Computed tomography atlas of the normal cranial canine abdominal vasculature enhanced by dual-phase angiography.

This study was performed to provide a detailed atlas of the normal arterial and venous canine vasculature in the cranial abdomen by dual-phase computed tomographic angiography. Five adult beagles were positioned in dorsal recumbency on a multislice helical CT scanner. An unenhanced survey CT scan from the diaphragm to the pelvic inlet was performed. Bolus-tracking software was used for the dual-phase angiogram, and contrast medium was administered in a cephalic vein. The arterial phase was scanned from the mid-abdomen to the cranial aspect of the diaphragm; the portal phase was scanned a few seconds after the arterial phase in the opposite direction. The DICOM studies from all dogs were analysed. Representative images were selected and anatomic structures labelled. Maximum intensity projections and three-dimensional images were generated using software techniques. A detailed atlas of the venous and arterial vasculature of the cranial canine abdomen was created with the help of bolus-tracking dual-phase computed tomographic angiography (CTA). Practitioners can use this anatomic atlas with its detailed venous and arterial phase CT angiograms of the canine cranial abdomen to compare normal versus abnormal vascular anatomy.

Comparison of radiography and CT to identify changes in the skulls of four rabbits with dental disease.

Four domestic pet rabbits with dental pathology were presented at a university clinic. In addition to conducting physical examinations of the rabbits, radiographic and computed tomographic (CT) images of the rabbits' heads were obtained. Three rabbits were euthanized at the owners' request, and anatomic sections of the skulls were made. The observations of the anatomic sections, radiographs, and CT images are described. The abnormalities found on the radiographs and CT images were very similar to the findings on the anatomic sections. Compared to radiography, the CT images provided more details about the extent of the dental pathology, which is likely to be important for establishing a more precise prognosis and a more informed decision making process.

Exposure to nuclear antigens contributes to the induction of humoral autoimmunity during tumour necrosis factor alpha blockade.

OBJECTIVE: Type I interferons and apoptotic particles contribute to antinuclear autoimmunity in experimental models. This study assessed whether similar mechanisms contribute to break peripheral B-cell tolerance in humans by studying the induction of antinuclear antibodies by tumour necrosis factor blockade in spondyloarthritis. METHODS: 40 spondyloarthritis patients treated with infliximab or etanercept and 20 renal cell carcinoma patients treated with sorafenib were studied. Serum antinucleosome IgM and nucleosomes were measured by ELISA. Type I interferon serum activity was measured using a functional reporter cell assay. Synovial apoptosis was assessed by terminal transferase nick end-labelling (TUNEL) assay and anti-active caspase-3 immunostaining. Complement was measured by nephelometry. RESULTS: Despite a similar clinical improvement and reduction of synovial inflammation, antinucleosome IgM were induced by infliximab but not etanercept. This induction did not correlate with type I interferon activity, which was transiently downmodulated by infliximab but persistently upregulated by etanercept. In contrast, antinucleosome IgM levels did correlate with serum nucleosome levels, which were significantly upregulated by infliximab but not by etanercept treatment. This increase in serum nucleosome levels was not directly related to massive cell death, but rather to a decrease of complement 3 and 4 serum levels during infliximab treatment. CONCLUSION: Infliximab and etanercept have a differential effect on both type I interferon activity and nucleosome levels. Only elevated serum nucleosomes relate to the induction of antinucleosome antibodies after infliximab treatment.

Melanoma inhibitory activity, a biomarker related to chondrocyte anabolism, is reversibly suppressed by proinflammatory cytokines in rheumatoid arthritis.

OBJECTIVE: In mice, melanoma inhibitory activity (MIA) is a chondrocyte-specific molecule with similar regulation to collagen type II. As MIA is a small secreted protein, its value as cartilage biomarker in human inflammatory arthritis was assessed. METHODS: MIA tissue distribution was studied by quantitative PCR and immunohistochemistry. The regulation of MIA production was studied in vivo in rheumatoid arthritis (RA) (n = 37) and spondyloarthritis (SpA) (n = 30) synovial fluid (SF), and in vitro in alginate embedded human chondrocytes. Therapeutic modulation of serum MIA was evaluated during tumour necrosis factor (TNF)alpha and interleukin (IL)1 blockade in RA. RESULTS: MIA was primarily expressed by chondrocytes in the human joint. SF MIA levels were lower in RA than in SpA despite similar levels of overall synovial inflammation. Further analysis indicated that these levels were inversely correlated with the degree of joint inflammation in RA, but not in SpA, and that the levels of TNFalpha and IL1beta were significantly increased in RA versus SpA. Accordingly, these proinflammatory cytokines suppressed MIA mRNA and protein in cultured chondrocytes. This suppression was paralleled by suppression of cartilage anabolism as assessed by collagen type 2 and aggrecan mRNA. Treatment of patients with RA with TNF blockade or IL1 blockade induced an increase of serum MIA levels. CONCLUSION: The decreased levels of MIA in the inflamed RA joint and the coregulation of MIA and cartilage matrix molecules by proinflammatory cytokines indicate that joint inflammation in RA not only drives accelerated cartilage degradation but also suppresses cartilage anabolism. This inflammation-driven suppression is reversible in vivo.

