Effect of durotomy in dogs with thoracolumbar disc herniation and without deep pain perception in the hind limbs.

OBJECTIVE: To determine the effectiveness of durotomy as an adjunct to surgical decompression in dogs with thoracolumbar intervertebral disc herniation (TL-IVDH) and loss of deep pain perception (DPP) in the hind limbs. STUDY DESIGN: Retrospective study. ANIMALS: Dogs (n = 116) with TL-IVDH and loss of DPP treated with hemilaminectomy. METHODS: Signalment, surgical site, recovery rate, incidence of progressive myelomalacia (PMM), time elapsed from onset of paraplegia of the hind limbs to surgery (TPS), and the length of area of hyperintensity of the spinal cord on magnetic resonance T2-weighted images compared with L2 vertebral body length (LHT2) were compared between dogs treated with hemilaminectomy alone and those treated with adjunct durotomy. Multivariate logistic regression analyses were used to test the association between outcomes and the external view of the spinal cord parenchyma after durotomy. RESULTS: The percentage of dogs regaining ambulation was greater when durotomy was performed (56.9%) than when dogs were treated with hemilaminectomy alone (38.5%; P = .04). In the hemilaminectomy group, 14 dogs died of suspected PMM, while no PMM was detected in the durotomy group. Durotomy, breed, surgical site, and LHT2 influenced recovery. No association was detected between age, sex, body weight, and TPS and recovery. CONCLUSION: Performing a durotomy in combination with decompression improved the return to function and prevented PMM in our clinical setting. CLINICAL SIGNIFICANCE: Surgeons should consider durotomy in dogs with TL-IVDH and loss of DPP in hind limbs to improve surgical outcome.

Establishment of the MID-NET® medical information database network as a reliable and valuable database for drug safety assessments in Japan.

PURPOSE: To establish a new medical information database network (designated MID-NET® ) to provide real-world data for drug safety assessments in Japan. METHODS: This network was designed and developed by the Ministry of Health, Labour and Welfare and the Pharmaceuticals and Medical Devices Agency in collaboration with 23 hospitals from 10 healthcare organizations across Japan. MID-NET® is a distributed and closed network system that connects all collaborative organizations through a central data center. A wide variety of data are available for analyses, including clinical and administrative information. Several coding standards are used to standardize the data stored in MID-NET® to allow the integration of information originating from different hospitals. A rigorous and consistent quality management system was implemented to ensure that MID-NET® data are of high quality and meet Japanese regulatory standards (good post-marketing study practice and related guidelines). RESULTS: MID-NET® was successfully established as a reliable and valuable medical information database and was officially launched in April 2018. High data quality with almost 100% consistency was confirmed between original data in hospitals and the data stored in MID-NET® . A major advantage is that approximately 260 clinical laboratory test results are available for analysis. CONCLUSIONS: MID-NET® is expected to be a major data source for drug safety assessments in Japan. Experiences and best practices established in MID-NET® may provide a model for the future development of similar database networks.

Vertebral fixation does not affect recovery or recurrence of cervical intervertebral disc herniation in small dogs (< 15 kg).

OBJECTIVE: To compare the prognosis of small dogs with cervical intervertebral disc herniation (C-IVDH) when treated with ventral slot decompression (VSD) alone or with concomitant vertebral fixation (VF). ANIMALS: Small dogs (n = 303) weighing < 15 kg diagnosed with C-IVDH and treated with VSD. PROCEDURES: We recorded signalment, cervical myelopathy grade, surgical site, use of VF, degree of adjacent disc degeneration, recovery, recurrence, recurrence site, and postoperative course, including the time elapsed from recovery to recurrence. We examined factors associated with recovery and recurrence during the 30-month postoperative period using multivariate logistic regression analysis. RESULTS: VF did not affect recovery (P = .79). However, nonchondrodystrophic breeds had poorer recovery (OR, 5.89; P = .023) than chondrodystrophic breeds, and a higher preoperative cervical myelopathy grade (grade 3 or 4) was associated with poorer recovery (OR, 7.09 or 3.46, respectively; P = .019 or .042, respectively), compared with grade 1. VF did not affect recurrence (P = .79); however, increasing age was associated with recurrence (OR, 1.79; P = .001). CLINICAL RELEVANCE: In small dogs weighing < 15 kg, there was no difference in postoperative recovery and recurrence rates after VSD with or without concomitant VF. Therefore, in small dogs with C-IVDH, even if the slot volume is increased to remove sufficient disc material during VSD, a good prognosis can be achieved with or without VF.

Spinal epidural arteriovenous fistula in 3 cats.

