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2.
  • Aulin, C., et al. (författare)
  • Cartilage repair of experimentally 11 induced osteochondral defects in New Zealand White rabbits
  • 2013
  • Ingår i: Laboratory Animals. - : SAGE Publications. - 0023-6772 .- 1758-1117. ; 47:1, s. 58-65
  • Tidskriftsartikel (refereegranskat)abstract
    • Articular cartilage has a limited capacity for self-repair in adult humans, and methods used to stimulate regeneration often result in re-growth of fibrous cartilage, which has lower durability. No current treatment option can provide complete repair. The possibility of growth factor delivery into the joint for cartilage regeneration after injury would be an attractive treatment option. A full thickness osteochondral defect of 4 mm in diameter and 2 mm deep was created by mechanical drilling in the medial femoral condyle in 20 female adult New Zealand White rabbits. In an attempt to improve regeneration a hyaluronic hydrogel system, with or without bone morphogenetic protein-2 (BMP-2) was delivered intraarticularly. The contralateral joint defect was treated with saline as control. Throughout the study, rabbits were clinically examined and after 12 (n = 6) or 24 (n = 9) weeks, the rabbits were euthanized and the joints evaluated by histology. The defects healed with fibrocartilage like tissue, and the filling of the defects ranged from less than 25% to complete. The healing of the defects varied both inter- and intra-group wise. Treatment with hyaluronan gel with or without BMP-2 had no effect on cartilage regeneration compared with controls. Instead, severe ectopic bone formation was found in seven joints treated with BMP-2. In conclusion, the present study shows that neither treatment with hyaluronic gel alone, nor in combination with BMP-2, improves the healing of an induced cartilage defect in rabbits. It further shows that BMP-2 can induce ectopic bone formation, which severely affects the functionality of the joint.
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3.
  • Bengtsdotter, Emma, et al. (författare)
  • Neuromas at the castration site in geldings
  • 2019
  • Ingår i: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 0044-605X .- 1751-0147. ; 61
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Inguinal pain, unexplained hind limb lameness, back pain or behavioural problems in geldings could be attributable to painful neuromas that develop as a consequence of crushing and severing the testicular nerves during castration. The presence of neuroma in this anatomical location has never been reported, hence the knowledge of possible clinical relevance is limited. The aim of this study was to histologically investigate the testicular nerves at the castration site in geldings for the presence of neuromas. Proximal spermatic cord remnants were collected from 20 geldings admitted to routine post mortem examination for various reasons. The time of castration was unknown, but it had not been performed during the last year. Spermatic cord specimens were immersed in 10% formalin, trimmed, dehydrated, embedded in paraffin, sectioned and stained with haematoxylin and eosin (HE) for light microscopy. Identification of nerve tissue was done by immuno-localization of nerve specific enolase (NSE). Results Neuromas were found in 21 spermatic cords from 13 geldings and were bilateral in eight of the horses. The neuromas consisted of areas with small groups of non-neoplastic proliferations of peripheral neural tissue. The tissue included neurofilaments and Schwann cells, intermingled or surrounded with, epineural, perineural and endoneural fibrous tissue. The neural tissue immunostained positive with NSE. Conclusions This study showed neuromas of the remnant testicular nerves at the site of castration. Further studies are required to establish if these neuromas in the castration site are painful and if certain castration methods promote their formation. Future studies should also investigate the clinical consequence of these neuromas for the individual horse.
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4.
  • Bratt, Ewa-Lena, 1970, et al. (författare)
  • Continuing pregnancy following a prenatal diagnosis of a cardiac defect: What support do parents need?
  • 2015
  • Ingår i: Cardiology 2015. 18th Annual Update on Pediatroc and Congenital Cardiovascular Disease. Challenges and Dilemmas. Feb 11-15, 2015. Scottsdale, Arizona, US..
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Purpose To explore pregnant women´s/couples’ experiences of counseling and need for support during continued pregnancy following a prenatal diagnosis of congenital heart disease (CHD). Conceptual framework Couples choosing continued pregnancy need support from the time of prenatal diagnosis until delivery. Method Design: Qualitative study, using in-depth interviews 4-8 weeks after prenatal diagnosis. Setting: A tertiary center fetal cardiology unit in Sweden Sample: 12 pregnant women and their partners, consecutively recruited after a prenatal diagnosis of an isolated and significant cardiac defect in their fetus. Data analysis: Qualitative content analysis. Major findings The analysis resulted in four themes: Making the decision: Short waiting time for specialist evaluation together with clear, honest and straightforward information was essential. The importance of knowledge: Parents called for written information together with a high-quality regulated website with information about CHD. The importance of support: Continued and easy access, throughout pregnancy, to health care professionals, including a pediatric specialist nurse, was important. Other parents with similar experiences and social media were also valuable sources of support. Future and daily life: Practical and economical issues during the hospital stay and the initial period after the hospital stay were common concerns. Conclusion The results provided valuable knowledge of how to improve information and support during pregnancy. Short waiting time from first suspicion to definitive diagnosis and continued support throughout pregnancy emphasizing the role of the pediatric cardiology specialist nurse was important. Web-based information was warranted Clinical implications These results provide important information for a future intervention study of a structured follow-up program in collaboration between antenatal- and pediatric cardiac caregivers.
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  • Bratt, Ewa-Lena, 1970, et al. (författare)
  • Parental reactions, distress, and sense of coherence after prenatal versus postnatal diagnosis of complex congenital heart disease
  • 2019
  • Ingår i: Cardiology in the Young. - 1047-9511 .- 1467-1107. ; 29:11, s. 1328-1334
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: A diagnosis of congenital heart disease (CHD) in offspring triggers psychological distress in parents. Results of previous studies have been inconsistent regarding the psychological impact of a prenatal versus a postnatal diagnosis. The aim of this study was to evaluate the influence of the time of diagnosis on levels of parental distress. Methods: Pregnant women and their partners with a fetus diagnosed with complex CHD, parents of children with postnatally diagnosed CHD, and pregnant women and their partners with uncomplicated pregnancies were invited to participate. Data were collected during pregnancy and 2–6 months after delivery using the Hospital Anxiety and Depression Scale, sense of coherence, life satisfaction, and Dyadic Adjustment Scale. Results: During pregnancy, the prenatal group scored lower sense of coherence compared to controls (p=0.044). Postnatally the prenatal group scored lower on sense of coherence compared to the postnatal group and controls (p=0.001; p=0.001). Postnatally, the prenatal and postnatal groups had higher levels of anxiety compared to controls (p=0.025; p=0.0003). Life satisfaction was lower in the prenatal group compared to that in the postnatal group and in controls (p=0.000; p=0.0004). Conclusion: Parents with a prenatal diagnosis of CHD in offspring report a low sense of coherence already during pregnancy which decreased further at follow-up. The same group reported a lower satisfaction with life compared to parents of a child with postnatal diagnosis of CHD and parents of a healthy child. This motivates further efforts to improve counselling and support during pregnancy and for parents after a prenatal diagnosis.
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6.
