Biomedical subjects
Publications and source records attributed to A Zoma.
A case is reported of tongue atrophy in a patient with mixed connective tissue disease (MCTD) and major myositic involvement. The case highlights oropharyngeal aspects of MCTD, including inability to wear dentures, dysarthria, and dysphagia. To our knowledge this is the first report of major tongue involvement in myositis as part of MCTD.
Penicillamine shows some structural similarities to carbocysteine. The ability to oxidize carbocysteine, i.e., the sulfoxidation status, shows a bimodal distribution in the general population. In this study, sulfoxidation status was determined in 50 of 60 rheumatoid arthritis patients receiving penicillamine. We found that poor sulfoxidation status, compared with good sulfoxidation status, was associated with a 3.9 times higher incidence of toxicity.
Measurement of the complement activation products C1s:C1-inh, C3bP and C5b-9 by ELISA in plasma samples from normals, rheumatoid arthritis (RA) and systemic lupus erythematosis (SLE) patients showed significantly elevated levels in the two patient groups (P less than 0.0001 for C1s:C1-inh, C3bP and C5b-9) compared to normals. In seropositive RA patients there were significant correlations between the levels of the three complement activation complexes and IgM-RF, IgG-RF and IgA-RF. However, IgM-RF did not interfere with any of the ELISA systems. Mean levels of C1s:C1-inh, C3bP and C5b-9 were the same in paired plasma and synovial fluids; however, C3bP levels in the paired samples did not correlate with one another by rank. Our conclusions are that: (a) elevated plasma levels of these complement activation products are detectable in rheumatic diseases; (b) plasma levels of these complement activation products are related to Rheumatoid factor (RF) levels in seropositive RA patients; and (c) IgM-RF does not influence these solid-phase ELISA procedures.
Myelopathy is a well recognised but infrequent neurological manifestation of systemic lupus erythematosus (SLE). The case of a 27 year old woman with SLE of seven years' duration who developed a spastic paraparesis during her second pregnancy is reported. Magnetic resonance imaging did not show any intrinsic abnormality of the spinal cord. Anticardiolipin antibody was weakly positive and C4 was low. The patient responded dramatically to steroids.
Intracellular thiols (LSH), superoxide dismutase (SOD) and plasma thiols (PSH) are thought to have an important role in the protection of tissues from damage by oxygen-derived free radicals. The change in the levels of activity of these substances in patients with active rheumatoid arthritis treated with sulphasalazine for 6 months was assessed in 22 patients. Over this time there was a marked improvement in disease activity. This was accompanied by an early increase in red cell LSH and decrease in SOD, although by 6 months these changes had completely reversed. In addition the negative correlation between these indices at week 0 had disappeared by week 6. Over the 6 months there was a steady rise in PSH. The change in PSH is slow and is thus more likely to reflect a change in the disease process rather than an active role for the thiol, but the early changes in intracellular parameters may be of importance in the action of this drug. These changes are similar to changes found with other second-line drugs. It is also of interest that a drug which does not itself possess a thiol group is capable of altering the thiol status of cells.
In systemic lupus erythematosus (SLE) the lupus anticoagulant is known to be associated with thrombosis. However, this anticoagulant only occurs in a small percentage of patients. Histopathological studies suggest a more generalized thrombotic tendency with platelets and fibrin within the microvasculature. Fibrinogen is elevated in SLE and this may lead to the fibrin deposition described. We wondered if decreased fibrinolysis contributed to this and we infused desamino D-arginine vasopressin (DDAVP) into ten patients with SLE and eight controls. DDAVP stimulates endothelial production of plasminogen activator (PA) and factor VIII. Baseline results showed a significant decrease in PA activity with a concomitant increase in fibrinogen in SLE. The t-PA and inhibitor levels were normal but factor VIII was increased. After infusion of DDAVP, results indicated that, despite baseline results, SLE patients were able to respond to stimulation and the increase in PA activity produced a decrease in plasma fibrinogen levels. These findings may have therapeutic implications.
We have reviewed 32 patients with rheumatoid disease of the cervical spine who underwent a total of 40 operations aimed at correcting instability and improving any associated neurovascular deficit. Apart from four patients with intractable pain, the main indication for surgery was progressive neurological impairment. Of the 32 primary operations, 19 (60%) were successful; the remainder failed to achieve their objective and there were two deaths in the immediate postoperative period. Of eight secondary operations performed for recurrence of symptoms or failure to relieve cervical myelopathy, only four were successful. Of nine operations for bony decompression to relieve cord compression from irreducible subluxation, only four were successful. The overall results show a success rate of 57% and a failure rate of 35% with early operative mortality in 8%. Indications for operation are discussed and earlier diagnosis is considered to be the key to improved results.
