Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A.

Objective To evaluate the extended follow-up of the CYCLOFA-LUNE trial, a randomized prospective trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide (CPH) or cyclosporine A (CyA). Patients and methods Data for kidney function and adverse events were collected by a cross-sectional survey for 38 of 40 patients initially randomized in the CYCLOFA-LUNE trial. Results The median follow-up time was 7.7 years (range 5.0-10.3). Rates of renal impairment and end-stage renal disease, adverse events (death, cardiovascular event, tumor, premature menopause) did not differ between the CPH and CyA group, nor did mean serum creatinine, 24 h proteinuria and SLICC damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. Conclusion An immunosuppressive regimen based on CyA achieved similar clinical results to that based on CPH in the very long term.

Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study.

Intravenous cyclophosphamide is considered to be the standard of care for the treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide. Forty patients with clinically active proliferative lupus nephritis were randomly assigned to one of two sequential induction and maintenance treatment regimens based either on cyclophosphamide or Cyclosporine A. The primary outcomes were remission (defined as normal urinary sediment, proteinuria <0.3 g/24 h, and stable s-creatinine) and response to therapy (defined as stable s-creatinine, 50% reduction in proteinuria, and either normalization of urinary sediment or significant improvement in C3) at the end of induction and maintenance phase. Secondary outcomes were incidence of adverse events, and relapse-free survival. At the end of the induction phase, 24% of the 21 patients treated by cyclophosphamide achieved remission, and 52% achieved response, as compared with 26% and 43%, respectively of the 19 patients treated by the Cyclosporine A. At the end of the maintenance phase, 14% of patients in cyclophosphamide group, and 37% in Cyclosporine A group had remission, and 38% and 58% respectively response. Treatment with Cyclosporine A was associated with transient increase in blood pressure and reversible decrease in glomerular filtration rate. There was no significant difference in median relapse-free survival. In conclusion, Cyclosporine A was as effective as cyclophosphamide in the trial of sequential induction and maintenance treatment in patients with proliferative lupus nephritis and preserved renal function.(ClinicalTrials.gov identifier: NCT00976300)

[Replacement of aortic valva and ascending aorta in patient with Takayasu's arteritis]. / Náhrada aortální chlopne a vzestupné aorty u pacienta s Takayasuovou arteritidou.

Takayasu's arteritis (TA) is a rare vascular disorder, which predominantlly affects aorta and its primary branches. TA has a worldwide distribution and it is most frequent in young women. We report the case report of 36-year-old women, who underwent replacement of aortic valve and ascending aorta due to signifiant aortic regurgitation and dilatation of ascending aorta as a consequence of TA.

[Cognitive dysfunction in patients with systemic lupus erythemathosus with or without antiphospholipid antibodies]. / Kognitivní dysfunkce u pacientu se systémovým lupus erythematodes a antifosfolipidovými protilátkami.

INTRODUCTION: Impairment of cognitive functions is one of the neuropsychiatric symptoms of systemic lupus erythemathosus (SLE), the association of which with secondary antiphospholipid syndrome is often mentioned in the literature on the subject. Ethiology has not yet been fully clarified. PATIENTS AND METHODS: The aim of the study was to compare the "mini-mental state examination" (MMSE) outcomes in SLE patients with and without antiphospholipid antibodies (APA). RESULTS: Probands producing APA presented with significantly worse results in MMSE when compared to patients without these antibodies. There was no difference between patients with antisphospholipid syndrome and those with APA only. DISCUSSION AND CONCLUSION: Our study supports the notion that association of SLE with APA (not only with antiphospholipid syndrome) aggravates the deterioration of cognitive functions. MMSE test should not be omitted in the follow-up of SLE patients.

[Retinopathy in dermatomyositis]. / Retinopatie pri dermatomyozitide.

