The effect of patient positioning on adrenal gland linear measurements estimated from computed tomographic images in healthy beagle dogs.

Considering that recumbency can lead to a change in localization, detectability of distinct margins and thus measurement of the organs and reconstruction quality, it is of value to evaluate the effect of positioning on the objective evaluation of abdominal organs in computed tomography (CT). The objective of the present study was to evaluate the effect of patient decubitus on adrenal gland CT biometry. For this purpose, 6 clinically healthy adult beagle dogs underwent CT examination in 4 recumbencies. The various adrenal gland's size measurements were performed by 2 observers. Statistical analyses revealed that repeatability and reproducibility was the highest on the ventral and right lateral recumbencies, respectively. Significant differences were found in the left adrenal gland's length between the different positions (P < 0.001) and the left adrenal gland's width of the cranial pole measured in the dorsal plane (P < 0.04). The measurements on the parasagittal images differed significantly for the left adrenal length (P = 0.01), cranial pole height (P = 0.03), the right adrenal gland's lateral limb's length (P = 0.05) and medial limb's caudal poles height (P < 0.01). The caudal pole height of the right adrenal gland's medial limb was significantly different (P < 0.01) in all positions on the transverse images. In addition, the adrenal position differed significantly, except for the left adrenal gland relative to the nearest renal vessel (P = 0.1). According to these results, it is recommended to perform a CT of adrenal glands always in the same recumbency. If adrenal glands are evaluated on images taken in various recumbencies, we suggest relying on the measurements made on transverse plane images.

Lesion detection on a combined "All-in-One" window compared to conventional window settings in thoracic oncology chest CT examinations.

PURPOSE: The purpose of this study was to investigate if lesion detection using a single "All-in-One" (AIO) window was non-inferior to lesion detection on conventional window settings in thoracic oncology chest computed tomography (CT) examinations. MATERIALS AND METHODS: In a retrospective study, 50 consecutive chest CT examinations of 50 patients (31 men, 19 women; mean age 64±10 [SD] years, range: 35-82 years) containing 417 lesions, were reviewed by 6 radiologists, subdivided into 2 groups of 3 radiologists each, with similar levels of expertise in each group (senior staff member, junior staff member and radiology resident). All examinations were reviewed in conventional or AIO window settings by one of the groups. A 'lesion' was defined as any abnormality seen on the chest CT examination, including both benign and malignant lesions, findings in chest and upper abdomen, and measurable and non-measurable disease. Lesions were listed as 'missed' when they were not seen by at least two out of three observers. F-tests were used to evaluate the significance of the variables of interest within a mixed model framework and kappa statistics to report interobserver agreement. RESULTS: On a reader level, 54/417 lesions (12.9%) were not detected by the senior staff member reading the studies in conventional window settings and 45/417 (10.8%) by the senior staff member reading the AIO images. For the junior staff member and radiology resident this was respectively 55/417 (13.2%) and 67/417 (16.1%) for the conventional window settings and 43/417 (10.3%) and 61/417 (14.6%) for the AIO window. On a lesion level, 68/417 (16.3%) were defined as 'missed' lesions (lesions not detected by at least 2 readers): 21/68 (30.9%) on the AIO-window, 30/68 (44.1%) on conventional views and 17/68 (25.0%) on both views. The use of the AIO window did not result in an increase of missed lesions (P>0.99). Interobserver agreement in both groups was similar (P=0.46). Regarding lesions that were categorized as 'missed' on the AIO window or on conventional window settings, there was no effect of location (chest or upper abdomen) (P=0.35), window (P=0.97) and organ (P=0.98). CONCLUSIONS: A single AIO-window is non-inferior to multiple conventional window settings for lesion detection on chest CT examinations in thoracic oncology patients.

Variability of serum concentrations of cystatin C and urinary retinol-binding protein, neutrophil gelatinase-associated lipocalin, immunoglobulin G, and C-reactive protein in dogs.