  • Bratt, Ewa-Lena, 1970, et al. (författare)
  • Parent’s experiences of counselling and their need for support following a prenatal diagnosis of congenital heart disease - a qualitative study in a Swedish context
  • 2015
  • Ingår i: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Prenatal screening for foetal cardiac abnormalities has been increasingly practiced in Sweden during the last 25 years. A prenatal diagnosis may have medical benefits but may also cause sustained parental psychological distress. The aim of this study was to explore pregnant women’s, and their partner’s, experiences of counselling and need for support during continued pregnancy following a prenatal diagnosis of a cardiac defect. A second aim was to use this information to propose a structured follow-up programme for continued support after the first counselling. Method: Design: Qualitative study, using interviews performed 5–9 weeks after a prenatal diagnosis of congenital heart disease. Setting: A tertiary foetal cardiology unit in Sweden Sample: Six pregnant women and their 6 partners, consecutively recruited after a prenatal diagnosis of an isolated and significant cardiac defect. Data analysis: Qualitative content analysis. Results: The analysis resulted in three themes. 1/ Counselling and making a decision - the importance of knowledge and understanding: Short waiting time for specialist evaluation together with clear and straightforward information was essential. Parents called for written information together with a high-quality website with relevant information about congenital heart disease. 2/ Continued support during pregnancy: Continued and easy access to health care professionals, including a paediatric specialist nurse, throughout pregnancy, was important. Contact with couples with similar experiences and social media were also considered valuable sources of support. 3/ Next step – the near future: Practical and economical issues during the postnatal hospital stay and the initial period following the hospital stay were common concerns. Conclusions: The following aspects should be considered in a structured follow up program during pregnancy after a prenatal diagnosis of CHD; written information, access to a safe web-site with information of high quality in their native language, support from parents with similar experiences and continued contact with a specialist liaison nurse with experience of paediatric cardiology.
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  • Carlström, Maria, et al. (författare)
  • Genetic support for the role of the NLRP3 inflammasome in psoriasis susceptibility
  • 2012
  • Ingår i: Experimental dermatology. - : John Wiley and Sons. - 0906-6705 .- 1600-0625. ; 21:12, s. 932-937
  • Tidskriftsartikel (refereegranskat)abstract
    • NACHT leucine-rich repeat- and PYD-containing (NLRP)3 protein controls the inflammasome by regulating caspase-1 activity and interleukin (IL)-1 beta processing. The contribution of IL-1 beta in the pathogenesis of psoriasis is well recognized. Polymorphisms in NLRP3 and caspase recruitment domaincontaining protein (CARD)8, a negative regulator of caspase-1 activity, have been associated with susceptibility to common inflammatory diseases, such as Crohns disease and rheumatoid arthritis. To investigate the role for genetic variants in the NLRP3 inflammasome in psoriasis susceptibility. In a patient sample comprising 1988 individuals from 491 families and 1002 healthy controls, genotypes for four selected single-nucleotide polymorphisms (SNPs) in NLRP3 (three SNPs) and CARD8 (one SNP) were determined by TaqMan (R) Allelic Discrimination. Using the transmission disequilibrium test (TDT), a significant increase in the transmission of the NLRP3 rs10733113G genotype to a subgroup of patients with more widespread psoriasis was demonstrated (P = 0.015). Using logistic regression analysis in 741 patients with psoriasis and 1002 controls, the CARD8 rs2043211 genotype was significantly different in cases and controls in overall terms [OR 1.3 (1.11.5), P = 0.004] and for both genders. Our data support the hypothesis that the inflammasome plays a role in psoriasis susceptibility.
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  • Cornell Kärnekull, Stina, et al. (författare)
  • Long-Term Memory for Odors : Influences of Familiarity and Identification Across 64 Days
  • 2015
  • Ingår i: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 40:4, s. 259-267
  • Tidskriftsartikel (refereegranskat)abstract
    • Few studies have investigated long-term odor recognition memory, although some early observations suggested that the forgetting rate of olfactory representations is slower than for other sensory modalities. This study investigated recognition memory across 64 days for high and low familiar odors and faces. Memory was assessed in 83 young participants at 4 occasions; immediate, 4, 16, and 64 days after encoding. The results indicated significant forgetting for odors and faces across the 64 days. The forgetting functions for the 2 modalities were not fundamentally different. Moreover, high familiar odors and faces were better remembered than low familiar ones, indicating an important role of semantic knowledge on recognition proficiency for both modalities. Although odor recognition was significantly better than chance at the 64 days testing, memory for the low familiar odors was relatively poor. Also, the results indicated that odor identification consistency across sessions, irrespective of accuracy, was positively related to successful recognition.
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  • Docherty-Skogh, Ann-Charlott, et al. (författare)
  • Bone morphogenetic protein-2 delivered by hyaluronan-based hydrogel induces massive bone formation and healing of cranial defects in minipigs
  • 2010
  • Ingår i: Plastic and reconstructive surgery (1963). - 0032-1052 .- 1529-4242. ; 125:5, s. 1383-1392
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Reconstruction of large craniofacial bone defects is a challenge using bone transplants or alloplastic materials. The use of bone morphogenetic protein (BMP)-2 together with a suitable carrier is an attractive option that may facilitate new bone formation. The authors have developed a hydrogel that is formed in situ by the cross-linking of multifunctional hyaluronic acid and polyvinyl alcohol derivatives mixed with hydroxyapatite nanoparticles, in the presence of BMP-2. The aim of this study was to evaluate the suitability of the hydrogel as a carrier for BMP-2 in repairing critical size cranial defects in a minipig model. Methods: Cranial defects (2 × 4 cm) were created in 14 minipigs. The experimental groups were as follows: group 1, craniotomy and application of 5 ml of hydrogel with 1.25 mg of BMP-2 (n = 6); group 2, craniotomy and application of 5 ml of hydrogel without BMP-2 (n = 6); and group 3, craniotomy with no further treatment (n = 2). Results: After 3 months, computed tomographic and histologic examinations were performed. There was spontaneous ossification in the untreated group, but the healing was incomplete. The hydrogel alone demonstrated no further effects. The addition of 1.25 mg of BMP-2 to the hydrogel induced a greater than 100 percent increase in bone volume (p = 0.003) and complete healing of the defects. Histologic examination revealed compact lamellar bone in the BMP group without intertrabecular fibrous tissue, as was seen in the other groups. The hydrogel was resorbed completely within 3 months and, importantly, caused no inflammatory reaction. Conclusion: The injectable hydrogel may be favorable as a BMP-2 carrier for bone reconstruction.
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13.
  • Ekman, Stina (författare)
  • An Update on the Pathogenesis of Osteochondrosis
  • 2015
  • Ingår i: Veterinary Pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217. ; 52, s. 785-802
  • Forskningsöversikt (refereegranskat)abstract
    • Osteochondrosis is defined as a focal disturbance in endochondral ossification. The cartilage superficial to an osteochondrosis lesion can fracture, giving rise to fragments in joints known as osteochondrosis dissecans (OCD). In pigs and horses, it has been confirmed that the disturbance in ossification is the result of failure of the blood supply to epiphyseal growth cartilage and associated ischemic chondronecrosis. The earliest lesion following vascular failure is an area of ischemic chondronecrosis at an intermediate depth of the growth cartilage (osteochondrosis latens) that is detectable ex vivo, indirectly using contrast-enhanced micro-and conventional computed tomography (CT) or directly using adiabatic T1 rho magnetic resonance imaging. More chronic lesions of ischemic chondronecrosis within the ossification front (osteochondrosis manifesta) are detectable by the same techniques and have also been followed longitudinally in pigs using plain CT. The results confirm that lesions sometimes undergo spontaneous resolution, and in combination, CT and histology observations indicate that this occurs by filling of radiolucent defects with bone from separate centers of endochondral ossification that form superficial to lesions and by phagocytosis and intramembranous ossification of granulation tissue that forms deep to lesions. Research is currently aimed at discovering the cause of the vascular failure in osteochondrosis, and studies of spontaneous lesions suggest that failure is associated with the process of incorporating blood vessels into the advancing ossification front during growth. Experimental studies also show that bacteremia can lead to vascular occlusion. Future challenges are to differentiate between causes of vascular failure and to discover the nature of the heritable predisposition for osteochondrosis.
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  • Ekman, Stina (författare)
  • Articular osteochondrosis: a comparison of naturally-occurring human and animal disease.
