The use of heart rate turbulence and heart rate variability in the assessment of autonomic regulation and circadian rhythm in patients with systemic lupus erythematosus without apparent heart disease.

Background Systemic lupus erythematosus is a progressive autoimmune disease. There are reports suggesting that patients even without overt signs of cardiovascular complications have impaired autonomic function. The aim of this study was to assess autonomic function using heart rate turbulence and heart rate variability parameters indicated in 24-hour ECG Holter monitoring. Methods Twenty-six women with systemic lupus erythematosus and 30 healthy women were included. Twenty-four hour ambulatory ECG-Holter was performed in home conditions. The basic parameters of heart rate turbulence and heart rate variability were calculated. The analyses were performed for the entire day and separately for daytime activity and night time rest. Results There were no statistically significant differences in the basic anthropometric parameters. The mean duration of disease was 11.52 ± 7.42. There was a statistically significant higher turbulence onset (To) value in patients with systemic lupus erythematosus, median To = -0.17% (minimum -1.47, maximum 3.0) versus To = -1.36% (minimum -4.53, maximum -0.41), P < 0.001. There were no such differences for turbulence slope (Ts). In the 24-hour analysis almost all heart rate variability parameters were significantly lower in the systemic lupus erythematosus group than in the healthy controls, including SDANN and r-MSSD and p50NN. Concerning the morning activity and night resting periods, the results were similar as for the whole day. In the control group, higher values in morning activity were noted for parameters that characterise sympathetic activity, especially SDANN, and were significantly lower for parasympathetic parameters, including r-MSSD and p50NN, which prevailed at night. There were no statistically significant changes for systemic lupus erythematosus patients for p50NN and low and very low frequency. There was a positive correlation between disease duration and SDNN, R = 0.417; P < 0.05 and SDANN, R = 0.464; P < 0.05, a negative correlation between low/high frequency ratio and r-MSSD, R = -0.454; P < 0.05; p50NN, R = -0.435; P < 0.05 and high frequency, R = -0.478; P < 0.05. In contrast, there was no statistically significant correlation between heart rate turbulence and other variables evaluated, including disease duration and the type of autoantibodies. CONCLUSION: Our study confirms the presence of autonomic disorders with respect to both heart rate variability and heart rate turbulence parameters and the presence of diurnal disturbances of sympathetic-parasympathetic balance. Further studies are required.

Decreased ratio of circulatory vascular endothelial growth factor to endostatin in patients with systemic sclerosis--association with pulmonary involvement.

OBJECTIVE: Vascular endothelial growth factor (VEGF) and endostatin appear to be involved in development of systemic sclerosis (SSc). We undertook this study to determine ratios of serum concentrations of VEGF to endostatin in SSc patients, healthy controls, assessments between cytokines, and lung-diffusing capacity (DLCO) as lung injury measurements related to interstitial lung disease (ILD). MATERIALS AND METHODS: Serum VEGF and endostatin levels were measured with ELISA in 28 SSc patients (16 with lcSSc) and 20-matched healthy volunteers, evaluating correlation and balance. DLCO was corrected for hemoglobin, alveolar volume, and determined with a single breath technique. RESULTS: SSc serum concentrations (median; range) of endostatin were higher than controls (107.2; 13.6-261.2 vs. 77.8; 18.0-110.4 ng/ml, p < 0.05); VEGF levels did not differ (151.2; 4.5-836.4 vs. 286.4; 23.7-708.5 pg/ml, p < 0.05). Ratios of VEGF to endostatin were 2.6 and 3.6 times lower (p < 0.05) in SSc and dcSSc in comparison to healthy subjects. There were significant negative correlations between VEGF, endostatin in SSc (r = -0.51), and controls (r = -0.57). SSc with ILD (n = 20) had similar concentrations of VEGF, endostatin, and ratios of VEGF to endostatin compared to SSc alone. No correlations were seen between DLCO, VEGF, endostatin and their ratios in the whole SSc group. Negative correlations were noted between DLCO and VEGF (r = -0.82), with DLCO and the ratio of VEGF to endostatin (-0.62) in lcSSc with ILD (n = 10). CONCLUSION: Decreased ratios of VEGF to endostatin may reflect imbalances between serum angiogenic, and anti-angiogenic activity in SSc, explaining impaired neoangiogenesis.

