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ABSTRACT: Autoimmune diseases (ADs) are more common in women than in men. Sex hormones may play a role. Sex hormone receptors (SHR) are expressed in cells of the immune system. We investigated the possible role of hormonal parameters and of common polymorphisms of the estrogen receptor alpha (ESR1), beta (ESR2), and androgen receptor (AR) genes in the appearance of AD in men. 277 men were studied; 125 with ≥1 AD: Hashimoto's autoimmune thyroiditis (n = 65), Graves' disease (n = 12), SLE (n = 10), and RA (n = 38). 152 were controls. Hormonal and biochemical parameters were measured after discontinuation for ≥1 month of any corticosteroid therapy. ESR1 PvuII, ESR2 AluI, and the AR (CAG)n repeats polymorphisms were analyzed. AD patients had higher estradiol levels (31.32 ± 12.10, controls 20.37 ± 7.91 pg/ml, p < 0.001). In multivariate analysis, significant predictors for AD were estrogen and BMI. The allele frequency of ESR1 PvuII and ESR2 AluI did not differ between patients and controls (AD: 47.8 %, 37.6 %; controls 49.8 %, 39.9 %). The distribution of (CAG)n did not differ between groups. In AD group, shorter (CAG)n alleles were associated with younger age of AD onset (short: 38.52 ± 14.8, long: 47.14 ± 17.34 years, p = 0.048). Carriers of ESR1 PvuII presented less frequently ≥2 AD (carriers 6.5 %, non-carriers 25.1 %, p = 0.019); carriers of AluI had lower SHBG levels and higher ΒΜΙ compared to non-carriers (p < 0.04). Higher estradiol may play a role in AD in men. Distribution of SHR gene polymorphisms is similar between patients and controls. Shorter AR (CAG)n repeats may predispose for younger AD onset. Coexistence of ≥2 AD is less frequent in carriers of ESR1 PvuII. ESR2 AluI may adversely affect obesity parameters.
Rheumatology International 03/2012; · 1.88 Impact Factor
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ABSTRACT: Mitral valve prolapse (MVP) is a benign valvular abnormality. However, an increased prevalence of MVP is reported in patients with systemic lupus erythematosus and autoimmune thyroid disease. Our aim was to evaluate whether the presence of MVP in healthy individuals might indicate a premature index of subclinical autoimmune disorder. A total of 75 individuals with MVP and 44 individuals without MVP were identified by echocardiography. Serum samples were examined for various organ and non-organ specific autoantibodies. In all, 35 of the 75 individuals with MVP had at least one autoantibody. ANA were detected in 17/75 in MVP(+) versus 1/44 in the MVP(-), (P < 0.05), and anti-ENA in 6/75 in the MVP(+) versus 0/44 in the control group, P = ns. In the MVP(+) group, thyroid autoantibodies, IgA and IgG RF were found at a statistically significant higher incidence, 16/75, 11/75 and 10/75 versus 1/44, 0/44 and 0/44 in the MVP(-)group, respectively (P < 0.05). The levels of IgG anticardiolipin antibodies were significantly higher in the MVP(+) group, P < 0.05. The presence of organ and non-organ specific autoantibodies in young healthy MVP(+) individuals insinuate the presence of subclinical autoimmunity and might suggest that autoimmune mechanisms might be involved in its pathogenesis. A follow-up of these individuals might elucidate whether MVP constitutes an early index of autoimmunity.
Lupus 02/2009; 18(5):436-40. · 2.34 Impact Factor
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ABSTRACT: In patients with connective tissue diseases (CTD), the early detection and evaluation of the severity of the pulmonary involvement is mandatory. High-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) are considered to be valuable noninvasive diagnostic modalities. Radiopharmaceuticals have also been used for this purpose. Our aim was the evaluation of technetium-labeled human polyclonal immunoglobulin G (HIG) lung scintigraphy in the early detection and assessment of the severity of the pulmonary involvement in CTD patients.
