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The toxicity of hydroxyurea, a treatment for specific neoplasms, sickle-cell disease, polycythemia, and thrombocytosis that kills cells in mitosis, was assessed in repeat-dose, oral gavage studies in rats and dogs and a cardiovascular study in telemetered dogs. Hydroxyurea produced hematopoietic, lymphoid, cardiovascular, and gastrointestinal toxicity with steep dose response curves. In rats dosed for 10 days, 50 mg/kg/day was tolerated; 500 mg/kg/day produced decreased body weight gain; decreased circulating leukocytes, erythrocytes, and platelets; decreased cellularity of thymus, lymph nodes, and bone marrow; and epithelial degeneration and/or dysplasia of the stomach and small intestine; 1,500 mg/kg/day resulted in deaths on day 5. In dogs, a single dose at ≥ 250 mg/kg caused prostration leading to unscheduled euthanasia. Dogs administered 50 mg/kg/day for 1 month had decreased circulating leukocytes, erythrocytes, and platelets; increased bone marrow cellularity with decreased maturing granulocytes; increased creatinine kinase activity; and increased iron pigment in bone marrow and hepatic sinusoidal cells. In telemetered dogs, doses ≥ 15 mg/kg decreased systolic blood pressure (BP); 50 mg/kg increased diastolic BP, heart rate, and change in blood pressure over time (+dP/dt), and decreased QT and PR intervals and maximum left ventricular systolic and end diastolic pressures with measures returning to control levels within 24 hr., (© 2014 by The Author(s).)

Extragonadal teratomas have not been reported in nonhuman primates. A female cynomolgus monkey, a vehicle control in an exploratory toxicity study, was necropsied. Microscopic examination of an extragonadal mass in the animal's craniodorsal retroperitoneum revealed a teratoma. This is the first report of an extragonadal teratoma in a nonhuman primate., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

IL-22 is made by a unique set of innate and adaptive immune cells, including the recently identified noncytolytic NK, lymphoid tissue-inducer, Th17, and Th22 cells. The direct effects of IL-22 are restricted to nonhematopoietic cells, its receptor expressed on the surface of only epithelial cells and some fibroblasts in various organs, including parenchymal tissue of the gut, lung, skin, and liver. Despite this cellular restriction on IL-22 activity, we demonstrate that IL-22 induces effects on systemic biochemical, cellular, and physiological parameters. By utilizing adenoviral-mediated delivery of IL-22 and systemic administration of IL-22 protein, we observed that IL-22 modulates factors involved in coagulation, including fibrinogen levels and platelet numbers, and cellular constituents of blood, such as neutrophil and RBC counts. Furthermore, we observed that IL-22 induces thymic atrophy, body weight loss, and renal proximal tubule metabolic activity. These cellular and physiological parameters are indicative of a systemic inflammatory state. We observed that IL-22 induces biochemical changes in the liver including induction of fibrinogen, CXCL1, and serum amyloid A that likely contribute to the reported cellular and physiological effects of IL-22. Based on these findings, we propose that downstream of its expression and impact in local tissue inflammation, circulating IL-22 can further induce changes in systemic physiology that is indicative of an acute-phase response.

