P. Puttini | Università Statale di Milano (original) (raw)

Papers by P. Puttini

Research paper thumbnail of Pharmakon or The Art That Heals: Trans-disciplinary artistictransformative workshops for fibromyalgia syndrome

Villani, 2023

Our research focused on the idea that art, when used in a transformative way (TA), can generate d... more Our research focused on the idea that art, when used in a transformative way (TA), can generate decisive and lasting changes.
Theoretical assumptions

  1. Approach FMS as a complex disease, hypothesizing its traumatic origin and a deficiency of the endocannabinoid system (ECS) resulting from organic, psycho-physical, interpersonal or environmental
  2. The transformative artistic experience (TA) can induce a change in thoughts, generating strong motivating and challenging beliefs (self-esteem and self-awareness), conditioning I behaviors towards generating novel responses to the same initial thoughts and actions, in one sort of "virtuous" circle, adaptive rather than maladaptive, with lasting and/or irreversible.
  3. Use art as an empowerment tool, considering the sick person as the first and fundamental "operator" of the care work for your health.

Our research shows that art, experienced as TA, leads to significant improvements of the psychophysical condition of FMS patients. TA can be seen as a crucial mediator for overcoming the trauma/stressors, probably through the generation of “pivotal mental states” (PIMS), defined as a "hyper-plastic state aiding rapid and deep learning that can mediate psychological transformation” .

Research paper thumbnail of Cost effectiveness analysis of disease modifying antirheumatic drugs in rheumatoid arthritis

Rheumatology International, 2007

The cost effectiveness of treatments that have changed the "natural history" of a chronic progres... more The cost effectiveness of treatments that have changed the "natural history" of a chronic progressive disease needs to be evaluated over the long term. Disease-modifying antirheumatic drugs (DMARDs) are the standard treatment of rheumatoid arthritis (RA) and should be started as early as possible. A number of studies have shown that they are effective in improving disease activity and function, and in joint damage. Our review was focused on revision and critical evaluation of the studies including the literature on cost effectiveness of DMARDs (cyclosporine A, sulphasalazine, leflunomide, and methotrexate). The European League Against Rheumatism (EULAR) recommendations showed that traditional DMARDs are cost effective at the time of disease onset. They are less expensive than biological DMARDs and can be useful in controlling disease activity in early RA.

Research paper thumbnail of Factors correlated with improvement of endothelial dysfunction during rituximab therapy in patients with rheumatoid arthritis

Biologics: Targets and Therapy, 2013

Increased cardiovascular mortality has been associated with rheumatoid arthritis (RA). There are ... more Increased cardiovascular mortality has been associated with rheumatoid arthritis (RA). There are reports indicating that tumor necrosis factor (TNF) blockers may exert favorable but transient effects on the lipid profile, flow-mediated vasodilatation (FMD) of the brachial artery, and the common carotid intima-media thickness (ccIMT) in RA. We evaluated 38 RA patients (33 females and five males with a mean age of 66.7 ± 10.2 years) who were unresponsive to TNF blockers. The patients received one or more courses of two rituximab (RTX) 1000 mg infusions. Disease activity was evaluated at each visit. Investigations included erythrocyte sedimentation rate, C-reactive protein (CRP) levels, the 28-joint disease activity score (DAS28), DAS28CRP, the Health Assessment Questionnaire, the FMD percent change from baseline (FMD%), and the postnitroglycerine endothelium-independent vasodilatation. In comparison with the baseline, there was a significant improvement in clinical variables and acute-phase reactants 24 months after the start of RTX therapy. There was also a major improvement in FMD% (from baseline 5.24 ± 1.12 to 5.43 ± 1.16; P =-0.03) and a smaller change in the ccIMT (from baseline 0.69 ± 0.16 to 0.67 ± 0.12 mm P = 0.25). Univariate analysis showed that global health (P , 0.034) was associated with the improvement in FMD%. Multivariate models showed that GH (odds ratio [OR] 0.91; 95% CI: 0.99-0.83; P = 0.032), CD19+ cells (OR 1.024; 95% CI: 1.045-1.003; P = 0.025), IgM (OR 1.025; 95% CI: 1.045-1.004; P = 0.016), and interleukin (IL)-8 (OR 0.487; 95% CI: 0.899-0.264; P = 0.021) were statistically associated with the improvement of FMD%, and that IL-8 (OR 0.717; 95% CI: 0.926-0.555; P = 0.018) was also statistically associated with improvement of ccIMT. The findings of the study confirm that RTX reduces the progression of accelerated atherosclerosis in patients with RA. They also show that improvement in CD19+ cells, IgM and GH after treatment are statistically associated with the improvement of FMD%, and that improvement in IL-8 levels after treatment is statistically associated with improved FMD% and with decrease in the ccIMT.

Research paper thumbnail of Validity and Reliability of the Italian Version of the Functioning Assessment Short Test (FAST) in Bipolar Disorder

Clinical Practice & Epidemiology in Mental Health, 2012

Background:Functioning Assessment Short Test (FAST) is a brief instrument designed to assess the ... more Background:Functioning Assessment Short Test (FAST) is a brief instrument designed to assess the main functioning problems experienced by psychiatric patients, specifically bipolar patients. It includes 24 items assessing impairment or disability in six domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships and leisure time. The aim of this study is to measure the validity and reliability of the Italian version of this instrument.Methods:Twenty-four patients with DSM-IV TR bipolar disorder and 20 healthy controls were recruited and evaluated in three private clinics in Cagliari (Sardinia, Italy). The psychometric properties of FAST (feasibility, internal consistency, concurrent validity, discriminant validity (patients vs controls and eutimic patients vs manic and depressed), and test-retest reliability were analyzed.Results:The internal consistency obtained was very high with a Cronbach's alpha of 0.955. ...

