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Biomedical subjects

A Shore

Publications and source records attributed to A Shore.

At least 37 records · Page 2Linked to original sources

Juvenile psoriatic arthritis and HLA antigens.

The clinical, laboratory, and radiological features, including histocompatibility typing, of 28 patients with juvenile psoriatic arthritis are reported. The most common presentation was that of psoriasis preceding or occurring simultaneously with arthritis. The most common course of juvenile psoriatic arthritis was to start as an oligoarthritis and progress, usually to polyarthritis. No patients with juvenile psoriatic arthritis had uveitis. Overall, most patients had a good outcome (93% in functional class I and II), though 8/28 (29%) did require disease modifying drugs over a mean period of 8.8 years of follow up. The clinical features of these patients were very similar to those of a group of 158 adult patients with psoriatic arthritis with the same disease duration followed up in the clinic. Although there was an increased prevalence of B17 in both juvenile and adult psoriatic arthritis, juvenile psoriatic arthritis showed increased prevalence of A2, whereas adult psoriatic arthritis showed increased prevalence of B27, Bw39, and Cw6. This HLA association differed from that reported in other forms of juvenile arthritis.

Adolescent↗

Endothelial cells modulate both T-cell-dependent and T-cell-independent plaque-forming cell generation in vitro.

The effects of live endothelial cells (EC), paraformaldehyde fixed EC, and EC supernatant were measured on pokeweed mitogen (PWM)-induced T-cell-dependent plaque-forming cell (PFC) generation by peripheral blood mononuclear cell (PBM). At low doses (less than or equal to 2 x 10(4) cells/culture) live EC helped PFC generation. At higher doses (greater than or equal to 10 x 10(4) cells/culture) the effect of live EC was always marked suppression (less than 10% of baseline PFC). In contrast both fixed EC and EC supernatant provided help exclusively over a wide dose range. The EC-helper effect enhanced the sensitivity of PBM to suboptimal PWM doses and also accelerated the rate of PFC generation during culture. EC influences on PFC could not be modified by gamma-interferon induction of surface DR which is known to modify EC accessory cell ability. There was also only minimal helper activity of live EC and fixed EC on the PFC generation by Epstein-Barr virus-induced cultures of purified B cells (which had been depleted of both T cells and monocytes). In contrast, suppression (greater than 97%) of PFC in isolated B-cell cultures was found even when EC constituted less than 1% of cultured cells. These results imply EC have the potential of providing multiple regulatory signals which modulate in vitro antibody production. EC-derived mechanisms are independent of their accessory cell function and require interaction with non-B cells for help, but suppression may occur directly at the B-cell level.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗

Methotrexate-nonsteroidal antiinflammatory drug interaction in children with arthritis.

In order to assess the interaction between methotrexate (MTX) and nonsteroidal antiinflammatory drugs (NSAID), we studied the pharmacokinetics of oral MTX alone and in the presence of the usually prescribed NSAID in 7 children with chronic arthritis. The NSAID studied included tolmetin, indomethacin, naproxen, and aspirin. Six patients were treated with multiple NSAID. The mean MTX elimination half-life was prolonged when NSAID were coadministered (1.7 +/- 0.5 vs 1.2 +/- 0.1 h; p = 0.03). However, neither the apparent MTX clearance (CI) (10.6 +/- 5.5 vs 13.1 +/- 3.5 l/h; p = 0.19), the area under the serum MTX concentration-time curve (Auc) (2.1 +/- 1.0 vs 1.5 +/- 0.6 mumol/l/h; p = 0.08) or the apparent volume of distribution (Vd) (23.0 +/- 6.2 vs 21.9 +/- 6.4 l; p = 0.53) was significantly altered by the administration of NSAID. Although the differences between the mean Cl and Auc were not statistically significant, a wide variation in the impact of NSAID on MTX Cl was observed. In 6 of 7 patients, the Auc increased during NSAID administration from 19 to 140%. This degree of increase may be clinically significant in some individuals. It is consequently recommended to closely monitor patients who are receiving MTX and NSAID for MTX toxicity until these results can be verified in a larger population.