Objective: All gamma-chain cytokines signal through JAK-3 and JAK-1 acting in tandem. We undertook this study to determine whether the JAK-3 selective inhibitor WYE-151650 would be sufficient to disrupt cytokine signaling and to ameliorate autoimmune disease pathology without inhibiting other pathways mediated by JAK-1, JAK-2, and Tyk-2., Methods: JAK-3 kinase selective compounds were characterized by kinase assay and JAK-3-dependent (interleukin-2 [IL-2]) and -independent (IL-6, granulocyte-macrophage colony-stimulating factor [GM-CSF]) cell-based assays measuring proliferation or STAT phosphorylation. In vivo, off-target signaling was measured by IL-22- and erythropoietin (EPO)-mediated models, while on-target signaling was measured by IL-2-mediated signaling. Efficacy of JAK-3 inhibitors was determined using delayed-type hypersensitivity (DTH) and collagen-induced arthritis (CIA) models in mice., Results: In vitro, WYE-151650 potently suppressed IL-2-induced STAT-5 phosphorylation and cell proliferation, while exhibiting 10-29-fold less activity against JAK-3-independent IL-6- or GM-CSF-induced STAT phosphorylation. Ex vivo, WYE-151650 suppressed IL-2-induced STAT phosphorylation, but not IL-6-induced STAT phosphorylation, as measured in whole blood. In vivo, WYE-151650 inhibited JAK-3-mediated IL-2-induced interferon-gamma production and decreased the natural killer cell population in mice, while not affecting IL-22-induced serum amyloid A production or EPO-induced reticulocytosis. WYE-151650 was efficacious in mouse DTH and CIA models., Conclusion: In vitro, ex vivo, and in vivo assays demonstrate that WYE-151650 is efficacious in mouse CIA despite JAK-3 selectivity. These data question the need to broadly inhibit JAK-1-, JAK-2-, or Tyk-2-dependent cytokine pathways for efficacy.

Selective estrogen receptor modulators (SERMs) have the potential to treat estrogen sensitive diseases such as uterine leiomyoma and endometriosis, which are prevalent in reproductive age women. However, SERMs also increase the risk of developing ovarian cysts in this population, a phenomenon that is not seen in postmenopausal women. It is believed that current SERMs partially block estradiol's ability to downregulate gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus thereby interfering with estradiol's negative feedback, leading to increased ovarian stimulation by gonadotropins, and cyst formation. It has been postulated that a SERM with poor brain exposure would have less negative effect on the HPO axis, therefore reducing the risk of developing ovarian cysts. In order to test this hypothesis, we identified an early marker of SERM-dependent ovarian effects: upregulation of Cyp17a1 mRNA. SERMs known to cause ovarian cysts upregulate Cyp17a1 after only 4 days of dosing and suppression of the HPO axis prevented this regulation, indicating that ovarian expression of Cyp17a1 was secondary to SERM's effect on the brain. We then characterized three SERMs with similar binding affinity and antagonist effects on the uterus for their relative brain/plasma exposure and ovarian effects. We found that the degree of brain exposure correlated very well with Cyp17a1 expression.

Background: Several studies indicate that selectin-mediated leukocyte migration may depend on the types of initiating inflammatory stimuli or on the vascular beds involved in the inflammatory response. Thus, targeting selectin interactions to treat inflammation may have variable effects depending on the site and origin of the inflammatory response., Objective: To address whether selectin-mediated leukocyte recruitment is stimulus or tissue dependent., Methods: We examined pulmonary and cutaneous allergic inflammatory responses and silica-induced nonallergic lung inflammation and fibrosis in wild-type and P- and E-selectin-deficient (P/E-/-) double knockout mice. Allergen-sensitized wild-type and P/E-/- double knockout mice were challenged either intradermally or via the airways to induce allergic responses in the skin or lung, respectively. Other animals were subjected to intranasal silica administration to induce a nonallergic lung inflammatory/fibrotic response., Results: The P/E-/- mice exhibited significantly reduced allergic inflammation in the skin and lung. Allergic late-phase ear swelling and allergic lung airway hyperresponsiveness were also significantly attenuated in the P/E-/- mice compared with identically treated wild-type animals. In contrast, pulmonary inflammation and fibrosis induced by intranasal administration of silica particles resulted in a more severe phenotype in the P/E-/- mice., Conclusions: Selectin interactions drive allergic inflammation in the lung and skin. Silica-induced pulmonary inflammation and fibrosis, however, was more pronounced in the absence of selectin interactions, suggesting that selectin-mediated leukocyte migration may depend on the types of initiating inflammatory stimuli.

A 19-yr-old spayed female coyote (Canis latrans) was evaluated for an elliptical swelling of the skin beneath its right eye and an elevated mass that involved the soft and hard palate and gingivae around the upper right carnassial tooth and molars. Histopathologic analysis revealed a squamous cell carcinoma, and a postmortem examination revealed no evidence of vascular invasion or dissemination to the regional lymph nodes or viscera. This report describes the biology and progresion of an oral squamous cell carcinoma in an aged captive coyote.

