Feasibility of targeting canine soft tissue sarcoma with MR-guided high-intensity focused ultrasound.

PURPOSE: Magnetic resonance imaging-guided high-intensity-focused ultrasound (MR-HIFU) is a non-invasive treatment modality that precisely focuses ultrasound energy within a tumour and can be customised to result in a wide range of local bioeffects. The purpose of this study was to determine the feasibility of using MR-HIFU to treat soft tissue sarcoma (STS) in dogs. MATERIALS AND METHODS: Medical records of dogs admitted to the Virginia-Maryland College of Veterinary Medicine from 1 January 2012 to 31 December 2016 were searched for a diagnosis of sarcoma with available cross-sectional imaging of the tumour (MRI or CT). Fifty-three (53) dogs were eligible for inclusion. Tumor tissue (in bone as well as in soft tissue) was considered targetable unless: (1) the ultrasound path was completely obstructed by bone or gas and (2) the MR-HIFU target was within the spinal cord or less than 1 cm from the margin of the spinal cord. Tumors were categorised as <50% targetable, ≥50% targetable or non-targetable. RESULTS: Eighty-one percent of STS (81.1%, 43/53) were targetable. The head/spine tumour sites had the highest proportion of non-targetable tumours (36%, 9/25). The majority of truncal and axillary tumours were ≥50% targetable (88.9%, 16/18) ,and all extremity tumours were considered ≥50% targetable (100%, 5/5). CONCLUSIONS: The majority of STS were targetable. This is the first study to evaluate MR-HIFU targetability of canine STS. HIFU has potential as a therapeutic modality for treating STS in dogs, and this veterinary application is a possible model for treatment of naturally occurring STS in humans.

EVALUATION OF THYROID TO BACKGROUND RATIOS AND COMPARISON OF VARIOUS SCINTIGRAPHIC MEASUREMENTS AND THEIR CORRELATION TO SERUM T4 IN HYPERTHYROID CATS.

Thyroid-to-salivary ratio and percent dose uptake are the most widely recognized scintigraphic measurements. Recently, the thyroid-to-background ratio has been proposed as an alternate method. However, this method has not been validated. The purpose of this observational, cross-sectional, prospective study was to determine the location of a background region of interest (ROI) that is most reflective of blood pool activity. We also hypothesized that the thyroid-to-background ratio using this background ROI would be a better predictor of thyroid function. Fifty-six cats presented to the Virginia-Maryland College of Veterinary Medicine seeking radioiodine therapy for hyperthyroidism were enrolled in this cross-sectional study to evaluating thyroid-to-background ratio. A blood sample for measuring plasma radioactivity was collected at the time of scintigraphy. The plasma radioactivity was compared to the background ROIs in eight anatomic regions. Scintigraphic measures of thyroid-to-background and thyroid-to-salivary ratios, and percent dose were then compared to serum T4 . The heart ROI was most closely correlated with plasma pertechnetate activity (r = 0.70). Percent dose uptake was most closely correlated with serum T4 (r = 0.74), followed by thyroid-to-salivary ratio (r = 0.66) and thyroid-to-background ratio using the heart ROI (r = 0.59). Thyroid-to-background ratio using the heart background ROI is a good predictor T4 but percent dose uptake and thyroid-to-salivary ratio proved to be better predictors of T4 than any of the thyroid-to-background ratios.

Invited review--neuroimaging response assessment criteria for brain tumors in veterinary patients.

The evaluation of therapeutic response using cross-sectional imaging techniques, particularly gadolinium-enhanced MRI, is an integral part of the clinical management of brain tumors in veterinary patients. Spontaneous canine brain tumors are increasingly recognized and utilized as a translational model for the study of human brain tumors. However, no standardized neuroimaging response assessment criteria have been formulated for use in veterinary clinical trials. Previous studies have found that the pathophysiologic features inherent to brain tumors and the surrounding brain complicate the use of the response evaluation criteria in solid tumors (RECIST) assessment system. Objectives of this review are to describe strengths and limitations of published imaging-based brain tumor response criteria and propose a system for use in veterinary patients. The widely used human Macdonald and response assessment in neuro-oncology (RANO) criteria are reviewed and described as to how they can be applied to veterinary brain tumors. Discussion points will include current challenges associated with the interpretation of brain tumor therapeutic responses such as imaging pseudophenomena and treatment-induced necrosis, and how advancements in perfusion imaging, positron emission tomography, and magnetic resonance spectroscopy have shown promise in differentiating tumor progression from therapy-induced changes. Finally, although objective endpoints such as MR imaging and survival estimates will likely continue to comprise the foundations for outcome measures in veterinary brain tumor clinical trials, we propose that in order to provide a more relevant therapeutic response metric for veterinary patients, composite response systems should be formulated and validated that combine imaging and clinical assessment criteria.

