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Biomedical subjects

U Fiocco

Publications and source records attributed to U Fiocco.

At least 19 recordsLinked to original sources

Etanercept and sulfasalazine, alone and combined, in patients with active rheumatoid arthritis despite receiving sulfasalazine: a double-blind comparison.

OBJECTIVE: To compare the efficacy and safety of etanercept and sulfasalazine, alone and in combination, in patients with active rheumatoid arthritis despite sulfasalazine treatment. METHODS: A double-blind, randomised study in adult patients with active rheumatoid arthritis despite stable sulfasalazine (2-3 g/day) treatment. The primary end point was a 20% response by the American College of Rheumatology (ACR) criteria at 24 weeks. RESULTS: At baseline, the three treatment groups (sulfasalazine, n = 50; etanercept, n = 103; etanercept and sulfasalazine, n = 101) were comparable for demographic variables and disease activity. Lack of efficacy was the primary reason for discontinuation (sulfasalazine, n = 12; etanercept, n = 1; etanercept and sulfasalazine, n = 4; p<0.001). Significantly more patients receiving etanercept, alone or in combination (74% for each), achieved ACR 20 responses at 24 weeks than those receiving sulfasalazine (28%; p<0.01). Similarly, more patients in the etanercept groups achieved ACR 50 and ACR 70 responses than those in the sulfasalazine group (p<0.01). In the groups receiving etanercept, significant differences in the ACR core components were observed by week 2 compared with those receiving sulfasalazine alone (p<0.01). The incidences of several common adverse events (headache, nausea, asthenia) were lower with etanercept alone than with the combination (p<0.05), but infections and injection site reactions were higher with etanercept alone (p<0.05). The safety profiles of both etanercept treatment groups were comparable with previous experience of etanercept. CONCLUSIONS: For all efficacy variables assessed, etanercept alone or in combination with sulfasalazine resulted in substantial and similar improvement in disease activity from baseline to week 24 compared with sulfasalazine alone in patients with active rheumatoid arthritis despite their sulfasalazine treatment. All three treatments were generally well tolerated.

Adult↗

[Differences in pharmacology of tumor necrosis factor (TNF) antagonists].

The commercially available inhibitors of TNF are constituted by two classes of molecules: the soluble receptors (Etanercept: Amgen Inc. Wyeth) and the monoclonal antibodies (Adalimumab: Abbott Laboratories and Infliximab: Centocor, Inc.). The differences in their molecular structure, mechanism of action, pharmacokinetics (PK) and pharmacodynamics (PD) are discussed, along with the differences concerning dose, administration regimens, drug concentrations and pharmacological interactions. In order to explain the clinical differences observed when these agents are used in the "real world", which can arise from the respective PK characteristics (kinetics, route and frequency of administration, type of TNF binding, effects on cytokines) and PD responses and peculiar mechanisms of action, with distinctive immune function (LFTα inactivation; apoptosis induction, TNF immunoprecipitation, C1q binding and CDC induction; Fcγ cross-linking and ADCC induction), the dynamics of interaction of the two classes of neutralizing molecules with TNF, and the ability in restoring TNF homeostasis, are outlined.

Adalimumab↗

Rheumatoid and psoriatic knee synovitis: clinical, grey scale, and power Doppler ultrasound assessment of the response to etanercept.

OBJECTIVE: To determine the effect of tumour necrosis factor alpha (TNFalpha) blockade with etanercept in refractory knee joint synovitis (KJS) in rheumatoid and psoriatic arthritis, by local and systemic disease activity assessment and combined grey scale and power Doppler ultrasonographic monitoring. METHODS: 27 knees affected by rheumatoid KJS (n = 12) and psoriatic KJS (n = 8) were assessed before receiving treatment and at 3 and 12 months' follow up. Time dependent clinical changes in disease activity were monitored by C reactive protein, erythrocyte sedimentation rate (ESR), global health status (GHS), and Ritchie (RAI) and knee joint articular (KJAI) indices; synovial changes were monitored by ultrasonographic and power Doppler indices for grey scale synovial thickening and for distinct intrasynovial vessel power Doppler flow configurations (fluid/synovium interface (F/SI-PD) and pannus/cartilage interface (P/CI-PD)). Interobserver and intraobserver variability of grey scale and power Doppler ultrasonographic was evaluated. Response to treatment was assessed by analysis of variance for repeated measures on clinical and ultrasonographic variables. RESULTS: Rapid (3 months) reduction in F/SI-PD flow (p<0.001), parallel to reductions of C reactive protein (p<0.05), ESR (p<0.001), KJAI (p<0.002), RAI, and GHS (p<0.001), was sustained at 12 months when it was accompanied by reduction in both synovial thickening and P/CI-PD flow (p<0.001). No differences (ANOVA) were noted at baseline or at 12 months in clinical and ultrasonographic variables between either the rheumatoid or the psoriatic KJS groups. CONCLUSION: Grey scale and power Doppler ultrasonography are reliable measures of long term change in rheumatoid and psoriatic KJS disease activity in response to anti-TNFalpha treatment with etanercept.

