Presenting signs and clinical outcome in dogs with metaphyseal osteopathy: 39 cases (2009-2018).

OBJECTIVE: To describe the presenting signs, concurrent conditions, treatment and outcome of dogs with metaphyseal osteopathy. MATERIALS AND METHODS: Multi-centre retrospective review of medical records from January 2009 to September 2018 at four referral centres to identify dogs with a radiographic diagnosis of metaphyseal osteopathy. RESULTS: Thirty-nine dogs were identified. The median age at onset was 14 weeks old (range, 8 to 32 weeks old). There was a higher proportion of male dogs (29 of 39 male entire, nine of 39 female entire, one of 39 female neutered and no male neutered dogs). Where information was available, median time from the most recent vaccination was 20 days (range, 2 to 144 days). The most commonly recorded clinical signs were pyrexia (34 of 39), lethargy (32 of 39), pain (30 of 39), and being non-ambulatory (17 of 39). Thirty-five dogs required hospitalisation for analgesia and supportive care, 19 of 39 were discharged on prednisolone (median dose 2.0 mg/kg/day; range, 0.9 to 2.6 mg/kg/day), 18 of 39 were discharged on non-steroidal anti-inflammatories, two of 39 did not receive NSAIDs or prednisolone at any time point. The median duration of hospitalisation for those admitted was 5 days (range, 1 to 21 days). Where follow-up was available, relapse occurred in eight of 25 cases before reaching skeletal maturity. At the time of metaphyseal osteopathy diagnosis, five of 39 cases had concurrent conditions. Where follow-up was available, four of 25 developed future immune-mediated conditions. CLINICAL SIGNIFICANCE: Metaphyseal osteopathy should be considered in non-ambulatory painful young dogs. Some dogs developed future immune-mediated conditions, which may support the hypothesis that metaphyseal osteopathy is an autoinflammatory bone disorder. Further studies with a larger cohort are required to determine the clinical significance of this.

Pyrexia in juvenile dogs: a review of 140 referred cases.

OBJECTIVES: To describe the presentation, influence of previous treatment and diagnosis in juvenile dogs presenting with pyrexia to a UK referral centre. MATERIALS AND METHODS: Clinical records of dogs aged 1 to 18 months presenting with a problem list including pyrexia (≥⃒39∙2°C) that was reproducible during referral hospitalisation were retrospectively reviewed. Signalment, history - including previous treatment, clinical examination findings and diagnosis were recorded. Diagnoses were categorised as non-infectious inflammatory, infectious, congenital, neoplastic and miscellaneous. The influence of previous treatment on the ability to reach a final diagnosis was analysed. RESULTS: A total of 140 cases was identified. Diagnosis was reached in 115 cases. Non-infectious inflammatory disease was identified in 91 cases (79%), infectious disease in 19 cases (17%), a congenital disorder in four dogs (3%) and neoplasia in one dog (1%). Breeds most commonly identified were Border collies (17/140; 12%), beagles (16/140; 11%), Labrador retrievers (11/140; 8%), springer spaniels (9/140; 6%) and cocker spaniels (8/140; 6%). Before presentation, most dogs had received antibiotics (83/140; 59%), non-steroidal anti-inflammatory drugs (84/140; 60%) or steroids (9/140; 6%), either alone or in combination. Neither antibiotics nor non-steroidal anti-inflammatory drugs influenced the ability to reach a diagnosis. Steroid-responsive meningitis-arteritis comprised 55 of 91 (60%) individuals of the non-infectious inflammatory cohort. All four dogs diagnosed with congenital disorders were Border collies. CLINICAL SIGNIFICANCE: Non-infectious inflammatory disease, particularly steroid-responsive meningitis-arteritis, immune-mediated polyarthritis and metaphyseal osteopathy, was commonly diagnosed in this population of pyrexic juvenile dogs.

Comparison of DNA polymerase alpha and delta from bone marrow.

DNA polymerases alpha and delta from rabbit bone marrow were purified to specific activities greater than 30 000 nM TMP incorporated (mg of protein)(-1)h(-1). alpha is quantitatively predominant. alpha and delta have the same reaction requirements and are both similarly sensitive to N-ethylmaleimide. The primary functional distinction is the association of 3' to 5' exonuclease activity with delta. Sedimentation coefficients obtained from zone sedimentation in glycerol gradients and Stokes radii values from gel filtration allow the calculation of true molecular weight and frictional ratios. alpha exhibits a bimodal pattern, sedimenting at 6 and 8 S on glycerol gradients and demonstrating components corresponding to 40.5- and 65-A Stokes radii upon gel filtration. The calculated molecular weights of the two forms of alpha are 100 000 and 215 000; the frictional ratios are 1.34 and 1.65. This and other data suggest a possible monomer-dimer relation. In contrast, delta sediments uniformly at 6.5 S and also behaves uniformly upon gel filtration at 4595 A. The molecular weight of delta is distinct at 122 000; its frictional ratio is 1.39. Because of similarities of the DNA polymerizing activities of both forms of alpha and of delta, it is postulated that alpha is derived from delta by structural modification, resulting in a decrease in molecular weight, the tendency to aggregate as dimers, and a concomitant loss of 3' to 5' exonuclease activity.

A new mammalian DNA polymerase with 3' to 5' exonuclease activity: DNA polymerase delta.

A new species of DNA polymerase has been purified more than 10 000-fold from the cytoplasm of erythroid hyperplastic bone marrow. This DNA polymerase, in contrast to previously described eukaryotic DNA polymerases, is associated with a very active 3' to 5' exonuclease activity. Similar to the 3' to 5' exonuclease activity associated with prokaryotic DNA polymerases, this enzyme catalyzes the removal of 3'-terminal nucleotides from DNA, as well as a template-dependent conversion of deoxyribonucleoside triphosphates to monophosphates. The exonuclease activity is not separable from the DNA polymerase activity by chromatography on DEAE-Sephadex or hydroxylapatite, and upon sucrose density gradient centrifugation the two activities cosediment at 7 S or at 11 S depending on the ionic strength. Both exonuclease and polymerase activities have identical rates of heat inactivation and both are equally sensitive to hemin and Rifamycin AF/013, inhibitors of DNA synthesis that act by binding to DNA polymerase and causing its dissociation from its template/primer. These results are consistent with the coexistence of two enzyme activities in a single protein.