Hormonal parameters and sex hormone receptor gene polymorphisms in men with autoimmune diseases.

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.

Abnormal spatial QRS-T angle, a marker of ventricular repolarisation, predicts serious ventricular arrhythmia in systemic sclerosis.

OBJECTIVES: Cardiac involvement may be under-diagnosed in asymptomatic patients with systemic sclerosis (SSc). Standard electrocardiography-derived spatial QRS-T angle (spQRS-Ta) is an established marker of ventricular repolarisation heterogeneity, and a strong independent predictor of cardiac morbidity and mortality, including sudden death, in the general population. We examined whether spQRS-Ta is abnormal in asymptomatic SSc patients and assessed its predictive value for possibly concurrent, serious ventricular arrhythmia. METHODS: SpQRS-Ta and 24-hour Holter recordings were obtained from 69 SSc patients (aged 51±13 years, 63 women) without clinically evident cardiac involvement and having left ventricular ejection fraction at least 50% by echocardiography. 'Healthy' subjects matched 1:1 with patients for age, gender and body mass index served as controls. RESULTS: SpQRS-Ta was wider in SSc (median value 15.6°, interquartile range 10.6-24.3°) than controls (10.5°, 7.3-13.5°, p=0.0001) and not associated with skin fibrosis extent or specific clinical manifestations and autoantibodies. Twenty-four-hour Holter recordings revealed couplets of ventricular beats in six (Lown class IVa) and non-sustained ventricular tachycardia in five patients (Lown class IVb); spQRS-Ta was wider in those eleven patients with serious ventricular arrhythmia than the remaining patients (24.9°, 14.9-31.3° vs. 14.4°, 9.6-22.3°; p=0.02). A spQRS-Ta>19.3° demonstrated 80% sensitivity and 68% specificity (area under the curve 0.81, p=0.02) to predict the presence of non-sustained ventricular tachycardia in Holter monitoring. CONCLUSIONS: Ventricular repolarisation heterogeneity, as reflected by wider spQRS-Ta, is common in SSc. Increased spQRS-Ta could serve as a simple screening test for further investigation to identify patients at risk or prone to develop life-threatening ventricular arrhythmia.

Modeling ethanol decomposition on transition metals: a combined application of scaling and Brønsted-Evans-Polanyi relations.

Applying density functional theory (DFT) calculations to the rational design of catalysts for complex reaction networks has been an ongoing challenge, primarily because of the high computational cost of these calculations. Certain correlations can be used to reduce the number and complexity of DFT calculations necessary to describe trends in activity and selectivity across metal and alloy surfaces, thus extending the reach of DFT to more complex systems. In this work, the well-known family of Brønsted-Evans-Polanyi (BEP) correlations, connecting minima with maxima in the potential energy surface of elementary steps, in tandem with a scaling relation, connecting binding energies of complex adsorbates with those of simpler ones (e.g., C, O), is used to develop a potential-energy surface for ethanol decomposition on 10 transition metal surfaces. Using a simple kinetic model, the selectivity and activity on a subset of these surfaces are calculated. Experiments on supported catalysts verify that this simple model is reasonably accurate in describing reactivity trends across metals, suggesting that the combination of BEP and scaling relations may substantially reduce the cost of DFT calculations required for identifying reactivity descriptors of more complex reactions.

Weak molecular chemisorption of N(2)/Pt(111).

The ordering in a higher-order-commensurate monolayer solid of Pt(111)- (3 × 3)-4  N(2), which has coexisting physisorbed and weakly chemisorbed N(2) species, is analyzed with model calculations. Density functional theory calculations are also used to evaluate properties of chemisorbed N(2) in a (2 × 2) unit cell on Pt(111). The relation of these results to the orientational ordering of N(2) on other metal surfaces is discussed.

Metformin administration improves endothelial function in women with polycystic ovary syndrome.

OBJECTIVE: 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. DESIGN: Descriptive clinical trial. METHODS: 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. RESULTS: 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. CONCLUSIONS: PCOS women were found to exhibit endothelial dysfunction compared with controls, which was reversed 6 months after metformin administration.

Common carotid artery intima-media thickness for the risk assessment of lacunar infarction versus intracerebral haemorrhage.

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The nature of the Fe-graphene interface at the nanometer level.

The emerging fields of graphene-based magnetic and spintronic devices require a deep understanding of the interface between graphene and ferromagnetic metals. This paper reports a detailed investigation at the nanometer level of the Fe-graphene interface carried out by angle-resolved photoemission, high-resolution photoemission from core levels, near edge X-ray absorption fine structure, scanning tunnelling microscopy and spin polarized density functional theory calculations. Quasi-free-standing graphene was grown on Pt(111), and the iron film was either deposited atop or intercalated beneath graphene. Calculations and experimental results show that iron strongly modifies the graphene band structure and lifts its π band spin degeneracy.

Cardiopulmonary hemodynamics in systemic sclerosis and response to nifedipine and captopril.

