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N Pipitone

Publications and source records attributed to N Pipitone.

At least 19 recordsLinked to original sources
PubMed2005

A two year randomised controlled trial of intramuscular depot steroids in patients with established rheumatoid arthritis who have shown an incomplete response to disease modifying antirheumatic drugs.

BACKGROUND: In rheumatoid arthritis (RA), intramuscular (IM) pulsed depomedrone expedites an immediate response to disease modifying antirheumatic drugs (DMARDs). Although IM depomedrone is also widely used to treat disease flares in patients treated with DMARDs, its effect on radiological progression has not been assessed. OBJECTIVE: To evaluate the benefits of 120 mg IM depomedrone versus placebo in patients with established RA whose disease was inadequately controlled by existing DMARDs. METHODS: In a 2 year prospective randomised controlled trial patients were assessed using the ILAR/WHO core dataset, disease activity score (DAS28), x ray examination of hands and feet scored by Larsen's method, and bone densitometry. RESULTS: 291 patients with RA were screened, 166 were eligible, and 91 consented and were randomised. Disease activity improved more rapidly in the steroid treated patients than with placebo, but after 6 months no difference remained. A small but significant reduction in erosive damage in the steroid group compared with placebo was also found. More adverse reactions occurred in the steroid treated group than in the placebo patients (55 v 42), especially those reactions traditionally related to steroids (16 v 2), including vertebral fracture, diabetes, and myocardial infarction. Hip bone density fell significantly in steroid treated but not placebo patients. CONCLUSIONS: IM depomedrone improved disease activity in the short term and produced a small reduction in bone erosion at the cost of a significant increase in adverse events. Despite the initial benefit of IM depomedrone, when patients respond suboptimally to a DMARD they should not be given long term additional steroids but should be treated with alternative or additional DMARDs.

Adult↗
PubMed2005

Behçet's disease and cardiovascular involvement.

Behcet's disease (BD) is a multisystem disease of unknown etiology characterized by chronic relapsing orogenital ulcers, uveitis and systemic involvement including articular, gastrointestinal, cardiopulmonary, neurological and vascular pathology. The incidence and nature of cardiac involvement are not clearly elucidated. Cardiovascular manifestations have been reported in 7-46% of patients and mortality occurs in up to 20% of those patients with marked vascular involvement. Sporadic cases of endocarditis, myocarditis, pericarditis, acute myocardial infarction, aortic aneurysm, ventricular thrombosis, congestive cardiomyopathy and valvular dysfunction have been reported. This review discusses the general aspects of the pathogenic mechanisms and clinical features cardiovascular involvement in BD, and provides the data of cardiovascular involvement in a cohort of Italian BD patients.

Behcet Syndrome↗
PubMed2004

Clinical manifestations of Behçet's disease in 137 Italian patients: results of a multicenter study.

OBJECTIVE: To determine the type and frequency of clinical features of Behçet's disease in a population of Italian patients. METHODS: We retrospectively studied 137 Italian patients (76 males and 61 females, age at onset 29.6 +/- 12.2 [mean +/- SD] years) seen consecutively in nine different referral centers. The duration of follow-up at study entry was 10.9 +/- 8.2 years. Virtually all patients fulfilled the classification criteria developed by the International Study Group for Behçet's disease. The clinical manifestations of the patients were recorded by the attending physicians using specifically designed forms. RESULTS: The most frequent manifestations at disease onset were oral (78.3%) and genital aphthae (29.2%) followed by inflammatory ocular involvement (20%) and arthritis (14.2%). The commonest (>50% of cases) manifestations observed throughout the disease course were oral aphthae (99.3%), genital aphthae (62.8%), various cutaneous lesions including erythema nodosum (81.8%), and inflammatory ocular disease (60.6%). Panuveitis and posterior uveitis/retinitis occurred more frequently in males compared with females (28.9% versus 11.5% and 57.9% versus 36.1%, respectively; p < 0.05). 61.6% of our patients were HLA-B51 positive. CONCLUSION: Behçet's disease in Italian patients is characterized by a variety of clinical manifestations in agreement with the medical literature. Panuveitis and posterior uveitis/retinitis occur more frequently in male patients.

Adult↗
PubMed2003

Current concepts and new developments in the treatment of psoriatic arthritis.

