Correlation of quantified contrast-enhanced power Doppler ultrasonography with immunofluorescent analysis of microvessel density in spontaneous canine tumours

Conventionally, tumour vascularity is assessed invasively by immunofluorescent analysis. Quantified contrast-enhanced power Doppler ultrasound has been used to measure tumour angiogenesis non-invasively in humans and experimental animals. The purpose of this study was to correlate quantified contrast-enhanced power Doppler ultrasound with immunofluorescent results in 45 spontaneous canine tumours. With power Doppler, mean vascularity was high in squamous cell carcinomas, moderate in malignant oral melanomas and low in sarcomas. There was high mean vascularity in squamous cell carcinomas and low mean vascularity in sarcomas and malignant oral melanomas. Although Doppler parameters correlated moderately with microvascular density for all tumours (P=0.004, r=0.4), they did not correlate within histology groups. These analyses show that vascularity differs among canine tumour histology groups. However, dependent on the method used, measurement of tumour vascularity can provide different biological information.     

Color and power Doppler ultrasonography for characterization of splenic masses in dogs

Benign and malignant splenic masses can appear similar on B-mode imaging, making ultrasound sensitive but not specific in their diagnosis. Our goal was to characterize color and/or power Doppler characteristics of vasculature within and adjacent to a splenic mass, which would distinguish benign vs. malignant lesions. The hypothesis was that malignant splenic masses will have altered vascular patterns compared with benign masses. Color and power Doppler cineloops evaluating the vasculature within the mass and normal splenic parenchyma were obtained in sagittal and transverse planes using a standardized protocol. Categories of evaluation included presence of peritoneal effusion, a large aberrant or tortuous vessel within the mass, relative blood flow within the mass compared with normal parenchyma, and path of vessels in the adjacent parenchyma entering into the mass. All patients had histopathologic or definitive cytologic diagnosis. Thirty-one dogs were included. There were 13 malignant masses and 18 were benign. Peritoneal effusion was significantly associated with malignancy (P = 0.0007). Presence of an aberrant or tortuous vessel within the mass was nearly significant (P = 0.059). There was no significant difference in any of the color or power Doppler blood flow evaluations. Ultrasonographic findings of a splenic mass and peritoneal effusion may indicate malignancy. The presence of an aberrant vessel within a splenic mass could suggest malignancy; however more data are needed.     

Contrast-enhanced power and color Doppler ultrasonography of the pancreas in healthy and diseased cats

Background: The diagnosis of feline pancreatic disease is difficult, because clinical abnormalities and routine noninvasive diagnostic tests are unreliable. Objective: The purpose of this study was to investigate by Doppler ultrasonography if vascularity and blood volume differs in the otherwise ultrasonographically normal and diseased feline pancreas. Animals: Thirty‐six client owned cats. Methods: The pancreas was examined with B‐mode and contrast‐enhanced color and power Doppler ultrasonography. Doppler images were analyzed with a computer program: parameter fractional area represents a vascularity index and color‐weighted fractional area assesses blood volume. Results: Based on the B‐mode findings, the pancreas was considered normal in 11 clinically healthy cats and diseased in 25 cats of which 4 were clinically healthy and 21 had clinical signs consistent with pancreatic disease. Histologic or cytologic samples were taken in all diseased pancreata. Fifteen samples were of diagnostic quality: purulent or mixed cellular inflammation (8), nodular hyperplasia (4), and neoplasia (3) were identified. Vascularity and blood volume for all Doppler methods was significantly higher in cats with pancreatic disease. Significantly higher Doppler values were detected with power Doppler than with color Doppler, and with postcontrast color and power Doppler than with precontrast Doppler technologies. Conclusion: Contrast‐enhanced Doppler ultrasonography appears feasible in the feline pancreas. Significant differences were found between normal cats and those with evidence of pancreatic pathology. Further studies are needed to evaluate its use for the differentiation of pancreatic disorders and in cats suspected to have pancreatic disease but without B‐mode ultrasonographic changes of the pancreas.     

