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Biomedical subjects

Piercarlo Sarzi-Puttini

Publications and source records attributed to Piercarlo Sarzi-Puttini.

At least 19 recordsLinked to original sources
PubMed2007

The genetics of fibromyalgia syndrome.

Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. Although the etiology of FMS is not completely understood, varieties of neuroendocrine disturbances, as well as abnormalities of autonomic function, have been implicated in its pathogenesis. The exposure of a genetically predisposed individual to a host of environmental stressors is presumed to lead to the development of FMS. Fibromyalgia overlaps with several related syndromes, collectively compromising the spectrum of the functional somatic disorder. FMS is characterized by a strong familial aggregation. Recent evidence suggests a role for polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems in the etiopathogenesis of FMS. These polymorphisms are not specific for FMS and are similarly associated with additional comorbid conditions. The mode of inheritance in FMS is unknown, but it is most probably polygenic. Recognition of these gene polymorphisms may help to better subgroup FMS patients and to guide a more rational pharmacological approach. Future genetic studies conducted in larger cohorts of FMS patients and matched control groups may further illuminate the role of genetics in FMS.

Animals↗
PubMed2006

Influence of coping skills on health-related quality of life in patients with systemic lupus erythematosus.

OBJECTIVE: To identify coping strategies used by patients with systemic lupus erythematosus (SLE), and to assess the influence of main clinical and coping variables on health-related quality of life (HRQOL). METHODS: We administered the Coping Orientation to Problems Experienced and the Short Form 36 questionnaire to a group of 144 patients with SLE and a group of 129 healthy controls. At the time of the psychological assessment, all patients underwent a complete clinical and laboratory evaluation. RESULTS: SLE patients had higher scores in acceptance (P < 0.001) and turning to religion (P = 0.05) and lower scores in planning (P = 0.001), suppression of competing activities (P = 0.010), restraint coping (P = 0.031), focusing on and venting of emotion (P = 0.009), and strategies focused on problem (P = 0.012) compared with controls. By means of linear regression analysis, HRQOL in SLE patients seemed to be influenced positively by restraint coping and positive reinterpretation and growth, and negatively by focusing on and venting of emotion, behavioral disengagement, and mental disengagement. When clinical variables were added to the multivariate analysis for coping strategies, more significant regression models that included joint pain were obtained. CONCLUSION: In facing stressful situations, patients with SLE tend to use coping skills that are generally adopted for events perceived as nonmodifiable. Strategies that show a passive attitude and joint pain seem to impair these patients' HRQOL.

Adaptation, Psychological↗
PubMed2006

Long-term prognosis and causes of death in systemic lupus erythematosus.

PURPOSE: We studied survival rate, prognostic factors, and causes of death in patients with systemic lupus erythematosus (SLE), particularly focusing on the influence of disease severity. PATIENTS AND METHODS: A cohort of 207 consecutive Italian patients with SLE were prospectively studied. All prominent clinical and serologic parameters were evaluated and considered as prognostic risk factors. Causes of death were defined on the basis of clinical data and, when available, postmortem examination. Survival was calculated from the time of diagnosis by Kaplan-Meier method. RESULTS: A total of 17 of 207 patients died; causes of death were active disease manifestations in 35.3% of cases and complication of the disease or its treatment in 64.7% of cases. The survival rates at 5, 10, and 15 years after the diagnosis were 96%, 93% and 76%, respectively. By multivariate analysis of the risk factors, a predictive model consisting of male gender, positive lupus anticoagulant, and "severe" SLE was identified. The survival curve of the patients with severe disease was similar to that of patients with mild disease until 10 to 15 years from the diagnosis. Thereafter the two curves tended to diverge, showing a clear survival decline in patients with severe disease. CONCLUSIONS: Our study confirms the increase of short- and medium-term survival in patients with SLE, but long-term prognosis remains poor in patients with severe SLE manifestations.

Adolescent↗
PubMed2006

Calcium deposition and associated chronic diseases (atherosclerosis, diffuse idiopathic skeletal hyperostosis, and others).

