the face of respiratory alkalosis indicated that a metabolic acidosis developed in the heated dogs. Transient but significant drops in serum potassium and phosphorus were also observed during hyperthermia. Other physiological data, including serum chemistries, complete blood count, colony-forming units, and urine electrolyte excretion, did not change significantly.

Unexpected toxicity associated with use of body surface area for dosing melphalan in the dog.

A multiinstitutional Phase I study using i.v. melphalan was conducted in dogs with spontaneously occurring neoplasia. Melphalan was administered at 7.5, 10, 11.25, 12.5, and 20 mg/m2 of body surface area. Disproportionately greater toxicity was observed in small dogs. Seven of the eight dogs (88%) weighing less than 14 kg experienced severe myelosuppression (neutropenia, less than 1500/mm3; and/or thrombocytopenia, less than 80,000/mm3), whereas only three of 13 dogs (23%) weighing greater than 14 kg developed severe myelosuppression (P = 0.016). We concluded that small dogs are at greater risk of developing bone marrow toxicity from i.v. melphalan than large dogs if body surface area is used to calculate the dose. Although both body surface area and weight were found to be significantly correlated with severity of toxicity, melphalan-induced toxicity in dogs can be more accurately estimated by body weight than by surface area, P = 0.008 versus P = 0.022, respectively. It may be necessary to prescribe antineoplastic agents that are eliminated by processes not primarily under metabolic influence or that produce side effects on tissue not correlated to basal metabolic rate on a parameter other than body surface area. In dogs, melphalan should be dosed on a weight basis, and treatment groups should be stratified by weight in randomized clinical studies, particularly when the weight range of treated subjects is great.

The synthesis of fluorine-18 lomefloxacin and its preliminary use in human studies.

Lomefloxacin is a new fluorine-containing antibiotic that has recently been approved for general use. Fluorine-18 lomefloxacin has been prepared by fluoride exchange between fluorine-18 fluoride and lomefloxacin in DMSO. Both time and temperature of the reaction have been optimized and conditions developed for the isolation and purification of the labeled product in a form suitable for oral administration. The exchange reaction provides sufficient labeled material for human studies with pharmacologically relevant quantities of the drug. We have performed preliminary human studies with this compound using positron emission tomography to estimate the tissue distribution of the compound and show the distribution of the compound into the liver and lungs.

Pathology of canine bladder and urethral cancer and correlation with tumour progression and survival.

Biopsy and necropsy specimens, comprising 107 primary carcinomas and three mesenchymal tumours, were reviewed from 110 dogs with cancer of the bladder, urethra, or both. Histological classifications developed for the assessment of human bladder cancer were found to be readily applicable to the dog. These classifications are based on histological features, including the pattern of growth, the cell type, the grade of transitional tumour and the depth of invasion of the bladder wall. Features associated with localized disease in canine transitional cell carcinoma included papillary architecture, "in-situ" tumour, low tumour grade and a strong peritumoral lymphoid cell reaction. Features of tumours with metastasis included infiltrating and non-papillary architecture, increasing tumour grade, depth of invasion, vascular invasion and presence of peritumoral fibrosing reaction. Wide variability was found within single tissue samples, indicating that multiple sample sites are necessary for the adequate characterization of a given lesion. Statistically significant correlations were found between: tumour grade and depth of invasion (P < 0.0001); tumour grade and presence of metastases (P < 0.029); and peritumoral desmoplasia and metastases (P < 0.029). It was concluded that canine bladder cancer could be classified for the purpose of clinical management with a modified World Health Organization system as developed for human tumours.

Phase I evaluation of doxorubicin and whole-body hyperthermia in dogs with lymphoma.

Fifteen previously untreated dogs with histologically confirmed, high-grade multicentric lymphoma were entered into a phase I study to evaluate combined doxorubicin and whole-body hyperthermia (DOX/WBH). Groups of three, four, and eight dogs were treated with whole-body hyperthermia and concurrent doxorubicin at 12 mg/m2, 24 mg/m2 and 30 mg/m2, respectively, after one doxorubicin induction dose at 30 mg/m2. Plateau temperature (42 +/- 0.1 degree C) was maintained for 90 minutes using a radiant heating device. A total of five DOX/WBH treatments per dog were planned, and these were given every 21 days. Treatment-related toxicity was not seen in the 12-mg/m2 doxorubicin dose group. Tumor progression prohibited administration of more than three DOX/WBH treatments to any dog in the 12-mg/m2 group. Premature ventricular contractions developed after the fifth treatment in one of the four dogs treated with 24 mg/m2 of doxorubicin. Two dogs (25%) in the 30-mg/m2 dose group had treatment-related toxicity. One dog experienced acute serious myelosuppression 1 week after the third treatment. This dog received all planned DOX/WBH treatments. Asymptomatic cardiac toxicosis consisting of decreased ejection fraction and fractional shortening developed in the second dog. This dog received only two DOX/WBH treatments. The three dogs treated at 12 mg/m2 had partial responses of short duration (60-83 days). Four dogs treated at 24 mg/m2 had complete responses for 150, 164, 186, and 200 days. Eight dogs treated at 30 mg/m2 had complete responses with a mean and median duration of 241 and 190 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Canine bladder and urethral tumors: a retrospective study of 115 cases (1980-1985).