Anti-citrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis: specificity and relation with rheumatoid factor.

Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific and sensitive markers for rheumatoid arthritis (RA). For instance, for the anti-CCP2 assay, sensitivities ranging from 55% to 80% and specificities ranging from 90% to 98% have been reported. Despite their high specificity, recent reports have suggested that ACPA may be found in some patients with other rheumatic autoimmune diseases, including psoriatic arthritis, systemic lupus erythematosus and Sjögren's syndrome. Also, the differences between the classical rheumatoid factor (RF) and ACPA, as well as the complementarity between both tests have recently been demonstrated more clearly. Indeed, both antibody systems have a different association with specific RA features like extra-articular manifestations, a different association with the HLA shared epitope and, behave differently following anti-TNF therapy.

Functional haplotypes of PADI4: relevance for rheumatoid arthritis specific synovial intracellular citrullinated proteins and anticitrullinated protein antibodies.

BACKGROUND: Haplotypes of PADI4, encoding for a citrullinating enzyme, were associated with rheumatoid arthritis in a Japanese population. It was suggested they were related to the presence of anticitrullinated protein antibodies (ACPA). OBJECTIVE: To explore the relation between PADI4 haplotypes, the presence of rheumatoid arthritis specific intracellular citrullinated proteins in synovial membrane, and serum ACPA titres. METHODS: Synovial biopsies and peripheral blood samples were obtained in 59 patients with rheumatoid arthritis. Synovial intracellular citrullinated proteins were detected by immunohistochemistry. Serum ACPA titres were measured by anti-CCP2 ELISA. PADI4 haplotypes were determined by direct sequencing of the four exonic PADI4 single nucleotide polymorphisms. RESULTS: PADI4 haplotype frequencies and the presence of synovial intracellular citrullinated proteins and ACPA were comparable with previous studies. There was no significant association between PADI4 haplotype 1 or 2 and the presence of synovial intracellular citrullinated proteins, although these proteins were associated with higher serum ACPA. There was no correlation between PADI4 haplotypes and serum ACPA, either by continuous analysis using the titres or by dichotomous analysis using the diagnostic cut off. Further analyses in homozygotes for haplotype 1 or 2 or in heterozygotes (1/2) also failed to show an association between PADI4 polymorphisms and ACPA. This contrasted with the clear association between ACPA levels and HLA-DR shared epitope. CONCLUSIONS: The link between synovial intracellular citrullinated proteins and ACPA emphasises the role of deimination of synovial proteins in rheumatoid arthritis, but the biological relevance of the PADI4 haplotypes for this autoimmune process is questionable, at least in a European population.

Anti-citrullinated peptide antibodies may occur in patients with psoriatic arthritis.

BACKGROUND: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are considered highly specific markers of rheumatoid arthritis. Despite the high specificity of the test, anti-CCP antibodies have also been observed in psoriatic arthritis. OBJECTIVE: To determine the frequency of anti-CCP antibodies in psoriatic arthritis and to describe the clinical characteristics of such patients. METHODS: Serum samples from 192 patients with psoriatic arthritis were analysed for anti-CCP antibodies. A previously defined cut off point was applied at a specificity level of > or =98.5% (42 U/ml). Antibodies against pepA and pepB (two synthetic citrullinated peptides) were determined on samples containing anti-CCP antibodies by line immune assay. The swollen joint count and the numbers of affected joints (present or past) were recorded. Clinical features were noted and if available radiographs of hands and feet were scored for erosions. Rheumatoid factor was determined in all samples. RESULTS: Anti-CCP antibodies were found in 15 patients (7.8%); 13 of 15 anti-CCP2 positive samples were also positive for anti-pepA or pepB antibodies. The prevalence of anti-CCP antibodies was higher than expected in view of the highly specific cut off applied in the test. Detailed analysis of the clinical and radiological features makes it improbable that the high prevalence of anti-CCP antibodies resulted solely from concomitant psoriasis and rheumatoid arthritis or from misclassification. CONCLUSIONS: Anti-CCP antibodies may be present in patients with psoriatic arthritis. Although some of the present cohort could have had psoriasis with concomitant rheumatoid arthritis, a proportion at least had the typical characteristics of psoriatic arthritis as the primary diagnosis.