Extracellular matrix mineralization or calcification occurs in many pathologic conditions, including atherosclerosis, medial wall calcification, diffuse idiopathic skeletal hyperostosis, and chondrocalcinosis. Vascular wall calcification is the most common and involves two mechanisms: passive calcification resulting from breakdown of the protection system and active calcification resulting from transdifferentiation of mesenchymal cells in the vascular wall to bone. Although reports are conflicting, several matrix proteins are identified as protective factors against dystrophic calcification in nonosseous tissues. Serum matrix Gla protein may be a marker of osteometabolic syndromes that cause hyperostosis and plays a role in Milwaukee shoulder syndrome.

Atherosclerosis↗
PubMed2006

Polymyositis-dermatomyositis and infections.

In genetically predisposed individuals, viruses, bacteria, or parasitic infectious agents are suspected to induce autoimmunity and/or to exacerbate the disease once the self-tolerance is broken. Although direct evidence for this association is still lacking, numerous data from animal models as well as from humans support the hypothesis of a direct contribution of pathogens to the induction of several autoimmune diseases. This review focused on the possible role of infectious agents as triggers of autoimmunity in polymyositis (PM) and dermatomyositis (DM). Epidemiological studies, clinical and experimental findings that support the hypothesis of infection-induced PM and DM are summarized and discussed. In addition, immune response abnormalities and immunosuppressive medications may be responsible for the high percentage of infectious complications in PM and DM patients. In this review, the increased risk of developing infections in these patients is also underlined and published data are reported.

Animals↗
PubMed2006

Adalimumab clinical efficacy is associated with rheumatoid factor and anti-cyclic citrullinated peptide antibody titer reduction: a one-year prospective study.

Studies on autoantibody production in patients treated with tumor necrosis factor-alpha (TNF-alpha) inhibitors reported contradictory results. We investigated in a prospective study the efficacy of a treatment with human monoclonal anti-TNF-alpha antibody (adalimumab) in patients with rheumatoid arthritis (RA) and we evaluated the relationship between treatment efficacy and the incidence and titers of disease-associated and non-organ-specific autoantibodies. Fifty-seven patients with RA not responsive to methotrexate and treated with adalimumab were enrolled. Antinuclear, anti-double-stranded(ds)DNA, anti-extractable nuclear antigens, anti-cardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI) autoantibodies, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibodies were investigated at baseline and after 6 and 12 months of follow-up. Comparable parameters were evaluated in a further 55 patients treated with methotrexate only. Treatment with adalimumab induced a significant decrease in RF and anti-CCP serum levels, and the decrease in antibody titers correlated with the clinical response to the therapy. A significant induction of antinuclear autoantibodies (ANA) and IgG/IgM anti-dsDNA autoantibodies were also found in 28% and 14.6% patients, respectively, whereas aCL and anti-beta2GPI autoantibodies were not detected in significant quantities. No association between ANA, anti-dsDNA, aCL and anti-beta2GPI autoantibodies and clinical manifestations was found. Clinical efficacy of adalimumab is associated with the decrease in RF and anti-CCP serum levels that was detected after 24 weeks and remained stable until the 48th week of treatment. Antinuclear and anti-dsDNA autoantibodies, but not anti-phospholipid autoantibodies, can be induced by adalimumab but to a lower extent than in studies with other anti-TNF blocking agents.

Adalimumab↗
PubMed2006

Biology and therapy of fibromyalgia. Genetic aspects of fibromyalgia syndrome.

Genetic and environmental factors may play a role in the etiopathology of fibromyalgia syndrome (FMS) and other related syndromes. There is a high aggregation of FMS in families of FMS patients. The mode of inheritance is unknown but it is most probably polygenic. There is evidence that polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems play a role in the etiology of FMS. These polymorphisms are not specific for FMS and are associated with other functional somatic disorders and depression. Future genetic studies in the field of FMS and related conditions should be conducted in larger cohorts of patients and ethnically matched control groups.

Catechol O-Methyltransferase↗
PubMed2006

Increased neural sympathetic activation in fibromyalgia syndrome.

