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Biomedical subjects

J Vencovský

Publications and source records attributed to J Vencovský.

At least 19 recordsLinked to original sources

[Rheumatologic manifestations in diabetes].

Patients with diabetes mellitus may encounter various musculoskeletal complications. Typical manifestations can be seen in the hand, such as limited joint mobility, flexor tendon synovitis, Dupuytren's contracture and carpal tunnel syndrome. Humeral periarthropathy is also more frequent. The most serious complications can occur in the form of diabetic foot, which may lead to severe deformities and disability. Diabetic amyotrophy and muscle infarction are more rare complications. While osteopenia has a well recognized association with type I diabetes mellitus, this probably is not true for type II. Similarly, the association between diabetes mellitus and osteoarthritis has not been proven.

Diabetes Complications↗

[Mutations in the HFE gene in patients with rheumatic diseases].

BACKGROUND: Hereditary hemochromatosis is one of the most common autosomal recessive diseases. Aim of the study. 1. To establish frequency of C282Y and H63D mutations in the HFE gene (the hemochromatosis gene) in general population of the Czech Republic and in patients with hemochromatosis. 2. To find out whether hemochromatosis in homo- or heterozygous state plays a role in the pathogenesis of rheumatic diseases. METHODS AND RESULTS: In 32 patients with hereditary hemochromatosis, in 84 patients with polymyositis or dermatomyositis, in 246 patients with juvenile idiopathic arthritis and in 481 persons of the control group the presence of HFE gene mutations was etablished. The HFE gene mutations were screened for by restriction enzyme analysis performed on PCR amplified products. In the control group, 6.86% carriers of the C282Y mutation and 26.61% those of H63D were found. Homozygous C282Y or H63D mutation was found in 90.6% (p<0.001) of patients with hemochromatosis. Heterozygous C282Y mutation was found in 12.2% (p<0.05) of patients with juvenile idiopathic arthritis. We didn't detected higher prevalence of HFE gene mutations in patients with polymyositis and dermatomyositis. CONCLUSIONS: Results of this study show that heterozygosity for C282Y mutation may be a risk factor for juvenile idiopathic arthritis but not for polymyositis and dermatomyositis.

Gene Frequency↗

Autoantibodies can be prognostic markers of an erosive disease in early rheumatoid arthritis.

OBJECTIVE: To evaluate a contribution of selected laboratory parameters for a prediction of progressive and erosive development in patients with early rheumatoid arthritis (RA). METHODS: In a prospective study baseline levels of antibodies to cyclic citrullinated peptide (anti-CCP), IgM, IgA, and IgG rheumatoid factors (RFs) were measured by enzyme linked immunosorbent assay (ELISA) in 104 patients with RA with disease duration <2 years. Antikeratin antibodies (AKA) and antiperinuclear factor (APF) were detected by indirect immunofluorescence. Patients were divided into two groups based either on the presence or absence of erosions or according to progression of Larsen score at the end of the 24 months' follow up. RESULTS: Sixty seven (64%) patients developed radiographic erosions, 49 (47%) had progression in Larsen score, and 36 (35%) progressed by more than 10 Larsen units. Significant differences in erosions and progression between the two groups were detected for anti-CCP, AKA, APF, IgM RF, IgA RF, and IgG RF. Baseline Larsen score correlated significantly with anti-CCP, IgM RF, and IgA RF levels, and all measured antibodies correlated with the progression >10 units. The combination of anti-CCP and IgM RF increased the ability to predict erosive and progressive disease. CONCLUSION: The data confirmed that measurement of anti-CCP, AKA, APF, and individual isotypes of RFs was useful for prediction of structural damage early in the disease course. Combined analysis of anti-CCP and IgM RF provides the most accurate prediction.

Antibodies, Antinuclear↗

Polymorphism in the immunoglobulin VH gene V1-69 affects susceptibility to rheumatoid arthritis in subjects lacking the HLA-DRB1 shared epitope.