Fifty-two nonsmoking CTD patients were studied by PFTs, HRCT, and HIG. According to PFTs, patients were divided in group A (impaired PFTs-abnormal pulmonary function) and group B (normal pulmonary function). Semiquantitative analysis was done on HIG and HRCT and corresponding scores were obtained.
Significant difference was found between HIG scores in the two groups (0.6 +/- 0.07 vs 0.51 +/- 0.08, P < 0.001). There was a statistically significant negative correlation between HIG scores and PFTs results and a positive correlation between HIG and HRCT scores. HIG demonstrated similar clinical performance to HRCT. At the best cut-off levels of their score (0.56 and 7, respectively), HIG had a superior sensitivity (77.5 vs 57.5%) with lower specificity (75 vs 91.7%). The combination of the two methods increased the sensitivity of abnormal findings at the expense of specificity.
HIG scintigraphy can be used in the early detection and evaluation of the severity of the pulmonary involvement in CTD, whereas, when used in combination with HRCT, the detection of affected patients can be further improved.
European journal of nuclear medicine and molecular imaging 02/2008; 35(2):343-51. · 4.99 Impact Factor
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ABSTRACT: Increased endothelin activity may play a role in the pathogenesis of vascular injury, a primary feature of systemic sclerosis (SSc; scleroderma). Our goal was to test the hypothesis that treatment with the oral endothelin receptor antagonist bosentan might improve vascular endothelial function in SSc patients.
A 4-week, prospective, parallel-group study compared 12 SSc patients who did not receive bosentan treatment with 12 patients who did receive treatment (125 mg/day) for pulmonary hypertension and/or digital ulcers. There were no differences in demographic and clinical characteristics or medications between the 2 groups. Baseline endothelial dysfunction was documented by decreased brachial artery ultrasound-derived flow-mediated dilation (FMD%; <5.5). Pulse wave analysis, venous occlusion plethysmography, and measurement of serum vascular markers were performed in parallel.
FMD%, the main end point, increased significantly from a mean +/- SD of 3.1 +/- 1.3% to 8.4 +/- 2.6% after 4 weeks of bosentan treatment (P < 0.001, compared with a change from 2.4 +/- 1.6% to 2.4 +/- 2.2% in control patients). Arterial blood pressure, endothelium-independent vascular function, augmentation index, peripheral flow reserve, as well as circulating intercellular adhesion molecule 1, E-selectin, vascular endothelial growth factor, and endothelin 1 were not significantly affected by bosentan treatment. In patients continuously treated for 4 months, during which the dosage of bosentan remained at 125 mg/day (n = 5) or increased to 250 mg/day (n = 5), the 4-week results remained unchanged.
Small doses of bosentan improve endothelial function without affecting hemodynamic parameters or endothelial activation-related processes, thus supporting a direct, reversible effect of endothelin in SSc-associated vascular injury. A long-term, controlled trial to examine the potentially global clinical benefit of endothelin receptor blockade in patients with early SSc may be warranted.
Arthritis & Rheumatism 06/2007; 56(6):1985-93. · 7.87 Impact Factor
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ABSTRACT: In the present case-control study we aimed to investigate the association of common carotid arterial (CCA) stiffness with ischaemic stroke (IS) and to determine whether this relationship was independent of conventional risk factors including CCA intima-media thickness (CCA-IMT). CCA distensibility, defined as the change of CCA-diameter during the cardiac cycle, and CCA-IMT were evaluated by means of high-resolution B-mode carotid ultrasound examination in consecutive, first-ever IS patients (n=193) and in age- and sex-matched control subjects (n=106). The CCA distensibility (inverse of CCA stiffness) was significantly (P=0.007) lower in IS (0.353 mm, 95% CI: 0.326-0.379) than in control subjects (0.415 mm, 95% CI: 0.378-0.451) even after adjusting for blood pressure values, diastolic CCA-diameter and height. The multivariate logistic regression procedure selected CCA-IMT and CCA distensibility as the only independent predictor variables of IS. Each 1 SD increase in the CCA-IMT and each 1 SD decrease in the CCA distensibility independently increased the likelihood of IS by 167.0% (OR: 2.67, 95% CI: 1.80-3.96, P<0.001) and 59.0% (OR: 1.59, 95% CI: 1.22-2.07, P=0.001) respectively. Increased CCA stiffness is associated with IS independent of conventional risk factors and CCA-IMT. The causal interrelationship between the elastic properties of the CCA and the risk of stroke deserves further investigation by longitudinal studies.