Elevated whole blood chemiluminescence in patients with systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is accompanied by oxidative stress that in turn may accelerate endothelium degeneration and thus disease progression. We tested whether phagocytes from SSc patients release more reactive oxygen species (ROS) and whether this release correlates with some clinical parameters. METHODS: ROS production by blood phagocytes was measured with the luminol enhanced whole blood chemiluminescence (CL). Resting and N-formyl-methionyl-leucyl-phenylalanine -induced CL (fMLP-induced CL) was measured in 30 patients with SSc and 30 healthy controls matched as to age, sex, and level of cigarette smoking. RESULTS: Resting CL and fMLP-induced CL calculated per 10(4) phagocytes present in the assayed blood sample were higher in patients with systemic sclerosis than in healthy controls (median; range, 0.88; 0.47-1.39 vs. 0.73; 0.13-1.07 aU/10(4)p and 621; 293-3522 vs. 411; 289-810 aUxs/10(4)p, p<0.02). Patients treated with cyclophosphamide and/or prednisone for 11; 3-168 months did not differ in respect to CL from those that never received the medications. Similarly, no significant differences were found between patients with limited and diffuse SSc. Resting CL correlated (p<0.05) with clinically manifested interstitial lung disease (r=0.59), single breath carbon monoxide diffusing capacity (r= -0.56) and serum autoantibodies titre (r= 0.43). CONCLUSIONS: Blood phagocytes from patients with systemic sclerosis, especially from those with interstitial lung disease, generate elevated amounts of ROS as assessed with CL. This confirms the presence of systemic oxidative stress in SSc patients.

Elevated exhalation of hydrogen peroxide in patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis is accompanied by an influx of activated phagocytes into distal airways. These cells release H2O2, which may evaporate from the airways surface and be detected in expired breath condensate. We tested whether patients with systemic sclerosis exhale more H2O2 than healthy subjects and whether breath condensate H2O2 levels correlate with some clinical parameters. MATERIAL AND METHODS: H2O2 was measured fluorimetrically in the expired breath condensate of 27 patients (22 women, five men, mean age 49 +/- 13.1 years) with systemic sclerosis and 27 age- and sex- matched healthy controls. RESULTS: Exhaled H2O2 levels were 3.5-fold higher (0.88 +/- 0.62 microM vs. 0.25 +/- 0.17 microM, P < 0.001) in the patients with systemic sclerosis than in the controls. Treatment with cyclophosphamide and/or prednisone (29 +/- 50 months, range 3-168 months) did not significantly decrease H2O2 exhalation (0.78 +/- 0.50 microM, n= 10 vs. 0.94 +/- 0.67 microM, n= 17, P > 0.05). No significant difference was found between patients with limited and diffuse scleroderma (1.03 +/- 0.69 microM, n= 17 vs. 0.63 +/- 0.41 microM, n= 10, P > 0.05). H2O2 levels correlated with disease duration (r = 0.38, P < 0.05) and time from the first Raynaud's episode (r = 0.44, P < 0.05). CONCLUSIONS: Patients with systemic sclerosis exhale more H2O2 than healthy controls, suggesting involvement of reactive oxygen species in disease processes. Lack of significant intergroups differences in H2O2 levels may have resulted from the small number of patients analyzed.

[Evaluation of early cardiovascular involvement in patients with systemic sclerosis]. / Ocena wczesnych zmian w ukladzie sercowonaczyniowym u pacjentów z twardzina ukladowa.

UNLABELLED: The aim of the study was to evaluate cardiac function in patients with systemic sclerosis by means of noninvasive methods in order to detect early dysfunction of cardiovascular system. MATERIAL AND METHODS: We studied a group of 19 patients (15 women, 4 men, aged 17-74 yrs, av. 51 +/- 11) with systemic sclerosis comparing the results with a group of 23 healthy volunteers (17 women, 6 men aged 21-69 yrs, av 53 +/- 15). All the patients with SSc were taking corticosteroids, immunosuppressants or vasodilators at the time of the study. In all the patients we performed 24-hour Holter monitoring for the evaluation of arrhythmias, conduction disturbances, ischaemia, heart rate variability (HRV) and late potentials (LP). The following parameters of HRV in time domain were analyzed: SDNN, SDANN, SDNNI, rMSSD, pNN50. Standard ECG was performed to assess QT interval (QT, QTc, QTd). In all the patients the echocardiography examination was performed (M-Mode, 2-D, Doppler echocardiography). The morphology of heart structures and haemodynamic function were analyzed. RESULTS: In patients with SSc Holter monitoring revealed tendency to tachycardia. The mean heart rate was 81 +/- 11 vs. 71 +/- 9 in controls. Conduction disturbances were observed in 3 pts. In 6 pts we found significant ventricular arrhythmia. Silent ischaemia episodes were detected in 6 pts. Concerning HRV analysis the significantly lower values were detected in pts with SSc vs. controls: SDNN 123 vs 170; SDNNI 51 vs 76; SDANN 110 vs 152; rMSSD 29.6 vs 54; pNN50 6.1 vs 21. Late potentials were present in one patient with SSc vs none in the control group. The mean values QT-371, QTc-419, QTd-40- did not exceed the ranges of normal values. No signs of systolic cardiac dysfunction were detected, while in 6 pts we recognized left ventricle diastolic dysfunction. Valvular lesions were observed in 8 pts, but only in 2 pts they were hemodynamically important. CONCLUSIONS: 24-hour Holter monitoring and ECHO examination are valuable methods, which allow to detect early dysfunction of cardiovascular system in patients with systemic scleroderma presenting no apparent cardiac impairment symptoms.

