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G Valesini

Publications and source records attributed to G Valesini.

At least 145 records · Page 8Linked to original sources

[Advances in immunology and rheumatoid arthritis pathogenesis].

The pathogenesis of Rheumatoid Arthritis (RA) is still largely unknown. From the seminal experimental studies, suggesting a multifactorial mechanism leaded by an antigen specific activation, the direct role of innate immunity in the disease progression has been recently emphasized. In the natural history of RA, characterized by the three phases of the induction, maintenance and tissue destruction, innate immunity seems to be the central player. On the other hands the recent advances about the molecules involved in the T lymphocyte activation, the T cell role in the mechanism of erosion, and the studies about chemokines in the homing and angiogenesis processes support the theory of an antigen specific activation of the adaptive immune system. Therefore, during RA, the pathogenesis of sinovitis and erosions comes from independent pathways involving either innate and adaptive immunity resulting in the final induction of the articular damage.

Animals↗

[Usefulness of anti-cyclic citrullinate peptide antibody determination in synovial fluid analysis of patients with rheumatoid arthritis].

OBJECTIVE: To assess the role of anti-cyclic citrullinated peptide (CCP) antibody detection in synovial fluid (SF) of RA patients compared to OA patients. METHODS: We evaluated in 25 RA subjects and 14 OA patients, presenting a knee-joint effusion, the main clinical and laboratory parameters including the number of painful and/or swollen joints, Ritchie index, morning stiffness, ESR, CRP and analysis of SF obtained by therapeutic arthrocentesis. IgG anti-CCP (ELISA), rheumatoid factor (RF) and total IgG (nephelometry method) were measured in SF and paired serum samples. RESULTS: We found anti-CCP antibodies and RF in 64% (16/25) and 60% (15/25) of RA sera, respectively; 72% (18/25) of RA patients were positive for anti-CCP antibodies or RF. We found a higher SF/serum ratio for anti-CCP (p<0.004) compared to that for total IgG. The calculation of anti-CCP concentration as IgG anti-CCP (units)/total IgG (g L-1) revealed higher values in SF than in serum (p<0.046) in RA patients. Among these, correlation analysis showed that anti-CCP/total IgG values in SF correlated with the relative concentration of serum anti-CCP/total IgG (rs=0.842; p<0.00001) and serum anti-CCP antibody levels (rs=0.799; p<0.0001). We did not find any correlation between SF anti-CCP levels and the main characteristics of SF as well as the clinical or laboratory parameters. CONCLUSION: Our study give evidence for a preferential production of anti-CCP antibodies at RA joint level, confirming the pathogenetic role of these autoantibodies. Moreover, SF determination of anti-CCP, corrected for the total amount of the corresponding immunoglobulin, may be helpful as diagnostic tool in selected cases.

Adult↗

[Occupational therapy in rheumatoid arthritis: short term prospective study in patients treated with anti-TNF-alpha drugs].

OBJECTIVE: To assess the effect of occupational therapy (OT) in rheumatoid arthritis (RA) patients treated with anti-TNF-alpha drugs in a short-term open controlled prospective study. METHODS: 31 RA subjects [(M/F=5/26; mean age= 56 (range=28-73) years; mean disease duration= 165 (range =15-432) months], treated with anti- TNF-alpha drugs, were allocated to OT (n=15) or control (n=16) group. We evaluated at entry and 12 weeks the following outcome parameters including Health Assessment Questionnaire (HAQ), Short-Form Health Survey (SF-36), Global Health (GH), Ritchie index, number of swollen or tender joints, pain, patient and physician disease activity, Disease Activity Score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein CRP) and the correct adherence to items regarding activity daily living (ADL). RESULTS: At baseline, OT and control group had similar demographic and clinical features. After 12 weeks, the changes from baseline of main outcome parameters were not significantly different between the two groups. After 12 weeks, in 7 out of 11 items regarding ADL, the percentage of patients showing a correct adherence was significantly increased in OT group only. Moreover at the end of the study, the OT group showed a correct adherence to 8 out of 11 ADL items in an higher percentage of patients respect to the control group. CONCLUSION: Our study sustains that OT improves self-management but not main parameters of disease activity or functional capacity. Nevertheless educational intervention should be considered as a useful tool in conjunction with pharmacological treatment.