OBJECTIVE: To investigate the contribution of polymorphism in the immunoglobulin heavy chain variable region V1-69 gene set to genetic susceptibility to rheumatoid arthritis (RA) in Czech and British patients. METHODS: We used V1-69 gene sequence-specific polymerase chain reaction (PCR) and restriction enzyme digestion to study polymorphism in the V1-69 gene set in germline DNA of 109 Czech and 159 British RA patients and 164 ethnically matched controls. Polymorphism was further studied by nucleotide sequencing of the V1-69 gene locus in germline DNA. RESULTS: We found that all patients and controls had at least one V1-69 gene copy. In the Czech RA cohort, the dimorphic nucleotide in codon 73 of V1-69 (GAA or AAA) was present in the homozygous form 73(A/A) in 31 of 109 (28.4%) RA patients vs 12 of 79 (15.2%) controls [odds ratio (OR)=2.22, P<0.001]. When the RA patients and controls were classified according to HLA shared epitope (SE) status, 73(A/A) was found in 18 of 76 (23.7%) SE(+) patients compared with 13 of 38 (34.2%) SE(-) patients, four of 12 (18.2) SE(+) controls and eight of 57 (14%) SE(-) controls. This suggests that homozygosity for the dimorphic sequence 73(A) contributed to susceptibility to RA in SE(-) Czech individuals (OR=3.2, P<0.001). The most striking observation was that none of the 38 SE(-) Czech patients, compared with 11 of 76 (14.5%) SE(+) RA patients, three of 22 (13.6%) SE(+) and 11 of 57 (19.3%) SE(-) ethnically matched controls, were homozygous for the alternative dimorphic sequence 73(G/G) (OR=9.1, P<0.05). These data, however, were not replicated in a Caucasoid British RA population. CONCLUSION: The dimorphic sequence at codon 73 (73(A/A)) of the V1-69 gene contributes to genetic susceptibility in SE(-) Czech RA patients.

Adult↗

Higher frequency of allele 2 of the interleukin-1 receptor antagonist gene in patients with juvenile idiopathic arthritis.

OBJECTIVE: An increased incidence of allele 2 of the interleukin-1 receptor antagonist gene (IL1RN*2) in several inflammatory diseases has recently been reported. The aim of this study was to examine a variable number tandem repeat (VNTR) polymorphism of the IL1RN gene in patients with juvenile idiopathic arthritis (JIA). METHODS: Findings in 185 Czech patients with JIA were compared with those in 168 Czech controls, 50 JIA patients and 52 controls of Turkish origin, and 79 controls from central England. VNTR polymorphism analysis of IL1RN was performed by polymerase chain reaction using 2 flanking primers to amplify an 86-bp tandem repeat region in intron 2. RESULTS: The frequency and carriage rate of IL1RN*2 were significantly increased in Czech JIA patients compared with the Czech controls (frequency 27.6% versus 15.8%; carriage rate 44.3% versus 26.2%). Increased frequency and carriage rate of IL1RN*2 were found in 23.3% and 40.0% of Turkish JIA patients and in 17.3% and 34.6% of ethnically matched controls. The high representation of IL1RN*2 in 52.3% of the 22 patients with extended oligoarthritis, 31.3% of the 56 patients with enthesitis-related arthritis, and 42.9% of the 14 patients with other arthritis was particularly responsible for the increased frequency of IL1RN*2 in the Czech JIA patients. We found no association of IL1RN*2 with disease activity or severity parameters. CONCLUSION: Inheritance of IL1RN*2 may contribute to genetic susceptibility in several forms of autoimmune diseases, including JIA. The IL1RN*2 allele may be useful as a prognostic indicator of the evolution of an extended oligoarticular course of JIA.

Alleles↗

Cyclosporine A versus methotrexate in the treatment of polymyositis and dermatomyositis.

