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Biomedical subjects

B Rozman

Publications and source records attributed to B Rozman.

At least 73 records · Page 4Linked to original sources
PubMed1995

Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis. Results of a randomized, placebo-controlled, phase II study.

OBJECTIVE: To assess the safety and effectiveness of leflunomide versus placebo in patients with active rheumatoid arthritis (RA) treated for 6 months. METHODS: Four hundred two patients were randomly assigned to receive placebo or leflunomide at 5 mg, 10 mg, or 25 mg daily. A washout period of 6-12 weeks from prior second-line therapy was required. RESULTS: Statistically significant improvement in primary and secondary outcome measures, as well as by responder analyses, occurred in the 10-mg and 25-mg dosage groups compared to placebo. Twenty-one patients (7.0%) in the active treatment groups withdrew due to adverse events (AEs). The incidence of AEs was higher with leflunomide than with placebo. Gastrointestinal symptoms, weight loss, allergic reactions, skin rash, and reversible alopecia were more common in the 10-mg and 25-mg dosage groups. The incidence of infections was similar between the treatment and placebo groups; no opportunistic infections were seen. Transient elevations in liver function studies were noted in a small number of patients. CONCLUSION: Leflunomide is effective in daily doses of 10 mg and 25 mg in patients with active RA. Improved efficacy at the 25-mg dose was associated with a higher incidence of AEs. Randomized, placebo-controlled trials using daily doses of 10 mg and 20 mg are under way in the US and Europe to confirm these positive results.

Adult↗
PubMed1995

Distinctive radiological features of small hand joints in rheumatoid arthritis and seronegative spondyloarthritis demonstrated by contrast-enhanced (Gd-DTPA) magnetic resonance imaging.

A series of patients with clinically early inflammatory joint disease due to rheumatoid arthritis, psoriatic arthritis and Reiter's syndrome were examined by plain film radiography and magnetic resonance imaging (MRI). The spin echo T1-weighted precontrast, T2-weighted, and, especially, T1-weighted postcontrast images demonstrated distinct differences in the distribution of inflammatory changes, both within and adjacent to involved small hand joints. Two major subtypes of inflammatory arthritis were shown, thus providing a specific differential diagnosis between rheumatoid arthritis and some patients with seronegative spondyloarthritis. In particular, all the patients with Reiter's syndrome who were studied, and half of those with psoriatic arthritis, had a distinctive pattern of extra-articular disease involvement. The need for a new classification of clinical subsets in psoriatic arthritis has been recently suggested. The present findings suggest that magnetic resonance imaging could be useful in such a reclassification of seronegative spondyloarthritis, as well as offering considerable potential for a reappraisal of pathogenesis and therapy. In this series, it was also noted that juxta-articular osteoporosis on plain film did not correlate with bone marrow oedema on MRI. Hence the aetiology of this common radiographic finding also merits further consideration.

Adult↗
PubMed1994

Arteritis of both carotid arteries in a patient with focal, crescentic glomerulonephritis and anti-neutrophil cytoplasmic autoantibodies.

We report a 32-yr-old woman who suffered a stroke as a consequence of arteritis of both internal carotid arteries confirmed by selective carotid arteriography. Laryngeal inflammation and kidney biopsy proven focal crescentic glomerulonephritis were also present in this patient. Anti-neutrophil cytoplasmic autoantibodies with specificity for proteinase 3 were detected in high titre during the active phase of the disease. This overlap syndrome with features indicating both Takayasu's arteritis and Wegener's granulomatosis suggests a common pathogenesis for these diseases.

Adult↗
PubMed1994

Anticardiolipin antibodies in infections are heterogenous in their dependency on beta 2-glycoprotein I: analysis of anticardiolipin antibodies in leprosy.