Research paper thumbnail of A Comparison of Dothiepin versus Placebo in the Treatment of Pain in Rheumatoid Arthritis and the Association of Pain with Depression

Journal of International Medical Research, 1988

The effectiveness of dothiepin (a tricyclic anti-depressant) at a dose of 75 mg given orally at n... more The effectiveness of dothiepin (a tricyclic anti-depressant) at a dose of 75 mg given orally at night was compared with placebo for 4 weeks in alleviating pain in 60 patients with classical or definite active rheumatoid arthritis. Patients were classified as either ‘depressed’ or ‘not depressed’. The week before, during and 2 weeks after the study, 600 mg ibuprofen was given orally three times daily to all patients. Compared with placebo, dothiepin produced a significant reduction in daytime pain by the end of the treatment period. The Hamilton rating scale in ‘depressed’ patients was significantly improved in patients given dothiepin. The Cassano–Castrogiovanni self-evaluation rating scale in both ‘depressed’ and ‘not depressed’ patients showed a tendency (not significant) to be improved following dothiepin treatment compared with placebo. These results suggest that patients with rheumatoid arthritis may experience an increase in pain symptoms due to an alteration of mood. Therapy ...

Research paper thumbnail of Vaccination with endosomal unknown epitopes produces therapeutic response in rheumatoid arthritis patients and modulates adjuvant arthritis of rats

Journal of translational medicine, Jun 7, 2016

Our previous results showed that intrasynovial Rifamycin SV caused the lysis of synoviocites and ... more Our previous results showed that intrasynovial Rifamycin SV caused the lysis of synoviocites and freed the autoantigens which in turn stimulated the immunoregulatory rather than autoreactive T cell response in rheumatoid patients. Here, we hypothesize that disruption in vitro of peripheral blood mononuclear cells, by freeze/thawing or by lytic action of Rifamycin SV, would induce the release of endosomal pathogenic autoantigens from APCs present in the circulation, which could then be isolated from degrading enzymes by ultrafiltration. The preparation of the ultrafiltrates are based on the rupture of PBMCs (5 × 10(6) cells/mL) by the addition of Rifamycin SV in culture (250 μg/mL), which causes the lysis of 90 % of the cells in 3 h, or by three cycles of freeze/thawing of the PBMC, from -80 °C to room temperature. The lysate and the fragmented cells were then centrifuged and ultrafiltered by passage through a filtration device with a cut-off of 10 kDa. Also the synovial fluid was su...

Research paper thumbnail of FRI0175 Anti-drug-antibodies but not igg-4 antibodies against tnf blockers influence the activity of anti-tnf drugs in rheumatoid arthritis

Annals of the Rheumatic Diseases, 2013

ABSTRACT Background Anti-TNF drugs have changed the clinical course of rheumatoid arthritis (RA),... more ABSTRACT Background Anti-TNF drugs have changed the clinical course of rheumatoid arthritis (RA), but the survival rate and the resistance to the therapy showed that about 30% of RA patients fail to respond to these drugs. Objectives The aim of our study was to evaluate the correlation between the development of anti-drug antibodies and specific IgG-4 antibodies against TNF inhibitors and the resistance to this therapy in RA patients. Methods The retrospective study involved 130 established RA patients [98 females and 32 males, mean age 56,7±12,3 years, disease duration 6,3±1.2] who fail to respond to conventional DMARDs treated with anti-TNF agents [32 pts with INF, 58 pts. with ETN, 40 pts with ADA] with a baseline DAS28 range between 3.2-5.6. After 6 months of treatment according to DAS28 values the patients were classified in remission for DAS28 <2.6 (R) and having low disease activity (LDA) for DAS28 range between 2.6-3.2 or non responder (NR)>3.2. The patients were tested for serum anti-drugs antibodies (Anti TNF-α Blocker ELISA kit Immundiagnostik AG, Bensheim - Listarfish, Milan, Italy) and IgG4 specific antibodies against TNF- inhibitors (ImmunoCAP® Assay fluoroenzyme immuno assay Kit for ImmunoCAP250, Phadia, Uppsala, Sweden). Results After a mean of 6 months in IFN group: 15.65% of the patients were in remission (R ), 31.2 % in LDA and 53.12% NRs; in ETN group 22.41% of the patients in R, 41.37% in LDA, 36.20% NRs, in ADA group 30% of the patients in R, 25% in LDA and 45% NRs. In the INF group the anti-drug antibodies were detected in 21. 87% of the patients and specific IgG-4 antibodies in18%, in ETN group the anti-drug antibodies were detected in 10.34% and specific IgG-4 antibodies in 8.67%, in ADA group the anti-drugs antibodies in 25% and specific IgG-4 antibodies in 5%. The presence of anti-drug antibodies in INF e ADA group correlate with the high percentage of NRs (R:0.032 ;R:0.039). No correlation with the specific IgG-4 antibodies against TNF and clinical response was observed. Conclusions In patients with RA the presence of all anti-drug antibodies but not the specific IgG-4 antibodies against TNF could influence the activity of TNFblockers in particular in INF and ADA group. This study also confirmed the low immunogenecity of ETN. Disclosure of Interest None Declared

Research paper thumbnail of SAT0152 Polymyalgia Rheumatica: A Comparative Study of Methylprednisolone and the Modified Release Prednisone

