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Biomedical subjects

S Fossati

Publications and source records attributed to S Fossati.

At least 19 recordsLinked to original sources
PubMed2002

Treatment of benign nodular goitre with mildly suppressive doses of L-thyroxine: effects on bone mineral density and on nodule size.

OBJECTIVES: To evaluate (i) the demineralizing effect of L-thyroxine (LT4) therapy at doses mildly inhibiting serum thyroid stimulating hormone (TSH) in patients with benign nodular goitre; (ii) the efficacy of treatment on nodule size. DESIGN: Cross-sectional study comparing euthyroid women with nodular goitre treated with LT4 for > or = 2 years (52 +/- 32 months, range 24-138, median 42) and a matched group with untreated goitre. SUBJECTS: A total of 89 female outpatients (53.3 +/- 9 years; 36 pre- and 53 postmenopausal), 43 treated and 46 untreated. MAIN OUTCOME MEASURES: Bone mineralization was measured with total body and regional mineralometry [dual energy X-ray absorptiometry (DEXA)], and indirectly evaluated with biochemical parameters (alkaline phosphatase, osteocalcin). Efficacy of LT4 therapy was assessed by measuring the nodule size during ultrasonography. The adequacy of the treatment was evaluated on the basis of serum TSH levels. RESULTS: No significant differences were found at DEXA for total body and regional mineralization (P > 0.05 for all comparisons) in treated and untreated patients, both in pre- and postmenopausal states. Evaluation of the nodule size during the ultrasound scan showed a reduction of > or = 30% in 11 of 43 treated patients (26%) versus none of the untreated, an unchanged size in 29 treated patients (67%) versus 18 untreated, an increase of nodules and/or new nodule development in three treated patients (7%) versus 28 untreated (61%). CONCLUSIONS: L-thyroxine (LT4) treatment at doses slightly suppressing TSH does not significantly affect bone mineralization, nor does it represent a risk factor for osteoporosis, even in postmenopausal patients. The efficacy of this therapeutic schedule on goitre size is comparable with the effects previously reported with suppressive doses.

Adult↗
PubMed2001

Evaluation of immune activation in HIV-infected and uninfected African individuals by single-cell analysis of cytokine production.

Immune activation has been observed in HIV-infected and uninfected Africans, among whom it is thought to modify interaction between the immune system and HIV. To characterize this phenomenon accurately, in-depth immunologic analyses were performed in a rural African population. Freshly drawn peripheral blood mononuclear cells (PBMCs) of HIV-infected African (from Gulu, Uganda) and Italian antiviral-naive patients and those of uninfected Ugandan and Italian study subjects were analyzed. Individuals were matched for age and sex and determined to be free from parasitic infections. Intracellular cytokines were measured in mitogen (M)- and gp160 peptides + staphylococcal enterotoxin B and alpha CD28 (env)-stimulated T lymphocytes. Interferon (IFN)-gamma-producing CD8(+) T cells were quantified in an enzyme-linked immunosorbent assay. Results showed that M-stimulated production of interleukin (IL)-10 and tumor necrosis factor (TNF)-alpha increases in CD4(+) and CD8(+) cells of African infected patients and uninfected study subject; and that env-stimulated IL-10 and TNF-alpha production is increased in CD8(+) T lymphocytes of African HIV-infected patients. M- and env-stimulated IFN-gamma-producing CD8(+) T cells were reduced in African participants and not increased by preincubation with alpha IL-10 monoclonal antibody. This is the first set of data that has reported immune activation in rural Africa by single-cell analysis of cytokine production. These results help in defining the immunologic background to be considered in the design of therapeutic and vaccine-based approaches to HIV infection in an African setting.

Black People↗
PubMed2001

Single-cell analysis of cytokine production shows different immune profiles in multiple sclerosis patients with active or quiescent disease.