Activities of Daily Living↗

[Ultrasonographic assessment of the response to Etanercept treatment in patients with rheumatoid arthritis].

OBJECTIVES: To evaluate, using musculoskeletal ultrasound (MSUS), the effects of Etanercept therapy in patients with rheumatoid arthritis (RA) over 3 months of treatment. METHODS: Eighteen consecutive patients, 3 male and 15 female, affected by RA (ACR criteria) who were non-responders or partial responders to DMARDs therapy were commenced on Etanercept treatment. MSUS was performed bilaterally in the 2nd and 5th metacarpophalangeal, 3rd interphalangeal, wrist and knee joints, using a Philips/HP Image Point HX machine with a 7,5 MHz linear probe for knee joints and a 14 MHz probe for the hands and wrists. In addition, power Doppler was used with the following settings: PRF 700-1000Hz, gain 60-65 dB, low filter. For all the changes a semi-quantitative score (0-3) was used to indicate the presence of a localised inflammatory process (synovitis, tenosynovitis). An overall score was then calculated based on the sum of the single scores in order to obtain a comprehensive score indicative of the global pathological change. RESULTS: The overall score significantly (p<10-5) reduced between T0 (8,5) and T3 (5). Even the most part of the local joint scores significantly reduced. CONCLUSIONS: A positive response to treatment with Etanercept was demonstrated by MSUS examination of several joints. The results of our study are supportive of those presented in other reports where MSUS was used to monitor disease activity. We were able however to demonstrate this in a wider range of anatomical targets than in previous studies. MSUS is a useful tool in the monitoring of biologic therapy in RA.

Adult↗

Five-year follow-up of 165 Italian patients with undifferentiated connective tissue diseases.

OBJECTIVE: To study those conditions with a proven or hypothesised immunologic pathogenesis and denominated under a working definition of undifferentiated connective tissue diseases (UCTD). METHODS: A multicentre prospective study was organised involving 10 tertiary referral centers of internal medicine in Italy, with the aim of describing the natural history of UCTD and the prevalence of its different clinical and immunological manifestations. RESULTS: After a five-year follow-up period, data on 165 patients were available for analysis. UCTDs occur mainly in females in their fourth decade of life. Articular and mucocutaneous features and Raynaud's phenomenon represent the most common findings. Nevertheless, we also detected a relatively high incidence of permanent major organ damage. Regarding the immunologic parameters, we documented some conflicting results in the correlation between serologic abnormalities and clinical features. In 10 patients UCTD evolved to a major disease, generally systemic lupus erythematosus or Sjögren's syndrome. CONCLUSION: A low rate of evolution to a defined autoimmune disease, the limited use of steroid or immunosuppressive therapy, and a favourable course in the majority of cases are the main characteristics of patients with UCTDs.

Adolescent↗

Primary aspergillosis of the larynx in a patient with Felty's syndrome.

Herein we report the first case of primary aspergillosis of the larynx in a patient with Felty's syndrome. A 53-year-old man, a florist by profession, with a 12-year history of rheumatoid arthritis and on treatment with steroids, was admitted because of hoarseness, and intermittent fever of 2 weeks' duration. On admission, physical examination and laboratory data showed, among other findings, splenomegalia and neutropenia. At bone marrow examination, normal cellularity with mild dyserythropoiesis was observed. A fiberoptic laryngoscopy showed white plaques on both the true vocal cords. Both culture and microscopic examination of these lesions provided the diagnosis of invasive process by Aspergillus flavus. A computed tomography of the middle ears, paranasal sinuses, and chest was normal. Thus, primary aspergillosis of the larynx and Felty's syndrome was diagnosed, and the patient was successfully treated with granulocyte colony-stimulating factor and systemic antifungal agents. Felty's syndrome, corticosteroid use, and occupational risk probably rendered our patient susceptible to Aspergillus infection.

Adrenal Cortex Hormones↗

Interleukin-13 in autoimmune rheumatic diseases: relationship with the autoantibody profile.

