Search PubMed⌕ Search

Biomedical subjects

A C Keat

Publications and source records attributed to A C Keat.

At least 19 recordsLinked to original sources
PubMed1997

Perioperative use of methotrexate--a survey of clinical practice in the UK.

We have surveyed the use of methotrexate in the perioperative period in patients with rheumatoid arthritis (RA) undergoing surgery. A total of 200 consultant rheumatologists and 200 consultant orthopaedic surgeons in the UK were sent a postal questionnaire. Thirty-five per cent of rheumatologists and 46% of orthopaedic surgeons were concerned that the drug may increase the risk of post-operative complications, although significantly less 'always' stopped the drug around the time of surgery. There was great variation in the timing of stopping the drug with most stopping treatment within 2 weeks before surgery and restarting within 2 weeks after surgery. The majority of clinicians surveyed (70%) felt that national guidelines for the perioperative use of methotrexate would be helpful.

Antirheumatic Agents↗
PubMed1996

Antigen-presenting cells but not lymphocytes in the joint may indicate the cause of reactive arthritis.

T cells and antigen-presenting cells (APC) accumulate in the joint in reactive arthritis and there are reports that the T cells are a population selected for responsiveness to the causative agent. In this work, the latter view is questioned by detailed studies of the antigen specificities of the lymphocytes within the joint (SFMC) and peripheral blood (PBMC) of patients with reactive arthritis triggered by infection with Chlamydia trachomatis. Using a hanging-drop microculture system. SFMC displayed enhanced responses not only to antigens from the triggering organism, but also to other antigens, including PPD and tetanus toxoid, to which the patients were likely to have had prior exposure. No evidence was obtained for a dominant cross-reactive T-cell response to epitopes common to these antigen preparations, confirming the polyclonal nature of the infiltrate. In contrast to the broad specificity of the T-cell infiltrate, two experimental approaches indicated that APC within the joint carried chlamydial antigen. The failure of antigen-bearing APC to interact with T cells at this site may underlie the inability to clear microbial antigen from the joint.

Antigen Presentation↗
PubMed1994

Reiter's syndrome and reactive arthritis: a current view.

This paper reviews advances in the understanding of the pathogenesis of reactive arthritis that have occurred over the last decade. Inflammatory aseptic joint disease has been linked with prior infection initiated by many different species of microorganisms. The presence of intra-articular bacterial antigens has now been firmly established with the demonstration of bacteria, bacterial fragments, DNA, RNA, and bacterial lipopolysaccharide in joints of patients with reactive arthritis. Chlamydia trachomatis, Salmonella enteritidis, and Shigella flexneri have all been detected in the joint by immunological techniques, although there is still some doubt as to the form in which they reach the joint and whether or not they persist. A number of phlogistic bacterial components could be acting as arthritogens. Negative joint culture results from patients with reactive arthritis make it unlikely that bacteria in the joint are viable, although chlamydial DNA has been shown in the joints of patients with sexually acquired reactive arthritis using the polymerase chain reaction. The use of antimicrobial therapy in the treatment of reactive arthritis is under review; data suggests that long-term antibiotic treatment warrants further study. The role of HLA-B27 in disease pathogenesis is discussed as are possible mechanisms of interplay between germ and gene. HLA-B27 might confer disease susceptibility by affecting immune mechanisms other than classical antigen presentation. The immunopathogenesis of joint inflammation in reactive arthritis is explored with reference to studies of humoral and cellular immune responses. Serological evidence to support the concept of molecular mimicry is far from conclusive; the results of relevant studies are summarized. Lymphocyte proliferation experiments suggest that antigen presenting cells play an important role. Finally, our views on reactive arthritis in the 1990s, and areas of new and potentially fruitful future research are presented.

Antigens, Bacterial↗
PubMed1993

Infectious agents in reactive arthritis.

