Systemic sclerosis medications and risk of scleroderma renal crisis.

BACKGROUND: Scleroderma Renal Crisis (SRC) is associated with significant morbidity and mortality. While prednisone is strongly associated with SRC, there are no previous large cohort studies that have evaluated ace inhibitor (ACEi) calcium channel blocker (CCB), angiotensin receptor blocker (ARB), endothelin receptor blocker (ERB), non-steroidal anti-inflammatory drug (NSAID), fluticasone, or mycophenolate mofetil (MMF) use in systemic sclerosis (SSc) and the risk of SRC. METHODS: In this retrospective cohort study of the entire military electronic medical record between 2005 and 2016, we compared the use of ACEi, ARB, CCB, NSAID, ERB, fluticasone, and MMF after SSc diagnosis for 31 cases who subsequently developed SRC to 322 SSc without SRC disease controls. RESULTS: ACEi was associated with an increased risk for SRC adjusted for age, race, and prednisone use [odds ratio (OR) 4.1, 95% confidence interval (CI) 1.6-10.2, P = 0.003]. On stratified analyses, ACEi was only associated with SRC in the presence [OR 5.3, 95% CI 1.1-29.2, p = 0.03], and not the absence of proteinuria. In addition, a doubling of ACEi dose [61% vs. 12%, p < 0.001) and achieving maximum ACEi dose [45% vs. 4%, p < 0.001] after SSc diagnosis was associated with future SRC. CCB, ARB, NSAIDs, ERB, fluticasone, and MMF use were not significantly associated with SRC. CONCLUSION: ACEi use at SSC diagnosis was associated with an increased risk for SRC. Results suggest that it may be a passive marker of known SRC risk factors, such as proteinuria, or evolving disease. SSC patients that require ACEi should be more closely monitored for SRC.

Annealing dynamics of waveguide Bragg gratings: evidence of femtosecond laser induced colour centres.

There is still significant speculation regarding the nature of femtosecond laser induced index change in bulk glasses with colour centre formation and densification the main candidates. In the work presented here, we fabricated waveguide Bragg gratings in doped and undoped phosphate glasses and use these as a diagnostic for monitoring subtle changes in the induced refractive index during photo- and thermal annealing experiments. Reductions in grating strengths during such experiments were attributed to the annihilation of colour centres.

Evaluation of a therapeutic diet for feline degenerative joint disease.

BACKGROUND: Feline degenerative joint disease (DJD) is common and there are no approved therapies for the alleviation of the associated pain. OBJECTIVE: To test a diet high in eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) content and supplemented with green-lipped mussel extract and glucosamine/chondroitin sulfate (test-diet) for its pain-relieving and activity-enhancing effects in cats with painful, mobility-impairing DJD over a 9-week period. ANIMALS: Forty client-owned cats. METHODS: Randomized, controlled, blinded, parallel group, prospective clinical study. Cats with no detectable systemic disease, and with at least 1 appendicular joint with radiographic evidence of DJD where manipulation elicited an aversive response were included. Cats were randomly allocated to the test-diet or control diet (C-diet). Outcome measures were subjective owner and veterinarian assessments, and objective activity monitoring (accelerometry). Nonparametric statistics were used to evaluate changes within and between groups for both subjective and objective data, and locally weighted scatterplot smoothing regression analysis was used to predict activity changes. RESULTS: The primary objective outcome measures indicated that activity declined significantly (P < .001) in the C-diet group, significantly increased (P < .001) in the test-diet group and there was a significant difference between the groups (P < .001). CONCLUSION AND CLINICAL IMPORTANCE: A diet high in EPA and DHA and supplemented with green-lipped mussel extract and glucosamine/chondroitin sulfate improved objective measures of mobility. Dietary modulation might be 1 method to use to improve mobility in cats with DJD-associated pain.

Total hip replacement in three cats: surgical technique, short-term outcome and comparison to femoral head ostectomy.

OBJECTIVE: To describe the surgical technique and clinical features of total hip replacement (THR) due to hip trauma in cats. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: Three client-owned cats that underwent THR to treat capital epiphyseal fractures, and five client-owned cats that underwent femoral head ostectomy (FHO). METHODS: The clinical data included signalment, body weight, body condition score, diagnosis, implant size, surgical technique, intraoperative observations, and postoperative complications. Radiographic evaluation included implant positioning, cement mantle quality, and follow-up examination of the cement-bone interfaces. Orthopaedic examinations and client interviews were used to evaluate limb function. RESULTS: The three cats that underwent THR had a mean body weight of 5.5 kg, a mean body condition score of 6/9, and a mean age of three years at the time of surgery. The average THR follow-up was 11 months. For the five cats that underwent FHO, the mean body weight was 6.3 kg, mean body score was 7/9, and mean age at the time of FHO was 2.5 years. The average FHO follow-up was 22 months. Hip flexion, hip extension, and thigh girth after THR compared favourably to similar measurements made after FHO. The functional outcomes after THR were excellent. The functional outcomes after FHO ranged from poor to excellent. CONCLUSION AND CLINICAL RELEVANCE: The recovery after THR was excellent based on clinical assessment of muscle mass, hip joint passive range of motion, gait, and owner assessment. Further blinded, randomised, and controlled trials of THR in cats are warranted.