Immunopathological examination of esophagus as a useful criterion of cure in pemphigus vulgaris.

BACKGROUND: We performed histopathological and immunopathological examinations of the esophagus in patients with pemphigus vulgaris during clinical remission. METHODS: In the group of 14 patients without serum antibodies, five were treated with low doses of steroids and cyclophosphamide (as maintenance treatment), while nine had already completed the therapy. RESULTS: In all five cases under maintenance treatment we found bound pemphigus antibodies in vivo. Acantholysis was present in two of these. In all nine non-treated patients, acantholysis and immunopathological findings were negative. CONCLUSIONS: Our studies reveal that the absence of bound 'pemphigus vulgaris' antibodies in the esophagus by immunological examination could be regarded as proof of complete cure and could be the decisive finding to stop pemphigus treatment.

Pemphigus foliaceus: an unusual clinical feature and case reports.

Two cases of pemphigus foliaceus in 70-year-old women have been presented. The initial clinical picture, as well as results of histopathologic examinations, suggested the diagnosis of eczema. Because the therapy was not successful and changes in the clinical picture were observed, repeated histopathologic and immunofluorescent examinations were carried out. Presence of immunologic findings characteristic for pemphigus foliaceus formed the basis for verification of the diagnosis and administration of an appropriate therapy.

Evaluation of esophageal passage in selected connective tissue diseases.

The objective of this study was to determine whether, as in with other types of connective tissue diseases, there exists esophageal passage dysfunction as it exists in systemic scleroderma. It was also interesting to establish whether there is any correlation between this kind of dysfunction and the subjective complaints connected with the esophagus as well as the occurrence of Raynaud's phenomenon. Evaluation of the esophageal passage was performed on the basis of scintigraphic examination. The delay of esophageal passage occurs, besides systemic scleroderma, in other types of connective tissue diseases. This examination is a valuable test, thanks to which changes in the esophagus can be discovered, despite the lack of subjective complaints. In addition to systemic scleroderma, there is no close correlation between dysphagia and Raynaud's phenomenon.

[Immunopathological studies of the skin of patients with pemphigoid at different stages of the disease]. / Badania immunopatologiczne skóry pacjentów z pemfigoidem w róznym okresie choroby.

The aim of the investigation was to demonstrate whether there is a correlation, in patients with bullous pemphigoid (BP), between the presence of immune deposits in the skin and the activity of the pathological process. We investigated 39 cases with a BP anamnese dating from 3 months up to 17 years. We repeated the investigations several times by means of direct immunofluorescence method in different disease activity. It was demonstrated that there is a complete correlation between the disappearance of the immune deposits in the skin and the remission of the disease. Moreover, it has been shown, that the complement disappears earlier than IgG fraction. These results show the role of the antibasement zone antibodies and especially the complement in the inducement of BP lesions.

[Clinical usefulness of determining the antibodies to soluble nuclear antigens in various collagen diseases]. / Przydatnosc kliniczna oznaczenia przeciwcial przeciw rozpuszczalnym antygenom jadrowym w grupie chorób tkanki lacznej.

The purpose of the study was evaluation of the clinical usefulness of determination of antibodies to soluble nuclear antigens. The study was carried out in 71 cases of various collagen diseases. Antibodies dsDNA (IIF method with Crithidium luciliae as substrate) were found only in patients with SLE and renal involvement. RNP antibodies (double immunodiffusion method) were demonstrated in 83.3% of cases of mixed connective tissue disease, and Sm antibodies in 8% of SLE patients. It is worth stressing that in the presented material Sm antibodies were present only in association with RNP antibodies. Antibodies Ro and/or La were present most often in the sera of patients with SCLE, while Scl 70 antibodies were a marker of systemic sclerosis, more frequent in patients with diffuse scleroderma, while their demonstration in acroscleroderma suggested a more severe course of the disease. The study showed a high diagnostic and prognostic value of antibodies to soluble nuclear antigens in collagen diseases.