Evaluation of nonunion fractures in dogs by use of B-mode ultrasonography, power Doppler ultrasonography, radiography, and histologic examination

OBJECTIVE: To investigate the use of ultrasonography to assess nonunion of fractures in dogs and to compare results of ultrasonography, radiography, and histologic examination. SAMPLE POPULATION: 8 nonunion fractures in 6 dogs (1 each in 5 dogs and 3 in 1 dog); dogs ranged from 7 to 94 months of age and weighed 6 to 30 kg. PROCEDURES: Diagnostic assessment consisted of complete clinical and orthopedic examinations, radiography, B-mode (brightness mode) ultrasonography, and power Doppler ultrasonography. Biopsy samples were obtained during surgery for histologic examination. They were stained with H&E and immunolabeled by use of anti-CD31 antibodies. Correlations of power Doppler score, power Doppler count, vessel area, and radiographic prediction with the mean number of vessels counted per hpf were derived. RESULTS: Radiographically, 7 of 8 nonunion fractures were diagnosed as atrophic and were therefore estimated to be nonviable. Vascularity of nonunion fractures during power Doppler ultrasonography ranged from nonvascularized to highly vascularized. Absolute vessel count during histologic examination ranged from 0 to 63 vessels/hpf; 5 nonunion sites had a mean count of > 10 vessels/hpf. Vascularity during power Doppler ultrasonography was highly correlated with the number of vessels per hpf, whereas the correlation between the radiographic assessment and histologic evaluation was low. CONCLUSIONS AND CLINICAL RELEVANCE: Radiographic prediction of the viability of nonunion fractures underestimated the histologically assessed vascularity of the tissue. Power Doppler ultrasonography provided a more accurate estimation of the viability of the tissue and therefore the necessity for debridement and autografts during revision surgery.     

Evaluation of pacing site in dogs with naturally occurring complete heart block

Objective

To compare left ventricular synchronization and systolic performance with transvenous pacing of the right ventricular apex (RVA), left ventricular free wall (LVF) or simultaneous pacing of the RVA and LVF (BiV).

Animals, materials and methods

Seven canine patients with complete heart block. Prospective study evaluating effect of pacing site. Twenty four hours following implantation of transvenous BiV pacing systems, electrocardiograms and echocardiograms were assessed during pacing from the: (1) Right Atrial Appendage/RVA (RAA/RVA), (2) RAA/LVF, and (3) RAA/BiV.

Results

QRS duration was significantly shorter with BiV pacing versus LVF pacing (p < 0.001), or RVA pacing (p < 0.001). Echocardiographic indices of systolic performance fractional shortening (FS), ejection fraction (EF), cardiac output (CO) were significantly higher with BiV pacing than with pacing from the RVA (P = 0.023, 0.006, and 0.002 respectively). Cardiac output, measured by the biplane Simpson's method, was higher with LVF versus RVA pacing (P = 0.036). There was no difference in FS or EF when comparing LVF to RVA pacing. Tissue Doppler measurements of synchronization and systolic performance did not show any difference between pacing mode, but a significantly increased number of segments were seen to contract following aortic valve closure during LVF pacing (P = 0.0268) and RVA pacing (P = 0.0197) as compared to BiV pacing.

Conclusions

Findings suggest that BiV pacing improves cardiac output and systolic performance versus RVA pacing. This improvement however, is not reflected in tissue Doppler indices of synchronization and systolic performance.     

Evaluation of satraplatin in dogs with spontaneously occurring malignant tumors

Background: Satraplatin is the 1st orally bioavailable platinum anticancer drug. Objective: Our objectives were to evaluate efficacy in vitro against a canine cancer cell line, to determine the maximally tolerated dose (MTD) of satraplatin in tumor‐bearing dogs, to identify the dose‐limiting and other toxicities in dogs, and to record pharmacokinetics (PK). Animals: Dogs with macro‐ or microscopic malignant neoplasia. Methods: D17 canine osteosarcoma cells first were evaluated in a clonogenic survival assay. Then, dogs with a diagnosis of malignant neoplasia were prospectively entered in standard 3 + 3 cohorts. Additional patients were entered at the MTD to assess efficacy. Total and free platinum (by ultrafiltrate) concentrations were determined with inductively coupled plasma mass spectroscopy. Results: Satraplatin inhibited clonogenic survival in vitro at clinically relevant and achievable concentrations. Twenty‐three dogs were treated, 14 with PK evaluation. The MTD was 35 mg/m²/d for 5 days, repeated every 3–4 weeks. Bioavailability was 41%. PK variables (mean ± SD) at the MTD included T_max 1.8 (± 0.7) hours, C_max 72 (± 26) ng/mL, area under concentration (AUC)_{0–24 h} 316 (± 63) h × ng/mL, and MRT 7 (± 1.3) hours. Higher AUC after the 5th versus the 1st dose suggested drug accumulation. Interestingly, platelets consistently reached nadir sooner than did neutrophils (day 14 versus 19). Myelosuppression was dose‐limiting and gastrointestinal toxicity was mild. Conclusions and Clinical Importance: Satraplatin was well tolerated in tumor‐bearing dogs, thus warranting further investigation in a phase II trial.     