It is now clear that the deposition and persistence of bacterial antigens in the joint are significant features of reactive arthritis. It is possible that in some instances this represents persistence of live bacteria, and several studies point to the potential value of antimicrobial therapy. Searches for bacterial DNA and RNA have yielded conflicting data, however, so further developments in this area will be of great importance. It is likely that bacterial antigens interact in some way with class I major histocompatibility complex (MHC) antigens in the pathogenesis of reactive arthritis. However, with the increasing understanding of the structure and function of HLA molecules, some evidence of a classic antigen-class I MHC-CD8 T-lymphocyte interaction is now emerging. Thus far, the mechanisms that link HLA-B27 and bacterial antigens with reactive arthritis remain unclear.

Adolescent↗
PubMed1993

HLA-B27 subtypes in the spondarthropathies.

The spondarthropathy (Sp)-associated HLA-B27 antigen includes at least seven subtypes, B*2701-07, of which 01, 02, 05 and 07 occur in Caucasians. This study examined the B27 subtype distribution in British patients with Sp. The 133 HLA-B27+ subjects comprised 94 European Caucasian Sp (58 ankylosing spondylitis (AS), 22 reactive arthritis (ReA; 11 sexually acquired (SARA), 11 enteric (EReA)), eight undifferentiated Sp (USp), and six pauciarticular juvenile-onset chronic arthritis (pJCA)) patients, and 34 healthy Caucasian controls, together with four Asian Indian and one Chinese. 35S-labelled B27 was immunoprecipitated with anti-B27 MoAbs, and subtyped according to isoelectric point (pI) following isoelectric focussing. The use of B27 MoAb permitted subtype assignment without full class I HLA typing. The vast majority (95%) were B*2705 (Caucasian controls 31/34; AS 55/58; ReA 21/22; USp 8/8, and pJCA 6/6; Indian control 1/1 and AS 2/3; Chinese pJCA 1/1), and the remainder B*2702. No B*2701 or 07 subjects were identified. AS occurs in both B*2702 and 05 subjects, and we extend this observation to small numbers of ReA and of Indian AS subjects. This implicates molecular features shared between B27 subtypes, rather than subtype-determining regions of the antigen, in Sp pathogenesis.

Antibodies, Monoclonal↗
PubMed1992

Detection of Chlamydia trachomatis DNA in joints of reactive arthritis patients by polymerase chain reaction.

In 1986, Chlamydia trachomatis elementary bodies were found by direct immunofluorescence (DIF) in synovial-fluid cell deposits and synovial-membrane biopsy samples from five of eight patients with sexually acquired reactive arthritis (SARA) but in none of eight controls with other types of arthritis. Cells from the original slides (stored at 4 degrees C) have now been examined by a polymerase chain reaction (PCR) that amplifies DNA for the major outer membrane protein of C trachomatis. Chlamydial DNA was found in samples from four DIF-positive patients, one DIF-negative patient, and one DIF-negative control. Overall, there was 80% concordance for DIF and PCR results. This study supports our previous finding of chlamydiae in joints in reactive arthritis.

Adult↗
PubMed1992

Septic bone, joint and muscle lesions associated with human immunodeficiency virus infection.

Ten episodes of musculoskeletal sepsis have been seen in nine patients with HIV infection. Seven patients had AIDS, circulating CD4-positive lymphocyte counts being less than 0.1 x 10(9)/l in six. Septic arthritis recurred in seven patients, osteomyelitis in three and pyomyositis and bursitis each occurred in one patient. Staphylococcus aureus was isolated from four patients, atypical micro-organisms being found in three. Presentation of musculoskeletal infection in this patient group may be atypical but rapid diagnosis is important as early antimicrobial therapy is often successful.

Adult↗
PubMed1991

Echocardiographic diastolic abnormalities of the left ventricle in inflammatory joint disease.