Amantadine in a multimodal analgesic regimen for alleviation of refractory osteoarthritis pain in dogs.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) do not always provide sufficient pain relief in dogs with osteoarthritis (OA). HYPOTHESIS: The use of amantadine in addition to NSAID therapy will provide improved pain relief when compared with the use of nonsteroidal analgesics alone in naturally occurring OA in dogs. ANIMALS: Thirty-one client-owned dogs with pelvic limb lameness despite the administration of an NSAID. METHODS: The study was randomized, blinded, and placebo controlled with parallel groups (days 21-42). On day 0, analgesic medications were discontinued. On day 7, all dogs received meloxicam for 5 weeks. On day 21, all dogs received amantadine (3-5 mg/kg once daily per os) or placebo for 21 days, in addition to receiving meloxicam. Assessments were performed before the study and on days 7, 21, and 42. Primary outcome measures were blinded owner assessments of activity using client-specific outcome measures (CSOM) on days 0, 7, 21, and 42. Data were analyzed by a mixed model approach. RESULTS: For CSOM activity, there was a significant time by treatment effect (P=.009). On the basis of the planned post hoc t-tests of postrandomization means, there was a significant difference between treatment groups on day 42 (P=.030), with the amantadine group being more active. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs with osteoarthritic pain refractory to an NSAID, physical activity is improved by the addition of amantadine. Amantadine might be a useful adjunct therapy for the clinical management of canine osteoarthritic pain.

Morphology and correction of distal tibial valgus deformities.

OBJECTIVES: To characterise distal tibial valgus deformities in dogs through physical examination and radiographic evaluation. METHODS: In a clinical study of 16 client-owned dogs, twelve unilateral and four bilateral distal tibial valgus deformities were evaluated using palpation and radiographs. The origin and amplitude of angulation, rotation and length deficits if present were measured. Radiographically, fibular length and position in relation to the tibia was compared in affected and clinically normal limbs. The dimensions of the fibular physes were also compared between clinically normal and affected limbs. RESULTS: Rottweilers and Shetland sheepdogs were overrepresented. Valgus deformities ranged from 16 degrees to 48 degrees (median, 32 degrees ) in affected and from 0 degrees to 13 degrees (median, 6 degrees ) in contralateral, clinically normal limbs. Fibular length, fibular position relative to the tibia or physeal dimensions were not statistically different between affected and clinically normal limbs. CONCLUSION AND CLINICAL RELEVANCE: Many distal tibial valgus deformities in dogs are a uniplanar deformity without concurrent craniocaudal or rotational changes or length deficits. A growth cessation in the fibula does not appear to be responsible for the development of the deformity.

Management of 49 antebrachial and crural fractures in dogs using circular external fixators.

OBJECTIVES: To evaluate frame constructs, postoperative fracture reduction, postoperative care, complications, treatment duration and outcome of circular external fixation for management of 49 antebrachial and crural fractures in dogs. METHODS: Medical records of dogs that underwent surgery with circular external fixation were examined for fracture location, frame configuration, postoperative fracture reduction, treatment duration, complications and outcome. RESULTS: Forty-nine fractures in 48 dogs were stabilised using circular external fixation. Frame removal occurred on average 61 days after surgery (median+/-sd, 52+/-30 days). Minor complications were observed in 35 cases (71 per cent) and major complications in seven (14 per cent). Radiographic outcome at frame removal was judged as excellent in 18 cases (37 per cent), as good in 26 (53 per cent), as fair in four (8 per cent) and poor in one (2 per cent). After frame removal, one fracture was stabilised with a plate, and eight patients were lost to follow-up. Functional and cosmetic outcome at follow-up was judged as excellent in 32 cases (80 per cent), good in seven (18 per cent) and fair in one (2 per cent). CLINICAL SIGNIFICANCE: Circular external fixation can effectively treat antebrachial and crural fractures in dogs, even geometrically complex fractures. Minor complications are frequent but easily managed in most instances. Healing time is comparable to that of other external fixation methods.