OBJECTIVE: To determine the effectiveness and tolerance of treatment with cyclosporine A (CyA) or methotrexate (MTX) added to corticosteroids in patients with severe, active polymyositis (PM) and dermatomyositis (DM). PATIENTS AND METHODS: Thirty-six patients (20 with DM, 16 with PM) were enrolled into the study and randomized in MTX (n = 17) and CyA (n = 19) groups. Muscle endurance and functional test (MEFT), clinical assessment (CA), global patient's assessment (GPA), muscle MRI, serum CK, myoglobin, IL-1Ra, and autoantibody status were used to assess the response to therapy after 1, 3, and 6 months. RESULTS: Significant improvement in MEFT, CA, GPA, and muscle MRI was found in both groups. Patients treated with MTX showed insignificantly better response than patients with CyA. CK levels in the MTX group decreased significantly after 1, 3, and 6 months, whereas a significant reduction in the CyA group was first observed after 6 months. IL-1Ra serum levels significantly dropped in the CyA group after two weeks, whereas in the MTX group the significant decrease was first seen after 3 months of treatment. Good correlation was found between each of the clinical parameters (MEFT, CA, and GPA), none of them showed any correlation with CK or IL-1Ra levels. CONCLUSIONS: Administration of MTX or CyA added to corticosteroids was associated with clinical and laboratory improvement. Changes in CK and IL-1Ra levels were not associated with parameters of clinical disease severity measured in this study.

Adrenal Cortex Hormones↗

Identification of common epitopes on gliadin, enterocytes, and calreticulin recognised by antigliadin antibodies of patients with coeliac disease.

BACKGROUND: Sera of patients with coeliac disease, containing IgA and IgG antigliadin antibodies (AGA) and various IgA autoantibodies, react with isolated enterocytes. AGA cross react with enterocyte antigens, one of which has been identified as calreticulin. AIMS: To characterise the antigenic structures of gliadin, enterocytes, and calreticulin recognised by AGA from patients with active coeliac disease. METHODS: AGA were isolated from sera of nine patients by affinity chromatography and tested by competitive ELISA using 40 alpha-gliadin synthetic dodecapeptides (A1-F6). RESULTS: Reactivity of gliadin with all purified AGA tested was inhibited by peptide A4 at the N-terminal region; by C2, C3, and D4 at the central region; and by F3 and F4 at the C-terminal region of the gliadin molecule. AGA cross reactivity with enterocytes was inhibited by peptides A4, D1-D4, and F6 and with calreticulin by peptides A4, D3, and D4. As dominant epitopes AGA of coeliac patients recognise similar structures corresponding to peptides A4, D3, D4, and F6 present on gliadin, enterocytes, and calreticulin. Substitution of glutamine in the A4 peptide by glutamic acid caused loss of inhibitory capacity. Shortening of peptide A4 on the N-terminal by three amino acids increased its inhibitory effect. CONCLUSIONS: AGA of patients with coeliac disease react with similar structures on gliadin and potential autoantigens on enterocytes.

Adult↗

Effect of 1 year cyclosporine A treatment on the activity and renal involvement of systemic lupus erythematosus: a pilot study.

Our objective was to determine the effect of 1 year low-dose cyclosporine A (CSA) treatment on disease activity and renal involvement in systemic lupus erythematosus (SLE). Patients included in the pilot study had an active form of the disease as defined by the SLE Disease Activity Index (SLEDAI). Main organ involvement was represented by lupus nephritis classified in repeated renal biopsies. Eleven patients with SLE were enrolled in the study. In eight of them, previous therapy with cyclophosphamide or azathioprine had to be interrupted due to serious adverse reaction or low efficacy. Nine patients experienced clinical nephrotic syndrome, and two the nephritic syndrome. After 12 months of CSA treatment, the mean SLEDAI score had decreased significantly from 26.18 to 4.00 (P < 0.01). Similarly, the titre of antinuclear and anti-dsDNA antibodies had dropped significantly (P < 0.01). Proteinuria decreased rapidly from 9.10 to 1.70 g/24 h (P < 0.001). According to the WHO classification of renal biopsies, three patients had their class altered from IV to III in response to CSA treatment and five patients had changed the status from the high severity grade to the mild. The adverse reactions included hypertension (45%), gingival hyperplasia (18%) and hirsutism (9%). No significant increase in serum creatinine or any CSA related toxic changes were found in renal biopsies. The favourable response observed in patients with active SLE and with major renal involvement strongly suggests that low-dose CSA is a potent drug as much for the reduction of the disease activity as for lupus nephropathy treatment.

