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1.
  • Bäcklin, B-M, et al. (author)
  • Histology of uterine leiomyoma and occurrence in relation to reproductive activity in the Baltic gray seal (Halichoerus grypus).
  • 2003
  • In: Veterinary pathology. - 0300-9858 .- 1544-2217. ; 40:2, s. 175-180
  • Journal article (peer-reviewed)abstract
    • A high prevalence of uterine leiomyoma has been reported in Baltic gray seals aged 15 years and above. Studies on Baltic seals during the 1970s revealed high tissue concentrations of the organochlorines bis(chlorophenyl)-1,1,1-trichloroethane (DDT) and polychlorinated biphenyls (PCBs), lowered reproduction rate, and pathologic changes. In the second half of the 1970s, decreases of PCB and DDT in Baltic biota occurred, and the prevalence of pregnancies in Baltic seals increased. Between 1975 and 1997, 53 Baltic gray seal females of age 15-40 years were found dead and sent to the Swedish Museum of Natural History. Seals were autopsied and 34/53 (64%) had uterine leiomyomas. Samples from 15 were sufficiently well preserved for histologic examination. Uterine leiomyomas were found most commonly in the uterine corpus but also were observed in the uterine horns, cervix, and vagina. Cut surfaces of the leiomyomas appeared as whorled white fibrous tissue. Histologically, spindle cells were arranged in a whorl-like pattern. The nuclei were rod-like and strikingly uniform in shape and size. Mitotic figures were rare. Immunohistochemical staining of the tumors showed a positive reaction to antibodies recognizing smooth muscle actin. Reproductively active gray seals have an ovarian corpus luteum or albicans for most of the year. In 22/34 (65%) gray seals with uterine leiomyomas, ovaries did not contain corpora. In gray seals without macroscopically detected uterine leiomyoma, ovaries from 6/19 (32%) seals had no corpora. It is possible that the development of leiomyoma in the seals is associated with organochlorines and the previous low reproductive activity.
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2.
  • Ekman, Stina (author)
  • An Update on the Pathogenesis of Osteochondrosis
  • 2015
  • In: Veterinary Pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217. ; 52, s. 785-802
  • Research review (peer-reviewed)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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3.
  • Ekman, Stina (author)
  • Early Lesions of Articular Osteochondrosis in the Distal Femur of Foals
  • 2011
  • In: Veterinary Pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217. ; 48, s. 1165-1175
  • Journal article (peer-reviewed)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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4.
  • Ekman, Stina (author)
  • Observational Study Design in Veterinary Pathology, Part 1: Study Design
  • 2018
  • In: Veterinary Pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217.
  • Other publication (other academic/artistic)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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5.
  • Ekman, Stina (author)
  • Observational Study Design in Veterinary Pathology, Part 2: Methodology
  • 2018
  • In: Veterinary Pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217. ; 55, s. 774-785
  • Other publication (peer-reviewed)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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6.
  • Ekman, Stina (author)
  • Osteochondrosis Can Lead to Formation of Pseudocysts and True Cysts in the Subchondral Bone of Horses
  • 2015
  • In: Veterinary Pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217. ; 52, s. 862-872
  • Journal article (peer-reviewed)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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7.
  • Ekman, Stina, et al. (author)
  • Osteochondrosis in the central and third tarsal bones of young horses
  • 2024
  • In: Veterinary Pathology. - 0300-9858 .- 1544-2217. ; 61, s. 74 - 87
  • Journal article (peer-reviewed)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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8.
  • Ekman, Stina (author)
  • Septic Arthritis/Osteomyelitis May Lead to Osteochondrosis-Like Lesions in Foals
  • 2018
  • In: Veterinary Pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217. ; 55, s. 693-702
  • Journal article (peer-reviewed)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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9.
  • Engelsen Etterlin, Pernille, et al. (author)
  • Osteochondrosis, Synovial Fossae, and Articular Indentations in the Talus and Distal Tibia of Growing Domestic Pigs and Wild Boars
  • 2017
  • In: Veterinary pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217. ; 54:3, s. 445-456
  • Journal article (peer-reviewed)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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10.
  • Frantz, A M, et al. (author)
  • Molecular Profiling Reveals Prognostically Significant Subtypes of Canine Lymphoma
  • 2013
  • In: Veterinary pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217. ; 50:4, s. 693-703
  • Journal article (peer-reviewed)abstract
    • We performed genomewide gene expression analysis of 35 samples representing 6 common histologic subtypes of canine lymphoma and bioinformatics analyses to define their molecular characteristics. Three major groups were defined on the basis of gene expression profiles: (1) low-grade T-cell lymphoma, composed entirely by T-zone lymphoma; (2) high-grade T-cell lymphoma, consisting of lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma not otherwise specified; and (3) B-cell lymphoma, consisting of marginal B-cell lymphoma, diffuse large B-cell lymphoma, and Burkitt lymphoma. Interspecies comparative analyses of gene expression profiles also showed that marginal B-cell lymphoma and diffuse large B-cell lymphoma in dogs and humans might represent a continuum of disease with similar drivers. The classification of these diverse tumors into 3 subgroups was prognostically significant, as the groups were directly correlated with event-free survival. Finally, we developed a benchtop diagnostic test based on expression of 4 genes that can robustly classify canine lymphomas into one of these 3 subgroups, enabling a direct clinical application for our results.
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