One hundred and fifteen dogs with neoplasms of the lower urinary tract (bladder and/or urethra) were retrospectively evaluated at five referral institutions participating in ongoing studies by the Veterinary Cooperative Oncology Group. Most tumors were malignant (97%) and of epithelial origin (97%). Lower urinary tract tumors were more common in older dogs weighing greater than 10 kg. The following significant (P less than 0.05) statistical associations were found using the University of Guelph hospital population as control; there was no sex predisposition although the female:male ratio was 1.95:1. Neutered dogs were predisposed as were Airedale Terriers, Beagles, and Scottish Terriers, whereas German Shepherds were significantly under-represented among dogs with lower urinary tract tumors. These statistical associations should be interpreted cautiously because of possible demographic differences in hospital populations among the University of Guelph and other cooperating institutions. There were no significant correlations between age, gender, weight, breed, response to therapy, and survival time. Clinical signs were indicative of lower urinary tract disease and included hematuria, stranguria, and pollakiuria. The laboratory data were nonspecific except for urinalysis test results. Hematuria and inflammatory urinary sediments were most commonly reported; neoplastic cells were identified in the urine sediment of 30% of dogs with lower urinary tract tumors. Contrast cystography was a useful noninvasive diagnostic method since 96% of the dogs had a mass or filling defect in the lower urinary tract demonstrated by this technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Nephelometric determination of serum amylase and lipase in naturally occurring azotemia in the dog.

Serum amylase and lipase were measured in 32 healthy dogs and in 55 dogs with serum urea nitrogen values greater than 40 mg/dl, using a nephelometric analyzer (Coleman analyzer model 91). Mean serum amylase and lipase values in normal dogs were 1,085.48 units and 3.98 units, respectively. In dogs with azotemia, the mean serum amylase and lipase values were 1,822.79 units and 12.57 units, respectively. Serum urea nitrogen values could not be correlated with amylase or lipase values.

In vitro susceptibility of canine tumor stem cells to doxorubicin.

Thirty-four canine tumor specimens (13 sarcomas and 21 carcinomas) were grown in soft agar gel. Susceptibility after continuous exposure to doxorubicin at concentrations of 1, 5, and 10 micrograms/ml was compared with that of control cultures. Plating efficiency averaged 0.096%. Doxorubicin at a concentration of 1 microgram/ml was found to result in greater than 70% inhibition of colony formation in 3 of 13 sarcomas and 1 of 21 carcinomas tested, and greater than 50%, but less than 70%, inhibition in 3 carcinomas and 1 sarcoma. Twenty-six tumors had less than 50% reduction in colony formation and were considered resistant. Minor differences in responses to drug in primary and metastatic locations were observed and attributed to tumor heterogeneity and test variability.

Morphologic characteristics of the parathyroid and thyroid glands and serum immunoreactive parathyroid hormone in dogs with pseudohyperparathyroidism.

Hypercalcemia, normo- or hypophosphatemia, and increased urinary calcium clearance were observed in 8 dogs with malignant disease consisting of lymphosarcoma (n = 4), lymphogenous leukemia with bone involvement (n = 2), or carcinoma arising in the perianal region (n = 2). Parathyroid glands from these dogs had a normal or atrophic microscopic appearance. Ultrastructurally, the chief cells of the parathyroid glands had small cytoplasmic areas devoid of secretory granules and containing few organelles associated with hormonal synthesis, which is indicative of an inactive phase of the secretory cycle. In relationship to total serum calcium, serum canine immunoreactive parathyroid hormone was moderately increased in 3 dogs whose parathyroid glands had morphologic characteristics of inactivity. As a result of prolonged hypercalcemia, the thyroid glands contained prominent areas of parafollicular cell hyperplasia. The ultrastructure of a typical hyperplastic parafollicular cells was characterized by a large cytoplasmic area filled with numerous secretory granules and moderate numbers of organelles associated with hormonal synthesis. The results of this study indicate that some nonendocrine malignant neoplasms of dogs may be capable of secreting a hypercalcemia substance immunologically indistinguishable from parathyroid hormone. In the absence of neoplastic involvement of bone, the canine disease has many similarities to pseudohyperparathyroidism.

Effect of ophthalmic prednisolone acetate on the canine adrenal gland and hepatic function.