OBJECTIVES: Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy characterized by the association of arthritis with psoriasis. Many agents have been proposed for the treatment of PsA, but their use is based more on clinical experience than on sound scientific evidence. METHODS: We reviewed MedLine up to November 2002, searching for 'psoriatic arthritis', 'drug therapy, 'controlled trials' and 'outcomes' and all possible acronyms for these terms. All relevant papers were then examined in detail. RESULTS: PsA is a condition that runs a variable clinical course. Mild forms can usually be controlled by non-steroidal anti-inflammatory drugs (NSAIDs). Intra-articular glucocorticoid injections are indicated in patients with persistent mono- or oligoarthritis. Patients with severe and progressive articular disease not responsive to NSAIDs should be treated with disease-modifying anti-rheumatic drugs (DMARDs) to prevent joint damage and disability. Currently, methotrexate and sulphasalazine are considered the DMARDs of choice, but the evidence for the use of methotrexate in PsA is still largely empirical, while the clinical benefit induced by sulphasalazine appears to be modest. Other DMARDs proposed for the treatment of PsA include cyclosporin, gold salts and, more recently, leflunomide. However, none of the DMARDs available to date are effective in the treatment of psoriatic pelvispondylitis; in addition, a number of patients with severe peripheral arthritis fail to respond to standard DMARDs. Recently, tumour necrosis factor alpha inhibitors have proved effective in many PsA patients with pelvispondylitis or recalcitrant peripheral synovitis. CONCLUSIONS: None of the current treatments for PsA is curative, but significant clinical amelioration can be achieved in the vast majority of patients. Identification and prompt treatment of patients with severe articular disease is crucial for the achievement of a satisfactory clinical response and the improvement of the long-term outcome.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

[Role of chemokines in the pathogenesis of chronic synovitis during rheumatoid arthritis].

Chemokines play a central role in the pathogenesis of rheumatoid arthritis (RA) synovitis which is characterised by new blood vessel formation, thickening of the lining layer and infiltration of immune cells. The inflammatory infiltrate is generated by a series of events which include the recruitment of leukocytes from the blood stream into the tissue, their local retention and activation to effector cells. All these processes are finely regulated by the interplay of different cell adhesion molecules (CAMs) and chemoattractant factors called chemokines (CK). CK are a superfamily of small proteins that play a crucial role in immune and inflammatory reactions. These chemoattractant cytokines share structural similarities including four conserved cysteine residues which form disulphide bonds in the tertiary structure of the proteins. CK mediate their effects by binding specific receptors (CK-R) characterised by a domain structure which spans the cell membrane seven times and signal through heterotrimeric GPT-binding proteins. Activation of the CK network results in an amplification of the inflammatory cascade and consequently in the progressive destruction of RA joints. The recognition of the central role of CK in inflammation has paved the way to the development of new agents capable of interfering with CK and CK-R. This review will focus in particular on the role of CK in regulating leukocyte trafficking in RA joints.

Arthritis, Rheumatoid↗
PubMed2001

The glucocorticoid inhibition of LFA-1 and CD2 expression by human mononuclear cells is reversed by IL-2, IL-7 and IL-15.

Glucocorticoids are agents endowed with powerful immunosuppressive and anti-inflammatory properties partially related to the inhibition of adhesion-related processes. We have previously demonstrated that glucocorticoids inhibit LFA-1 and CD2 expression in human peripheral blood mononuclear cells (PBMC) by down-regulating mRNA steady-state levels. In this study, we investigated whether glucocorticoids could also act indirectly by modulating the effect/function of cytokines whose expression are known to inhibit. To test this hypothesis, we replenished the following cytokines IL-2, IL-7, IL-15, TNF-alpha, IL-1beta, IL-4 and IL-10, in an in vitro PBMC culture system. Our results indicate that only the IL-2Rgamma-chain-dependent cytokines IL-2, IL-7 and IL-15, among the cytokines of this panel, could reverse the inhibition of glucocorticoids on PBMC adhesion molecule expression and the related functions of intercellular aggregation and proliferation. Furthermore, we also demonstrated that IL-2, IL-7 and IL-15 could induce de novo the synthesis of LFA-1 and CD2. Taken together, these data suggest that glucocorticoids inhibit PBMC LFA-1 and CD2 expression not only directly by modulating transcriptional events, but also indirectly through the inhibition of IL-2Rgamma-dependent cytokines.

CD2 Antigens↗
PubMed2001

Magnetic pulse treatment for knee osteoarthritis: a randomised, double-blind, placebo-controlled study.