Polymorphonuclear leukocytes (PMN) C3b receptor (CR1) numbers have been measured in 14 normal individuals and 15 patients with SLE. The results in the normals showed that PMN possess three distinct pools of CR1. CR1 expression was lowest at 0 degrees C (mean 86,000 +/- s.e.m. 7,000), but increased when the cells were incubated at 37 degrees C (125,000 +/- 16,000) or when the cells were exposed to the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP, 10(-5) mol 1) at 37 degrees C (207,000 +/- 21,000). The increased expression at 37 degrees C was not dependent upon protein synthesis, an intact cytoskeleton or energy. Although the response to FMLP did not require de novo protein synthesis, increased CR1 expression was dependent upon an intact cytoskeleton and energy. All three PMN CR1 pools were reduced in patients with active SLE, but were normal in those in whom the disease was inactive. Serial studies performed on three SLE patients showed that PMN CR1 numbers were low during periods of disease activity and increased during remission. These data suggest that low PMN CR1 numbers in SLE are a consequence of the disease.
Erythrocyte C3b receptors (ECR1) have been measured in 122 pairs of twins (60 monozygotic, 62 dizygotic) using an [125I]-labelled monoclonal antibody (E11). The range of ECR1 numbers was wide, 99-4179 sites/cell, with a log-normal distribution around a geometric mean of 837 sites/cell. The intra-pair variance in dizygotic twins was no greater than that in monozygotic twins. These data indicate that ECR1 numerical expression is governed by environmental rather than genetic factors.
In normal serum complement prevents precipitation of antigen-antibody complexes (PIP). However rheumatoid arthritis (RA) serum contains an inhibitor of this complement-mediated function. We have undertaken two prospective studies in order to look for any relationship between the presence and levels of inhibitory activity in sera and synovial fluids (SF) of patients with RA and disease activity (study A), and the presence of systemic manifestations (nodules and vasculitis) of RA (study B). In study A, levels of inhibitory activity were highest in the sera and synovial fluids of patients with seropositive RA. However there was no correlation between the inhibitory levels and indices of generalised disease activity (articular index, erythrocyte sedimentation rate (ESR), haemoglobin, white cell and platelet counts). Local joint tenderness score correlated weakly with the inhibitory level in SF (P less than 0.05). There was no correlation, however, with either the SF protein concentration or white cell count. In study B, PIP was shown to be lower in patients with the systemic manifestations of RA than in those with purely articular manifestations. PIP was particularly low in those patients with vasculitis compared to those with subcutaneous nodules. Serum levels of inhibitory activity were highest in patients with vasculitis and lowest in those with articular disease only, whereas patients with nodules had intermediate levels. Our conclusion is that inhibition of immune precipitation is not associated with disease activity, but is associated with the extra-articular manifestations of RA. The inhibitory factor may play a role in the pathogenesis of RA.
Control of immune complex formation is important to limit disease resulting from their deposition in tissues. Any inhibition of immune complex solubilisation is thus significant in the pathogenesis of immune complex diseases. More than half of our patients with various rheumatic connective tissue diseases were demonstrated to have serum inhibition of immune complex solubilisation (12/16 rheumatoid arthritis, 22/37 systemic lupus erythematosus, 16/29 primary Sjogren's syndrome, and eight of nine with mixed connective tissue disease). This serum inhibitory activity did not correlate well with serum levels of IgM rheumatoid factor or circulating immune complexes, and its nature remains to be elucidated.
Using 125I-F(ab')2 anti-CR1 we have measured C3b receptors (CR1) on the erythrocytes of 56 normal individuals 26 patients with systemic lupus erythematosus (SLE) and 24 with rheumatoid arthritis (RA). The mean number of CR1 sites in SLE (1150/cell) but not RA (1460/cell) was significantly lower (P less than 0.01) than normal (2200/cell). Although the cumulative frequency curve for normals showed minor inflections at frequencies of 18% and 64%, these were not sufficiently marked to permit us to conclude that they distinguished subpopulations of different CR1 phenotypes. Measurement of CR1 numbers of two normal families and four families of SLE patients indicated that low CR1 numbers aggregated in families as did high CR1 numbers, a finding which suggests that CR1 numbers are under genetic control. However, certain observations in SLE patients indicated that low CR1 numbers could be an acquired abnormality. These included, (a) absent CR1 phenotype in a patient whose family had moderate and high CR1 numbers, (b) increasing CR1 numbers as SLE patients went into remission, (c) CR1 numbers were lower in patients with active compared with inactive disease and (d) CR1 numbers were different in each of two sets of identical twins (Fig. 4A). Our conclusions are that, (a) genetic factors probably influence CR1 numbers in normal individuals, (b) that our findings were not inconsistent with the two codominant allele models (Wilson et al., 1982), and (c) the low CR1 phenotype of SLE patients may be secondary to the disease process.
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The ability of human sera to prevent the precipitation of antigen-antibody complexes has been investigated. The early complement components including C3 are required for optimal prevention of immune precipitation, whereas the later components are not required. The sera of 36 of 75 patients with seropositive rheumatoid arthritis (RA), 14 of 32 with SLE and four of 17 with glomerulonephritis exhibited reduced capacities to prevent immune precipitation. In contrast sera from patients with seronegative RA, ankylosing spondylitis, psoriatic arthritis or degenerative joint disease were normal in this respect. In SLE and GN sera hypocomplementaemia was frequently associated but not always with failure to prevent immune precipitation, whereas only a small proportion of the patients with seropositive RA and reduced capacity to retain complexes in a soluble form were hypocomplementaemic. Thus the failure of sera to prevent the precipitation of antigen-antibody complexes is not always associated with hypocomplementaemia.