Valerie F. Samii

Biological Effects of Short-Term or Prolonged Administration of 9-[2-(Phosphonomethoxy)Propyl]Adenine (Tenofovir) to Newborn and Infant Rhesus Macaques

ABSTRACT The reverse transcriptase inhibitor 9-[2-(phosphonomethoxy)propyl]adenine (PMPA; tenofovir) was previously found to offer strong prophylactic and therapeutic benefits in an infant macaque model of pediatric human immunodeficiency virus (HIV) infection. We now summarize the toxicity and safety of PMPA in these studies. When a range of PMPA doses (4 to 30 mg/kg of body weight administered subcutaneously once daily) was administered to 39 infant macaques for a short period of time (range, 1 day to 12 weeks), no adverse effects on their health or growth were observed; this included a subset of 12 animals which were monitored for more than 2 years. In contrast, daily administration of a high dose of PMPA (30 mg/kg subcutaneously) for prolonged periods of time (>8 to 21 months) to 13 animals resulted in a Fanconi-like syndrome (proximal renal tubular disorder) with glucosuria, aminoaciduria, hypophosphatemia, growth restriction, bone pathology (osteomalacia), and reduced clearance of PMPA. The adverse effects were reversible or were alleviated following either complete withdrawal of PMPA treatment or reduction of the daily regimen from 30 mg/kg to 2.5 to 10 mg/kg subcutaneously. Finally, to evaluate the safety of a prolonged low-dose treatment regimen, two newborn macaques were started on a 10-mg/kg/day subcutaneous regimen; these animals are healthy and have normal bone density and growth after 5 years of daily treatment. In conclusion, our findings suggest that chronic daily administration of a high dose of PMPA results in adverse effects on kidney and bone, while short-term administration of relatively high doses and prolonged low-dose administration are safe.

Detection of congestive heart failure in dogs by Doppler echocardiography.

BACKGROUND Echocardiographic prediction of congestive heart failure (CHF) in dogs has not been prospectively evaluated. HYPOTHESIS CHF can be predicted by Doppler echocardiographic (DE) variables of left ventricular (LV) filling in dogs with degenerative mitral valve disease (MVD) and dilated cardiomyopathy (DCM). ANIMALS Sixty-three client-owned dogs. METHODS Prospective clinical cohort study. Physical examination, thoracic radiography, analysis of natriuretic peptides, and transthoracic echocardiography were performed. Diagnosis of CHF was based upon clinical and radiographic findings. Presence or absence of CHF was predicted using receiver-operating characteristic (ROC) curve, multivariate logistic and stepwise regression, and best subsets analyses. RESULTS Presence of CHF secondary to MVD or DCM could best be predicted by E:isovolumic relaxation time (IVRT) (area under the ROC curve [AUC]=0.97, P<.001), respiration rate (AUC=0.94, P<.001), Diastolic Functional Class (AUC=0.93, P<.001), and a combination of Diastolic Functional Class, IVRT, and respiration rate (R2=0.80, P<.001) or Diastolic Functional Class (AUC=1.00, P<.001), respiration rate (AUC=1.00, P<.001), and E:IVRT (AUC=0.99, P<.001), and a combination of Diastolic Functional Class and E:IVRT (R2=0.94, P<.001), respectively, whereas other variables including N-terminal pro-brain natriuretic peptide, E:Ea, and E:Vp were less useful. CONCLUSION AND CLINICAL IMPORTANCE Various DE variables can be used to predict CHF in dogs with MVD and DCM. Determination of the clinical benefit of such variables in initiating, modulating, and assessing success of treatments for CHF needs further study.

Results of excision of thymoma in cats and dogs: 20 cases (1984–2005)

OBJECTIVE To provide long-term follow-up information for a series of dogs and cats with invasive and noninvasive thymomas treated by excision alone. DESIGN Retrospective case series. ANIMALS 9 cats and 11 dogs with thymoma. PROCEDURES Medical records were reviewed. The following factors were analyzed for their effect on prognosis: age of dog or cat, invasiveness of the tumor, percentage of lymphocytes in the mass (percentage lymphocyte composition) on histologic evaluation, and mitotic index of the mass. RESULTS All patients were treated with excision of the tumor alone. Median overall survival time for the cats was 1,825 days, with a 1-year survival rate of 89% and a 3-year survival rate of 74%. Median overall survival time for the dogs was 790 days, with a 1-year survival rate of 64% and a 3-year survival rate of 42%. Recurrence of thymoma was observed in 2 cats and 1 dog, and a second surgery was performed in each, with subsequent survival times of 5, 3, and 4 years following the first surgery. Percentage lymphocyte composition of the mass was the only factor that was significantly correlated with survival time; animals with a high percentage of lymphocytes lived longer. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study indicated that most cats and dogs with thymomas did well after excision. Even cats and dogs with invasive masses that survived the surgery and the few cats and dogs with recurrent thymomas or paraneoplastic syndromes had a good long-term outcome. Excision should be considered an effective treatment option for dogs and cats with thymomas.

