Serum anti-GM2 and anti-GalNAc-GD1a IgG antibodies are biomarkers for acute canine polyradiculoneuritis.

OBJECTIVES: A previous single-country pilot study indicated serum anti-GM2 and anti-GA1 anti-glycolipid antibodies as potential biomarkers for acute canine polyradiculoneuritis. This study aims to validate these findings in a large geographically heterogenous cohort. MATERIALS AND METHODS: Sera from 175 dogs clinically diagnosed with acute canine polyradiculoneuritis, 112 dogs with other peripheral nerve, cranial nerve or neuromuscular disorders and 226 neurologically normal dogs were screened for anti-glycolipid antibodies against 11 common glycolipid targets to determine the immunoglobulin G anti-glycolipid antibodies with the highest combined sensitivity and specificity for acute canine polyradiculoneuritis. RESULTS: Anti-GM2 anti-glycolipid antibodies reached the highest combined sensitivity and specificity (sensitivity: 65.1%, 95% confidence interval 57.6 to 72.2%; specificity: 90.2%, 95% confidence interval 83.1 to 95.0%), followed by anti-GalNAc-GD1a anti-glycolipid antibodies (sensitivity: 61.7%, 95% confidence interval 54.1 to 68.9%; specificity: 89.3%, 95% confidence interval 82.0 to 94.3%) and these anti-glycolipid antibodies were frequently present concomitantly. Anti-GA1 anti-glycolipid antibodies were detected in both acute canine polyradiculoneuritis and control animals. Both for anti-GM2 and anti-GalNAc-GD1a anti-glycolipid antibodies, sex was found a significantly associated factor with a female to male odds ratio of 2.55 (1.27 to 5.31) and 3.00 (1.22 to 7.89), respectively. Anti-GalNAc-GD1a anti-glycolipid antibodies were more commonly observed in dogs unable to walk (OR 4.56, 1.56 to 14.87). CLINICAL SIGNIFICANCE: Anti-GM2 and anti-GalNAc-GD1a immunoglobulin G anti-glycolipid antibodies represent serum biomarkers for acute canine polyradiculoneuritis.

Iron catalyzed diastereoselective hydrogenation of chiral imines.

Cyclopentadienone-based iron complexes were used for the first time to successfully catalyze the diastereoselective hydrogenation of enantiopure imines. Chiral amines, including valuable biologically active products, were obtained often as enantiomerically pure compounds. Computational studies helped to elucidate the chemical and stereochemical aspects of the iron-catalyzed reaction.

Surgical Management of Aneurysmal Hematomas: Prognostic Factors and Outcome.

From 1991 until 2013, 304 patients with intracranial hematomas from aneurysmal rupture were managed surgically in our department, constituting 17 % of all patients with aneurysmal rupture. Of them, 242 patents presented with isolated intracerebral hematomas (in 69 cases associated with significant intraventricular hemorrhage), 50 patients presented with combined intracerebral and subdural hematomas (in 11 cases associated with significant intraventricular hemorrhage), and 12 presented with an isolated subdural hematoma. The surgical procedure consisted of simultaneous clipping of the aneurysm and evacuation of the hematoma in all cases. After surgery, 16 patients (5 %) submitted to an additional decompressive hemicraniectomy, and 66 patients (21 %) submitted to a ventriculo-peritoneal shunt. Clinical outcomes were assessed at discharge and at 6 months, using the modified Rankin Scale (mRS); a favorable outcome (mRS 0-2) was observed in 10 % of the cases at discharge, increasing to 31 % at 6 months; 6-month mortality was 40 %. Applying uni- and multivariate analysis, the following risk factors were associated with a significantly worse outcome: age >60; preoperative Hunt-Hess grades IV-V; pupillary mydriasis (only on univariate); midline shift >10 mm; hematoma volume >30 cc; and the presence of hemocephalus (i.e., packed intraventricular hemorrhage). Based on these results, an aggressive surgical treatment should be adopted for most cases with aneurysmal hematomas, excluding patients with bilateral mydriasis persisting after rescue therapy.

Evaluation of right ventricular function performed by 3D-echocardiography in scleroderma patients.