Anti-Inflammatory Agents, Non-Steroidal↗

Impaired late suppression of Epstein-Barr virus (EBV)-induced immunoglobulin synthesis: a common feature of autoimmune disease.

We examined regulation of Epstein-Barr virus-induced plaque-forming cell generation in peripheral blood mononuclear cells from several autoimmune and seronegative diseases and correlated these results with Epstein-Barr virus-induced proliferation. We confirmed the defective regulation of Epstein-Barr virus-induced plaque-forming cells in peripheral blood mononuclear cells of patients with rheumatoid arthritis and scleroderma. Peripheral blood mononuclear cells from patients with seronegative arthropathies and chronic infective inflammation (cystic fibrosis) had normal regulation of Epstein-Barr virus-induced plaque-forming cells. Peripheral blood mononuclear cells from rheumatoid arthritis had excessive plaque-forming cell generation in the face of a normally regulated decrease in Epstein-Barr virus-induced proliferation. In contrast, peripheral blood mononuclear cells from scleroderma had defective suppression of both Epstein-Barr virus-induced proliferation and plaque-forming cell generation. Thus, impaired regulation of Epstein-Barr virus-induced plaque-forming cell generation is a common feature of autoimmune disease and demonstrates some specificity for these disorders.

Adult↗

Enhanced T-cell-activation due to combined stimulation by both endothelial cells and monocytes.

Mitogen-induced interleukin 2 (IL-2) secretion by T cells was greatly enhanced by the combined presence of endothelial cells (EC) and monocytes (AC). EC also altered the time course of IL-2 secretion by peripheral blood mononuclear cells (PBM) in response to mitogens. The response to EC did not require expression of HLA-DR antigen and occurred equally well in response to autologous EC. At least one live accessory cell was required to induce T cells to secrete IL-2. When added to T cells plus live AC, both fixed EC and EC supernatant partially reproduced the enhancing effect of EC. Surface membrane IL-1 was present on both live and fixed EC. However, active EC supernatant contained no detectable IL-1 activity. Anti-IL-1 abolished the enhancement of T-cell responses by fixed but not live EC.

Endothelium, Vascular↗

A new technique of experimental heterotopic cardiac transplantation.

Heterotopic cardiac transplantation is a useful method for studying allograft rejection. In this study a new technique of cardiac transplantation was carried out, which involved retroperitoneal anastomoses of the donor ascending aorta and main pulmonary artery with the recipient abdominal aorta and inferior vena cava respectively. The procedure was simple and effective and was accomplished with minimal operative mortality and postoperative morbidity. The method allows better access to the allograft for repeated open myocardial biopsies, obviating the limitations of transvenous fluoroscopically directed endomyocardial biopsy. This technique of retroperitoneal heterotopic cardiac transplantation has important advantages compared with similar procedures performed in the neck, abdomen, or thorax.

Animals↗

Pauciarticular juvenile rheumatoid arthritis presenting in an adult.

Type I pauciarticular juvenile rheumatoid arthritis (PA-JRA) is characterized by a female predominance, chronic iridocyclitis and a positive antinuclear antibody (ANA) test. In contrast, patients with type II PA-JRA are usually male, have a negative ANA test, but are HLA-B27 positive. We report a patient with longstanding iridocyclitis who presented at age 20 with oligoarthritis, whom we believe has Type I PA-JRA. Slit lamp examination should be considered in patients with oligoarthritis; the detection of asymptomatic chronic iridocyclitis may aid in the diagnosis. Untreated, this condition may cause irreversible ocular damage.

Adult↗

Transient fall in serum salicylate levels following intraarticular injection of steroid in patients with rheumatoid arthritis.

Our study of 13 hospitalized patients with rheumatoid arthritis examined the effect of intraarticular injection of steroid on serum salicylate levels. A mean decrease in serum salicylate levels of 42 +/- 14.5% was observed in 12 patients within 12-36 hours post-injection (P less than 0.005). This interaction, though transient, may be very significant clinically. It may lead to erroneous conclusions concerning patient compliance, unwarranted increases in salicylate dosage and resultant toxicity, and delay of appropriate therapeutic maneuvers.

