135 research outputs found
Osteochondral lesions in distal tarsal joints of Icelandic horses reveal strong associations between hyaline and calcified cartilage abnormalities
Osteochondral lesions in the joints of the distal tarsal
region of young Icelandic horses provide a natural model
for the early stages of osteoarthritis (OA) in low-motion
joints. We describe and characterise mineralised and
non-mineralised osteochondral lesions in left distal tarsal
region joint specimens from twenty-two 30 ±1 month-old
Icelandic horses. Combinations of confocal scanning light
microscopy, backscattered electron scanning electron
microscopy (including, importantly, iodine staining) and
three-dimensional microcomputed tomography were used
on specimens obtained with guidance from clinical imaging.
Lesion-types were described and classified into groups
according to morphological features. Their locations in
the hyaline articular cartilage (HAC), articular calcified
cartilage (ACC), subchondral bone (SCB) and the joint
margin tissues were identified and their frequency in the
joints recorded. Associations and correlations between
lesion-types were investigated for centrodistal joints only.
In centrodistal joints the lesion-types HAC chondrocyte
loss, HAC fibrillation, HAC central chondrocyte clusters,
ACC arrest and ACC advance had significant associations
and strong correlations. These lesion-types had moderate
to high frequency in centrodistal joints but low frequencies
in tarsometatarsal and talocalcaneal-centroquartal joints.
Joint margin lesion-types had no significant associations
with other lesion-types in the centrodistal joints but high
frequency in both the centrodistal and tarsometatarsal
joints. The frequency of SCB lesion-types in all joints
was low. Hypermineralised infill phase lesion-types were
detected. Our results emphasise close associations between
HAC and ACC lesions in equine centrodistal joints and the
importance of ACC lesions in the development of OA in
low-motion compression-loaded equine joints
Ligation of the spermatic cord in dogs with a self-locking device of a resorbable polyglycolic based co-polymer
Background: New surgical techniques are developed to enable a quicker, easier and safer surgery with reduced risk of complications and shortened time needed for recovery. A resorbable device, a self-locking loop, was designed for surgical ligation. The objective of this pilot study was to investigate the feasibility of ligating the spermatic cord with the device, its biocompatibility and long-term resorption in dogs. Results: The device was made of a block co-polymer (glycolide and trimethylene carbonate), manufactured by injection moulding and consisted of a flexible band running through a case with a locking mechanism. Ten devices were tested for ligation of the spermatic cords in five dogs admitted for routine neutering. The dogs were monitored by physical examination and ultrasonography of the site of ligation, area of spermatic cord and medial iliac lymph nodes regularly until no hyperechoic remnants of the device or acoustic shadowing or local tissue reactions were observed. Haemostasis of the spermatic cords was achieved with the devices. On ultrasonography the devices were seen as hyperechoic structures for 2 months after neutering causing acoustic shadowing for 1 month. The dogs were monitored for 3 - 5 months after surgery. Gradual decrease in echogenicity and final disappearance of the hyperechoic structures suggested resorption. Macroscopic and histological post mortem examinations were performed in one dog at 3 months after surgery. Post mortem examination showed a tissue reaction of a suture granuloma that was restricted in extent at site of the device.
Conclusions: The results of this pilot study suggest biocompatibility and indicate that ligation of the spermatic cord is feasible with the device
Online dosimetry for temoporfin-mediated interstitial photodynamic therapy using the canine prostate as model.
