Jerzy Stańczyk

Methods of evaluation of autonomic nervous system function

Disturbances of the autonomic nervous system play a crucial role in the pathogenesis and clinical course of many diseases. Recently, rapid development has occurred in the clinical assessment of autonomic function. Various procedures have been described as diagnostic tools to monitor autonomic dysfunction. Some of them are mostly used for research purposes. Many, however, have found their place in routine clinical evaluation. Our paper presents selected methods of assessment of the autonomic nervous system with particular emphasis on those that are useful in diagnosis and treatment of diseases of the cardiovascular system. We discuss multiple tests based on cardiovascular reflexes, methods of studying heart rate variability as well as direct catecholamine measurements. Moreover, we outline tests of sudomotor function and microneurography.

Distribution and clinical significance of blood dendritic cells in children with juvenile idiopathic arthritis

Background: A role for dendritic cells (DC) in the development of adult rheumatoid arthritis has been suggested. To date, this problem has been poorly explored in juvenile idiopathic arthritis (JIA). Objective: To analyse distribution and maturation status of blood DC (BDC) in JIA. Methods: Absolute BDC counts were assessed by the “single platform” method in peripheral blood (PB) of 47 untreated children with JIA and 32 healthy controls. Moreover, BDC were investigated in JIA synovial fluid (SF). When the panel of monoclonal antibodies against BDC antigens (BDCA) was used, three BDC subpopulations were determined: myeloid type 1 (mDC1; BDCA-1+/HLA-DR+/CD19−), myeloid type 2 (mDC2; BDCA-3+/HLA-DR+/CD14−) and plasmacytoid (pDC; BDCA-2+/HLA-DR+/CD123+). Results: A considerable deficiency of all subtypes of BDC was found in the PB of children with JIA. BDC counts in JIA SF were significantly higher than in PB both from children with JIA (p<0.001) and healthy children (p<0.001). SF BDC, especially mDC1 and mDC2 subtypes, had significantly higher expression of maturation markers (CD40, CD80, CD86 or CD83 antigens) than those from PB. A smaller number of PB BDC at diagnosis correlated significantly with poor response to treatment. Conclusions: A deficiency of BDC in PB is accompanied by enrichment of SF with those cells. Probably, circulating BDC migrate to joints where they undergo maturation and help to mediate and maintain the local immune response. Interestingly, the level of PD BDC deficiency seems to influence the outcome in children with JIA.

Apoptosis of peripheral blood lymphocytes in patients with juvenile idiopathic arthritis

Background: Recent data suggested that abnormalities in mechanisms regulating apoptosis may have a role in the development of the rheumatoid process. Objective: To evaluate different aspects of apoptosis in children with juvenile idiopathic arthritis (JIA). Methods: The frequency of TUNEL positive peripheral blood (PB) lymphocytes (apoptotic index (AI)), as well as serum CD95 (APO1/Fas) antigen expression and serum levels of sFas and interleukin 15 (IL15), were examined in 44 cases of JIA. Results were correlated with type of onset, activity of JIA, and acute phase indicators. Results: The AI of lymphocytes was significantly higher in patients with JIA than in controls (p=0.020). The mean AI of lymphocytes was increased in JIA with systemic type of onset and high activity (p=0.001). Moreover, IL15 levels in systemic disease were higher than in controls (p=0.012). An increased AI correlated with raised IL15 (p=0.046), erythrocyte sedimentation rate (p=0.005) and C reactive protein (CRP; p=0.017). Additionally, correlation was found between IL15 and CRP levels (p=0.039). CD95 and sFas levels were unchanged compared with controls. Conclusion: PB lymphocytes of children with JIA have an increased tendency to undergo apoptosis. The degree of apoptosis depends on the type of onset and activity of JIA and correlates with serum levels of IL15. Further studies are needed to explain whether this is an epiphenomenon of the disease activity or is related to the pathogenesis of JIA.

Prenatal diagnosis and follow-up of 23 cases of cardiac tumors

To evaluate the prenatal characteristics and postnatal outcome of cardiac tumors diagnosed at two prenatal Polish cardiology centers.

Heart rate variability in children with neurocardiogenic syncope.