Annals of the Rheumatic Diseases, 2013

ABSTRACT Background Polymyalgia rheumatica (PM) is a common inflammatory disease that affects eld... more ABSTRACT Background Polymyalgia rheumatica (PM) is a common inflammatory disease that affects elderly patients in Western countries, and is usually treated using glucocorticoid (GC) therapy that still play the major role in the treatment of the disease by rapidly recunding and suppressing inflammation within a few week. The circadian administration of prednisone in rheumatoid arthritis showed that optimizing the timing of GC administration with low-dose modified-release prednisone (MR-P)improves the benefit ratio of long-term GC treatment (CAPRA 1-2 studies). Objectives To compare changes in inflammation markers and their correlations with cortisol levels in PM patients treated with the new MR-P tablet or 6-methylprednisolone (6-MP). Methods The 42 enrolled patients fulfilled the 2012 EULAR/ACR criteria for PM: 17 were treated with 6-MP 12 mg at 8.00 a.m. then gradually tapered to 2 mg/daily (group A: 10 females; mean age 72.5 years), and 25 were treated with MR-P10 mg at 10.00 p.m, tapered to 1 mg (group B: 14 females; mean age 74.6 years). Their erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), fibrinogen, cortisol levels, cytokine (TNF-α and IL6)were measured at baseline and after six months. Circulating cytokine levels were determined using Human IL-6 Instant ELISA Bioscience, Bender, MedSystems, GmbH (Vienna, Austria) and Human TNFa Quantikine immunoassay RD System INC.(Minneapolis, USA). Results The baseline laboratory parameters in group A and B were respectively: ESR 30.6±18.2 vs33.3±17.6 mm/h (p=n.s.); CRP 1.5±1.8 vs2.5±3.6 mg/dL (p=n.s.); fibrinogen 456±161 vs482±160 mg/dL (p=n.s.); cortisol 16.1±7.2 vs11.2±6.2 μg/dL (p=n.s.) and TNF-α1.0±0.6 vs1.2±0.7 pg/mL (p=n.s.). Baseline IL6 values were lower in group A 1.7±1.1 vs4.5±5.0 pg/mL in group B, p<0.01) and abnormal IL6 values at baseline were in eight (47%) group A vs twenty(84%) group B patients (p<0.05). After the first month oftreatment, the decrease in IL-6 levels in group A and B were respectively 50% and 85.7% (p <0.001). After six months of treatment, the same parameters were: ESR 18.2±15.6 vs20.5±16.5 mm/h (p=n.s.); CRP 0.7±0.6 vs0.6±0.8 mg/dL (p=n.s.); fibrinogen 441±101 vs372±85 mg/dL (p=n.s.); cortisol 14.1±5.4 vs11,7±4.8 μg/dL (p=n.s.); TNF-α2.9±7.2 vs3.6±11.4 pg/mL (p=n.s.); and IL-6 1.2±0.5 vs1.6±1.4 pg/mL (p=n.s.). After six months of treatment, there wasn’t a statistically significant difference in the GC dose between group A and group B (3.9±1.8 mg vs3.5±1.8 mg). Conclusions In this non-randomized prospective observational study the response of inflammation markers to low-dose GC was similar in patients with PM treated with 6-MP or MR-P, and morning cortisol levels were unaffected. However, the patients treated with MR-P showed a greater decrease in IL-6 levels after the first month. Disclosure of Interest None Declared

Research paper thumbnail of THU0319 Determination of the Serological Profiles in Anti-Ro-52-Positive Patients with Systemic Autoimmune Rheumatic Diseases

Annals of the Rheumatic Diseases, 2013

Synthesis and characterization of mechanically milled nanocomposites-carbon nanotubereinforced al... more Synthesis and characterization of mechanically milled nanocomposites-carbon nanotubereinforced aluminium ABSTRACT. Ever since the discovery of carbon nanotubes (CNTs), their interesting properties have captured the interest of researchers for commercial applications. Exceptional mechanical properties, with an average elastic modulus of 1-2 TPa and fracture strength of 200 GPa, provide the motivation for CNTs to be used in service conditions requiring high strength-to-weight ratios. The present research aims at the incorporation and characterization of CNT-reinforced aluminium nanocomposites. High energy ball milling was used to embed CNTs in a soft and ductile aluminium matrix. Milled powders having CNTs sandwiched in between aluminium grains were characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD). The results revealed the presence of CNTs at the aluminium powder cold weld interfaces, which was further confirmed by diffraction analysis.

Research paper thumbnail of The treatment of idiopathic and secondary hydrarthrosis of the knee by intra-articular Rifamycin SV

La Chirurgia degli organi di movimento

Fifty-three patients, 28 females and 25 males, aged from 21 to 68 years, affected with mono- and ... more Fifty-three patients, 28 females and 25 males, aged from 21 to 68 years, affected with mono- and bilateral intermittent hydrarthrosis of the knee and of a non-inflammatory nature, were included in an open study. All of the knees involved were treated with intra-articular infiltrations with Rifamycin SV. The weekly dosage of Rifamycin SV was 500 mg; the average duration of treatment was 6 weeks. Follow-up 1 year after the end of treatment showed a decrease or regression in joint effusion in all of the knees treated.

Research paper thumbnail of Old and new criteria for the classification and diagnosis of fibromyalgia: comparison and evaluation

Clinical and experimental rheumatology

ABSTRACT

Research paper thumbnail of Psychometric properties of the Fibromyalgia Assessment Status (FAS) index: a national web-based study of fibromyalgia

Clinical and experimental rheumatology

Fibromyalgia (FM) is a generalized chronic pain condition that is often accompanied by symptoms s... more Fibromyalgia (FM) is a generalized chronic pain condition that is often accompanied by symptoms such as fatigue, sleep disturbances, psychological and cognitive alterations, headache, migraine, variable bowel habits, diffuse abdominal pain, and urinary frequency. Its key assessment domains include pain, fatigue, disturbed sleep, physical and emotional functioning, and patient global satisfaction and health-related quality of life (HRQL). A number of evaluation measures have been adapted from the fields of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, and others such as the Fibromyalgia Assessment Status (FAS) index and the Fibromyalgia Impact Questionnaire (FIQ) have been specifically developed. The aim of this study was to assess the impact of FM on HRQL by comparing the performance of the FAS index, the FIQ and the Health Assessment Questionnaire [HAQ] in 541 female and 31 male FM patients (mean age 50 years; mean disease duration 7.7 years) entered in the ...