Middiaphyseal 2.5-cm segmental defects in the right femurs of 12 sheep were stabilized with stainless steel plates and implanted with (1) 2 mg recombinant human bone morphogenetic protein 2 and poly[D,L-(lactide-co-glycolide)] bioerodible polymer with autologous blood (n = 7), (2) 4 mg recombinant human bone morphogenetic protein 2 and poly[D,L-(lactide-co-glycolide)] and blood (n = 3), or (3) poly[D,L-(lactide-co-glycolide)] and blood only (n = 2). Bone healing was evaluated for 1 year using clinical, radiographic, gross pathologic, and histologic techniques. Union occurred in three sheep in Group 1, two in Group 2, and none in Group 3. In the animals that healed, new bone first was visible radiographically between Weeks 2 and 6 after implantation; new bone mineral content equaled that of the intact femur not surgically treated by Week 16; recanalization of the medullary cavity approached completion at Week 52; and at necropsy the surgical treated femurs were rigidly healed, the poly[D,L-(lactide-co-glycolide)] was resorbed completely, and woven and lamellar bone bridged the defect site. In two Group 1 sheep euthanized at Weeks 2 and 6, polymer particles were permeated by occasional multinucleated giant cells. Some plasma cells, lymphocytes, and neutrophils were present locally. The poly[D,L-(lactide-co-glycolide)] tended to fragment during surgical implantation. Despite these observations, the recombinant human bone morphogenetic protein 2/poly[D,L-(lactide-co-glycolide)] implant was able to heal large segmental bone defects in this demanding model.

This study describes a novel animal model of the maxillary sinus floor augmentation procedure used to assess bone formation during 12 weeks in response to a recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) sinus implant. A buffer-ACS implant was used as a control. Animal response was monitored using computerized tomography and physical, hematologic, gross pathologic, and histologic evaluations. The rhBMP-2/ACS implants maintained a relatively constant size postsurgery and showed a time-dependent increase in mineralization. The buffer/ACS control implants failed to mineralize and were resorbed by 4 weeks. The model served effectively and without complication. Results indicate rhBMP-2/ACS implants deserve consideration as alternatives to traditional grafting procedures.

Medical records of 3 cats and 12 dogs with lesions of the brain (3 cats, 2 dogs) or vertebral canal (10 dogs) that underwent intraoperative ultrasonography were reviewed. Ultrasonography was performed after craniotomy, a ventral slot procedure, or laminectomy, using a real-time sector scanner with a 7.5- or 10-MHz transducer. In the 3 cats and 2 dogs with brain lesions, cerebral masses were hyperechoic, compared with normal brain, and were easily located. In the 2 dogs, ultrasonography was necessary to localize deep-seated cerebral lesions that could not be seen following craniotomy. In 7 dogs that underwent a ventral slot procedure because of prolapse of an intervertebral disk, ultrasonography was successfully used to assess completeness of disk removal. The remaining 3 dogs underwent dorsal laminectomy because intradural enlargement of the spinal cord (1 dog) or an intradural mass (2 dogs) could be seen myelographically. In the 2 dogs with intradural masses, intraoperative ultrasonography helped to delineate the extent of the tumor. In the third dog, spinal cord swelling was seen ultrasonographically; the histologic diagnosis was spinal cord edema.

A 4-month-old female Bernese Mountain Dog that was examined because of abdominal distention was found to have a nephroblastoma during exploratory laparotomy. Nephrectomy was performed, but the tumor could not be completely resected. A chemotherapeutic plan for this dog was created by adapting current recommendations for treatment of people with nephroblastoma. Chemotherapy was tolerated extremely well; however, tumor progression became evident after 15 weeks of treatment, and the dog was euthanatized. Widespread metastasis was found at necropsy. Little is known about the natural behavior of this tumor in dogs.