Adult↗

Comparison of accessory cell functions of endothelial cells and monocytes: IL-2 production by T cells and PFC generation.

It has been previously shown that endothelial cells (EC) can modulate T-cell responsiveness by mimicking monocyte (AC) function in several different in vitro systems. We now report that EC and AC differ quantitatively in their ability to provide help for IL-2 generation and T-cell induced B-cell differentiation into immunoglobulin secreting cells (ISC). Equal numbers of EC were deficient when compared to AC for promoting ISC generation, but exceeded AC for IL-2 production. Adding optimal numbers of EC drive non-adherent cell cultures to produce more than twice as much IL-2 as adding any number of AC. Furthermore, small numbers of EC were capable of modulating ongoing immune responses when added to cultures containing AC. IL-2 production by PBM was doubled by the addition of enough EC to comprise only 3% of the total culture. EC do not just mimic monocytes in immune responses, but modulate these responses in unique ways.

Antibody-Producing Cells↗

The musculoskeletal manifestations of cystic fibrosis.

Twenty-seven patients with CF and joint complaints were reviewed. Twelve patients had arthritis, 11 had HPO, and four had symptoms of mechanical neck and back pain. We have confirmed the association of CF with an episodic form of arthritis. For the first time, we have reported that a subgroup of these patients later develop persistent synovitis with progressive asymmetric, erosive disease. The etiology of CF arthritis is unclear, but may relate to chronic infection and immune complex mechanisms. CF arthritis can be contrasted with CF induced HPO, which is associated with worse lung disease, a male predominance, and an older mean age of onset of symptoms. Mechanical neck and back pain may relate to an associated scoliosis or kyphosis in CF.

Adolescent↗

Arthritis associated with Haemophilus influenzae meningitis: septic or reactive?

We reviewed 165 pediatric cases of Haemophilus influenzae type b meningitis and found 11 (6.7%) with associated arthritis. Synovial fluid culture and Gram stain suggested that only three of these 11 cases were caused by a septic process. In all three children with septic arthritis, joint symptoms were present on admission or within 24 hours. In contrast, of the eight who had reactive arthritis, arthritis did not appear in six until after 1 week of antibiotic therapy. Patients with septic arthritis were older than patients with reactive arthritis (mean 31 months vs 17 months), had a longer duration of symptoms before the start of antibiotic therapy (mean 6.0 days vs 2.5 days), and were more likely to have a positive blood culture (67% vs 18%). It is probable that the majority of episodes of synovitis occurring after H. influenzae meningitis occur as a result of a reactive rather than a septic process. Treatment of reactive arthritis should be with anti-inflammatory agents rather than with multiple joint aspirations and prolonged antibiotic therapy.

Arthritis↗

Correlation of renal histology with outcome in children with lupus nephritis.

We assessed renal histological features in 20 children with diffuse proliferative lupus nephritis (DPLN) to determine whether they were useful in predicting clinical outcome. Renal biopsies were analyzed by assigning scores indicating an activity index (AI) and chronicity index (CI). Clinical assessment of renal function at biopsy and outcome were graded according to urinalysis, serum creatinine, need for dialysis and/or transplantation, and/or death from end-stage renal failure. Renal function at biopsy correlated significantly with AI and CI. Serum complement (C3 and C4) correlated significantly with CI but not with AI. The usefulness of the clinical grading system was confirmed in ten patients who underwent repeat biopsies. Of these, four converted from DPLN to mesangial or membranous lupus and showed improvement in their grade, while only one of the six with DPLN on both biopsies improved. After a mean follow-up of 4.0 years, 14 of the 20 patients showed clinical improvement, four were unchanged, and two were worse. CI predicted clinical outcome (P less than 0.01) but AI did not. Histologic scores of AI and CI obtained from renal biopsies showing DPLN may be useful in predicting therapeutic responses and designing prospective clinical trials to determine optimum management of children with DPLN.

Adolescent↗