European Journal of Neurology 05/2006; 13(5):475-81. · 3.69 Impact Factor
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ABSTRACT: Arterial hypertension is the major risk factor for intracerebral haemorrhage (ICH) and lacunar infarction (LI) and both types of cerebral lesions originate from pathology of the same deep perforating small arteries. We aimed to evaluate the relationship between vascular risk factors including common carotid artery intima-media thickness (CCA-IMT) with LI versus ICH.
We prospectively collected data from 159 first ever stroke patients (67 cases with ICH and 92 cases with LI) with documented history of hypertension. All subjects underwent B-mode ultrasonographic measurements of the CCA-IMT. Logistic regression modelling was used to determine the factors (established vascular risk factors, severity and duration of hypertension, concomitant medications and CCA-IMT) that may significantly differentiate LI from ICH.
Patients with LI had significantly (p=0.002) larger CCA-IMT values (0.926 mm, 95% CI: 0.881-0.971) than subjects with ICH (0.815 mm, 95% CI: 0.762-0.868) even after adjusting for baseline characteristics and cardiovascular medications. The multivariate logistic regression procedure selected CCA-IMT, diabetes mellitus and hypercholesterolaemia as the only independent factors able to discriminate between LI and ICH. The risk for LI versus ICH increased continuously with increasing CCA-IMT. For each increment of 0.1 mm in CCA-IMT the probability of suffering from LI versus ICH increased by 36.6% (95 % CI: 13%-65.2%, p=0.001) even after adjustment for cardiovascular risk factors.
Increased CCA-IMT values are a factor favouring LI over ICH in hypertensive patients. The measurement of CCA-IMT may be a useful non-invasive diagnostic tool for the risk assessment of LI with respect to ICH in such patients.
Journal of Neurology 10/2005; 252(9):1093-100. · 3.47 Impact Factor
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ABSTRACT: The aim of this study was to investigate the endothelial status in young women with polycystic ovary syndrome (PCOS), using a simple and easily reproducible hemodynamic method combined with a biological marker and to evaluate the effect of metformin treatment on these parameters.
Descriptive clinical trial.
Forty young women, 20 with PCOS and 20 normal women of similar age and body mass index were studied. Metformin (1700 mg daily) was administered for 6 months to the PCOS group. The endothelium status and the metabolic and hormonal profile were studied in both groups, as well as after metformin, by flow-mediated dilatation (FMD) on the brachial artery and by measurements of plasma endothelin-1 (ET-1) levels.
FMD was impaired in the PCOS group when compared with controls (3.24+/-0.71% vs 8.81+/-1.07% respectively, P<0.0001), but this difference normalized after metformin treatment (PCOS(post-metformin) vs controls: 8.17+/-1.26 vs 8.81+/-1.07%, P = 0.70) since the values significantly improved after metformin treatment (PCOS(pre-metformin) vs PCOS(post-metformin): 3.24+/-0.71 vs 8.17+/-1.26%, P=0.003). ET-1 levels were significantly higher in the PCOS women compared with the control group (7.23+/-0.50 vs 4.99+/-0.69 fmol/l, P=0.01), they improved significantly after metformin treatment (PCOS(pre-metformin) vs PCOS(post-metformin): 7.23+/-0.50 vs 3.57+/-0.60 fmol/l, P<0.0001) and their difference compared with the control group was reversed (PCOS(post-metformin) vs controls: 3.57+/-0.60 vs 4.99+/-0.69 fmol/l, P=0.13). Metformin administration improved hyperandrogenemia. However, in this study, mathematical methods used to assess insulin resistance failed to show any detected alteration after treatment with metformin.
