Local Hemodynamic Conditions Associated with Focal Changes in the Intracranial Aneurysm Wall.

BACKGROUND AND PURPOSE: Aneurysm hemodynamics has been associated with wall histology and inflammation. We investigated associations between local hemodynamics and focal wall changes visible intraoperatively. MATERIALS AND METHODS: Computational fluid dynamics models were constructed from 3D images of 65 aneurysms treated surgically. Aneurysm regions with different visual appearances were identified in intraoperative videos: 1) "atherosclerotic" (yellow), 2) "hyperplastic" (white), 3) "thin" (red), 4) rupture site, and 5) "normal" (similar to parent artery), They were marked on 3D reconstructions. Regional hemodynamics was characterized by the following: wall shear stress, oscillatory shear index, relative residence time, wall shear stress gradient and divergence, gradient oscillatory number, and dynamic pressure; these were compared using the Mann-Whitney test. RESULTS: Hyperplastic regions had lower average wall shear stress (P = .005) and pressure (P = .009) than normal regions. Flow conditions in atherosclerotic and hyperplastic regions were similar but had higher average relative residence time (P = .03) and oscillatory shear index (P = .04) than thin regions. Hyperplastic regions also had a higher average gradient oscillatory number (P = .002) than thin regions. Thin regions had lower average relative residence time (P < .001), oscillatory shear index (P = .006), and gradient oscillatory number (P < .001) than normal regions, and higher average wall shear stress (P = .006) and pressure (P = .009) than hyperplastic regions. Thin regions tended to be aligned with the flow stream, while atherosclerotic and hyperplastic regions tended to be aligned with recirculation zones. CONCLUSIONS: Local hemodynamics is associated with visible focal wall changes. Slow swirling flow with low and oscillatory wall shear stress was associated with atherosclerotic and hyperplastic changes. High flow conditions prevalent in regions near the flow impingement site characterized by higher and less oscillatory wall shear stress were associated with local "thinning" of the wall.

Predicting risk of rupture and rupture-preventing reinterventions following endovascular abdominal aortic aneurysm repair.

BACKGROUND: Clinical and imaging surveillance practices following endovascular aneurysm repair (EVAR) for intact abdominal aortic aneurysm (AAA) vary considerably and compliance with recommended lifelong surveillance is poor. The aim of this study was to develop a dynamic prognostic model to enable stratification of patients at risk of future secondary aortic rupture or the need for intervention to prevent rupture (rupture-preventing reintervention) to enable the development of personalized surveillance intervals. METHODS: Baseline data and repeat measurements of postoperative aneurysm sac diameter from the EVAR-1 and EVAR-2 trials were used to develop the model, with external validation in a cohort from a single-centre vascular database. Longitudinal mixed-effects models were fitted to trajectories of sac diameter, and model-predicted sac diameter and rate of growth were used in prognostic Cox proportional hazards models. RESULTS: Some 785 patients from the EVAR trials were included, of whom 155 (19·7 per cent) experienced at least one rupture or required a rupture-preventing reintervention during follow-up. An increased risk was associated with preoperative AAA size, rate of sac growth and the number of previously detected complications. A prognostic model using predicted sac growth alone had good discrimination at 2 years (C-index 0·68), 3 years (C-index 0·72) and 5 years (C-index 0·75) after operation and had excellent external validation (C-index 0·76-0·79). More than 5 years after operation, growth rates above 1 mm/year had a sensitivity of over 80 per cent and specificity over 50 per cent in identifying events occurring within 2 years. CONCLUSION: Secondary sac growth is an important predictor of rupture or rupture-preventing reintervention to enable the development of personalized surveillance intervals. A dynamic prognostic model has the potential to tailor surveillance by identifying a large proportion of patients who may require less intensive follow-up.

Flow Conditions in the Intracranial Aneurysm Lumen Are Associated with Inflammation and Degenerative Changes of the Aneurysm Wall.

