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Biomedical subjects

J Zuckner

Publications and source records attributed to J Zuckner.

At least 19 recordsLinked to original sources

Rheumatologic complications of vitamin A and retinoids.

Retinoids are synthetic derivatives of vitamin A. They are administered primarily for dermatological conditions, such as psoriasis, acne, and disorders of keratinization. Toxicity has proven a significant problem with long-term administration of the retinoids. Bone abnormalities mimicking seronegative spondyloarthropathy or diffuse idiopathic skeletal hyperostosis have been described in many cases, as well as other rheumatologic manifestations such as arthritis, myopathy, and vasculitis. These retinoid-related adverse effects are reviewed.

Humans

Drug-related myopathies.

Myopathies produced by drugs are of vital concern and often confused with other more frequently diagnosed causes, such as the inflammatory myopathies of polymyositis/dermatomyositis and myositis secondary to toxic agents, metabolic and endocrine abnormalities, genetic predisposition, malignancies, and infections, particularly viruses. The drug-induced causes of myopathy warrant special emphasis because they are often overlooked, resulting in misdiagnosis and improper care.

Humans

Heart disease in systemic sclerosis.

Primary cardiovascular manifestations of SSc include pericardial disease, myocardial disease, conduction abnormalities, and cardiac arrhythmias. Significant cardiac abnormalities are present in more than half of SSc patients at autopsy. As the frequency of subclinical cardiac involvement is now appreciated and noninvasive cardiac diagnostic modalities continue to improve, the ability to detect early asymptomatic involvement in SSc has improved. Two-dimensional echocardiography, radionucleotide imaging, and ambulatory ECG allow recurrent serial testing with virtually no morbidity. The current treatment of cardiac involvement in SSc is emperic and primarily directed at symptomatology. Large prospective randomized trials are needed to determine if preventive therapy is effective. With the advent of new immunological and cardiotropic agents and a better understanding of the primary disease process, our ability to alter the pathogenesis and final outcome of cardiac involvement in SSc should improve.

Arrhythmias, Cardiac

International experience with diclofenac in rheumatoid arthritis.

Rheumatoid arthritis, although not the most common of the rheumatic diseases, is potentially the most disabling. For this reason, it is considered the principal disorder for determining the therapeutic effectiveness of any new antirheumatic agent. Diclofenac sodium, a nonsteroidal anti-inflammatory drug, has been studied extensively in international clinical trials since the early 1970s. It has proved to be at least equal in efficacy to other nonsteroidal anti-inflammatory drugs. In addition, its superior safety profile suggests that diclofenac will be a valuable agent in the treatment of rheumatoid arthritis, for which long-term drug therapy is usually required.

Arthritis, Rheumatoid

19S IgM rheumatoid factor-7S IgG rheumatoid factor immune complexes isolated in patients with rheumatoid arthritis.

Sera of 12 patients with rheumatoid arthritis (RA) who had positive IgM-rheumatoid factor (RF) tests were separated by use of immunoabsorbent columns (goat anti-human C3 [alpha HC3] and rabbit anti-human C1q [alpha HC1q]) and polyethylene glycol (PEG) precipitation-protein A affinity chromatography to isolate their immune complexes (IC). The isolated fractions were assayed for 19S IgM RF and 7S IgG RF by enzyme-linked immunosorbent assay (ELISA). The sera were further analyzed by preparative isoelectric focusing (IEF). The alpha HC1q and alpha HC3 columns were sequentially eluted with barbital buffer, 0.02 mol/L EDTA, 0.5 mol/L NaCl, and 1 mol/L propionic acid. All 12 patients had IgM RF and IgG RF in the EDTA fractions from both immunoabsorbent columns, but only IgM RF in the NaCl fractions. The PEG precipitation-protein A preparations were eluted with 0.5 mol/L glycine HCl and 3.5 mol/L MgCl2. All 12 patients had significant titers of 19S IgM RF (greater than or equal to 1:192) and 7S IgG RF (greater than or equal to 1:96) in the acid-eluted fraction. Analysis of the sera by preparative IEF revealed IgM RF with a polyclonal spectrotype pattern with pH of 3.0 to 10.0, but predominantly acidic proteins with isoelectric points of 4.0 to 5.5 IgG RF were found in the same restricted spectrotypic pattern. These studies demonstrated that IC can be detected in the sera of patients with RA by isolation with alpha HC1q and alpha HC3 immunoabsorbent columns and PEG precipitation-protein A affinity chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Ulcerative colitis with arthritis and vasculitis.