Peripheral blood mononuclear cells of multiple sclerosis (MS) patients were stimulated with myelin basic protein (MBP) together with anti-CD28 monoclonal antibody and staphylococcal enterotoxin B to optimize cytokine production by antigen-specific cells. Type 1 (IL-2, IL-12, IFNgamma) and pro-inflammatory (TNFalpha, IL-1beta, IL-6) cytokines were augmented in CD4+, CD8+, and CD14+ cells of acute MS patients and of patients undergoing disease reactivation. These cytokines were reduced in IFNbeta-treated and in stable MS patients; type 2 cytokines (IL-4, IL-10) were increased in these patients. Similar immune profiles are seen in MS patients in whom remission is naturally or pharmacologically (IFNbeta) achieved. Cytokine alterations are particularly evident in CD14+ cells, underlying their critical role in the modulation of the immune response.

Adjuvants, Immunologic↗
PubMed2001

Human herpesvirus 8 DNA in the skin and blood of patients with Mediterranean Kaposi's sarcoma: clinical correlations.

BACKGROUND: Kaposi's sarcoma is a multifocal lympho-angioproliferative disease that appears in elderly subjects of Mediterranean origin (classical form), young Africans and immunodepressed patients (as a result of organ transplantation or AIDS). In 1994, DNA sequences of a new human herpesvirus, called HHV-8, were detected in skin lesions and peripheral blood of patients with AIDS-related Kaposi's sarcoma by confirmational display analysis and polymerase chain reaction. OBJECTIVE: As HHV-8 in peripheral blood mononuclear cells is detected in about 50% of Mediterranean Kaposi's sarcoma patients and its presence fluctuates in time in the same patient, maybe its detection correlates with the clinical behaviour of the disease. METHODS: By using routine and nested polymerase chain reaction we evaluated the presence of HHV-8-specific DNA sequences in the skin lesions, perilesional healthy skin and peripheral blood mononuclear cells of a group of 40 HIV-negative patients with Mediterranean Kaposi's sarcoma. RESULTS: HHV-8 DNA sequences have been found in 40/40 (100%) lesional skin of Mediterranean Kaposi's sarcoma, in 35/40 (85%) perilesional apparently normal skin and in 24/40 (60%) peripheral blood monuclear cell samples. The results of polymerase chain reaction on peripheral blood monuclear cells were positive in 41% of the patients with slowly evolving disease as opposed to 74% of those with rapidly evolving disease, and in 47.6% of the patients with stage I-II disease as opposed to 73.6% of those with stage III-IV. CONCLUSION: The detection of HHV-8 in peripheral blood monuclear cells seems to correlate with the more aggressive stages and the rapid evolution behaviour of Mediterranean Kaposi's sarcoma.

Adult↗
PubMed2000

T-lymphocyte maturation abnormalities in uninfected newborns and children with vertical exposure to HIV.

Cell-mediated immunity and T-lymphocyte maturation are impaired in HIV-infected children. These abnormalities would be detected in HIV-uninfected offspring of HIV women (seroreverters [SR]) if HIV or its soluble proteins could cross the placental barrier. Immunophenotypic analyses were performed in 20 healthy HIV-uninfected newborns of HIV-infected mothers (SR), and in 14 healthy newborns of HIV-negative women (UC). The same analyses were performed in 3 groups of older children: SR (n = 41); UC (n = 15); and HIV-infected children (n = 25). Antigen-specific cells were evaluated with ELISpot and fluorimetric analyses; IL-7 serum concentration was measured by enzyme-linked immunosorbent assay (ELISA). Results showed that in SR newborns: (1) the CD4/CD8 ratio was reduced, (2) CD4(+) and CD8(+) naive T-cell percentages were decreased, (3) percentage of activated CD8(+) T cells was increased, and (4) percentages of CD3(+)/4(-)/8(-) (DN) and DN/25(-)/44(+) were augmented. These abnormalities were partially retained in older SR children. CD4(+) and CD8(+) HIV-specific cells were detected in a portion of newborn SRs but not in older SRs. Serum IL-7 was augmented both in newborn and older SRs. Cell-mediated immunity and T-cell maturation are altered even in HIV-uninfected newborns of HIV-infected mothers; these abnormalities persist over time. The biologic significance of these observations and potential subsequent clinical events should be investigated in larger cohorts of seroreverters. (Blood. 2000;96:3866-3871)

Adult↗
PubMed2000

Author reply

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Journal Article↗
PubMed2000

In vitro immunomodulatory properties of tucaresol in HIV infection.