A 2.5-cm-long middiaphyseal plate-stabilized segmental defect in the right femora of 5 adult sheep was implanted with 1.5 mg of recombinant human bone morphogenetic protein 2 mixed with inactivated demineralized ovine bone matrix. Bone healing was evaluated for 12 months using clinical, radiographic, gross pathologic, and histologic techniques. Bone formation within the defect was first visible radiographically between Weeks 2 and 4 after surgery; bone union was apparent between Weeks 12 and 16, at which time the plates were removed. Recanalization of the medullary cavity with neocortex formation was near completion at Week 52. Bone mineral content at the defect sites equaled that of the nonsurgically treated intact femora by Week 16. Perifemoral soft tissue mineralization did not occur, and callus size was not greater than that formed with autograft. By Week 52, the sheep were not lame, and at necropsy the surgically treated femora were rigidly healed. Woven and lamellar bone bridged the defect site. An apparently normal sequence of ossification, modeling, and remodeling events had occurred. Recombinant human bone morphogenetic protein 2 mixed with a suitable carrier could provide an alternative to autograft for use in a variety of orthopaedic procedures.

Twelve adrenocortical tumours with a variable spindle-cell component in ferrets (six spayed females, three intact females, two castrated males, and one intact male) were examined by light microscopy. One tumour with a moderate spindle-cell component was examined ultrastructurally, and three tumours were studied immunohistochemically. Light microscopy revealed a spindle-cell component in the tumours that varied from a few such cells occupying the stroma between packets of adrenocortical cells to cells in such large numbers that they formed almost the entire substance of the tumour. By light microscopy these spindle cells resembled smooth muscle cells, and the ultrastructural findings, particularly the presence of thin contractile filaments, suggested that the spindle cells were of smooth muscle origin. Immunohistochemical staining revealed that the spindle cells were negative for cytokeratins and S-100 protein but positive for smooth muscle actin. Desmin was readily demonstrated in two tumours but not in the other examined. Vimentin was variable, generally producing a small to moderate amount of reaction product.

Medical records of 5 cats with hepatobiliary cystadenomas treated by means of surgical excision were reviewed. All cats were examined because of lethargy or abdominal enlargement. A cystic liver mass was seen in each cat ultrasonographically. Postoperative complications did not develop, and none of the cats developed evidence of tumor recurrence. Four cats died 12 to 44 months after surgery. Two cats were euthanatized for unrelated problems, and 2 cats died suddenly 25 and 44 months after surgery; the causes of death were not determined in either case. One cat was alive and considered clinically normal on physical examination 42 months after surgery.

A 6-year-old Nubian doe was evaluated because of slowly progressive abdominal enlargement of 1 month's duration. Five days prior to examination at our hospital, the doe was examined by a local veterinarian. False pregnancy was suspected, and 10 mg of prostaglandin F2 alpha was injected IM. Abdominal distention did not decrease, and the doe did not develop a vaginal discharge. An additional 10 mg of prostaglandin and 24 mg of dexamethasone were injected IM, about 80 hours after the first injection, again without any apparent effect. On arrival at our hospital, the doe was in sternal recumbency and was too weak to stand unassisted. Its abdomen was distended. The body of the uterus and part of 1 uterine horn could be examined by means of transrectal ultrasonography, both appeared normal. The doe was admitted to the hospital, but its condition worsened, and it died during the night. Postmortem examination revealed approximately 30 L of clear, pale, straw-colored fluid in the peritoneal cavity. The caudal pole of the left ovary contained an indistinct, firm, slightly raised, gray-tan mass. The final diagnosis was mucinous adenocarcinoma of the ovary metastatic to the partietal peritoneum, pericardium, and lungs. In adult female goats with bilateral abdominal distention, hydrometra associated with false pregnancy should always be considered; however, if there is no response to prostaglandin administration, distention is more likely to be a result of ascites.