BACKGROUND: Markers of kidney dysfunction and damage have potential to detect chronic kidney disease (CKD) in early stages. However, data on long-term variation of these markers in healthy dogs is lacking and is crucial for the interpretation of results. HYPOTHESIS/OBJECTIVES: To determine temporal variations of serum cystatin C (sCysC) and urinary retinol-binding protein (uRBP), neutrophil gelatinase-associated lipocalin (uNGAL), immunoglobulin G (uIgG), and C-reactive protein (uCRP) in healthy dogs. ANIMALS: Eight clinically healthy adult Beagles were evaluated. METHODS: Longitudinal observational study. Serum cystatin C was determined by particle-enhanced nephelometric immunoassay. Urinary retinol-binding protein, uNGAL, uIgG and uCRP were determined by ELISA and concentrations were indexed to urinary creatinine. Within- and between-dog variance components (VC) and within-dog coefficients of variation (CV) were determined from blood and urine collected at eight time points over 1.5 years. RESULTS: Urinary C-reactive protein (uCRP) concentrations were consistently below the detection limit (5.28 ng/mL). Mean ± within-dog standard deviation for sCysC, uRBP/c, uNGAL/c and uIgG/c was 0.15 ± 0.01 mg/L, 0.09 ± 0.03 mg/g, 2.32 ± 2.03 µg/g and 12.47 ± 10.98 mg/g, respectively. Within-dog CV for sCysC, uRBP/c, uNGAL/c and uIgG/c was 8.1%, 33.7%, 87.2% and 88.1%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum cystatin C, uRBP/c, uNGAL/c and uIgG/c exhibit a wide range of long-term within-dog variability. Researchers and veterinarians might need to take this into account when interpreting their results. To assess their diagnostic and predictive ability, future studies need to establish reference ranges for healthy dogs and dogs with CKD.

Imepitoin withdrawal in dogs with idiopathic epilepsy well-controlled with imepitoin and phenobarbital and/or potassium bromide does not increase seizure frequency.

Phenobarbital or potassium bromide (KBr) add-on treatment decreases the average monthly seizure frequency in dogs with idiopathic epilepsy resistant to a maximum dose of imepitoin. The importance of continued administration of imepitoin in these dogs is currently unknown. The goal of this study was to assess whether imepitoin withdrawal would destabilize epileptic seizure control. In this prospective clinical trial epileptic seizure control was evaluated by comparing the monthly seizure frequency of 13 dogs with well-controlled idiopathic epilepsy receiving a combination of imepitoin and phenobarbital (n=4), imepitoin and KBr (n=7), and imepitoin, phenobarbital and KBr (n=2) during a period of 3-6 months (pre-withdrawal period), with a follow-up period of 9-12 months after withdrawal of imepitoin (post-withdrawal period). Adverse effects were also recorded before and after withdrawal of imepitoin. Imepitoin was tapered off over 3 months as follows: 20mg/kg twice daily for 1 month, then 10mg/kg twice daily for 1 month, then once daily for 1 month. Withdrawal of imepitoin did not increase monthly seizure frequency (P=0.9). Moreover, all owners reported improvement in the adverse effects experienced by their dog after withdrawal of imepitoin. Imepitoin withdrawal in epileptic dogs that were well-controlled with imepitoin and phenobarbital and/or KBr did not worsen epileptic seizure control, and possibly decreased antiepileptic treatment-related adverse effects. However, a worsening of seizure frequency could occur in individual cases.

Phenobarbital or potassium bromide as an add-on antiepileptic drug for the management of canine idiopathic epilepsy refractory to imepitoin.