Magnetic resonance and computed tomographic imaging characteristics and potential molecular mechanisms of feline meningioma associated calvarial hyperostosis.

Meningiomas are the most common feline primary brain tumours, and calvarial hyperostosis (CH) is frequently documented in association with this neoplastic entity. The clinical significance of and mechanisms driving the formation of CH in cats with meningiomas are poorly understood, although tumour invasion into the skull and tumour production of cytokines and enzymes have been implicated as causes of CH in humans. This retrospective study investigated relationships between signalment, MRI or CT imaging features, histopathologic tumour characteristics, alkaline phosphatase (ALP) isoenzyme concentrations, tumour expression of matrix metalloproteinases (MMP)-2, MMP-9, and interleukin-6 (IL-6), and progression free survival times (PFS) following surgical treatment in 27 cats with meningiomas with (n = 15) or without (n = 12) evidence of CH. No significant differences in breed, age, sex, body weight, tumour grade, tumour volume, peritumoral edema burden, ALP isoenzyme concentrations, tumour Ki-67 labelling indices or MMP-2 or MMP-9 expression and activity, or PFS were noted between cats with or without CH. There was a trend towards higher serum (p = .06) and intratumoral (p = .07) concentrations of IL-6 in cats with CH, but these comparisons were not statistically significant. Histologic evidence of tumour invasion into bone was observed in 5/12 (42%) with CH and in no (0/6) cats without CH, although this was not statistically significant (p = .07). Tumour invasion into bone and tumour production of IL-6 may contribute to the formation of meningioma associated CH in cats, although larger studies are required to further substantiate these findings and determine their clinical relevance.

Mechanical High-Intensity Focused Ultrasound (Histotripsy) in Dogs With Spontaneously Occurring Soft Tissue Sarcomas.

INTRODUCTION: Histotripsy is a non-invasive focused ultrasound therapy that uses controlled acoustic cavitation to mechanically disintegrate tissue. To date, there are no reports investigating histotripsy for the treatment of soft tissue sarcoma (STS). OBJECTIVE: This study aimed to investigate the in vivo feasibility of ablating STS with histotripsy and to characterize the impact of partial histotripsy ablation on the acute immunologic response in canine patients with spontaneous STS. METHODS: A custom 500 kHz histotripsy system was used to treat ten dogs with naturally occurring STS. Four to six days after histotripsy, tumors were surgically resected. Safety was determined by monitoring vital signs during treatment and post-treatment physical examinations, routine lab work, and owners' reports. Ablation was characterized using radiologic and histopathologic analyses. Systemic immunological impact was evaluated by measuring changes in cytokine concentrations, and tumor microenvironment changes were evaluated by characterizing changes in infiltration with tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) using multiplex immunohistochemistry and differential gene expression. RESULTS: Results showed histotripsy ablation was achievable and well-tolerated in all ten dogs. Immunological results showed histotripsy induced pro-inflammatory changes in the tumor microenvironment. Conclusion & Significance: Overall, this study demonstrates histotripsy's potential as a precise, non-invasive treatment for STS.

Characterizing the Ablative Effects of Histotripsy for Osteosarcoma: In Vivo Study in Dogs.