The impairment of the right ventricle (RV) in systemic sclerosis (SSc) is usually related to pulmonary arterial hypertension (PAH). New echocardiographic techniques, such as 3-dimensional echocardiography (3DE) and 2-dimensional speckle tracking (2DSTE), allow an accurate evaluation of the RV function. The aim of this study was to evaluate the RV function using 3DE and 2DSTE in SSc patients with no history of heart disease and no PAH. Forty-five SSc patients, 42 females and 3 males, 28 with limited cutaneous SSc (lcSSc) and 17 with diffuse cutaneous SSc (dcSSc), were studied. Forty-three age- and gender-matched healthy subjects were enrolled as controls. All of them underwent a 3DE and 2DSTE ecocardiographic evaluation of the RV function. Systolic pulmonary arterial pressure (sPAP) and total pulmonary vascular resistance (tPVR) were also estimated by power doppler. RV echocardiographic parameters were compared in the different subsets of SSc patients. A statistical analysis was performed by t-test, ANOVA and multiple logistic regression. RV areas in 2DSTE and volumes in 3DE were higher and RV function parameters were reduced in SSc patients compared with controls. Also sPAP and tVPR were higher, but they did not reach pathological values. Echocardiographic alterations were more pronounced in patients with lcSSc. 3DE and 2DSTE echocardiography allowed us to detect morphological and functional alterations of the RV in a group of SSc patients with no clinical signs of heart disease and no PAH. These patients had significantly higher sPAP and tPVR than healthy controls without reporting values compatible with PAH. These data suggest that RV alterations are related to a pressure overload rather than to an intrinsic myocardial involvement in SSc.

Surgical exclusion of unruptured middle cerebral artery aneurysms: experience of 126 cases.

A group of 126 surgical patients with 143 unruptured MCA aneurysms was evaluated in order to determine the risks of treatment and possible adjuncts for safer surgery. The precise location and size of the aneurysms were determined in each case; 21 aneurysms were located on the M1 tract, 109 on the main division - which consisted of more than two branches in 10 cases and was proximally located in 12 cases - and 13 were distal; 36 aneurysms were small (<7 mm), 90 standard, and 17 large or giant (>15 mm); 45 patients harbored multiple aneurysms (12 on the ipsilateral MCA). The aneurysms were excluded by clip in most cases, with the assistance of intraoperative flowmetry in 78 patients. Temporary proximal vessel occlusion was used in 57 patients (>10 min in 8 cases), without significant effects on radiological or clinical outcome. After surgery, newly occurring minor deficits were observed in 5 patients and significant deficits in 4; one patient died from an intractable coagulopathy. The low rate (3.9 %) of unfavorable results (modified Rankin Score > 2) linked to surgery justifies serious consideration for treatment in these patients, especially when facing the high disability rate after the rupture of aneurysms in this anatomical location.

Surgery after embolization of cerebral arterio-venous malformation: experience of 123 cases.

A group of 123 patients with large or critically located arterio-venous malformations (AVMs), operated on between 1990 and 2011 and who underwent preoperative embolization, was assessed in order to clarify the risks of this combined treatment. AVM location, volume, and Spetzler's grade were assessed in each case; AVM volume was over 20 cm(3) in 49 % of the cases; Spetzler's grade was 3 or above in 76 % of the cases (with 34 cases in grades 4-5). A mean of 2.3 embolization procedures per patient were carried out, using bucrylate and, more recently, Onyx and/or Glubran; a 4.5 % procedure-related complication rate was observed. Complications occurring after surgery were classified as hemorrhagic (16 cases, 8 requiring surgical evacuation) or ischemic (4 cases); hemorrhagic complications were more common for AVMs with volumes >20 cm(3) and/or deep feeders. Surgery-related unfavorable results (modified Rankin Score > 2) were observed in 6 % of patients in Spetzler's grade 3, and in 20-25 % of patients in grades 4-5. More recently, a triple treatment (radiosurgery + embolization + surgery) allowed for obtaining favorable results (mRS 0-2) in all patients. It has been concluded that a combined treatment with embolization and surgery constitutes a reasonable choice for complex cerebral AVMs; the association of radiosurgery may improve the patients outcome.

Low occurrence of digital ulcers in scleroderma patients treated with bosentan for pulmonary arterial hypertension: a retrospective case-control study.

