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Biomedical subjects

A K So

Publications and source records attributed to A K So.

At least 19 recordsLinked to original sources

Association of spondylarthropathies with lumbar synovial cysts.

Intraspinal synovial cysts presenting with lower back pain and radiculopathy are well known but rare. They are associated with facet joint arthopathy, generally degenerative in nature. Spinal synovial cysts have not been described in spondyloarthropathies (SpA). We report a case of a 66-year-old man with a chronic undifferentiated SpA who presented with severe weakness of both legs. A centrally located spinal cyst was encountered on MRI and led to excision of a highly inflammatory synovial cyst. This association may not be fortuitous and be related to inflammation of the facet joint in SpA.

Aged↗

Arthritis is linked to local and systemic activation of coagulation and fibrinolysis pathways.

BACKGROUND: Activation of coagulation and fibrinolysis play a role in the pathophysiology of experimental arthritis. OBJECTIVE: To determine the extent of activation of the coagulation and fibrinolytic pathways in different joint diseases in humans and to ascertain the factors that may influence fibrin deposition within the joint. METHODS: Plasma from normal subjects (controls, n= 21) and plasma and synovial fluid samples from patients with rheumatoid arthritis (RA; n = 64), osteoarthritis (OA; n = 29), spondyloarthropathy (SpA; n = 22) and crystal arthritis (CA; n = 25) were analyzed for the levels of TF (tissue factor) and tissue factor pathway inhibitor (TFPI) activities, thrombin-antithrombin III (TAT) complexes, and F1 + 2 (thrombin fragment), fibrin d-dimer and thrombin-activated fibrinolysis inhibitor (TAFI) antigenic levels. The measurements were analyzed by pairwise correlation with each other as well as with standard parameters of inflammation [C-reactive protein (CRP), joint leukocyte count]. Inter-group comparisons were performed to look for disease-specific differences. RESULTS: Compared with healthy controls, patients with joint diseases had higher levels of TAT, F1 + 2 and d-dimers in their plasma. In the synovial fluid, TF activity, TAT, d-dimers, and TAFI were significantly higher in inflammatory arthritides than in OA. The levels were highest in RA patients. In the plasma, TF activity was correlated with TAT and d-dimer levels with CRP, TFPI, and TAT. In the synovial fluid, TF activity correlated with plasma CRP levels, synovial fluid leukocyte count, and synovial TAT and TAFI levels. In addition, synovial d-dimers correlated with CRP, and synovial TAFI levels were correlated with synovial F1 + 2 and TAT. CONCLUSIONS: Activation of the coagulation and fibrinolytic cascades in the joint and in the circulation is evident in both inflammatory and degenerative joint diseases. Within the joint, inflammatory mechanisms leading to TF-mediated activation of the coagulation pathway and subsequent fibrin deposition is the most likely explanation for the observed findings. In the plasma, the link between inflammation (CRP increase) and TF activation is weak, and a non-TF-mediated mechanism of coagulation activation could explain these findings. RA is characterized by significantly higher levels of TAT in the synovial fluid and plasma than other arthritides. Although fibrinolytic activity is linked to inflammation, the increased amounts of TAFI in the joint, particularly in RA, may explain why fibrin formation is so prominent in this condition compared with other joint diseases.

Adult↗

Identification of case complexity and increased health care utilization in patients with rheumatoid arthritis.

OBJECTIVES: To document biopsychosocial profiles of patients with rheumatoid arthritis (RA) by means of the INTERMED and to correlate the results with conventional methods of disease assessment and health care utilization. METHODS: Patients with RA (n = 75) were evaluated with the INTERMED, an instrument for assessing case complexity and care needs. Based on their INTERMED scores, patients were compared with regard to severity of illness, functional status, and health care utilization. RESULTS: In cluster analysis, a 2-cluster solution emerged, with about half of the patients characterized as complex. Complex patients scoring especially high in the psychosocial domain of the INTERMED were disabled significantly more often and took more psychotropic drugs. Although the 2 patient groups did not differ in severity of illness and functional status, complex patients rated their illness as more severe on subjective measures and on most items of the Medical Outcomes Study Short Form 36. Complex patients showed increased health care utilization despite a similar biologic profile. CONCLUSIONS: The INTERMED identified complex patients with increased health care utilization, provided meaningful and comprehensive patient information, and proved to be easy to implement and advantageous compared with conventional methods of disease assessment. Intervention studies will have to demonstrate whether management strategies based on INTERMED profiles can improve treatment response and outcome of complex patients.

Adult↗

Plasma apolipoprotein(a) co-deposits with fibrin in inflammatory arthritic joints.