Osteosarcoma (OS) is a malignant bone tumor treated by limb amputation or limb salvage surgeries and chemotherapy. Histotripsy is a non-thermal, non-invasive focused ultrasound therapy using controlled acoustic cavitation to mechanically disintegrate tissue. Recent ex vivo and in vivo pilot studies have demonstrated the ability of histotripsy for ablating OS but were limited in scope. This study expands on these initial findings to more fully characterize the effects of histotripsy for bone tumors, particularly in tumors with different compositions. A prototype 500 kHz histotripsy system was used to treat ten dogs with suspected OS at an intermediate treatment dose of 1000 pulses per location. One day after histotripsy, treated tumors were resected via limb amputation, and radiologic and histopathologic analyses were conducted to determine the effects of histotripsy for each patient. The results of this study demonstrated that histotripsy ablation is safe and feasible in canine patients with spontaneous OS, while offering new insights into the characteristics of the achieved ablation zone. More extensive tissue destruction was observed after histotripsy compared to that in previous reports, and radiographic changes in tumor size and contrast uptake following histotripsy were reported for the first time. Overall, this study significantly expands our understanding of histotripsy bone tumor ablation and informs future studies for this application.

Non-coagulopathic hemothorax in a dog: A case report.

An 8-year-old, female-spayed, Blue Heeler presented with suspected non-coagulopathic spontaneous, hemothorax with neoplasia as the most likely differential as coagulation parameters were normal and no obvious history of trauma was reported. Computed tomography scan was crucial for diagnosis of a traumatic partial vascular avulsion injury that was successfully managed supportively.

Histotripsy Ablation of Spontaneously Occurring Canine Bone Tumors In Vivo.

OBJECTIVE: Osteosarcoma (OS) is a devastating primary bone tumor in dogs and humans with limited non-surgical treatment options. As the first completely non-invasive and non-thermal ablation technique, histotripsy has the potential to significantly improve the standard of care for patients with primary bone tumors. INTRODUCTION: Standard of care treatment for primary appendicular OS involves surgical resection via either limb amputation or limb-salvage surgery for suitable candidates. Biological similarities between canine and human OS make the dog an informative comparative oncology research model to advance treatment options for primary OS. Evaluating histotripsy for ablating spontaneous canine primary OS will build a foundation upon which histotripsy can be translated clinically into a standard of care therapy for canine and human OS. METHODS: Five dogs with suspected spontaneous OS were treated with a 500 kHz histotripsy system guided by real-time ultrasound image guidance. Spherical ablation volumes within each tumor (1.25-3 cm in diameter) were treated with single cycle histotripsy pulses applied at a pulse repetition frequency of 500 Hz and a dose of 500 pulses/point. RESULTS: Tumor ablation was successfully identified grossly and histologically within the targeted treatment regions of all subjects. Histotripsy treatments were well-tolerated amongst all patients with no significant clinical adverse effects. Conclusion & Significance: Histotripsy safely and effectively ablated the targeted treatment volumes in all subjects, demonstrating its potential to serve as a non-invasive treatment modality for primary bone tumors.

Evaluation of a procaspase-3 activator with hydroxyurea or temozolomide against high-grade meningioma in cell culture and canine cancer patients.

BACKGROUND: High-grade meningioma is an aggressive type of brain cancer that is often recalcitrant to surgery and radiotherapy, leading to poor overall survival. Currently, there are no FDA-approved drugs for meningioma, highlighting the need for new therapeutic options, but development is challenging due to the lack of predictive preclinical models. METHODS: To leverage the known overexpression of procaspase-3 in meningioma, PAC-1, a blood-brain barrier penetrant procaspase-3 activator, was evaluated for its ability to induce apoptosis in meningioma cells. To enhance the effects of PAC-1, combinations with either hydroxyurea or temozolomide were explored in cell culture. Both combinations were further investigated in small groups of canine meningioma patients and assessed by MRI, and the novel apoptosis tracer, [18F]C-SNAT4, was evaluated in patients treated with PAC-1 + HU. RESULTS: In meningioma cell lines in culture, PAC-1 + HU are synergistic while PAC-1 + TMZ show additive-to-synergistic effects. In canine meningioma patients, PAC-1 + HU led to stabilization of disease and no change in apoptosis within the tumor, whereas PAC-1 + TMZ reduced tumor burden in all three canine patients treated. CONCLUSIONS: Our results suggest PAC-1 + TMZ as a potentially efficacious combination for the treatment of human meningioma, and also demonstrate the utility of including pet dogs with meningioma as a means to assess anticancer strategies for this common brain tumor.