We studied the effect of beta 2-GPI on binding of antibodies in sera from patients with leprosy and patients with the antiphospholipid syndrome (APS) to CL in enzyme-linked immunosorbent assays (ELISAs). Increased levels of IgG aCL were detected in 59 of 61 leprosy patients' sera by the standard aCL-ELISA in the presence of bovine beta 2-GPI and in 60 of the 61 leprosy patients' sera by the modified aCL-ELISA without beta 2-GPI. When tested by both aCL-ELISAs on the same plate, 10/31 leprosy sera and 9/10 APS sera bound better in the standard aCL-ELISA, 16/31 leprosy sera bound better in the modified aCL-ELISA and in five leprosy and one APS sera the difference was not significant. A dose-dependent enhancing effect of beta 2-GPI on the leprosy and APS sera binding to CL was confirmed using purified human beta 2-GPI. Enhanced binding was seen if beta 2-GPI was added either before or together with the test serum. In 11/61 leprosy sera increased levels of IgG antibodies against beta 2-GPI were found by ELISA. Leprosy anti-beta 2-GPI antibodies appear to be a separate antibody population recognizing only beta 2-GPI adsorbed on the ELISA plate. These results demonstrate heterogeneity of leprosy aCL with respect to their beta 2-GPI requirement for binding to CL.

Antibodies, Anticardiolipin↗
PubMed1993

Precontrast and postcontrast (Gd-DTPA) magnetic resonance imaging of hand joints in patients with rheumatoid arthritis.

In an attempt to demonstrate whether clinically selected joints of the hand in active rheumatoid disease had consistent MRI findings, 45 patients were examined, in whom one joint in each was selected by both the referring clinician and patient as being active and symptomatic. Such joints, in order to be included in the study, were required to conform to ARA criteria of activity and usually mild to moderate X-ray changes. The joints were imaged using spin-echo sequences with T1W and T2W precontrast images, followed by T1W images after intravenous administration of Gd-DTPA. Different patterns of joint abnormalities were found. In 27 joints MRI findings suggested highly active synovitis and/or destructive pannus. In four, crescentic enhancement was thought to be compatible with simple synovitis, but in 23 rounded masses of synovial proliferation were characterized by marked, diffuse contrast enhancement on T1W postcontrast images, which corresponded well with high signal intensity on T2W images. Synovial proliferation in a further 12 joints was shown by only moderate stippled contrast enhancement and nonhomogeneous intermediate to high signal intensity on T2W images. These findings were thought to represent less active synovitis and pannus. MRI did not demonstrate inflammatory activity in six joints. In two of these pannus was of low signal intensity on T2W images, without contrast enhancement after Gd-DTPA infection presumed fibrotic and inert, and four were normal on all pulse sequences. These results suggest that clinical features of synovitis, even in carefully selected joints clinically, do not produce a homogeneous group when examined by MRI imaging. Indeed, a spectrum exists from presumed marked, active synovitis to total normality. If MRI is to be used as a clinical and research tool in the assessment of rheumatoid disease, and its therapeutic manipulation, these results are of some importance, since the variable findings indicate an appreciable heterogeneity of appearances in joints thought clinically to be of relatively uniform severity.

Adult↗
PubMed1993

Sera from patients with rheumatic diseases recognize different epitope regions on the 52-kD Ro/SS-A protein.

Patients suffering from systemic lupus erythematosus (SLE) or Sjögren's syndrome (SS) often contain autoantibodies directed to the Ro(SS-A) complex. In this study the antigenic determinants on two of the components of the Ro complex, i.e. the Ro60 and the Ro52 polypeptides, were investigated. Anti-Ro+ sera were selected by counter-immunoelectrophoresis. Depending on the detection method, 59-68% of the SLE patients produced anti-Ro but not anti-La antibody, while 72-81% of the SS patients produced both anti-Ro and anti-La antibody. Immunoprecipitation of recombinant Ro-proteins showed that 61 sera (87%) were reactive with both Ro proteins, seven sera with Ro60 only, one serum with Ro52 only, and one serum did not precipitate the proteins at all. The anti-Ro60 reactivity of human sera is strongly associated with the native form of Ro60, suggesting that conformational autoepitopes are an important feature of Ro60. In the case of Ro52, frequently the residues located between amino acids 216 and 292 were essential for reactivity with the antibodies. With 70% of the lupus sera tested this appeared to be the only region important for reactivity. The antibodies of SS patients generally recognized multiple B cell epitopes located between amino acids 55 and 292. The results of this study indicate that the antigenic determinants on Ro52 are different for autoantibodies produced by lupus patients compared with those of SS patients.

Adolescent↗
PubMed1993

The dissociation of arterial hypertension and lupus glomerulonephritis in systemic lupus erythematosus.

