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Biomedical subjects

G F Ferraccioli

Publications and source records attributed to G F Ferraccioli.

At least 19 recordsLinked to original sources
PubMed2002

Rescue of combination therapy failures using infliximab, while maintaining the combination or monotherapy with methotrexate: results of an open trial.

OBJECTIVE: To assess the possible clinical and biological rescue of rheumatoid arthritis (RA) in 16 patients who were still active despite intensive combination therapy after receiving infliximab following the Anti-Tumour necrosis factor Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) schedule. METHODS: Sixteen patients who were still active despite combination therapy with optimal doses of methotrexate (MTX 15-17.5 mg/week) and cyclosporin A (CsA 2.5-3.5 mg/day) received infliximab. Ten received their combination plus infliximab (Combi), and six received infliximab plus MTX alone (Mono). The follow-up was carried out for 30 weeks in all patients and for 46 weeks in eight. Efficacy and safety were examined. RESULTS: At entry, the mean disease activity score (DAS) was 5.6 (all patients had a DAS >3.7). After therapy, eight of 10 patients in Combi and four out of six in Mono showed an improvement of >50% in the initial swollen joint count, yet only one patient reached 50% improvement in the initial DAS after 30 weeks, and one patient had a DAS <2.4 (low disease activity). Of the eight patients who reached 46 weeks of follow-up, three showed an improvement in DAS of 50% and two had a DAS <2.4. When considering the change over time, the difference between DAS at entry and at week 30 was statistically significant only in patients receiving MTX plus CsA, while it was not significant in those receiving MTX only. Two patients developed recurrent febrile upper respiratory infections in the Combi therapy group, while two had a single febrile infection in the MTX alone group. Two patients became strongly anti-cardiolipin positive (IgM >40 MPL) and one developed a coronary syndrome. CONCLUSION: Infliximab can be added incrementally to MTX plus CsA, with favourable results in terms of efficacy and safety over time in severe rapidly aggressive and progressive RA. Finally, minor evidence emerged for a stronger efficacy of the Combi treatment compared with Mono.

Adult↗
PubMed2002

Analysis of improvements, full responses, remission and toxicity in rheumatoid patients treated with step-up combination therapy (methotrexate, cyclosporin A, sulphasalazine) or monotherapy for three years.

OBJECTIVE: To evaluate two monotherapies followed by step-up combination therapy with two or three complementary drugs in active rheumatoid arthritis (RA) in comparison with sulphasalazine (SSZ) alone. METHODS: One hundred and twenty-six consecutive patients with early active RA were enrolled in this open controlled clinical trial. The primary end-point was 50% improvement according to the ACR criteria (ACR50) at 6, 12 or 18 months. The secondary end-points were a full response (Magnusson criteria) and/or remission (ACR criteria) at 3 yr. Methotrexate (MTX) (group 1), cyclosporin A (CsA) (group 2) or SSZ (group 3) was used first. After 6 months, a combination of two drugs (CsA and MTX) was employed in groups 1 and 2. SSZ was added after 12 months if improvement was less than ACR50 with the combination. Group 3 continued with SSZ alone. RESULTS: After 6 months, 57% of patients in group 1, 31% of group 2 (MTX vs CsA, P=0.002) and 33% of group 3 (MTX vs SSZ, P=0.01) had reached ACR50 improvement according to intention-to-treat analysis. At month 12 after starting a drug combination, 67% of group 1 and 76% of group 2 had reached ACR50 compared with 24% of group 3. At the 18-month follow-up, 90% of group 1 and 88% of group 2 but only 24% of group 3 had reached ACR50. After 18 months, 62% of group 1, 60% of group 2 and 48% of group 3 showed side-effects and three, five and eight patients in the three groups respectively had dropped out of the study. At the 3-yr follow-up, 9% of the patients in groups 1 and 2 and 7% of group 3 were in remission according to the ACR criteria; according to the Magnusson criteria, 40% showed a full response in groups 1 and 2 but only 21% did so in group 3. CONCLUSION: MTX appears to be the fastest-acting agent. A step-up approach with MTX plus CsA plus SSZ led to a 50% improvement according to the ACR criteria in most patients. After 3 yr, 40% of patients receiving combination therapy and 21% of patients receiving monotherapy showed a full response, while 9 and 7% respectively attained remission.

Acetaminophen↗
PubMed2000

Discriminating ability of composite indices for measuring disease activity in rheumatoid arthritis: a comparison of the Chronic Arthritis Systemic Index, Disease Activity Score and Thompson's articular index.