Digital ulcers (DU) are one of the most common and debilitating manifestations of vasculopathy in systemic sclerosis (SSc). Their prevention is important in order to improve patients' outcome and as a result of the economic impact they have on society. Randomised controlled studies have demonstrated that bosentan, an endothelin receptor antagonist, reduces the appearance of new DU. The aim of this retrospective study was to evaluate the occurrence of DU in a group of patients receiving long-term bosentan treatment for pulmonary arterial hypertension associated with SSc (PAH-SSc). Patients with PAH-SSc and treated with bosentan for at least 6 months (n = 30) were evaluated. Thirty patients with SSc not treated with bosentan, but matched for sex, age, disease duration and cutaneous form of SSc, were considered as a control group. The occurrence of DU, defined as loss of tissue of varying degrees in the epidermis, dermis and subcutaneous tissue, was determined in the bosentan-treated and untreated groups. Mean duration of bosentan treatment was 3.6 years. DU were detected in six patients in the bosentan-treated group (20.0 %) and 16 patients (53.3 %) in the untreated group (p = 0.0015). There were no significant differences in demographic or clinical characteristics between patients with or without DU at study end. The occurrence of DU in patients with PAH-SSc receiving long-term bosentan treatment was significantly lower than in untreated patients. The results from this long-term observational study provide valuable information on management of patients with PAH-SSc.

Hypovitaminosis D in an hospitalized old population of Western Friuli.

OBJECTIVES: Hypovitaminosis D is very common in the elderly in Italy and generally in the world, contributing to bone fractures and muscle weakness. The aim of the study was to evaluate bone metabolism in an old population of patients hospitalized not for musculo-skeletal complaints. METHODS: The clinical records of 175 patients, 98 female and 77 male, aged >65 years, hospitalized in a Department of Internal Medicine (Sacile, Western Friuli) were retrospectively reviewed. Serum levels of calcium, phosphorous, alkaline phosphatase, parathyroid hormone (PTH) and 25-OH vitamin D were evaluated. Correlations between these parameters were investigate. RESULTS: Abnormalities of bone metabolism parameters were frequently founded, particularly hypocalcemia, increased PTH and reduced 25-OH vitamin D. Hypovitaminosis D were detected in 88% of patients, low levels in 30.28% and very low levels in 57.72%. Hypovitaminosis D was related to female sex, old age of patients and high levels of PTH. CONCLUSIONS: Our data confirm that hypovitaminosis D is very common in elderly population. The study has been performed in an Italian Region where the supplementation of vitamin D in the elderly is not performed, suggesting that a awareness campaign of the doctors could be very useful to prevent bone metabolism abnormalities.

Characteristics of joint involvement and relationships with systemic inflammation in systemic sclerosis: results from the EULAR Scleroderma Trial and Research Group (EUSTAR) database.

OBJECTIVE: To determine the prevalence of and independent factors associated with joint involvement in a large population of patients with systemic sclerosis (SSc). METHODS: This study was cross-sectional, based on data collected on patients included in the European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) registry. We queried this database to extract data regarding global evaluation of patients with SSc and the presence of any clinical articular involvement: synovitis (tender and swollen joints), tendon friction rubs (rubbing sensation detected as the tendon was moved), and joint contracture (stiffness of the joints that decreased their range of motion). Overall joint involvement was defined by the occurrence of synovitis and/or joint contracture and/or tendon friction rubs. RESULTS: We recruited 7286 patients with SSc; their mean age was 56 +/- 14 years, disease duration 10 +/- 9 years, and 4210 (58%) had a limited cutaneous disease subset. Frequencies of synovitis, tendon friction rubs, and joint contractures were 16%, 11%, and 31%, respectively. Synovitis, tendon friction rubs, and joint contracture were more prevalent in patients with the diffuse cutaneous subset and were associated together and with severe vascular, muscular, renal, and interstitial lung involvement. Moreover, synovitis had the highest strength of association with elevated acute-phase reactants taken as the dependent variable. CONCLUSION: Our results highlight the striking level of articular involvement in SSc, as evaluated by systematic examination in a large cohort of patients with SSc. Our data also show that synovitis, joint contracture, and tendon friction rubs are associated with a more severe disease and with systemic inflammation.

Prevalence and factors associated with left ventricular dysfunction in the EULAR Scleroderma Trial and Research group (EUSTAR) database of patients with systemic sclerosis.