The effect of TNFalpha blockade on the antinuclear antibody profile in patients with chronic arthritis: biological and clinical implications.

Since the first proof of efficacy of TNFalpha blockade, both the number of patients treated worldwide and the number of indications for treatment with TNFalpha blockers have grown steadily. Surprisingly, the profound immunomodulation induced by anti-TNFalpha therapy is associated with a relatively low incidence of immune-related complications such as lupus-like syndromes and demyelinating disease. This contrasts sharply with the prominent induction of autoantibodies such as antinuclear antibodies (ANA) and anti-dsDNA antibodies during TNFalpha blockade. Although this phenomenon has been recognized for several years, the clinical and biological implications are not yet fully understood. In this review, recent studies analysing the effect of TNFalpha blockade (infliximab and etanercept) on the ANA profile in autoimmune arthritis will be discussed. Taken together, these reports indicate that the prominent ANA and anti-dsDNA autoantibody response is 1) not a pure class effect of TNFalpha blockers, 2) independent of the disease background, 3) largely restricted to the induction of short-term IgM anti-dsDNA antibodies, and 4) not associated with other serological or clinically relevant signs of lupus. Nevertheless, a careful follow-up of patients treated with TNFalpha blockers remains mandatory, including monitoring for lupus-like characteristics.

Rheumatoid factor, but not anti-cyclic citrullinated peptide antibodies, is modulated by infliximab treatment in rheumatoid arthritis.

OBJECTIVES: To analyse the effect of infliximab on IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies, and determine whether baseline autoantibody titres (IgM RF and anti-CCP antibodies) are associated with changes in acute phase reactants. PATIENTS AND METHODS: 62 patients with refractory RA were treated with infliximab combined with methotrexate. At baseline and week 30, serum samples were tested for IgM RF by two agglutination assays, and for anti-CCP antibodies by an ELISA. Percentage change in C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) was calculated. RESULTS: At baseline and week 30 RF titres were reduced significantly during infliximab treatment (p<0.001 and p = 0.038, respectively), whereas anti-CCP antibodies were unchanged (p = 0.240). Baseline IgM RF titres, but not anti-CCP antibodies, correlated inversely with changes in CRP and ESR during treatment. Patients with a marked decrease in acute phase reactants had lower IgM RF titres than those with a smaller decrease in CRP and ESR; no significant differences were found for anti-CCP antibodies. CONCLUSION: The differential effect of infliximab treatment on IgM RF and anti-CCP antibodies, and the different predictive value on changes in acute phase reactants during infliximab treatment support the existing evidence that RF and anti-CCP antibodies are independent autoantibody systems in RA.

Rheumatoid factor and anticitrullinated protein antibodies in rheumatoid arthritis: diagnostic value, associations with radiological progression rate, and extra-articular manifestations.

BACKGROUND: Autoantibodies such as rheumatoid factor (RF) and anticitrullinated protein antibodies can be detected in rheumatoid arthritis (RA) sera. OBJECTIVE: To determine the diagnostic values of RF, anticitrullinated protein antibodies, and the shared epitope (SE), and their associations with radiological progression rates and extra-articular manifestations. METHODS: Population 1 consisted of sera from 315 patients, consecutively sent for detection of anticitrullinated protein antibodies, of which 264 were used to determine the sensitivity and specificity of RF and of antibodies against three synthetic citrullinated peptides: peptide A (pepA), peptide B (pepB), and CCP2. Population 2 consisted of sera from 180 longstanding RA patients and was used to determine associations of RA associated antibodies and the SE with radiological progression rates and extra-articular manifestations. Antibodies to pepA and pepB were detected by line immunoassay, and antibodies to CCP2 by ELISA. HLA Class II typing was performed by LiPA. RESULTS: In population 1, we defined adapted cut offs corresponding to a specificity of >/=98.5%. This yielded the following sensitivities: RF 12.8%; anti-pepA antibodies 63.6%; anti-pepB antibodies 54.2%; and anti-CCP2 antibodies 73.7%. In population 2, significant differences in radiological progression rates were found between positive and negative patients for different RA antibodies and the SE. RF, but not anticitrullinated protein antibodies or the SE, were more frequent in patients with extra-articular manifestations. CONCLUSION: A valid comparison of RA associated antibodies shows superior sensitivity of the anticitrullinated protein antibodies compared with RF. The presence of RA associated antibodies and the SE are indicative for poorer radiological outcome, and presence of extra-articular manifestations is associated with RF but not with anticitrullinated protein antibodies.