Imepitoin has recently been approved in Europe for the management of dogs with idiopathic epilepsy. Currently, there is no evidence-based information available on the efficacy of antiepileptic drugs used as additions to the therapeutic regimen in dogs with idiopathic epilepsy that are not well controlled with imepitoin. The goal of this study was to evaluate the efficacy of phenobarbital or potassium bromide (KBr) as add-on antiepileptic drugs for controlling dogs refractory to a maximum dose of imepitoin (30 mg/kg twice daily). The study was performed as a prospective, randomised, controlled clinical trial. The efficacy of phenobarbital and KBr was evaluated by comparing monthly seizure frequency (MSF), monthly seizure day frequency (MSDF), the presence of cluster seizures during a retrospective 2-month period with a prospective follow-up of 6 months, and the overall responder rate. Twenty-seven dogs were included in the study, 14 dogs in the phenobarbital group and 13 dogs in the KBr group. Both median MSF and MSDF decreased in the phenobarbital group (both P = 0.001) and in the KBr group (P = 0.004 and P = 0.003, respectively). Overall, the number of dogs with cluster seizures decreased (P = 0.0005). The responder rate was 79% vs. 69% in the phenobarbital and KBr groups, respectively. We conclude that phenobarbital or KBr add-on treatment decreases median MSF and MSDF in epileptic dogs refractory to a maximum dose of imepitoin. Combination therapy was generally well tolerated and resulted in an improvement in seizure management in the majority of the dogs.

The Influence of the Size, Age and Sex on the Computed Tomographic Measured Size of the Pituitary Gland in Normal Horses.

The objective of this study was to examine the influence of the size, age and sex of the horse on the size of the pituitary gland and determine the possibility of using the pituitary gland height-to-brain area ratio (P:B ratio) to allow comparison of different sized and aged horses. Thirty-two horses without pituitary pars inter-media dysfunction that underwent a contrast-enhanced computed tomographic (CT) examination were included in a cross-sectional study. On the CT images, the pituitary gland height was measured and the P:B ratio was calculated. These measurements were correlated to the size, age and sex of the horses. The pituitary gland height was significantly associated with the size (P < 0.001) and the age (P < 0.001), but not with the sex (P = 0.40), of the horses. No significant association was found between the P:B ratio and the size (P = 0.25), the age (P = 0.06) or the sex (P = 0.25) of the horses. In conclusion, the pituitary gland size varies between different sized and aged horses. The use of the P:B ratio is a valuable metric for making comparisons between the pituitary glands of these horses.

Bone density of elbow joints in Labrador retrievers and Golden retrievers: Comparison of healthy joints and joints with medial coronoid disease.

The aims of this study were: (1) to determine the inter-observer repeatability of particular regions of the canine elbow joints; (2) to assess the effect of age, bodyweight and breed on bone density in healthy young dogs; (3) to compare Hounsfield units (HU) and bone density (BD) measurements between normal elbow joints and diseased elbow joints; and (4) to determine the sensitivity and specificity for HU and BD measurements in specific regions in the canine elbow joint. Regions with the highest repeatability were located at the medial coronoid process (MCP) base and apex, and at the level of the humerus, on the sagittal and sagittal oblique planes of the elbow joint. Age and breed were significantly associated with several regions of interest; conversely, none of the measurements were associated with bodyweight. Increased HU and BD values in the MCP base and apex regions are likely to be related to medial coronoid disease. Labrador retrievers had higher HU and BD values than Golden retrievers and an increase in BD was found in older animals. Cut-offs determined with receiver operating characteristic plots of the MCP base and apex suggested fairly good sensitivity and specificity (base: area under the curve 0.85, sensitivity 75.0%, specificity 88.8%; apex: area under the curve 0.89, sensitivity 80.0%, specificity 92.5%).

Detection of compressive hydrated nucleus pulposus extrusion in dogs with multislice computed tomography.

