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  • Author or Editor: James M. Van Gilder x
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Objective—To determine the effect of pamidronate disodium on the in vitro viability of osteosarcoma cells and non-neoplastic cells from dogs.

Sample Population—3 osteosarcoma and 1 fibroblast cell lines derived from dogs.

Procedure—Cell counts and cell viability assays were performed in cultures of osteosarcoma cells (POS, HMPOS, and COS31 cell lines) and fibroblasts after 24, 48, and 72 hours of incubation with pamidronate at concentrations of 0.001 to 1,000µM or with no drug (control treatment). Percentage viability was determined in cell samples for each concentration of pamidronate and each incubation time. A DNA fragmentation analysis was performed to assess bisphosphonate- induced apoptosis.

Results—Osteosarcoma cell viability decreased significantly in a concentration- and time-dependent manner at pamidronate concentrations ranging from 100 to 1,000µM, most consistently after 48 and 72 hours' exposure. In treated osteosarcoma cells, the lowest percentage cell viability was 34% (detected after 72 hours' exposure to 1,000µM pamidronate). Conversely, 72 hours' exposure to 1,000µM pamidronate did not significantly reduce fibroblast viability (the lowest percentage viability was 76%). After 72 hours of exposure, pamidronate did not cause DNA fragmentation in POS or HMPOS cells.

Conclusions and Clinical Relevance—Results indicate that pamidronate may have the potential to inhibit osteosarcoma growth in dogs, possibly through a nonapoptotic mechanism. The clinical relevance of these in vitro findings remains to be determined, but administration of pamidronate may potentially be indicated as an adjuvant treatment in chemotherapeutic protocols used in dogs. (Am J Vet Res 2005;66: 885–891)

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in American Journal of Veterinary Research


Objective—To determine whether thalidomide inhibits the growth of primary and pulmonary metastatic canine osteosarcoma in mice after xenotransplantation.

Animals—Athymic nude mice.

Procedure—Canine osteosarcoma cells were injected SC in 50 mice. Mice were randomly placed into the following groups: control group (n = 13; DMSO [drug vehicle] alone [0.1 mL/d, IP]); low-dose group (12; thalidomide [100 mg/kg, IP]), mid-dose group (13; thalidomide [200 mg/kg, IP]); and high-dose group (12; thalidomide [400 mg/kg, IP]). Starting on day 8, treatments were administered daily and tumor measurements were performed for 20 days. On day 28, mice were euthanatized and primary tumors were weighed. Lungs were examined histologically to determine the number of mice with metastasis and tumor emboli. Mean area of the pulmonary micrometastatic foci was determined for mice from each group.

Results—Primary tumor size and weight were not significantly different among groups. The number of mice in the mid-dose (200 mg/kg) and high-dose (400 mg/kg) groups with micrometastasis was significantly less than the number of control group mice; however, the number of mice with tumor emboli was not affected by thalidomide treatment. Size of micrometastasis lesions was not affected by thalidomide treatment.

Conclusions and Clinical Relevance—Mean area of micrometastases was not affected by treatment; however, growth of micrometastases had not yet reached an angiogenesis-dependent size. Although thalidomide did not affect growth of primary tumors in mice after xenotransplantation of canine osteosarcoma cells, our findings indicate that thalidomide may interfere with the ability of embolic tumor cells to complete the metastatic process within the lungs. ( Am J Vet Res 2004;65:659–664)

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in American Journal of Veterinary Research



To determine scintigraphic, sonographic, and histologic changes associated with renal autotransplantation in cats.


7 adult specific-pathogen-free cats: 5 males, 2 females, 1 to 9 years old.


Renal autotransplantation was performed by moving a kidney (5 left, 2 right) to the left iliac fossa. Before and at multiple times after surgery, for a total of 28 days, cats were evaluated by B-mode and Doppler ultrasonography, scintigraphy, and renal biopsy.