A child with ulcerative colitis is described in whom many unusual complications of the disease occurred. Arthritis was present and preceded the onset of the colitis. The patient also developed vasculitis, hepatitis, pleuritis, pericarditis, cryoglobulinemia, and disseminated intra-vascular coagulopathy. A review of the literature on ulcerative colitis revealed the relative infrequent occurrence of many of these manifestations in the pediatric age group.

Adolescent

Hidden 19S IgM rheumatoid factor in adults with juvenile rheumatoid arthritis onset.

Forty-eight adult patients with juvenile rheumatoid arthritis (JRA) (onset before age 16 years) were evaluated at the age of 17 years or more for the presence of hidden 19S IgM rheumatoid factors (RF), i.e., 19S IgM RF that can be detected by the complement-dependent haemolytic assay in the IgM-containing fraction after separation of the serum by acid gel filtration. The average age of the patients was 25.3 years. The mean duration of disease was 16.5 years. Thirty-two of 48 patients (67%) showed the presence of hidden 19S IgM RF in their serum. Disease activity correlated with hidden RF titres in 62% (55/88) of the evaluations. The results indicate that patients with seronegative JRA onset continue to have significant titres of hidden 19S IgM RF in their sera into early adulthood.

Adolescent

Hidden and classical 19S IgM rheumatoid factor in a juvenile rheumatoid arthritis patient.

Hidden 19S IgM rheumatoid factors (RF), i.e., 19S IgM RF which can be detected in the IgM containing fraction after acid gel filtration of serum, are found in 59-68% of patients with juvenile rheumatoid arthritis (JRA). Their presence generally correlates with disease activity. We describe a 12 year-old female with a polyarticular onset of JRA who, during her first 15 months of disease, was seronegative but had hidden RF titers of 1:128----1:256. Inhibition studies on her hidden RF showed specificity for HIgG greater than RIgG and equal specificity for the human IgG subclasses (IgG1 = IgG3). In the second and third year of disease, she became seropositive with RF titers varying from 1:40 to 1:320 while her hemolytic titers on her IgM fractions were decreased from 1:128 to 1:32. Inhibition studies now demonstrated a higher avidity for RIgG; and HIgG3 inhibited more than HIgG1. These studies documented for the first time a JRA patient who early in the disease was negative for RF and positive for hidden RF, and who later became seropositive.

Arthritis, Juvenile

Use of the HEp-2 cell substrate in the detection of antinuclear antibodies in juvenile rheumatoid arthritis.

Presence and titer of antinuclear antibodies (ANA) were determined in 217 juvenile rheumatoid arthritis (JRA) patients, by indirect immunofluorescence using HEp-2 cells as substrate. Positive ANA titers (greater than or equal to 1:40) were present in 131 (60%) of the JRA patients. All 3 JRA onset types demonstrated increased percentages of ANA positivity compared with healthy children. Sixty-seven percent of the patients in the polyarticular onset group had positive titers; titers were positive in 62% of the pauciarticular onset group and in 32% of the systemic onset group. ANA were also found in 45% of control patients with other connective tissue diseases. In JRA patients, the speckled pattern occurred most commonly (72%). Fourteen patients (8 with pauciarticular onset and 6 with polyarticular onset) had iridocyclitis; all of them had high titers (greater than or equal to 1:80) of ANA. The use of HEp-2 cells provided a sensitive substrate for detecting ANA in JRA. It proved to be of value in differentiating JRA patients from healthy controls, but not from patients with other connective tissue diseases.

Adolescent

Autoantibodies in juvenile arthritis.