  • 2013
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584 .- 1522-9653. ; 21, s. 1638-1647
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND: Osteochondrosis (OC) is a common developmental orthopedic disease affecting both humans and animals. Despite increasing recognition of this disease among children and adolescents, its pathogenesis is incompletely understood because clinical signs are often not apparent until lesions have progressed to end-stage, and examination of cadaveric early lesions is not feasible. In contrast, both naturally-occurring and surgically-induced animal models of disease have been extensively studied, most notably in horses and swine, species in which OC is recognized to have profound health and economic implications. The potential for a translational model of human OC has not been recognized in the existing human literature. OBJECTIVE: The purpose of this review is to highlight the similarities in signalment, predilection sites and clinical presentation of naturally-occurring OC in humans and animals and to propose a common pathogenesis for this condition across species. STUDY DESIGN: Review. METHODS: The published human and veterinary literature for the various manifestations of OC was reviewed. Peer-reviewed original scientific articles and species-specific review articles accessible in PubMed (US National Library of Medicine) were eligible for inclusion. RESULTS: A broad range of similarities exists between OC affecting humans and animals, including predilection sites, clinical presentation, radiographic/MRI changes, and histological appearance of the end-stage lesion, suggesting a shared pathogenesis across species. CONCLUSION: This proposed shared pathogenesis for OC between species implies that naturally-occurring and surgically-induced models of OC in animals may be useful in determining risk factors and for testing new diagnostic and therapeutic interventions that can be used in humans. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved
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15.
  • Ekman, Stina (författare)
  • Broskets Biokemi och Morfologi
  • 2014
  • Ingår i: Broskskador och artros. - 9789144072159 ; , s. 9-18
  • Bokkapitel (populärvet., debatt m.m.)
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16.
  • Ekman, Stina (författare)
  • Cartilage canals in the distal intermediate ridge of the tibia of fetuses and foals are surrounded by different types of collagen
  • 2017
  • Ingår i: Journal of Anatomy. - : Wiley. - 0021-8782 .- 1469-7580. ; 231, s. 615-625
  • Tidskriftsartikel (refereegranskat)abstract
    • Some epiphyseal growth cartilage canals are surrounded by a ring of hypereosinophilic matrix consisting of collagen type I. Absence of the collagen type I ring may predispose canal vessels to failure and osteochondrosis, which can lead to fragments in joints (osteochondrosis dissecans). It is not known whether the ring develops in response to programming or biomechanical force. The distribution that may reveal the function of the ring has only been described in the distal femur of a limited number of foals. It is also not known which cells are responsible for producing the collagen ring. The aims of the current study were to examine fetuses and foals to infer whether the ring forms in response to biomechanical force or programming, to describe distribution and to investigate which cell type produces the ring. The material consisted of 46 fetuses and foals from 293days of gestation to 142days old, of both sexes and different breeds, divided into three groups, designated the naive group up to and including the day of birth, the adapting group from 2days up to and including 14days old, and the loaded group from 15days and older. The distal tibia was sawn into parasagittal slabs and the cranial half of the central slab from the intermediate ridge was examined by light microscopy and immunohistochemical staining for collagen type I. Presence, completeness and location of the collagen ring was compared, as was the quantity of perivascular mesenchymal cells. An eosinophilic ring present on HE-stained sections was seen in every single fetus and foal examined, which corresponded to collagen type I in immunostained sections. A higher proportion of cartilage canals were surrounded by an eosinophilic ring in the naive and adapting groups at 73 and 76%, respectively, compared with the loaded group at 51%. When considering only patent canals, the proportion of canals with an eosinophilic ring was higher in the adapting and loaded than the naive group of foals. The ring was present around 90 and 81% of patent canals in the deep and middle layers, respectively, compared with 58% in the superficial layer, and the ring was more often complete around deep compared with superficial canals. The ring was absent or partial around chondrifying canals. When an eosinophilic ring was present around patent canals, it was more common for the canal to contain one or more layers of perivascular mesenchymal cells rather than few to no layers. It was also more common for the collagen ring to be more complete around canals that contained many as opposed to few mesenchymal cells. In conclusion, the proportion of cartilage canals that had an eosinophilic ring was similar in all three groups of fetuses and foals, indicating that the presence of the collagen ring was mostly programmed, although some adaptation was evident. The ring was more often present around deep, compared with superficial canals, indicating a role in preparation for ossification. The collagen ring appeared to be produced by perivascular mesenchymal cells.
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17.
  • Ekman, Stina (författare)
  • Early Lesions of Articular Osteochondrosis in the Distal Femur of Foals
  • 2011
  • Ingår i: Veterinary Pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217. ; 48, s. 1165-1175
  • Tidskriftsartikel (refereegranskat)abstract
    • Failure of cartilage canal blood supply to epiphyseal growth cartilage has been implicated in the pathogenesis of articular osteochondrosis in horse and other animal species
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18.
  • Ekman, Stina, et al. (författare)
  • Effect of circadian rhythm, age, training and acute lameness on serum concentrations of cartilage oligomeric matrix protein (COMP) neo-epitope in horses
  • 2019
  • Ingår i: Equine Veterinary Journal. - : Wiley. - 0425-1644 .- 2042-3306. ; 51:5, s. 674-680
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Molecular serum markers that can identify early reversible osteoarthritis (OA) in horses are lacking. Objectives We studied serum concentrations of a novel cartilage oligomeric matrix protein (COMP) neo-epitope in horses subjected to short-term exercise and with acute lameness. The effects of circadian rhythm and age were also evaluated. Study design Longitudinal studies in healthy horses and cross-sectional comparison of lame and non-lame horses. Methods Sera were collected from five horses before and after short-term interval exercise and during full-day box rest. Sera from 32 acutely lame horses were used to evaluate age-related effects. Independent samples from control horses (n = 41) and horses with acute lameness (n = 71) were included. COMP neo-epitope concentrations were analysed using custom-developed inhibition ELISAs validated for equine serum. The presence of COMP neo-epitope was delineated in healthy and osteoarthritic articular cartilage with immunohistochemistry. Results COMP neo-epitope concentrations decreased after speed training but returned to baseline levels post-exercise. No correlations between age and serum COMP neo-epitope concentrations were found (r = 0.0013). The mean (+/- s.d.) serum concentration of COMP neo-epitope in independent samples from non-lame horses was 0.84 +/- 0.38 mu g/mL, and for lame horses was 5.24 +/- 1.83 mu g/mL (P<0.001). Antibodies against COMP neo-epitope did not stain normal articular cartilage, but intracytoplasmic staining was found in superficial chondrocytes of mild OA cartilage and in the extracellular matrix of moderately osteoarthritic cartilage. Main limitations ELISA was based on polyclonal antisera rather than a monoclonal antibody. There is a sex and breed bias within the groups of horses, also it could have been of value to include horses with septic arthritis and tendonitis and investigated joint differences. Conclusions This COMP neo-epitope can be measured in sera, and results indicate that it could be a biomarker for pathologic fragmentation of cartilage in connection with acute joint lameness.
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22.