Adult↗

Vascular changes in psoriatic knee joint synovitis.

OBJECTIVE: To evaluate the diagnostic utility of standard arthroscopy supported by a computerized image analysis system; and to examine and quantify the macroscopic appearance of blood vessels in selected anatomical areas, comparing 2 groups of patients with PsA and RA with refractory knee joint synovitis (KJS) for vascular marking (VM) features and VM scores, as well as for the relationship between respective VM scores and local and systemic KJS disease activity indices. METHODS: Standard arthroscopy was carried out on 39 knees (20 PsA, 19 RA). Videorecordings of the examination were reanalyzed using a computer image analysis system and software. The appearance of vascular markings was assessed and separately scored for the areas of surface synovium (capsular, CVM), villous proliferation (villous, VVM), and synovium adherent to cartilage (pannus, PVM). Indices of systemic (erythrocyte sedimentation rate, ESR) and local KJS disease activity (clinical index) were obtained before arthroscopy. The morphology and scores of the distinct VM were compared between PsA and RA groups, as was the relationship between respective VM scores and ESR and KJS clinical indices. RESULTS: Distinctive VM features were observed for PsA and RA KJS in each separate synovial architecture examined. VVM and CVM scores were significantly correlated with each other in PsA knees, and were significantly higher in PsA compared with RA. In both diseases, VVM and CVM scores were not related to KJS duration or activity or to ESR values, but in RA they were directly correlated with KJS activity. Moreover, the VVM capillary feature "meandering with tight convolutions," considered unique to psoriatic skin, was observed in the synovium of 13 PsA (65%) and one RA KJS (5.5%). The mean KJS duration of the PsA group with typical VVM was significantly lower than the group without VVM (2.6 +/- 1.77 vs 9.4 +/- 8.28 yrs). CONCLUSION: Our macroscopic observations of distinct changes in VM expression in selected anatomical areas of PsA and RA KJS suggest possible pathogenetic differences between the 2 diseases. The typical morphology and higher intensity of villous vascularization, in both early and chronic disease, and the different clinical relevance of VVM scores in PsA compared with RA KJS support the potential use of vascular markings as reliable outcome measures of the PsA process in KJS.

Arthritis, Psoriatic↗

Long-term sonographic follow-up of rheumatoid and psoriatic proliferative knee joint synovitis.

The potential role of sonography in evaluating the response to therapy of persistent knee joint synovitis (KJS) was assessed in a longitudinal study in pre-and post-arthroscopic (AS) synovectomy in rheumatoid and psoriatic patients. At entry to the study ultrasound (US) detection of synovial proliferation was compared with arthroscopic visualization as the 'gold standard' reference. US joint effusion and synovial thickness measures and predominant patterns of synovial proliferation were recorded by comparing clinical and US indices before and at 2, 6 and 12 months after AS synovectomy, or after KJS relapse up to 24 months. A 12 month survival analysis of clinical and US outcomes of arthroscopic synovectomy was also performed. US detection of morphology and degree of synovial proliferation was correlated with AS macroscopic evaluation. After AS synovectomy, the clinical index and both US joint effusion and synovial thickness were significantly reduced, whereas US patterns of synovial proliferation did not show significant changes. US and clinical indices were significantly correlated in all follow-up measurements and US joint effusion was significantly increased in the relapsed compared with the non-relapsed KJS group. The probability at 12 months of reaching maximum improvement in US joint effusion and synovial thickness outcomes was 99 and 58%, respectively; that for clinical remission of KJS was 72%. Ultrasound evaluation has proven reliable and accurate by the arthroscopic gold standard in detecting changes of rheumatoid arthritis and psoriatic arthritis knee joint synovitis. The correlation of US with clinical findings in pre-and post synovectomy patients suggests that sonography can be used as an objective method in monitoring the response to therapy of inflammatory knee joint disease.

Adolescent↗

Arthroscopic synovectomy in rheumatoid and psoriatic knee joint synovitis: long-term outcome.

