Jeffrey S. Klausner

Interleukin‐2 liposome inhalation therapy is safe and effective for dogs with spontaneous pulmonary metastases

Systemic in vivo toxicity of interleukin‐2 (IL‐2) has been problematic. Antineoplastic activity of IL‐2 has been modest. The authors have previously demonstrated the biologic activity and safety of aerosols of IL‐2 liposomes in normal dogs. They now report objective regression of naturally occurring pulmonary metastases in dogs after 1 month of nebulized IL‐2 liposome therapy.

Prostatic intraepithelial neoplasia in dogs with spontaneous prostate cancer

Prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer. The prevalence and immunophenotype of PIN in dogs with spontaneous prostate cancer has not been previously described. To investigate the association between PIN and prostate cancer, we evaluated the prostates of dogs with spontaneous prostate carcinoma. The prevalence of PIN was determined in formalin‐fixed prostates from 29 dogs with spontaneous prostate cancer. Using immunoperoxidase techniques, we compared basal cell layer integrity (high molecular weight keratin 34 beta‐E12), proliferative index (MIB‐1), and microvessel density (Factor VIII‐related antigen) in 14 prostates which contained benign epithelium, PIN, and carcinoma. PIN was present in 19 of 29 (66%) prostates from dogs with spontaneous prostate cancer. The basal cell layer was intact in benign epithelium, disrupted in 72% of acini with PIN, and absent in carcinoma. The mean proliferative index was 17%, 25%, and 40% for benign epithelium, PIN, and carcinoma, respectively, and these differences were significant. The mean microvessel density in foci of PIN and carcinoma (32 and 39 vessels per mm2, respectively) was greater than in benign epithelium (23 vessels per mm2). High‐grade PIN is common in the prostates of dogs with spontaneous carcinoma. The basal cell layer is partially disrupted in PIN, whereas it is absent in prostate cancer. The proliferative index and microvessel density of PIN are intermediate between benign epithelium and cancer. These results are similar to those reported for human PIN and prostate cancer, and indicate that PIN is part of a morphologic continuum in the progression of prostate cancer. To our knowledge, this is the first description of high‐grade PIN spontaneously occurring in animals. The canine prostate may serve as a useful model for examining factors that modulate PIN and prostate cancer progression. Prostate 30:92–97, 1997.

Nebulized Interleukin 2 Liposomes: Aerosol Characteristics and Biodistribution

Although interleukin 2 (IL‐2) has been associated with modest anti‐tumour responses in man, treatment‐related toxicity has limited its widespread use. The local delivery of liposomal formulations of interleukin 2 to the lung as aerosols has been demonstrated to be non‐toxic, biologically active, and associated with regression of spontaneous pulmonary metastases in dogs. This study was undertaken to evaluate the physical and biological characteristics of nebulized interleukin 2 liposomes.

Neutrophil-induced Erythrocyte Injury: A Potential Cause of Erythrocyte Destruction in the Anemia Associated with Inflammatory Disease

Activated neutrophils at effector/target ratios of 1:20 to 1:2,000 induced depletion of red blood cell (RBC)-reduced glutathione, increased membrane-bound hemoglobin and methemoglobin, and promoted immunoglobulin binding to the cell membrane. Superoxide dismutase/catalase ameliorated the decrease in reduced glutathione and the increase in methemoglobin and immunoglobulin binding. This is interpreted as evidence that activated neutrophils can alter the antigenic nature of the RBC membrane through generation of toxic oxygen radicals.

Acute Myelomonocytic Leukemia with Neurologic Manifestations in the Dog

A dog was presented with mandibular paralysis, photophobia, and diffuse atrophy of the cranial skeletal muscles. Physical examination also revealed glossal paralysis, reduction of the swallowing reflex, reduction of the pupillary light response, and generalized lymphadenopathy. Cytologic and ultrastructural examinations of blood films, bone marrow, and lymph node aspirates were consistent with acute myelomonocytic leukemia. Post-mortem examination revealed extensive, multisystemic neoplastic infiltration with marked involvement of the central and peripheral nervous systems, especially the cranial and lumbar spinal nerves and associated ganglia. Neurologic manifestations arc unusual in acute myelomonocytic leukemia in the dog.

Etiopathogenesis of canine struvite urolithiasis.