  • Ekman, Stina (författare)
  • Juvenile osteochondritis dissecans of the knee is a result of failure of the blood supply to growth cartilage and osteochondrosis
  • 2018
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584 .- 1522-9653. ; 26, s. 1691-1698
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Juvenile osteochondritis dissecans (JOCD) is similar to osteochondrosis dissecans (OCD) in animals, which is the result of failure of the cartilage canal blood supply, ischemic chondronecrosis and delayed ossification, or osteochondrosis. The aim of the current study was to determine if osteochondrosis lesions occur at predilection sites for JOCD in children. Method: Computed tomographic (CT) scans of 23 knees (13 right, 10 left) from 13 children (9 male, 4 female; 1 month to 11 years old) were evaluated for lesions consisting of focal, sharply demarcated, uniformly hypodense defects in the ossification front. Histological validation was performed in 11 lesions from eight femurs. Results: Thirty-two lesions consisting of focal, uniformly hypodense defects in the ossification front were identified in the CT scans of 14 human femurs (7 left, 7 right; male, 7–11 years old). Defects corresponded to areas of ischemic chondronecrosis in sections from all 11 histologically validated lesions. Intra-cartilaginous secondary responses comprising proliferation of adjacent chondrocytes and vessels were detected in six and two lesions, whereas intra-osseous responses including accumulation of chondroclasts and formation of granulation tissue occurred in 10 and six lesions, respectively. One CT cyst-like lesion contained both a pseudocyst and a true cyst in histological sections. Conclusion: Changes identical to osteochondrosis in animals were detected at predilection sites for JOCD in children, and confirmed to represent failure of the cartilage canal blood supply and ischemic chondronecrosis in histological sections.
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23.
  • Ekman, Stina (författare)
  • Local Morphological Response of the Distal Femoral Articular–Epiphyseal Cartilage Complex of Young Foals to Surgical Stab Incision and Potential Relevance to Cartilage Injury and Repair in Children
  • 2013
  • Ingår i: Cartilage. - : SAGE Publications. - 1947-6035 .- 1947-6043. ; 4, s. 239-248
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Describe the local morphological response of the articular-epiphyseal cartilage complex to surgical stab incision in the distal femur of foals, with emphasis on the relationship between growth cartilage injury, enchondral ossification, and repair. Design: Nine foals were induced into general anesthesia at the age of 13 to 15 days. Four full-thickness stab incision defects were created in the cartilage on the lateral aspect of the lateral trochlear ridge of the left distal femur. Follow-up examination was carried out from 1 to 49 days postoperatively, including examination of intact bones, sawed slabs, and histological sections. Results: Incision defects filled with cells displaying fibroblast-, chondrocyte-, and osteoblast-like characteristics, potentially validating the rationale behind the drilling of stable juvenile osteochondritis dissecans lesions in children. Incisions induced necrosis within the cartilage on the margins at all depths of the defects. Sharp dissection may therefore be contraindicated in cartilage repair in young individuals. Incisions caused a focal delay in enchondral ossification in 2 foals, apparently related to the orientation of the incision defect relative to the direction of ossification. Defects became progressively surrounded by subchondral bone, in which granulation tissue containing clasts and foci of osteoblast-like cells was observed. Continued enchondral ossification was therefore likely to result in healing of uncomplicated defects to morphologically normal bone. Conclusions: Epiphyseal growth cartilage injury had the potential to exert a negative effect on enchondral ossification. Enchondral ossification exerted a beneficial effect on repair. This relationship warrants consideration in future studies of cartilage injury and repair within the articular-epiphyseal cartilage complex of all species.
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24.
  • Ekman, Stina (författare)
  • Observational Study Design in Veterinary Pathology, Part 1: Study Design
  • 2018
  • Ingår i: Veterinary Pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217.
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Observational studies are the basis for much of our knowledge of veterinary pathology and are highly relevant to the daily practice of pathology. However, recommendations for conducting pathology-based observational studies are not readily available. In part 1 of this series, we offer advice on planning and conducting an observational study with examples from the veterinary pathology literature. Investigators should recognize the importance of creativity, insight, and innovation in devising studies that solve problems and fill important gaps in knowledge. Studies should focus on specific and testable hypotheses, questions, or objectives. The methodology is developed to support these goals. We consider the merits and limitations of different types of analytic and descriptive studies, as well as of prospective vs retrospective enrollment. Investigators should define clear inclusion and exclusion criteria and select adequate numbers of study subjects, including careful selection of the most appropriate controls. Studies of causality must consider the temporal relationships between variables and the advantages of measuring incident cases rather than prevalent cases. Investigators must consider unique aspects of studies based on archived laboratory case material and take particular care to consider and mitigate the potential for selection bias and information bias. We close by discussing approaches to adding value and impact to observational studies. Part 2 of the series focuses on methodology and validation of methods.
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25.
  • Ekman, Stina (författare)
  • Observational Study Design in Veterinary Pathology, Part 2: Methodology
  • 2018
  • Ingår i: Veterinary Pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217. ; 55, s. 774-785
  • Annan publikation (refereegranskat)abstract
    • Observational studies are a basis for much of our knowledge of veterinary pathology, yet considerations for conducting pathology-based observational studies are not readily available. In part 1 of this series, we offered advice on planning and carrying out an observational study. Part 2 of the series focuses on methodology. Our general recommendations are to consider using already-validated methods, published guidelines, data from primary sources, and quantitative analyses. We discuss 3 common methods in pathology research-histopathologic scoring, immunohistochemistry, and polymerase chain reaction-to illustrate principles of method validation. Some aspects of quality control include use of clear objective grading criteria, validation of key reagents, assessing sample quality, determining specificity and sensitivity, use of technical and biologic negative and positive controls, blinding of investigators, approaches to minimizing operator-dependent variation, measuring technical variation, and consistency in analysis of the different study groups. We close by discussing approaches to increasing the rigor of observational studies by corroborating results with complementary methods, using sufficiently large numbers of study subjects, consideration of the data in light of similar published studies, replicating the results in a second study population, and critical analysis of the study findings.
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26.
  • Ekman, Stina (författare)
  • Osteochondrosis Can Lead to Formation of Pseudocysts and True Cysts in the Subchondral Bone of Horses
  • 2015
  • Ingår i: Veterinary Pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217. ; 52, s. 862-872
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteochondrosis arises as a result of focal failure of the blood supply to growth cartilage. The current aim was to examine the pathogenesis of pseudocysts and true cysts in subchondral bone following failure of the blood supply to the articular-epiphyseal cartilage complex in horses. Cases were recruited based on identification of lesions (n = 17) that were considered likely to progress to or to represent pseudocysts or true cysts in epiphyseal bone in histological sections and included 10 horses ranging in age from 48 days to 5 years old. Cases comprised 3 warmbloods, 3 Standardbreds, 1 Quarter horse and 1 Arabian with spontaneous lesions and 2 Fjord ponies with experimentally induced lesions. Seven lesions consisted of areas of ischemic chondronecrosis and were compatible with pseudocysts. Two lesions were located at intermediate depth in epiphyseal growth cartilage, 2 lesions were located in the ossification front, 2 lesions were located in epiphyseal bone and 1 lesion was located in the metaphyseal growth plate (physis). Ten lesions contained dilated blood vessels and were compatible with true cysts. In 2 lesions the dilated blood vessels were located within the lumina of failed cartilage canals. In the 8 remaining lesions areas of ischemic chondronecrosis were associated with granulation tissue in the subjacent bone and dilated vessels were located within this granulation tissue. Failure of the blood supply and ischemic chondronecrosis can lead to formation of pseudocysts or dilatation of blood vessels and formation of true cysts in the epiphyseal bone of horses.
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27.