PURPOSE: This prospective study was performed to evaluate the response of the cardiopulmonary vasculature to two vasodilators in patients with systemic sclerosis and either minimal or no central hemodynamic abnormalities. PATIENTS AND METHODS: Twenty patients with systemic sclerosis, Raynaud's phenomenon (19 of 20 patients), and clinically normal cardiac function underwent right heart catheterization. Rest and exercise hemodynamic measurements, including cardiac output by thermodilution, were performed before and after oral administration of nifedipine 20 mg and captopril 25 mg. RESULTS: Half of the patients had normal hemodynamics (Group A); the other half (Group B) had abnormal baseline elevations in pulmonary vascular resistance and four of them showed "borderline" pulmonary arterial hypertension. Group A, with significantly shorter disease duration compared with Group B, responded poorly to nifedipine and captopril. However, Group B had significant decreases in pulmonary vascular resistance (from 148 +/- 20 to normal levels of 94 +/- 21 dynes.second.cm-5) and pulmonary mean pressure in response to nifedipine treatment but not to captopril. CONCLUSION: These observations show a short-term beneficial effect of nifedipine in the cardiopulmonary vasculature of patients with systemic sclerosis and suggest that a potentially reversible vasoconstrictive element is included in the vascular lesion of this disorder.

Effect of long-term estrogen therapy on brachial arterial endothelium-dependent vasodilation in women with Raynaud's phenomenon secondary to systemic sclerosis.

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.

Small airways dysfunction in systemic sclerosis. A controlled study.

A debate exists regarding the importance of small airways disease in systemic sclerosis, while smoking seems to have a major effect on the exact prevalence. In order to evaluate small airways dysfunction (SAD) in a pure systemic sclerosis population, we performed pulmonary function studies in 31 nonsmoking patients and 31 age- and sex-matched nonsmoking control subjects. Patients' FVC, TLC, and Dco mean values were significantly lower compared with the corresponding values of the controls (p less than 0.05), while there was no difference in MEF25, RV, and RV/TLC. Seven (22.6 percent) of 31 patients and four controls (a nonsignificant difference) had evidence of SAD, namely a maximum expiratory flow at 25 percent of vital capacity (MEF25) less than 60 percent of predicted. Positive correlation (p less than 0.001) was found between MEF25 and FEV1/FVC in the patients. Moreover, no differences were found in abnormal lung function patients with and those without SAD in demographic, clinical, roentgenologic, and serologic features and results of pulmonary function tests. These findings suggest that SAD in our patients is not a characteristic and early manifestation of systemic sclerosis and that, when present, it is not correlated with the severity of the pulmonary involvement in scleroderma.

Microfilaremia from a Dirofilaria-like parasite in Greece. Case report.

In Europe, zoonotic filarial infections in humans are caused by two species, Dirofilaria immitis and Dirofilaria repens. These parasites are associated mainly with embolic infarcts of the pulmonary artery and subcutaneous nodules, respectively. An unusual dirofilarial infection in a Greek patient who showed marked eosinophilia and microfilaremia is presented. Although the identification of Dirofilaria species is not conclusive, this report is the first on a case of microfilaremia from a Dirofilaria infection in an immunocompetent patient.

Diffusion of N adatoms on the Fe(100) surface

The diffusion of individual N adatoms on Fe(100) has been studied using scanning tunneling microscopy and ab initio density functional theory (DFT) calculations. The measured diffusion barrier for isolated N adatoms is E(d) = (0.92+/-0.04) eV, with a prefactor of nu(0) = 4.3x10(12) s(-1), which is in quantitative agreement with the DFT calculations. The diffusion is strongly coupled to lattice distortions, and, as a consequence, the presence of other N adatoms introduces an anisotropy in the diffusion. Based on experimentally determined values of the diffusion barriers and adsorbate-adsorbate interactions, the potential energy surface experienced by a N adatom is determined.

Immunocytochemical detection of P-glycoprotein in the management of malignant effusions.

P-glycoprotein (P-gp), a cell membrane protein, has been found in multidrug-resistant cancer cells. A total of 104 smears from patients with breast-cancer-associated pleural effusions and ovarian-cancer-related peritoneal effusions were studied for P-gp with the antibody C-219 and the avidin-biotin-immunoperoxidase method. Samples were taken before and 3 and 7 days after intracavitary bleomycin therapy and reaccumulation of effusion was assessed at 30 days. Smears that were P-gp-negative by the 7th day were associated with a good 30-day response to bleomycin in the majority of cases, while P-gp-positive smears were associated with a significant reaccumulation of fluid at 30 days. P-gp status is a valuable prognostic indicator of response to intracavitary bleomycin treatment in effusions from breast or ovarian cancer.

A comparative trial of large doses of ketoprofen and indomethacin in the treatment of rheumatoid arthritis.