Echocardiographic early diastolic abnormalities have been shown recently in 50% of men with ankylosing spondylitis. Similar techniques were used to investigate subjects with rheumatoid arthritis and psoriatic arthritis with or without spondylitis. These subjects had no clinical, radiographic, or electrocardiographic evidence of cardiac or respiratory disease. Echocardiographic abnormalities seen resembled those of ankylosing spondylitis in that the interval between minimum left ventricular dimension and mitral valve opening was prolonged in 12 of 22 subjects with rheumatoid arthritis and in seven of 11 subjects with psoriatic arthritis. Isovolumic relaxation time was significantly prolonged in four subjects with rheumatoid arthritis and one with psoriatic arthritis. Unlike ankylosing spondylitis, however, there was consistent reduction in peak rate of left ventricular dimension increase in subjects with rheumatoid arthritis and psoriatic arthritis. In addition, the dimension increase during atrial systole was greater than normal in nine subjects with rheumatoid arthritis and two with psoriatic arthritis. The most likely cause of these abnormalities is increased connective tissue deposition in the myocardium.

Adult↗
PubMed1991

Intra-articular chlamydial antigen and inflammatory arthritis.

Joint material from 133 patients with well-characterized inflammatory arthritis, including individuals likely to have suffered reactive arthritis, was studied. The majority of patients were also examined for the presence of genital tract infection with Chlamydia trachomatis. Fluorescein-conjugated monoclonal antibodies demonstrated the presence of C. trachomatis antigen in synovial fluid cell deposits or synovial sections from inflamed knee joints of seven patients with reactive arthritis. The significance of these findings is discussed, as is the low rate of detection of chlamydial antigen in either the genital tract or the joint from patients in this study. We emphasize the need for further work aimed at identifying the relevant immunogenic chlamydial antigens responsible for the initiation of reactive arthritis.

Adult↗
PubMed1990

The detection of human immunodeficiency virus DNA in dendritic cells from the joints of patients with aseptic arthritis.

Three patients with inflammatory arthritis were found to be seropositive for human immunodeficiency virus (HIV). Two of these individuals developed synovitis following an episode of yersinia bowel infection. We have studied joint material from all three in an attempt to define the role that HIV may be playing in the aetiology or maintenance of arthritis. Cell-associated HIV DNA was detected within joint fluid by in situ hybridization and the phenotypes of infected cells were established using a double-labelling immunocytochemical technique. Viral DNA was detected in dendritic cells (4-25%) isolated from both the peripheral blood and synovial fluid and in occasional lymphocytes from peripheral blood (less than 0.1%). No infected macrophages were seen. Functional studies using the mixed leucocyte reaction showed that the dendritic cells from synovial fluid were poor stimulators of allogenic peripheral blood lymphocytes whilst being effective at stimulating autologous lymphocytes. In addition, synovial fluid lymphocytes responded poorly to normal control dendritic cells. Infection of these cells with HIV could be contributing to this low stimulatory activity of antigen-presenting cells and to the unresponsiveness of lymphocytes.

Adult↗
PubMed1990

Chlamydial DNA is absent from the joints of patients with sexually acquired reactive arthritis.

The polymerase chain reaction was used to detect the presence of a plasmid essential for the growth of Chlamydia trachomatis. As few as 10 copies of the plasmid in the initial reaction mix were detectable using this technique. In contrast, chlamydial DNA was not detectable in the knee joints of nine patients with definite sexually acquired reactive arthritis (SARA) or nine patients with suspected SARA. Five patients with an undifferentiated seronegative lower limb oligoarthropathy, one with Crohn's disease and another with post-enteric reactive arthritis had evidence of intra-articular chlamydial antigens as judged by fluorescein-labelled monoclonal antibody staining of joint material but, again, no chlamydia plasmid DNA was detected. The nature of the immunofluorescent staining seen in some of these samples remains to be elucidated. It could be due to the presence of chlamydial outer membrane protein or lipopolysaccharide antigens in the joints, either free or in immune complexes, or it may be artefactual. Our results indicate that viable C. trachomatis is not present in the joints of the patients in this study even in the presence of chlamydial antigen detected by fluorescence antibody testing.

Arthritis, Infectious↗