The development of skeletal lesions in two canine models of GM1-gangliosidosis, English springer spaniels and Portuguese water dogs, has been studied and compared to osseous abnormalities in a child with the infantile form of the disease. In the canine models, skeletal dysplasia was progressive. Lesions were noted at 2 months of age and characterized by retarded endochondral ossification and osteoporosis. Older puppies had focal cartilage necrosis within lumbar vertebral epiphyses. At the cellular level, lesions were characterized by chondrocytic hypertrohy and lysosomal accumulation of storage compounds. Our studies illustrate that the skeletal lesions in both canine models are similar to those in a child with GM1-gangliosidosis. Furthermore, we proposed that the abnormal storage of partially degraded compounds in affected chondrocytes might explain, at least in part, the retarded bone formation noted in patients with GM1-gangliosidosis.

Questionnaires were sent to veterinarians who had submitted a fibrosarcoma from a cat to the surgical pathology services of the veterinary schools of the University of Pennsylvania and Tufts University between Jan 1, 1991 and June 30, 1992. Questionnaire items included signalment, FeLV and feline immunodeficiency virus status, site of sarcoma, vaccination site, vaccines used, treatment, biologic behavior of the tumor, and final outcome. Data were analyzed, using Student's t-test for continuous data, chi 2 test for categoric data, and log-rank test for survival estimates. Comparing results for cats with vaccination-site (VS) tumors and nonvaccination-site (NVS) tumors, we determined that VS tumors developed in younger cats and were larger than NVS tumors. Although VS sarcomas were biologically aggressive and redeveloped more often than NVS sarcomas, metastasis was not detected, and cats with VS tumors survived longer than cats with NVS tumors. Vaccination-site sarcomas developed in cats after injection of many types of vaccines, administered singularly or in combination. Of the cats in the VS group administered a single vaccine, 37% were given rabies, 33% were given feline viral rhinotracheitis/calicivirus/panleukopenia virus, and 30% were given FeLV vaccines. Cats with VS tumors were more likely to have received FeLV vaccine and less likely to have received rabies vaccine than those with NVS tumors. Although vaccines produced by certain manufacturers were used most often in cats with VS and NVS sarcomas, it was believed that this probably represented marketing practices and brand popularity.(ABSTRACT TRUNCATED AT 250 WORDS)

A 9-year-old castrated male Doberman Pinscher was admitted for evaluation of lameness of the left forelimb. Radiography and examination of biopsy specimens revealed a moderately differentiated chondrosarcoma of the proximal portion of the radius. The dog was treated by local excision of the neoplasm, which involved resection of the radial head and proximal portion of the radius. Despite the large size of the dog and the weight-bearing forces exerted on the cubital joint, major problems with ambulation did not develop after surgery. Functional use of the limb returned slowly; however, substantial limb use was observed despite the development of mild degenerative changes of the joint and migration of the humeroulnar articulation. Six months after surgery, metastasis of a widely disseminated, poorly differentiated chondrosarcoma to the subcutaneous tissues and thoracic and abdominal cavities was diagnosed. Local redevelopment of the chondrosarcoma in the area of the cubital joint was not detected. Resection of the radial head and proximal portion of the radius may be considered a viable, alternative, limb-sparing technique. The biologically aggressive nature of this chondrosarcoma of the appendicular skeleton indicated that additional information was needed before a reliable prognosis could be established for this dog with this tumor type. Reports of low rates of metastasis have been based on insufficient numbers of dogs to adequately or accurately determine the long-term prognosis of dogs with chondrosarcoma of the appendicular skeleton.

In this article, some of the common and not-so-common neuropediatric disorders were discussed. As in the full-grown animal, abnormalities of the CNS in the pediatric animal patient may be classified according to the type of insult present (eg, malformation, injury, neoplasia, inflammation, or degeneration). To recognize the imaging manifestations of such disorders, an appreciation of normal anatomy, the pathological response of nervous system tissue to insult, and the principles of image interpretation is required. These fundamentals may then be applied to any CNS disease, regardless of frequency and to any animal patient, regardless of age.