(99m)Tc-DTPA diuretic renal scintigraphy in dogs with nephroureterolithiasis.

This study evaluated the results of diuretic renal scintigraphy in dogs with urolithiasis. Eighty-three kidneys with nephroureterolithiasis +/- renal pelvis/ureteral dilation were included in the study. Sixty-three kidneys showed a non-obstructive pattern, with a steep drop or gradual downward slope of renal time-activity curve (TAC). Excretion half-time of radiopharmaceutical (T(1/2)) was 3.99 (2.99 to 7.95) min. Three kidneys showed an obstructive pattern, with continuous rise of the TAC and median T(1/2) of -10.71 (-5.20 to -17.56) min. Fifteen kidneys had non-diagnostic studies characterized by flat TAC. Individual kidney glomerular filtration rate was <0.5 mL/min/kg body weight in most non-diagnostic studies. Diuretic renal scintigraphy appears to be a useful adjunct modality to rule out or confirm ureteral obstruction in dogs. Additional diagnostic procedures may be necessary to achieve a definitive diagnosis in cases of severely impaired renal function.

Determination of an oral aflatoxin dose that acutely impairs hepatic function in domestic pigeons (Columba livia).

Aflatoxin B1 is a common hepatotoxin in birds. The goal of this study was to establish an acute model for hepatotoxicosis and decreased hepatic function in the white Carneaux pigeon (Columba livia) via oral administration of this mycotoxin. Aflatoxin B1 was orally administered at a dose of 3 mg/kg dissolved in dimethyl sulfoxide to 3 groups of pigeons every 24 hours for 2, 4, and 6 consecutive days, respectively. Diagnostic modalities used to evaluate hepatic damage and impaired hepatic function pre- and postaflatoxin administration included liver enzyme activity, bile acid levels, scintigraphy, and histopathologic evaluation of liver biopsy specimens. Deaths occurred in all groups, increasing with the number of consecutive days the aflatoxin B1 was dosed. Significant histopathologic lesions were seen on evaluation of hepatic tissue from each group after accumulated aflatoxin exposure (P < .05); therefore, an oral aflatoxin B1 dose of 3 mg/kg given for 2 consecutive days was selected for the purpose of inducing acute hepatic damage while minimizing mortality. However, although increased liver enzyme activity indicated hepatocellular damage at this dosage, bile acids testing and hepatobiliary scintigraphy did not show significantly decreased hepatic function.

Changes in hepatic gene expression in dogs with experimentally induced nutritional iron deficiency.

BACKGROUND AND OBJECTIVE: We investigated hepatic gene expression in dogs with experimentally induced nutritional iron deficiency (ID). Our hypothesis was that ID would result in decreased hepcidin gene expression, and possibly in altered expression of other genes associated with iron metabolism. METHODS: Liver biopsies were collected from each of 3 dogs before induction of ID, at the point of maximal ID, and after resolution of ID. Using Affymetrix microarray technology and analytical tools specifically designed for microarray data, we identified genes that had at least a 2-fold change in expression in response to ID. Four genes were selected for further analysis by reverse transcriptase PCR (RT-PCR). RESULTS: Dogs with ID had markedly decreased expression of the hepcidin gene (mean decrease of 40-fold for one probe and >100-fold for another probe) and increased expression of the transferrin receptor gene (mean increase of >7-fold). There was also mildly decreased expression of the "similar to calreticulin" gene and a gene of unknown function. Results of RT-PCR analysis were consistent with microarray findings. CONCLUSION: Changes in hepcidin and transferrin receptor gene expression were consistent with the known biology of iron metabolism. The decrease in expression of a gene identified as "similar to calreticulin," while not statistically significant, was consistent with the findings of other investigators that suggest iron plays a role in calreticulin expression.

Effects of dietary milk thistle on blood parameters, liver pathology, and hepatobiliary scintigraphy in white carneaux pigeons (Columba livia) challenged with B1 aflatoxin.