PCOS women were found to exhibit endothelial dysfunction compared with controls, which was reversed 6 months after metformin administration.
European Journal of Endocrinology 05/2005; 152(5):749-56. · 3.42 Impact Factor
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ABSTRACT: To evaluate the relationship between systolic blood pressure (SBP) or diastolic blood pressure (DBP) on admission and early or late mortality in patients with acute stroke.
Prospective study of hospitalized first-ever stroke patients over 8 years.
Stroke unit and medical wards in a University hospital.
A total of 1121 patients admitted within 24 h from stroke onset and followed up for 12 months.
Mortality at 1 and 12 months after stroke in relation to admission SBP and DBP.
Early and late mortality in patients with acute ischaemic or haemorrhagic stroke in relation to admission SBP and DBP followed a 'U-curve pattern'. After adjusting for known outcome predictors, the relative risk of 1-month and 1-year mortality associated with a 10-mmHg SBP increase above 130 mmHg (U-point of the curve) increased by 10.2% (95% CI: 4.2-16.6%) and 7.2% (95% CI: 2.2-12.3%), respectively. For every 10 mmHg SBP decrease, below the U-point, the relative risk of 1-month and 1-year mortality rose by 28.2% (95% CI: 8.6-51.3%) and 17.5% (95% CI: 3.1-34.0%), respectively. Low admission SBP-values were associated with heart failure (P < 0.001) and coronary artery disease (P = 0.006), whilst high values were associated with history of hypertension (P < 0.001) and lacunar stroke (P < 0.001). Death due to cerebral oedema was significantly (P = 0.005) more frequent in patients with high admission SBP-values, whereas death due to cardiovascular disease was more frequent (P = 0.004) in patients with low admission SBP-values.
Acute ischaemic or haemorrhagic stroke patients with high and low admission BP-values have a higher early and late mortality. Coincidence of heart disease is associated with low initial BP-values. Death due to neurological damage from brain oedema is associated with high initial BP-values.
Journal of Internal Medicine 02/2004; 255(2):257-65. · 5.48 Impact Factor
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ABSTRACT: Endothelial vasomotor dysfunction was observed in patients with ABD in both active and inactive stages of the disease, thus
brachial artery flow-mediated dilation test seems unable to detect activity of the disease. No sign of peripheral atherosclerosis
as assessed by IMT was observed in our study group. Arterial stiffness was reduced in patients with active disease, and AI
could be useful in the future for detecting ABD activity; more studies are needed on this issue. Our study is being continued
in order to increase the number of our study objects and validate the use of AI and FMD for the control of the activity of
ABD, and prediction of vascular complications, respectively.
12/2003: pages 399-404;
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ABSTRACT: The role of androgens in the pathogenesis of coronary artery disease (CAD) remains controversial. The length of the polyglutamine stretch of the transactivation domain (CAG repeat) of the androgen receptor (AR) inversely affects androgen activity. The aim of this study was to investigate the effect of this polymorphism of the AR gene in the extent of CAD in male patients.
The relationship of the length of the AR gene CAG repeat on the severity of CAD was examined in 131 men (36-86 years old) undergoing coronary angiography.
The severity of CAD was assessed by the number (0-3) of coronary vessels with > 50% reduction in the luminal diameter. The interaction of the AR gene polymorphism with the intima media thickness (IMT) of peripheral arteries and serum levels of sex steroids, insulin and biochemical parameters were also studied.
The upper quartile of CAG length (range 9-30) was > or = 23 repeats (longAR). The mean body mass index (BMI) of patients with shorter repeats (< 23; shortAR) was significantly lower than in men with longAR (26.1 vs. 27.6, respectively; P = 0.043 M-W Rank test). There was no correlation between the AR gene repeat length and serum testosterone. Oestradiol levels were significantly higher in longAR (0.19 +/- 0.08 nmol/l vs. 0.14 +/- 0.07 in shortAR, P = 0.031). This difference was independent of BMI. Men with shortAR had significant CAD (i.e. one to three arteries with stenosis) more frequently (79.5%) than men with longAR (20.5%); of the subjects with stenosis in no arteries, 56.5% had shortAR and 43.5% longAR (chi2 = 4.3, P = 0.038). This association was independent of age and BMI. The IMT of peripheral arteries, lipid parameters, basal insulin resistance, blood pressure and family history for early CAD, did not differ according to AR length.