A 1.5-year-old female goat was examined for recurrence of lameness involving the right forelimb. Radiography of the thorax and right scapulohumeral joint revealed a pathologic fracture of the supraglenoid tubercle, and circumscribed radiolucent lesions in the right third and fourth ribs, and the base of the spinous process of T3. Bone scintigraphy demonstrated additional lesions in the lumbar spine and the wings of the ilium. At necropsy, disseminated infection and hematogenous osteomyelitis were diagnosed. Corynebacterium renale was cultured from the rib lesions. In food animals, osteomyelitis usually develops secondary to traumatic wounds, and members of the genus Actinomyces are frequently incriminated as the causative organism. This case is unusual because the osteomyelitis was unrelated to a traumatic wound, and the gross and microscopic lesions were reminiscent of caseous lymphadenitis, an infection caused by C pseudotuberculosis.

Controlled tissue expansion using a 100 cc rectangular silicone elastomer expander was performed in the mid-antebrachium and mid-crus of eight adult mixed-breed dogs. Two expander inflation schedules were followed. Group 1 dogs (n = 4) underwent expander inflation using 10 cc sterile saline every other day, and group 2 dogs (n = 4) underwent expander inflation using 15 cc sterile saline every other day until the nominal volume (100 cc) was attained. Significant mean postexpansion increases in skin surface area of 94.1 cm2 (35.9%) and 108.9 cm2 (37.3%) were measured in the antebrachium and crus, respectively (p < .05). In a second procedure, the expanders were removed and skin flaps were developed from the redundant tissue generated during the expansion process. Single pedicle advancement flaps and transposition flaps were used to cover surgically created defects measuring 5 x 10 cm in the antebrachium and crus. Single pedicle advancement flaps consistently measured 10 x 10 cm and could be advanced to cover defects involving one third of the mid-antebrachial or mid-crural circumference. Transposition flaps were rotated up to 170 degrees and the donor site defects were easily closed under minimal or no tension. Complications included an abscess in one dog and seroma formation in four dogs. Differences in success or complication rates between group 1 dogs and group 2 dogs were not observed; an accelerated inflation schedule using 15 cc sterile saline every other day was recommended.

A middiaphyseal, 2.5-cm osteoperiosteal segmental defect stabilized by plate fixation was created in the right femur of 17 sheep. Four treatment groups were included: Group I, no implant; Group II, inactive bone matrix; Group III, recombinant human bone morphogenetic protein (rhBMP-2) mixed with inactive bone matrix; and Group IV, autogeneic bone graft. Three animals had early failure of fixation, and the remaining 14 were evaluated at three months after implantation. Radiographs showed bony union of all defects treated with rhBMP-2 (six) and a lack of bony union in the negative-control groups treated with no implant (three) and inactive bone matrix without BMP (three). Both defects treated with autograft healed. New bone formation in the defect sites treated with rhBMP-2 first appeared one month after implantation and had a mean bending strength (expressed as a percentage of the contralateral femur) of 91% +/- 59% (mean +/- standard deviation) for defects treated with BMP-2, 77% +/- 34% for autograft, 9% +/- 8% for no implant, and 11% +/- 7% for inactive matrix without BMP. Three sheep treated with rhBMP-2 had their fixation plates removed at four months and were followed for one year. Their bone defect sites remained solidly healed one year after the initial operation.

A 4-year-old male cat was referred because of aggressive behavior and spraying urine. When the cat was 6 months old, only 1 testis was found in the scrotum. When the cat was 1 year old, the scrotal right testis was surgically removed and the left testis was not found, either within the scrotum or within the abdomen. The cat developed male behavior and another laparotomy was performed 1 year later, at which time the left testis could not be located. The cat continued to show male behavior. On referral, the penis was well developed and had spines. Human chorionic gonadotropin (HCG), 500 IU, was administered IV. At baseline, 30, and 120 minutes after HCG administration, serum testosterone activity (ng/ml) was 0.68, 5.0, and 10.5, respectively. Laparotomy was performed with the cat under general anesthesia. The left testis was found in the facial plane lateral to the symphysis pubis. Six weeks after the surgery, the HCG stimulation test was repeated and testosterone was not detected in any serum sample. The most practical solution to locate the undescended testis would have been to follow the intact ductus deferens to the testis adjacent to the pubic symphysis.