Research paper thumbnail of Fibromyalgia: who should reshape the pain perception of these patients?

Research paper thumbnail of Cyclosporine in addition to infliximab and methotrexate in refractory rheumatoid arthritis

Clinical and experimental rheumatology

Research paper thumbnail of Effect of adalimumab on neutrophil function in patients with rheumatoid arthritis

Arthritis research & therapy, 2005

Neutrophils are known to be targets for the biological activity of tumour necrosis factor (TNF)-a... more 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 adali...

Research paper thumbnail of Chlamydophila psittaci subclinical infection in chronic polyarthritis

Clinical and experimental rheumatology

Recent evidence indicates that Chlamydophila psittaci (Cp) may establish chronic infections, whic... more Recent evidence indicates that Chlamydophila psittaci (Cp) may establish chronic infections, which may promote autoimmunity and/or B cell lymphoproliferation. The presence of a subclinical Cp infection was investigated in 293 patients with chronic inflammatory polyarthritis, including 175 patients with rheumatoid factor (RF)-positive and/or anti-CCP-positive rheumatoid arthritis (RA) and 118 with seronegative polyarthritis (46 RF-negative/anti-CCP-negative RA, 36 psoriatic arthritis and 36 undifferentiated spondyloarthritis). One hundred and eighty-five healthy controls were also investigated. The presence of Cp infection was assessed in peripheral blood mononuclear cells using several PCR protocols targeting different regions of the Cp genome (16S-23S spacer rRNA, OMP-A, and Gro-EL). The DNA of other Chlamydia species (C. Pneumoniae and C. Trachomatis) was also investigated. Amplicons were sequenced to confirm the specificity of PCR products. The presence of a subclinical chronic C...

Research paper thumbnail of 2 Prevalence of mixed cryoglobulinaemia Q 4 syndrome and circulating 3 cryoglobulins in a population-based survey: The Origgio study

Research paper thumbnail of Pain in fibromyalgia and related conditions

Reumatismo, 2014

Pain is the hallmark symptom of fibromyalgia (FM) and other related syndromes, but quite differen... more Pain is the hallmark symptom of fibromyalgia (FM) and other related syndromes, but quite different from that of other rheumatic diseases, which depends on the degree of damage or inflammation in peripheral tissues. Sufferers are often defined as patients with chronic pain without an underlying mechanistic cause, and these syndromes and their symptoms are most appropriately described as “central pain”, “neuropathic pain”, “nonnociceptive pain” or “central sensitivity syndromes”. The pain is particular, regional or widespread, and mainly relates to the musculoskeletal system; hyperalgesia or allodynia are typical. Its origin is currently considered to be distorted pain or sensory processing, rather than a local or regional abnormality. FM is probably the most important and extensively described central pain syndrome, but the characteristics and features of FM-related pain are similar in other disorders of particular interest for rheumatologists, such as myofascial pain syndromes and t...

Research paper thumbnail of Poster session II * Thursday 9 December 2010, 14:00-18:00

European Journal of Echocardiography, 2010

Background: In optimisation of CRT (and even selection for implantation) we may underestimate the... more Background: In optimisation of CRT (and even selection for implantation) we may underestimate the impact of beat-to-beat variation on echo measurements. This can be quantified in the optimisation process, in which genuine small changes in cardiac function (signal) must be detected amongst beat-to-beat variation (noise). Methods and Results: To focus on biological variability we performed 2046 echo measurements in 11 patients by separate, replicate measurements at a series of interventricular delays of each potential optimisation modality including (i)3D SDI, (ii)aortic pre-ejection time, (iii)IVMD, (iv)LVOT VTI and (v)ECG. The equivalent of 31 optimisations per patient were performed. For single measurements at each setting, agreement between successive optimisations was low: 38% for SDI, 46% for aortic pre-ejection time, 30% for IVMD, 40% for LVOT VTI and 58% for ECG. Agreement between two methods,was similarly low, with agreement between optima being 20%. Guesswork would have given 17%. The intraclass correlation coefficient was low for all methods at 0.11, 0.48, 0.33, 0.40 and 0.52 respectively. Changing the protocol to average multiple measurements numerically improved agreement between successive optima. The intraclass correlation coefficients improved to 0.21(p ¼ ns), 0.70(p ¼ 0.002), 0.50(p ¼ 0.013), 0.52(p ¼ 0.012) and 0.65(p ¼ 0.012) respectively. Conclusions: Attempting optimisation of interventricular delay using single measurements at each setting is inherently unrealistic, because of beat-to-beat variability. Protocols that average multiple replicate measurements improve consistency of optimisation, but still with any of these methods, dozens or hundreds of replicates would be needed for realistic optimisation. Use as selection criteria for implantation may also need such multiplicate averaging.

Research paper thumbnail of Pain and systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by heterogeneous clinic... more Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by heterogeneous clinical manifestations involving virtually the entire body. The pain in SLE can have different causes. The SLE classification criteria include mainly the musculoskeletal manifestations of pain, which are commonly reported as initial symptoms of SLE, such as arthralgia, arthritis and/or myalgia. Chronic widespread pain, which is typical of fibromyalgia (FM), is frequently associated with SLE. The aim of this review is to describe widespread pain and fatigue in SLE, and the association of SLE and FM. Although secondary FM is not correlated with the disease activity, it may interfere with the daily activities of SLE patients. Therefore it is necessary to identify its symptoms and treat them promptly to improve the quality of life of patients. In conclusion, it is essential to identify the origin of pain in SLE in order to avoid dangerous over-treatment in patients with co-existing widespread pain and FM.

