Use of cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II), a liposomal cisplatin analogue, in cats with oral squamous cell carcinoma.

OBJECTIVE: To determine clinical response and toxic effects of cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II) (L-NDDP) administered i.v. at escalating doses to cats with oral squamous cell carcinoma (SCC). ANIMALS: 18 cats with oral SCC. PROCEDURE: Cats that failed to respond to conventional treatment or had nonresectable tumors were included. Data included a CBC, serum biochemical analyses, urinalysis, cytologic examination of a fine-needle aspirate of enlarged lymph nodes, and thoracic and oral radiographs for clinical staging. A starting dose (75 to 100 mg/m2 of L-NDDP) was administered i.v.. At 21-day intervals, subsequent doses increased by the rate of 5 or 10 mg/m2. Response was evaluated every 21 days by tumor measurement and thoracic radiography. Quality of life was assessed by owners, using a performance status questionnaire. RESULTS: On average, cats received 2 treatments. Toxicoses included an intermittent, acute anaphylactoid-parasympathomimetic reaction, lethargy or sedation (< or = 24 hours), inappetence or signs of depression (< or = 72 hours), mild to moderate increase in hepatic enzyme activity, and melena. Pulmonary, renal, or hematopoietic abnormalities were not evident. Performance status surveys indicated normal behavior and grooming or decreased activity and self-care (19/20 assessments), ate well with or without assistance (15/20), and did not lose weight (15/20). Median survival time was 59.8 days (mean, 54.1 days). CONCLUSIONS AND CLINICAL RELEVANCE: L-NDDP was ineffective for treatment of cats with oral SCC. None of the cats had a complete or partial remission. Acute toxicoses and poor therapeutic response limit therapeutic usefulness of L-NDDP in cats, unless dosage, frequency, and administration procedures can be improved.

Evaluation of toxicosis of liposome-encapsulated cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II) in clinically normal cats.

OBJECTIVE: To determine adverse effects of single and multiple doses of liposome-encapsulated cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II) (L-NDDP) administered IV to healthy adult cats. ANIMALS: 10 healthy adult cats. PROCEDURE: 8 cats were given a single dose of L-NDDP (at rates of 75, 100, 150, or 200 mg/m2), and 2 cats were given liposomal lipid (1,500 mg/m2). Six of the 10 cats were given doses of L-NDDP at the maximum tolerated dosage (100 mg/m2) or a lower dosage (75 mg of L-NDDP/m2) at 21-day intervals, for a total of 4 treatments. Hematologic and serum biochemical analyses, urinalyses, and physical examinations were used to monitor effects of L-NDDP. RESULTS: All cats had transient pyrexia, lethargy, vomiting (1 to 3 times/24 h), inappetence, and an acute species-specific infusion reaction that was prevented by administration of atropine-diphenhydramine. Dose-limiting toxicosis was evident as a 10-day course of lethargy, intermittent vomiting, and diarrhea. In cats given multiple doses, dose-related thrombocytopenia, cumulative myelosuppression, transient increased hepatic transaminase activity, and mild to moderate hepatic hydropic degeneration and proximal renal tubular lipidosis in excess of lipidosis expected for this species were detected. Bone marrow hypoplasia was detected in some cats that received higher doses (cumulative dosages of 300 or 400 mg of L-NDDP/m2). CONCLUSION: Cats can safely be given L-NDDP at potentially therapeutic dosages without inducing renal or pulmonary toxicoses. CLINICAL RELEVANCE: Because L-NDDP has better tumoricidal activity than cisplatin (in vivo and in vitro) and is not cross resistant, it may be similarly or more efficacious than cisplatin in humans and dogs.

Adrenal ultrasonography correlated with histopathology in ferrets.

The adrenal glands of twenty-six, 12- to 53-month-old, ferrets without clinical signs of adrenal disease were examined and measured by ultrasonography and the findings compared with those from gross examination and histopathology. Of 51 adrenal glands examined, 27 were normal, 23 had either nodular or diffuse cortical hyperplasia and 1 had an adenocarcinoma. There was no statistically significant difference between the sonographic nor gross size of normal adrenal glands and those with hyperplasia. Moderate correlation was found between gross and sonographic measurements of length for both right (r = 0.783; p < 0.0001) and left (r = 0.609; p < 0.001) and width (p < 0.02). In female ferrets, the length, width, and depth of the right adrenal gland sonographically measured (mean +/- sd) 7.5 +/- 1.2 mm, 3.7 +/- 0.6 mm, 2.8 +/- 0.4 mm, respectively, and the left measured 7.4 +/- 1.0 mm, 3.7 +/- 0.4 mm, 2.8 +/- 0.4 mm; in males, the right adrenal measured 8.9 +/- 1.6 mm, 3.8 +/- 0.6 mm, 3.0 +/- 0.8 mm and the left measured 8.6 +/- 1.2 mm, 4.2 +/- 0.6 mm, 3.0 +/- 0.6 mm. Accessory adrenal tissue was not identified during the sonographic examination but was grossly found in 10 of the ferrets. It was associated with either the right, left or both adrenal glands.