OBJECTIVE: To compare the discriminating ability of the chronic arthritis systemic index (CASI), an index that uses the Health Assessment Questionnaire (HAQ) as the main variable, with the disease activity score (DAS) and Thompson's articular index (TAI) to detect high and low disease activity in rheumatoid arthritis (RA). METHODS: Two hundred and two RA patients were examined. According to criteria proposed previously, they were divided into two subgroups: those with active disease and those with low activity. The areas under receiver operating characteristic (ROC) curves were employed to assess the diagnostic accuracy of the CASI in comparison with the DAS and TAI for the discrimination of disease activity. RESULTS: The difference between areas under the ROC curves of the CASI and TAI (0. 897+/-0.023 vs 0.780+/-0.032) and between the DAS and TAI (0.933+/-0. 018 vs 0.780+/-0.032) was highly significant (P=0.0001), thus reflecting the accuracy of the diagnostic assessment. No difference arose between areas under the ROC curves of the CASI and the DAS (difference between areas=0.036+/-0.022; P=0.103). CONCLUSION: The CASI discriminates just as well between high and low disease activity as does the DAS. Either index consisting of more than one variable performs better than TAI. We conclude that even including the HAQ, a severity parameter in the long term, it is possible to construct an index that, at any time point, evaluates disease activity as well.

Adolescent↗
PubMed1998

Helicobacter pylori infection and autoimmune processes: an emerging field of study.

Evidence is accumulating that Helicobacter pylori infection may be closely associated with autoimmunity. However, whether autoimmunity plays a causal role in the pathogenesis of some of the diseases attributed to this bacterium or whether it is rather an epiphenomenon remains to be determined. In this brief review, a summary is made of current knowledge regarding the potential general mechanisms by which Helicobacter pylori causes mucosal damage. A review is then made of the evidence linking this bacterium to the production of different gastric autoantibodies. Finally, the reported association between Helicobacter pylori infection and some known autoimmune diseases is discussed. Although the data are still not sufficiently complete to draw definite conclusions, autoimmunity appears to be an important aspect of this infection and will certainly become a major field of study in the next few years.

Antigens, Bacterial↗
PubMed1997

Chronic lymphocytic sialoadenitis in HCV-related chronic liver disease: comparison of Sjögren's syndrome.

With the aim of morphologically characterizing chronic sialoadenitis in patients with hepatitis C virus (HCV) chronic liver disease, labial salivary gland biopsies from 22 chronic HCV liver disease and from 10 primary Sjögren's syndrome patients were compared. Only focus score (number of aggregates with more than 50 lymphocytes per 4 mm2 of glandular tissue) and grading of inflammation were able to discriminate significantly between the two patient groups. Duct ectasia, acinar depletion, presence of lymphoid aggregates with less than 50 lymphocytes and of lymphoid infiltration within intralobular salivary duct epithelium were evident in both disease groups and appeared to be non-specific, mostly age-related changes. In both patient groups plasma cell and lymphocyte typing showed similar features: T-lymphocytes represented most of the lymphoid population, B lymphocytes were few unless follicles were present. Higher focus score values were associated with a plasma cell switch from an IgA to an IgM and/or IgG predominance. A greater morphological similarity was seen between biopsies of the primary Sjögren's syndrome group and those of female rather than male chronic HCV liver disease patients. Salivary gland tissue in HCV patients responds to damage in a fashion similar to primary Sjögren's syndrome, the only difference being a lesser degree of inflammation.

Adult↗
PubMed1997

Clinical trials in rheumatoid arthritis: methodological suggestions for assessing radiographs arising from the GRISAR Study. Gruppo Reumatologi Italiani Studio Artrite Reumatoide.

OBJECTIVES: The three x ray assessors of the GRISAR study (blinded to treatment) gave consensual erosion and damage scores to the baseline and 12 month radiographs of 284 rheumatoid arthritis (RA) patients using three different methods: single readings (blinded as to patient and chronological sequence of the x rays), paired readings (blinded as to sequence), and chronologically ordered paired readings. The aim was to evaluate which of these reading procedures is the most appropriate for clinical trials. METHODS: The progression of the scores obtained using each procedure was compared by means of descriptive statistics, principal components analysis, and intra-patient correlation coefficients of pairs of methods. Bootstrap estimates of the variance of the difference in the means of two equally sized random samples were calculated to evaluate the power of the statistical analysis performed to assess the possible treatment effect for both paired and chronological reading methods. RESULTS: (a) The standard deviations of the paired and chronological readings were similar, but that of the single readings was higher. (b) The knowledge that two x rays were of the same patient accounted for a sizeable proportion of the between method variability. (c) Agreement was satisfactory between the paired and chronological methods for both scores but, between them and the single readings, it was modest for erosions and poor for damage. (d) The bootstrap estimate of the variance of the difference was smaller for the paired than the chronological method, possibly giving it greater power to test treatment effect. CONCLUSIONS: These results suggested that paired readings were the most suitable for evaluating the progression of joint damage in the GRISAR study.