Fibromyalgia (FM) is a syndrome characterized by widespread musculoskeletal pain, although the mechanisms underlying the pain have not been fully elucidated. FM patients describe a number of nonspecific symptoms, such as anxiety, depression, fatigue, unrefreshing sleep, and gastrointestinal complaints, which appear after a flu-like illness, or after physical or emotional trauma in half of the patients, and are often exacerbated by exertion, stress, lack of sleep, and weather changes. There may also be symptoms of orthostatic intolerance, which suggests underlying abnormalities in cardiovascular neural regulation. Research suggests that various components of the central nervous system are involved, including the hypothalamic-pituitary-adrenal (HPA) axis, pain-processing pathways, and the autonomic nervous system (ANS). This review discusses the general aspects of the altered HPA and ANS, sympathetic overactivity, and alterations in cardiovascular autonomic responses to gravitational stimuli.

Fibromyalgia↗
PubMed2006

Estrogens in pregnancy and systemic lupus erythematosus.

Successful pregnancy depends on an adaptation of the maternal immune system that becomes tolerant to fetal antigens of paternal origin. The altered immune regulation induced by pregnancy occurs predominantly at the maternal-fetal interface, but it has also been observed in the maternal circulation. Th1/Th2 shift is one of the most important immunologic changes during gestation. It is due to the progressive increase of estrogens, which reach peak level in the third trimester of pregnancy. At these high levels, estrogens suppress the Th1-mediated responses and stimulate Th2-mediated immunologic responses. For this reason Th1-mediated diseases, such as rheumatoid arthritis, tend to improve, while Th2-mediated diseases, such as systemic lupus erythematosus (SLE) tend to worsen during pregnancy. However, in some recent studies SLE flare-ups were less frequently observed in the third trimester of gestation in comparison to the second trimester and postpartum period. These data are apparently in contrast to the Th2 immune-response polarization expected during pregnancy due to the progressive increase of estrogens. Some further data suggest that in SLE patients estradiol serum levels are surprisingly lower than expected during the third trimester of pregnancy, probably due to a placental compromise. This occurrence could lead to a lower-than-expected increase of IL-6, accounting for the low humoral immune response and the low disease activity observed in the third trimester of pregnancy in such patients.

Animals↗
PubMed2005

Primary and secondary autoimmune neutropenia.

Antineutrophil antibodies are well recognized causes of neutropenia, producing both quantitative and qualitative defects in neutrophils and increased risk for infection. In primary autoimmune neutropenia (AIN) of infancy, a moderate to severe neutropenia is the sole abnormality; it is rarely associated with serious infections and exhibits a self-limited course. Chronic idiopathic neutropenia of adults is characterized by occurrence in late childhood or adulthood, greater prevalence among females than among males, and rare spontaneous remission. Secondary AIN is more commonly seen in adults and underlying causes include collagen disorders, drugs, viruses and lymphoproliferative disorders. In most patients with AIN, antibodies recognize antigens located on the IgG Fc receptor type 3b but other target antigens have been recently identified in secondary AIN. Granulocyte colony-stimulating factor is a proven treatment in patients with AIN of all types and is now preferred to other possible therapies.

Adult↗
PubMed2005

Five-year follow-up by transesophageal echocardiographic studies in primary antiphospholipid syndrome.

This prospective study describes valvular abnormalities assessed by transesophageal echocardiography (TEE) in patients with primary antiphospholipid syndrome (APLS) over a 5-year follow-up. Of the 56 patients with APLS evaluated at baseline, 47 (84%) had repeat TEE examinations, including 3 patients who died before the end of the follow-up. The first TEE study showed cardiac involvement (thickening or vegetations and embolic sources) in 34 subjects (61%), with mitral valve thickening, the most common abnormality, present in 30 patients (54%). Embolic sources were found in 14 patients (25%; 9 severe spontaneous echocardiographic contrast, 5 Libman-Sacks endocarditis), associated with mitral valve thickening or stenosis in 10 patients. Over the 5-year follow-up, cardiac involvement was unchanged in 30 subjects (64%). New cardiac abnormalities were observed in 17 patients (36%), 15 (88%) with high immunoglobulin-G (IgG) anticardiolipin antibody (aCL) titers and 2 (12%) with low IgG aCL titers. In conclusion, this study showed that mitral valve thickening and embolic sources are frequently observed in patients with APLS. Anticoagulant and/or antiplatelet treatment was ineffective in terms of valvular lesion regression. New appearances of cardiac involvement are significantly related to high IgG aCL titers.