Seventeen dogs were diagnosed with leptospirosis on the basis of clinical findings, laboratory abnormalities, and serology. This article summarizes and characterizes the historical and physical findings, laboratory data, serology, treatment, and outcome of these dogs. All of the dogs had serologic evidence of infection with interrogans serovars pomona and grippotyphosa. These findings are compared with previous reports of canine infection with Leptospira interrogans serovars icteroaemorrhagiae and canicola. The clinical presentation of these dogs did not correspond to the classic description of the disease in dogs in which concurrent renal and hepatic diseases are present. This may be due to infection with different serovars than those previously reported. In addition, this article suggests that canine leptospirosis should be considered in the differential diagnosis of dogs with acute or subacute renal failure.

Twenty-two dogs with appendicular osteosarcoma were treated by amputation (n = 17) or limb-sparing surgery (n = 5). All dogs were given cisplatin (60 mg/m2 of body surface, IV) at 3-week intervals, beginning 1 week after surgery. Number of cisplatin treatments ranged from 1 to 6. Survival data for the 22 dogs were compared with survival data from a historical control group consisting of 162 dogs with appendicular osteosarcoma treated by amputation alone. Median survival time for the 22 dogs given cisplatin was estimated to be 46.4 weeks, and 1- and 2-year survival rates were estimated to be 45.5 and 20.9%, respectively. Survival time was significantly (P less than 0.0001) longer for treated dogs than for control dogs. Statistically significant relation was not found between survival time and number of cisplatin treatments. Three dogs were alive with no evidence of disease at the time of reporting. Of the remaining 19 dogs, 14 (73.4%) were euthanatized for problems documented to be related to metastases. Nine (47.4%) dogs were euthanatized because of bone metastases, and 5 (26.3%) were euthanatized because of pulmonary metastases. The proportion of dogs euthanatized because of bone metastases was significantly (P less than 0.0001) higher for treated than for control dogs. Median survival times for dogs developing bone and lung metastases were estimated to be 51.2 weeks and 21.2 weeks, respectively; however, this difference was not statistically significant. One local tumor recurrence was observed among dogs that had limb-sparing surgery. Significant difference in survival time was not observed between dogs that had limb-sparing surgery and dogs that underwent amputation.

Long-term follow-up information pertaining to 162 dogs with appendicular osteosarcoma treated by amputation alone was collected from 17 veterinary institutions. The majority (72.5%) of dogs died or were euthanatized because of problems documented to be related to metastases. The first clinically apparent sites of metastasis were the lungs (60.8% of total), the skeleton (5.2%), or both (4.6%). A Kaplan-Meier survivorship distribution was plotted on the basis of available survival time data in all 162 dogs. The mean and median survival times were estimated to be 19.8 and 19.2 weeks, respectively, and the 1- and 2-year survival rates were estimated to be 11.5 and 2.0% respectively. Statistically significant relationships were not found between survival time and reporting institution, gender, site of primary tumor, whether the primary tumor was proximally or distally located, whether the primary tumor was located in the forelimb or hind limb, whether presurgical biopsy was performed, and whether death was tumor related. A significant (P less than 0.01) quadratic relationship was found between age and survival time. Survival time was longest in dogs 7 to 10 years old and was shorter in older and younger dogs.

A granulosa-theca cell tumor was found in an ovary that had an ovulation fossa and normal ovarian tissue. The ovary was removed from a mare with a history of ovarian enlargement and behavioral changes. The affected ovary had a multicystic appearance on ultrasonographic examination performed before surgery, and an ovulation fossa was not palpable on examination per rectum. However, during surgery, the affected ovary was found to be within normal size limits, with an enlargement on 1 pole, and to contain an ovulation fossa. Atrophy of the infundibulum of the affected ovary helped to confirm the diagnosis of granulosa-theca cell tumor, and the ovary was removed. The mare's testosterone concentrations were normal. Granulosa-theca cell tumors are usually associated with a spherical ovary, attributable to ablation of the ovulation fossa, with no normal ovarian tissue present.