Cranial cruciate ligament rupture in large and giant dogs. A retrospective evaluation of a modified lateral extracapsular stabilization.

Forty-two dogs weighing between 30 and 87 kg (mean body weight of 49 kg) with cranial cruciate ligament ruptures (CCLR) were treated with a modified lateral extra-capsular stabilization using braided polyester prosthetic ligament-suture anchor technique. Clinical and radiographic outcomes of 48 stifles were retrospectively evaluated with a mean follow-up of 18 months. Ten dogs had pulled out their bone anchors with no clinical relevance. Draining tracts did not appear. Despite mild radiographic progression of osteoarthritis, all of the dogs regained acceptable function of the operated limb.

Anti-Myeloperoxidase Antibodies Associate with Future Proliferative Lupus Nephritis.

BACKGROUND: The subclinical pathophysiology of proliferative lupus nephritis (PLN) has not been fully elucidated. Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) is associated with PLN, but prediagnostic levels have not been reported. METHODS: We performed a retrospective case-control Department of Defense Serum Repository (DoDSR) study comparing MPO-ANCA levels in longitudinal prediagnostic serum samples for 23 biopsy confirmed proliferative lupus nephritis (PLN) patients to DoDSR identified age, sex, race, and age of serum matched healthy and SLE without LN disease controls. We also compared the temporal relationship of MPO-ANCA to anti-double stranded DNA antibodies (dsDNAab). RESULTS: A greater proportion of PLN patients had prediagnostic MPO-ANCA levels above ≥3 U/mL and ≥6 U/mL compared to SLE without LN (91% versus 43%, p < 0.001; 57% versus 5%, p < 0.001, resp.). In subgroup analysis, the MPO-ANCA threshold of ≥3 U/mL was significant at <1 year (88% versus 39%, p = 0.007) and 1-4 years (87% versus 38%, p = 0.009) prior to diagnosis. Statistically significant subclinical MPO-ANCA levels (≥3 U/mL) occurred prior to statistically significant dsDNAab ≥ 3 IU/ml (89% versus 11%, p = 0.003). CONCLUSIONS: Subclinical MPO-ANCA levels could distinguish future PLN from SLE without LN. MPO-ANCA manifests prior to clinical disease and subclinical dsDNAab to suggest that it may contribute directly to PLN pathogenicity.

Construction and characterisation of a functional CD19 specific single chain Fv fragment for immunotherapy of B lineage leukaemia and lymphoma.

The B cell specific antigen CD19 is a target for the immunotherapy of B lineage leukaemias and lymphomas. We have engineered a single chain Fv (scFv) fragment from the mouse hybridoma cell line FMC63 which produces monoclonal antibody specific for CD19. The genes encoding the FMC63 heavy and light chain variable regions were amplified from cDNA and a scFv was constructed by splice overlap extension PCR. Analysis of staining of lymphoblastoid cell lines, peripheral blood lymphocytes and tonsil sections demonstrated that the monovalent scFv fragment has the same cellular specificity as the parent hybridoma antibody. Kinetic studies with radiolabelled material showed that the scFv binds target cells with a Ka of 2.3 x 10(-9), compared with 4.2 x 10(-9) for the parent antibody. This CD19 scFv will be used in experimental models to test its therapeutic efficacy and immunogenicity, with a view to application in the diagnosis and treatment of human B cell cancers.

Planned wedge size compared to achieved advancement in dogs undergoing the modified Maquet procedure.

OBJECTIVES: To evaluate the patellar ligament to tibial plateau angle (PL-TPA) and amount of achieved advancement in dogs that underwent the modified Maquet procedure; compare wedge sizes recommended using two different planning techniques (Orthomed and modified tibial tuberosity advancement); and evaluate anatomical factors that predict the wedge size required to obtain a 90° PL-TPA. METHODS: Pre- and postoperative radiographs of dogs that had a modified Maquet procedure performed were evaluated for the following: calculated wedge size using two different planning techniques, the actual wedge size used, the achieved tibial tuberosity advancement, and the changes in PL-TPA. Anatomical measurements of the tibia were evaluated and correlated with the actual wedge size. RESULTS: Of the 38 modified Maquet procedures identified, 53% (n = 20) had a PL-TPA of 90° ± 5°. Actual achieved advancement of the tibial tuberosity was 30% less than the wedge size used. Changes in PL-TPA and tibial width persisted at eight weeks postoperatively without loss of advancement. The two planning techniques did not result in a significantly different selection of wedge size. CLINICAL RELEVANCE: Current planning techniques for the modified Maquet procedure result in under-advancement of the tibial tuberosity. Both measurement techniques evaluated do not result in appropriate advancement.