Research paper thumbnail of Pharmakon or The Art That Heals: Trans-disciplinary artistictransformative workshops for fibromyalgia syndrome

Villani, 2023

Our research focused on the idea that art, when used in a transformative way (TA), can generate d... more Our research focused on the idea that art, when used in a transformative way (TA), can generate decisive and lasting changes.
Theoretical assumptions

  1. Approach FMS as a complex disease, hypothesizing its traumatic origin and a deficiency of the endocannabinoid system (ECS) resulting from organic, psycho-physical, interpersonal or environmental
  2. The transformative artistic experience (TA) can induce a change in thoughts, generating strong motivating and challenging beliefs (self-esteem and self-awareness), conditioning I behaviors towards generating novel responses to the same initial thoughts and actions, in one sort of "virtuous" circle, adaptive rather than maladaptive, with lasting and/or irreversible.
  3. Use art as an empowerment tool, considering the sick person as the first and fundamental "operator" of the care work for your health.

Our research shows that art, experienced as TA, leads to significant improvements of the psychophysical condition of FMS patients. TA can be seen as a crucial mediator for overcoming the trauma/stressors, probably through the generation of “pivotal mental states” (PIMS), defined as a "hyper-plastic state aiding rapid and deep learning that can mediate psychological transformation” .

Research paper thumbnail of Cost effectiveness analysis of disease modifying antirheumatic drugs in rheumatoid arthritis

Rheumatology International, 2007

The cost effectiveness of treatments that have changed the "natural history" of a chronic progres... more The cost effectiveness of treatments that have changed the "natural history" of a chronic progressive disease needs to be evaluated over the long term. Disease-modifying antirheumatic drugs (DMARDs) are the standard treatment of rheumatoid arthritis (RA) and should be started as early as possible. A number of studies have shown that they are effective in improving disease activity and function, and in joint damage. Our review was focused on revision and critical evaluation of the studies including the literature on cost effectiveness of DMARDs (cyclosporine A, sulphasalazine, leflunomide, and methotrexate). The European League Against Rheumatism (EULAR) recommendations showed that traditional DMARDs are cost effective at the time of disease onset. They are less expensive than biological DMARDs and can be useful in controlling disease activity in early RA.

Research paper thumbnail of Factors correlated with improvement of endothelial dysfunction during rituximab therapy in patients with rheumatoid arthritis

Biologics: Targets and Therapy, 2013

Increased cardiovascular mortality has been associated with rheumatoid arthritis (RA). There are ... more Increased cardiovascular mortality has been associated with rheumatoid arthritis (RA). There are reports indicating that tumor necrosis factor (TNF) blockers may exert favorable but transient effects on the lipid profile, flow-mediated vasodilatation (FMD) of the brachial artery, and the common carotid intima-media thickness (ccIMT) in RA. We evaluated 38 RA patients (33 females and five males with a mean age of 66.7 ± 10.2 years) who were unresponsive to TNF blockers. The patients received one or more courses of two rituximab (RTX) 1000 mg infusions. Disease activity was evaluated at each visit. Investigations included erythrocyte sedimentation rate, C-reactive protein (CRP) levels, the 28-joint disease activity score (DAS28), DAS28CRP, the Health Assessment Questionnaire, the FMD percent change from baseline (FMD%), and the postnitroglycerine endothelium-independent vasodilatation. In comparison with the baseline, there was a significant improvement in clinical variables and acute-phase reactants 24 months after the start of RTX therapy. There was also a major improvement in FMD% (from baseline 5.24 ± 1.12 to 5.43 ± 1.16; P =-0.03) and a smaller change in the ccIMT (from baseline 0.69 ± 0.16 to 0.67 ± 0.12 mm P = 0.25). Univariate analysis showed that global health (P , 0.034) was associated with the improvement in FMD%. Multivariate models showed that GH (odds ratio [OR] 0.91; 95% CI: 0.99-0.83; P = 0.032), CD19+ cells (OR 1.024; 95% CI: 1.045-1.003; P = 0.025), IgM (OR 1.025; 95% CI: 1.045-1.004; P = 0.016), and interleukin (IL)-8 (OR 0.487; 95% CI: 0.899-0.264; P = 0.021) were statistically associated with the improvement of FMD%, and that IL-8 (OR 0.717; 95% CI: 0.926-0.555; P = 0.018) was also statistically associated with improvement of ccIMT. The findings of the study confirm that RTX reduces the progression of accelerated atherosclerosis in patients with RA. They also show that improvement in CD19+ cells, IgM and GH after treatment are statistically associated with the improvement of FMD%, and that improvement in IL-8 levels after treatment is statistically associated with improved FMD% and with decrease in the ccIMT.

Research paper thumbnail of Validity and Reliability of the Italian Version of the Functioning Assessment Short Test (FAST) in Bipolar Disorder

Clinical Practice & Epidemiology in Mental Health, 2012

Background:Functioning Assessment Short Test (FAST) is a brief instrument designed to assess the ... more Background:Functioning Assessment Short Test (FAST) is a brief instrument designed to assess the main functioning problems experienced by psychiatric patients, specifically bipolar patients. It includes 24 items assessing impairment or disability in six domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships and leisure time. The aim of this study is to measure the validity and reliability of the Italian version of this instrument.Methods:Twenty-four patients with DSM-IV TR bipolar disorder and 20 healthy controls were recruited and evaluated in three private clinics in Cagliari (Sardinia, Italy). The psychometric properties of FAST (feasibility, internal consistency, concurrent validity, discriminant validity (patients vs controls and eutimic patients vs manic and depressed), and test-retest reliability were analyzed.Results:The internal consistency obtained was very high with a Cronbach's alpha of 0.955. ...