History and diagnostic value of antibodies to citrullinated proteins in rheumatoid arthritis.

Rheumatoid arthritis is a chronic inflammatory joint disease characterized by the presence of autoantibodies. The best known autoantibody is the rheumatoid factor. Another group of antibodies directed against citrullinated epitopes is proven to be more specific for rheumatoid arthritis. This review gives an overview of the history of the different anti-citrullinated protein antibody detection methods and their diagnostic and prognostic properties in RA.

Thoracoscopic anatomy of dogs positioned in lateral recumbency.

In four healthy, adult male German shepherd dogs, thoracoscopy was performed to provide a detailed description and illustration of the endoscopic anatomy of the normal intrathoracic structures of dogs. The dogs were anesthetized and placed in left or right lateral recumbency. The cannula and the endoscope were advanced into the thoracic cavity via entry of the free upper side in the dorsal third of the eighth intercostal space. Most intrathoracic structures of the left and right hemithorax were endoscopically visible. During the four thoracoscopic procedures, endoscopic photographs were taken and are illustrated in this paper. A sound knowledge of the anatomy of intrathoracic structures is a prerequisite for diagnostic and therapeutic thoracoscopy.

Computed tomography of the tarsal joint in clinically normal dogs.

OBJECTIVE: To use computed tomography to provide a detailed description of tarsal joint structures in clinically normal dogs. ANIMALS: 6 clinically normal adult mixed-breed dogs weighing 25 to 35 kg and one 12-month-old Bullmastiff weighing 65 kg. PROCEDURE: To perform computed tomography (CT) of both tarsal regions, dogs were anesthetized and placed in ventral recumbency. One- and 2-mm contiguous slices were obtained, using a third generation CT scanner Individual images were reviewed, using bone (window width = 3,500 Hounsfield units; window level = 500 Hounsfield units) and soft-tissue (window width = 400 Hounsfield units; window level = 66 Hounsfield units) settings. After euthanasia, the hind limbs from the Bullmastiff were removed and frozen at -18 C. Tarsal joints were sectioned into approximately 1-mm-thick slab sections, using a cryomicrotome. Anatomic sections were photographed and compared with the corresponding CT images. Computed tomographic reconstructions of the tarsocrural joint were created in sagittal and dorsal planes. RESULTS: Structures on the CT images were matched with structures in the corresponding anatomic sections. The entire tarsocrural joint surface could be evaluated on the reconstructed images in the sagittal and dorsal planes. CONCLUSIONS AND CLINICAL RELEVANCE: CT images provide full anatomic detail of the bony structures of the tarsal joint in dogs. Tendons and large blood vessels can also be evaluated. These results could be used as a basis for evaluation of CT images of the hind limbs of dogs with tarsal joint injuries.

Ultrasound-guided tissue-core biopsy of liver, spleen and kidney in normal dogs.

Six normal dogs were subjected to ultrasound-guided biopsy of the liver, spleen and kidney to examine the accuracy of the technique (i.e. the presence of targeted tissue) and the histologic quality of the biopsies. Five consecutive tissue-core biopsies of each organ were taken on one or more occasions. The accuracy of the technique was 77% for hepatic, 90% for splenic, 53.5% for left kidney and 40% for right kidney biopsies. The histologic quality of the liver and kidney samples was sufficient, although for some samples the diagnostic value was limited by their size and in renal samples either cortical or medullary tissue was sometimes lacking. In contrast, the quality of the splenic sections was not good. The effect of reused and resterilized needles on the quality of the specimens was evaluated by histologic inspection of the samples and by the amount of biopsies lacking tissue. All tissue samples, including those taken with reused or resterilized needles had sharp-cut edges. Twenty-two of the total number of 120 biopsies (18%) contained no tissue. Absence of tissue in the samples was observed in biopsies taken with all needle types. The animals were observed for possible complications of the repeated needle biopsy. Apart from one case of hematuria, no complications were encountered.