In spite of several articles questioning the general opinion that arterial hypertension in patients with systemic lupus erythematosus (SLE) is only the consequence of lupus glomerulonephritis (LGN), this still remains the usual pathophysiologic explanation. The purpose of this study was to explore the correlations between hypertension and LGN and to assess the importance of hypertension control for the prognosis of patients. A retrospective analysis of 173 patients with SLE over a period of 14 years was performed. For most of the patients, data were available from regular follow-up visits over an average of 6 years. Our results show a dissociation of hypertension and LGN and an association of hypertension and renal dysfunction. Severe hypertensive renal vascular lesions correlated well with a decrease of renal function. Successful treatment of hypertension is therefore essential in order to prevent deterioration of renal function in patients with LGN.

Adolescent↗
PubMed1992

Antimitochondrial (pyruvate dehydrogenase) autoantibodies in autoimmune rheumatic diseases.

Anti-pyruvate dehydrogenase (PDH) antibodies were determined in 1451 sera of patients with primary biliary cirrhosis (PBC) and several autoimmune rheumatic conditions by ELISA and immunoblotting. They were detected in sera of 93% of the patients with PBC (179 of 192 patients) in 60 of 277 (22%) patients with Sjogren's syndrome (SjS), 34 of 437 (8%) patients with scleroderma, 33 of 191 patients with SLE (17%), and 5 of 55 (10%) patients with rheumatoid arthritis (RA) but in none of the patients with polymyositis or the antiphospholipid syndrome. The ELISA studies were confirmed by immunoblots showing binding of autoimmune rheumatic sera to the same epitope (74 kd) of mitochondria that the PBC sera reacted with. The identical binding characteristics were also confirmed by protein competition assays with purified PDH. In 4 of 53 patients with SjS who were positive for anti-PDH, high titers as in PBC were detected. The anti-PDH antibodies in Sjogren's patients were associated with deranged liver function tests and extraglandular features but did not correlate with any other non-organ-specific antibody. Follow-up studies confirmed the association of the emergence of anti-PDH antibodies with defects in liver function tests. The antibodies were more prevalent in SLE and RA when they were associated with Sjogren's syndrome (30 and 18.8%, respectively). Among patients with different forms of scleroderma, anti-PDH antibodies were noted in subjects with systemic sclerosis, morphea, and Raynaud's phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Antinuclear↗
PubMed1992

Mixed connective tissue disease associated with autoimmune hepatitis and thyroiditis.

The case is reported of a 27 year old woman who had mixed connective tissue disease (MCTD) associated with chronic active hepatitis and thyroiditis. Although hepatomegaly is sometimes observed in MCTD, only four cases of MCTD and chronic active hepatitis have been described. It is thought that this is the first report of an association between MCTD, chronic active hepatitis and thyroiditis.

Adult↗
PubMed1991

Prevalence of antiphospholipid antibodies in deep vein thrombosis and their relationship to blood coagulation and fibrinolysis.

Elevated levels of antiphospholipid antibodies are associated with an increased risk of thrombosis. To establish the prevalence of these antibodies in deep vein thrombosis (DVT), IgG and IgM antibodies to cardiolipin (aCL) and phosphatidylserine (aPS) were determined by enzyme-linked immunosorbent assay in 118 patients with DVT either during an acute episode (N = 53) or at least 2 months after acute DVT (N = 65). Most patients (76%) had proximal leg DVT and no one had evident autoimmune disorder. aCL and aPS values higher than 4 standard deviations above the mean value of the control group (147 blood donors) were considered increased. Increased IgG aCL were observed in 10% of DVT patients (controls: 5%, not significant), increased IgG aPS in 16% of DVT patients (controls: 5%, p less than 0.005) and both types in 4% of DVT patients (controls: 3%, not significant). In the subgroup of 41 patients with previous idiopathic DVT, prevalence of increased IgG aPS was the highest: 27% (p less than 0.001). Increased antibodies of IgM isotype were observed in 3% (aCL) and 2% (aPS) of all DVT patients (controls: 8% and 4%, respectively, not significant). Elevated IgG aCL or aPS were not associated with significant changes in platelet count, antithrombin III and protein C. However, in patients with increased IgG aPS deficient fibrinolysis due to high plasminogen activator inhibitor activity was observed before and after 20 min upper arm venous occlusion. DVT patients with increased IgG aPS might be exposed to a greater risk of rethrombosis due to deficient fibrinolysis than DVT patients without these antibodies.

Adolescent↗
PubMed1990

Possible association between anti-Ro antibodies and myocarditis or cardiac conduction defects in adults with systemic lupus erythematosus.