Distribution and appearance of elastic fibers in the dermis of clinically normal dogs and dogs with solar dermatitis and other dermatoses.

OBJECTIVE: To determine the distribution and amount of elastic fibers in the dermis of clinically normal dogs and dogs with dermatoses, particularly solar dermatitis. DESIGN: Skin specimens from 7 anatomic sites were obtained from 19 clinically normal dogs after euthanasia to evaluate the normal distribution of elastic fibers. Biopsy specimens also were obtained from 34 dogs with dermatoses, including 16 with solar dermatitis. Tissue sections were stained with H&E, Verhoeff-van Gieson, and periodic acid-Schiff. ANIMALS: 19 clinically normal dogs and 34 dogs with dermatoses. PROCEDURE: Numbers of elastic fibers were graded subjectively. Comparisons between clinically normal dogs and dogs with dermatoses were made. RESULTS: Normal elastic fibers were present in low numbers in the dermis of adult dogs, regardless of anatomic site or presence or severity of dermatitis. Condensed elastotic material was visualized in only 2 dogs with solar dermatitis. In both dogs, the elastotic material was Verhoeff-van Gieson and periodic acid-Schiff stain positive but was not visible with H&E stain. The most frequent histopathologic finding in the dermis of dogs with solar dermatitis was superficial dermal fibrosis. CONCLUSIONS: The dermis of clinically normal dogs does not contain abundant elastic fibers. Alterations of elastic fibers in dogs with solar dermatitis are rare. Superficial dermal fibrosis may be a better indicator of solar damage.

Cutaneous hemangiosarcoma in 25 dogs: a retrospective study.

Hemangiosarcomas confined to the skin and underlying muscle were surgically excised in 25 dogs. Tumors were staged based on their histological location (ie, dermal, hypodermal, and deep). Dermal (stage I) hemangiosarcomas were small, most commonly ventral-abdominal or prepucial in location, and were associated with prolonged survival times (median survival, 780 days). Tumors with hypodermal (stage II) and underlying muscular involvement (stage III) were grouped together because of their larger size, bruise-like appearance, lack of anatomic predilection, biological behavior, and shorter survival times (median survival of 172 and 307 days for dogs with stages II and III, respectively). We conclude that dermal hemangiosarcomas may be effectively treated with surgery alone, whereas hemangiosarcomas located within the hypodermal tissues bear a poor prognosis and warrant wide surgical excision with adjuvant chemotherapy.

Focal gingival hyperplasia in a horse.

A diagnosis of gingival hyperplasia in a 22-year-old Quarter Horse gelding was confirmed by histologic examination. Clinical signs included difficulty eating hay, and a large, intraoral soft tissue mass measuring 13 x 8 x 4.5 cm. The mass was located in the mucosa on the lingual aspect of the caudal left portion of the mandible, ventral to the base of the tongue, and covered the second and third lower molars, extending rostrally along the buccal mucosa to the premolars. The left maxillary second and third molars were overgrown with sharp edges. Lateral radiography of the mandible revealed absence of the left third molar, with associated bony irregularity and sclerosis. The horse was positioned in right lateral recumbency under general anesthesia, and the entire mass was resected. It was speculated that the lesion developed secondary to chronic irritation from opposing teeth and food-packing after loss of the lower third molar; this would not be an unexpected development in a species with continuously advancing molars.

Focal metatarsal fistulas in five dogs.

Focal metatarsal fistulas were identified in 5 young adult German Shepherd Dogs or dogs of similar breeding. A specific cause was not identified when biopsy specimens for culture and histologic examination were evaluated. Corticosteroid treatment was beneficial for some lesions. The dogs did not have other dermatologic diseases, and the clinical course, although chronic, was generally benign.

Arteriovenous differences for glutamine in the equine gastrointestinal tract.