OBJECTIVES: To measure the prevalence of, and factors associated with, left ventricular (LV) dysfunction in systemic sclerosis (SSc). METHODS: The EUSTAR database was first searched. A case-control study of a patient subset was then performed to further identify independent factors associated with LV dysfunction by simple and multiple regression. RESULTS: Of 7073 patients, 383 (5.4%) had an LV ejection fraction (EF) of <55%. By multiple regression analysis, age, sex, diffuse cutaneous disease, disease duration, digital ulcerations, renal and muscle involvement, disease activity score, pulmonary fibrosis and pulmonary arterial hypertension were associated with LV dysfunction. In the second phase, 129 patients with SSc with LVEF <55% were compared with 256 patients with SSc with normal LVEF. Male sex (OR 3.48; 95% CI 1.74 to 6.98), age (OR 1.03; 95% CI 1.01 to 1.06), digital ulcerations (OR 1.91; 95% CI 1.05 to 3.50), myositis (OR 2.88; 95% CI 1.15 to 7.19) and use of calcium channel blockers (OR 0.41; 95% CI 0.22 to 0.74) were independent factors associated with LV dysfunction. CONCLUSION: The prevalence of LV dysfunction in SSc is 5.4%. Age, male gender, digital ulcerations, myositis and lung involvement are independently associated with an increased prevalence of LV dysfunction. Conversely, the use of calcium channel blockers may be protective.

Pentraxins, anti-pentraxin antibodies, and atherosclerosis.

Atherosclerosis is a disease of the vascular wall, which predominantly affects large and medium-sized arteries. It represents a leading cause of morbidity and mortality in the Western world. In the last few decades, it has been clearly shown that immune system plays a relevant role in atherogenesis. The effectors of both innate and adaptive immunity, including immune cells, cell or soluble receptors, cytokines, chemokines, complement components or coagulation systems, and autoantibodies are able to modulate atherosclerosis. Among proteins belonging to innate immunity, the highly conserved pentraxin family, which encompass C-reactive protein (CRP), serum amyloid P (SAP), and the long pentraxin 3 (PTX3) seems to be directly involved in the induction and progression of atherosclerosis. By immunohistochemical staining, pentraxins were found within the atherosclerotic plaques where they could play a key role interacting with atherogenic-modified lipoproteins, favoring the formation of foam cells, and exerting a proinflammatory action. Pentraxin serum levels have been shown to be associated with clinical and subclinical atherosclerosis in general population. Antibodies against pentraxins have been demonstrated in patients with autoimmune diseases, but their role in atherogenesis is still controversial.

Is PM(10) mass measurement a reliable index for air quality assessment? An environmental study in a geographical area of north-eastern Italy.

The aim of this study was to measure the concentration of some metals (Cd, Cr, Cu, Fe, Mn, Ni, Pb, and Ti) in PM(10) samples collected in one urban and one industrial site and to assess that PM(10) total mass measurement may be not sufficient as air quality index due to its complex composition. Metals were determined by inductively coupled plasma-atomic emission spectroscopy (ICP-AES) and differential pulsed anodic stripping voltammetry (DPASV). The measured concentrations were used to calculate the content of metals in the PM(10) total mass, and to estimate the enrichment factors and the correlations between PM(10), metal concentrations and meteorological data for the two sites. The mean PM10 concentration during the sampling period in the urban site exceeded the annual European Union (EU) standard (40 microg/m(3)) and, for some sampling days, the daily EU standard (50 microg/m(3)) was also exceeded. In opposite, both EU standards were never exceeded in the industrial site. The overall metal content was nearly double in the industrial site compared to the urban one, and the mean Ni concentration exceeded the EU annual limit value (10 ng/m(3)). The metals with the highest enrichment factor were Cd, Cu, Ni and Pb for both sites, suggesting a dominant anthropogenic source for these metals. Metal concentrations were very low and typical of rural background during Christmas holidays, when factories were closed. PM(10) total mass measurement is not a sufficient air quality index since the metal content of PM(10) is not related to its total mass, especially in sites with industrial activities. This measurement should be associated with the analysis of toxic metals.

Compensatory renal growth in children with unilateral renal tumor treated by nephron-sparing surgery or nephrectomy.