Variability associated with assessing changes in position of a canine uncemented femoral stem prosthesis.

OBJECTIVE: Evaluate variability associated with assessing changes in the position of uncemented femoral stems. METHODS: Stem level, canal fill, stem angle, and version angle were measured on craniocaudal horizontal beam (CCHB) and open leg lateral (OLL) radiographic projections of the femur of 20 dogs that had uncemented total hip replacement. Intraobserver and interobserver repeatability were determined on immediate postoperative (PO) images. Differences in position were calculated between the first (3 months - R1) and second (6 months - R2) re-evaluation (R1-R2) time points, and between PO and R1. RESULTS: The measurement process was very repeatable. For R1-R2, the stem appeared to subside 0.8 ± 1.4 mm for measurements based on the greater trochanter on the CCHB images, but there was a wide range (-3.9 to 2 mm; positive values indicate proximad movement). Measurements based on the intertrochanteric crest on the OLL images had the same mean, and also a wide range (-4.4 to 2.1 mm; negative values indicate proximad movement). For PO-R1, the stem appeared to subside 1.8 ± 2.0 mm (CCHB, based on the greater trochanter, range -7.7 to 2.2 mm), 1.6 ± 1.5 mm (CCHB, based on the intertrochanteric crest, range -0.7 to 4.3 mm); and 2.1 ± 2.1 mm (OLL, based on the intertrochanteric crest, range -1.6 to 6.8 mm). CONCLUSION: The position of a stable stem can appear different on subsequent re-evaluations, but this may be due to variability associated with inconsistency of positioning of the patient and limb. CLINICAL SIGNIFICANCE: Documenting subsidence in individual patients should not rely on calculations based on a single measurement.

Revision of a loose cementless short-stem threaded femoral component using a standard cementless stem in a canine hip arthroplasty.

A Helica short-stemmed femoral prosthesis that was identified as being loose one year after implantation was revised with a standard long stem cementless BFX femoral prosthesis. A double pelvic osteotomy was also performed to improve the orientation of the stable acetabular cup. Despite complete resorption of the femoral neck, and a large perforation of the lateral femoral cortex, the revision stem did not subside or rotate. The prosthetic joint did not dislocate. At re-evaluation two years after revision surgery, the prosthetic components were stable. Signs of bone ingrowth into the stem and cup were evident on radiographs. The dog had a seven percent greater thigh muscle girth in the limb implanted with the hip prosthesis compared to the contralateral limb, and was very active with no lameness.

Acetabular cup liner and prosthetic head exchange to increase the head diameter for management of recurrent luxation of a prosthetic hip in two dogs.

Component malalignment and impingement are possible causes of recurrent luxation following total hip replacement in the dog. In the two cases presented in this report, luxation that was probably due to impingement was managed by exchanging the standard 17 mm prosthetic head for a 24 mm prosthetic head. This required removal of the original acetabular cup liner and placement of a new polyethylene liner that would accept the 24 mm head into the stable acetabular shell. In the first case, a 50 kg Malamute dog, recurrent luxation was initially managed by component alignment revision, iliofemoral suture, triple pelvic osteotomy and a novel lasso technique, without long-term success. After exchanging the head and cup liner, luxation did not recur over a 12-month period. In the second case, a 65 kg Newfoundland dog, impingement was suspected after a second luxation event. Luxation did not recur during the nine months after exchange of the head and cup liner. The larger prosthetic head used in these two cases increased the impingement-free range-of-motion of the joint and increased the translation distance required for luxation (jump distance).

Single-stage bilateral tibial tuberosity advancement for treatment of bilateral canine cranial cruciate ligament deficiency.

OBJECTIVE: To report complications in dogs with naturally occurring cranial cruciate ligament rupture following single-stage bilateral tibial tuberosity advancement (SS-BTTA) procedures, and to compare these complications to a population of dogs undergoing unilateral tibial tuberosity advancement (UTTA). METHODS: Medical records and radiographs of client-owned dogs treated with tibial tuberosity advancement between August 2008 and December 2011 were reviewed. Forty-four client-owned dogs with bilateral cranial cruciate ligament rupture that underwent SS-BTTA procedures and 82 client-owned dogs that underwent UTTA procedures were randomly selected from our hospital population. Complications were recorded and analysed. Major complications were defined as fractures or any complication requiring a second surgery. Minor complications were any problem identified that did not require surgical management. RESULTS: Incidence for major and minor complications in the UTTA group was 2.3% and 24.4%, respectively. Incidence for major and minor complications in the SS-BTTA group was 12.5% and 26.1%, respectively. Single-stage bilateral tibial tuberosity advancement procedures had a four- to five-fold increase in odds of a major complication (p <0.050) compared to UTTA. CLINICAL SIGNIFICANCE: The findings of our study indicate that SS-BTTA procedures are associated with an increased risk of major complications compared to UTTA procedures.

