Biomedical subjects
Publications and source records attributed to J V Bertouch.
Six patients with Felty's syndrome were reevaluated after a course of chrysotherapy. In 5 patients, white cells and absolute neutrophil counts had returned to normal. In 4 of these, there was significant concomitant improvement in neutrophil function as assessed by the ability of cells to generate superoxide radicals.
Paired samples of synovial fluid (SF) and blood were obtained prior to and at 4 and 24 hours following high-dose methylprednisolone infusion therapy in a group of patients with refractory rheumatoid arthritis. After therapy there was a significant decrease in numbers of polymorphonuclear leukocytes, lymphocytes, immune complexes, and C-reactive protein in the SF. Measurement of lymphocyte subsets, using monoclonal antibodies, revealed that at 4 hours postinfusion, there was a disproportionate decrease in the percentage of SF lymphocytes expressing class II antigens (HLA-DR or Ia-like). These data suggest that glucocorticoids induce rapid changes in SF indices of disease activity and may directly influence T cell activation within the rheumatoid joint.
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Membrane activation of human neutrophils by preformed immune complexes and heat aggregated human gammaglobulins was studied by chemiluminescence. Strong neutrophil activation was found with human-albumin rabbit-antialbumin complexes prepared at equivalence, with maximal activation occurring in slight antigen excess. Furthermore different preparations of heat aggregated gammaglobulin which were of large size also showed similar activity. In contrast, heat aggregates of small size were inactive and blocked the chemiluminescent response found with larger active aggregates. A purified monoclonal rheumatoid factor with specificity for IgG modulated these responses when preincubated with preformed complexes or aggregates. Both enhancement of the neutrophil chemiluminescence response with inactive preparations and suppression of the response with highly active preparations were observed. Kinetic studies of the neutrophil chemiluminescent response varied with respect to the activating preparation, but were generally biphasic. This observation suggested an initial direct membrane activation followed by a more delayed response reflecting phagocytosis of complexes. We have demonstrated the direct activation of neutrophil chemiluminescence by laboratory preparations of immune complexes. The chemiluminescent responses observed were influenced by both the size and immunochemical properties of the activating complexes and by the presence of rheumatoid factor. These observations may have important implications in the immunopathogenesis of immune-complex-mediated diseases.
Lymphocyte subsets defined by monoclonal antibodies, C reactive protein (CRP), immune complexes (IC), rheumatoid factor (RF), C3, C4 and neutrophil and lymphocyte numbers were measured in synovial fluid (SF) and blood samples from 11 patients with rheumatoid arthritis. SF showed an increased percentage of T cells, Ia+ cells and OKT8+ cells and a reduced percentage of B cells and OKT4+ cells, when compared with blood. Reduced levels of CRP, RF, C3 and C4 were found in SF compared with blood. Comparisons between cellular subsets and other indices in SF revealed a positive correlation between neutrophil numbers and IC, CRP, and RF with a negative correlation between neutrophil numbers and numbers of T cells and OKT8+ cells. A similar negative correlation was found in blood between OKT8+ cells and both CRP and RF. These results indicate an association between increasing disease activity and a lack of suppressor/cytotoxic cells in both circulating and intraarticular compartments. An additional important finding was the lack of correlation of Ia+ cells in both SF and blood with neutrophil numbers, CRP, IC, C3 and C4 or RF.
Computed tomography (CT) was used to delineate the paraspinal musculature in 14 patients with ankylosing spondylitis (AS). Abnormal atrophy of the erector spinae muscles and multifidi was demonstrated in all 8 patients with total bony ankylosis of the spine, but was not present in those with isolated syndesmophyte formation, vertebral squaring alone or sacroiliac joint ankylosis with normal spinal radiographs. There was a significant positive correlation between a CT score of paravertebral muscle wasting and clinical parameters of disease duration and restriction of spinal mobility. Wasting and asymmetry of the psoas muscles was seen in 3 patients with unilateral hip joint involvement. These findings suggest that a relationship exists between decreased or absent spinal movement and atrophy of the paraspinal musculature in AS.
Monoclonal antibodies specific for lymphocyte subsets were used to examine circulating lymphocytes obtained at frequent intervals from healthy subjects. A diurnal rhythm was found in the total numbers of lymphocytes, T cells, inducer/helper cells, suppressor/cytotoxic cells, Ia positive cells, and B cells. The lowest levels of all subsets were seen at 0900 hours and the highest levels at 2100. In some subjects the ratio of helper to suppressor cells varied considerably during the sample period, though the ratio was relatively constant for the group as a whole.