Advanced Imaging of the Spine in Small Animals

Computed tomography (CT) and magnetic resonance imaging (MRI) are extremely valuable techniques in the diagnosis of spinal disorders. This article reviews the fundamentals, indications, key technical aspects, and advantages and disadvantages of each modality. The CT and MRI features of common spinal diseases are discussed and illustrated. Comparative studies using advanced and nonadvanced imaging modalities are also presented.

Thoracic radiography, bronchoalveolar lavage cytopathology, and pulmonary parenchymal histopathology: A comparison of diagnostic results in 11 cats

The purpose of this study was to compare the diagnostic results and value of thoracic radiography, bronchoalveolar lavage (BAL) fluid cytopathology, and lung histopathology in 11 cats with spontaneous respiratory disease in which radiography and cytopathology were inadequate in establishing a definitive diagnosis. In these cats, radiographic patterns were characterized as bronchial (n=6), interstitial (n=3), and alveolar (n=2); other features included hyperinflation (n=3), bronchiectasis (n=2), pleural fissure lines (n=2), pulmonary nodules (n=2), atelectasis (n=1), and a tracheal mass (n=1). Bronchoalveolar lavage fluid was unremarkable in two cats. Abnormal BAL fluid showed inflammation (n=5), hemorrhage (n=2), epithelial hyperplasia (n=1), or was suspicious for neoplasia (n=1). Histopathological evaluation revealed inflammation (n=8), neoplasia (n=2), and vascular congestion (n=1). The predominant radiographic location of disease correlated with the same histopathological location in seven cats, and the cytopathological class of BAL fluid was consistent with the histopathological class of disease in seven cats. There was poor correlation between the types of cells found in the BAL fluid and the pathologists prediction of the types of cells likely to be found in the BAL fluid based on the amount and type of airway cellularity seen on histopathological examination. The results of this study suggest that in some cats, BAL fluid cytopathology does not always correlate with the type of pulmonary disease identified on histopathology. In respiratory diseases where radiography and cytopathology fail to provide a definitive diagnosis, histopathological examination of the lung may be necessary.

Ultrasonographic Evaluation of the Thyroid Gland in Healthy, Hypothyroid, and Euthyroid Golden Retrievers with Nonthyroidal Illness

Ultrasound evaluation of the thyroid gland was performed in healthy, hypothyroid, and euthyroid Golden Retriever dogs with nonthyroidal illness (NTI) to determine the diagnostic usefulness of ultrasound for differentiating between euthyroid and hypothyroid dogs. Thirty-six healthy, 11 hypothyroid, and 35 euthyroid dogs with NTI were evaluated. Each thyroid lobe was examined ultrasonographically for size, shape, echogenicity, and homogeneity. Thyroid lobe volume was estimated by using the equation for an ellipsoid: pi/6(length X height x width). No differences were found between healthy dogs and euthyroid dogs with NTI. In the majority of euthyroid dogs, the thyroid lobes were fusiform and triangular in shape in longitudinal and transverse planes, respectively. The thyroid capsule appeared smooth. The thyroid parenchyma had a homogeneous echogenic pattern and usually was hyperechoic or isoechoic compared with the surrounding musculature. Ultrasound findings in hypothyroid dogs were more variable, including a greater frequency of round to oval-shaped thyroid lobes in the transverse imaging plane (P < .05), hypoechogenicity of the thyroid parenchyma compared with surrounding musculature (P < .001), and a decrease in the size and volume of the thyroid lobes and total volume of the thyroid gland (P < .05) compared with euthyroid dogs. Other findings in hypothyroid dogs included an irregular surface to the thyroid capsule, a heterogeneous pattern to the thyroid parenchyma, and differences in the echogenic pattern between the left and right thyroid lobes. Results suggest that determination of thyroid size and volume by ultrasound may be a useful adjunctive test for differentiating between hypothyroid and euthyroid dogs with NTI.