A 4-weeks' double-blind, crossover study in 30 patients with definite or classical rheumatoid arthritis is reported using 300 mg ketoprofen per day and 150 mg indomethacin per day. Both drugs had similar effects upon the patients' subjective improvement of pain. Objectively, the results also suggest that ketoprofen may be more effective in reducing the articular index, i.e. a superior analgesic effect. Further studies are underway to assess the value of ketoprofen administered in high dosage for longer duration.

Mefenamic acid: an under-rated antirheumatic?

A double-blind crossover study was carried out in 18 patients with classical rheumatoid arthritis to assess the effectiveness of mefenamic acid (500 mg t.d.s.) compared with placebo or indomethacin (25 mg q.d.s.). Each treatment was given for 1 week and subjective and objective assessments were carried out at the end of each period. Results showed that both mefenamic acid and indomethacin were significantly better than placebo in most parameters. Although duration of morning stiffness and patient preference favoured indomethacin it was considered that there was no demonstrable difference of any clinical significance between the two active medications.

Mitral valve prolapse in autoimmune thyroid disease: an index of systemic autoimmunity?

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.

Glucocorticoid effects on myocardial performance in patients with systemic sclerosis.

OBJECTIVE: Myocardial inflammation andfibrosis are common autopsyfindings in systemic sclerosis (SSc) and, although symptomatic cardiac involvement occurs less often, current therapies remain empiric and do not prevent or modify its course. In this open, uncontrolled study we assessed the short-term effects of glucocorticoid administration on myocardial performance in patients with SSc in the absence of clinically overt cardiac disease. METHODS: Resting radionuclide ventriculography with 99mTc was performed before and 20 days after the administration of prednisolone, 20 mg daily, in 32 patients with SSc without clinically evident myocardial dysfunction at rest; 13 and 19 patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), respectively, were studied in parallel as controls. RESULTS: The mean left ventricular ejection fraction (LVEF) value at baseline was 59% in the SSc group; similar values were found for the SLE (61%) and RA (59%) groups. An impaired LVEF (i.e., <50%) was found in 6 patients with SSc and in 1 patient with SLE. Prednisolone administration resulted in a significant percent improvement in the baseline LVEF (mean 18%, p = 0.0001) in the SSc group; this improvement was greater in the patients with diffuse SSc than in those with limited skin disease (27% vs 10%, p = 0.02). The improvement was most prominent in the 6 patients with an initial impaired LVEF No significant improvement was observed in the SLE or RA control groups. The linear trend betveen the individual baseline LVEF values in patients with SSc and their percent changes after treatment (r2 = 0.55, p: 0.00001) showed that the lower the initial LVEF the greater the improvement caused by prednisolone. The degree of LVEF improvement was also associated with the individual erythrocvte sedimentation rate values and serum IgG concentrations at baseline. Prednisolone-induced changes in LVEF were not associated with any changes in blood pressure, heart rate, blood, plasma, or red cell volumes. CONCLUSION: Glucocorticoid administration may improve myocardial performance in some patients with SSc. Although further double-blind controlled studies of the long-term effects are warranted, such treatment may be useful in those patients with SSc and documented low LVEF if they are kept under careful observation for objective improvement.

Paget's bone disease, anaemia and vitiligo: a case report.

The coexistence of Paget's bone disease, pernicious anaemia and vitiligo is very rare. The pathogenesis of Paget's bone disease remains still unknown. We report here a patient having these three entities simultaneously and we suggest that some cases of Paget's bone disease be due to autoimmunity.

HLA antigens in diabetics with calcified shoulder periarthritis (CSP).

The distribution frequencies of HLA-A and B antigens was determined in 94 maturity onset diabetics (40 with CSP and 54 without CSP), as well as in 400 unrelated age- and sex-matched Greek controls. The standard NIH technique was used for tissue typing. There was an increased prevalence of the antigen B27 only in diabetics with CSP (35%) when compared either to the controls (6.8%) or to diabetics without CSP (9.2%). The calculated p-corrected values were Pc = 0.00027 and Pc greater than 0.005 respectively. These findings indicate that the MHC in man may control the genetic susceptibility of a subgroup of insulin-independent diabetics to develop CSP.

Cardiac performance in collagen diseases estimated by non-invasive methods.

The myocardial performance was studied in 3 collagen diseases, i.e. rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS). Sixteen patients with SLE, 12 with RA and 11 with PSS were examined, measuring the systolic time intervals from the first derivative of the carotid pulse in all cases. The ejection fraction (EF), was evaluated in 33 patients using radionuclide left ventricular angiography. The systolic time intervals were compared to those of 103 normal persons and the EF to that of 22 normal controls. In the SLE group the pre-ejection period was significantly shorter, while the ejection period was longer than normally expected. In the same group, the EF was significantly higher that the EF of the control group. These differences could not be related to age, blood pressure, disease duration, coronary risk factors, heart rate or blood values. Most findings in the RA group tended to be opposite to those of SLE. It is concluded that in SLE before any direct involvement of the heart the systolic time intervals and the EF present features similar to those of increased cardiac performance.