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Biomedical subjects

Florenzo Iannone

Publications and source records attributed to Florenzo Iannone.

10 recordsLinked to original sources

Etanercept maintains the clinical benefit achieved by infliximab in patients with rheumatoid arthritis who discontinued infliximab because of side effects.

OBJECTIVE: To evaluate the efficacy of switching to etanercept treatment in patients with rheumatoid arthritis who already responded to infliximab, but presented side effects. METHODS: Charts of 553 patients with rheumatoid arthritis were retrospectively reviewed to select patients who responded to the treatment with infliximab and switched to etanercept because of occurrence of adverse effects. Clinical data were gathered during 24 weeks of etanercept treatment and for the same period of infliximab treatment before infliximab was stopped. Disease Activity Score computed on 44 joints (DAS-44), erythrocyte sedimentation rate (ESR) 1st hour, Visual Analogue Scale (VAS) of pain, Health Assessment Questionnaire (HAQ), and C reactive protein (CRP) were assessed every 8 weeks. RESULTS: 37 patients were analysed. Adverse events to infliximab were mostly infusion reactions. No statistically significant difference between infliximab, before withdrawal, and etanercept, after 24 weeks, was detected in terms of DAS-44 (2.7 and 1.9, respectively), HAQ (0.75 and 0.75, respectively), ESR (21 and 14, respectively) and CRP (0.5 and 0.3, respectively). VAS pain decreased significantly after switching to etanercept treatment (40 and 24, respectively; p<0.05). CONCLUSIONS: Our study shows that etanercept maintains the clinical benefit achieved by infliximab, and suggests that a second tumour necrosis factor (TNF) alpha inhibitor can be the favourable treatment for rheumatoid arthritis when the first TNFalpha blocker has been withdrawn because of adverse events.

Adult↗

Use of etanercept in the treatment of dermatomyositis: a case series.

OBJECTIVE: To evaluate the efficacy of etanercept, a recombinant human soluble fusion protein of tumor necrosis factor-alpha (TNF-alpha) type II receptor and IgG1, in patients with adult dermatomyositis (DM). METHODS: Five patients with active DM were studied. All patients reported muscle weakness and had elevated muscle enzymes creatine kinase and lactate dehydrogenase. Because of lack of response to steroid and cytotoxic therapy, etanercept was given at a dose of 25 mg subcutaneously twice a week for at least 3 months. RESULTS: All patients experienced an exacerbation of disease, with increase of muscle weakness, elevation of muscle enzyme levels, and unchanged rash. Treatment with etanercept was stopped. After receiving a combination of methotrexate (MTX) and azathioprine, disease manifestations improved in all patients. CONCLUSIONS: In our case series, TNF-alpha inhibition by etanercept was not effective, suggesting that a broad immunosuppressive therapy is needed to treat DM.

Adult↗

Cutaneous lesions as presenting symptoms of primary biliary cirrhosis: an undifferentiated connective tissue disease-like onset.

We describe two patients with primary biliary cirrhosis (PBC) who presented with specific symptoms mimicking an undifferentiated connective tissue disease (arthromyalgia, fatigue, cutaneous lesions either morbillous-like or urticarial, the latter with an eosinophil infiltrate of upper dermis). Subsequent detection firstly of eosinophilia in the blood and secondarily of antimitochondrial antibodies with results of liver biopsy allowed a diagnosis of asymptomatic PBC. In our cases, a peculiar sign of early stage of PBC was represented also by the eosinophilia in the liver.

Autoantibodies↗

The effect of bosentan on matrix metalloproteinase-9 levels in patients with systemic sclerosis-induced pulmonary hypertension.

OBJECTIVE: Systemic sclerosis (SSc) is an autoimmune disease that can potentially involve all tissues and organs of the human body. Based on the extent of the disease and organ involvement, different subsets of patients and organ involvement, different subsets of patients have been identified and several classifications proposed have been identified and several classifications proposed aiming to better stratify affected patients. The occurrence aiming to better stratify affected patients. The occurrence of pulmonary arterial hypertension (PAH), characterized of pulmonary arterial hypertension (PAH), characterized by altered tissue remodelling of the entire vessel wall, is the most severe complication that influences prognosis and survival. The molecular basis underlying the vascular damage is not yet known, but a family of enzymes named matrix metalloproteinases (MMPs), with a proteolytic activity towards several extra-cellular matrix (ECM) components, is likely to be involved. Recently, a dual inhibitor of endothelin-1, bosentan, has been successfully evaluated in clinical trials in PAH patients. RESEARCH DESIGN AND METHOD: The aim of this study is to investigate the expression of MMP-2 and MMP-9 in the serum of different subsets of SSc patients, and in patients treated with bosentan. Thirty-five Caucasian patients with SSc were enrolled in the study, 12 of whom were found to have isolated PAH assessed by Doppler echocardiography. Eight patients fully met the inclusion criteria and were eligible for therapy with bosentan given at the dosage of 62.5 mg twice daily for 4 weeks followed by 125 mg twice daily for 50 weeks(15). The remaining patients (4/12) initiated bosentan therapy for a few weeks and, therefore, were considered at the baseline level only. Serum samples were analysed by gelatine zymography. RESULTS: The results suggest that MMP-9 but not MMP-2 is differently expressed according to the degree of organ involvement. In particular, MMP-9 serum levels are significantly decreased in PAH with respect to other subsets of SSc patients. Moreover, in bosentan-treated patients, after 12 months of therapy MMP-9 significantly (p < 0.05) increased and correlated with an improved clinical outcome, as measured by the '6-minutes walking' test. CONCLUSIONS: This is the first time that MMP-9 serum levels are reported to be down-regulated in PAH patients and up-regulated following bosentan treatment. Whether MMP-9 has a pathogenetic role in the vascular damage observed in PAH patients or it is a marker of bosentan effectiveness is not yet known. However, MMP-9 may be an important molecule that needs further investigation in SSc patients to better define its role.