The authors describe a patient with acute onset dermatomyositis, "probable", according to criteria of Bohan and Peter, as well as the development of the disease in the course of 21 months. A special feature was the decline of visual acuity (practically to the level of blindness). The cause was severe retinopathy with dominance of macular oedema, "cotton wool" spots and haemorrhages, as apparent from photographs of the fundus and findings obtained by fluorescein angiography. The problem of initial treatment was resistance to megadoses of glucocorticoid (i.v. pulses). A favourable change occurred only after i.v. administration of polyvalent immunoglobulin in a total dose of 600 mg/kg body weight. Then the authors observed the unique phenomenon of regression of retinal oedema incl. the macula, of the haemorrhages and "cotton wool" spots. Consistent with it vision off the right eye improved to 1.0 and the left eye to 0.66 in the course of 11 months. Stabilized retinal neovascularizations persist. On account of the latter the authors treated the retina by laser panretinocoagulation.

Synchronization as adjustment of information rates: detection from bivariate time series.

An information-theoretic approach for studying synchronization phenomena in experimental bivariate time series is presented. "Coarse-grained" information rates are introduced and their ability to indicate generalized synchronization as well as to establish a "direction of information flow" between coupled systems, i.e., to discern the driving from the driven (response) system, is demonstrated using numerically generated time series from unidirectionally coupled chaotic systems. The method introduced is then applied in a case study of electroencephalogram recordings of an epileptic patient. Synchronization events leading to seizures have been found on two levels of organization of brain tissues and "directions of information flow" among brain areas have been identified. This allows localization of the primary epileptogenic areas, also confirmed by magnetic resonance imaging and pasitron emission tomography scans.

[Pulse therapy in diffuse connective tissue diseases]. / Pulzní lécba u difuzních nemocí pojiva.

Methods of i.v. pulsed treatment using methyl prednisolone, cyclophosphamide or polyvalent immunoglobulin made it possible to suppress rapidly and effectively the activity of prognostically serious (clinical and laboratory) manifestations in diffuse connective tissue diseases (systemic autoimmune diseases). The author presents a general justification of this therapeutic method with emphasis on the immunogenetics of pathological autoimmunity (autogenes, apoptosis), he describes methodical aspects, the asset and partial clinical indications in rheumatoid arthritis, systemic lupus erythematosus, polymyositis and dermatomyositis, and primary systemic vasculitis. The author mentions also prerequisites of further development of i.v. pulsed treatment in diffuse connective tissue diseases.

[The importance of administration of a series of methylprednisolone minipulses in the treatment of active rheumatoid arthritis]. / Význam série minipulzu metylprednizolonu v lécbe aktivní revmatoidní artritidy.

BACKGROUND: Rapid, safe and persisting suppression of rheumatoid arthritis activity (RA) reduces the risk of destructive changes of the joints. Initial methylprednisolone (MP) treatment helps to implement task, optimal dosage is, however, a yet unresolved problem. METHODS AND RESULTS: In an open clinical trial 20 women with active RA were treated by a series of five minipulses á 125 mg MP in daily intravenous infusions. Within 60 days from the first MP minipulse onwards the authors monitored the morning stiffness, pain according to a visual analogue scale, Ritchie's index and five laboratory indicators. A significant decline of values (p < 0.05 < 0.001) in all clinical and some laboratory signs revealed that the response to the administered treatment was prompt and sufficiently protracted to bridge the gap before the onset of the effect produced by parallel basal treatment. CONCLUSIONS: The results provide evidence that treatment by a series of minipulses of MP can be considered the method of choice to suppress the acme of RA activity and to bridge the gap before the onset of response to basal treatment.

[The importance of the HLA complex antigens in systemic rheumatoid diseases]. / Antigen HLA-komplexu s vyznamem u systémových revmatických nemocí.

