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Biomedical subjects

Gabriele Valentini

Publications and source records attributed to Gabriele Valentini.

6 recordsLinked to original sources

Type-1 response in peripheral CD4+ and CD8+ T cells from patients with Hashimoto's thyroiditis.

OBJECTIVE: In this study we performed single-cell analysis of the intracellular cytokine expression in peripheral CD4+ and CD8+ lymphocytes from patients with Hashimoto's thyroiditis (HT) to investigate the type-1 response separately for the two lymphocyte sub-populations. DESIGN AND METHODS: Twenty-nine patients affected by HT and 20 healthy subjects, matched for sex and age, were enrolled. After the analysis of the lymphocyte sub-populations, the intracellular content of interferon-gamma (IFN-gamma) in phorbolmyristate acetate (PMA)-stimulated CD4+ and CD8+ lymphocytes was assayed. Moreover, the CD4+ lymphocytes were also evaluated for the intracellular expression of IL-4. RESULTS: No significant differences in CD3+, CD4+ and CD8+ lymphocytes were found between HT patients and control subjects. However, the HT patients showed higher numbers of CD4+ IFN-gamma+, CD4+ IL-4+ and CD8+ IFN-gamma+ (t-test, P< or =0.001) cells than the control subjects. Analysing the intracellular expression of IFN-gamma and IL-4 in relation to thyroid function, we found that the euthyroid patients (18 cases) showed more expression of IL-4 in CD4+ lymphocytes than the control subjects, without any significant modification of IFN-gamma expression in CD4+ and CD8+ lymphocytes. However, the hypothyroid patients (11 cases) showed an increase of IFN-gamma expression in both CD4+ and CD8+ lymphocytes with respect to the control subjects and the euthyroid patients. Moreover, the expression of IL-4 in CD4+ cells from hypothyroid patients was significantly lower than that seen in the euthyroid cases and comparable to that found in the control subjects. CONCLUSIONS: Our study has demonstrated that the peripheral CD4+ and CD8+ T lymphocytes from the HT patients show a type-1 activation strictly correlated to the occurrence of hypothyroidism. Further studies will be needed to clarify the exact role of peripheral lymphocytes in HT and whether they could provide a reliable marker of thyroid immune involvement.

Adolescent↗

Current status of outcome measure development for clinical trials in systemic sclerosis. Report from OMERACT 6.

Systemic sclerosis (SSc), also known as scleroderma, is a complex, multisystem disease that results in severe morbidity, disability, and life-threatening complications. The wide range of biological systems clinically involved, and the large spectrum of disease activity and damage that occurs in this disease have limited clinical investigation of SSc, especially therapeutic trials. The OMERACT 6 Workshop on Systemic Sclerosis was conceived as a starting point for the process of assessing the current state of the science in outcome assessment in SSc and then setting a realistic research agenda and priorities for future work in this area This article reviews the current status of assessment tools for research in SSc within the main fundamental domains of illness in SSc, including problems related to skin, pulmonary, cardiac, peripheral vascular (Raynaud's phenomenon and digital ulceration), renal, and musculoskeletal systems as well as health-related quality of life and physical functioning. The current level of validation of outcome measures in SSc is assessed according to the guidelines set forth by prior OMERACT meetings.

Clinical Trials as Topic↗

Systemic sclerosis.

Systemic sclerosis (SSc) presents with a great deal of variability from patient to patient and classification and subset criteria will be analysed and discussed. SSc has been reported in people from all over the world. The prevalence and incidence, however, varies from country to country and within the same country in different ethnic groups. These differences will be elucidated. Genetic and environmental factors associated with the disease will be discussed.SSc is predominantly a female disease, with the female:male ratio ranging from 3:1 to 8:1 and being higher in childbearing years. Progenitor cells acquired during pregnancy have been suggested to play a role by inducing a graft-versus-host disease (microchimerism). Recent epidemiological studies on the relationship between SSc and previous pregnancies will be discussed. SSc is associated with a significant morbidity and mortality. Survival has improved in the last 15 years. Factors associated with such improvement will be analysed.

Adult↗

Foot involvement in systemic sclerosis: a longitudinal study of 100 patients.