INTRODUCTION: In children with an unilateral renal tumor, nephron-sparing surgery (NSS) results in a more adequate renal function adaptation compared to nephrectomy. In the present study, we investigated whether nephron-sparing surgery is followed by a different renal structure adaptation compared to nephrectomy. METHODS: Sixteen patients with unilateral renal tumor treated by nephrectomy (Group 1) and 10 treated by nephron-sparing surgery (Group 2) were enrolled in the study. Kidney volume was estimated by ultrasonography, using the formula for a prolate ellipsoid. Kidney volume was adjusted to the patient's weight and kidney laterality and expressed as a percentage of the expected volume of two kidneys in a healthy child. Total kidney volume (TKV) corresponded to the volume of the contralateral kidney in Group 1 patients, and to the volume of contralateral kidney + kidney remnant in Group 2 patients. Renal function was evaluated by serum creatinine values adjusted for sex and age and expressed as standard deviation scores (SDS). RESULTS: Group 2 patients presented with a greater indexed TKV compared to Group 1 patients, (97.4 +/- 18.8 % vs. 77.0 +/- 17.7 %; p = 0.005). Indexed TKV below the reference range for healthy controls with two kidneys was found in 4 of 10 Group 2 patients vs. 14 of 16 Group 1 patients (p = 0.017). In both patient groups, correlation analysis of indexed TKV and creatinine SDS showed a negative correlation (r = - 0.47; p = 0.01). CONCLUSION: In children with unilateral renal tumor, NSS is followed by a more adequate compensatory restoration of TKV compared with nephrectomy.

[Two-years therapy with bosentan of pulmonary arterial hypertension related to connective tissue diseases]. / Due anni di terapia con bosentan dell'ipertensione arteriosa polmonare associata a connettiviti sistemiche.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a rare but severe complication of connective tissue diseases (CTD), with a negative impact on patients survival. Bosentan, a receptor antagonist of endothelin, has been proved effective for the treatment of PAH. The aim of this study was to evaluate the effects and the safety of bosentan administered for 2 years in a group of patients with PAH related to CTD. METHODS: Twelve patients with PAH related to systemic sclerosis (8 cases), SLE (2 cases), mixed connective tissue disease (1 case) and polymyositis (1 case) attending the Rheumatology Unit of Padova University were treated with bosentan for two years. Distance walked in 6 minutes, right ventricular systolic pressure and mean pulmonary artery pressure estimated by doppler echocardiography were evaluated at baseline and after 6, 12, 18 and 24 months of treatment. Safety was assessed by laboratory tests performed every two months. RESULTS: During bosentan treatment, a significant decrease of right ventricular systolic pressure was observed after 6, 12, 18 and 24 months in comparison to baseline, whereas pulmonary artery mean pressure remained unchanged. Distance walked in 6 minutes slightly increased after 6 and 12 months, but significantly decreased after 18 and 24 months, mostly because complications of CTD which compromised the ability to walk arose in 4 patients. Adverse events related to bosentan were observed in 2 cases. CONCLUSIONS: Bosentan has been demonstrated effective in reducing pulmonary arterial pressure in a two-year period of treatment. Exercise capacity improved only in the first year of therapy and worsened thereafter, suggesting the opportunity of a combination therapy for a long-term treatment of PAH related to CTD.

Anti-fibroblast antibodies detected by cell-based ELISA in systemic sclerosis enhance the collagenolytic activity and matrix metalloproteinase-1 production in dermal fibroblasts.

OBJECTIVES: Antibodies binding to the surface of fibroblasts (anti-fibroblast antibodies: AFA) have been described in systemic sclerosis (SSc). We aimed to assess the effect of AFA on extracellular matrix (ECM) turnover and whether AFA were associated with anti-topoisomerase-I antibody. METHODS: IgG were purified from AFA-positive and AFA-negative sera selected within 20 SSc and 20 healthy individuals, and tested on normal dermal fibroblasts, at protein and mRNA level, for their capacity to induce collagen deposition or degradation. RESULTS: Fibroblasts stimulated with AFA-positive but not with AFA-negative and control IgG showed an increased capacity to digest collagen matrix and produce metalloproteinase-1 (MMP-1) while their production of total collagen, type I collagen and tissue inhibitor of metalloproteinase-1 (TIMP-1) was unaffected. The steady-state mRNA levels of MMP-1, COL1A1 and TIMP-1 paralleled the protein levels. AFA-positive IgG did not induce Smad 2/3 phosphorylation, indicating that this transforming growth factor-beta signalling pathway was not involved. IL-1 and tumour necrosis factor (TNF) neutralization did not reverse the enhanced production of MMP-1, suggesting a direct effect of AFA on fibroblasts. Finally, anti-topoisomerase-I antibodies were present in 11 of 12 AFA-negative IgG, and an anti-topoisomerase-I monoclonal antibody failed to enhance MMP-1 production, thus indicating a lack of correlation between AFA and anti-topoisomerase-I antibody. CONCLUSIONS: These results indicate that SSc antibodies binding to fibroblasts enhance matrix degradation and MMP production events that may favour inflammation but do not directly impact on fibrosis development.