Three young adult cats with intermittent spinal hyperesthesia and paraparesis and diagnosed with spinal epidural arteriovenous fistula are described. In all 3 cases, magnetic resonance imaging (MRI) showed focal dilatation of the veins in the epidural space of the thoracic spinal cord, whereas computed tomography angiography (CTA) showed dilatation and enhancement from the intercostal vein to the azygos vein at the same site in the arterial phase. Dorsal laminectomy and occlusion of the interarcuate branches running across the dorsal aspect of the spinal cord were performed in all 3 cats to decompress the spinal cord, which resulted in a remission of clinical signs and no recurrence during 14 to 40 months of follow-up after surgery in all cases.

Influence of ventral fixation techniques on atlantoaxial joint fusion in canine models with dens partial resection.

We evaluated the completeness of bony fusion of the atlantoaxial joint (AAJ) through polymethylmethacrylate fixation (PMF) and atlantoaxial plate fixation (APF) using six canine models with dens partial resection. In both groups, the hydroxyapatite content at the AAJ was measured up to 7 months postoperatively using quantitative computed tomography. Histological assessment revealed fibrous fusion in the PMF group. Meanwhile, in the APF group, only one dog achieved fibrous fusion, whereas the remaining three showed bony fusion. To our knowledge, this study was the first to evaluate AAJ fusion histologically after PMF and APF. The present study demonstrates that PMF and APF may stabilize the AAJ without clinical complications. Therefore, PMF and APF are clinically useful fixation methods for atlantoaxial instability.

Functional dissection of siRNA sequence by systematic DNA substitution: modified siRNA with a DNA seed arm is a powerful tool for mammalian gene silencing with significantly reduced off-target effect.

Short interfering RNA (siRNA)-based RNA interference (RNAi) is widely used for target gene knockdown in mammalian cells. To clarify the position-dependent functions of ribonucleotides in siRNA, siRNAs with various DNA substitutions were constructed. The following could be simultaneously replaced with DNA without substantial loss of gene-silencing activity: the seed arm, which occupies positions 2-8 from the 5'end of the guide strand; its complementary sequence; the 5'end of the guide strand and the 3'overhang of the passenger strand. However, most part of the 3' two-thirds of the guide strand could not be replaced with DNA, possibly due to binding of RNA-recognition proteins such as TRBP2 and Ago2. The passenger strand with DNA in the 3'end proximal region was incapable of inducing off-target effect. Owing to lesser stability of DNA-RNA hybrid than RNA duplex, modified siRNAs with DNA substitution in the seed region were, in most cases, incapable to exert unintended gene silencing due to seed sequence homology. Thus, it may be possible to design DNA-RNA chimeras which effectively silence mammalian target genes without silencing unintended genes.

Evaluation of atlantooccipital overlapping and cerebral ventricle size in dogs with atlantoaxial instability.

This study investigated cerebral ventricle size and concurrent craniocervical junction abnormality in relation to atlantooccipital overlapping (AOO) in dogs with atlantoaxial instability (AAI). A total of 61 dogs were treated with atlantoaxial ventral fixation. Medical records of each dog, including magnetic resonance (MR) and computed tomography (CT) images, were retrospectively reviewed. CT images were assessed for the presence of AOO and the dogs were then assigned to either an AOO group or a non-AOO group accordingly. CT images were also evaluated to determine the foramen magnum (FM) index. Syringomyelia, cerebellar compression, dorsal compression, and the degree of enlargement of each cerebral ventricle were evaluated using MR images. Of the 61 dogs, 23 had AOO and 38 did not. Furthermore, the ventricle/brain height ratio, the fourth ventricle height/cerebellum length ratio, and the fourth ventricle width/cerebellum length ratio were significantly higher in the AOO group than in the non-AOO group. However, the FM index, third ventricle/brain height ratio, and incidence of syringomyelia did not differ significantly between the two groups. Dogs with concurrent AOO exhibited significantly more dilatation of the lateral and fourth ventricles.

Epidemiological and morphological characteristics of incomplete ossification of the dorsal neural arch of the atlas in dogs with atlantoaxial instability.