Research paper thumbnail of A Comparison of Dothiepin versus Placebo in the Treatment of Pain in Rheumatoid Arthritis and the Association of Pain with Depression

Journal of International Medical Research, 1988

The effectiveness of dothiepin (a tricyclic anti-depressant) at a dose of 75 mg given orally at n... more The effectiveness of dothiepin (a tricyclic anti-depressant) at a dose of 75 mg given orally at night was compared with placebo for 4 weeks in alleviating pain in 60 patients with classical or definite active rheumatoid arthritis. Patients were classified as either ‘depressed’ or ‘not depressed’. The week before, during and 2 weeks after the study, 600 mg ibuprofen was given orally three times daily to all patients. Compared with placebo, dothiepin produced a significant reduction in daytime pain by the end of the treatment period. The Hamilton rating scale in ‘depressed’ patients was significantly improved in patients given dothiepin. The Cassano–Castrogiovanni self-evaluation rating scale in both ‘depressed’ and ‘not depressed’ patients showed a tendency (not significant) to be improved following dothiepin treatment compared with placebo. These results suggest that patients with rheumatoid arthritis may experience an increase in pain symptoms due to an alteration of mood. Therapy ...

Research paper thumbnail of Vaccination with endosomal unknown epitopes produces therapeutic response in rheumatoid arthritis patients and modulates adjuvant arthritis of rats

Journal of translational medicine, Jun 7, 2016

Our previous results showed that intrasynovial Rifamycin SV caused the lysis of synoviocites and ... more Our previous results showed that intrasynovial Rifamycin SV caused the lysis of synoviocites and freed the autoantigens which in turn stimulated the immunoregulatory rather than autoreactive T cell response in rheumatoid patients. Here, we hypothesize that disruption in vitro of peripheral blood mononuclear cells, by freeze/thawing or by lytic action of Rifamycin SV, would induce the release of endosomal pathogenic autoantigens from APCs present in the circulation, which could then be isolated from degrading enzymes by ultrafiltration. The preparation of the ultrafiltrates are based on the rupture of PBMCs (5 × 10(6) cells/mL) by the addition of Rifamycin SV in culture (250 μg/mL), which causes the lysis of 90 % of the cells in 3 h, or by three cycles of freeze/thawing of the PBMC, from -80 °C to room temperature. The lysate and the fragmented cells were then centrifuged and ultrafiltered by passage through a filtration device with a cut-off of 10 kDa. Also the synovial fluid was su...

Research paper thumbnail of FRI0175 Anti-drug-antibodies but not igg-4 antibodies against tnf blockers influence the activity of anti-tnf drugs in rheumatoid arthritis

Annals of the Rheumatic Diseases, 2013

ABSTRACT Background Anti-TNF drugs have changed the clinical course of rheumatoid arthritis (RA),... more ABSTRACT Background Anti-TNF drugs have changed the clinical course of rheumatoid arthritis (RA), but the survival rate and the resistance to the therapy showed that about 30% of RA patients fail to respond to these drugs. Objectives The aim of our study was to evaluate the correlation between the development of anti-drug antibodies and specific IgG-4 antibodies against TNF inhibitors and the resistance to this therapy in RA patients. Methods The retrospective study involved 130 established RA patients [98 females and 32 males, mean age 56,7±12,3 years, disease duration 6,3±1.2] who fail to respond to conventional DMARDs treated with anti-TNF agents [32 pts with INF, 58 pts. with ETN, 40 pts with ADA] with a baseline DAS28 range between 3.2-5.6. After 6 months of treatment according to DAS28 values the patients were classified in remission for DAS28 &lt;2.6 (R) and having low disease activity (LDA) for DAS28 range between 2.6-3.2 or non responder (NR)&gt;3.2. The patients were tested for serum anti-drugs antibodies (Anti TNF-α Blocker ELISA kit Immundiagnostik AG, Bensheim - Listarfish, Milan, Italy) and IgG4 specific antibodies against TNF- inhibitors (ImmunoCAP® Assay fluoroenzyme immuno assay Kit for ImmunoCAP250, Phadia, Uppsala, Sweden). Results After a mean of 6 months in IFN group: 15.65% of the patients were in remission (R ), 31.2 % in LDA and 53.12% NRs; in ETN group 22.41% of the patients in R, 41.37% in LDA, 36.20% NRs, in ADA group 30% of the patients in R, 25% in LDA and 45% NRs. In the INF group the anti-drug antibodies were detected in 21. 87% of the patients and specific IgG-4 antibodies in18%, in ETN group the anti-drug antibodies were detected in 10.34% and specific IgG-4 antibodies in 8.67%, in ADA group the anti-drugs antibodies in 25% and specific IgG-4 antibodies in 5%. The presence of anti-drug antibodies in INF e ADA group correlate with the high percentage of NRs (R:0.032 ;R:0.039). No correlation with the specific IgG-4 antibodies against TNF and clinical response was observed. Conclusions In patients with RA the presence of all anti-drug antibodies but not the specific IgG-4 antibodies against TNF could influence the activity of TNFblockers in particular in INF and ADA group. This study also confirmed the low immunogenecity of ETN. Disclosure of Interest None Declared

Research paper thumbnail of SAT0152 Polymyalgia Rheumatica: A Comparative Study of Methylprednisolone and the Modified Release Prednisone