The submitted paper reviews contemporary knowledge on the clinical impact of assessment of HLA-complex antigens in systemic rheumatic diseases. The authors explain the term "relative risk" and its practical importance. As to antigens of the HLA-complex class I, attention was paid in particular to the importance of HLA B 27 in ankylosing spondylitis, other spondylarthropathies and reactive arthritis; in this part the review is supplemented by results of the authors' own research. As to antigens of the HLA-complex class II, attention was paid to the sub-area DR in rheumatoid arthritis and other diffuse affections of connective tissue. The advance in knowledge of the clinical impact of investigations of selected HLA-complex antigens in systemic rheumatic diseases is that in many instances it reveals an association not only at the level of the nosological unit but frequently also sub-unit with prognostically important clinical and biochemical manifestations, a typical autoantibody profile and sometimes also with the risk of a greater organ toxicity of drugs.

[Behçet's disease and IgG lambda paraproteinemia]. / Behcetova choroba a paraproteinémie IgG lambda.

The authors describe the clinical observation and therapeutic experience of the seven-year follow-up of a female patient with Behcet's disease according to the diagnostic classification criteria of the International Study Group (1990). The remarkable feature of the described observation is evidence of the herpes simplex virus type I in the oral cavity and in particular the five-year follow-up of stabilized paraproteinaemia IgG lambda of obscure impact.

[Favorable effect of methylprednisolone pulse therapy in dysphagia and primary idiopathic polymyositis/dermatomyositis]. / Príznivý vliv pulsní lécby metylprednisolonem na dysfagii u primární idiopatické polymyozitidy/dermatomyozitidy.

In five previously not treated patients with active primary idiopathic polymyositis/dermatomyositis and severe dysphagia persisting for 3-8 weeks treatment with a series of 4-5 intravenous pulses a 1 g methylprednisolone was provided. In four patients dysphagia disappeared within 2-14 days, in one patient within 30 days marked improvement was recorded. During the 12-64-month follow up period in none of the patients relapse or deterioration of dysphagia was observed. One female patient died 12 months after establishment of the diagnosis during reactivation of the basic disease with marked fibrosis of the pulmonary interstitium, the remaining patients are in permanent remission.

[Systemic lupus erythematosus after thymectomy in myasthenia gravis]. / Systémový lupus erythematosus po thymektomii pro myasthenia gravis.

The authors describe a case of systemic lupus erythematosus in a 33-year-old female patient who developed the disease 12 years after thymectomy on account of myasthenia gravis. The activity of systemic lupus erythematosus was controlled by pulsed treatment with methyl prednisolone followed by long-term oral glucocorticoid and immunosuppressive therapy. The authors discuss the risk of systemic lupus erythematosus after thymectomy on account of myasthenia gravis with regard to the HLA haplotype.

[Thymoma in the anterior mediastinum and systemic lupus erythematosus]. / Thymóm predního mediastina a systémový lupus erythematosus.

The authors describe an observation of a thymoma and systemic lupus erythematosus (SLE) in a 48-year-old woman with an analysis of clinical and laboratory indicators justifying this diagnosis. Improvement of SLE and the lupus nephropathy was achieved by three pulses of methyl prednisolone à 1000 mg in an intravenous infusion with subsequent Prednisone therapy, using conventional doses. After thymectomy on account of a benign thymoma activation of SLE did not occur. The objective of the presented paper is to draw attention to the infrequent possible concurrent incidence of thymoma and SLE and the influence of thymectomy and the subsequent development of SLE.

[Rheumatoid arthritis developing into systemic lupus erythematosus during long-term treatment with penicillamine and sulfasalazine]. / Prechod revmatoidní artritidy v systémový lupus erythematosus pri dlouhodobé lécbé penicilaminem a sulfasalazinem.

A female patient with IgM RF seropositive rheumatoid arthritis according to criteria of the American Rheumatism Association was treated for 133 months with Penicillamine and for 17 months also with Sulfasalazine. Both types of treatment were discontinued because the patient developed symptoms meeting diagnostic criteria of systemic lupus erythematosus, as defined by the same society. Early recognition of this diagnosis was made possible by regular follow up of clinical and laboratory data (ANA, anti DNP, anti dsDNA, C3, C4 and others). Marked improvement, incl. improvement of the nephropathy, was recorded after pulsed treatment with methylprednisolone.