Abstract.In order to characterize the autonomic profile of syncopal children, we have studied heart rate variability (HRV) of 73 children, ages 11–18, with neurocardiogenic syncope and a positive outcome of head-up tilt testing (HUT).HRV was calculated over a 24-hour period for the time-domain indices (SDNN, SDANNi, SDNN, rMSSD, pNN50), and over 5-minute segments from night and day for frequency-domain indices (LF, HF, LF/HF). The obtained results were compared to reference values calculated for Polish children. 55% of the children had mixed response to HUT, 41% vasodepressor and 4% cardioinhibitory. Patients with syncope had significantly lower values of rMSSD and pNN50 in comparison to healthy children. Moreover, in the frequency-domain analysis they exhibited significantly higher LF and lower HF values. The day-night rhythm of HRV and the age-related changes of HRV were, however, similar in syncopal and healthy children. In addition to this, we found a significantly lower SDNN value in children with cardioinhibitory response during HUT in comparison to children with mixed response. We concluded that 1) based on HRV analysis children with neurocardiogenic syncope had alterations in basal autonomic balance, which indicated an increased sympathetic modulation in these patients, 2) syncopal children had adequate circadian rhythm of autonomic activity, 3) the changes of HRV indices with age in these groups are not altered in comparison to healthy children, 4) syncopal children may exhibit differences in HRV indices values depending on the kind of vasovagal response observed during HUT.

Intra-uterine growth restriction as a risk factor for hypertension in children six to 10 years old

Summary Introduction Intra-uterine growth restriction (IUGR) is present in about 3–10% of live-born newborns and it is as high as 20–30% in developing countries. Since the 1990s, it has been known that abnormalities during foetal growth may result in cardiovascular disease, including hypertension in adulthood. Methods This study evaluated blood pressure parameters (using ambulatory blood pressure monitoring) in children aged six to 10 years old, born as small for gestational age (SGA), and compared them to their healthy peers born as appropriate for gestational age (AGA). Results In the SGA group, an abnormal blood pressure level (prehypertension or hypertension) was present significantly more often than in the AGA group (50 vs 16%, p < 0.01). This relationship also occurred in association with the type of IUGR (asymmetric p < 0.01, symmetric p < 0.05). Conclusion In SGA children, abnormal blood pressure values occurred more frequently than in AGA children.

Anticitrullinated Protein Antibodies and Radiological Progression in Juvenile Idiopathic Arthritis

Objective. The aim of the study was to investigate whether determination of anticitrullinated protein antibodies (ACPA) provides predictive information on severity of disease course and joint destruction in children with juvenile idiopathic arthritis (JIA). Methods. Sera from 74 children with JIA were examined for ACPA using the ELISA test. To assess joint destruction, plain radiographs of both hands were scored twice according to the Steinbrocker scale: at the beginning of observation and after 8.9 to 15.2 months (median 11.5 months) of the followup. Correlations between ACPA serum levels and the disease characteristics (type of JIA onset, disease activity, disease duration, radiological status) were investigated. Results. Twenty-six out of 74 examined children with JIA (35.0%) were ACPA-positive [> 5 relative units (RU)/ml]. ACPA were present in all types of JIA onset, including 36.6% of children with early stage JIA (disease duration < 6 months). All of the IgM-rheumatoid factor (RF)-positive children with polyarticular type of JIA onset were simultaneously positive for ACPA. ACPA levels correlated positively with disease activity at the beginning of the study (rho = 0.7196; p < 0.0001) and after followup (rho = 0.2485; p = 0.0486). Disease duration did not significantly affect ACPA serum levels. ACPA levels correlated positively with radiological joint destruction in children with JIA, both at the beginning of the study (rho = 0.4599; p = 0.0004) and after the followup period (rho = 0.5523; p < 0.0001). Conclusion. ACPA were superior to IgM-RF in diagnosing JIA and provided predictive information on severity of disease course and radiological outcome.

Relationship between impaired apoptosis of lymphocytes and distribution of dendritic cells in peripheral blood and synovial fluid of children with juvenile idiopathic arthritis