We assessed the efficacy and tolerability of low-frequency pulsed electromagnetic fields (PEMF) therapy in patients with clinically symptomatic knee osteoarthritis (OA) in a randomised, placebo-controlled, double-blind study of six weeks' duration. Patients with radiographic evidence and symptoms of OA (incompletely relieved by conventional treatments), according to the criteria of the American College of Rheumatology, were recruited from a single tertiary referral centre. 75 patients fulfilling the above criteria were randomised to receive active PEMF treatment by unipolar magnetic devices (Medicur) manufactured by Snowden Healthcare (Nottingham, UK) or placebo. Six patients failed to attend after the screening and were excluded from analysis. The primary outcome measure was reduction in overall pain assessed on a four-point Likert scale ranging from nil to severe. Secondary outcome measures included the WOMAC Osteoarthritis Index (Likert scale) and the EuroQol (Euro-Quality of Life, EQ-5D). Baseline assessments showed that the treatment groups were equally matched. Although there were no significant differences between active and sham treatment groups in respect of any outcome measure after treatment, paired analysis of the follow-up observations on each patient showed significant improvements in the actively treated group in the WOMAC global score (p = 0.018), WOMAC pain score (p = 0.065), WOMAC disability score (p = 0.019) and EuroQol score (p = 0.001) at study end compared to baseline. In contrast, there were no improvements in any variable in the placebo-treated group. There were no clinically relevant adverse effects attributable to active treatment. These results suggest that the Medicur unipolar magnetic devices are beneficial in reducing pain and disability in patients with knee OA resistant to conventional treatment in the absence of significant side-effects. Further studies using different types of magnetic devices, treatment protocols and patient populations are warranted to confirm the general efficacy of PEMF therapy in OA and other conditions.

Adult↗
PubMed2001

[Articular involvement in the course of primary hypogammaglobulinemia].

The Authors describe the main features of the most common forms of primary hypogammaglobulinaemia (PH) focusing on the articular involvement. Patients with Bruton's agammaglobulinemia (BA) and common variable immune deficiency (CVID) are predisposed to develop septic arthritis (including arthritis due to atypical microorganisms such as mycoplasma), arthralgia and symmetrical (usually non-erosive) polyarthritis. In BA and CVID complicated by recurrent infections, amyloidosis, which may be itself a cause of arthropathy, can occur. In addition, patients with CVID and selective IgA deficiency show an increased prevalence of juvenile rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome and primary biliary cirrhosis, while patients with selective IgA deficiency are prone to developing seronegative spondylarthropathies, including ankylosing spondylitis. The mainstay of treatment for BA and CVID is replacement therapy with human immunoglobulins. Septic arthritis should be promptly treated with antibiotics, whereas other types of arthritis usually respond well to non-steroidal antiinflammatory medications. In contrast, the second line agents commonly used to treat rheumatoid arthritis do not appear to be beneficial in patients with PH-associated arthritis.

Agammaglobulinemia↗
PubMed2001

[Rheumatoid arthritis. Recent findings and new pathogenic concepts].

The etiology of rheumatoid arthritis (RA) is still unknown, and many uncertainties regarding its pathogenetic mechanisms persist. During the past decade, various hypotheses have been advanced, yet none of these has been able to explain the complexity of the disease. In light of the most recent research, a sub-division of the pathogenesis of RA, in four phases, has been proposed. The first phase is that of tissue damage, induced by unknown infective or traumatic factors with the liberation of possible arthrogenic antigens that are presented to the immune system. In the second phase the immune and inflammatory mechanisms should begin to function and, if they are effective, they should determine the resolution of the process; the failure of these mechanisms would create a further amplification of the immuno-inflammation response (the third phase). The fourth phase would then be a chronic inflammatory with progressive articular destruction, as well as anatomical and functional damage. This evolution, in response to common pathogenic agents, is dependent upon a particular hereditary genetic asset (not only the HLA system) that is able to control the production of citokines and also upon the neuroendocrine system. The final outcome of the process is, therefore, determinated by multiple interference between the inflammatory/immune system and other systems that also interact with it (the integrated pathogenetic hypothesis). This hypothesis reflects the complexity of the immune/inflammatory system that must be considered to be an acting part of an integrated network of diverse systems. A better knowledge of these interactions needed for the discovery of potential new therapies for RA.

Arthritis, Rheumatoid↗
PubMed2000

Do B cells influence disease progression in chronic synovitis? Lessons from primary hypogammaglobulinaemia.