We describe a novel late-onset lysosomal lipid storage disease affecting a Tibetan terrier. The principal clinical manifestations include visual loss, progressive cerebellar ataxia and dementia. A necropsy of an affected 10-year-old dog demonstrated cerebellar atrophy. Histological analysis revealed extensive loss of retinal ganglion cells and cerebellar Purkinje cells, and mild to moderate loss of neurons in the cerebrum, basal ganglia and spinal cord. There were generalized neuronal hypertrophy and multifocal neuronal necrosis associated with the presence of enlarged macrophages. Neurons and perineuronal macrophages contained cytoplasmic granules that stained with PAS, luxol fast blue and several lectins. The granules were sudanophilic and autofluorescent. Electron microscopic analysis revealed lysosomes laden with lamellated membrane structures in neurons, pancreatic ductal and centroacinar cells and in cultured fibroblasts. These findings indicate lysosomal storage of both lipid and carbohydrate. Biochemical analysis of brain lipids and numerous lysosomal enzyme assays of leukocytes and cultured fibroblasts were unsuccessful in elucidating the underlying enzyme defect, although a generalized increase of brain gangliosides was noted.

The uptake of the bone-seeking radiopharmaceutical 99mTc-MDP by damaged skeletal muscle in horses is evaluated. Twenty-four hours following strenuous exercise, 109 racehorses with a history of inadequate athletic performance and subtle lameness were imaged using scintigraphic techniques. Ten horses (9.2 per cent) demonstrated abnormal uptake of the radioisotope within skeletal muscles. A muscle biopsy from one of these horses confirmed that the muscles with increased scintigraphic activity had histologic evidence of rhabdomyolysis. This technique allows localisation and relative quantification of muscle damage and is a valuable aid in the evaluation of the athletic horse.

The principal determinants of the resolution of any wound are the type and extent of injury, the regenerative capacity of the constituent cells, and the extent of damage to the extracellular matrix. As stated previously, in the repair of a fracture, anything other than the final formation of bone tissue at the fracture site represents incomplete healing. Nature has provided bone with a remarkable array of mechanisms by which to effect fracture repair. An understanding of secondary (classical) bone healing is important to prevent any untoward effects that might ensue if an injury were left untreated, to select a form of fracture treatment that would complement nature's mechanisms, and to facilitate the interpretation of sequential radiographs obtained to evaluate the healing process.

A juvenile rhesus macaque (Macaca mulatta) developed a symmetrical erosive polyarthritis involving both large and small diarthrodial joints. Neither an infectious nor a metabolic etiology could be determined. This case shares many clinical and pathological features with the polyarticular form of human juvenile rheumatoid arthritis.

Five Basset Hounds (2 females and 3 males) under the age of 5 years, acquired systemic tuberculosis. We suspected tuberculosis in one dog, because it had histologic lesions similar to those in 4 dogs in which bacteria were identified as Mycobacterium avium complex. A review of canine tuberculosis revealed a similar diagnosis in a Basset Hound. The association of this infection in Basset Hounds suggests an inherited immunologic defect. Results of our survey suggest that the defect might exist in cell-mediated immunity.

Beta-galactosidase-deficient siblings in two litters of English springer spaniel puppies showed a progressive neurological impairment, dwarfism, orbital hypertelorism, and dysostosis multiplex. An excess of GM1-ganglioside was found in the brain. Three abnormal oligosaccharides were present in samples of urine, brain, liver, and cartilage. Light microscopy of selected tissue specimens revealed cytoplasmic vacuoles in neurons, circulating blood cells, macrophages, and chondrocytes. Ultrastructural studies demonstrated that these membrane-bound vacuoles were of two types--one containing lamellated membranes and the other, finely granular material. These clinical and pathological findings are similar to those observed in human patients affected by the infantile form of GM1-gangliosidosis.