OBJECTIVE To retrospectively evaluate the epidemiological and morphological features and outcome of surgical treatment of incomplete ossification of the dorsal neural arch of the atlas (IODA) in dogs with atlantoaxial instability (AAI). ANIMALS 106 AAI-affected dogs that underwent ventral fixation of the atlantoaxial joint. PROCEDURES Medical records and CT images for each dog were reviewed. Dogs were allocated to 1 of 2 groups on the basis of the presence or absence of IODA or of dens abnormalities (DAs) in CT images. RESULTS Of the 106 dogs with AAI, 75 had and 31 did not have IODA; 70 had and 36 did not have DAs. Incomplete ossification was present in the cranialmost, central, or caudalmost portion of the dorsal neural arch of the atlas in 59, 39, and 28 dogs, respectively; 2 or 3 portions were affected in 29 and 11 dogs, respectively. The mean CT value (in Hounsfield units) for the midline of the dorsal neural arch of the atlas in dogs with IODA was significantly lower than that for the same site in the dogs without IODA. The mean age at surgery for dogs with central IODA was significantly higher than that of the non-IODA group. The severity of spinal cord injury before or after atlantoaxial ventral fixation did not differ between the IODA and non-IODA groups. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that concomitant DAs or IODA is common in dogs with AAI. In dogs with incomplete ossification in the central part of the dorsal neural arch of the atlas, surgical treatment of AAI generally occurs at a middle to advanced age.

Atlantooccipital overlapping and its effect on outcomes after ventral fixation in dogs with atlantoaxial instability.

We compared clinical outcomes after ventral fixation in dogs with atlantoaxial instability (AAI) on the basis of the presence or absence of atlantooccipital overlapping (AOO). Of 41 dogs diagnosed with AAI and treated ventral fixation, 12 exhibited AOO (AOO group), whereas 29 did not (non-AOO group). The AOO group had significantly higher neurological scores before (P=0.024) and 1 month after (P=0.033) surgery compared with the non-AOO group; however, no significant differences were observed between the groups 2 months after surgery. The presence of complicating AOO affected the clinical signs for dogs with AAI, but did not directly affect the outcome of surgical stabilization of AAI.

Biomechanical evaluation of three ventral fixation methods for canine atlantoaxial instability: a cadaveric study.

We evaluated comparatively the mechanical strength in three kinds of surgical fixation techniques for canine atlantoaxial joint. Atlantoaxial plate fixation (APF), polymethylmethacrylate (PMMA) fixation (PMF) and transarticular fixation (TAF) were applied to the atlas and axis harvested from healthy beagle dogs, and then, the specimens were tested. The PMF group had significantly higher resistance to flexion than the APF group (P=0.030) and the TAF group (P=0.004). There were no significant differences in resistance to torsion between the APF group and the PMF group, while the APF group had significantly higher resistance to torsion than the TAF group (P=0.037). Considering the possible drawbacks of using PMMA, the APF method is proposed as an alternative to the PMF method.

Evaluation of the dens-to-axis length ratio and dens angle in toy-breed dogs with and without atlantoaxial instability and in healthy Beagles.

OBJECTIVE To evaluate and compare morphological characteristics of the dens in atlantoaxial instability (AAI)-predisposed toy-breed dogs (TBDs) with and without AAI and non-AAI-predisposed healthy Beagles. ANIMALS 80 AAI-affected and 40 nonaffected TBDs and 40 Beagles. PROCEDURES Each dog underwent CT examination of the cervical vertebral column. On median 3-D multiplanar reconstruction images, the dens angle (DA) was measured as were the lengths of the dens and the body of the axis; the dens-to-axis length ratio (ratio of the dens length to the axis body length [DALR]) was calculated. Data were compared among dog groups. RESULTS The DALR in nonaffected TBDs and Beagles did not differ significantly. The mean DALR for AAI-affected TBDs was significantly lower than that for nonaffected TBDs. The mean DA of AAI-affected TBDs was significantly greater than that of Beagles and nonaffected TBDs. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that a low DALR might be associated with a high probability of dens abnormalities in TBDs. Additionally, dens length in AAI-affected TBDs appeared to be smaller than that in non-AAI-affected TBDs, given the low DALR in AAI-affected TBDs. Further investigations to determine reference ranges of the DA and DALR and the potential usefulness of those variables as diagnostic markers for AAI in TBDs are warranted.

Biomechanical evaluation of three ventral fixation methods for canine atlantoaxial instability: a cadaveric study.

Vol. 78, No. 12 (2016), The "received date" year in the manuscript was printed incorrectly. Error: Received 25 March 2015 ↓ Correction: Received 25 March 2016 The Journal of Veterinary Medical Science Editorial Office would like to offer our sincere apologies for this mistake.

Assessment of T2 Relaxation Times for Normal Canine Knee Articular Cartilage by T2 Mapping Using 1.5-T Magnetic Resonance Imaging.