Evaluation of an insulin zinc suspension for control of naturally occurring diabetes mellitus in dogs

OBJECTIVE: To evaluate duration of action of an insulin zinc suspension (Caninsulin, Intervet) in spontaneously occurring cases of canine diabetes mellitus and suitability of its use as a once daily administered insulin for treatment of this disease. DESIGN: Eight client-owned canine diabetics were included in a prospective pilot study. All dogs had been treated with Caninsulin for a minimum of 2 months and were considered on clinical grounds to be adequately stabilised. PROCEDURE: Dogs were hospitalised for 24 h and blood collected every 2 h via indwelling venous catheters for blood glucose determination. RESULTS: Once daily Caninsulin administration failed to maintain glycaemic control for greater than 13 h in five of eight dogs, but acceptable blood glucose concentrations were maintained for 22 h and greater than 24 h in two others. One dog became distressed during hospitalisation and the blood glucose curve did not show an identifiable response to the insulin. CONCLUSION: Most diabetic dogs may require twice daily administration of Caninsulin for satisfactory glycaemic control, but once daily administration may be adequate in some animals. More comprehensive investigation into duration of activity of Caninsulin is warranted.     

A review of Doppler sonography for the assessment of tumour vascularity

During the past decade, the vascular biology of cancer has become a highly interesting research field. To assess tumour vascularity and perfusion, various strategies such as computed tomography, magnetic resonance imaging and positron emission tomography have been investigated. Over the last years, important advances have taken place in the Doppler technology which dramatically improved its ability to evaluate the vascular system, even small and deep vessels. Doppler sonography provides a non‐invasive means to assess the extent and morphology of tumour vascularity. This information is clinically important regarding diagnosis, prognosis and response to treatment, particularly in connection with the development of novel angiogenesis inhibitors. This article describes the different Doppler technologies most commonly used in human and experimental animal oncology. Based on in vivo tumour models and extensive clinical experience in humans, their significance and potential clinical applications are illustrated. First clinical reports in veterinary medicine are also reviewed.     

Diagnosis and treatment of naturally occurring hypoadrenocorticism in 42 dogs

Hypoadrenocorticism was diagnosed in 42 dogs over a two-and-a-half-year period. The disease occurred more commonly in young to middle-aged dogs, with a female:male ratio of 2:1. Most dogs had chronic intermittent signs (eg, poor appetite, lethargy and vomiting), but more than a third were in acute adrenal crisis at the time of diagnosis. Serum biochemical testing revealed azotaemia, hyperphosphataemia, hyper-kalaemia and hyponatraemia in almost all the dogs. In all dogs, results of adrenocorticotrophic hormone (ACTH) stimulation testing revealed a low to low-normal serum baseline Cortisol concentration that failed to increase after ACTH administration. In two dogs with persistently normal serum electrolytes concentration, one had a markedly high plasma ACTH concentration diagnostic for primary hypoadrenocorticism, whereas the other had a low concentration confirming secondary hypoadrenocorticism. Fludrocortisone acetate was initially used for mineralocorticoid replacement in 33 of the 37 treated dogs withprimary hypoadrenocorticism (final median dosage, 27-0 μg/kg/day), but supplementation was changed to desoxycorticos-terone pivalate (DOCP) in four dogs because of poor response or adverse effects. Seven dogs with primary hypoadrenocorticism were treated with DOCP (final median dosage, 2-02 mg/kg/month). Prednisone, initially administered to 36 dogs, was discontinued in 11 dogs because of side effects. Of the dogs treated with fludrocortisone, the response was considered good to excellent in 26 dogs (78.8 per cent), fair in three, and poor in four. All dogs treated with DOCP responded well.     