OBJECTIVE: To investigate the clinical and radiologic features of foot involvement in systemic sclerosis (SSc). PATIENTS: One hundred patients (91 women, 9 men; mean age, 51.9 +/- 11 years) with SSc (mean disease duration, 17.4 +/- 10.5 years) were retrospectively studied. Seventy-four subjects had limited scleroderma and 26 diffuse scleroderma. METHODS: Radiologic changes of foot involvement were assessed at presentation (time of diagnosis) and follow-up ranging from 1 to 28 years (median range, 7 years) and were compared with changes detected in the hands of each patient at the same presentation and follow-up. Correlations with skin and internal organ involvement were assessed. RESULTS: Ninety patients had foot involvement clinically. Forty-three had it at initial evaluation; 47 developed it during follow-up. Median time to clinical event occurrence was 10 years (95% CI, 6.7-13.3) with 44% censored case probability at this time. The onset of clinically evident foot involvement was later in limited SSc than in diffuse SSc. In comparison with hands with SSc, feet with SSc had lower rates of necrotizing Raynaud's phenomenon and tendon friction rubs and decreased skin thickening scores, whereas arthralgias occurred significantly more often. At presentation, 37 patients had radiologic abnormalities of their feet compared with 69 of their hands (P <.001); the hands had a significantly higher prevalence of acroosteolysis (P <.001). At the end of the follow-up, 35 of 50 SSc patients had radiographic foot involvement compared with 50 of 51 with hand involvement (P <.001). A significantly higher prevalence of acroosteolysis (P <.001), calcinosis (P <.05), and erosions (P <.05) of the hands were detected at that time. CONCLUSION: This study shows that compared with hand involvement in SSc, foot involvement in SSc has a later onset and is relatively less frequent but can be disabling.

Female↗

Cyclophosphamide pulse regimen in the treatment of alveolitis in systemic sclerosis.

OBJECTIVE: To evaluate, in a pilot study, the efficacy of a short term cyclophosphamide (CYC) pulse regimen on alveolitis in a cohort of patients with systemic sclerosis (SSc). METHODS: Twenty-three patients with SSc (17 diffuse SSc and 6 limited SSc) were selected in 5 centers in Italy, based on the findings of an abnormal bronchoalveolar lavage (BAL) cell analysis in association with altered pulmonary function tests (PFT) or recent deterioration in flow volume curve (FVC). Patients were also evaluated by skin score (Rodnan), esophageal manometry and barium swallow radiography, and electrocardiography and 2-mode echocardiography. The pre-enrolment pulmonary evaluation and after 6 months of therapy included evaluation of the clinical status, PFT (FVC, FEV1, DLCO), BAL. standard chest radiograph, and chest high resolution computed tomography. All patients received i.v. CYC (1000 mg/m2 of body surface monthly for 6 mo) and oral prednisone (25 mg daily for the first month and subsequently 5 mg daily of maintenance dosage for the remaining 5 mo). A complete blood count and urinalysis were obtained at monthly intervals. RESULTS: After 6 months of therapy the values for FVC did not change significantly. Individually, 8 of 23 patients showed an improvement (> 15% increase) in FVC after 6 months, while FVC in 13 cases remained stable. Only 2 patients had an important decline in FVC after 6 months of therapy (17 and 24% decrease). Improvement in DLCO was noted in 15 of 23 patients after 6 months of therapy. Four patients were stable and 4 patients had a worsened DLCO at the end of the study. After therapy the mean value of BAL fluid recovery did not change. There was a reduction in total cell number although this value did not reach statistical significance. The levels of neutrophils, eosinophils, lymphocytes, and macrophages did not change significantly. Scans for patients with grades 1, 2, and 3 did not differ significantly after 6 months of therapy, and 14 patients were stable. Changes in appearance, in relation to changes in extent of disease, were seen in 8 patients and consisted of an extension of reticular pattern and transformation from grade 1 to 2 (6/8 patients). All patients showed a ground-glass appearance indicating an acute alveolitis. Improvement in ground-glass was noted in 10 of 23 patients after 6 mo therapy. At the end of the study, 8 patients were stable and 5 patients had a diffusion of the ground-glass to other segments. No side effects were experienced during the treatment except for mild nausea in 4 patients; no patients discontinued therapy during the study. CONCLUSION: CYC pulse regimen seems to stabilize alveolitis in the majority of cases. The association of CYC pulsed modality with prednisone may be useful in SSc patients to control disease evolution in the lung.

Adult↗