In view of the association of congenital heart block with maternal antibody to cellular antigen Ro (SSA), and one report linking anti-Ro with myocarditis in a patient with myositis an association between anti-Ro antibodies and cardiac disease was sought in adults with systemic lupus erythematosus (SLE). Among 67 patients with SLE, of whom 36 were anti-Ro positive, a significantly higher prevalence of myocarditis and conduction defects was found in the anti-Ro positive group (eight of 36) than in those who were anti-Ro negative (one of 31) and healthy controls (one of 50). Of the 36 anti-Ro positive patients with SLE, three had symptoms diagnostic of myocarditis, and an electrocardiogram showed first degree atrioventricular block and unifascicular block in three cases (including one with myocarditis), right bundle branch block alone (two cases), and first degree atrioventricular block alone (one case). Complete atrioventricular block was not seen. In the anti-Ro negative group there was no myocarditis and only one case of conduction defect (right bundle branch block). Among healthy controls only one of 50 had first degree atrioventricular block. It is concluded that myocarditis and conduction defects are reasonably common in adults with SLE and are associated with anti-Ro antibodies.

Adolescent↗
PubMed1990

Determination of cathepsins B and H in sera and synovial fluids of patients with different joint diseases.

Synovial fluids and sera of patients with inflammatory and metabolic joint diseases contain different cysteine proteinases. The quantities of cathepsins B and H were determined by newly developed specific enzyme-linked immunoassay tests (ELISA), with detection limits of 0.5 microgram/l for cathepsin B and 3 micrograms/l for cathepsin H. The values of cathepsin B in normal sera ranged from 0.6 microgram/l to 2 micrograms/l, whereas in sera of patients with joint diseases they ranged from 1.7 micrograms/l to 18 micrograms/l. Cathepsin H was not found in sera (values below 3 micrograms/l), but was measurable in patients' synovial fluids. Patients with rheumatoid arthritis have on average the highest values of cathepsin B in synovial fluids, whereas patients with undifferentiated arthritis have the highest values of cathepsin H. The results show that cathepsins B and H are present in arthritic synovial fluids, where they may be implicated in destructive processes. There is yet no clear correlation between the quantity of each cathepsin released in synovia and the clinical diagnosis or the stage of the disease.

Antibodies↗
PubMed1988

Human cathepsin B and cysteine proteinase inhibitors (CPIs) in inflammatory and metabolic joint diseases.

Synovial fluid of patients with different inflammatory and metabolic joint diseases contains low-molecular CPIs (stefins and cystatins) and high-molecular CPIs (kininogens). An additional inhibitory fragment with a molecular mass of about 20 kDa, which is a part of the kininogen molecule, has been detected. Cathepsin B and cystatin C were determined by ELISA test in 47 patients with rheumatoid arthritis, seronegative spondylarthritis, osteoarthritis, undifferentiated arthritis and gout. A significantly higher amount of cathepsin B was found in patients with rheumatoid arthritis. The elevation of cathepsin B was accompanied by an increased amount of cystatin C.

Amino Acid Sequence↗
PubMed1988

The significance of some immunoserologic diagnostic tests in systemic diseases.

The sensitivity and specificity of immunoserologic tests included in the diagnostic criteria of systemic lupus erythematosus are shown. The frequencies of some rare autoantibodies (PCNA, PL-4, SL, PM-Scl, Scl-70, Jo-1) in systemic connective tissue diseases of mixed Yugoslav population are demonstrated. The results from different laboratories differ considerably and the possible reasons are described.

Antibodies, Antinuclear↗
PubMed1985

Human leucocyte urokinase inhibitor--purification, characterization and comparative studies against different plasminogen activators.

A plasminogen activator inhibitor (PA-I) which inhibits primarily plasminogen activator of the urokinase type (u-PA) was isolated from the cytosol of human peripheral leukocytes. The inhibitor was isolated using ion exchange chromatography, gel filtration and FPLC. This inhibitor has an apparent molecular weight of 45 kDa, determined by SDS-PAGE, and a pI of 5.5-5.7. The inhibitor is a fast reacting inhibitor, is thermally unstable and is inactivated outside the pH range 7-9. Treatment of cytosol to pH 9 for 30 min at 37 degrees C resulted in a large increase in inhibitory activity. Antibodies against human placental UK-I completely quenched the inhibitory activity of human leucocyte UK-I.

Blood Proteins↗