Pharmacokinetic model for cefazolin distribution during total hip arthroplasty in dogs.

OBJECTIVES: To compare cefazolin pharmacokinetics in serum and concentrations in tissues during total hip arthroplasty in dogs with and without hip dysplasia, and to calculate the optimal dosage of cefazolin for prophylactic use during total hip arthroplasty. ANIMALS: 10 dogs with hip dysplasia and 3 clinically normal dogs. PROCEDURE: Blood samples and tissue specimens from the coxofemoral joint capsule, acetabulum, and femur were obtained during unilateral total hip arthroplasty. Cefazolin concentrations in serum and tissue specimen supernatant were determined, using high-performance liquid chromatography, for use in pharmacokinetic analysis. Mathematical simulation of serum cefazolin concentration was used to to predict the optimal dose. RESULTS: Mean pharmacokinetic constants (SEM) were 0.146 (0.013) min-1 for alpha, 4.47 min for t1/2 alpha 0.015 (0.004) min-1 for beta, 46.83 min for t1/2 beta. Significant different was not detected for cefazolin distribution and elimination between dogs with and without hip dysplasia. Additional, significant difference was not observed in pharmacokinetic parameters describing distribution and elimination between the first and second doses of cefazolin. The predicted optimal dosage regimen was 8 mg/kg of body weight, i.v. every hour or mg/kg, i.v. every 2 hours. CLINICAL RELEVANCE: For prophylactic i.v. treatment during total hip arthroplasty, use of cefazolin at a dosage of 8 mg/kg every hour or 22 mg/kg every 2 hours should maintain serum cefazolin concentrations at least 10x the minimum inhibitory concentration for 3 to 4 hours.

Chronic localized osteomyelitis caused by atypical infection with Blastomyces dermatitidis in a dog.

A 4-year-old male Golden Retriever was evaluated because of chronic non-weight-bearing lameness of the right hind limb associated with penetrating tarsal wounds. Arthritis of the tarsal joint and osteomyelitis of the talus were initially evident. Tarsal arthrodesis was performed 7 months after initial injury, but the lameness persisted. Ten months later, blastomycosis was diagnosed on the basis of results of histologic examination of bone biopsy specimens and serologic tests. No other site of involvement was detected. The limb was amputated, and Blastomyces dermatitidis was isolated from the affected bone. Adjuvant antifungal treatment was not given. Ten months after amputation, the dog was in good health, and the antibody titer for B dermatitidis was low, indicating resolution of the infection. Localized bone infection with B dermatitidis is rare in dogs. In this dog, it was believed that blastomycosis was contracted through direct inoculation of the organism, because the lesion was associated with puncture wounds and other sites of involvement were not found.

Fracture treatment with circular external fixation.

Circular external skeletal fixation (CEF) has been used in recent years to treat acute and chronic fractures and bone deformities, to stabilize joints while maintaining range of motion, and to perform arthrodeses and limb-sparing in dogs. Dr. Ilizarov defined the general principles and methods of CEF. This article reviews these principles. It also describes the indications, preoperative planning, surgical placement, postoperative management, clinical results, and complications of CEF used to treat fractures in dogs.

Stabilisation of scoliosis in two koi (Cyprinus carpio).

Two koi (Cyprinus carpio) from the same pond developed similar lesions of scoliosis. Radiographic examinations showed that their spines had become malaligned as a result of vertebral compression fractures involving T14 to T16. The vertebrae in both fish were stabilised with screws, k-wire and polymethylmethacrylate. They both appeared to improve after surgery, but they began to decline and died within three months. A postmortem examination revealed multi-organ inflammation that was not associated with the surgical implants.

Incomplete ossification of the humeral condyle in two Labrador retrievers.

Incomplete ossification of the humeral condyle (IOHC) was identified in two Labrador retrievers using computed tomography. Both dogs were non-weightbearing on the affected forelimbs. The dogs were treated by means of a bone screw placed across the humeral condyle. IOHC was originally reported in spaniel and chondrodystrophic breeds. The pathogenesis of the condition remains unknown, but may be related to impaired antebrachial bone growth, similarly to the pathogeneses of elbow dysplasia and radius curvus.