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Biomedical subjects

U Fiocco

Publications and source records attributed to U Fiocco.

28 records · Page 2Linked to original sources
PubMedDate not supplied

[Infections in patients with rheumatoid arthritis receiving anti-cytokine therapy: biological mechanisms and clinical aspects].

Different animal studies show that several proinflammatory cytokines are essential for natural resistance to specific infections, particularly versus intracellular organisms. However, uncontrolled overproduction of some proinflammatory cytokines, in diseases such as rheumatoid arthritis, can be just as dangerous to the host as the absence of the same cytokines. Reduction in the production and/or activities of proinflammatory cytokines in rheumatoid arthritis remains a therapeutic objective for many patients. The tumour necrosis factor-alpha (TNF-alpha) blockers infliximab, etanercept and adalimumab and the recombinant interleukin 1 (IL-1) receptor antagonist anakinra are effective in patients with active rheumatoid arthritis. However, there is a growing body of clinical evidence that neutralization of TNF-alpha is associated with an increased risk of opportunistic infections, including mycobacterial diseases. Blockade of IL-1 activity with the IL-1 receptor antagonist (IL-1Ra) appears, at present, to be relatively safe. Postmarketing experience and pharmacovigilance programs are necessary to determine the overall safety profile of the new agents. At this time, treating physicians must weigh carefully the benefits of biologics against their safety, particularly in patients at risk of infection.

Adalimumab↗
PubMedDate not supplied

[IL-1Ra (recombinant human IL-1 receptor antagonist) in the treatment of rheumatoid arthritis: the efficacy].

Interleukin 1 receptor antagonist (IL-1Ra) is a naturally occurring IL-1 inhibitor, acting as a "receptor antagonist", which blocks IL-1 mediated signal transduction. In 1990 IL-1Ra was cloned and later on, a large numbers of studies led to disclosure of the crucial importance of the imbalance between IL-1 and IL-1Ra in the pathogenesis of rheumatoid arthritis (RA). In 1991, almost 8 years after the initial isolation of IL-1, recombinant IL-1Ra (IL-1ra, Kineret) was introduced in clinical trials involving patients with RA. Between 2001 and 2002 IL-1ra was approved by the US Food and Drug Administration and by the European Agency for the Evaluation of the Medicinal Products and in 2003 it was registered in Italy, too. In RA recombinant IL-1ra has been evaluated in 5 randomized, placebo-controlled clinical trials involving more than 2900 patients. Two of the trials involved the use of IL-1ra as monotherapy versus placebo and two trials in combination with methotrexate (MTX); the last trial explored the use of a fixed 100 mg/day IL-1ra dosage in a RA patient population including a wide array of co-morbid conditions as well as concomitant medications. The studies confirmed both the efficacy and the safety of IL-1ra in patients with active and severe RA. 43% of patients receiving 150 mg/day IL-1ra achieved a 20% response according to the American College of Rheumatology criteria (ACR20), compared to 27% in the placebo group. In the MTX combination therapy study, 42% of the patients receiving 1 mg/Kg/day of IL-1ra achieved an ACR20, 24% an ACR50 and 10% an ACR70. In each study, significant improvements in the Health Assessment Questionnaire scores (HAQ) were observed. There were rapid gains in the number of days at work or domestic activity in the treated patients, and the increases in productivity were dose related. At early 24 weeks, there was significant reduction of both the score for progression of joint space narrowing (JSN) and the Total modified Sharp-Genant score (a combination of erosion and JSN) in all treatment groups (30,75 and 150mg/day). The clinical benefits of treatment with daily subcutaneous injections of IL-1ra in active RA patients were maintained for up to 48 weeks. IL-1ra, a selective inhibitor of the IL-1 pathway, represents an important new biologic approach to treating patients with RA, that significantly reduces clinical signs and symptoms of the disease and joint destruction and has proved safe and well tolerated also in combination with other DMARDs and concomitant medications.

Arthritis, Rheumatoid↗
PubMedDate not supplied

[Antinuclear, anti-dsDNA and anti-ENA antibodies in patients affected with rheumatoid arthritis or ankylosing spondylitis during treatment with infliximab].

OBJECTIVE: We evaluated the induction and clinical significance of ANA, anti-dsDNA and anti-ENA during infliximab therapy in patients with Rheumatoid Arthritis (RA) or Ankylosing Spondylitis (AS). METHODS: We tested sera from 30 RA and 30 AS patients before and during treatment with infliximab. ANA and antidsDNA were determined by indirect immunofluorescence and anti-ENA by an "in house" counterimmunoelectrophoresis. Statistical analysis was performed by X2 and McNemar's tests and U-test of Mann-Whitney. RESULTS: Eight of the 30 RA patients and 1 of the 30 AS patients were positive for ANA before treatment with infliximab. Eighteen of the 22 (81.8%) negative patients with RA and 11 of the 29 (37.9%) negative patients with AS became positive for ANA during infliximab treatment. No ANA positive patients became negative during the therapy. The difference between ANA before and after treatment resulted significant in both RA and AS patients (p=0.001). The frequency of anti-dsDNA and anti-ENA did not change significantly from baseline, in both RA and AS patients. Acquired ANA positivity was not associated with clinical signs of lupus syndrome and was not correlated with adverse events. The mean values of ESR and CRP in RA patients who became positive for ANA were significantly decreased (p=0.01 and p=0.02 respectively). CONCLUSIONS: Infliximab treatment induced a significant increase in the frequency of ANA in RA and AS patients. The significance of ANA development in these diseases is at present unknown. The significant decrease of ESR and CRP in RA patients who became positive for ANA after treatment should be investigated in a larger number of patients.