Compressive hydrated nucleus pulposus extrusion (HNPE) in dogs is defined as acute extradural compression by hydrated nucleus pulposus material at the level of the associated intervertebral disc. Magnetic resonance imaging (MRI) is the imaging modality of choice for diagnosis of HNPE. The aims of this study were to determine the usefulness of unenhanced computed tomography (CT) and contrast enhanced CT (CE-CT), and the sensitivity and specificity of CE-CT, for detection of compressive HNPE. Using CE-CT, HNPE was visualised as a hypodense extradural compressive lesion with rim enhancement immediately dorsal to the intervertebral disc space, with a sensitivity of 91% and a specificity of 100%. CE-CT is a useful technique to detect compressive HNPE in dogs. However, if no clear lesion is identified with CE-CT, or if additional information about intramedullary changes is required, MRI still needs to be performed.

Toward the most ideal case-control design with related and unrelated dogs in whole-exome sequencing studies.

With the recent development of whole-exome sequencing enrichment designs for the dog, a novel tool for disease-association studies became available. The aim of disease-association studies is to identify one or a very limited number of putative causal variants or genes from the large pool of genetic variation. To maximize the efficiency of these studies and to provide some directions of what to expect, we evaluated the effect on variant reduction for various combinations of cases and controls for both dominant and recessive types of inheritance assuming variable degrees of penetrance and detectance. In this study, variant data of 14 dogs (13 Labrador Retrievers and one Dogue de Bordeaux), obtained by whole-exome sequencing, were analyzed. In the filtering process, we found that unrelated dogs from the same breed share up to 70% of their variants, which is likely a consequence of the breeding history of the dog. For the designs tested with unrelated dogs, combining two cases and two controls gave the best result. These results were improved further by adding closely related dogs. Reduced penetrance and/or detectance has a drastic effect on the efficiency and is likely to have a profound effect on the sample size needed to elucidate the causal variant. Overall, we demonstrated that sequencing a small number of dogs results in a marked reduction of variants that are likely sufficient to pinpoint causal variants or genes.

Low-Field Magnetic Resonance Imaging and Multislice Computed Tomography for the Detection of Cervical Syringomyelia in Dogs.

BACKGROUND: Syringomyelia (SM) is defined as the presence of fluid-containing cavities within the parenchyma of the spinal cord. Sagittal magnetic resonance (MR) images have been described as the preferred technique for visualizing SM in dogs and humans. OBJECTIVE: To investigate whether computed tomography (CT) can be used to diagnose SM. ANIMALS: Thirty-two client-owned dogs referred for investigation of the cervical spine on magnetic resonance imaging (MRI) and CT. METHODS: Two reviewers retrospectively analyzed sagittal and transverse T1-weighted spin echo (T1WSE) MR images and CT images from each dog for the presence of SM and, if SM was present, the width (mm, syrinx width [SW]) was measured. The results were analyzed statistically. RESULTS: For the presence of SM there was a moderate interobserver agreement for MR (81%, κ = 0.54) and almost perfect agreement for CT (94%, κ = 0.87). There was a moderate intramodality agreement for both observers (observer 1 81%, κ = 0.59; observer 2 81%, κ = 0.57). For measurement of SW the repeatability was the best on the midsagittal T1WSE images (95% repeatability coefficient <0.52 mm) and the reproducibility was the best on midsagittal images in both modalities (95% limits of agreement -0.55-0.45; P = 0.002). CONCLUSION AND CLINICAL IMPORTANCE: Both techniques can be used to detect SM. Midsagittal MR and CT images are best used for measuring SW. Computed tomography can be used as a diagnostic tool for SM when MRI is not available, but CT cannot replace MRI as the standard screening technique for the detection of SM in Cavalier King Charles Spaniel for breeding purposes.

Fluoxetine suppresses calcium signaling in human T lymphocytes through depletion of intracellular calcium stores.