BACKGROUND AND PURPOSE: Saccular intracranial aneurysm is a common disease that may cause devastating intracranial hemorrhage. Hemodynamics, wall remodeling, and wall inflammation have been associated with saccular intracranial aneurysm rupture. We investigated how saccular intracranial aneurysm hemodynamics is associated with wall remodeling and inflammation of the saccular intracranial aneurysm wall. MATERIALS AND METHODS: Tissue samples resected during a saccular intracranial aneurysm operation (11 unruptured, 9 ruptured) were studied with histology and immunohistochemistry. Patient-specific computational models of hemodynamics were created from preoperative CT angiographies. RESULTS: More stable and less complex flows were associated with thick, hyperplastic saccular intracranial aneurysm walls, while slower flows with more diffuse inflow were associated with degenerated and decellularized saccular intracranial aneurysm walls. Wall degeneration (P = .041) and rupture were associated with increased inflammation (CD45+, P = .031). High wall shear stress (P = .018), higher vorticity (P = .046), higher viscous dissipation (P = .046), and high shear rate (P = .046) were associated with increased inflammation. Inflammation was also associated with lack of an intact endothelium (P = .034) and the presence of organized luminal thrombosis (P = .018), though overall organized thrombosis was associated with low minimum wall shear stress (P = .034) and not with the flow conditions associated with inflammation. CONCLUSIONS: Flow conditions in the saccular intracranial aneurysm are associated with wall remodeling. Inflammation, which is associated with degenerative wall remodeling and rupture, is related to high flow activity, including elevated wall shear stress. Endothelial injury may be a mechanism by which flow induces inflammation in the saccular intracranial aneurysm wall. Hemodynamic simulations might prove useful in identifying saccular intracranial aneurysms at risk of developing inflammation, a potential biomarker for rupture.

Semi-automated International Cartilage Repair Society scoring of equine articular cartilage lesions in optical coherence tomography images.

BACKGROUND: Arthroscopic optical coherence tomography (OCT) is a promising tool for the detailed evaluation of articular cartilage injuries. However, OCT-based articular cartilage scoring still relies on the operator's visual estimation. OBJECTIVES: To test the hypothesis that semi-automated International Cartilage Repair Society (ICRS) scoring of chondral lesions seen in OCT images could enhance intra- and interobserver agreement of scoring and its accuracy. STUDY DESIGN: Validation study using equine cadaver tissue. METHODS: Osteochondral samples (n = 99) were prepared from 18 equine metacarpophalangeal joints and imaged using OCT. Custom-made software was developed for semi-automated ICRS scoring of cartilage lesions on OCT images. Scoring was performed visually and semi-automatically by five observers, and levels of inter- and intraobserver agreement were calculated. Subsequently, OCT-based scores were compared with ICRS scores based on light microscopy images of the histological sections of matching locations (n = 82). RESULTS: When semi-automated scoring of the OCT images was performed by multiple observers, mean levels of intraobserver and interobserver agreement were higher than those achieved with visual OCT scoring (83% vs. 77% and 74% vs. 33%, respectively). Histology-based scores from matching regions of interest agreed better with visual OCT-based scoring than with semi-automated OCT scoring; however, the accuracy of the software was improved by optimising the threshold combinations used to determine the ICRS score. MAIN LIMITATIONS: Images were obtained from cadavers. CONCLUSIONS: Semi-automated scoring software improved the reproducibility of ICRS scoring of chondral lesions in OCT images and made scoring less observer-dependent. The image analysis and segmentation techniques adopted in this study warrant further optimisation to achieve better accuracy with semi-automated ICRS scoring. In addition, studies on in vivo applications are required.

Pathology of Natural Cases of Equine Endocrinopathic Laminitis Associated With Hyperinsulinemia.

Laminitis in equids is a clinical syndrome usually associated with systemic disease. Endocrinopathies recently have been recognized as the most common cause of laminitis, with hyperinsulinemia playing a key role. Descriptions of laminitis-associated lesions have been confusing due to the wide range of experimental models used, failure of adequate clinical documentation for naturally occurring cases, lack of separate analysis of inflammatory and endocrinopathic laminitis, and uncertainty regarding normal morphological variation of lamellae. In this study, lamellar morphology and pathology were described in 14 laminitic horses and ponies that had hyperinsulinemia (>20 mIU/l), with reference to 25 age- and breed-matched controls. The type and severity of lesions noted had no correlation with reported clinical duration and in at least some cases must have preceded it. Lesions were largely localized abaxially within the lamellar tissue and included apoptotic cell death, as well as lamellar fusion, hyperplasia, and partial replacement with aberrant keratin containing nucleated debris and proteinaceous lakes. The lesions resulted in irregular margins between the inner horn and the lamellar tissue. Acute separation originated from the abaxial region, with minimal associated inflammation. Axially, epidermal lamellar tapering was the most frequent morphological observation. The lesions in these chronic cases of laminitis were similar to those described in some inflammatory laminitis models and contained features seen in developmental phases of hyperinsulinemic models. These findings support the theory that repeated episodes of subclinical laminitis occur prior to clinical presentation. In addition, the pathology does not include extensive basement membrane failure seen in some inflammatory models.