Osteochondrosis in the central and third tarsal bones of young horses
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
Context dependent development of lymphoid organ mesenchymal subsets fromBP3<sup>-</sup>Gp38<sup>+</sup> PDGFRβ<sup>+</sup>/α<sup>+</sup>CD34<sup>+</sup> vascular adventitial precursors
Concentrations of canine prostate specific esterase, CPSE, at baseline are associated with the relative size of the prostate at three-year follow-up
BackgroundEnlargement of the prostate is associated with prostatic diseases in dogs, and an estimation of prostatic size is a central part in the diagnostic workup. Ultrasonography is often the method of choice, but biomarkers constitute an alternative. Canine prostate specific esterase (CPSE) shares many characteristics with human prostate specific antigen (PSA) and is related to prostate size. In men with clinical symptoms of prostatic disease, PSA concentrations are related to prostate growth. The aims of the present follow-up study were to evaluate if the concentration of CPSE is associated with future growth of the prostate, and if analysis of a panel of 16 steroids gives further information on prostatic growth. Owners of dogs included in a previous study were 3 years later contacted for a follow-up study that included an interview and a clinical examination. The prostate was examined by ultrasonography. Serum concentrations of CPSE were measured, as was a panel of steroids.ResultsOf the 79 dogs included at baseline, owners of 77 dogs (97%) were reached for an interview, and 22 were available for a follow-up examination. Six of the 79 dogs had clinical signs of prostatic disease at baseline, and eight of the remaining 73 dogs (11%) developed clinical signs between baseline and follow-up, information was lacking for two dogs. Development of clinical signs was significantly more common in dogs with a relative prostate size of >= 2.5 at baseline (n=20) than in dogs with smaller prostates (n=51). Serum concentrations of CPSE at baseline were not associated with the change in prostatic size between baseline and follow-up. Serum concentrations of CPSE at baseline and at follow-up were positively associated with the relative prostatic size (S-rel) at follow-up. Concentrations of corticosterone (P = 0.024), and the class corticosteroids (P = 0.0035) were positively associated with the difference in S-rel between baseline and follow-up.ConclusionsThe results support the use of CPSE for estimating present and future prostatic size in dogs >= 4years, and the clinical usefulness of prostatic size for predicting development of clinical signs of prostatic disease in the dog. The association between corticosteroids and prostate growth warrants further investigation
Predictors of the first cardiovascular event in patients with systemic lupus erythematosus - a prospective cohort study
Systemic Lupus Erythematosus (SLE) is an autoimmune, inflammatory disease that mainly affects
women. The prognosis of SLE has improved dramatically, but mortality rates are still higher than in the
general population. With the improved general prognosis, cardiovascular disease (CVD) has emerged as a
major cause of morbidity and mortality among SLE patients. Previous studies have demonstrated that the
development of atherosclerosis is accelerated in SLE, and have identified a set of traditional and nontraditional
risk factors that characterize SLE patients with CVD. Nevertheless, many unsolved issues with
respect to SLE related CVD remain. The general aim of this thesis was to investigate risk factors for
manifest CVD and for cardiovascular mortality (CVM) in SLE, with special focus on traditional risk
factors, lupus phenotype, inflammatory and endothelial biomarkers, autoantibodies and genetic
predisposition.
In the first paper, we prospectively studied traditional and non-traditional risk factors for
the development of the first cardiovascular event (CVE) in 182 SLE patients with a follow-up time of 8
years. 24(13%) patients had a first event. We demonstrated that of the traditional risk factors, only age
and smoking predicted the first CVE. Additionally, antiphospholipid antibodies (aPL), endothelial
biomarkers, represented by soluble vascular cell adhesion molecule 1(sVCAM-1), and absence of
thrombocytopenia were independent predictors of CVE. Thus, activation of the endothelium and the
coagulation system are important features in SLE-related CVD and the importance to advocate smoking
cessation among SLE patients is underscored
In the second paper, we prospectively investigated causes of mortality and risk factors for
overall mortality and CVM in a cohort of 208 SLE patients, with a follow-up time of 12 years. We also
evaluated Systematic coronary risk evaluation (SCORE, tool for evaluating the 10 year risk for
cardiovascular death in the age span 40-65 years, based on traditional risk factors) in this population.
Cystatin C, a sensitive measure of renal function, in addition to traditional and non-traditional risk
factors, were evaluated as risk factors. 42 patients died, 48 % of which were due to CVM. Age, previous
arterial events and high cystatin C levels were the strongest predictors for overall mortality and for CVM.
After adjusting for these three variables, smoking, sVCAM-1 and high sensitiviy C-reactive protein
(hsCRP) predicted CVM. SCORE estimated 4 but we observed 9 cases of CVM, a non-significant
difference. We conclude that except for smoking, traditional risk factors are less important than cystatin
C, endothelial and inflammatory biomarkers as predictors of CVM in SLE patients.
In the third paper, we investigated whether a risk allele for SLE in the signal transducer
and activator of transcription factor 4 gene (STAT4) was associated with vascular events or presence of
antiphospholipid antibodies (aPL). A total of 578 unrelated SLE patients (424 from mid-Sweden and 154
from southern-Sweden) were included in a cross-sectional design. Occurrence of previous cardiovascular
events and aPL were tabulated. Matched controls (N=651) were genotyped as a comparison. The results
demonstrate that the STAT4 risk allele was associated with ischemic cerebrovascular disease (ICVD),
with a dose-dependent relationship between ICVD and number of risk alleles. The risk allele was
furthermore associated with the presence of two or more aPLs, also in a dose-dependent manner. The
association remained after adjustment for known traditional risk factors. We conclude that patients with
the STAT4 risk allele have an increased risk of ICVD. Our results imply that genetic predisposition is an
important risk factor for ICVD in SLE patients, and that aPL may be one underlying mechanism.