OBJECTIVE: Several cytokines play a role in the production of autoantibodies such as RF and ANA by B-lymphocytes; the role of IL-13 in this process has not been previously studied. We investigated the relationship between the serum concentration of this cytokine and circulating autoantibodies. METHODS: IL-13 serum levels, as well as RF and ANA, were evaluated in 282 patients with autoimmune rheumatic diseases including RA (n=84), SLE (n= 114), SS (n=52) and Scl (n=32). RESULTS: Serum levels of IL-13 (pg/ml) were significantly higher in patients with RA (p < 0.00003), SLE (p < 0.03), SS (p < 0.0007), or Scl (p < 0.025) compared to controls. IL-13 serum levels correlated with those of RF in RA (p < 0.00001), SLE (p < 0.003) and Scl (p < 0.03). IL-13 levels were higher in RA (p<0.0003), SLE (p<0.005) and Scl (p<0.05) patients with RF than in patients without RF. SS patients with antiSSA/Ro antibodies had significantly higher IL-13 levels than SS patients without this autoantibody (p < 0.04). No statistically significant correlation was found between IL-13 levels and any other antinuclear autoantibody, total immunoglobulin levels or the main clinicalfeatures of each disease. CONCLUSION: The evidence of higher IL-13 levels in our RA, SLE, SS and Scl patients confirms that this cytokine is involved in the pathogenesis of autoimmune rheumatic diseases. The relationship of this cytokine with RF in RA, SLE and Scl, as well as with antiSSA/ Ro antibody in SS, strengthens the hypothesis that it plays a role in autoantibody production. However, the different autoantibody synthesis by B-cells recognises different pathways depending on the underlying autoimmune disease.

Adolescent↗

Thalidomide: focus on its employment in rheumatologic diseases.

Thalidomide is an immunomodulatory agent; although its mechanisms of action are not fully understood, many authors have described its anti-inflammatory and immunosuppressive properties. More interestingly, thalidomide has shown the ability to suppress tumor necrosis factor alpha (TNF alpha) production and to modify the expression of TNF alpha induced adhesion molecules on endothelial cells and on human leukocytes. Thalidomide has been used in several diseases (i.e. dermatological, autoimmune, gastrointestinal). In this review we focus specifically on the use of this drug in disorders with rheumatological features such as lupus erythematosus, rheumatoid arthritis and Still's disease, ankylosing spondylitis, and Behçet's disease. Despite its well known side effects, first of all peripheral nerve involvement and teratogenesis, which can be avoided by following strict guidelines, thalidomide could represent an alternative drug in some rheumatological conditions, particularly in patients who show resistance, contraindication or toxicity with other conventional treatments.

Abnormalities, Drug-Induced↗

Sonographic study of painful shoulder.

OBJECTIVE: To identify sonographically the site and entity of alterations in a high number of patients with shoulder pain. METHODS: Two different experienced operators (both rheumatologists), who were blinded to the clinical data, performed sonographic examinations on 528 shoulders of 425 consecutive patients with painful shoulder and in both shoulders of 198 control subjects. They carried out ultrasound examinations separately using a 7.5 MHz linear transducer. Investigation included the long head of the biceps tendon, the supraspinatus tendon, infraspinatus tendon, subscapularis tendon, acromioclavicular joint, glenohumeral joint, subacromial-subdeltoid bursa, subscapularis bursa, and finally identification of calcifications. Before the ultrasonographic exam, a third experienced rheumatologist performed a physical examination in all patients using specific tests of movement for evaluation of the long head of biceps tendon, the supraspinatus tendon, infraspinatus tendon, subscapularis tendon, and acromioclavicular joint. RESULTS: Sonographic alterations were found in a total of 94.1% of patients. The structure most frequently involved was the supraspinatus tendon (64.6%). The long head of the biceps tendon (48.1%) and the acromioclavicular joint (51.5%) were also frequently involved. Different types of alterations in the various structures were detected. Significant differences were found with respect to controls. A high sensitivity and specificity of sonography was demonstrated compared to physical examination. CONCLUSIONS: Sonography evaluates accurately the single anatomic structures of the shoulder and identifies both the site and type of changes in patients with painful shoulder. The high sensitivity/specificity, non-invasiveness and low costs of this technique justify its routine utilisation in clinical rheumatological practice.

Adolescent↗

Specificity of antinuclear and antiphospholipid antibodies in sera of patients with autoimmune lymphoproliferative disease (ALD).