Sera from 104 children with JA with different onset-types of disease were evaluated for 19S IgM RF by the LFT , hidden 19S IgM RF by the hemolytic assay, ANA by HEp-2 cell substrate, and levels of IC by the C1qSPA . Their relationship to active disease was determined. Classical 19S IgM RF were detected by the LFT in only seven patients. All were late-onset polyarticular females. Hidden 19S IgM RF were detected by the hemolytic assay in the separated IgM-containing fraction in 55 patients of all onset-types. Clinical activity correlated with the presence of hidden 19S IgM RF in 82% of cases. ANA, using the HEp-2 cell substrate, were found in 61 patients, the majority showing a speckled, immunofluorescent pattern. ANA were noted in all RF positive patients and in nine of 10 patients with iridocyclitis. IC were found in 39 patients, and correlation with clinical activity occurred in 54% of cases. A search for positive associations among the four parameters showed no statistically significant correlations except for the concordance of ANA positivity in all seven RF positive patients. The presence of hidden RF correlated more closely with disease activity (P less than 0.001) than did that of ANA or IC. The significance of these data and previous studies remains to be determined. We have demonstrated that in the average JA population 7% have 19S IgM RF and about 60% have hidden RF, ANA, or elevated levels of IC. The present findings of 98 of 104 patients with at least one of the abnormal immunoproteins , the association of ANA in patients with iridocyclitis or with RF positivity, of hidden RF with disease activity, and the presence of 19S IgM RF in isolated IC suggest a possible immunologic etiology for JA.

Antibodies, Antinuclear

HLA antigens in black and white patients with juvenile arthritis: associations with rheumatoid factor, hidden rheumatoid factor, antinuclear antibodies, and immune complex levels.

HLA typing for -A, -B, -C, -DR, and -MT antigens and simultaneous studies for the presence of 19S IgM rheumatoid factor (RF), hidden 19S IgM RF, antinuclear antibodies (ANA), and immune complexes (IC) were performed on 24 black and 80 white patients with juvenile arthritis (JA) of different onset types. HLA-DRW6 (p less than 0.05) was associated with pauciarticular onset and early onset pauciarticular black patients. HLA-DR4 was found in both blacks and whites with chronic disease (p less than 0.01) and with the presence of RF (p less than 0.05) and hidden RF (p less than 0.05). In the whites, HLA-DR5 (p less than 0.05) and DRW8 (p less than 0.001) were associated with pauciarticular onset and early onset pauciarticular patients. HLA- DRW8 was also associated with white JA patients with iridocyclitis (p less than 0.001) and black (p less than 0.01) and white patients (p less than 0.001) with the presence of ANA. HLA-MT2 was demonstrated in all 24 black patients (p less than 0.001) and in 54/80 white patients (p less than 0.001). HLA-MT2 was associated with black (p less than 0.01) and white (p less than 0.001) patients with early onset pauciarticular disease and the presence of iridocyclitis in white patients (p less than 0.001). The association of HLA antigens in black JA patients has not been reported before.

Antibodies, Antinuclear

Precipitation of 19S IgM rheumatoid factor-IgG circulating immune complexes in patients with juvenile arthritis by polyethylene glycol and separation by immobilized protein A.

Immune complexes (IC) in sera and synovial fluid (SF) from patients with juvenile (rheumatoid) arthritis (JA) were isolated by making use of polyethylene glycol (PEG) to precipitate IC and then using staphylococcal protein A to separate the IC. The isolated IC were compared to IC in sera analysed by sucrose density gradients and measured by the C1q solid phase assay (ClqSPA). Isolated IC from sera of 10 of 16 JA patients demonstrated significant 19S IgM rheumatoid factor (RF) titres in their acid elutes utilizing the haemolytic assay. IgM and IgG were detected by low level radial immunodiffusion in the acid eluate of sera in all 10 patients who had significant RF titres. In isolated IC from SF, three of five JA patients had significant 19S IgM RF titres detected in their acid eluates. By sucrose density gradient analysis of these sera, elevated levels of IC detected by ClqSPA were found in the fractions of greater than or equal to 19S comparable to the previous isolated 19S IgM-IgG complexes. This detection of IC like material containing 19S IgM and IgG by the present method further supports the participation of classic and hidden 19S IgM RF in IC formation in JA patients.

Antigen-Antibody Complex