  • Ekman, Stina, et al. (författare)
  • Osteochondrosis in the central and third tarsal bones of young horses
  • 2024
  • Ingår i: Veterinary Pathology. - 0300-9858 .- 1544-2217. ; 61, s. 74 - 87
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, the central and third tarsal bones of 23 equine fetuses and foals were examined using micro-computed tomography. Radiological changes, including incomplete ossification and focal ossification defects interpreted as osteochondrosis, were detected in 16 of 23 cases. The geometry of the osteochondrosis defects suggested they were the result of vascular failure, but this requires histological confirmation. The study aim was to examine central and third tarsal bones from the 16 cases and to describe the tissues present, cartilage canals, and lesions, including suspected osteochondrosis lesions. Cases included 9 males and 7 females from 0 to 150 days of age, comprising 11 Icelandic horses, 2 standardbred horses, 2 warmblood riding horses, and 1 coldblooded trotting horse. Until 4 days of age, all aspects of the bones were covered by growth cartilage, but from 105 days, the dorsal and plantar aspects were covered by fibrous tissue undergoing intramembranous ossification. Cartilage canal vessels gradually decreased but were present in most cases up to 122 days and were absent in the next available case at 150 days. Radiological osteochondrosis defects were confirmed in histological sections from 3 cases and consisted of necrotic vessels surrounded by ischemic chondronecrosis (articular osteochondrosis) and areas of retained, morphologically viable hypertrophic chondrocytes (physeal osteochondrosis). The central and third tarsal bones formed by both endochondral and intramembranous ossification. The blood supply to the growth cartilage of the central and third tarsal bones regressed between 122 and 150 days of age. Radiological osteochondrosis defects represented vascular failure, with chondrocyte necrosis and retention, or a combination of articular and physeal osteochondrosis.
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28.
  • Ekman, Stina (författare)
  • Septic Arthritis/Osteomyelitis May Lead to Osteochondrosis-Like Lesions in Foals
  • 2018
  • Ingår i: Veterinary Pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217. ; 55, s. 693-702
  • Tidskriftsartikel (refereegranskat)abstract
    • Failure of the cartilage canal blood supply leads to ischemic chondronecrosis which causes osteochondrosis, and osteochondral lesions. Osteochondrosis is a disease with a heritable component and usually occurs under aseptic conditions. Because bacteria can bind to growth cartilage and disrupt the blood supply in pigs and chickens, we considered whether this might play a role in development of equine osteochondrosis. The aim of this study was to examine whether bacteria are present in canals in the growth cartilage of foals with septic arthritis/osteomyelitis, and whether this is associated with osteochondrosis. The material consisted of 7 foals aged 9-117 days euthanized because of septic arthritis/osteomyelitis. The 7 cases had 16 lesions in growth cartilage that were evaluated histologically. Bacteria were present in cartilage canals in foals with septic arthritis/osteomyelitis. Portions of necrotic canals adjacent to bacteria frequently contained neutrophils, termed acute septic canals; or granulation tissue with neutrophils, termed chronic septic canals. Acute and chronic septic canals were associated with ischemic chondronecrosis in the articular-epiphyseal cartilage complex (AECC) of 5 cases and in the physis of 2 cases, and ossification was focally delayed in 5 of those 7 cases. Lesions occurred with and without adjacent osteomyelitis. Bacteria were present in cartilage canals and were associated with focal chondronecrosis in both the AECC and the physis. This establishes sepsis as a plausible cause of some osteochondral lesions in horses. It is recommended that horses with sepsis-related osteochondral lesions may be used for breeding without increasing the prevalence of OCD-predisposing genes in the population.
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29.
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30.
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31.
  • Engelsen Etterlin, Pernille, et al. (författare)
  • Effects of free-range and confined housing on joint health in a herd of fattening pigs
  • 2014
  • Ingår i: BMC Veterinary Research. - : Springer Science and Business Media LLC. - 1746-6148. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Free-range housing, in which pigs have access to both indoor and outdoor areas, is mandatory in organic pig production in Europe, but little is known about the effects of this housing on joint health in pigs. A high level of joint condemnations at slaughter has been reported in organic free-range pigs in Sweden, compared with pigs raised in conventional confined housing. We hypothesised that biomechanical forces imposed on the joints of pigs that range freely promote the development of osteochondrosis and lead to joint condemnation. We compared the prevalence of osteochondrosis and other joint lesions (e.g. arthritis, traumatic) in the elbow and hock joints of 91 crossbred Hampshire (Yorkshire x Landrace) fattening pigs that were housed in a free-range indoor/outdoor system with that in 45 pigs housed in confined indoor pens.Results: A larger proportion of free-range than confined pigs had osteochondrosis in the elbow joints (69 vs. 50%, p < 0.05), and a higher proportion of these joints in free-range pigs showed moderate or severe lesions (33 vs. 16%, p < 0.05). The free-range pigs also showed a higher prevalence of osteochondrosis in the hock joints (83 vs. 62%, p < 0.05) and a larger proportion of these joints had moderate or severe lesions (69 vs. 33%, p < 0.001). At slaughter, 4.2% of the free-range pigs had condemned joints, all of which showed severe osteochondrosis, while no joints of confined pigs were condemned.Conclusions: In this experiment the prevalence of osteochondrosis in the elbow and the hock was higher, and lesions were more severe, in free-range than in confined pigs, suggesting that free-range housing increases the risk of acquiring osteochondrosis. Increased biomechanical stress to vulnerable joint structures may be the mechanism behind this effect, however more studies are needed to verify these results. This study suggests that modification of housing, and breeding for joints that are more adapted to free-range movement may be needed in free-range pig production. Severe osteochondrosis is a cause of joint condemnation, but the condemnation rate at slaughter underestimates the actual frequency of joint lesions and hence is a poor assessment of joint health.
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32.
  • Engelsen Etterlin, Pernille, et al. (författare)
  • Osteochondrosis, but not lameness, is more frequent among free-range pigs than confined herd-mates
  • 2015
  • Ingår i: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 0044-605X .- 1751-0147. ; 57
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Organic pig production is expanding and amongst the objectives of organic farming are enhancing animal health and welfare. However, some studies have reported a higher prevalence of lameness and joint condemnation at slaughter in free-range/organic pigs than in conventionally raised pigs. Organic slaughter pigs have free-range housing in which indoor and outdoor access is compulsory, while in conventional farming the pigs are commonly confined to indoor pens. The present study evaluated the effects of free-range and confined housing on lameness prevalence in a herd of 106 finisher pigs, and whether osteochondrosis and Erysipelothrix rhusiopathiae associated arthritis influences these effects. We also evaluated the association between clinical lameness during the rearing period and joint condemnations at slaughter. Results: Seventy free-range and 36 confined housed fattener pigs were scored for their gait twice during the rearing period and 848 joints were evaluated post mortem. Osteochondrosis was more frequent among free-range than confined pigs (P < 0.05), and when present it was also more severe (P < 0.001). Pigs with more numerous and more severe osteochondral lesions had their gait affected more than did pigs with fewer such lesions (P < 0.05). Hence it was a paradox that we did not detect more lameness among the free-range pigs than the confined pigs. E. rhusiopathiae associated arthritis was not diagnosed. The association between gait remarks/clinical lameness and joint condemnations at slaughter was not significant. Conclusions: The results indicate that free-range housing may have both positive and negative effects on locomotory traits. Free-range pigs may be less clinically affected by osteochondrosis than are confined pigs. One explanation for this effect may be strengthening of joint supportive tissue and pain relief promoted by exercise. Visual gait scoring missed serious joint lesions that probably were harmful to the pigs, and should therefore not be used as a sole indicator of joint/leg health in welfare inspection of pigs. The association between gait scores and joint condemnation appeared to be poor. This study was limited to one herd, and so more and larger studies on the effects of free-range housing on lameness severity and osteochondrosis development in pigs are recommended.
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33.