OBJECTIVE: A human lymphoproliferative syndrome characterized by a defect of the Fas-mediated apoptosis pathway in the absence of a fas gene mutation (Autoimmune Lymphoproliferative Disease) has recently been described and characterized by autoimmune phenomena. The aim of this study was to investigate the presence of antinuclear and antiphospholipid antibodies and to define their specificity in 5 pediatric patients with this syndrome. METHODS: Antinuclear antibodies were investigated by Western Blot and IIF performed under standard as well as apoptotic conditions. The fine specificity of antiphospholipid antibodies was dissected by an ELISA for anti-beta 2-glycoprotein I, anti-prothrombin, anti-annexin V and anti-protein S antibodies, and by immunostaining on thin layer chromatography plates for antiphospholipid molecule antibodies. RESULTS: This study showed that the autoantibodies found in these patients targeted a broad spectrum of nuclear antigens which undergo redistribution from the nucleus to the cytoplasm and plasma membrane during the course of the apoptotic process. This reactivity does not comprise known specificities such as anti-extractable nuclear antigens or anti-dsDNA. Antiphospholipid antibodies were also found in these sera. A further characterization of the antiphospholipid antibodies showed the presence of a heterogeneous response with antibodies directed to negatively-charged phospholipids and antibodies targeting coagulation-related proteins (beta 2-GPI, prothrombin, annexin V) which are considered relevant antigens in the antiphospholipid syndrome. CONCLUSIONS: These results suggest that lack of tolerance due to a defect of Fas-mediated apoptosis allows the survival of B and T clones involved in the antinuclear and antiphospholipid immune responses.

Adolescent↗

Joint sonography in asymptomatic patients with HCV correlated hepatitis.

OBJECTIVES: Many different articular symptoms may appear in patients with HCV hepatitis, but in a relatively large number of patients no rheumatic symptoms are present. This sonographic study was undertaken to detect the possible presence of early articular changes in HCV patients without any rheumatic manifestations. METHODS: The knee, hip and shoulder were evaluated in a cohort of 29 consecutive HCV patients without any rheumatic symptoms. Results were compared with those obtained by the evaluation of 29 healthy subjects who were negative for markers of HCV and HBV infections. RESULTS: Results showed the presence of alterations in 96.5% of the patients, with significant differences in comparison to controls (p < 0.0001). Slight inflammatory changes were found in all the joints examined. The knee was involved in 79.3% of the cases, the hip in 27.6% and the shoulder in 89.6%. CONCLUSIONS: Our preliminary study shows the presence of joint changes in the majority of cases. To the best of our knowledge this is the first ultrasonographic study to focus on joint evaluation in patients with HCV hepatitis. Broader epidemiological and virological investigations, in particular for the HCV subtype and HLA genotype, will be required to elucidate the relationship between HCV infection and rheumatic symptoms.

Adult↗

Natural killer cells and gamma/delta T cells in synovial fluid and in peripheral blood of patients with psoriatic arthritis.

OBJECTIVE: NK surface markers and gamma/delta TCR antigen are involved in non-MHC-restricted cytotoxicity, which represents a major effector mechanism of the cell-mediated immune response. We evaluated in PsA patients SF and PB lymphocytes expressing these cellular subsets in order to obtain information on the possible role played by them in the disease. METHODS: We studied 29 PsA and 27 RA patients, as well as 27 healthy controls. In 17 PsA and 16 RA patients with knee joint effusion, analysis of SF was performed. SF and PB lymphocyte analysis was performed by direct dual immunofluorescence flow cytomettry using anti-CD3, anti-CD4, anti-CD8, anti-CD19, anti-TCR-gamma/delta-1 and anti-CD16 and anti-CD56 monoclonal antibodies. RESULTS: PsA and RA patients had, with respect to controls, lower values (both as percentages and in absolute numbers) of PB T cells expressing gamma/delta TCR. SF Iymphocytes of PsA and RA patients were characterised, as compared to PB lymphocytes, by lower numbers (both in absolute numbers and in relative terms) of NK and NK-T cells. Considering the absolute numbers of the various lymphocyte subsets, a strong correlation was found in PsA SF between gamma/delta T cells and NK (p < 0.0007) or NK-T cells (p < 0.0003), as well as between NK and NK-T cells (p < 0.0019). There was instead no statistically significant correlation among the different SF or PB lymphocytes and the most relevant clinical or serological parameters. CONCLUSION: This study, analyzing the impairment of different subsets involved in non-MHC-restricted cytotoxicity, suggests that this component of the cell-mediated immune response seems to play a pivotal role in the development of PsA.