Extravascular coagulation and diminished fibrinolysis are processes that contribute to the pathology of both inflammatory arthritis and atherosclerosis. We hypothesized that, given its homology with plasminogen, apolipoprotein (apo) (a), the distinctive glycoprotein of the atherogenic lipoprotein (Lp) (a), may be equally implicated in inflammatory arthritis. We detected the presence of apo(a) as part of Lp(a) in human arthritic synovial fluid. The abundance of apo(a) in synovial fluid rose in proportion to plasma apo(a) levels and was higher in inflammatory arthritides than in osteoarthritis. In addition, apo(a) immunoreactive material, but not apo(a) transcripts, was detected in inflammatory arthritic synovial tissues. These data indicated that synovial fluid apo(a) originates from circulating Lp(a) and that diffusion of Lp(a) through synovial tissue is facilitated in inflammatory types of arthritis. In synovial tissues, apo(a) co-localized with fibrin. These observations could be reproduced in a model of antigen-induced arthritis, using transgenic mice expressing human Lp(a). Although in this mouse model the presence of apo(a) did not change the severity of arthritis, the co-localization of apo(a) with fibrin in synovial tissue suggests that, in humans, apo(a) may modulate locally the fibrinolytic activity and may thus contribute to the persistence of intra-articular fibrin in inflammatory arthritis.

Animals↗

Secondary amyloidosis: a severe complication of ankylosing spondylitis. Two case-reports.

STUDY OBJECTIVE: To report two cases of amyloidosis secondary to ankylosing spondylitis. PATIENTS AND RESULTS: Of the 47 ankylosing spondylitis patients who have received follow-up at our department over the last few years, two have developed AA amyloidosis. Both have extremely severe, long-standing joint disease, with virtually complete spinal ankylosis and destructive peripheral arthritis of the hips and wrists; one also has tarsal joint destruction. Renal dysfunction was the first manifestation of amyloidosis in both cases. One patient required chronic hemodialysis and developed peritonitis due to colonic perforation, probably at a site of amyloid deposition. CONCLUSIONS: Secondary amyloidosis is a rare complication of ankylosing spondylitis that can cause severe renal and gastrointestinal complications. No treatment capable of clearing established amyloid deposits is available to date.

Adult↗

[Prognostic aspects of scintigraphy and MRI during the first 6 months of reflex sympathetic dystrophy of the distal lower limb: a preliminary prospective study of 4 cases].

PURPOSE: The appearance of scintigraphic and magnetic resonance imaging during the evolution of reflex sympathetic dystrophy of the foot is not well known and subject to controversies. The purpose of this preliminary study is to compare these two types of investigation during the first 6 months of evolution. METHODS: 4 non-selected patients with a diagnosis of acute reflex sympathetic dystrophy of the foot (no more than 2 months of evolution and more than 3 out of 6 clinical criteria suggesting a "warm" phase) were studied prospectively. A clinical evaluation, scintigraphy and magnetic resonance imaging (MRI) were performed at diagnosis and after 3 and 6 months. All available examinations (n = 22) were analyzed independently by independent observers. RESULTS: Clinically 3 of 4 patients developed or previously had another site of sympathetic dystrophy confirmed by total body scintigraphy. After 6 months 2 of 4 patients still have a "warm" dystrophy. Bone scanning showed localized or diffuse tracer uptake and MRI showed bone and soft tissue edema when the sympathetic dystrophy was and/or remained clinically "warm". MRI bone edema moved from one location to another in 3 of 4 patients during the follow-up. There was a good correlation between bone scan and MRI images. In "warm" dystrophy, MRI was positive 5 out of 7 times and scintigraphy in all cases. Bone edema and tracer uptake faded simultaneously although the latter was more diffuse and more persistent than the former. CONCLUSION: MRI as well as bone scintigraphy are suitable for the diagnosis of warm dystrophy of the foot. Both exams remain positive when the dystrophy is still "warm" after 6 months. The radiographic evolution after 6 months still has to be evaluated.

Bone Diseases↗

[Systemic corticosteroid therapy in rheumatology, advantages and risks].

Apart from the therapy of autoimmune diseases, corticosteroids have an important position in the treatment of rheumatoid arthritis. Corticosteroids are used after the failure of non-steroidal antiinflammatory agents or of the basis therapies to control the illness. When the rheumatoid arthritis is accompanied by a systemic disease, they will be used earlier and in higher dosages. For polymyalgia rheumatica, independently of an association with temporal arteritis, corticosteroids are the therapy of choice. Risks of long-time corticosteroid therapy are a higher incidence of infection and bone demineralisation, especially in postmenopausal women. A careful prevention with Calcium and Vitamin D must be carried out systematically. The demineralisation can be limited by the use of Deflazacort, a corticosteroid, which decreases the loss of calcium.