Adult↗

Heterogenous nuclear RNP C1 and C2 core proteins are targets for an autoantibody found in the serum of a patient with systemic sclerosis and psoriatic arthritis.

OBJECTIVE: To determine a target recognized by anti-Bh autoantibody, found in the serum of a patient with the unusual coexistence of systemic sclerosis (SSc) and psoriatic arthritis (PsA). METHODS: Antigens recognized by the anti-Bh serum were characterized by indirect immunofluorescence on HeLa cells, by conventional immunoblotting using nuclear extract or partially purified preparation of heterogenous nuclear RNP (hnRNP) proteins, and by 2-dimensional immunoblotting. For the analysis of cross-reactivity and immunofluorescence patterns, autoantibodies were affinity-purified by blot elution and then retested. RESULTS: Comparison of the reactivity of the anti-Bh antibody with the monoclonal antibody 4F4 against both the hnRNP C proteins, together with the determination of biochemical properties of the autoantigens, led to the identification of C1 and C2 core proteins as the targets for the anti-Bh autoantibody. CONCLUSION: Several essential components of the spliceosome are targeted by autoantibodies that are present in the sera of patients with systemic rheumatic diseases. We also found that the hnRNP core proteins C1 and C2 are recognized by the autoantibody present in the serum of a patient with SSc and PsA. C1 and C2 hnRNP proteins should be added to the several intracellular autoantigens recently shown to be cleaved by interleukin-1beta-converting enzyme-like enzymes during apoptosis.

Aged↗

[Practical results of monitoring pregnancy in women with systemic lupus erythematosus].

BACKGROUND: The authors dealt with the urgent problem under what conditions it is possible to achieve in a woman with systemic lupus erythematosus (SLE) or another collagenosis, or secondary antiphospholipid syndrome (APS) a favourable outcome of pregnancy and the delivery of a healthy infant. METHODS AND RESULTS: The investigation comprised 23 women incl. 20 with SLE, two with the mixed form of a diffuse connective tissue disease (MCTD) and one with Sjögren's syndrome of the primary type. From the total number of 20 pregnancies six were consulted in advance with a doctor (group I-s-called planned pregnancies) and all terminated by a successful delivery. Of 11 pregnancies which were not consulted with a doctor in advance (group II-so-called unplanned pregnancies) 9 were terminated in term, however, only 5 with a successful delivery (55.5%), two women are still pregnant. Exacerbation of the basic disease during pregnancy was recorded only once and did not lead to discontinuation of the pregnancy. CONCLUSIONS: The authors provide evidence that desired pregnancy of informed women suffering from SLE or another collagenosis when assisted by a specialized medical team can lead to a successful delivery of an infant.

Adult↗

[Rheumatoid pericarditis: correlation with immunologic parameters].

In 35 patients with rheumatoid pericarditis the laboratory findings were compared with those of a group of 65 patients with rheumatoid arthritis without a pericardial exudate. The authors assessed the red cell sedimentation rate and serum levels of immunoglobulins G, M, A, semiquantitative values of the rheumatoid factor, circulating immunocomplexes, C3 and C4 complement components, the positivity of antinuclear antibodies and values of C-reactive protein. The authors found significantly elevated values of immunoglobulins M in patients with rheumatoid arthritis without a pericardial exudate. As regards the other investigated parameters the two compared groups did not differ.

Adult↗

[Antineutrophil cytoplasmic antibodies--ANCA].