Arthritis, Rheumatoid↗
PubMed1997

Gastric B-cell clonal expansion and Helicobacter pylori infection in patients with autoimmune diseases and with dyspepsia. A follow-up study.

BACKGROUND: It is not clear whether gastric B-cell clonal expansion, a possible precursor of mucosa-associated lymphatic tissue (MALT) lymphoma, is exclusively linked to Helicobacter pylori infection and virulence. METHODS: In this study we followed up, for up to 33 months, 16 VDJ polymerase chain reaction-positive patients (4 with dyspepsia, 9 with Sjögren's syndrome, and 3 with other autoimmune diseases). Of these, 12 were H. pylori-positive. In addition, in H. pylori-positive patients we tested whether the serum anti-cag-A (a potential marker of virulence) was preferentially associated with B-cell clonality. RESULTS: In all but one patient clonality appeared temporally unrelated to H. pylori infection. The prevalence of anti-cagA was not higher in H. pylori/VDJ-positive patients than in controls. CONCLUSIONS: These data indicate that, in addition to H. pylori, gastric B-cell clonality may be sustained by other agents/mechanisms. Anti-cag-A does not appear to be involved in the pathogenesis of clonality.

Adult↗
PubMed1996

Is the control of disease progression within our grasp? Review of the GRISAR study. (Gruppo Reumatologi Italiani Studio Artrite Reumatoide).

A prospective, open, multicentre, randomized study with a blinded radiological end-point was started in 1991. The aim of the study was to assess whether cyclosporin A (CyA) controls ongoing anatomical damage in active early rheumatoid arthritis (RA) better than conventional disease-modifying anti-rheumatic drugs (DMARDs) as used in everyday clinical practice. A total of 340 consenting patients with early RA (mean duration 1.4 yr) were recruited; 167 were randomized to CyA 3mg/kg per day and 173 to DMARDs. Hand, wrist and foot X-rays were blindly scored by a central committee of three radiologists using the Larsen-Dale method. Any side-effects were carefully recorded. The control of clinical symptoms was similar in both groups. Radiological evaluation of 284 patients (141 on CyA; 143 on DMARDs) after 12 months showed a significant decrease in the mean progression in the eroded joint count (1.3 +/- 3.1 vs 2.4 +/- 3.0, P < 0.001). There was also better maintenance on treatment with CyA than in the group treated with DMARDs (89.2 vs 77.5%, respectively; P = 0.002). CyA seems to offer greater control of ongoing anatomical joint damage in early RA than conventional DMARDs after 12 months.

Adult↗
PubMed1996

B cell clonality in gastric lymphoid tissues of patients with Sjögren's syndrome.

OBJECTIVE: To determine the prevalence of mucosa associated lymphoid tissue (MALT) in the stomach and of a possible antigen driven proliferation, in patients with Sjögren's syndrome (SS). METHODS: Twenty one patients with primary SS and 80 dyspeptic controls underwent upper endoscopy. Lymphoid tissue and Helicobacter pylori were assessed by histopathological analysis. Epstein-Barr virus (EBV) or human herpes virus-6 (HHV-6) genome were studied by polymerase chain reaction (PCR) DNA amplification. Two PCR VDJ procedures were used to detect immunoglobulin heavy chain (IgH) gene rearrangement. RESULTS: Organised MALT was found in 33.3% of the patients, compared with 21.5% of the controls (NS). H pylori infection was seen in 71% of patients and 63% of controls. Genomic EBV or HHV-6 was found in a minor portion of SS gastric tissues. B cell expansion was detected in nine of the 21 patients. Infectious agents in the stomach might have contributed to B cell clonality only in 55.5% of the cases. No strict relationship was found between lymphoid follicles and clonality. CONCLUSION: Lymphoid accumulation in the gastric mucosa is common in Sjögren's syndrome, but full evidence for an antigen driven B cell expansion could not be demonstrated. Only a portion of those with clonal B cell expansion had evidence of an infectious agent. Other unknown infectious agents or factors related to the underlying disease (autoantigen) and its tissue environment may have a further role as possible causes of B clonal expansion in the gastric mucosa.

Adult↗