We describe a 62-yr-old male patient with primary hypogammaglobulinaemia (PH) who fulfilled the 1987 American Rheumatism Association/American College of Rheumatology revised diagnostic criteria for rheumatoid arthritis (RA) but, despite persistent symmetrical synovitis, did not develop erosions. Virology studies and blood and synovial fluid (SF) cultures were consistently negative; a search for crystals in the SF was unrevealing. Peripheral blood (PB) B cells were absent, whilst the PB CD3(+) cell count was normal. The ratio of naive (CD45RA(+)) to memory (CD45R0(+)) cells was also normal (1:1) but the CD4:CD8 ratio was reversed. To our knowledge, this is the first report which combines the immunophenotypic analysis of the PB with that of the SF and synovial membrane (SM). This confirmed the absence of B cells and the reversed CD4:CD8 ratio. However, as in other chronic arthropathies, the SF and SM cellular infiltrate consisted almost exclusively of memory T cells, consistent with the preferential localization of this subset to inflamed tissues. This case indicates that synovitis can proceed persistently in the absence of B cells and that the migratory mechanisms of T cells are not altered. However, the case suggests that the absence of B cells and negativity for rheumatoid factor, combined with an increased presence of CD8(+) (suppresser/cytotoxic) T cells in the joint, might contribute to the non-erosive nature of the synovitis.

Agammaglobulinemia↗
PubMed2000

Psoriatic arthritis.

Explore the source record for details and available documents.

Arthritis, Psoriatic↗
PubMed1999

The inhibitory effect of dexamethasone on lymphocyte adhesion molecule expression and intercellular aggregation is not mediated by lipocortin 1.

Glucocorticoids exert their anti-inflammatory activity through multiple pathways which include the inhibition of cell adhesion events. The glucocorticoid-induced protein lipocortin 1 (LC1) has reported anti-inflammatory properties and has been proposed as a putative mediator of the anti-inflammatory effects of glucocorticoids. The role of LC1 in mediating the glucocorticoid inhibition of lymphocyte adhesion and cell adhesion molecule (CAM) expression was investigated in vitro using a microaggregation assay, flow cytometry and confocal microscopy. Lymphocytes stimulated for 96 h with plastic-bound OKT3 antibody showed significant increases in LFA-1 and CD2 expression. Dexamethasone (DEX; 10(-6) M) inhibited this increase but the neutralizing anti-LC1 MoAb 1A (5 microg/ml) failed to reverse the DEX effect; neither was purified human LC1 (50 x 10(-9) M) able to inhibit CAM expression. The biological activity of the LC1 was confirmed by its ability to suppress monocyte phagocytosis and respiratory burst in response to bovine serum albumin (BSA)-anti-BSA complexes. OKT3 stimulation of cultured mononuclear cells resulted in intercellular aggregation, scored microscopically using a visual index. This aggregation was completely reversed by 10-6 M DEX but unaffected by LC1 (50 x 10(-9) M). Significant intracellular expression of lymphocyte LC1 was observed using the anti-LC1 MoAb 1B in saponin-permeabilized cells. Distribution of LC1 had a diffuse, cytoplasmic pattern. LC1 expression was reduced following 3 h treatment with 10(-6) M DEX. These findings indicate that the DEX effects on lymphocyte adhesion and CAM expression are not mediated by LC1. Thus the reported in vivo effects of LC1 on leucocyte adhesion and transmigration probably occur through functional/conformation changes of surface CAM, rather than by alteration in expression.

Annexin A1↗
PubMed1998

[Fever of unknown origin in rheumatology].

Fever occurs frequently in several rheumatic disorders, and remains a diagnostic and therapeutic challenge to the rheumatologist in spite of the great advances made in the fields of medical diagnosis and technology. It can be the initial symptom of a rheumatic disease, but it can also be the expression of a disease flare, of an infectious complication, of a secondary neoplasm or be of iatrogenic origin. The pathogenesis of fever in rheumatic diseases is still quite unclear; however, recently IL-1, IL-6 and other endogenous pyrogens, such as Tumor necrosis factor, have been shown to play a pivotal role in causing pyrexia during inflammatory conditions. In the presence of longstanding fever of unknown origin, it is mandatory to carry out a number of selected appropriate examinations with the patient's informed consent. The aim of this study was to review the frequency and the characteristics of fever at the onset and in the course of a number of rheumatic diseases, such as chronic inflammatory arthropathies, connective tissue diseases, reactive arthritis and dysmetabolic arthropathies. Finally, we have reviewed the features of fever during arthritis complicating non-rheumatic diseases and during adverse reactions related to drugs that are widely prescribed for the treatment of rheumatic disorders.