Glutamine has been shown to be an important metabolic substrate of enterocytes in many animals, including cats, dogs, hamsters, human beings, monkeys, rabbits, rats, and sheep. To determine whether glutamine is important in the metabolism of cells of the equine gastrointestinal tract, we examined transintestinal differences in glutamine concentrations in the arterial and venous circulation, and measured activity of the major glutamine catabolizing enzyme, glutaminase. Arteriovenous differences provide an index of the amount of a given substrate removed by the tissue across which the measurements are made, and commonly are expressed as a percentage of substrate removed, or percent extraction. Arteriovenous differences for glutamine were determined in 7 anesthetized adult horses (weight, 450 to 500 kg) before and after an i.v. glutamine infusion. The mean baseline arterial glutamine concentration (+/- SEM) was 572 +/- 24 microM; this concentration quadrupled (to 2,167 +/- 135 microM, P less than 0.01) 1 minute after i.v. bolus infusion of a 17.5-g glutamine load. Baseline extraction by the portal-drained viscera was 7.5 +/- 1.5%; this value increased to 18 +/- 2% at 1 minute (P less than 0.01) and had returned to baseline values 60 minutes later. Arteriovenous differences were greatest across the jejunum (11.8 +/- 1.8% in the baseline period vs 33.1 +/- 3.1% at 1 minute, P less than 0.001), with smaller differences across the colon, suggesting that the jejunum was the more avid utilizer of glutamine. Glutaminase activity was 4.38 +/- 0.16 and 4.00 +/- 0.60 mumol/mg of protein/h under standard conditions in jejunal and ileal mucosa, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholinergic pruritus in a horse.

An 8-year-old gelding, with a 1-year history of intense pruritus only after exercise, was diagnosed as having cholinergic pruritus. Provocative testing, using exercise and hot-water baths to increase core body temperature, assisted in the diagnosis. Cholinergic pruritus in human beings is a variant of the more common syndrome, cholinergic urticaria, which is characterized by intense pruritus and pinpoint urticaria. With cholinergic pruritus, intense itching results without urticaria. Specific diagnostic laboratory tests have not been developed.

Hyperthyroidism associated with a thyroid adenoma in a dog.

Hyperthyroidism associated with thyroid adenoma was diagnosed in a dog. Typical clinical signs of hyperthyroidism were resolved with surgical excision of the adenoma. Hyperthyroidism in dogs usually is associated with thyroid carcinoma, which has a poor prognosis. This case emphasizes the importance of obtaining a histologic diagnosis of thyroid tumors in hyperthyroid dogs before giving a prognosis.

Characteristics of canine melanomas and comparison of histology and DNA ploidy to their biologic behavior.

The biologic behavior of 179 formalin-fixed, paraffin-embedded canine melanomas was correlated with their histologic appearance. In addition, flow cytometric analysis of DNA content was performed on 54 of these tumors. Histologic examination accurately predicted clinical course in 89% of the melanomas with known behavior. Flow cytometry accurately predicted behavior in 93% of tumors with diagnostic histograms and demonstrated malignant features in 100% of metastases from malignant oral tumors; histograms were non-diagnostic for 15% of tumors tested. Histologic examination, flow cytometry, and biologic behavior were in agreement for 93% of the tumors with diagnostic histograms. Interpretive problems were encountered in analyzing heavily pigmented melanomas using this flow cytometry technique.

Polysaccharide storage myopathy in canine phosphofructokinase deficiency (type VII glycogen storage disease).

A severe, progressive myopathy developed in an 11-year-old, phosphofructokinase (PFK)-deficient, male, English Springer Spaniel dog. Results from a routine neurological examination were normal. Examination of histologic sections of skeletal muscle revealed large accumulations of material in some myofibers. These deposits were pale, basophilic, somewhat flocculent, and slightly granular with hematoxylin and eosin stain. Most fascicles examined in sections of limb and trunk muscles were affected to some degree, with up to 10% of muscle fibers being involved. Deposits stained strongly with periodic acid-Schiff and were resistant to digestion by alpha amylase but were removed by incubation with gamma amylase. Deposits were faintly positive with Gomori's methenamine silver technique and alcian blue (pH 2.5) and were brown-gray with Lugol's iodine solution but were negative with other stains. Based on staining characteristics, the deposits seemed to consist primarily of an amylopectin-like polysaccharide(s). Alcian blue staining (pH 2.5) was removed by treatment with neuraminidase but not with hyaluronidase, indicating that some sialic acid residues were also present. Electron microscopically, the deposits were composed of short granular filaments, small granules and amorphous material. They were not membrane bound. The morphologic appearance and staining characteristics of the deposits were remarkably similar to deposits previously described in human PFK-deficient myopathy. As expected, total PFK activities were markedly reduced when assayed in skeletal muscles of this dog. In contrast with other PFK-deficient dogs, muscle glycogen in this animal was not increased above that of normal dogs.

Medical and surgical management of multiple organ infarctions secondary to bacterial endocarditis in a dog.

A 6-year-old male Doberman Pinscher developed multiple organ infarctions secondary to vegetative endocarditis. Clinical signs included fever, nystagmus, head-tilt, inappetence, dehydration, hematuria, and dysuria. The dog was azotemic and anemic and had a high WBC count and high liver enzyme activities. Disseminated intravascular coagulation was diagnosed on the basis of thrombocytopenia and prolonged activated clotting times. Vegetative mitral valvular lesions were evident on M-mode echocardiography. The dog underwent diuresis with physiologic saline solution and was treated parenterally with antibacterial and anticoagulant agents. Surgery was performed to remove an infarcted kidney and an infarcted spleen and to relieve urethral obstruction caused by a large blood clot. Gram-positive cocci were noticed in the biopsy specimens. Mortality associated with organ infarctions secondary to bacterial endocarditis is high, and combined medical and surgical therapy is rarely reported. This dog survived and was alive 38 months after surgery.