The shorter CAG repeat of the AR gene is associated with more severe CAD, which suggests a role for the sensitivity to androgens in the increased frequency of CAD in males. In addition, a protective role of endogenous oestrogen, which is higher in the longAR subgroup, can contribute to the observed difference.
Clinical Endocrinology 12/2003; 59(6):749-55. · 3.17 Impact Factor
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Advances in experimental medicine and biology 02/2003; 528:399-404. · 1.09 Impact Factor
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ABSTRACT: Mitral valve prolapse (MVP) has been reported to be associated with systemic lupus erythematosus (SLE). The aim of the present study was to determine the prevalence of MVP in SLE patients, assess its clinical significance and examine the possible association of this entity with other autoimmune indices. Eighty-seven consecutive SLE patients attending the rheumatology clinic and 73 normal control subjects were examined by M-mode, two-dimensional color-Doppler echocardiography. Serum samples were examined for various organ and non-organ specific autoantibodies. MVP was detected in 19/87 patients with SLE and in four of the healthy controls(P = 0.0057). SLE patients with MVP were younger (33.6 +/- 12.4 years) than those without MVP (41. +/- 12.9, P = 0.04) and with shorter duration of the disease (P = 0.03). We found a statistically higher prevalence of anticardiolipin antibodies (aCL) in SLE patients with prolapse (11/19) compared with SLE patients without prolapse (15/68, P = 0.04). This association was independent of age. The aCL-lgG levels were significantly higher in SLE patients with MVP (32.37 +/- 43.26) compared with SLE patients without MVP (22.24 +/- 29.95, P = 0.04). Thyroid autoantibodies tended to be more common in S LE patients with MVP. Th e prevalence of MVP is increased in SLE patients. The presence of aCL and of organ-specific autoantibodies in SLE patients with MVP might indicate the autoimmune origin of MVP. The possibility that SLE patients with MVP may be predisposed to further autoimmune diseases should be considered.
Lupus 02/2003; 12(4):308-11. · 2.34 Impact Factor
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ABSTRACT: To explore the regulatory defects underlying the overexpression of CD40 ligand (CD40L, CD154) in human lupus we studied the effects of cyclosporin-A (CsA), which blocks Ca2+/calcineurin-dependent CD40L gene expression, on peripheral blood-derived T cells and monocytes. In contrast to control subjects, CsA failed to inhibit the prolonged CD40L expression observed in vitro on anti-CD3-activated lupus T cells. Resistance to CsA was not restricted to CD4+ or CD8+ T cell subsets and was disease activity-independent. Experiments assessing the effects of dexamethasone on CD40L expression, as well as of CsA on the early activation marker CD69 expression and on surface CD40L cleavage, confirmed the unique regulation of CD40L in lupus T cells. On the other hand, co-culture with anti-CD3-activated T cells caused surface CD40L expression on monocytes, which was not an Fc receptor-mediated event. Lupus monocytes clearly overexpressed CD40L comparing to healthy and disease-control monocytes, and, similarly to lupus T cells, displayed a prominent resistance to CsA inhibitory effects. These findings indicate that, besides Ca2+/calcineurin-dependent mechanisms, other pathways are involved in the dysregulation of CD40L in SLE immune cells, dissection of which may have important therapeutic implications.