Antibodies against cytoplasm of neutrophil leucocytes (ANCA) with a high sensitivity are found in idiopathic necrotizing vasculitis and idiopathic glomerulonephritis with formation of sickles (IGS). C-ANCA are directed against the myeloid lysosomal enzyme--proteinase 3 and are found above all in Wegener's granulomatosis and microscopic polyarteritis. P-ANCA are directed mainly against myeloperoxidase, less against leucocytic elastase or lactoferrin and are found above all in microscopic polyarteritis, IGS, polyarteritis nodosa or Churg-Strauss syndrome. The elevated ANCA level correlates with the activity of the disease or precedes a relapse. These autoantibodies activate probably neutrophil leucocytes for respiratory exacerbation and degranulation which may lead to extensive tissue damage.

Autoantibodies↗

[Use of pulsed steroid therapy in active rheumatoid arthritis].

The authors implemented a prospective double blind, controlled study where they administered to a group of 34 patients with active rheumatoid arthritis either three pulses a 1000 mg methyl prednisolone in a small infusion or an infusion with placebo. They proved a very favourable effect--after five days a marked diminution of morning stiffness was recorded, as well as a diminution of pain during locomotion and rest and general improvement of the patient's condition. After two weeks the effect declines but even after 8 weeks the difference, as compared with the initial value, was still significant, while this was not the case after placebo. The sedimentation rate increased after the initial decline to the baseline level. A number of immunological indicators (decline of immunoglobulins, IgG rheumatoid factor, rise of C3 and C4 complement levels and rise of T lymphocytes) suggest an anti-inflammatory and immunosuppressive action persisting for several weeks although the mentioned results were not statistically significant (the majority at the very borderline of significance, probably significant in a larger number of patients). The authors confirm the reactive safety of this treatment, emphasize the necessity to investigate contraindications of treatment (diabetes mellitus) and the necessity to follow up patients in inpatient facilities.

Arthritis, Rheumatoid↗

[Rheumatoid factor in rheumatoid arthritis in old age].

Rheumatoid factors (RF) detected by agglutination methods (latex fixation test, haemagglutination test) were found in a group of patients with rheumatoid arthritis which started in advanced age (RAVV) less frequently than in a group with RA in middle age (RAMV). The author describes the ELISA method for assessment of RF which makes it possible to estimate immunoglobulin classes RF (IgM-RF, IgA-RF, IgG-RF). By this method RF were detected in class IgM in 15% of patients and in some immunoglobulin classes in 20 per cent where are RF negative when assessed by agglutination methods. The ELISA method detects probably also so-called "hidden" RF. In the group of healthy subjects above 60 years at least one class of RF rises to 17.5%. On correlation with the clinical status an association was found with the degree of affection according to the functional score, with the presence of rheumatoid nodes and muscular affection in RA. Patients with RA treated with Methotrexate and Sulfasalazine tend to have declining IgG RF levels.

Age Factors↗

[New findings on the pathogenesis of rheumatoid arthritis].

In the submitted review the authors present some new findings and approaches pertaining to the pathogenesis of rheumatoid arthritis (RA). First they describe cells participating in the development of the articular inflammation and mediators which transmit signals between these cells and which may lead to their activation. The authors mention the immune complex role of rheumatoid factors and some new theories on their development. They describe effector substances directly responsible for the resulting damage and emphasize their final role in the entire cycle preceding the inflammatory reaction in which lymphocytes, macrophages, polymorphonuclear leucocytes and dendritic cells participate. The possible role of viruses in the aetiology of RA is also mentioned. In the conclusion the authors present the sequence of mechanisms which lead to the development and maintenance of the chronic inflammatory reaction which develops probably on the background of the persisting autologous mixed lymphocytic reaction.

Arthritis, Rheumatoid↗

Acute cricopharyngeal obstruction in dermatomyositis.

We report a case of a 44-year-old woman with dermatomyositis complicated by acute total cricopharyngeal obstruction resistant to corticosteroid therapy. This condition was successfully resolved by cricopharyngeal myotomy.

Adult↗