Mucopolysaccharidosis VI in cats - clarification regarding genetic testing

Debate. Published online: 02 July 2016.The release of new DNA-based diagnostic tools has increased tremendously in companion animals. Over 70 different DNA variants are now known for the cat, including DNA variants in disease-associated genes and genes causing aesthetically interesting traits. The impact genetic tests have on animal breeding and health management is significant because of the ability to control the breeding of domestic cats, especially breed cats. If used properly, genetic testing can prevent the production of diseased animals, causing the reduction of the frequency of the causal variant in the population, and, potentially, the eventual eradication of the disease. However, testing of some identified DNA variants may be unwarranted and cause undo strife within the cat breeding community and unnecessary reduction of gene pools and availability of breeding animals. Testing for mucopolysaccharidosis Type VI (MPS VI) in cats, specifically the genetic testing of the L476P (c.1427T>C) and the D520N (c.1558G>A) variants in arylsulfatase B (ARSB), has come under scrutiny. No health problems are associated with the D520N (c.1558G>A) variant, however, breeders that obtain positive results for this variant are speculating as to possible correlation with health concerns. Birman cats already have a markedly reduced gene pool and have a high frequency of the MPS VI D520N variant. Further reduction of the gene pool by eliminating cats that are heterozygous or homozygous for only the MPS VI D520N variant could lead to more inbreeding depression effects on the breed population. Herein is debated the genetic testing of the MPS VI D520N variant in cats. Surveys from different laboratories suggest the L476P (c.1427T>C) disease-associated variant should be monitored in the cat breed populations, particularly breeds with Siamese derivations and outcrosses. However, the D520N has no evidence of association with disease in cats and testing is not recommended in the absence of L476P genotyping. Selection against the D520N is not warranted in cat populations. More rigorous guidelines may be required to support the genetic testing of DNA variants in all animal species.Leslie A. Lyons, Robert A. Grahn, Francesca Genova, Michela Beccaglia, John J. Hopwood and Maria Longer

Effectiveness of abiraterone acetate plus prednisone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer in a large prospective real-world cohort: the ABItude study

Background: Real-world data on chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone plus prednisone are limited, largely deriving from small retrospective studies. Methods: ABitude is an Italian, observational, prospective, multicenter study of mCRPC patients receiving abiraterone plus prednisone in clinical practice. Chemotherapy-naïve mCRPC patients were consecutively enrolled at abiraterone start (February 2016 to June 2017) and are being followed for 3 years, with evaluation approximately every 6 months. Several clinical and patients reported outcomes were examined. Results: In this second interim analysis, among 481 enrolled patients, 453 were evaluable for analyses. At baseline, the median age was 77 years and ~69% of patients had comorbidities (mainly cardiovascular diseases). Metastases were located mainly at bones and lymph nodes; 8.4% of patients had visceral metastases. During a median follow-up of 18 months, 1- and 2-year probability of radiographic progression-free survival were 73.9% and 56.2%, respectively; the corresponding rates for overall survival were 87.3% and 70.4%. In multivariable analyses, the number of bone metastases significantly affected radiographic progression-free survival and overall survival. During abiraterone plus prednisone treatment, 65% of patients had a ⩾50% prostate-specific antigen decline, and quality of life remained appreciably high. Among symptomatic patients according to the Brief Pain Inventory) (32%), scores significantly declined after 6 months of treatment. Overall, eight patients (1.7%) had serious adverse reactions to abiraterone. Conclusions: Abiraterone plus prednisone is effective and safe for chemotherapy-naïve mCRPC patients in clinical practice

MRI in the acute phase of spinal cord traumatic lesions: Relationship between MRI findings and neurological outcome.

To evaluate the role of emergency MRI in the diagnosis of acute spinal injuries, and to correlate the MRI pattern with the neurological outcome.Thirty-eight patients with MRI-proven spinal cord injury were classified according to the Frankel classification. MRI was always performed within 8 hours from trauma. Frankel classification divides spinal cord injuries into 5 classes of decreasing severity based on the presence of motor and/or sensory function loss. On the basis of the MRI findings the patients were classified in 3 groups: group 1 (intramedullary haematoma), group 2 (multi-metamer oedema), group 3 (single-metamer oedema). All patients underwent neurosurgery and were clinically evaluated until the stabilization of neurological recovery. Mean follow-up time was 12 months. The MR images were retrospectively evaluated and correlated to the neurological outcome.Twenty-eight patients showed complete motor loss (Frankel classes A and B); of these 28 patients 12 (42.8\%) had MRI evidence of intramedullary haematoma, 12 (42.8\%) had multi-metamer oedema and 4 (14.4\%) had single-metamer oedema. Of the 10 patients with incomplete motor loss, none had MRI evidence of haemorrhage, 4 (40\%) showed multi-metamer oedema and 6 (60\%) showed single-metamer oedema. Follow-up clinical assessment revealed that 14/38 patients (36,8\%) had clinical improvement and 2/38 cases (5\%) had a complete motor recovery, as demonstrated by the move to a higher Frankel class.Our results, consistent with previous reports, confirm a strong correlation between the MRI appearance of traumatic spinal cord injuries in acute phase and long-term recovery of motor and sensory function: patients with initial haemorrhage had a poor prognosis, whereas those with spinal cord oedema had a good clinical outcome, as demonstrated by the passage to a higher Frankel class. MRI is particularly important in the initial evaluation of unconscious patients who cannot undergo a motor and sensory neurological evaluation, and to define the prognosis, which will influence the correct therapeutic choice