Comparison of staple and suture techniques for end-to-end anastomosis of the small colon in horses.

Two techniques for end-to-end anastomosis of the small colon were evaluated in each of 6 horses. A simple interrupted suture pattern that excluded the mucosa and was oversewn with an inverting suture was compared with a triangulated double-row pattern of stainless steel staples. Anastomotic sites were evaluated at 2 weeks, 2 months, and 6 months for extent of abdominal adhesions, lumen diameter at anastomotic sites, bursting pressures, and healing response. Clinical postoperative complications were not associated with either technique. At postmortem examination, there was extensive adhesion formation from the mesocolon to the stapled anastomotic site. The suture technique resulted in greater luminal diameters (P less than or equal to 0.05), with good apposition of the tissue layers. Staples were missing as early as 2 weeks after surgery, and their loss was associated with separation of the muscularis at later evaluation periods. Regardless of technique, all but one anastomotic segment burst away from the anastomotic site along the mesenteric taenial band. For the 12 anastomoses performed in normal horses, the suturing technique was better than the stapling technique because of significantly larger lumen diameters, better anastomotic healing, and minimal intra-abdominal adhesion formation.

Malignant lymphoma in three horses with ulcerative pharyngitis.

Three horses were examined for ulcerative pharyngitis, which had been unresponsive to treatment. Biopsy specimens of the pharyngeal lesions were characterized histologically by a mixed population of lymphocytes and histiocytes, suggesting chronic inflammation. Only when biopsy specimens of regional lymph nodes revealed this cell population disrupting the lymph node architecture was the diagnosis of malignant lymphoma made.

Excision of cutaneous tumors in the horse using histologic guidance.

A highly successful surgical technique for removing cutaneous tumors in humans was used in seven horses with cutaneous squamous cell carcinoma (n = 3) or sarcoid (n = 4). In humans, the complete underside of the tumor is evaluated histologically by processing horizontal sections from the tumor base, and orientation between the wound surface and the undersurface of the excised tumor is maintained by mapping both surfaces. The technique ensures that small foci of residual tumor can be located accurately and removed. Based on our experience, three modifications of the human technique are suggested for its use in horses. The equine patient should be placed under general anesthesia rather than using local anesthesia if the tumor is in a difficult position for standing surgery or the patient is uncooperative; useful information can be obtained from tissue processed in buffered formalin if frozen sections are not available; and optimal tumor size for this procedure is no larger than 3 x 2 cm.

Evaluation of three techniques for end-to end anastomosis of the small colon in horses.

In an attempt to determine the best method for surgical removal of devitalized small colon lesions, 12 horses underwent a double small colon resection and end-to-end anastomosis. In 4 horses (study 1), an appositional single-layer (APP-1) suture pattern was compared with an inverting 2-layer (INV-2) suture pattern. In 8 horses (study 2), an appositional 2-layer (APP-2) suture pattern was compared with the INV-2 suture technique. Polydioxanone suture (size 1-0), was used. Horses were evaluated at necropsy 3, 10, 14, 28, or 56 days after surgery. Postoperative complications (peritonitis, impaction, or excessive adhesions) were encountered in 100, 42, and 13% of the APP-1, INV-2, and APP-2 anastomoses, respectively. Postmortem evaluation of the small colon revealed dehiscence of the anastomotic site, diffuse peritonitis, and adhesion formation in 3 of the 4 horses in which the resection line was closed with the APP-1 pattern. With the INV-2 and APP-2 techniques, more intestinal inversion was present in the nontaenial than in the taenial portion of the small colon. More postoperative impactions were found with the INV-2 (n = 5) anastomoses than with the APP-2 (n = 1) technique; this appeared to be the result of excessive tissue inversion. There was no difference in lumen diameter between the INV-2 and the APP-2 techniques (P greater than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Canine laryngeal rhabdomyoma.

Three canine laryngeal tumors were diagnosed as oncocytomas by light microscopy, but were determined to be rhabdomyomas following ultrastructural and immunocytochemical examination. Tumors consisted of large eosinophilic cells interspersed with smaller dark cells. Large tumor cells had a granular, intensely eosinophilic cytoplasm. Scattered through the tumors were a few elongated cells with cytoplasmic cross striations and multiple nuclei. Tumor cells from all three dogs contained numerous mitochondria and bundles of myofibrils with electron-dense Z-lines typical of striated muscle cells. Intracellular myoglobin and desmin were detected in the tumors by immunocytochemistry. Comparisons are made with a previous report of canine laryngeal oncocytomas.