A long-term prospective study was performed to evaluate the safety and long-term outcome of surgical arthroscopy (AS) for persistent rheumatoid (RA) and psoriatic (PsA) knee joint synovitis (KJS). Local signs of joint inflammation (tenderness, swelling, "ballottement') and range of motion (ROM) were scored and the sum, taken as a global outcome measure, was recorded in 17 RA and 18 PsA knees, both before and at follow-up periods of 2, 6, 12, 24 and 36 months after surgical AS (knee joint synovectomy; meniscal curettage, cartilage shaving or chondrectomy, according to the degree of cartilage damage). A survival analysis (Kaplan-Meier) of the long-term outcome of surgical AS treatment and of the predictive value of clinical parameters of knee joint involvement was also performed. No intra- or post-operative morbidity, pain worsening or loss of joint motion was observed and all patients were discharged within 48 h. Comparison of the parameters of knee joint evaluation showed a significant reduction of the signs of joint inflammation and a significant increase in the ROM in all follow-up periods. At 36 months, the survival curves showed a 61.2% cumulative probability of clinical remission and 72.8% of definite improvement. No significant differences in the prognostic importance of RA, compared to PsA diagnosis, were observed, although higher percentages of PsA compared to RA knees (86.3% and 45.7% respectively) reached the end point of clinical remission at 36 months. KJS duration, radiographic severity and cartilage damage were not predictors of poor long-term outcome of AS synovectomy. Surgical AS treatment for PsA knees with more advanced cartilage damage gave a better long-term outcome. A total of 50.7% of operated knees reached the end point of a KJS relapse at 36 months, the majority (82%) within the initial 18 months of follow-up. Our study indicates that AS synovectomy is a safe procedure requiring short hospitalization which, in combination with second-line medical treatment, can reduce local inflammation in RA and PsA KJS, and preserve knee joint ROM for up to 3 yr.

Adult↗

Prospective sonographic and arthroscopic evaluation of proliferative knee joint synovitis.

The objective of this study was to verify the accuracy of ultrasonography in assessing the topography, morphology, and extent of synovial proliferation in rheumatoid and psoriatic knee joint synovitis. Findings were compared to those obtained using prospective arthroscopy as the gold standard; in addition, topographically defined sonographic findings before and after arthroscopic synovectomy were compared. Sonographic examination was performed in 12 patients with rheumatoid arthritis (13 knees) and 13 patients with psoriatic arthritis (14 knees) who had synovitis of the knee using an electronic linear transducer (7.5 MHz) or a mechanical sector transducer (10 MHz). This examination was followed within 1 week by arthroscopy, to compare the topography (intra-articular localization) and the morphology (sonographic patterns) of synovial proliferation. In 15 knees undergoing arthroscopic synovectomy, preoperative sonographic measurement of synovial thickness in the suprapatellar, medial parapatellar, and lateral parapatellar recesses was compared with arthroscopic visualization of synovial proliferation; 13 knees were reevaluated 2 months after arthroscopic synovectomy by sonography at the same sites. Three distinct sonographic patterns of synovial proliferation were confirmed by arthroscopic examination: a villonodular aspect in 12 knees; uniform thickening in eight knees, and overlapping layers in seven knees. About 50% of the knees showed more than one sonographic pattern, with no differences in pattern distribution between rheumatoid arthritis and psoriatic arthritis patients. A significant correlation was found between sonographic and arthroscopic evaluations of synovial thickness in the suprapatellar (P < 0.02) and medial parapateoffr recesses (P < 0.02), the sites of maximal synovial proliferation in our patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Early phenotypic activation of circulating helper memory T cells in scleroderma: correlation with disease activity.

OBJECTIVES: The differential expression of several accessory/activation molecules (CD26, CD29, CD45RA, CD25, MLR4, HLA-DR) on peripheral blood CD4+ and CD8+ T lymphocytes in patients with scleroderma was compared with that in controls and patients with other connective systemic diseases to look for evidence of the involvement of T cells in the disease process of scleroderma. METHODS: The two colour expression of surface molecules by circulating T cells was analysed with a panel of monoclonal antibodies and flow cytometry in 17 patients with scleroderma, 10 patients with systemic lupus erythematosus, and five patients with rheumatoid arthritis, and the results compared with those for 10 normal controls. The two colour T CD4+ phenotype was further compared between patients with active and quiescent disease in these patients with scleroderma. The coexpression of surface molecules by CD4+ T cells was also analysed by three colour flow cytometry in eight patients with scleroderma. RESULTS: Patients with scleroderma showed increased CD4+CD26+ and CD4+CD25+ percentages and absolute numbers and decreased CD8+CD29+ percentages compared with controls. Moreover, a significant correlation between the higher CD4+CD26+ T cell percentage and absolute cell numbers with disease activity was observed. Most of the CD4+ peripheral blood T cells from patients with scleroderma showed the CD26+CD45RA- phenotype by three colour flow cytometry analysis. CONCLUSIONS: The distinctive pattern of early helper memory T cell activation in these patients with rapidly evolving scleroderma supports the role of a T cell mediated mechanism in the progression of scleroderma.