Adolescent↗

T-cell receptor variable alpha (TCRAV) polymorphisms in European, Chinese, South American, AfroCaribbean, and Gambian populations.

Interactions involving the T-cell receptor (TCR) and major histocompatibility complex (MHC) are fundamental to the generation of a specific immune response. The study of interpopulation differences in TCR genes may identify those genes which are subject to selection, and also provides useful information for future genetic studies in these populations. In this study we present analysis of five TCRAV polymorphisms, for V5S1, V6S1, V8S1, V17S1, and V21S1 loci in five human populations by single-strand conformational polymorphism (SSCP) analysis. Caucasian, Chinese, Gambian, AfroCaribbean, and South American Indians (Mapuches) showed marked interpopulation variation for both the silent (V5S1, V17S1, and V21S1) and coding (V6S1 and V8S1) polymorphisms. In general the alleles were conserved in the different populations, but new, additional variants were found for V5S1 and V17S1 in Gambians and Caucasians. V6S1 overall showed the highest nucleotide diversity, and V6S1 genotype distributions were skewed away from expected values in Chinese and Mapuches. Analysis of allelic associations showed a general lack of linkage disequilibrium between the loci, which was reflected by the absence of strong population-specific haplotypes.

Adult↗

Cloning, characterization and expression of carbonic anhydrase from the cyanobacterium Synechocystis PCC6803.

A 3.3 kb HindIII restriction-digest DNA fragment was isolated from a Synechocystis sp. strain PCC6803 subgenomic plasmid library which strongly hybridized to a 349 bp fragment of the icfA (ccaA) gene from Synechococcus sp. strain PCC7942. DNA sequence analysis of the fragment revealed three open reading frames (ORFs), two of which potentially coded for pantothenate synthetase (ORF275) and cytidylate kinase (ORF230). The third, ORF274, was 825 bp in length, encoding a deduced polypeptide of 274 aa (Mr, 30747) that bears 55% sequence identity to the Synechococcus icfA (ccaA) translation product, a beta-type carbonic anhydrase (CA). A 932 bp EcoRI fragment containing ORF274 was subcloned into an expression vector and the construct was transformed into Escherichia coli for overexpression. Electrometric assays for CA activity revealed that whole cell extracts containing the recombinant protein significantly enhanced the rate of conversion of CO2 to HCO3- and that 98% of this catalytic activity was inhibited by ethoxyzolamide, a well-characterized CA inhibitor. Antisera derived against the overexpressed protein recognized a 30.7 kDa protein that was predominantly associated with the isolated carboxysome fraction from Synechocystis. These results provide molecular and physiological evidence for the identification of a ccaA homologue in Synechocystis PCC6803 that encodes a carboxysomal beta-type CA.

Amino Acid Sequence↗

T cells and related cytokines.

T cells play a critical role in rheumatoid arthritis. They are probably continuously involved in pathogenesis, from the initiation to the chronic stage. As recent studies have demonstrated, the part they play in rheumatoid arthritis is closely linked to the roles of macrophages and mesenchymal cells, because they all interact through autocrine, paracrine, and cell-contact pathways. This paper reviews recent work and research regarding the specific role of T cells in the pathogenesis of rheumatoid arthritis.

Animals↗

Analysis of T cell receptor V alpha polymorphisms in rheumatoid arthritis.

OBJECTIVE: To test for association of T cell receptor (TCR) V alpha polymorphisms and rheumatoid arthritis (RA) in British and Swiss white populations. METHODS: TCRAV polymorphisms were analysed in RA patients and controls by single strand conformational polymorphism (SSCP) analysis. Associations were sought between defined genotypes and RA, and the effect of HLA-DR4 status analysed. Putative associations were then retested further in new groups of patients and controls. Overall, 360 RA patients and 197 controls were studied. RESULTS: No association between TCRAV5S1, V6S1, V8S1, V17S1 or V21S1 polymorphisms and RA were observed in the initial population screened. Stratification for DR4 status showed an increase of V5S1*01/*01 in DR4 positive versus DR4 negative patients (chi 2 = 7.19, p = 0.028 (2df), p = 0.14 after correction for multiple comparisons). This putative association was tested in three further patient groups, none of which showed significant increase of V5S1*01/*01 in DR4 positive patients, although an overall trend towards an increase in V5S1*01/*01 was observed. CONCLUSION: No evidence was found for a strong association of TCRAV genes and RA in a white population. However, these results suggest a weak association of V5S1*01/*01 with DR4 positive RA, although this requires confirmation using larger groups of patients and controls.

Arthritis, Rheumatoid↗

Similarities of specificity and cofactor dependence in serum antiphospholipid antibodies from patients with human parvovirus B19 infection and from those with systemic lupus erythematosus.