Effects of treatment on respiratory rate, serum natriuretic peptide concentration, and Doppler echocardiographic indices of left ventricular filling pressure in dogs with congestive heart failure secondary to degenerative mitral valve disease and dilated cardiomyopathy

OBJECTIVE To evaluate the effects of treatment on respiratory rate, serum natriuretic peptide concentrations, and Doppler echocardiographic indices of left ventricular filling pressure in dogs with congestive heart failure (CHF) secondary to degenerative mitral valve disease (MVD) and dilated cardiomyopathy (DCM). DESIGN Prospective cohort study. ANIMALS 63 client-owned dogs. PROCEDURES Physical examination, thoracic radiography, analysis of natriuretic peptide concentrations, and Doppler echocardiography were performed twice, at baseline (examination 1) and 5 to 14 days later (examination 2). Home monitoring of respiratory rate was performed by the owners between examinations. RESULTS In dogs with MVD, resolution of CHF was associated with a decrease in respiratory rate, serum N-terminal probrain natriuretic peptide (NT-proBNP) concentration, and diastolic functional class and an increase of the ratio of peak velocity of early diastolic transmitral flow to peak velocity of early diastolic lateral mitral annulus motion (E:Ea Lat). In dogs with DCM, resolution of CHF was associated with a decrease in respiratory rate and serum NT-proBNP concentration and significant changes in 7 Doppler echocardiographic variables, including a decrease of E:Ea Lat and the ratio of peak velocity of early diastolic transmitral flow to isovolumic relaxation time. Only respiratory rate predicted the presence of CHF at examination 2 with high accuracy. CONCLUSIONS AND CLINICAL RELEVANCE Resolution of CHF was associated with predictable changes in respiratory rate, serum NT-proBNP concentration, and selected Doppler echocardiographic variables in dogs with DCM and MVD. Home monitoring of respiratory rate was simple and was the most useful in the assessment of successful treatment of CHF.

Correlation between fine-needle aspiration cytopathology and histopathology of the lung in dogs and cats

Medical records from 28 patients having fine-needle aspiration (FNA) cytopathology and histopathology of pulmonary lesions were reviewed. Clinical signs, thoracic radiographs, cytopathology, histopathology, and complications associated with FNA were evaluated. Correlation between cytopathological and histopathological diagnoses was determined. Cytopathological specimens were classified as neoplastic, inflammatory, or nondiagnostic. Histopathological diagnoses were categorized as neoplastic or inflammatory. No complications were observed following FNA. Diagnoses obtained by FNA cytopathology accurately reflected the diagnosis obtained on histopathological examination in 82% of cases. Fine-needle aspiration cytopathology of the lung is a useful and safe diagnostic tool in dogs and cats with pulmonary parenchymal lesions.

Ectopic Ureters in Male Dogs: Review of 16 Clinical Cases (1999–2007)

Ureteral ectopia is a well-described cause of urinary incontinence in female dogs, but this condition has not been completely characterized in male dogs. Sixteen male dogs with ectopic ureters were evaluated between Jan 1999 and Mar 2007. Male dogs were similar to female dogs with ectopic ureters in terms of breed, presenting complaint, age of onset, and bilateral nature of the ectopia. Diagnosis was made by expert interpretation of imaging techniques such as excretory urography and contrast-enhanced computed tomography (CT). Overall, 11 of 13 dogs that had surgical correction of ectopic ureters were incontinent preoperatively. Urinary continence was restored in 82% of those dogs.

Computed tomographic assessment of vascular invasion and resectability of mediastinal masses in dogs and a cat

Abstract AIMS: To assess the sensitivity of non-angiographic contrast-enhanced computed tomography (CT) to determine the presence of vascular invasion of cranial mediastinal masses in dogs and a cat, and to evaluate the association between vascular invasion and peri-operative mortality. METHODS: A retrospective study was conducted on 25 dogs and one cat. CT scans were completed with slices ranging from 2 to 10 mm. CT images were evaluated by a board-certifi ed radiologist blinded to previous diagnoses and surgical fi ndings. Each CT study was evaluated for vascular invasion, defi ned as disruption of the vessel wall and extension of the mass into the vessel lumen. Data retrieved from the surgery reports included surgical approach, whether vascular invasion was present, the surgeons decision on operability, and post-operative complications. RESULTS: Computed tomographic evaluation revealed 25/26 masses had no evidence of vascular invasion. During surgical exploration, 10/26 masses were found to invade major regional vasculature; the cranial vena cava (CVC) was the vessel most commonly invaded (7/10 animals), and 4/7 (57%) patients with invasion of the CVC were euthanised or died in the perioperative period, from surgical or disease-related problems, which was signifi cantly higher than patients without vascular invasion (p=0.045). CONCLUSIONS: Non-angiographic contrast-enhanced CT was signifi cantly less sensitive for detecting vascular invasion of cranial mediastinal masses when compared with surgical evaluation. If the CVC was invaded by a tumour there was a signifi cant risk of death peri-operatively when compared with non-invasive cases. CLINICAL RELEVANCE: Due to the signifi cantly higher mortality risk associated with invasion of the CVC, a more sensitive method than CT should be investigated to determine vascular invasion of mediastinal masses pre-operatively.