Diagnostic exercise: intraosseous epidermoid cysts in the third phalanx of a dressage mare.

An 11-yr-old Dressage mare had abnormal gait, and an abscess of the left hoof was suspected but not observed. Radiographic and computerized tomographic evaluations showed a large cystic lesion near the apex of the pedal bone, and a smaller, similar lesion at the lateral wing. Sagittal sections through the affected member revealed two intraosseous cysts at the third phalanx. Histologic and histochemical results characterized the lesions as intraosseous epidermoid cysts of the third phalanx.

Polyneuropathy of Finnish horses characterised by inflammatory demyelination and intracisternal Schwann cell inclusions.

REASON FOR PERFORMING STUDY: A neurological disorder characterised by pelvic limb metatarsophalangeal joint extensor paresis has been observed in numerous horses in Scandinavia for the last decade. Very little has been formally reported and there have been no detailed assessments of the neurological signs or neuropathological lesions. OBJECTIVES: To describe the epidemiological and pathological features of an outbreak of 'Scandinavian knuckling syndrome' in a riding stable in southern Finland. METHODS: Clinical neurological examination of 4 cases and neuropathological assessment of tissues of one case were performed. RESULTS: Eleven out of 17 horses fed on ryegrass from a common source showed progressive clinical signs of metatarsophalangeal extensor paresis necessitating euthanasia of 7 horses. Nervous system lesions in one horse consisted of a novel demyelinating, mildly inflammatory peripheral neuropathy, with BiP/GRP positive rough endoplasmatic reticulum Schwann cell inclusions. CONCLUSIONS: The clinical signs and lesions documented differ from any previously described equine polyneuropathy and suggest a primary Schwann cell lesion. POTENTIAL RELEVANCE: The classification of this disease as a novel demyelinating polyneuropathy may assist focused epidemiological investigations.

Panax Ginseng in combination with brewers' yeast (Gerivet) as a stimulant for geriatric dogs: a controlled-randomized blinded study.

The study was performed on two groups of dogs, one (n = 41) given Ginseng (Panax Ginseng) together with brewers' yeast (Saccharomyces cerevisae) and the other (n = 39) given only brewers' yeast (control group, but not a true placebo), for 8 weeks. Using a questionnaire and three visual analogue scales, the blinded owners evaluated the dogs before the trial, weekly for the 8 weeks of the trial and twice, at 12th and 16th weeks, after the trial (follow-up). At 8th, 12th and 16th weeks the owners also answered questions concerning what treatment their dogs likely had been getting, willingness to continue medication and the dogs' general status. The changes from baseline to the end of the treatment period in the variable scores were calculated for each dog and used in statistics. Panax Ginseng plus yeast significantly improved all evaluated variables within the group. Four of the seven primary (mentally) outcome measures were significant when comparing the changes in the Ginseng group with the control group, and six of the seven were significant when compared to an external group. As the secondary (physical) outcome measures were significantly better in both the Ginseng and the control group compared to the external group, it indicates that brewers' yeast is the ingredient that has impact on physical performance. No significant changes in blood- or urine analyses and no side effects were seen.

Clinical efficacy and safety of dexmedetomidine and buprenorphine, butorphanol or diazepam for canine hip radiography.

OBJECTIVES: To investigate the usefulness of dexmedetomidine for restraint and sedation during hip radiographic examination of hip-extended or stress-radiography views when combined with either buprenorphine, butorphanol or diazepam. METHODS: One hundred and twenty-seven client-owned clinically healthy golden retrievers or rottweilers were enrolled in a clinical trial that compared hip-extended and PennHIP methods for diagnosing hip dysplasia and were randomly allocated to receive dexmedetomidine or medetomidine in combination with buprenorphine, butorphanol or diazepam. Subjective assessments were made for response to pain, response to noise, palpebral reflex, muscle tone and overall quality of sedation; non-invasive physiological variables were also recorded. RESULTS: Overall quality of sedation was graded as good or excellent for dogs administered with a combination of butorphanol or diazepam. However, more dogs that received a combination involving buprenorphine had overall a relatively poorer quality of sedation and required additional administration of buprenorphine before the radiographic procedure could commence. Once sedated, clinically sufficient muscle relaxation accompanied by a very low proportion of dogs responding to pain or noise stimuli were observed in all treatment groups. Heart and respiratory rate, and procedure and recovery times were similar for all treatment groups, and no adverse events were observed during the study. CLINICAL SIGNIFICANCE: Dexmedetomidine sedative protocols, particularly in combination with butorphanol and diazepam, can be used effectively and safely in dogs for radiographic procedures.