Pharmacokinetics and perioperative efficacy of intravenous ketorolac in dogs

Ketorolac (KET) is a nonsteroidal anti-inflammatory drug approved for the use in humans that possesses a potent analgesic activity, comparable to morphine, and could represent a useful tool to control acute pain also in animals. The clinical efficacy and pharmacokinetic profile of intravenous (IV) ketorolac tromethamine (0.5 mg/kg) were studied in 15 dogs undergoing gonadectomy. Intra-operative cardiorespiratory variables were monitored, and post-operative pain was assessed using a subjective pain score (0-24) in all dogs, whereas the pharmacokinetic profile of the drug was determined in 10 animals. During surgery, mean minimal alveolar concentration of isoflurane was 1.69 \ub1 0.11%, and normocapnia and spontaneous ventilation were maintained in all animals. During pain assessment, no significant differences between males and females were found, and in no case rescue analgesia was necessary. No adverse effects were reported. Serum samples were purified by solid-phase extraction and analysed by HPLC with UV-Vis detection. A large variability was observed in serum concentrations. The kinetics of ketorolac was described by a noncompartmental analysis. The elimination half-life (t\ubd\u3bbz ) and ClB were 10.95 \ub1 7.06 h and 92.66 \ub1 84.49 mL/h/kg, respectively, and Vdss and Vz were 1030.09 \ub1 620.50 mL/kg and 1512.25 \ub1 799.13 mL/kg, respectively. AUC(0\u2192last) and MRT(0\u2192last) were 6.08 \ub1 3.28 h 7 \u3bcg/mL and 5.59 \ub1 2.12 h, respectively. The results indicate that ketorolac possess good post-operative analgesic effects until about 6 h after administration in dogs undergoing moderately painful surgery

Pharmacokinetics and efficacy of extradural tramadol in dogs

Tramadol is a synthetic opioid agonist used extensively in human and, to a lesser extent, veterinary medicine throughout the world. The clinical efficacy and pharmacokinetic profile of intravenous (i.v.) and extradural (e.d.) tramadol (2 mg/kg) and its o-desmethyl metabolite were studied in dogs undergoing tibial plateau levelling osteotomy (TPLO). Intra-operative cardiorespiratory variables were monitored and post-operative pain was assessed using the short form of the Glasgow Composite Pain Scale. A rapid (<5 min) and effective production of o-desmethyl tramadol was recorded. The pharmacokinetic profile was similar for tramadol and its metabolite irrespective of the route of administration. E.d. tramadol provided sufficient intra- and post-operative analgesia without significant clinical side-effects, but the post-operative analgesia was comparable to that following i.v. administration and the e.d. route could therefore not be considered a practical alternative to the i.v. rout

Imaging of acute brain inflammatory disease

The central nervous system inflammatory disease can be due to any kind of infective agent (bacterial viral, fungal and parasitic), but entails also multiple sclerosis, a primary demyelinating disease in which the causal agent is unknown. MR imaging is, in most often, the procedure of choice, due to her multiplanar and multiparametric imaging, and to her better contrast resolution. The post-contrast imaging with double dose of gadolinium and late sequences enable visualisation of smallest pathologic foci or slightest blood-brain barrier alterations, with a sensibility very higher than post-contrast CT scan. In addition, RM provide to many functional informations, by means of diffusion, perfusion and spectroscopy studies, Bold technique for cortical activation studies and Fiber Tracking technique, in order to demonstrate pathologic modification earlier than they are evident on morphologic imaging. Functional imaging is also employed to monitor response to treatment and damage reversibility

A novel Fibroblast Growth Factor Receptor 2 (FGFR2) mutation associated with a mild Crouzon syndrome

[No abstract available