Iatrogenic hypothalamic-hypophysis-adrenal axis suppression occurred in 5 small dogs as a result of ophthalmic instillation of 1% prednisolone acetate. An ophthalmic suspension was applied 4 times a day to each eye, such that 4 mg/day was delivered for 2 weeks followed by 2.67 mg/day for 2 weeks. After treatment week 2, serum cortisol decreased from base-line mean values of 17.66 ng/ml (before ACTH) and 139.16 ng/ml (60 minutes after ACTH) to 3.22 ng/ml (before ACTH) and 13.58 ng/ml (60 minutes after ACTH). After treatment week 4, serum cortisol values decreased to a mean of 1.76 ng/ml (before ACTH) and 4.82 ng/ml (60 minutes after ACTH). Before ACTH cortisol values returned to base line 2 weeks after discontinuing treatment. Values after ACTH administration remained 26% lower than base line (P = 0.0132), although within a normal response range. Hepatic carbohydrate metabolism was altered, allowing marked glycogen accumulation. Marked increases in the blood glucose values after glucagon stimulation testing occurred at 3, 5, 15, 30, and 60 minutes after glucagon administration. The greatest increase corresponded to the 30-minute sample with a mean glucose increase of 112.40 mg/dl from base-line values (P = 0.0022) as a result of the ophthalmic corticosteroid applied. Seemingly, topical ophthalmic corticosteroids have the potential for causing adrenocortical suppression and hepatic metabolic changes. The dosage level of treatment was low enough to avoid major hematologic changes. The exaggerated response to the glucagon tolerance test indicates that this test can be used in detecting hyperglucocorticism.

Morphologic measurements of the external horizontal ear canal of dogs.

Microscopic anatomy of the horizontal part of the external ear canal was evaluated in 24 dogs. Sixteen dogs were from breeds known to have a predisposition to otitis externa. The remaining 8 dogs were from breeds that do not have a predisposition to otitis externa. Dogs were separated into groups according to predisposition to otitis externa: group 1-predisposed dogs without otic inflammation, group 2-predisposed dogs with otic inflammation, and group 3-nonpredisposed dogs without otic inflammation. Qualitative microscopic evaluation of distribution of hair follicles revealed hair within proximal, middle, and distal regions of the horizontal ear canal in all breeds. The degree of keratinization was directly proportional to the presence of otic inflammation and was excessive in group-2 dogs. Quality of sebaceous glands within the horizontal ear canal was similar among dogs with and without otitis externa, whereas the quantity of apocrine tubular glands was significantly increased (P less than 0.05) in dogs with otitis. Quantity of apocrine tubular glands was also greater in group-1 dogs than in group-3 dogs. Thickness of the soft tissue in the external ear canal increased in direct proportion to the progression of disease and was greatest in the proximal region of the affected ear canal. Soft tissue located caudally between nonopposing ends of the annular cartilage, within the proximal region of the horizontal ear canal, contained few glands and hair follicles in dogs without otitis externa. In dogs with otitis externa, this region was infiltrated by distended apocrine tubular glands.

Treatment with a combination of doxorubicin, surgery, and radiation versus surgery and radiation alone for cats with vaccine-associated sarcomas: 25 cases (1995-2000).

OBJECTIVE: To compare use of doxorubicin, surgery, and radiation versus surgery and radiation alone for treatment of cats with vaccine-associated sarcoma. DESIGN: Retrospective study. ANIMALS: 25 cats with vaccine-associated sarcomas. PROCEDURE: Time to first recurrence and survival time were compared between the 2 treatment groups. The number of surgeries (1 or > 1) were compared with respect to time to first recurrence and survival time. RESULTS: Median time to first recurrence was 661 days for the group that received doxorubicin, surgery, and radiation. Median time to first recurrence has not yet been attained for the group treated with surgery and radiation alone. Median survival time was 674 days for the group treated with doxorubicin, surgery, and radiation and 842 days for the group treated with surgery and radiation alone. For time to first recurrence and survival time, significant differences were not detected between cats that had 1 surgery and those that had > 1 surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Significant differences between the 2 treatment groups were not detected. The efficacy of doxorubicin in the treatment of vaccine-associated sarcomas is uncertain.

Canine mast cell tumors.

Despite the fact that the mast cell tumor is a common neoplasm of the dog, we still have only a meager understanding of its etiology and biologic behavior. Many of the published recommendations for treatment are based on opinion rather than facts derived from careful studies and should be viewed with some skepticism. Because of the infrequent occurrence of this tumor in man, only a limited amount of help can be expected from human oncologists; therefore, burden of responsibility for progress in predicting behavior and developing treatment effective for canine mast cell tumors must fall on the shoulders of the veterinary profession.

The potential role of inflammation in the development of postvaccinal sarcomas in cats.

Epidemiologic evidence shows a strong association between the administration of inactivated feline vaccines (feline leukemia virus and rabies) and subsequent soft tissue sarcoma development at vaccine sites. Although more research is needed to understand the complete pathogenesis of vaccine-induced tumors in cats, good evidence exists that inflammation plays a role.

Involving parents in special programming.

Parent programming is defined as direct services to parents which may include assistance in managing personal or family life as well as assistance in developing knowledge, skills and attitudes. The content and methodology of parent programming should be based on the beliefs and assumptions of both parents and professionals. Competency-based programming is presented as a promising approach to improving parent competence. Results of initial studies in parent competency identification, prioritization and assessment are discussed along with procedures for instructional programming.