Urine must be oversaturated with magnesium ammonium phosphate for struvite uroliths to form. Oversaturation of urine with magnesium ammonium phosphate may be associated with several factors, including urinary tract infections with urease-producing microbes, alkaline urine, diet, and genetic predisposition. Of the urease-producing microbes, staphylococci are most struvitogenic in dogs. The precise mechanisms resulting in formation of sterile struvite uroliths in dogs have not been determined.

Two-dimensional, gray-scale ultrasonography. Applications in canine prostatic disease.

The technique of and general appearance of suprapubic gray-scale prostatic ultrasonography in the dog are described. Using case examples, the various spontaneous diseases of the canine prostate are described and compared to the defined normal appearance of the prostate. An integrated approach to imaging the canine prostate gland is advocated and includes radiographic techniques, specifically distension retrograde urethrocystography. A clinically relevant classification scheme for use with microbiologic, cytologic, and imaging techniques is proposed.

Etiopathogenesis, Clinical Manifestations, and Management of Canine Calcium Oxalate Urolithiasis

Calcium oxalate uroliths are commonly called metabolic uroliths because they are sequelae of a variety of metabolic abnormalities that alter the composition of body fluids and urine. Factors incriminated in the etiopathogenesis of calcium oxalate urolithiasis include hypercalciuria, hyperoxaluria, and hyperuricosuria. The predominant type of calcium oxalate urolith encountered in dogs is the monohydrate form; however, the dihydrate form may also occur. Male dogs have been more frequently affected than female dogs. Medical therapy should be formulated with the goal of reducing urine concentration of calculogenic substances.

Prostatic Hemangiosarcoma in a Dog: Clinical and Pathologic Findings:

Prostatic hemangiosarcoma (HS) appears to be rare in the dog. In 3 of 4 previously reported cases, the prostate was involved via metastasis. For 1 dog, the primary tumor presumably was located in the prostate gland, but no details were given. The present report documents what we believe is a primary HS of the prostate in a dog that presented with clinical signs of urinary tract disease. The prostate tumor and metastases had microscopic features of a poorly differentiated HS, and the diagnosis was confirmed by immunohistochemistry. An 11-year-old male Miniature poodle was admitted to a veterinary hospital because of straining to urinate and defecate and passing “ribbon-like” feces for approximately 1 month. Physical examination revealed prostatomegaly. The dog was castrated and given an injection of 0.25 mg of estradiol cypionate intramuscularly. Clinical signs persisted, and the dog was referred to the University of Minnesota Veterinary Teaching Hospital (UMVTH) 6 days after castration. Physical examination revealed a thin dog with prostatomegaly and a very distended urinary bladder. A complete blood count revealed a normochromic normocytic anemia (PCV = 23%, normal > 37%) without significant regenerative response. The dog was catheterized without difficulty, and 225 ml of yellow urine were removed. A urinalysis was consistent with urinary tract infection, and a urine culture revealed Klebsiella pneumoniae and Proteus mirabilis (> 10 colony forming units/ml). Prostatomegaly was identified on abdominal radiographs. A sonogram revealed diffuse prostatic hyperechogenicity with irregular multifocal hypoechoic masses. A prostatic biopsy was performed with a Tru-Cut biopsy needle via a perineal approach. Microscopic examination revealed neoplastic polyhedral and spindle cells of uncertain tissue type. Following a course of radiation therapy, which failed to shrink the prostate, the dog was euthanized. At necropsy, the prostate gland protruded from the cranial rim of the pelvis and was tightly adhered to the pelvic canal, especially on the right side. Although both lobes of the prostate were enlarged, the right lobe was more severely affected. The prostate was 10.5 x 6.0 x 4.0 cm and weighed 125 g. Transverse sections of the prostate revealed a large yellow core encircled by a rim of red tissue. Reddish-yellow tissue was present within the right obturator foramen. Soft red and white nodules 0.7 cm and 4 cm in diameter were found in the left and right medial thigh muscles, respectively.

Canine Calcium Phosphate Uroliths

Uroliths composed primarily of calcium phosphate are identified in approximately 3 per cent of canine stone patients. Predisposing factors to the formation of calcium phosphate uroliths include elevated urine pH, hypercalciuria, and the presence of crystallization inhibitors and promoters. Medical therapy of patients forming calcium phosphate uroliths should initially be directed at removing factors contributing to urine supersaturation with calcium phosphate.