Evaluation of intracranial pressure by transcranial Doppler ultrasonography in dogs with intracranial hypertension

Transcranial Doppler ultrasonography (TCD) has been used to confirm changes in cerebral hemodynamics. In this study, we investigated whether the parameters for the basilar artery measured by TCD were correlated with the intracranial and cerebral perfusion pressures in extreme intracranial hypertension. An intracranial hypertension model was produced in seven dogs by inflating a balloon inserted into the epidural space. The resistance index was compared with the corresponding intracranial pressure and cerebral perfusion pressure values during intracranial hypertension. A significant correlation was recognized between the resistance index and cerebral perfusion pressure. Therefore, measurement of the basilar artery by TCD in the dog with intracranial hypertension is useful in estimating the intracranial circulation in cases where the measurement of intracranial pressure is not available or not indicated.     

Evaluation of twice-daily, low-dose trilostane treatment administered orally in dogs with naturally occurring hyperadrenocorticism

OBJECTIVE: To evaluate the effects of twice-daily oral administration of a low-dose of trilostane treatment and assess the duration of effects after once-daily trilostane administration in dogs with naturally occurring hyperadrenocorticism (NOH). DESIGN: Prospective study. ANIMALS: 28 dogs with NOH. PROCEDURES: 22 dogs received 0.5 to 2.5 mg of trilostane/kg (0.23 to 1.14 mg/lb) orally every 12 hours initially. At intervals, dogs were reevaluated; owner assessment of treatment response was recorded. To assess drug effect duration, 16 of the 22 dogs and 6 additional dogs underwent 2 ACTH stimulation tests 3 to 4 hours and 8 to 9 hours after once-daily trilostane administration. RESULTS: After 1 to 2 weeks, mean trilostane dosage was 1.4 mg/kg (0.64 mg/lb) every 12 hours (n = 22 dogs; good response [resolution of signs], 8; poor response, 14). Four to 8 weeks later, mean dosage was 1.8 mg/kg (0.82 mg/lb) every 12 or 8 hours (n = 21 and 1 dogs, respectively; good response, 15; poor response, 5; 2 dogs were ill). Eight to 16 weeks after the second reevaluation, remaining dogs had good responses (mean dosages, 1.9 mg/kg [0.86 mg/lb], q 12 h [n = 13 dogs] and 1.3 mg/kg [0.59 mg/lb], q 8 h [3]). At 3 to 4 hours and 8 to 9 hours after once-daily dosing, mean post-ACTH stimulation serum cortisol concentrations were 2.60 and 8.09 Pg/dL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with NOH, administration of trilostane at low doses every 12 hours was effective, although 2 dogs became ill during treatment. Drug effects diminished within 8 to 9 hours. Because of potential adverse effects, lower doses should be evaluated.     

Nephrotomography and ultrasonography for the localization of hyperfunctioning adrenocortical tumors in dogs

Nephrotomography and ultrasonography were used in 11 dogs with hyperadrenocroticism to assess the value of these techniques for the localization of biochemically diagnosed hyperfunctioning adrenocortical tumors. Both techniques enabled accurate localization of a unilateral adrenal mass in each of the dogs. Cross-sectional diameters of the masses ranged from 1 to 4 cm. In 1 dog, expansion of tumor into the caudal vena cava was revealed by caudal venacavography and ultrasonography. Mineralization in the tumor mass in 2 dogs was easily recognized by nephrotomography, but not by ultrasonography. Paracostal laparotomy confirmed the presence of an adrenocortical tumor in each dog, and expansion of tumor into the caudal vena cava in 1 dog. Cross-sectional diameters of the tumors ranged from 1.2 to 4.5 cm and corresponded well with cross-sectional measurements by nephrotomography and ultrasonography. It was concluded that nephrotomography and ultrasonography have similar diagnostic accuracies for the detection and localization of hyperfunctioning adrenocortical tumors.