Milk thistle (Silybum marianum) has been used in humans for the treatment of liver disease because of its antioxidant properties and its ability to stabilize cell membranes and regulate cell permeability. To investigate possible hepatoprotective effects in birds, standardized extracts (80%) of silymarin from milk thistle were tested in white Carneaux pigeons (Columba livia). Pigeons were separated into 3 groups and fed diets formulated to provide milk thistle at a level of 0, 10, or 100 mg/kg body weight per day. After acclimation, the birds were challenged with B1 aflatoxin (3 mg/kg body weight for 2 consecutive days) by oral gavage. Liver function then was assessed by hematologic testing and plasma biochemical analysis, liver histopathology, and hepatobiliary scintigraphy. Results of histopathology and hepatobiliary scintigraphy showed no protective effects from milk-thistle administration. Aflatoxin challenge resulted in hepatic inflammation and necrosis, biliary-duct hyperplasia, and lymphocyte infiltration. All hepatobiliary scintigraphy elements increased significantly after aflatoxin challenge. Bile acid levels and plasma enzyme concentrations of aspartate aminotransferase, lactate dehydrogenase, alanine aminotransferase, and creatine phosphokinase all increased after aflatoxin exposure and were mostly unchanged with consumption of milk thistle. Only birds fed 10 mg/kg body weight milk thistle showed significant reductions in lactate dehydrogenase, alanine aminotransferase, and creatine phosphokinase concentrations after aflatoxin exposure. Our results show that consumption of milk thistle is not associated with hepatoprotective effects against acute B1 aflatoxin exposure in pigeons.

Diffuse intestinal T-cell lymphosarcoma in a yellow-naped Amazon parrot (Amazona ochrocephala auropalliata).

A 10-year-old, intact, female yellow-naped Amazon parrot was examined because of anemia, lymphocytic leukocytosis, regurgitation, and weight loss. A positive fecal occult blood and monoclonal globulinopathy were present. A distended proventriculus and diffusely thickened loops of small intestine with irregular luminal surfaces were identified with contrast radiography and contrast computed tomography. A micro positron emission tomography scan was performed with (18)F-fluorodeoxyglucose. Diffuse intestinal T-cell lymphosarcoma was diagnosed based on histopathology and immunohistochemistry of full thickness small intestinal biopsies. The patient was treated with a multidrug chemotherapy protocol with little to no effect. Euthanasia was elected, and intestinal lymphosarcoma was confirmed on histopathology of necropsy intestinal samples; no other organs demonstrated neoplastic infiltration. To the authors' knowledge, no reports are currently available detailing the clinical presentation or diagnosis of diffuse intestinal T-cell lymphosarcoma in any avian species.

Investigation of a novel variable dosing protocol for radioiodine treatment of feline hyperthyroidism.

BACKGROUND: Radioiodine is the treatment of choice for hyperthyroidism in cats. The ideal method of dose determination of radioiodine remains controversial. OBJECTIVE: To compare a method of radioiodine dose determination that utilized thyroid scintigraphy with a standard fixed dose for treatment of hyperthyroidism. ANIMALS: Fifty-seven and 23 client-owned hyperthyroid cats in the variable and fixed dose groups, respectively. METHODS: Cats with a percent dose uptake using 99m Tc-pertechnetate uptake on thyroid scintigraphy <5%, 5%-10%, and >10% were to receive 3, 3.5, or 4.5 millicuries (mCi) of radioiodine, respectively, administered SC. Radioiodine dose was adjusted according to thyroid gland size as determined by the thyroid:salivary size ratio and categorized as <5:1, 5-10:1, and >10:1. If the thyroid size fell into a higher dosing category than the percent dose uptake, the dose was increased accordingly. Cats in the fixed dose group received 4.5 mCi. Six months after treatment, cats were determined to be euthyroid, hypothyroid, or hyperthyroid based on serum thyroxine and thyroid stimulating hormone concentrations. RESULTS: No difference in outcome was found between the variable and fixed dose treatment groups. Euthyroidism, hypothyroidism, and persistent hyperthyroidism developed in 61, 30, and 9% of cats in the fixed dose group compared to 58, 26, and 16%, respectively, in the variable dose group. CONCLUSIONS: A variable dosing method of radioiodine based on percent dose uptake primarily and thyroid gland size secondarily did not improve outcome compared to a standard fixed dose method.