Objectives This study aims to assess and compare the T2 relaxation times for articular cartilage of normal canine stifle joints in four regions by T2 mapping using a 1.5-T magnetic resonance imaging (MRI). Methods In vivo prospective study: 20 hindlimbs (left and right) from 10 normal healthy beagle dogs (n = 20). The region of interest (ROI) was subdivided into medial and lateral condyles of femoral cartilage (MF and LF, respectively) and medial and lateral condyles of tibial cartilage (MT and LT, respectively). The T2 relaxation times were assessed in regions where the cartilage thickness was greater than 0.5 mm. Results The median maximum cartilage thickness (mm) of the four ROI were 0.7 (range: 0.9-0.6), 0.6 (range: 0.7-0.5), 0.7 (range: 0.9-0.5) and 0.6 (range: 0.8-0.5) at MF, LF, MT and LT, respectively. The errors in the measurement (%) of the four ROI were 64.3 (range: 50.0-75.0), 75.0 (range: 64.3-90.0), 64.3 (range: 20.0-90.0) and 75.0 (range: 56.3-90.0) at MF, LF, MT and LT, respectively. The median T2 relaxation times (ms) for the articular cartilage of the four ROI were 70.2 (range: 57.9-87.9), 57.5 (range: 46.8-66.9), 65.0 (range: 52.0-92.0) and 57.0 (range: 49.0-66.2) at MF, LF, MT and LT, respectively. The inter-observer correlation coefficient (ICC, 2.1) for the T2 relaxation times of MF was 0.644. Clinical Significance This study offers useful information on T2 relaxation times for articular cartilage of the stifle joint using a 1.5-T MRI in normal dogs.

Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference.

In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi.

The expression of SCDGF/PDGF-C/fallotein and SCDGF-B/PDGF-D in the rat central nervous system.

We examined the expression patterns of the two homologous genes, spinal cord-derived growth factor (SCDGF)/platelet-derived growth factor (PDGF)-C/fallotein and SCDGF-B/PDGF-D in the rat central nervous system. In the spinal cord, SCDGF/PDGF-C/fallotein was expressed in the floor plate at embryonic day (E) 11 and also in the ventricular zone at E16 but not in adult. However, SCDGF-B/PDGF-D was prominently expressed in the adult motoneurons, although faint expression was observed in the ventral ventricular zone at E16. Also in the brain, the expression of SCDGF/PDGF-C/fallotein was more remarkable at E16 than at adult. It was highly expressed in the cortex, pontine area and choroid plexus at E16. Contrary to SCDGF/PDGF-C/fallotein, SCDGF-B/PDGF-D expression was notable in several nuclei at adult.

Expression of DDAH1 in chick and rat embryos.

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an enzyme that metabolizes methylated arginine to citrulline and methylamine, thus working to produce nitric oxide (NO). We isolated a gene encoding chick DDAH1. In situ hybridization analysis revealed characteristic DDAH1 mRNA expression in the embryonic spinal cord, which was especially strong in the ventral horn and dorsal root ganglion (DRG). DDAH1 was also detected in the brain, kidney, digestive tract, and in other tissues. We examined the expression pattern of DDAH1 in developing rats and compared this with the expression pattern in chicks. The expression pattern in the rats was very similar to that in the chicks, but there were some differences between the chicks and rats in the amount of DDAH1 detected in the heart, liver, lung, and DRG. We also investigated neural nitric oxide synthase (nNOS) mRNA expression patterns in rat embryos. The DDAH1 expression patterns were completely different from nNOS expression patterns. Our study suggests that DDAH1 plays an important role in development.

Requirements of genetic interactions between Src42A, armadillo and shotgun, a gene encoding E-cadherin, for normal development in Drosophila.

Src42A is one of the two Src homologs in Drosophila. Src42A protein accumulates at sites of cell-cell or cell-matrix adhesion. Anti-Engrailed antibody staining of Src42A protein-null mutant embryos indicated that Src42A is essential for proper cell-cell matching during dorsal closure. Src42A, which is functionally redundant to Src64, was found to interact genetically with shotgun, a gene encoding E-cadherin, and armadillo, a Drosophila beta-catenin. Immunoprecipitation and a pull-down assay indicated that Src42A forms a ternary complex with E-cadherin and Armadillo, and that Src42A binds to Armadillo repeats via a 14 amino acid region, which contains the major autophosphorylation site. The leading edge of Src mutant embryos exhibiting the dorsal open phenotype was frequently kinked and associated with significant reduction in E-cadherin, Armadillo and F-actin accumulation, suggesting that not only Src signaling but also Src-dependent adherens-junction stabilization would appear likely to be essential for normal dorsal closure. Src42A and Src64 were required for Armadillo tyrosine residue phosphorylation but Src activity may not be directly involved in Armadillo tyrosine residue phosphorylation at the adherens junction.