Lupus 02/2002; 11(6):370-8. · 2.34 Impact Factor
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ABSTRACT: A coexistence of mitral valve prolapse (MVP) with autoimmune thyroid disease (AITD) has been described, but there are not sufficient data to explain this association. The aim of the present study was to investigate the prevalence of MVP in patients with AITD and to evaluate whether any correlation between MVP and certain immunological parameters exists. M-mode, two-dimensional Doppler echocardiography was performed in 29 patients with Graves' disease (GD), 35 with Hashimoto's thyroiditis (HT), 20 with nonautoimmune goiter, and 30 normal controls. Serum samples were examined for antinuclear antibodies (ANA), antibodies against extractable nuclear antigen (ENA), antiphospholipid antibodies (aCL), rheumatoid factor (RF), thyroid autoantibodies (TAAb), immunoglobulins and C3, C4. Eight of 29 GD patients and 8 of 35 HT patients had MVP, while none of the control group and 2 of 20 of the simple goiter group had MVP (p < 0.05). ANA were detected at low titers in 5 of 8 in MVP(+) GD versus 3 of 21 in MVP(-) GD (p < 0.05). In the HT group the MVP(+) patients had a significantly higher incidence of ANA and ENA, 5 of 8 and 2 of 8 versus 5 of 27 and 0 of 27 of MVP(-) patients, respectively, p < 0.05. A statistically significant higher incidence of aCL was found in HT MVP(+) patients. (3/8) versus HT MVP(-) 1/27, p < 0.05. RF levels (immunoglobulin A [IgA]) were significantly higher in MVP(+) patients. The association of MVP with nonorgan-specific autoantibodies indicates that MVP may also be an autoimmune disease. It is possible that patients with AITD who also have MVP may be at an increased risk to develop systemic autoimmunity.
Thyroid 10/1999; 9(10):973-7. · 4.79 Impact Factor
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ABSTRACT: Impaired endothelium-dependent, flow-mediated dilatation of the brachial artery was observed in a 50-year-old premenopausal female non-smoker with idiopathic hemochromatosis. Endothelial dysfunction observed in this patient supports a relationship between body iron stores and early atherosclerotic process.
Vascular Medicine 02/1999; 4(3):147-8. · 1.46 Impact Factor
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ABSTRACT: The objective of this study was to screen for thyroidopathies in patients with rheumatoid arthritis (RA). Screening for thyroid disorders is advocated in patients with autoimmune diseases, and rheumatoid arthritis has been linked to thyroid autoimmune disorders, more particularly Hashimoto's thyroiditis and sometimes Graves' disease. We performed thyroid disease screening in 69 patients with RA free of medication for at least a 2 weeks period, not in remission, and in 65 patients with osteoarthritis (OA). The latter were studied as a control group of non-autoimmune arthritis patients. Basal levels of thyrotrophin (TSH) were measured using a sensitive chemiluminescence serum TSH assay. Serum antithyroperoxidase and antithyroglobulin (anti-Tg) autoantibodies were measured as well. If TSH values were found to be outside the normal limits, serum total thyroxine, total triiodothyronine (T3), resin T3 uptake, the free thyroxine index (FT4I) and free triiodothyronine index (FT3I) were evaluated. Rheumatoid arthritis patients exhibited statistically significant lower mean TSH values as compared to OA patients. However, RA patients with low TSH values did not have elevated FT4I. Previous use of corticosteroids in some of the RA patients may be responsible for these results. The autoantibodies levels did not differ between the two groups. We conclude that thyroid function screening with sensitive TSH assays is not sufficient for assessment of early stages of autoimmune thyroidopathies in patients with RA. Thyroid hormones should also be estimated.
Acta Medica Austriaca 02/1999; 26(1):26-8.
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ABSTRACT: Circulating levels of P- and L-selectins and the degree of T-lymphocyte activation were assessed by enzyme-linked immunosorbent assays in 75 selected patients with rheumatoid arthritis (RA), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) at various clinical stages, and in 40 healthy blood donors matched for age and gender. Mean levels of P-selectin were significantly higher than normal in RA (lower in patients with clinical remission) and SSc (higher in patients with early-onset diffuse disease), but not in SLE. In contrast, mean L-selectin levels were significantly higher than normal in SLE (no correlation to the degree of disease activity), but not in RA or SSc. Mean levels of soluble interleukin-2 receptors (sIL-2R), reflecting mainly T-lymphocyte activation, in patients with active RA, SSc and SLE were almost double the normal level; however, correlations between individual levels of circulating P- or L-selectins and sIL-2R within groups revealed a strong positive correlation only between L-selectin and sIL-2R (r = 0.66, p<0.001), and only in patients with SLE. Given the different expression of P- and L-selectins, these findings indicate a distinct pattern of immune cell activation in chronic diseases that share an overactivation of T-lymphocytes. The possible clinical value of quantitation of circulating P-selectin in patients with RA and SSc on the one hand, and L-selectin in patients with SLE on the other, should be investigated by prospective studies.