Advanced imaging for veterinary cancer patients.

This article presents an update on the recent advances made in veterinary advanced imaging specifically with regard to cross-sectional modalities (CT and MRI) and nuclear medicine (positron emission tomography [PET] and PET/CT). A brief summary of technical improvements and a review of recent literature are included to provide an overview of the progress made in this important element of the practicing veterinary oncologist's repertoire. An in-depth summary of PET is also included to introduce the technical aspects and potential clinical and research applications of this novel imaging modality in veterinary medicine.

Comparison of 99mTcO4(-) trans-splenic portal scintigraphy with per-rectal portal scintigraphy for diagnosis of portosystemic shunts in dogs.

OBJECTIVE: To evaluate trans-splenic portal scintigraphy (TSPS) and per-rectal portal scintigraphy (PRPS) for diagnosis of congenital portosystemic shunts (CPSS) in dogs, and compare these results with surgical findings. STUDY DESIGN: Prospective, randomized cross over clinical trial. ANIMALS: Dogs (n=42) with suspected CPSS. METHODS: Dogs had TSPS and PRPS 48 hours apart; quantity of radionuclide administered was recorded. Three independent, blinded reviewers evaluated each scintigraphic study for study quality, shunt presence, number, and location of shunt termination (caudal vena cava, azygos vein). All dogs had exploratory celiotomy. Negative scintigraphic findings were confirmed with intraoperative mesenteric portography. Ameroid constrictors were placed on all extrahepatic CPSS, and hepatic biopsies were obtained. RESULTS: TSPS was 100% sensitive and specific for diagnosis of CPSS and significantly (P<.05) more likely than PRPS to detect shunt number and termination. Interpretation was consistent between observers, and TSPS required significantly less radionuclide than PRPS. CONCLUSION: TSPS was as sensitive as PRPS for detection of shunting vessels, and consistently yielded studies of higher quality, allowing detection of shunt number and location with consistent interpretation among radiologists. CLINICAL RELEVANCE: TSPS provides information about shunt number and location, which allows improved surgical planning. Because it requires significantly less radionuclide, TSPS improves safety, allows for more comprehensive patient care, and earlier surgical intervention.

Thyrotoxicosis induced by excessive 3,5,3'-triiodothyronine in a dog.

CASE DESCRIPTION A 7-year-old castrated male Havanese was evaluated at a veterinary teaching hospital because of a 12-week history of hyperactivity, aggression, and progressive weight loss despite a healthy appetite. CLINICAL FINDINGS Tachycardia was the only remarkable finding during physical examination. Serum 3,5,3'-triiodothyronine (T3) and free T3 concentrations were markedly increased, and thyroxine (T4), free T4, and thyroid-stimulating hormone concentrations were at or decreased from the respective reference ranges. Thyroid scintigraphy revealed suppressed uptake of sodium pertechnetate Tc 99m by the thyroid gland but no ectopic thyroid tissue, which was indicative of thyrotoxicosis induced by an exogenous source of T3. TREATMENT AND OUTCOME The dog was hospitalized for 24 hours, and its diet was changed, after which the clinical signs rapidly resolved and serum T3 and free T3 concentrations returned to within the respective reference ranges. This raised suspicion of an exogenous source of T3 in the dog's home environment. Analysis of the commercial beef-based canned food the dog was being fed revealed a high concentration of T3 (1.39 µg/g) and an iodine (82.44 µg/g) concentration that exceeded industry recommendations. No other source of T3 was identified in the dog's environment. CLINICAL RELEVANCE To our knowledge, this is the first report of clinical thyrotoxicosis in a dog induced by exogenous T3, although the source of exogenous T3 was not identified. This case highlights the importance of measuring serum T3 and thyroid-stimulating hormone concentrations in addition to T4 and free T4 concentrations when there is incongruity between clinical findings and thyroid function test results.