  • Engelsen Etterlin, Pernille, et al. (författare)
  • Osteochondrosis, Synovial Fossae, and Articular Indentations in the Talus and Distal Tibia of Growing Domestic Pigs and Wild Boars
  • 2017
  • Ingår i: Veterinary pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217. ; 54:3, s. 445-456
  • Tidskriftsartikel (refereegranskat)abstract
    • Articular osteochondrosis (OC) often develops in typical locations within joints, and the characterization of OC distribution in the pig tarsus is incomplete. Prevalence of OC is high in domestic pigs but is presumed to be low in wild boars. Postmortem and computed tomography (CT) examinations of the talus and distal tibia from 40 domestic pigs and 39 wild boars were evaluated for the locations and frequencies of OC, synovial fossae, and other articular indentations, and frequency distribution maps were made. All domestic pigs but only 5 wild boars (13%) had OC on the talus. In domestic pigs, OC consistently affected the axial aspect of the medial trochlea tali in 11 (28%) joints and the distomedial talus in 26 (65%) joints. In wild boars, all OC lesions consistently affected the distomedial talus. On the articular surface of the distal tibia, all domestic pigs and 34 wild boars (87%) had synovial fossae and 7 domestic pigs (18%) had superficial cartilage fibrillation opposite an OC lesion (kissing lesion). Other articular indentations occurred in the intertrochlear groove of the talus in all domestic pigs and 13 wild boars (33%) and were less common on the trochlea tali. The prevalence of tarsal OC in wild boars is low. In domestic pigs and wild boars, OC is typically localized to the distomedial talus and in domestic pigs also to the medial trochlea tali. Further investigations into the reasons for the low OC prevalence in wild boars may help in developing strategies to reduce OC incidence in domestic pigs.
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34.
  • Frostadottir, Drifa, et al. (författare)
  • Cold sensitivity, functional disability and predicting factors after a repaired digital nerve injury
  • 2022
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate self-reported cold sensitivity and functional disability after a repaired digital nerve injury. We identified 3204 individuals operated with digital nerve repair in the Swedish national quality registry for hand surgery (HAKIR). Patient-reported symptoms, including cold sensitivity and perceived disability, were examined using two questionnaires (HQ-8 and QuickDASH), three and 12 months postoperatively. Patients with diabetes (n = 48; 3%) were identified in the Swedish National Diabetes Register (NDR). Cold sensitivity (scored 0–100) was the most prominent symptom among 1553 included individuals (998 men, 555 women; median age 41 [IQR 27–54] years). In the regression analysis, flexor tendon injury, hand fracture and injury to multiple structures predicted worsened cold sensitivity (6.9, 15.5 and 25.0 points; p = 0.005, 0.046 and < 0.001) at 12 months. Individuals with moderate (30–70) and severe (> 70) cold sensitivity had higher QuickDASH scores at three and 12 months postoperatively than individuals with mild cold sensitivity (6.0 and 5.5; 19.8 and 21.0 points; p = 0.001). Flexor tendon injury, injuries to multiple structures and diabetes had significant effect on QuickDASH scores at three, but not at 12, months postoperatively. Cold sensitivity is common after a digital nerve repair and impacts self-reported disability. A concomitant injury, particularly multiple injuries, predicts postoperative cold sensitivity.
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35.
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36.
  • Hansson, Kerstin, et al. (författare)
  • A new ultrasound technique to evaluate the soundness of bovine stifle joints in beef bulls.
  • 2019
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • In beef bulls, a common cause of lameness is osteochondrosis with lateral trochlear ridge of distal femur as predilection site. The aim of the study was to investigate the possibility of using a basic portable ultrasound equipment in stifle examinations of bulls in order to potentially add the protocol to bull breeding soundness evaluation for field conditions.
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37.
  • Hedenqvist, Patricia, et al. (författare)
  • Carprofen neither reduces postoperative facial expression scores in rabbits treated with buprenorphine nor alters long term bone formation after maxillary sinus grafting
  • 2016
  • Ingår i: Research in Veterinary Science. - : Elsevier BV. - 0034-5288 .- 1532-2661. ; 107, s. 123-131
  • Tidskriftsartikel (refereegranskat)abstract
    • In connection with bilateral maxillary sinus augmentation, the acute effects of the nonsteroidal anti-inflammatory drug carprofen on facial expressions and long-term effects on bone formation were evaluated in 18 male New Zealand White rabbits. A 10 x 10 mm bone window was drilled in the maxilla, the sinus membrane elevated and a titanium mini-implant inserted. One of two test materials was randomly inserted unilaterally and bovine bone chips (control) on the contralateral side in the created space. Rabbits were randomly allocated to receive buprenorphine plus carprofen (n = 9) or buprenorphine plus saline (n = 9) postoperatively. Buprenorphine was administered subcutaneously every 6 h for 3 days in a tapered dose (0.05-0.01 mg/kg) and carprofen (5 mg/kg) or saline administered subcutaneously 1 h before, and daily for 4 days postoperatively. To assess pain, clinical examination, body weight recording and scoring of facial expressions from photos taken before, and 6-13 h after surgery were performed. Twelve weeks after surgery the rabbits were euthanized and sections of maxillary bones and sinuses were analysed with histomorphometry and by qualitative histology. Carprofen had no effect on mean facial expression scores, which increased from 0.0 to 3.6 (carprofen) and 43 (saline), of a maximum of 8.0. Neither did carprofen have an effect on bone formation or implant incorporation, whereas the test materials had. In conclusion, treatment with 5 mg/kg carprofen once daily for 5 days did not reduce facial expression scores after maxillary sinus augmentation in buprenorphine treated rabbits and did not affect long term bone formation.
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38.
  • Hedenqvist, Patricia, et al. (författare)
  • The effect of housing environment on bone healing in a critical radius defect in New Zealand White rabbits
  • 2020
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 15:5
  • Tidskriftsartikel (refereegranskat)abstract
    • In animal studies on bone healing, the effect of housing space and physical activity are seldom taken into account. Bone formation was evaluated in New Zealand White rabbits (mean ± SEM BW: 3.9 ± 0.11 kg) with a critical bone defect after 12 weeks of rehabilitation in pair-housing in 3 m2 large floor pens (Floor, n = 10) or standard single housing in 0.43 m2 cages (Cage, n = 10). In the randomised full-factorial study, a bone replica of calcium phosphate cement (CPC, n = 10) or autologous bone (AB, n = 10) was implanted in the unilateral 20 mm radius defect. Post-mortem, the oxidative capacity was measured by citrate synthase (CS) activity in M. quadriceps and the defect filling volume and density evaluated by microcomputer tomography (μ-CT). Histology sections were evaluated by subjective scoring and histomorphometry. Fourteen rabbits remained until the end of the study. Group Floor (n = 7; 3 CPC + 4 AB) had a higher CS activity and a larger bone defect filling volume and lower density by μ-CT measurements than group Cage (n = 7; 3 CPC + 4 AB). Three out of four rabbits in AB-Floor presented fusion of the defect with reorganisation of trabecular bone, whereas three of four in AB-Cage showed areas of incomplete healing. Floor rabbits had a higher score of bony fusion between the radius and ulna than Cage rabbits. There were no differences between groups in histomorphometry. The study found that a larger housing space increased physical activity and promoted bone formation. © 2020 Hedenqvist et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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39.
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40.