Changes in MMP-2 and -9 activity and MMP-8 reactivity after amphotericin B induced synovitis and treatment with bufexamac.

The objective here was to evaluate the acute effects of induced arthritis on synovial fluid (SF) levels of matrix metalloproteinases (MMP) -2, -8 and -9 in horses. To evaluate MMP-2 and -9 activities and the effect of non-steroidal anti-inflammatory drug (NSAID) bufexamac during remission from acute arthritis. Aseptic arthritis was induced in 24 Standardbred horses using 20 mg of amphotericin B as a single intra-articular (IA) injection in the right intercarpal joint. After 1 week and 2 weeks, horses were treated intra-articularly with 10, 20, or 40 mg of bufexamac suspension or with sterile saline solution as control. SF was sampled prior to induction and at weekly intervals for 5 weeks. Fluids were evaluated for MMP-2 and MMP-9 activity by gelatin zymography or for MMP-8 immunoreactivity by Western Blotting. IA injection of amphotericin B consistently resulted in significant increase in the immunoreactivity of MMP-8 and activity of both the latent and the active forms of MMP-2 and -9, among which the active form of MMP-2 increased the most. MMP-9 levels declined to pre-induction levels within 2 weeks, whereas levels of MMP-2 remained still high after 5 weeks. Treatment with bufexamac did not significantly affect levels of gelatinolytic MMP. Results suggest that after acute arthritis of horses, elevated MMP activity is present in the joint, for several weeks, to a degree that could promote cartilage degradation, and treatment with the NSAID bufexamac is not likely to affect that. Furthermore, analysing levels of MMP-9 activity and especially levels of active forms of MMP-2 activity may be valuable to predict the time of occurrence of arthritis in horses.

Mice with a deletion in the first intron of the Col1a1 gene develop dissection and rupture of aorta in the absence of aneurysms: high-resolution magnetic resonance imaging, at 4.7 T, of the aorta and cerebral arteries.

Deletion of the majority of the first intron of the Col1a1 gene in mice leads to decreased type I collagen synthesis and content in the aortic wall. In 54% of cases, mice homozygous for the Col1a1 mutation die of thoracic hemorrhage by the age of 18 months. It is unknown whether the fatal bleeding results from an acute dissection of the aortic wall or a gradually developing dilatation of the medial layer prior to rupture. We optimized high-resolution MRI methods using a 4.7 T MR scanner to obtain in vivo images of the entire mouse aorta. The MR images were acquired in three imaging planes using gradient echo, spin echo, and spin echo with inversion recovery pulse sequences with a maximum in-plane resolution of 68 x 68 microm and acquisition times less than 10 min. In five Col1a1 mutated mice aged 16 months, the MR images showed no signs of aneurysmal dilatation, wall defects, or former dissection, suggesting that the mechanism for aortic rupture is an acute dissection of the aortic medial layer. Cerebral arteries were imaged using a three-dimensional time of fight pulse sequence. The resolution of 73 x 73 x 94 microm showed normal cerebral arteries. Histology showed a 22% thinner cerebral artery wall in Col1a1 mutated mice.

The copolymer of epsilon-caprolactone-lactide and tricalcium phosphate does not enhance bone growth in mandibular defect of sheep.

In the field of craniomaxillofacial and orthopaedic surgery there is a constant need for bone or bone substitute. At the present, the most effective way to enhance bone healing clinically is to use autogenous bone grafts. The problems associated with the use of these autografts are donor site morbidity, limited supply and need for a second operative site. Currently there are several different synthetic products commercially available in the market; nevertheless, none of them is ideal for filling bone defects. Therefore, search for new synthetic materials for bone replacement is necessary. A mixture of tricalcium phosphate (TCP) and epsilon-caprolactone-lactide copolymer P(epsilon -CL/DL-LA) was prepared and implanted in critical size mandibular bone defects in twelve sheep. Contralateral side was used as a control. Follow-up times for histological and radiological studies were 9, 14, 24 and 52 weeks. We found that the implanted material did not enhance bone formation compared to control site. We also confirmed that defect size was of critical size, since there was no complete healing of the control site either. The results do not encourage us to continue our studies with the mixture of TCP and P(epsilon-CL/DL-LA) as a filling material for bone defects. Therefore the search for the ideal material is still ongoing.