Adult↗
PubMed1997

Corticosteroids inhibit lymphocyte binding to endothelium and intercellular adhesion: an additional mechanism for their anti-inflammatory and immunosuppressive effect.

Glucocorticosteroids (GCS) are potent anti-inflammatory and immunosuppressive agents widely used in the treatment of many medical conditions, but their mechanism of action is not yet fully understood. Some of the anti-inflammatory effects of GCS have been attributed to the synthesis of lipocortins, whereas the immunosuppressive effects are thought to be mediated through the inhibition of several immune functions through a down-regulation of cytokine gene expression. Another important mechanism of action of GCS may relate to their ability to interfere with the phenomena of adhesion and migration of inflammatory cells. In this study, the direct effects of GCS on lymphocyte adhesion capacity in vitro were investigated. We demonstrate that GCS inhibit lymphocyte adhesion to endothelium through the down-modulation of lymphocyte adhesion molecules. We also provide evidence that GCS inhibit cell aggregate formation induced by TCR ligation, which directly correlates with the down-modulation of LFA-1 and CD2, but not LFA-3 or ICAM-1. Such down-modulation was paralleled by a decrease in the steady state mRNA level of LFA-1 and CD2 gene products, which suggests a direct GCS control of the expression of these genes. Finally, we show that GCS effects are mediated through the GCS receptor, since they can be completely reversed by the GCS-R antagonist RU-486. This study supports the concept that some of the immunosuppressive and anti-inflammatory effects of GCS are likely to be exerted by the inhibition of adhesion-dependent lymphocyte functions.

Adrenal Cortex Hormones↗
PubMed1997

[Monoclonal antibody therapy].

Monoclonal antibodies (mAb) are antibodies, produced by cell clones, directed against specific antigens (Ag), which act by binding specifically to the target Ag. Depending on the mAb used, this binding may have different effects on the target (neutralizing, lytic, opsonizing or antibody dependent cytotoxicity, ADCC). In clinical practice, mAb are used as immunosuppressants, antineoplastic agents, or for diagnostic purposes. mAb are given i.v. by slow infusion; the dosage depends on the mAb used. Contraindications include allergic, neoplastic, infective diseases, but also hypertension, cardiac failure and pregnancy. Infusions are usually well tolerated, headache and skin rashes being recorded only rarely; however, little is known about long-term effects (possible derangement of the immune response and/or increase in neoplasms). mAb are potentially a powerful tool in medicine, but more studies are required to define their role and establish their possible adverse effects in humans.

Animals↗
PubMed1996

Cutaneous lymphocyte antigen-positive T lymphocytes preferentially migrate to the skin but not to the joint in psoriatic arthritis.

OBJECTIVE: To investigate whether T cell migration into different sites of inflammation (skin and synovium) within the same individual is principally regulated by tissue-specific homing or by more general mechanisms related to inflammation. METHODS: Expression of cutaneous lymphocyte antigen (CLA) and its ligand, E-selectin, was analyzed by immunohistochemistry and immunofluorescence using paired skin and synovial membrane (SM) samples from patients with psoriatic arthritis (PsA). To investigate disease specificity, delayed-type hypersensitivity (DTH) skin lesions, induced by tuberculin purified protein derivative, and SM from patients with rheumatoid arthritis (RA), were studied as controls. To directly examine cell migration in in vivo, the proportion of CLA+ T lymphocytes migrating into suction-induced skin blisters was assessed by flow cytometry. Using the same technique, levels of paired peripheral blood and synovial fluid (SF) T cells were also analyzed. RESULTS: CLA+ T cells preferentially accumulated in the skin, but not in the joint, of patients with PsA. Similarly, CLA+ T lymphocytes predominated in the DTH skin lesions of RA patients, but were very rare in the SM of RA patients, and were scarcely represented in the SF of patients with several chronic inflammatory arthropathies. In addition, CLA+ T lymphocytes preferentially migrated into epidermal skin blisters. This preferential pattern of CLA+ T cell accumulation was not related to the selective expression of E-selectin, since this was similar in the skin and SM of both PsA and RA patients. CONCLUSION: The distinct pattern of T cell infiltration into sites of inflammation within the skin and synovium is regulated by both organ-specific homing and general inflammation-related mechanisms.

Adult↗