  • Hertil, Eva, et al. (författare)
  • Retinal degeneration in nine Swedish Jämthund dogs
  • 2010
  • Ingår i: Veterinary Ophthalmology. - : Wiley. - 1463-5216 .- 1463-5224. ; 13, s. 110-116
  • Tidskriftsartikel (refereegranskat)abstract
    • The Jamthund is the fourth most common breed in Sweden with approximately 1600 pups registered each year. Although it has been known that some adult dogs go blind, so they cannot hunt, the Jamthund dog has historically not been screened for hereditary eye diseases. This report describes nine Swedish Jamthund dogs with retinal degeneration. These dogs represent all Jamthund dogs diagnosed with progressive retinal atrophy (PRA) by the Swedish Eye Panel and registered with the Swedish Kennel Club from January 1998 to September 2008. The dogs were examined with indirect opthalmoscopy and slitlamp biomicroscopy. Additionally, electroretinograms (ERGs) following ECVO guidelines were performed in two dogs (one affected and one normal) and the eyes from three affected dogs were examined by light-microscopy postmortem. Typical findings were bilateral symmetric generalized retinal degeneration with tapetal hyper-reflectivity, attenuation of blood vessels and pigment clumping in the nontapetal fundus. These retinal findings progressed with time in two dogs after re-examination. Visual impairment, especially under dim light conditions, was observed in the affected dogs. ERG from one affected dog showed profoundly reduced rod responses, whereas cone responses were better preserved. Microscopic changes in the eyes from three dogs were characterized by a severe diffuse predominantly outer retinal degeneration and atrophy. Re-sequencing of the prcd-gene for eight of the nine investigated dogs revealed that none of the individuals carried disease allele that has been associated with prcd-PRA in other breeds. In conclusion, ophthalmoscopic, electroretinographic, and light-microscopic alterations observed in nine Jamthund dogs were compatible with PRA. The prcd mutation was excluded as a cause of this retinopathy.
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41.
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42.
  • Kendall, Anna, et al. (författare)
  • Nerve growth factor in the equine joint
  • 2021
  • Ingår i: Veterinary Journal. - : Elsevier BV. - 1090-0233 .- 1532-2971. ; 267
  • Tidskriftsartikel (refereegranskat)abstract
    • Nerve growth factor (NGF) is a neurotrophin with many functions. In humans, it is involved in inflammation, nerve growth, apoptosis and pain signalling. Increased concentrations of NGF in synovial fluid has been shown in humans and dogs with osteoarthritis. Despite osteoarthritis being a common problem in horses, no studies have previously been published on NGF in the equine joint. The aim of this study was to quantify NGF in equine synovial fluid from healthy joints, acutely inflamed septic joints and joints with structural changes associated with osteoarthritis. A secondary aim was to identify the localisation of NGF and its two receptors, TrkA and p75(NTR) in healthy and osteoarthritic articular cartilage. NGF concentrations in synovial fluid from osteoarthritic joints (n = 27), septic joints (n = 9) and healthy joints (n = 16) were determined by ELISA. In addition, articular cartilage from osteoarthritic and healthy joints was examined for NGF, TrkA and P75(NTR) using immunohistochemistry staining. NGF was present in equine synovial fluid and articular cartilage. Compared to synovial fluid from healthy joints, NGF concentration was higher in synovial fluid from joints with structural osteoarthritic changes (P = 0.032) or acute septic inflammation (P = 0.006). In articular cartilage with severe osteoarthritic changes, there was more abundant positive immunohistochemistry staining for NGF and its receptors than in normal articular cartilage. Further studies should focus on identifying precursor forms of NGF, and on receptor expression and downstream signalling of TrkA and P75(NTR) in health and disease. (C) 2020 The Author(s). Published by Elsevier Ltd.
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43.
  • Kendall, Anna, et al. (författare)
  • Nerve growth factor receptors in equine synovial membranes vary with osteoarthritic disease severity
  • 2023
  • Ingår i: Journal of Orthopaedic Research. - : Wiley. - 0736-0266 .- 1554-527X. ; 41, s. 316-324
  • Tidskriftsartikel (refereegranskat)abstract
    • Nerve growth factor (NGF) is a neurotrophin that has been implicated in pain signaling, apoptosis, inflammation and proliferation. The resultant effects depend on interaction with two different receptors; tyrosine kinase A (TrkA) and p75(NTR). NGF increases in synovial fluid from osteoarthritic joints, and monoclonal antibody therapy is trialed to treat osteoarthritis (OA)-related pain. Investigation of the complex and somewhat contradictory signaling pathways of NGF is conducted in neural research, but has not followed through to orthopaedic studies. The objectives of this study were to compare the expression of NGF receptors and the downstream regulator BAX in synovial membranes from joints in various stages of OA. The horse was used as a model. Synovial membranes were harvested from five healthy horses postmortem and from clinical cases with spontaneous OA undergoing arthroscopic surgery for lameness. Four horses with synovitis without gross cartilage changes, four horses with synovitis and cartilage damage, and four horses with synovitis and intracarpal fractures were included. Samples were investigated by immunohistochemistry and results showed that nuclear staining of TrkA, p75(NTR) and BAX increases in OA-associated synovitis. TrkA expression increased in early disease stages whereas increases in p75(NTR) were most prominent in later disease stages with cartilage damage and fibrosis. Clinical significance: Suppression of NGF may result in varied effects depending on different stages of the osteoarthritic disease process.
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44.
  • Ley, Charles, et al. (författare)
  • Detection of early osteoarthritis in the centrodistal joints of Icelandic horses: Evaluation of radiography and low-field magnetic resonance imaging
  • 2016
  • Ingår i: Equine Veterinary Journal. - : Wiley. - 0425-1644 .- 2042-3306. ; 48, s. 57-64
  • Tidskriftsartikel (refereegranskat)abstract
    • Reasons for performing studyValidated noninvasive detection methods for early osteoarthritis (OA) are required for OA prevention and early intervention treatment strategies.ObjectivesTo evaluate radiography and low-field magnetic resonance imaging (MRI) for the detection of early stage OA osteochondral lesions in equine centrodistal joints using microscopy as the reference standard.Study designProspective imaging of live horses and imaging and microscopy of cadaver tarsal joints.MethodsCentrodistal (distal intertarsal) joints of 38 Icelandic research horses aged 27-29 months were radiographed. Horses were subjected to euthanasia approximately 2 months later and cadaver joints examined with low-field MRI. Osteochondral joint specimens were classified as negative or positive for OA using light microscopy histology or scanning electron microscopy. Radiographs and MRIs were evaluated for osteochondral lesions and results compared with microscopy.ResultsForty-two joints were classified OA positive with microscopy. Associations were detected between microscopic OA and the radiography lesion categories; mineralisation front defect (P<0.0001), joint margin lesion (P<0.0001), central osteophyte (P = 0.03) and the low-field MRI lesion categories; mineralisation front defect (P = 0.01), joint margin lesion (P = 0.02) and articular cartilage lesion (P = 0.0003). The most frequent lesion category detected in microscopic OA positive joints was the mineralisation front defect in radiographs (28/42 OA positive joints, specificity 97%, sensitivity 67%). No significant differences were detected between the sensitivity and specificity of radiography and low-field MRI pooled lesion categories, but radiography was often superior when individual lesion categories were compared.ConclusionsEarly stage centrodistal joint OA changes may be detected with radiography and low-field MRI. Detection of mineralisation front defects in radiographs may be a useful screening method for detection of early OA in centrodistal joints of young Icelandic horses.
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45.