In the fourth paper, we evaluated the potential association between smoking and aPL. 367
SLE patients were investigated in a cross-sectional study. Occurrence of aPL (anticardiolipin (aCL) IgG
and IgM, anti-β2 glycoprotein-1 IgG (aβ2GP1 IgG), lupus anticoagulant (LAC)) and smoking habits
(never, ever, former, current) were tabulated. Never smoking was used as reference in all calculations. In
multivariable models, adjusted for age, sex and age at disease onset, aCL and aβ2GP1 of the IgG isotype
and LAC were associated with ever smoking, this association seemed to be driven mainly by the former
smoking group. Our results demonstrate that smoking is associated with pro-thrombotic aPL in SLE
patients, though we can not from this study draw firm conclusions about the temporal relationship
between exposure to smoking and occurrence of aPL. Further studies are warranted to investigate the
mechanisms behind these observations.
In prospective studies we have demonstrated that in particular smoking, systemic
inflammation, endothelial activation and aPL are major risk factors for SLE related CVD and CVM.
Furthermore, genetic predisposition, in our studies represented by a STAT4 SLE risk allele, contributes to
the high risk of ICVD and to the occurrence of aPL, a possible underlying pathogenic mechanism. Finally
we demonstrate that smoking, known to have unfavorable effects on the immune system and to
significantly increase cardiovascular risk in SLE patients, is also associated with pro-thrombotic aPL in
patients with SLE. Thus in SLE smoking stands out as the most important of the traditional risk factors
with potential influence also on lupus related risk factors such as aPL
Online dosimetry for temoporfin-mediated interstitial photodynamic therapy using the canine prostate as model
Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease
The complexity of clinical manifestations commonly observed in autoimmune disorders poses a major challenge to genetic studies of such diseases. Systemic lupus erythematosus (SLE) affects humans as well as other mammals, and is characterized by the presence of antinuclear antibodies (ANA) in patients' sera and multiple disparate clinical features. Here we present evidence that particular sub-phenotypes of canine SLE-related disease, based on homogenous (ANA(H)) and speckled ANA (ANA(S)) staining pattern, and also steroid-responsive meningitis-arteritis (SRMA) are associated with different but overlapping sets of genes. In addition to association to certain MHC alleles and haplotypes, we identified 11 genes (WFDC3, HOMER2, VRK1, PTPN3, WHAMM, BANK1, AP3B2, DAPP1, LAM-TOR3, DDIT4L and PPP3CA) located on five chromosomes that contain multiple risk haplotypes correlated with gene expression and disease sub-phenotypes in an intricate manner. Intriguingly, the association of BANK1 with both human and canine SLE appears to lead to similar changes in gene expression levels in both species. Our results suggest that molecular definition may help unravel the mechanisms of different clinical features common between and specific to various autoimmune disease phenotypes in dogs and humans.Peer reviewe
Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease
The complexity of clinical manifestations commonly observed in autoimmune disorders poses a major challenge to genetic studies of such diseases. Systemic lupus erythematosus (SLE) affects humans as well as other mammals, and is characterized by the presence of antinuclear antibodies (ANA) in patients' sera and multiple disparate clinical features. Here we present evidence that particular sub-phenotypes of canine SLE-related disease, based on homogenous (ANA(H)) and speckled ANA (ANA(S)) staining pattern, and also steroid-responsive meningitis-arteritis (SRMA) are associated with different but overlapping sets of genes. In addition to association to certain MHC alleles and haplotypes, we identified 11 genes (WFDC3, HOMER2, VRK1, PTPN3, WHAMM, BANK1, AP3B2, DAPP1, LAM-TOR3, DDIT4L and PPP3CA) located on five chromosomes that contain multiple risk haplotypes correlated with gene expression and disease sub-phenotypes in an intricate manner. Intriguingly, the association of BANK1 with both human and canine SLE appears to lead to similar changes in gene expression levels in both species. Our results suggest that molecular definition may help unravel the mechanisms of different clinical features common between and specific to various autoimmune disease phenotypes in dogs and humans.Peer reviewe
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