Adolescent↗

[Treatment of Wegener's granulomatosis].

Treatment of Wegener's granulomatosis, often a life-threatening disease, has greatly improved, considering that before corticosteroids and immunosuppressives were available, the average survival time of patients amounted to no more than 5 months. The management of Wegener's granulomatosis can be divided in two stages: induction of remission and maintenance of remission. The standard regimen for the induction of remission consists of cyclophosphamide, 2 mg/kg/day orally, in combination with prednisone, 1 mg/Kg/day orally, with a gradual tapering once remission has been obtained. To lower the overall cumulative dose, monthly intravenous pulses of cyclophosphamide have been evaluated. Other alternative treatments as high doses of corticosteroids, methotrexate, or plasmapheresis have been proposed, together as prophylaxis with trimethoprim-sulfamethoxazole. To minimize toxicity, for maintenance therapy other drugs are also used such as methotrexate, azathioprine, cyclosporine. Frequent therapeutic changes are needed due to the great variability of the disease; while important aspects are the recognition and treatment of relapse, and include not only the management of resistant disease, but also some particular aspects such as disease in chronic dialysis, renal transplant, pregnancy. Other cytotoxic drugs like leflunomide or mycofenolic mofetil appear to be promising, while new efforts to identify more effective and less toxic therapies include biologic products, such as high-dose immunoglobulin, TNF antagonists and other monoclonal antibodies. Many different kind of clinical trials are going on to better evaluate the real efficacy and safety of these treatments in Wegener's granulomatosis.

Adjuvants, Immunologic↗

Wrist joint involvement in systemic lupus erythematosus. An ultrasonographic study.

OBJECTIVE: To define joint alterations in the wrists of patients with systemic lupus erythematosus (SLE) by ultrasonography (US). METHODS: Fifty-two wrists of 26 SLE patients and 30 wrists of 15 healthy controls were evaluated using US by two different experienced operators, blinded to the clinical data. A 14 MHz linear probe was used. Power Doppler (PD) was applied to evaluate the presence of synovial neoangiogenesis as a parameter of active local synovitis. The findings were correlated to the clinical evaluation, serological systemic disease activity parameters (ESR, C3 levels) and the SLE-disease activity score (SLEDAI). Statistical analysis was performed by the EPISTAT program. RESULTS: Signs of synovitis were found in 22 wrists (42.3%). Synovial proliferation was present in 10 joints (19.2%), PD positivity in 5 (9.6%) and joint effusion in 13 (25%). Erosions were present in both wrists (3.8%) of one patient. Signs of tenosynovitis of one or more tendons were shown in 23 cases (44.2%). Ganglia were found in 2 joints (3.8%). Changes of the median nerve, joint dislocations, tendons' ruptures, cysts and nodules were never detected. In 14 wrists (26.9%) no alterations were found. There was no correlation between sonographic findings and clinical, laboratory and indexes signs of disease activity. In the control group the only alteration found was tenosynovitis in 1 joint (p < 0.0001). CONCLUSION: US proved to be an useful technique to detect wrist joint alterations in SLE. These findings may help the physician to modulate treatment strategies and to perform a low cost monitoring of joint disease activity.

Adult↗

Ultrasound imaging for the rheumatologist.

Over the last few years, technological advances have resulted in dramatic improvements in quality and resolution of ultrasonography (US), allowing it to become a very powerful tool in rheumatological clinical practice. Despite the fact that the impact of US on final diagnosis or therapeutic options for rheumatic patients has not yet been defined, there is now growing evidence that US improves clinical diagnosis and intervention skills. This review discusses the most important issues connected with the practice of US in rheumatology including: basic requirements, scanning technique, clinical applications, training and future developments. Moreover, it provides a general overview of both US anatomy and pathology relevant for the rheumatologist.

Humans↗