By 24 hours after surgery, a significant decrease (42%) in mean glomerular filtration rate (GFR) and an increase in mean renal size (81% increase in cross-sectional area) were evident in the transplanted kidney, compared with preoperative values. By postsurgery day 28, reduction in GFR was 23%. Significant changes in renal blood flow velocity were identified in both kidneys. Consistent changes in resistive index or pulsatility index for either kidney could not be identified. When all postoperative histologic data were combined, the histologic score, indicating degree and numbers of abnormalities detected, for the transplanted kidney was significantly higher than that for the control kidney.


Significant changes in renal function, size, and histologic abnormalities develop secondary to acute tubular necrosis in cats after uncomplicated renal autotransplantation.

Clinical Relevance

Evaluation of renal size and function may be of benefit for clinical evaluation of feline renal transplant patients, whereas measurement of the resistive index may be of little clinical value. (Am J Vet Res 1999;60:775–779)

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in American Journal of Veterinary Research


Objective—To evaluate postmortem surgery site leakage by use of in situ isolated pulsatile perfusion after partial liver lobectomies.

Animals—10 healthy mixed-breed male dogs.

Procedures—Dogs were anesthetized, and 5 surgical techniques (pretied suture loop, energy-based sealer-divider, harmonic scalpel, suction with clip application, or suction with use of a thoracoabdominal stapler) were used to perform 5 partial liver lobectomies in each dog. Dogs were euthanatized, and the portal vein and hepatic artery were cannulated and perfused with a modified kidney perfusion machine (pulsatile flow for arterial perfusion and nonpulsatile flow for portal perfusion). Lobectomy sites were inspected for leakage of perfusate, and time until detection of leakage was recorded. The techniques in each dog were ranked on the basis of time until leakage. Time until leakage and rankings for each surgical technique were analyzed by use of an ANOVA.

Results—Leakage of perfusate was recorded in 44 lobes at supraphysiologic pressures. Of the 6 lobes without leakage, a pretied suture loop procedure was performed in 5 and a harmonic scalpel procedure was performed in 1. Time until leakage and the ranking differed significantly between the pretied suture loop and the other techniques. Time until leakage and ranking did not differ significantly among the other techniques.

Conclusions and Clinical Relevance—Time until leakage of perfusate was greater for the pretied suture loop technique than for the other techniques, and that technique did not fail in 5 of 10 lobes. However, all techniques appeared to be safe for clinical use.

Full access
in American Journal of Veterinary Research


Objective—To biomechanically and histologically compare single-layer continuous Cushing and simple continuous appositional cystotomy closure in rats with xylene-induced cystitis.

Animals—40 female Sprague-Dawley rats.

Procedure—Rats were anesthetized, their urinary bladders catheterized and evacuated, and xylene instilled in each bladder for 5 minutes and then aspirated. Forty-eight hours later, ventral midline celiotomy and cystotomy (8 mm) were performed. Cystotomies were closed with 6-0 poliglecaprone 25 by use of a single-layer continuous Cushing or simple continuous appositional pattern (20 rats/group), and cystotomy times were recorded. Rats were allocated to healing durations (5 rats/group) of 0, 3, 7, and 14 days. Celiotomies were closed in a routine manner. After the allotted healing interval, another celiotomy was performed, the urethra cannulated, and ureters ligated. The cannula was secured to the urethra, and the bladder infused at 0.1 mL/min. Leak pressure volume, leak pressure, peak pressure volume, and peak pressure were recorded via a pressure transducer. Bladders were harvested and histologically assessed.

Results—Cystotomy time, biomechanical testing values, and overall inflammation scores did not differ between closure methods for any healing duration. Both methods had significantly greater leak pressures, with the appositional method also having significantly greater peak pressures on day 7, compared to day 0. Biomechanical testing values decreased from day 7 to 14 as a result of juxtaincisional weakening of the bladder and xylene-induced changes in collagen.

Conclusions and Clinical Relevance—Simple continuous appositional was equal biomechanically and histologically to continuous Cushing for all comparison variables. Poliglecaprone 25 was acceptable for cystotomy closure.

Full access
in American Journal of Veterinary Research