  • Ley, Cecilia, et al. (författare)
  • Effects of high mobility group box protein-1, interleukin-1 beta, and interleukin-6 on cartilage matrix metabolism in three-dimensional equine chondrocyte cultures
  • 2011
  • Ingår i: Connective Tissue Research. - : Informa UK Limited. - 0300-8207 .- 1607-8438. ; 52, s. 290-300
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects of high mobility group box protein (HMGB)-1, interleukin (IL)-1 beta, and IL-6 on equine articular chondrocytes were investigated, with emphasis on detecting differences between anatomical sites exposed to different loading in vivo, using three-dimensional (3D) cell cultures established with chondrocytes from dorsal radial facet (DRF, highly loaded) and palmar condyle (PC, less loaded) of the third carpal bone (C3). Expression of important genes involved in cartilage metabolism, presence of glycosaminoglycans and cartilage oligomeric matrix protein (COMP) in pellets, and concentrations of matrix metalloproteinase (MMP)-13 and aggrecan epitope CS 846 were evaluated. Compared to controls, IL-1 beta treatment increased gene expression of versican, matrix-degrading enzymes, and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased aggrecan and collagen type I and type II expression. In addition, IL-1 beta-treated pellets showed decreased safranin O staining and increased COMP immunostaining and MMP-13 concentrations in culture supernatants. Effects of IL-6 and HMGB-1 on gene expression were variable, although upregulation of Sry-related high-mobility group box 9 (Sox9) was often present and statistically increased in HMGB-1-treated pellets. Response to cytokines rarely differed between DRF and PC pellets. Thus, site-associated cartilage deterioration in equine carpal osteoarthritis (OA) is not explained by topographically different responses to inflammatory mediators. Differences in gene expressions of structural matrix proteins in untreated DRF and PC pellets were noted in the youngest horses, which may indicate differences in the chondrocytes potential to produce matrix in vivo. Overall, a strong catabolic response was induced by IL-1 beta, whereas slight anabolic effects were induced by IL-6 and HMGB-1.
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46.
  • Ley, Cecilia, et al. (författare)
  • Effects of high mobility group box protein-1, interleukin-1β, and interleukin-6 on cartilage matrix metabolism in three-dimensional equine chondrocyte cultures.
  • 2011
  • Ingår i: Connective tissue research. - : Informa UK Limited. - 1607-8438 .- 0300-8207. ; 52:4, s. 290-300
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects of high mobility group box protein (HMGB)-1, interleukin (IL)-1β, and IL-6 on equine articular chondrocytes were investigated, with emphasis on detecting differences between anatomical sites exposed to different loading in vivo, using three-dimensional (3D) cell cultures established with chondrocytes from dorsal radial facet (DRF, highly loaded) and palmar condyle (PC, less loaded) of the third carpal bone (C3). Expression of important genes involved in cartilage metabolism, presence of glycosaminoglycans and cartilage oligomeric matrix protein (COMP) in pellets, and concentrations of matrix metalloproteinase (MMP)-13 and aggrecan epitope CS 846 were evaluated. Compared to controls, IL-1β treatment increased gene expression of versican, matrix-degrading enzymes, and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased aggrecan and collagen type I and type II expression. In addition, IL-1β-treated pellets showed decreased safranin O staining and increased COMP immunostaining and MMP-13 concentrations in culture supernatants. Effects of IL-6 and HMGB-1 on gene expression were variable, although upregulation of Sry-related high-mobility group box 9 (Sox9) was often present and statistically increased in HMGB-1-treated pellets. Response to cytokines rarely differed between DRF and PC pellets. Thus, site-associated cartilage deterioration in equine carpal osteoarthritis (OA) is not explained by topographically different responses to inflammatory mediators. Differences in gene expressions of structural matrix proteins in untreated DRF and PC pellets were noted in the youngest horses, which may indicate differences in the chondrocytes potential to produce matrix in vivo. Overall, a strong catabolic response was induced by IL-1β, whereas slight anabolic effects were induced by IL-6 and HMGB-1.
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47.
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48.
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49.
  • Ley, Charles, et al. (författare)
  • Evaluation of osteochondral sample collection guided by computed tomography and magnetic resonance imaging for early detection of osteoarthritis in centrodistal joints of young icelandic horses
  • 2013
  • Ingår i: Veterinary Radiology and Ultrasound. - 1058-8183 .- 1740-8261. ; 55, s. 1-
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Histologic examination with light microscopy is considered the reference standard to detect osteoarthritis (OA) in its earliest stages1, 2. In early OA, articular cartilage changes develop in focal and specific regions of the affected joint3 but the locations of these regions in specific joints and species are uncertain and are likely to vary among individuals. When osteochondral samples are collected from predetermined anatomic sites for histologic examination of joints early in the disease process, then it is possible that OA will fail to be detected because the associated lesions may not be included in the collection site. This study evaluates a method for computed tomography (CT) and magnetic resonance imaging (MRI) guided osteochondral sample collection for the detection of early stage OA lesions in joints from young Icelandic horses. Materials and Methods: CT and MRI were semiquanitatively graded to evaluate the extent of suspected OA changes in right centrodistal joints from the cadavers of 24 Icelandic horses aged 29 to 31 months. The anatomic regions with the highest grade of change were identified, and osteochondral samples were obtained from these regions. Samples were also obtained from the same centrodistal joints at predetermined sites. Histologic examination of all samples was performed, with samples classified as negative or positive for OA, and results were compared between sample collection method. Results: Histologic examination revealed OA lesions in 29% (7/24) of centrodistal joints with predetermined method and in 62% (15/24) with the image-guided method. Significant associations were detected between histologic OA and the summed image-guided sample collection site image grades, central osteophytes, articular cartilage thickness abnormalities, grade-2 articular mineralisation front defects, and grade-2 marginal osteophytes. Discussion/Conclusion:An image-guided sample collection method is recommended when histologic examination will be used as the reference standard for the detection of early-stage OA in centrodistal joints of horses. CT and MRI aided the detection of focal changes suggestive of early stage OA in the centrodistal joints of equine cadavers and may be useful for detection of similar disease in live horses. The first morphological changes of centrodistal joint OA are suspected to be in the articular cartilage and the articular mineralisation front regions.
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50.
  • Ley, Charles, et al. (författare)
  • High-resolution microscopy of osteochondral lesions in the distal tarsal joints of young icelandic horses
  • 2013
  • Ingår i: Veterinary Radiology and Ultrasound. - 1058-8183 .- 1740-8261. ; 55, s. 1-
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Distal tarsal joint osteoarthritis (OA) is a common cause of lameness in adult Icelandic horses1 and high-detail radiography and microscopic OA changes are reported in young Icelandic horses suggesting the disease starts when the horses are young and develops slowly2. Thus young Icelandic horses are potentially an excellent natural model for the early stages of osteoarthritis. This study describes and characterises novel mineralised and non-mineralised osteochondral lesion types in left distal tarsal region joint samples from twenty-two 29 to 31 month-old Icelandic horses. Materials and Methods: Combinations of confocal scanning light microscopy, backscattered electron scanning electron microscopy (including novel iodine staining methods) and three-dimensional microcomputed tomography were used on samples obtained with guidance from clinical computed tomography and magnetic resonance imaging equipment. Osteochondral lesion types were described and the frequency of lesion types calculated. Associations and correlations between osteochondral lesion types were investigated for centrodistal joints. Results: Lesion types were identified in hyaline articular cartilage (HAC), articular calcified cartilage (ACC), subchondral bone (SCB) and the joint margin tissues. The highest lesion frequency was in the centrodistal joint where several lesion types including HAC chondrocyte necrosis, HAC fibrillation, HAC central chondrocyte clusters, ACC arrest and ACC advancement had moderate to high frequency, significant associations and strong correlations. Joint margin lesions had high frequency in centrodistal and tarsometatarsal joints but no significant associations with other lesion types. The frequency of SCB lesions in all joints was low. Hypermineralised protrusions and cracks of the ACC were detected. Discussion/Conclusions: Our results provide detailed morphological information about how tissues respond during the early stages of OA and that these changes occur in HAC and ACC, rather than in the SCB. We speculate that chondrocyte death and chondrocyte hyperplasia in the HAC result in the ACC arrest and ACC advancement respectively. Thinning or loss of the ACC resulting from ACC arrest may have a key role in the development and perpetuation of OA since this likely results in areas in the ACC that allow increased transfer of substances between the SCB and the intra-articular compartments. Young Icelandic horses offer a promising model for the study of ACC behaviour in early OA, a morphological region that we believe is crucial in the early stages of OA development.
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