Anti-Inflammatory Agents↗
PubMedDate not supplied

[Intra-articular treatment with the TNF-alpha antagonist, etanercept, in severe diffuse pigmented villonodular synovitis of the knee].

Pigmented villonodular synovitis (PVNS) is a rare pre-malignant disease that require aggressive treatment as surgical synovectomy, eventually followed by radiosynovectomy. Nevertheless, the disease often reoccurs after these treatments. To determine the safety and efficacy of intra-articular (IA) TNFalpha blockade with etanercept (ETN), before extended arthroscopic synovectomy, in severe PVNS of the knee, two patients, (a 26-year-old man with B27+ undifferentiated spondylarthropathy and a 32-year-old femal with seronegative oligoarthritis), affected by diffuse knee PVNS (diagnosis made by histological examination), resistant to IA corticosteroid injections and to repeated arthroscopic synovectomy, were submitted, after protocol approval by human research committee and patient's written informed consent to intra-articular etanercept (IA-ETN) treatment with a different dosage schedule: 12.5 mg weekly IA-ETN injection for 4 weeks, followed by extended arthroscopic synovectomy and of 25 mg IA-ETN injection for 4 weeks, respectively. Previous DMARDs treatment was continued in stable appropriate doses. Any adverse events were recorded throughout the study. The following parameters were considered as clinical endpoints: 1) Knee Joint Index (KJI: range 0-14); 2) Thompson index (THI: range 0-9) At the study entry and at the end of follow-up, high frequency ultrasound grey scale synovial thickening (US-ST) was also assessed. No adverse events were observed due to IA-ETN and to arthroscopic synovectomy. Marked improvement of knee disease activity over time and sustained functional recover was obtained. US-ST evaluation before treatment initiation and at the end of follow-up confirmed the regression of knee joint synovial proliferation.

Adult↗
PubMedDate not supplied

Fructose-induced hyperuricemia in psoriasis and psoriatic arthritis.

Acute intravenous infusion of fructose was given to 30 normal subjects and 27 normo-uricemic patients affected by psoriasis, 12 with cutaneous involvement only and 15 with psoriatic arthritis. Serum uric acid was measured before and after infusion. A significantly lower increase in serum uric acid levels was found in psoriatic patients in comparison to controls, and the increase rate appeared to be significant only in controls. Moreover, the overall fructose-induced hyperuricemia was significantly lower in the group of patients with psoriatic arthritis than in normal subjects. Since the fructose-induced increase of serum uric acid is most probably achieved by an augmented turnover of preformed purine nucleotides, it is suggested that in normouricemic patients with psoriasis the "pool" of purine nucleotides is lower than normal. Such a condition seems to be more evident in psoriatic arthritis.

Adolescent↗
PubMedDate not supplied

Therapy of acute pancreatitis in systemic lupus erythematosus with plasmapheresis and corticosteroids.

A 24-year-old woman with systemic lupus erythematosus had, after reduction of corticosteroid therapy, a severe relapse of the disease with hepatitis, nephritis and pleurisy. After admission to the hospital, she was given 60-80 mg/day of prednisone and acute pancreatitis developed on the third day. Plasmapheresis, followed by injection of 1 g of methylprednisolone, was started. This combined therapy induced a prompt and complete recovery in a few days.

Acute Disease↗
PubMedDate not supplied

Effect of D-penicillamine on the T cell phenotype in scleroderma. Comparison between treated and untreated patients.

To investigate the possible immunomodulatory mechanism of D-penicillamine in Scleroderma (Scl), we analysed the surface phenotype of circulating T lymphocytes in 17 Scl patients, 6 of these studied before and after D-penicillamine treatment, 8 only before and 3 only after treatment. The drug was administered for 6 to 24 consecutive months with a median daily dose of 500 mg. The study of peripheral blood purified T cells was carried out using single-colour immunofluorescence and flow cytometry analysis (Ortho Diagnostic System) with monoclonal antibodies such as OKT4 (CD4, helper/inducer), OKT8 (CD8, cytotoxic/suppressor), OKDR and MLR4 (activated T cells), and Tec-5/9 (CD26, activated T cells with specific helper function for B cell differentiation). All of the patients showed lower CD8+ and higher MLR4+ and DR+ T cells than the controls, while CD26+ and CD4+ circulating T lymphocytes were lower in all of the treated in comparison with all of the untreated patients. A decrease in CD26+, CD4+ and total T cells was also observed after treatment in the 6 patients studied pre- and post-therapy. These results support the hypothesis that D-penicillamine selectively impairs the helper T cell subset in Scl patients.

Adult↗