Annals of the Rheumatic Diseases, 2013

ABSTRACT Background Polymyalgia rheumatica (PM) is a common inflammatory disease that affects eld... more ABSTRACT Background Polymyalgia rheumatica (PM) is a common inflammatory disease that affects elderly patients in Western countries, and is usually treated using glucocorticoid (GC) therapy that still play the major role in the treatment of the disease by rapidly recunding and suppressing inflammation within a few week. The circadian administration of prednisone in rheumatoid arthritis showed that optimizing the timing of GC administration with low-dose modified-release prednisone (MR-P)improves the benefit ratio of long-term GC treatment (CAPRA 1-2 studies). Objectives To compare changes in inflammation markers and their correlations with cortisol levels in PM patients treated with the new MR-P tablet or 6-methylprednisolone (6-MP). Methods The 42 enrolled patients fulfilled the 2012 EULAR/ACR criteria for PM: 17 were treated with 6-MP 12 mg at 8.00 a.m. then gradually tapered to 2 mg/daily (group A: 10 females; mean age 72.5 years), and 25 were treated with MR-P10 mg at 10.00 p.m, tapered to 1 mg (group B: 14 females; mean age 74.6 years). Their erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), fibrinogen, cortisol levels, cytokine (TNF-α and IL6)were measured at baseline and after six months. Circulating cytokine levels were determined using Human IL-6 Instant ELISA Bioscience, Bender, MedSystems, GmbH (Vienna, Austria) and Human TNFa Quantikine immunoassay RD System INC.(Minneapolis, USA). Results The baseline laboratory parameters in group A and B were respectively: ESR 30.6±18.2 vs33.3±17.6 mm/h (p=n.s.); CRP 1.5±1.8 vs2.5±3.6 mg/dL (p=n.s.); fibrinogen 456±161 vs482±160 mg/dL (p=n.s.); cortisol 16.1±7.2 vs11.2±6.2 μg/dL (p=n.s.) and TNF-α1.0±0.6 vs1.2±0.7 pg/mL (p=n.s.). Baseline IL6 values were lower in group A 1.7±1.1 vs4.5±5.0 pg/mL in group B, p&lt;0.01) and abnormal IL6 values at baseline were in eight (47%) group A vs twenty(84%) group B patients (p&lt;0.05). After the first month oftreatment, the decrease in IL-6 levels in group A and B were respectively 50% and 85.7% (p &lt;0.001). After six months of treatment, the same parameters were: ESR 18.2±15.6 vs20.5±16.5 mm/h (p=n.s.); CRP 0.7±0.6 vs0.6±0.8 mg/dL (p=n.s.); fibrinogen 441±101 vs372±85 mg/dL (p=n.s.); cortisol 14.1±5.4 vs11,7±4.8 μg/dL (p=n.s.); TNF-α2.9±7.2 vs3.6±11.4 pg/mL (p=n.s.); and IL-6 1.2±0.5 vs1.6±1.4 pg/mL (p=n.s.). After six months of treatment, there wasn’t a statistically significant difference in the GC dose between group A and group B (3.9±1.8 mg vs3.5±1.8 mg). Conclusions In this non-randomized prospective observational study the response of inflammation markers to low-dose GC was similar in patients with PM treated with 6-MP or MR-P, and morning cortisol levels were unaffected. However, the patients treated with MR-P showed a greater decrease in IL-6 levels after the first month. Disclosure of Interest None Declared

Research paper thumbnail of THU0319 Determination of the Serological Profiles in Anti-Ro-52-Positive Patients with Systemic Autoimmune Rheumatic Diseases

Annals of the Rheumatic Diseases, 2013

Synthesis and characterization of mechanically milled nanocomposites-carbon nanotubereinforced al... more Synthesis and characterization of mechanically milled nanocomposites-carbon nanotubereinforced aluminium ABSTRACT. Ever since the discovery of carbon nanotubes (CNTs), their interesting properties have captured the interest of researchers for commercial applications. Exceptional mechanical properties, with an average elastic modulus of 1-2 TPa and fracture strength of 200 GPa, provide the motivation for CNTs to be used in service conditions requiring high strength-to-weight ratios. The present research aims at the incorporation and characterization of CNT-reinforced aluminium nanocomposites. High energy ball milling was used to embed CNTs in a soft and ductile aluminium matrix. Milled powders having CNTs sandwiched in between aluminium grains were characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD). The results revealed the presence of CNTs at the aluminium powder cold weld interfaces, which was further confirmed by diffraction analysis.

Research paper thumbnail of The treatment of idiopathic and secondary hydrarthrosis of the knee by intra-articular Rifamycin SV

La Chirurgia degli organi di movimento

Fifty-three patients, 28 females and 25 males, aged from 21 to 68 years, affected with mono- and ... more Fifty-three patients, 28 females and 25 males, aged from 21 to 68 years, affected with mono- and bilateral intermittent hydrarthrosis of the knee and of a non-inflammatory nature, were included in an open study. All of the knees involved were treated with intra-articular infiltrations with Rifamycin SV. The weekly dosage of Rifamycin SV was 500 mg; the average duration of treatment was 6 weeks. Follow-up 1 year after the end of treatment showed a decrease or regression in joint effusion in all of the knees treated.

Research paper thumbnail of Old and new criteria for the classification and diagnosis of fibromyalgia: comparison and evaluation

Clinical and experimental rheumatology

ABSTRACT

Research paper thumbnail of Psychometric properties of the Fibromyalgia Assessment Status (FAS) index: a national web-based study of fibromyalgia

Clinical and experimental rheumatology

Fibromyalgia (FM) is a generalized chronic pain condition that is often accompanied by symptoms s... more Fibromyalgia (FM) is a generalized chronic pain condition that is often accompanied by symptoms such as fatigue, sleep disturbances, psychological and cognitive alterations, headache, migraine, variable bowel habits, diffuse abdominal pain, and urinary frequency. Its key assessment domains include pain, fatigue, disturbed sleep, physical and emotional functioning, and patient global satisfaction and health-related quality of life (HRQL). A number of evaluation measures have been adapted from the fields of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, and others such as the Fibromyalgia Assessment Status (FAS) index and the Fibromyalgia Impact Questionnaire (FIQ) have been specifically developed. The aim of this study was to assess the impact of FM on HRQL by comparing the performance of the FAS index, the FIQ and the Health Assessment Questionnaire [HAQ] in 541 female and 31 male FM patients (mean age 50 years; mean disease duration 7.7 years) entered in the ...