Adult↗

Distinct expression of adhesion molecules on skin fibroblasts from patients with diffuse and limited systemic sclerosis. A pilot study.

OBJECTIVE: . Systemic sclerosis (SSc) is characterized by excessive production of collagen and other components of the extracellular matrix (ECM) by fibroblasts. The ECM receptors, integrins and CD44 (hyaluronan receptor), play a key role in the homeostasis of connective tissue and may also have a role in the pathogenesis of fibrosis. We investigated the expression of integrins and CD44 on skin fibroblasts from patients with limited and diffuse SSc. METHODS: We studied 13 patients with SSc, 8 with limited SSc, and 5 with diffuse SSc, and 8 control subjects. Fibroblasts were isolated and cultured from biopsies taken from the lesional skin of the second finger of the left hand. Cell-surface expression of beta1, beta3, alpha1-alpha6, alphav integrins, and CD44 was evaluated by immunofluorescence and flow cytometry analysis. RESULTS: Fibroblasts from limited SSc showed significantly decreased expression of alpha2, alpha3, alpha4 integrins, while diffuse SSc fibroblasts had significantly reduced expression of alpha5, alphav integrins, and CD44. Diffuse SSc also had significantly increased expression of alpha6 integrin on fibroblasts. In controls, the expression of alpha4 and alpha5 correlated positively, while in limited and diffuse SSc it did not. CONCLUSION: This is the first study evaluating separately the expression of adhesion molecules on skin fibroblasts from limited and diffuse subsets of SSc. We detected a distinct pattern of expression with decrease of collagen and fibronectin receptors in limited SSc, and downregulation of fibronectin and hyaluronan receptors in diffuse SSc. These results suggest that changes of fibroblasts/ECM interactions and mechanisms underlying the pathogenesis of fibrosis in SSc may differ in the single subset of the disease.

Cells, Cultured↗

The pathophysiology of osteoarthritis.

Osteoarthritis (OA) is a complex disease whose pathogenesis includes the contribution of biomechanical and metabolic factors which, altering the tissue homeostasis of articular cartilage and subchondral bone, determine the predominance of destructive over productive processes. A key role in the pathophysiology of articular cartilage is played by cell/extra-cellular matrix (ECM) interactions, which are mediated by cell surface integrins. In a physiologic setting, integrins modulate cell/ECM signaling, essential for regulating growth and differentiation and maintaining cartilage homeostasis. During OA, abnormal integrin expression alters cell/ECM signaling and modifies chondrocyte synthesis, with the following imbalance of destructive cytokines over regulatory factors. IL-1, TNF-alpha and other pro-catabolic cytokines activate the enzymatic degradation of cartilage matrix and are not counterbalanced by adequate synthesis of inhibitors. The main enzymes involved in ECM breakdown are metalloproteinases (MMPs), which are sequentially activated by an amplifying cascade. MMP activity is partially inhibited by the tissue inhibitors of MMPs (TIMPs), whose synthesis is low compared with MMP production in OA cartilage. Intriguing is the role of growth factors such as TGF-beta, IFG, BMP, NGF, and others, which do not simply repair the tissue damage induced by catabolic factors, but play an important role in OA pathogenesis.

Aging↗

Microscopic polyangiitis associated with primary biliary cirrhosis.

We describe a patient with microscopic polyangiitis and primary biliary cirrhosis (PBC) who presented with a non-erosive polyarthritis followed by pulmonary and renal involvement and signs of liver disorder. Detection of pANCA and antimitochondrial antibodies with results of renal and liver biopsies allowed a diagnosis of microscopic polyangiitis and PBC. To our knowledge, this is the first report of an association between the 2 diseases.

Antibodies, Antineutrophil Cytoplasmic↗