Intramedullary fixation of femoral cortical osteotomies with interlocked biodegradable self-reinforced poly-96L/4D-lactide (SR-PLA96) nails.

Femoral diaphyseal osteotomies of adult sheep were fixed with intramedullary (i.m.) biodegradable self-reinforced poly-96L/4D-lactide (SR-PLA96) nails (Phi 10.66-10.78 mmx195-199 mm) that were interlocked with four Phi 1.5 mm metallic Kirschner (K) wires. Hollow i.m. nails used in the pilot study resulted in implant failure and only two of these sheep were followed long term (18 months and 3 years). In the main study, solid nails were used and this resulted in consolidation in 5/6 cases and in one non-union due to failure of both proximal K wires at 3 weeks. Sheep in the main study were followed for 6 and 12 months. Femurs were studied radiographically, microradiographically, histologically and by oxytetracycline labelling. Good bone healing was achieved and histology showed only a mild tissue reaction to the implant at 6-18 months. At 3 years, the implant had almost degraded and numerous foamy macrophages were ingesting the disintegrated material. No accumulations of lymphocytes implying an immunological inflammatory reaction were seen. This investigation demonstrated that absorbable SR-PLA96 i.m. nails can be used together with interlocking metallic K wires in fixation of simple cortical osteotomies in large animals weighing up to 63 kg. The long-term biocompatibility should be studied in a larger population.

Biochemical characterisation of navicular hyaline cartilage, navicular fibrocartilage and the deep digital flexor tendon in horses with navicular disease.

The study hypothesis was that navicular disease is a process analogous to degenerative joint disease, which leads to changes in navicular fibrocartilage and in deep digital flexor tendon (DDFT) matrix composition and that the process extends to the adjacent distal interphalangeal joint. The objectives were to compare the biochemical composition of the navicular articular and palmar cartilages from 18 horses with navicular disease with 49 horses with no history of front limb lameness, and to compare navicular fibrocartilage with medial meniscus of the stifle and collateral cartilage of the hoof. Cartilage oligomeric matrix protein (COMP), deoxyribonucleic acid (DNA), total glycosaminoglycan (GAG), metalloproteinases MMP-2 and MMP-9 and water content in tissues were measured. Hyaline cartilage had the highest content of COMP and COMP content in hyaline cartilage and tendon was higher in lame horses than in sound horses (p<0.05). The concentration of MMP-2 amount in hyaline cartilage was higher in lame horses than in sound horses. The MMP-2 amounts were significantly higher in tendons compared to other tissue types. Overall, 79% of the lame horses with lesions had MMP-9 in their tendons and the amount was higher than in sound horses (p<0.05). In horses with navicular disease there were matrix changes in navicular hyaline and fibrocartilage as well as the DDFT with potential implications for the pathogenesis and management of the condition.

Analysis of lapine cartilage matrix after radiosynovectomy with holmium-166 ferric hydroxide macroaggregate.

OBJECTIVE: To study the short and long term effects of radiosynovectomy on articular cartilage in growing and mature rabbits. METHODS: The articular cartilage of the distal femurs of rabbits was examined four days, two months, and one year after radiosynovectomy with holmium-166 ferric hydroxide macroaggregate ([(166)Ho]FHMA). Arthritic changes were evaluated from histological sections by conventional and polarised light microscopy, and glycosaminoglycan measurements using safranin O staining, digital densitometry, and uronic acid determination. Proteoglycan synthesis was studied by metabolic [(35)]sulphate labelling followed by autoradiography, and electrophoretic analysis of extracted proteoglycans. Northern analyses were performed to determine the mRNA levels of type II collagen, aggrecan, and Sox9 in cartilage samples. RESULTS: Radiosynovectomy had no major effect on the histological appearance of articular cartilage in mature rabbits, whereas more fibrillation was seen in [(166)Ho]FHMA radiosynovectomised knee joints of growing rabbits two months after treatment, but not after one year. Radiosynovectomy did not cause changes in the glycosaminoglycan content of cartilage or in the synthesis or chemical structure of proteoglycans. No radiosynovectomy related changes were seen in the mRNA levels of type II collagen, whereas a transient down regulation of aggrecan and Sox9 mRNA levels was seen in young rabbits two months after [(166)Ho]FHMA radiosynovectomy. CONCLUSIONS: [(166)Ho]FHMA radiosynovectomy caused no obvious chondrocyte damage or osteoarthritic changes in mature rabbits, but in growing rabbits some transient radiation induced effects were seen--for example, mild cartilage fibrillation and down regulation of cartilage-specific genes.