[Long-term study of diffuse connective tissue disease after methylprednisolone pulsed therapy]. / Dlouhodobé sledování difúzních nemocí pojiva po pulzní lécbe metylprednizolonem.

Pulsed i.v. treatment with methylprednisolone (MP) infusions à 1 g 3-5 times on alternate days was administered in 22 diffuse connective tissue diseases: 13X systemic lupus erythematosus (SLE), 1X Sharp's syndrome and 8X polymyositis/dermatomyositis (PM/DM). In all instances active disease was involved with serious organ manifestations; 17 patients had no aimed treatment so far, in 5 previous treatment had failed. A total of 101 pulsed MP was administered. Initial MP treatment was always successful. The patients were then followed up during oral maintenance treatment for 3-60 months (mean 27 months) in a stage of persistent, inconstant or partial remission. In six patients treatment was repeated 8X after reactivation. The response was always favourable and did not differ from that to initial MP treatment, except for one female patient who died from progression of PM/DM (one female patient died from the sequels of oncological disease associated with SLE).

[Anticardiolipin antibodies in diffuse connective tissue diseases with IgG, IgM and IgA isotypes]. / Antikardiolipinové protilátky u difúzních nemocí pojiva v izotypech IgG, IgM a IgA.

Anticardiolipin (aCL) antibodies were assessed in isotypes IgG, IgM and IgA by the enzyme immunochemical technique in serum of 86 subjects with diffuse connective tissue affections and in 75 subjects of three control groups (syphilis, syndrome of common variable immunodeficiency and blood donors). In systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and syphilis the mean values of the three isotypes of aCL antibodies were significantly higher than in blood donors (p = 0.05 to 0.001); in diffuse scleroderma and primary polymyositis/dermatomyositis in isotype IgG (p = 0.01-0.001). Positive findings of aCL antibodies (isolated or in combinations of Ig isotypes (were found most frequently in SLE (34.4%), RA (33.3%) and syphilis (66.6%); sera of blood donors were positive in 8.7%. Venous thrombosis was recorded in the case-records of 28% patients with SLE but only in 5.4% of those with RA. Spontaneous abortion terminated 8/66 pregnancies in 28 women with SLE. In one female patient with SLE the aCL syndrome was detected. On account of frequent positivity of aCL antibodies in syphilis, the authors consider it essential to rule out the coincidence of this disease. Examination of aCL-IgA antibodies extends the detection of positive cases (isolated or in combinations of Ig) in SLE and RA.

IgG1-4 subclasses in paraproteinemias.

The concentration of IgG1-4 subclasses was determined in a series of 10 IgG1 paraproteinemias (5 multiple myelomas and 5 non-myeloma paraproteinemias) and in a series of 11 IgA paraproteinemias (7 multiple myelomas and 4 non-myeloma paraproteinemias). In the group of IgG1 myelomas, deficiency was established in the subclasses IgG2-4, in the group of IgA myelomas, deficiency was proved in all IgG1-4 subclasses as compared with non-myeloma paraproteinemias. Decreased IgG heterogeneity in IgG1 myelomas was demonstrated by the method of isoelectric focusing.

Index of light kappa/lambda and lambda/kappa chains in monoclonal gammopathies.

Concentrations of the light chains kappa and lambda were determined by simple radial immunodiffusion in the blood sera of 437 patients with monoclonal gammopathies. The kappa/lambda index was calculated in monoclonal gammopathies with the antigenic type of kappa light chains, while in monoclonal gammopathies with the antigenic type of lambda light chains the lambda/kappa index was calculated. The results obtained in malignant monoclonal gammopathies were compared with the results obtained in monoclonal gammopathies of undetermined significance for IgG and IgM paraproteinemias. Differences of high statistical significance were established (for IgG and IgA p less than 0.001, for IgM p less than 0.005) and thus the light-chain index can be used as another marker in differential diagnosis of monoclonal gammopathies.