Clinical Rheumatology 02/1999; 18(1):28-32. · 2.00 Impact Factor
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ABSTRACT: Adhesion molecules expressed on the surface of immune cells transduce a variety of cell-activating signals and mediate important interactions by binding to multiple specific counter-receptors expressed on other cells or on extracellular matrix components. A large number of aberrations in the expression of cell-bound molecules at the mRNA and protein level in vivo have been described in patients with autoimmune connective tissue diseases. In vitro studies suggest the presence of functional abnormalities of adhesive pathways, at least at some points of the disease. Increased circulating levels of isoforms of several adhesion molecules have also been demonstrated in these patients. The possible involvement in the pathogenesis of rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome and systemic sclerosis of E-, P- and L-selectins, of some integrins and of several adhesion molecules of the immunoglobulin superfamily that in addition participate in lymphocyte costimulation will be discussed in this review. Further studies on migration and recruitment patterns of immune cells into inflamed tissues, as well as on possible defects of lymphocyte activation in these patients, are expected to expand our knowledge on systemic autoimmune responses and identify targets for specific immunotherapy.
Clinical Rheumatology 02/1999; 18(4):317-27. · 2.00 Impact Factor
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ABSTRACT: Endothelium-dependent and endothelium-independent dilation were reduced in patients with Raynaud's phenomenon secondary to systemic sclerosis. Conjugated estrogen given for 4 weeks significantly improved endothelial function compared with placebo.
The American Journal of Cardiology 01/1999; 82(12):1555-7, A8. · 3.37 Impact Factor
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ABSTRACT: Morphologic changes of the vascular endothelium are common in patients with systemic sclerosis and Raynaud's phenomenon. The aim of this study was to evaluate the endothelium-dependent vasodilatation and endothelium-independent vasodilatation and to examine the effects of short-term estrogen administration on vascular responses in these patients.
The study included 12 female patients with systemic sclerosis and Raynaud's phenomenon (aged 49+/-14 years) and 12 age- and sex-matched healthy control subjects. With the use of high-resolution ultrasound imaging, brachial artery diameter was measured at rest, during reactive hyperemia (endothelium-dependent response), and after administration of sublingual nitroglycerin (endothelium-independent dilatation). Intima-media thickness of the common carotid artery was also measured. Baseline diameter was similar in patients and control subjects; intima-media thickness was significantly higher in patients (0.83+/-0.3 vs 0.46+/-0.2 mm, P= .002) than in control subjects. Flow-mediated dilatation was reduced in patients (3.6%+/-7% vs 11.9%+/- 4.6%, P = .003); endothelium-independent dilatation also was reduced in patients with Raynaud's phenomenon (14%+/-7% vs 23%+/-6%, P= .003). Vascular responses in 10 patients were examined 15 minutes after administration of conjugated estrogens (25 mg intravenously); there was a significant increase of endothelium-dependent dilatation after estrogen administration (1.7%+/-4% to 6.3%+/-4%, P= .01), whereas endothelium-independent dilatation did not change (13.4%+/-8% to 15.5%+/-7%, not significant).
Endothelium-dependent vasodilatation and endothelium-independent vasodilatation are impaired in patients with Raynaud's phenomenon secondary to systemic sclerosis, whereas intima-media thickness is increased. Short-term estrogen administration can improve endothelial dysfunction in this group of patients.
American Heart Journal 12/1998; 136(5):905-12. · 4.65 Impact Factor