Dynamics in serum of the inflammatory markers serum amyloid A (SAA), haptoglobin, fibrinogen and alpha2-globulins during induced noninfectious arthritis in the horse.

Despite the importance of noninfectious joint diseases in equine medicine, little is known about the acute phase response which may be elicited if the local inflammatory process of noninfectious arthritis is sufficiently strong, Therefore the aim of this study was to monitor the systemic inflammatory response during experimentally-induced noninfectious arthritis by studying the dynamics in serum of the acute phase proteins serum amyloid A (SAA), haptoglobin, fibrinogen and alpha2-globulins. Twenty-four Standardbred horses, age 3-7 years, found healthy on thorough clinical, radiological, haematological and serum biochemical examination, were injected aseptically into the right midcarpal joint with amphotericin B. Blood samples were drawn before induction of arthritis (0 h), and at 8, 16, 24, 36 and 48 h postinduction and then on Days 3, 4, 5 and 15 postinduction. All horses developed lameness with joint effusion and joint heat as well as increased respiratory rate, heart rate and body temperature. The lameness started to decline after 24-36 h and, in most animals, systemic signs disappeared on Day 2 postinjection. The concentration of the acute phase proteins increased following induction of arthritis. The SAA concentrations were higher than baseline concentrations from 16 h postinduction and were maximal at 36-48 h (227 times baseline concentration). The haptoglobin concentrations were higher than baseline concentrations from 24 h and were maximal at 48-96 h (1.14 times baseline concentration). The maximal concentrations of fibrinogen were seen between 36-72 h postinjection and increased on average 0.87 times from baseline concentrations. The fibrinogen concentrations were higher than baseline concentrations from 24 h postinjection. Alpha2-globulins concentrations showed a minor increase and increased 0.55 times from baseline concentrations. The markers had returned to baseline concentrations by Day 15. Our results demonstrate that amphotericin B-induced arthritis in a single joint gives rise to a systemic acute phase response measurable as increased concentrations in serum SAA, haptoglobin, fibrinogen and alpha2-globulins during the first 2 weeks of the condition and, thereby, that such an increase need not be indicative of infectious arthritis. Further research should be aimed at determining whether chronic noninfectious arthritis in the horse gives rise to increased acute phase protein concentrations in serum.

Double-blind evaluation of implants of gold wire at acupuncture points in the dog as a treatment for osteoarthritis induced by hip dysplasia.

Thirty-eight dogs with hip dysplasia were studied to evaluate the use of gold wire implants at acupuncture points around the hip joints. They were assigned at random into two groups of 19. In the treated group, gold wire was inserted through hypodermic needles at electrically found acupuncture points around both hips. In the control group, the areas were prepared in the same way but had only the skin pierced at sites which were not acupuncture points, with a needle of the same size as that used in the treated group. Over a period of six months the dogs were studied repeatedly by two veterinarians and by the dogs' owners who were unaware of the treatments the dogs had received; they assessed the dogs' locomotion, hip function and signs of pain. Radiographs were taken at the beginning and end of the study. Although the data collected from both groups by the veterinarians and the owners showed a significant improvement of locomotion and reduction in signs of pain (P=0.036 for the veterinary evaluation and locomotion and P=0.0001 and P=0.0034 for the owners' evaluation of locomotion and pain, respectively), there were no statistically significant differences between the treated and control groups (P=0.19 and P=0.41, P=0.24, respectively).

Effects of intra-articular injections of bufexamac suspension in healthy horses.