Adult↗
PubMed2005

2nd conference on heart, rheumatism and autoimmunity, Pescara, Italy, May 19-20, 2005.

Systemic autoimmune diseases, which comprise a family of conditions which share common pathogenetic mechanisms, are frequently associated to cardiac involvement and to a high prevalence of ischemic coronary events often occurring at a younger age than in normal population. A large increase in mortality is related to premature atherosclerosis with coronary artery disease and stroke in patients with connective tissue diseases. Coronary heart disease is responsible for 40-50% of the death of patients with rheumatoid arthritis. Moreover, a growing body of evidence supports the view that autoimmune mechanisms are involved in the pathogenesis of cardiovascular disease. Inflammatory heart disease is a rising concern worldwide. Similar mechanisms link autoimmune diseases, including the association of increased disease with proinflammatory cytokines and the importance of regulatory mechanisms in the control of chronic inflammation. The role of the immune system in modulating atherosclerosis has recently been well documented. Studies have revealed that cellular and humoral immunity plays crucial roles in atherogenic plaque formation. This includes macrophages, CD4+ T cells and dendritic cells as well as autoantigens such as oxidized low-density lipoprotein (oxLDL), heat shock proteins and beta2-glycoprotein I. The inflammatory component is not localized to the "culprit" plaque, but it is diffused to the entire coronary vascular bed, and involves also the myocardium. The aim of the conference (2nd conference on heart, rheumatism and autoimmunity) was to focus the attention of the participants on some pathogenetic, clinical and therapeutic aspects at the boundary between cardiology and rheumatology and to encourage the debate among clinicians and basic researchers with different backgrounds and experiences.

Autoimmunity↗
PubMed2005

Thrombotic risk factors in primary antiphospholipid syndrome: a 5-year prospective study.

BACKGROUND AND PURPOSE: Because thromboembolic events are frequently observed in primary antiphospholipid syndrome (PAPS), we assessed the risk factors for new thrombotic episodes. METHODS: Fifty-six PAPS patients (mean age, 37+/-10 years) were prospectively studied for 5 years. The preliminary Sapporo classification criteria for antiphospholipid syndrome (APS; a medium-high anticardiolipin antibody [aCL] titer and/or a positive lupus anticoagulant [LA] test in the presence of vascular thrombosis and/or pregnancy morbidity) were used to confirm the diagnosis. Thrombotic episodes or pregnancy losses before a diagnosis of PAPS were considered events, and any new disease manifestation other than thrombocytopenia was considered a recurrent event. Only patients with objectively verified thrombotic events were included in the study. RESULTS: Twenty-one new thrombotic events were observed in 15 subjects (26.8%), including 3 (5.4%) who died during the follow-up. The patients with IgG aCL levels of >40 IgG phospholipid unit (GPL-U) showed a higher incidence of new thrombotic events (43.3%) than those with levels of < or =40 GPL-U (7.7%). Univariate analysis identified a history of recurrent clinical events (P=0.004), a highly positive aCL titer (P=0.007), and the presence of cardiac abnormalities (P=0.036) as significant risk factors for new thrombotic events. A multivariate regression model confirmed that an IgG aCL titer of >40 GPL-U was an independent risk factor for thrombosis (odds ratio, 9.17; 95% confidence interval, 1.83 to 46.05). CONCLUSIONS: A high IgG aCL titer is the strongest predictor of new thrombotic events in PAPS patients.

Abortion, Spontaneous↗
PubMed2005

Effect of adalimumab on neutrophil function in patients with rheumatoid arthritis.