OBJECTIVE: To assess the phospholipid specificity and immunoglobulin isotype of antiphospholipid (aPL) antibodies in patients with acute parvovirus B19 infection. METHODS: Specificity of aPL and isotype distribution in the negatively charged phospholipids, cardiolipin and phosphatidyl serine, and in the neutral phospholipid, phosphatidyl ethanolamine, were measured in the sera of patients with acute parvovirus B19 infections (n = 12), in those with other acute viral infections (n = 10), and in those with syphilis (n = 15) by enzyme-linked immunosorbent assays. The dependence of anticardiolipin (aCL) binding on the presence of beta 2-glycoprotein I (beta 2-GPI) as a binding cofactor was assessed in these same groups, and was compared with sera from systemic lupus erythematosus (SLE) patients (n = 11) with raised aCL antibody reactivity. RESULTS: Antibodies against any of the 3 phospholipids were found in all 3 groups of patients with infections (B19 in 11 of 12 patients, other viral infections in 8 of 10 patients, and syphilis in 14 of 15 patients). B19 patients' sera contained predominantly IgG antibodies against the negatively charged phospholipids, cardiolipin and phosphatidyl serine, and differed in their specificity and isotype distribution from those found in the other 2 patient groups. B19-associated aCL increased their binding to antigen in the presence of beta 2-GPI as a binding cofactor, similar to aCL found in SLE patients, but unlike antibodies from patients with other viral infections or from those with syphilis. CONCLUSION: The results show the remarkable similarity in specificity of aPL antibodies between B19-infected patients and SLE patients, and raise the question of whether parvovirus infection may be a trigger for the development of aPL antibodies in autoimmune diseases.

Antibodies, Anticardiolipin↗

Anti-PL 4 in patients with systemic lupus erythematosus with severe renal and haematological disease.

Anti-PL 4 is an autoantibody which binds to a 150 kDa polypeptide and is found in approximately 1% of SLE sera. The clinical and laboratory features of 16 patients who have had anti-PL 4 detected in their serum are presented. Anti-PL 4 is highly specific for SLE (100%) and identifies a population of patients who typically develop severe renal (75%) and haematological disease (100%).

Antibody Specificity↗

Propionibacterium avidum sacroiliitis and osteomyelitis.

The anaerobic Gram-positive bacterium Propionibacterium avidum is a common inhabitant of the skin with low pathogenicity. We report a case of P. avidum sacroilitis, psoas abscess and osteomyelitis in a 67-year-old male who had recently undergone surgical repair of an inguinal hernia. The organism was recovered from blood cultures, a bone biopsy specimen and specimens from the abscess. The spectrum of bone and joint infections caused by Propionibacterium is discussed. Infection by Propionibacterium spp. should be considered in patients with bone and joint infections.

Aged↗

[Anti-synthetase syndrome: a special subgroup of idiopathic inflammatory myopathies. Apropos of 3 case reports].

Anti-synthetase antibodies are found in 20 to 25% of all idiopathic inflammatory myopathies and allow identification of a syndrome associating myositis with interstitial pulmonary disease (50 to 70%), polyarthritis, Raynaud's phenomenon and mechanic's hands. Anti-Jo-1 is the most common anti-synthetase antibody. If anti-Jo-1 is present, interstitial lung disease must be looked for, because this is the most important determinant of the outcome. Treatment with high doses of corticosteroids is required. Immunosuppressive drugs are added in resistant cases or as corticosteroid-sparing agents.

Adult↗

Miscellaneous metabolic diseases.

Musculoskeletal manifestations are commonly observed in metabolic disorders. Here we review the recent literature on several metabolic arthropathies. Hemochromatosis should be suspected in patients with the sign of the "iron salute". Screening for this disorder by routine measurement of transferrin saturation appears to be a cost-effective procedure in white men aged 30 years or older. In dialysis arthropathy, radiologic lesions of the hand joints increased in size and frequency with the duration of dialysis. However, destructive arthropathy of the fingers is not necessarily related to amyloid deposition. In patients with dialysis-related beta 2-microglobulin amyloid deposition, renal transplantation improved clinical rheumatologic manifestations but did not prevent progression of destructive arthropathies nor dissolution of amyloid deposits. In ochronotic arthropathy, spinal changes may resemble those seen in ankylosing spondylitis and can lead to cord compression. The presence of brownish-blackish rods in the synovial fluid is an unusual but useful diagnostic tool. Metabolic factors are likely to play a role in the pathogenesis of diffuse idiopathic skeletal hyperostosis, and recent studies have demonstrated elevated insulin and growth hormone but normal insulin-like growth factor-1 levels in these patients. Other metabolites that may play a role in this condition include retinoids and bone morphogenetic protein-2.

Humans↗