Evaluation of an implanted osmotic pump for delivery of amikacin to corn snakes (Elaphe guttata guttata).

The risk of accidental envenomation to the handler of venomous snakes during drug administration limits the ability to treat these animals. One commercially available osmotic pump is a miniature self-contained cylindrical implant that operates on the basis of an osmotic pressure difference between the extracellular fluid and the osmotic agent in the pump. Osmotic pumps loaded with amikacin were surgically placed into the coelomic cavity of five adult corn snakes (Elaphe guttata guttata) (group A). Four snakes (group B) received an intramuscular injection of amikacin at 5 mg/kg followed by 2.5 mg/kg q 72 hr for a total of four injections. Plasma concentrations of amikacin were measured in both groups. Renal function was evaluated pre- and posttreatment via scintigraphy with 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) and measurement of plasma uric acid concentrations. Mean (+/- SD) steady state amikacin concentration for group A was 6.9 +/- 1.7 microg/ml (predicted = 8.0 microg/ml), and the measured pump rate was 0.134 +/- 0.017 microl/hr (predicted = 0.130 microl/hr). Mean (+/- SD) peak and trough plasma amikacin concentrations for group B were 22.7 +/- 8.5 microg/ml and 14.3 +/- 7.0 microg/ml, respectively. While neither scintigraphy nor plasma uric acid concentrations indicated toxicity in either group, continuous administration of aminoglycosides may cause nephrotoxicity, and it is unknown whether this delivery method of amikacin would be efficacious in treating bacterial infections in snakes. In addition, due to migration of one pump into the trachea causing asphyxiation and death, these pumps may not be appropriate for intracoelomic placement in corn snakes. Nonetheless, the pumps delivered the drug at a predictable rate and were efficacious in achieving a constant plasma concentration of amikacin at the predicted level. Osmotic pumps may offer a safer alternative to periodic intramuscular injections for drug delivery in venomous or aggressive snakes.

Quantitative assessment of hepatic function by means of 99mTc-mebrofenin in healthy horses.

99mTc-mebrofenin is used in humans and small animals to assess hepatic function. This study was undertaken to measure hepatic clearance of 99mTc-mebrofenin in healthy horses and to determine whether feed deprivation and increased serum total bilirubin (TBIL) concentration alter 99mTc-mebrofenin clearance. Plasma clearance of 99mTc-mebrofenin was determirned in 7 healthy horses at 0, 48, and 96 hours of feed withholding. Serum TBIL and nonesterified fatty acid (NEFA) concentrations were measured every 24 hours. 99mTc-mebrofenin (4.16 +/- 0.62 mCi, mean +/- SD) was injected into a jugular vein, and blood samples were retrieved from the contralateral jugular vein. A plasma time-activity curve of 99mTc-mebrofenin was generated, from which the area under the curve (AUC) and the T1/2 of the fast-phase (T1/2) and slow-phase (T1/2f) were calculated. Mean +/- SD AUC was 17,700 +/- 4,257, 18,616 +/- 8,078, and 16,168 +/- 6,031 counts per minute (cpm) at 0, 48, and 96 hours, respectively; mean +/- SD T1/2f was 2.80 +/- 0.38 minutes, 3.52 +/- 1.46 minutes, and 3.82 +/- 1.29 minutes at 0, 48, and 96 hours, respectively; median T1/2s was 63.9, 49.2, and 45.8 minutes at 0, 48, and 96 hours, respectively. No difference was detected between the values of AUC, T1/2f, and T1/2s at 0, 48, and 96 hours. There was a significant increase in TBIL with fasting, with a mean +/- SD of 6.3 +/- 1.3 mg/dL at 26 hours. NEFAs increased, reaching a plateau at 48 hours (650 +/- 152 micromol/L). Plasma TBIL concentrations did not correlate with AUC or T1/2s but correlated weakly with T1/2f (r = 0.50). Plasma NEFA concentrations did not correlate with AUC, T1/2s, or T1/2f values. This study suggests that 99mTc-mebrofenin plasma clearance is not affected by feed withholding and that hyperbilirubinemia associated with feed withholding does not affect the hepatic extraction efficiency of this radiopharmaceutical.