Introduction:The pathogenesis of juvenile idiopathic arthritis (JIA) is not fully understood. Recently the present authors described disturbed apoptosis of JIA lymphocytes in both peripheral blood (PB) and synovial fluid (SF) as well as an abnormal distribution of blood dendritic cells (BDCs) between the PB and SF in this disease. Possible relationships between these events during the development of JIA process are assessed here.Materials and Methods:Lymphocyte apoptosis and BDC counts were assessed in the PB and SF of untreated JIA children. Lymphocyte apoptosis was analyzed by the Annexin-V/propydium iodide assay. Total DC (TDC) number was based on the sum of three BDC subpopulations determined using a panel of monoclonal antibodies against BDC antigens (BDCA): myeloid type 1 (mDC1, BDCA-1+/HLA-DR+/CD19-), myeloid type 2 (mDC2, BDCA-3+/HLA-DR+/CD14-), and plasmacytoid (pDC, BDCA-2+/HLA-DR+/CD123+). Cells were enumerated by the flow cytometric “single-platform” method. The concentration of tumor necrosis factor (TNF)-α and the distribution of particular lymphocyte subtypes in both PB and SF were also investigated.Results:There was significant positive correlation between apoptosis of PB lymphocytes and SF TDC count (p=0.002) as well as SF TNF-α concentration (p=0.007). SF TNF-α levels also correlated with SF TDC count (p=0.003). Moreover, JIA SF was distinctly enriched with CD4+ and CD8+ T lymphocytes and included CD4+/CD25high cells as well. There was significant positive correlation between the number of CD4+/CD25high cells and SF JIA BDC count (p=0.015).Conclusions:These data suggest a possible link between impaired apoptosis of PB/SF lymphocytes and increased recruitment of PB BDCs to SF and other elements of the immune system in JIA, including regulatory CD4+/CD25high cells.

Imbalance of Th17 and T-regulatory cells in peripheral blood and synovial fluid in treatment naïve children with juvenile idiopathic arthritis

Objectives The imbalance between Th17 and T regulatory cells (Tregs) may be a key event in development of autoimmunity. The problem is poorly explored in juvenile idiopathic arthritis (JIA) so far. In this study, peripheral blood (PB) and synovial fluid (SF) Tregs and Th17 cells from were assessed in untreated JIA children. Material and methods In 50 children with JIA the PB or SF percentages of Tregs and Th17 cells were assessed by flow cytometry, in comparison with PB Tregs and Th17 cells from 28 healthy controls. Additionally, in both groups the levels of proinfammatory cytokines, such as interleukin (IL)-1β, IL -6, IL -17, IL -21, IL -23 and tumor necrosis factor α (TN F-α) were assessed using ELI SA method. Results The proportion of JIA PB Th17 cells was significantly higher than in the controls (p = 0.01). Serum levels of IL -1β, IL -6, IL -17, IL -23 were also significantly higher in JIA (p = 0.011, p = 0.007, p = 0.008 and p = 0.023, respectively). The highest serum IL -6 levels were observed in oligoarthritis JIA (p = 0.031). Synovial fluid IL -21 concentration was distinctly higher in polyarticular JIA. Synovial fluid levels of TN F-α, IL -1β and IL -6 were significantly higher than in JIA PB (p = 0.038, p = 0.013 and p < 0.001, respectively). There was a significant correlation between IL -6 and PB Tregs (p = 0.02). Conclusions The results of this comprehensive analysis indicate a role of Th17 cell activation in the pathogenesis of JIA.

Recurrent arterial and venous thrombosis in a 16-year-old boy in the course of primary antiphospholipid syndrome despite treatment with low-molecular-weight heparin: a case report

IntroductionAntiphospholipid syndrome is a multisystem autoimmune disease characterized by arterial and/or venous thrombosis and persistent presence of antiphospholipid antibodies. It can be a primary disease or secondary when associated with other autoimmune diseases.Case presentationWe present a case of a 16-year-old Caucasian boy with a massive arterial and venous thrombosis in his lower limbs as well as in his central nervous system with clinical symptoms such as headaches and chorea. He did not present any clinical or laboratory signs of a systemic inflammatory connective tissue disease, including systemic lupus erythematosus. Based on the clinical picture and results of the diagnostic tests (positive antibodies against β2-glycoprotein and a high titre of anticardiolipin antibodies) we finally diagnosed primary antiphospholipid syndrome. During a 9-month follow up after the acute phase of the disease, he was treated with low-molecular-weight heparin. Neurological symptoms were relieved. Features of recanalization in the vessels of his lower limbs were observed. After a subsequent 6 months, because of the failure of preventive treatment – an incident of thrombosis of the vessels of his testis – treatment was modified and heparin was replaced with warfarin.ConclusionAlthough the preventive treatment with warfarin in our patient has continued for 1 year of follow up without new symptoms, further observation is needed.