Research paper thumbnail of Fibromyalgia: who should reshape the pain perception of these patients?

Research paper thumbnail of Cyclosporine in addition to infliximab and methotrexate in refractory rheumatoid arthritis

Clinical and experimental rheumatology

Research paper thumbnail of Effect of adalimumab on neutrophil function in patients with rheumatoid arthritis

Arthritis research & therapy, 2005

Neutrophils are known to be targets for the biological activity of tumour necrosis factor (TNF)-a... more 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 adali...

Research paper thumbnail of Chlamydophila psittaci subclinical infection in chronic polyarthritis

Clinical and experimental rheumatology

Recent evidence indicates that Chlamydophila psittaci (Cp) may establish chronic infections, whic... more Recent evidence indicates that Chlamydophila psittaci (Cp) may establish chronic infections, which may promote autoimmunity and/or B cell lymphoproliferation. The presence of a subclinical Cp infection was investigated in 293 patients with chronic inflammatory polyarthritis, including 175 patients with rheumatoid factor (RF)-positive and/or anti-CCP-positive rheumatoid arthritis (RA) and 118 with seronegative polyarthritis (46 RF-negative/anti-CCP-negative RA, 36 psoriatic arthritis and 36 undifferentiated spondyloarthritis). One hundred and eighty-five healthy controls were also investigated. The presence of Cp infection was assessed in peripheral blood mononuclear cells using several PCR protocols targeting different regions of the Cp genome (16S-23S spacer rRNA, OMP-A, and Gro-EL). The DNA of other Chlamydia species (C. Pneumoniae and C. Trachomatis) was also investigated. Amplicons were sequenced to confirm the specificity of PCR products. The presence of a subclinical chronic C...

Research paper thumbnail of 2 Prevalence of mixed cryoglobulinaemia Q 4 syndrome and circulating 3 cryoglobulins in a population-based survey: The Origgio study

Research paper thumbnail of Pain in fibromyalgia and related conditions

Reumatismo, 2014

Pain is the hallmark symptom of fibromyalgia (FM) and other related syndromes, but quite differen... more Pain is the hallmark symptom of fibromyalgia (FM) and other related syndromes, but quite different from that of other rheumatic diseases, which depends on the degree of damage or inflammation in peripheral tissues. Sufferers are often defined as patients with chronic pain without an underlying mechanistic cause, and these syndromes and their symptoms are most appropriately described as “central pain”, “neuropathic pain”, “nonnociceptive pain” or “central sensitivity syndromes”. The pain is particular, regional or widespread, and mainly relates to the musculoskeletal system; hyperalgesia or allodynia are typical. Its origin is currently considered to be distorted pain or sensory processing, rather than a local or regional abnormality. FM is probably the most important and extensively described central pain syndrome, but the characteristics and features of FM-related pain are similar in other disorders of particular interest for rheumatologists, such as myofascial pain syndromes and t...

Research paper thumbnail of Poster session II * Thursday 9 December 2010, 14:00-18:00

European Journal of Echocardiography, 2010

Background: In optimisation of CRT (and even selection for implantation) we may underestimate the... more Background: In optimisation of CRT (and even selection for implantation) we may underestimate the impact of beat-to-beat variation on echo measurements. This can be quantified in the optimisation process, in which genuine small changes in cardiac function (signal) must be detected amongst beat-to-beat variation (noise). Methods and Results: To focus on biological variability we performed 2046 echo measurements in 11 patients by separate, replicate measurements at a series of interventricular delays of each potential optimisation modality including (i)3D SDI, (ii)aortic pre-ejection time, (iii)IVMD, (iv)LVOT VTI and (v)ECG. The equivalent of 31 optimisations per patient were performed. For single measurements at each setting, agreement between successive optimisations was low: 38% for SDI, 46% for aortic pre-ejection time, 30% for IVMD, 40% for LVOT VTI and 58% for ECG. Agreement between two methods,was similarly low, with agreement between optima being 20%. Guesswork would have given 17%. The intraclass correlation coefficient was low for all methods at 0.11, 0.48, 0.33, 0.40 and 0.52 respectively. Changing the protocol to average multiple measurements numerically improved agreement between successive optima. The intraclass correlation coefficients improved to 0.21(p ¼ ns), 0.70(p ¼ 0.002), 0.50(p ¼ 0.013), 0.52(p ¼ 0.012) and 0.65(p ¼ 0.012) respectively. Conclusions: Attempting optimisation of interventricular delay using single measurements at each setting is inherently unrealistic, because of beat-to-beat variability. Protocols that average multiple replicate measurements improve consistency of optimisation, but still with any of these methods, dozens or hundreds of replicates would be needed for realistic optimisation. Use as selection criteria for implantation may also need such multiplicate averaging.

Research paper thumbnail of Pain and systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by heterogeneous clinic... more Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by heterogeneous clinical manifestations involving virtually the entire body. The pain in SLE can have different causes. The SLE classification criteria include mainly the musculoskeletal manifestations of pain, which are commonly reported as initial symptoms of SLE, such as arthralgia, arthritis and/or myalgia. Chronic widespread pain, which is typical of fibromyalgia (FM), is frequently associated with SLE. The aim of this review is to describe widespread pain and fatigue in SLE, and the association of SLE and FM. Although secondary FM is not correlated with the disease activity, it may interfere with the daily activities of SLE patients. Therefore it is necessary to identify its symptoms and treat them promptly to improve the quality of life of patients. In conclusion, it is essential to identify the origin of pain in SLE in order to avoid dangerous over-treatment in patients with co-existing widespread pain and FM.