Neutrophils are known to be targets for the biological activity of tumour necrosis factor (TNF)-alpha in the pathogenesis of rheumatoid arthritis (RA). Therefore, these cells may be among the targets of anti-TNF-alpha therapy. In this study we evaluated the effect of therapy with adalimumab (a fully human anti-TNF-alpha mAb; dosage: 40 mg subcutaneously every other week) on certain phenotypic and functional aspects of neutrophils obtained from 10 selected patients with RA and 20 healthy control individuals. Peripheral blood neutrophils were obtained at baseline and during anti-TNF-alpha therapy (2, 6 and 12 weeks after the first administration of adalimumab). All patients had been receiving a stable regimen of hydroxychloroquine, methotrexate and prednisone for at least 3 months before and during the study. Baseline neutrophil chemotaxis was significantly decreased in RA patients when compared with control individuals (P < 0.001). Two weeks after the first administration of adalimumab, chemotactic activity was completely restored, with no differences noted between patients and control individuals; these normal values were confirmed 6 and 12 weeks after the start of anti-TNF-alpha therapy. Phagocytic activity and CD11b membrane expression on neutrophils were similar between RA patients and control individuals; no modifications were observed during TNF-alpha neutralization. The production of reactive oxygen species, both in resting and PMA (phorbol 12-myristate 13-acetate)-stimulated cells, was significantly higher in RA patients at baseline (P < 0.05) and was unmodified by anti-TNF-alpha mAb. Finally, we showed that the activation antigen CD69, which was absent on control neutrophils, was significantly expressed on neutrophils from RA patients at baseline (P < 0.001, versus control individuals); however, the molecule was barely detectable on cells obtained from RA patients during adalimumab therapy. Because CD69 potentially plays a role in the pathogenesis of arthritis, our findings suggest that neutrophils are among the targets of anti-TNF-alpha activity in RA and may provide an insight into a new and interesting mechanism of action of anti-TNF-alpha mAbs in the control of inflammatory arthritis.

Adalimumab↗
PubMed2005

Potential off-label use of infliximab in autoimmune and non-autoimmune diseases: a review.

TNF-alpha is a crucial cytokine in the establishment and maintenance of inflammation in multiple autoimmune and non-autoimmune disorders. A number of large placebo-controlled trials have shown that infliximab, a chimeric monoclonal antibody against TNF-alpha, is effective and well-tolerated in patients with Crohn's disease and rheumatoid arthritis (RA) and has become a widely used treatment for these diseases. More recent controlled trials have also shown the effectiveness of TNF-alpha blockers in psoriasis, psoriatic arthritis, and ankylosing spondylitis. The results of clinical trials, open-label studies, and case studies indicate that TNF inhibitors (alone or in combination with other protocols) look very promising for the treatment of a variety of other conditions, including uveitis, sarcoidosis, Sjögren's syndrome (SS), Behcet's syndrome, vasculitis, and graft versus host disease. There is a rationale for using TNF blockade even in systemic lupus erythematosus, a prototype of autoantibody-mediated disease, and a pilot study seems to confirm this potential effective approach. The neutralisation of TNF might therefore play a role in the treatment of many autoimmune and non-autoimmune disorders other than Crohn's disease or RA. We here review the current and prospective roles of infliximab in the treatment of autoimmune diseases and other conditions that do not currently have FDA or EMEA approval.

Animals↗
PubMed2005

The role of echocardiographic techniques in connective tissue diseases.

Connective tissue diseases (CTD) lead to a high prevalence of common cardiac manifestations (pericarditis and myocarditis) and of ischemic coronary events with a considerable increase in cardiac mortality related to premature atherosclerosis. Although there are several techniques able to detect cardiac involvement in CTD patients, the most useful and non-invasive technique is echocardiographic exam which is able to detect not only valvular abnormalities, pericardial diseases and pulmonary hypertension but also left ventricular (LV) systolic or diastolic (regional or global) wall motion dysfunction. It is also well known that transesophageal echocardiography (TEE) can better identify cardiac abnormalities, vegetations and embolic sources. Symptomatic patients with positive stress echocardiographic exam or dipyridamole thallium imaging test should be referred for possible cardiac catheterization, especially if a large ischemic territory is involved. Until now, the echocardiographic evaluation of coronary artery tree consisted of assessing regional and global left ventricular systolic and diastolic function at rest and during pharmacological stress test. Recently, a new echocardiographic noninvasive method that allows direct assessment of coronary flow velocity in the mid-distal portion of left anterior descending artery (LAD) has been developed and validated. Advanced ultrasound technology (high-frequency broadband transducer with second harmonic capability) has now made possible a direct arterial visualization and measurement of coronary artery flow in left anterior descending in CTD patients with the assessment of coronary flow reserve (CFR).

Adult↗