Adult↗

Intestinal permeability and antigen absorption in rheumatoid arthritis. Effects of acetylsalicylic acid and sodium chromoglycate.

Intestinal permeability was measured using cow's milk beta-lactoglobulin absorption (BLG) as a permeability marker in 14 patients with active and inactive rheumatoid arthritis (RA) under three different conditions: after a washout period, after treatment with acetylsalicylic acid (ASA) associated with disodium chromoglycate (DSCG), and with ASA only. No intolerance to cow's milk was present and serum IgE levels were in the normal range in 12 of 14 patients. IgG anti-IgE were present in 7 of 13 patients tested. When off treatment the intestinal permeability to BLG in RA patients was not increased as compared to controls, but we found a significative difference between active and inactive RA. ASA administration strongly increased BLG absorption, not prevented by DSCG pretreatment. In normal controls treated with a single dose of ASA we obtained similar results. Our results suggest that prolonged treatment with nonsteroidal anti-inflammatory drugs induces an increase of food antigen absorption, apparently not related to anaphylaxis mediator release, with possible clinical effects.

Adult↗

Anticentromere antibody in localized scleroderma.

Using metaphase chromosome spreads as substrate for indirect immunofluorescence technic, we observed anticentromere antibody in three of twenty-five patients affected with various clinical forms of localized scleroderma. Anticentromere antibody is generally considered a serologic marker of the CREST syndrome, a more benign subset of systemic sclerosis. However, none of the three anticentromere antibody-positive patients with localized scleroderma had Raynaud's phenomenon, acrosclerosis, or any signs or symptoms of systemic disease; on physical and laboratory examination, they showed only typical cutaneous features of localized scleroderma: two showed linear scleroderma, and one showed localized morphea. A 2-year 8-month follow-up of two patients did not disclose any clinical evidence of systemic sclerosis. The occurrence of anticentromere antibody in patients with localized scleroderma seems to offer supportive evidence that a relationship exists between localized scleroderma and systemic sclerosis.

Adolescent↗

[Tissue autoantibodies during therapy with levamisole for rheumatoid arthritis].

In 20 patients affected with rheumatoid arthritis, tissue autoantibodies were studied during a year of treatment with levamisole. Before therapy, antinuclear antibodies were present in 11 cases, anti-thyroid microsomes in 1 and anti-smooth muscle in 6. During therapy, autoantibodies remained almost unchanged in all patients, thus indicating that levamisole does not influence this aspect of humoral immunity in rheumatoid arthritis. Furthermore, no correlation was found between autoantibody pattern before treatment and effects of levamisole on clinical course of disease.

Antibodies, Antinuclear↗

Functional renal involvement in normotensive patients with progressive systemic sclerosis: impaired sodium excretion during isotonic saline infusion.

An intravenous infusion of 2,000 ml isotonic saline was performed in 8 normotensive, normoreninemic patients with progressive systemic sclerosis. None of them had clinical evidence of renal disease. Total and proximal fractional excretion of sodium was reduced when compared with that of 8 normal subjects. No correlation was found with para-aminohippurate (PAH) clearance values. Two years after this study was done, 4 patients developed arterial hypertension; interestingly, plasma renin activity remained within the normal range. Reduced sodium excretion is suggested as having a pathogenetic role in the hypertension of progressive systemic sclerosis.

Adolescent↗

[Early effect of levamisole on plasma immunoglobulins in rheumatoid arthritis].

In 8 patients affected with rheumatoid arthritis the effects of levamisole administration (150 mg/day once a week) on plasma immunoglobulins were studied. The concentration of IgG, IgA and IgM was measured before and after 15,30,60 and 90 days of treatment. We observed a significant increase of IgG after 30, 60 and 90 days, of IgA after 30 and 90 days, and of IgM after 15 and 30 dyas. Such response is in contrast with previously reported decreased of immunoglobulins most frequently observed after 6 months of drug administration. Therefore, it seems that levamisole at the beginning of its activity on immunocompetent cells enhances rather than decreases the antibody production.

Antibody Formation↗

[Degradation products of fibrinogen in synovial fluid].

The fibrin/fibrinogen degradation products were measured in 24 synovial fluids sampled from patients with knee joint effusion. It has been observed that they are increased in synovial fluid involved in inflammatory processes. Their presence and concentration seem to be related to the control of local inflammation.

Arthritis↗