Selective serotonin reuptake inhibitors, such as fluoxetine, have recently been shown to exert anti-inflammatory and immunosuppressive effects. Although the effects on cytokine secretion, proliferation and viability of T lymphocytes have been extensively characterized, little is known about the mechanism behind these effects. It is well known that Ca(2+) signaling is an important step in the signaling transduction pathway following T cell receptor activation. Therefore, we investigated if fluoxetine interferes with Ca(2+) signaling in Jurkat T lymphocytes. Fluoxetine was found to suppress Ca(2+) signaling in response to T cell receptor activation. Moreover, fluoxetine was found to deplete intracellular Ca(2+) stores, thereby leaving less Ca(2+) available for release upon IP3- and ryanodine-receptor activation. The Ca(2+)-modifying effects of fluoxetine are not related to its capability to block the serotonin transporter, as even a large excess of 5HT did not abolish the effects. In conclusion, these data show that fluoxetine decreases IP3- and ryanodine-receptor mediated Ca(2+) release in Jurkat T lymphocytes, an effect likely to be at the basis of the observed immunosuppression.

Low-field MRI and multislice CT for the detection of cerebellar (foramen magnum) herniation in Cavalier King Charles Spaniels.

BACKGROUND: Cavalier King Charles Spaniels (CKCS) have a high prevalence of Chiari-like malformation (CM). Herniation of the cerebellum into the foramen magnum is a key diagnostic feature for CM. Midsagittal MR images are the preferred technique for visualizing cerebellar herniation (CH). OBJECTIVE: To investigate whether CT can be used to diagnose CH. ANIMALS: Fifteen client-owned CKCS dogs referred for investigation of the brain and cranial cervical spine on MRI and CT. METHODS: Two reviewers retrospectively analyzed midsagittal T1WSE and T2WSE MR images and midsagittal pre- and postcontrast 2D multiplanar reformatted CT images from each dog for the presence of CH. And, if present, the length (mm, CHL) of the herniation was measured. The results were analyzed statistically. RESULTS: There was no significant difference between the different observers and techniques for the detection of CH and measurement of CHL. Overall, the CHL was longer on the CT images. CONCLUSION AND CLINICAL IMPORTANCE: Both techniques are useful for detecting CH and measuring CHL. Because CHL does not have a known direct impact on the clinical presentation of CM, CT can be used as a diagnostic tool in a routine clinical practice for CM in CKCS when MRI is not available. We emphasize that MRI is the standard screening technique in CKCS for breeding purposes to detect the presence of CM and SM and, at the current time, CT cannot replace MRI.

The effects of positioning, reason for screening and the referring veterinarian on prevalence estimates of canine hip dysplasia.

Although the prevalence of canine hip dysplasia (HD) has been the subject of a number of published studies, estimates vary widely. This study evaluated several possible causes for these differences. Sixty Belgian, Dutch and German veterinarians were asked to submit all hip radiographs obtained for screening purposes (irrespective of HD status) over a 2-year period, resulting in a database of 583 dogs. Each set of radiographs was accompanied by information on the reason for screening (breeding soundness examination, clinical complaint, assistance dogs, or other reasons), and dog breed, date of birth and age. Dog positioning exerted an effect at multiple levels. The agreement among different observers regarding correct or incorrect positioning was limited and incorrect positioning itself reduced the inter-observer agreement for radiographic hip conformation. Dysplastic dogs were more commonly positioned incorrectly than non-dysplastic dogs. The clinical complaint population had a high prevalence of dysplastic dogs (>70%) compared with the breeding population (11%) and the assistance dogs (6%). There was a significantly lower prevalence of HD among cases referred by veterinarians who frequently submitted hip-extended radiographs for evaluation (P = 0.002) compared to those who refer less frequently. However, this was likely to be selection bias, as radiographs that were from dogs suspected to be dysplastic were not submitted by frequent senders. The prevalence of dysplastic dogs varied widely between breeds (16.7-71.4%). Dogs diagnosed with dysplasia were significantly older than dogs considered healthy (P = 0.001) and dogs classified as borderline dysplastic (P = 0.035). Inter-observer agreement for hip conformation was moderately low, resulting in >7% variation in prevalence estimates for dysplasia.