OBJECTIVE: To evaluate the effects of intra-articular (IA) injections of bufexamac in horses, focusing particularly on the effects of bufexamac on articular cartilage. ANIMALS: 20 Standardbreds. PROCEDURE: Horses were randomly allocated into 4 groups consisting of 5 horses each, and 20, 60, or 100 mg of bufexamac or 1 ml of sterile saline (0.9% NaCl) solution (control) was injected into 1 intercarpal joint at weekly intervals for 6 treatments (days 0, 7, 14, 21, 28, and 35). Clinical signs and results of hematologic, serum biochemical, and synovial fluid (SF) analyses and radiography were used to evaluate treatment effects. On day 49, all horses were euthanatized; gross necropsy and histologic examinations of internal organs and articular tissues were performed. Glycosaminoglycan concentration of the articular cartilage was evaluated in safranin O-stained sections by use of a semiquantitative microspectrophotometric method. RESULTS: No systemic signs were observed. Temporary mild to moderate heat and effusion were the only clinical signs observed in a number of joints after IA injections and more often only in the 100 mg group, compared with controls. The 100 mg dose resulted in significant increases in SF WBC counts, with relative neutrophilia and SF total protein concentration 24 hours after injection (day 1). No lesions suggestive of toxic effects were detected at necropsy or on histologic examination. No changes in articular cartilage glycosaminoglycan concentration were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Six injections of 20, 60, or 100 mg of bufexamac at weekly intervals did not cause any untoward systemic or local effects. These data suggest that bufexamac is a safe nonsteroidal anti-inflammatory drug for IA administration in horses.

Intramedullary fixation of cortical bone osteotomies with absorbable self-reinforced fibrillated poly-96L/4D-lactide (SR-PLA96) rods in rabbits.

Osteotomies of the femoral diaphysis were fixed with absorbable self-reinforced fibrillated poly-96L/4D-lactide (SR-PLA96) intramedullary rods (4.5 mm x 50-60 mm) in 43 adult rabbits. Follow-up times varied from 3 weeks to 3 yr. After sacrifice histological, oxytetracycline-fluorescence and microradiographic studies of the bones were performed. Strength characteristics and changes in crystallinity and molecular weight of the rods were also measured. All osteotomies were evaluated radiographically. Thirty-six osteotomies (84%) healed uneventfully. The implant disappeared almost totally within 3 yr and histology showed only a minor foreign body reaction. From 6 weeks on, the bending force needed to break the osteotomy was comparable to the bending force needed to break the control bone. The shear strength of the rods displayed only minor changes for the first 24 weeks. Subsequently, the rods rapidly lost their strength and at 48 weeks there was practically no shear strength left, which is ideal for healing of an osteotomy. The present investigation demonstrated, that absorbable. fibrillated SR-PLA96-rods can be used for the intramedullar fixation of simple cortical bone osteotomies in rabbits. These results have encouraged us to continue our studies with the fixation of experimental cortical bone osteotomies in larger species.

Synovial fluid studies in navicular disease.

The purpose of this study was to investigate biochemical changes in synovial fluid in navicular disease, and to establish if synovial fluid from the distal interphalangeal joint (DIP) could be used diagnostically to assess alterations in the synovial fluid of the navicular bursa. Cartilage oligomeric matrix protein (COMP), total glycosaminoglycans (GAG), hyaluronan (HA), metalloproteinases 2 and -9 (MMP-2 and MMP-9) and total protein (TP) levels were determined in synovial fluids obtained from 18 navicular bursae and 35 DIP -joints from animals suffering from navicular disease, and the same synovial structures in 16 joints of horses with no evidence of abnormalities involving the foot. To avoid dilution effects, GAG/COMP, HA/COMP, MMP-2/ COMP and MMP-9/COMP ratios were also calculated for different synovial cavities. There was a good correlation, for COMP, GAG, HA, MMP-2 and TP levels, between synovial fluid from the navicular bursa and fluid from the DIP -joint in healthy animals. However, in animals with navicular disease, only COMP levels showed no difference between the navicular bursal fluid and the DIP-joint fluid concentration. Thus, enabling the use of COMP to standardise other biochemical concentration measurements from the synovial joint fluids. In horses with navicular disease, there was a significantly lower absolute concentration of GAG, and a significantly lower GAG/COMP ratio, in the synovial fluid of the navicular bursa and the DIP-joint compared to synovial fluid from the same joints from healthy horses. In contrast, the absolute HA concentration and HA/ COMP, MMP-2/COMP and MMP-9/COMP ratios were higher in synovial fluid from the DIP-joint of horses with navicular disease, and MMP-2 and MMP-9 relative activity levels and MMP-2/COMP and MMP-9/ COMP ratios were increased in fluid from navicular bursae in horses with navicular disease when compared to a control group.