Plasma concentrations of methylprednisolone following intra-articular injection were measured in rheumatoid arthritis and osteoarthritis patients. While substantial plasma concentrations were seen in both groups of patients there was no significant difference in the rate or extent of absorption of methylprednisolone from osteoarthritic or rheumatoid knees. This study suggests that it is the dissolution rate of the steroid formulation rather than the characteristics of the synovial membrane which determine rate and extent of systemic absorption of methylprednisolone after intra-articular injection.
The majority of paired sera and synovial fluids from 21 patients with rheumatoid arthritis produced a rapid chemiluminescent response when incubated with human neutrophils. Synovial fluid gave considerably higher responses than the paired serum specimen. In contrast little or no response was found with paired sera and joint fluid taken from patients with gout, psoriasis, and osteoarthritis and with sera from healthy donors. A similar chemiluminescent response was observed when neutrophils were preincubated with large aggregates of heated human gammaglobulin (HAGG), which were used as a model of immune complexes. Smaller nonreactive aggregates of gammaglobulin became reactive after preincubation with a purified monoclonal rheumatoid factor (mRF) which had a high avidity for aggregated IgG. The addition of this monoclonal rheumatoid factor also caused enhancement of chemiluminescence by rheumatoid sera. Further evidence suggesting that the active material found in these rheumatoid specimens contained complexed immunoglobulin was obtained by indirect immunofluorescence. Neutrophils developed intracellular immunoglobulin inclusions after preincubation in reactive rheumatoid sera but not with nonreactive or normal sera. However, activation of neutrophil chemiluminescence by rheumatoid specimens did not correlate significantly with levels of rheumatoid factor or immune complexes suggesting that the activating complexes were of a particular type. In conclusion we have shown the direct activation of neutrophil chemiluminescence by rheumatoid sera synovial fluid and suggest that the activation is caused by large IgG-containing immune complexes. It is possible that this activation may have important implications in the immunopathogenesis of the rheumatoid inflammatory process.
The concentration of C-reactive protein (CRP) in sera from 70 patients with systemic lupus erythematosus (SLE) showed no correlation with commonly accepted laboratory indices of disease activity. Most patients had detectable serum CRP, but in some patients CRP was not found despite repeated testing. This absence of a CRP response did not appear to be related to medication. In some patients high levels of CRP were seen in the absence of infection. Measurement of serum CRP in SLE is unlikely to be useful in the laboratory diagnosis of disease activity.
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Indomethacin is still used commonly for the treatment of rheumatic diseases but is associated with side effects, particularly headache, in a number of patients. A controlled or sustained release formulation of indomethacin might provide lower peak plasma levels and thus reduce side effects while still maintaining adequate plasma levels to control pain and inflammation. In this single dose crossover study, normal volunteers received the new formulation of indomethacin (Indocid GITS 6/85) fasting or with a standard meal, indomethacin 75 mg with a standard meal or indomethacin 25 mg three times daily with a standard meal. Plasma concentration data showed that peak plasma levels were reduced but the area under the plasma concentration curve was not significantly different between the four treatments.
AIMS: The aim of the present study was to determine if urinary excretion of type I collagen N-terminal telopeptides (UrNTx) and deoxypyridinoline (UrDPD) and serum levels of type I collagen C-terminal telopeptides (SeCTx) differed in patients with rheumatoid arthritis (RA) compared with populations matched for age and gender with and without osteoarthritis (OA). The correlation of markers of bone turnover with disease activity in patients with RA or radiographic severity in patients with OA was also examined. METHODS: Patients with RA aged >50 years (men) and >60 years (women) were identified from computer databases at two tertiary referral centres for rheumatology. Strict exclusion criteria were applied to avoid the effects of factors known to influence markers of bone turnover. Patients with RA and OA were matched for age and sex with a control population free of known arthritic disease and a population with OA. Bone markers were assayed in serum and urine. Urine markers were measured on three consecutive days and mean values used to minimize day-to-day variability of these analytes. RESULTS: The level of UrNTx was elevated in patients with RA compared with normal controls and patients with OA. UrNTx and UrDPD correlated with markers of disease activity in patients with RA (erythrocyte -sedimentation rate and C-reactive protein), but not with -clinical signs of inflammation (swollen and tender joint counts). Patients with OA failed to show any correlation between markers of bone turnover and radiographic severity. CONCLUSIONS: These data support a role for the use of UrNTx and UrDPD in further studies of the patho-physiology of RA and in longitudinal studies designed to modify the course of clinical disease.
Monosodium urate (MSU) crystals were shown in synovial (SF) fluid taken from the asymptomatic knee joints of 11 out of 13 patients with tophaceous gout. Intracellular crystals were identified in some cases. Examination of synovial biopsies taken concurrently revealed MSU crystals in 2 out of 6 cases. The results show that MSU crystals can be found in SF and synovium in the absence of acute gout. This implies that additional factors are important in the pathogenesis of gouty inflammation.