[Digital ulcers in a cohort of 333 scleroderma patients]. / Ulcere digitali in una coorte di 333 pazienti sclerodermici.

Digital ulcers (DU) at the hands are one of the more frequent and severe complications in systemic sclerosis. Data on their prevalence and distribution in the different subsets of disease are variable in the literature. We studied the frequency of DU in a cohort of 333 scleroderma patients followed in the last 10 years in our Unit. DU have been recorded in 133 patients (39,9%), more frequently in males, in patients with cutaneous diffuse form of disease and in patients with anti-Scl70 ANA specificity. Complications of DU have been observed in 12,3% of cases. Surgery of the hands has been required in 8,7% of patients. The more effective treatment of DU are i.v. prostanoids, performed usually in day hospital, with high costs for the National Health Service. Recently the efficacy of bosentan, an oral receptor antagonist of endothelin, has been demonstrated, thus opening new perspectives in the treatment of DU in systemic sclerosis.

Relational competence and eating disorders.

Eating Disorders are very widespread within the adolescent population. A possible interpretation and the comprehension of such forms of psychopathology may revolve around the failure to develop a well-defined personal identity, an incapacity to achieve a sense of differentiation with respect to others, an incapacity to measure oneself against others, dependence on others, the fear of rejection and a sense of inadequacy. This study explores the relational styles and behaviour of individuals suffering from eating disorders and their influence on the development of the personality, with reference being made in particular to self-valuation, dependence on others and levels of differentiation. A sample population of 90 women with eating disorders was studied. The subjects were subdivided into 3 groups (30 with restricting anorexia nervosa, 30 with binge-eating/purging anorexia nervosa and 30 with bulimia nervosa), overlapping in terms of age, duration of disorders and interrelation style, using the Relational Competence Test. The most significant results of this study concern the question of the definition of an autonomous personal identity. This process seems to be in progress in young women suffering from bulimia nervosa who appear to be driven towards a "definition of the self in opposition" with the consequent tendency towards relational experiences outside their own family. In women with binge-eating/purging AN moreover an awareness of the difference between the self and others and of their state of dependence would appear to be present, however behaviour aimed at the determination of an autonomous self is not evident. In women with restricting anorexia nervosa a definition of the identity is totally absent; these women develop an omnipotent self in their 'oneness' with others. These relational aspects lead to the identification of a continuum between restricting anorexia nervosa, binge-eating/purging anorexia nervosa and bulimia nervosa in an evolutionary perspective regarding the self-with-others.

Bosentan therapy of pulmonary arterial hypertension in connective tissue diseases.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening and debilitating complication of several connective tissue diseases. We aimed to evaluate the effects of long-term treatment with bosentan, an oral dual endothelin ET(A)/ET(B) receptor antagonist, in a cohort of patients with PAH related to connective tissue diseases. MATERIALS AND METHODS: In the present prospective, noncontrolled study, 13 patients (nine with systemic sclerosis, two with systemic lupus erythematosus, one with mixed connective tissue disease and one with overlap syndrome including scleroderma and myositis), mostly nonresponders to prostanoids therapy, were treated for 1 year with bosentan. Cardiac haemodynamics and the diagnosis of PAH were performed by Doppler ultrasound examination. Exercise capacity was assessed by 6-min walking test at baseline and at 3, 6 and 12 months of therapy. RESULTS: During bosentan treatment, progressive improvement of exercise capacity was observed. Walk distance increased in seven patients, remained unchanged in three and slightly decreased in three patients. A progressive significant decrease of right ventricular systolic pressure was also observed, whereas pulmonary artery mean pressure remained unchanged. Adverse effects related to bosentan (elevation of hepatic aminotransferases) were noted in two patients. CONCLUSION: Long-term treatment with bosentan was effective in improving exercise capacity and pulmonary haemodynamics in patients with PAH related to connective tissue diseases.