The immunomodulatory properties of tucaresol (compound 589C80) were tested on in vitro antigen- and mitogen-stimulated proliferation and cytokine production by peripheral blood mononuclear cells (PBMC) of HIV-infected individuals and healthy controls (HC). Results showed that tucaresol: (1) increases influenza A virus-, gp 160 peptide-, and HLA alloantigen-stimulated proliferation as well as interleukin (IL)-2 and interferon gamma (IFN gamma) production by PBMC of HIV-infected individuals with higher CD4 counts (>500/microl) but had only a marginal immunomodulatory effect on PBMC of patients with lower CD4 counts (<500/microl); (2) did not modify IL-10 production; (3) augmented CD25 expression on mitogen-stimulated T cells of HC but not of HIV-infected individuals; and (4) marginally increased CTL activity. The immunomodulatory properties of tucaresol were confirmed by PCR analyses; additional data showed that tucaresol costimulated CD3-dependent triggering of T cells and that this stimulation was independent of CD28 costimulation. The immunomodulatory effects of tucaresol on T cell functions are characterized by a bell-shaped dose response curve; the action of the compound is optimal in the 100 to 300 microM range. Analyses of mitogen-stimulated apoptosis demonstrated that the lack of effect of tucaresol at higher doses is not the result of increased cell death, suggesting a role of functional impairment. These data confirm that tucaresol can stimulate T helper cell function and enhance the production of type 1 cytokines, thus eliciting cell-mediated immunity, and warrant its potential utility in the therapy of HIV infection.

Adjuvants, Immunologic↗
PubMed2000

Photopheresis in cutaneous T-cell lymphoma: five-year experience.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) includes several lymphoproliferative disorders involving mature T-lymphocyte proliferation initially confined to the cutis. These affections, after variable periods, may progress to the blood, limph nodes and visceral organs. Mycosis fungoides (MF) is the most frequent form of CTCL and has an indolent clinical course. The therapy of CTCL depends on the stage of the disease and the patient's general conditions. For advanced cases it includes chemotherapy, retinoids, and interferon-alpha. Since 1987 extracorporeal photochemotherapy (ECP), a novel immunomodulatory approach based on apheresis and photoirradiation of leukocytes, has been successfully introduced for the treatment of advanced CTCL. It can prolong survival of patients with erythrodermic CTCL without significant side effects. OBJECTIVE: To review our five-year experience with ECP in CTCL. METHODS: Since June 1994, 33 CTCL patients have been recruited for ECP, using two different regimens: two procedures on two consecutive days at four-week intervals for six months, or at two-week intervals for three months with progressive tapering in the second three-month period for the more severe forms. Six patients received ECP with IFN-alpha. ECP was done using the photopheresis UVAR system and UVAR XTS (Therakos, West Chester, Pa) and always with 8-MOP liquid formulation injected directly into the buffy coat bag. Lymphocytes in peripheral blood were immunophenotypically characterized for each patient and every ECP session. RESULTS: All patients tolerated ECP well, without significant side effects. Thirty patients are clinically evaluable (at least three ECP cycles). A favourable clinical response was obtained in 80.9% (16/21) of MF patients (complete response 33%, partial response 47.6%) and in 66% (6/9) of patients in the Sézary's syndrome phase (complete response 33.3%, partial response 33.3%). Five of the six patients given IFN-alpha as adjunctive therapy had a PR and one a CR. Four patients are in CR without therapy at follow-ups of 46, 20, 10 and 8 months. There have been no changes in the peripheral lymphocyte immunophenotype during the follow-up. In 19/30 patients the CD95 antigen, correlated with cellular apoptosis, was expressed and was frequently associated with a good clinical response. CONCLUSIONS: In our experience ECP achieved favourable clinical responses in 73% of patients, in monotherapy or in combination with IFN-alpha, without significant side effects.

Adult↗
PubMed1999

Human immunodeficiency virus negative Kaposi sarcoma and lymphoproliferative disorders.

BACKGROUND: The concomitant occurrence of more than one primary neoplasm in the same individual has led researchers to seek possible common etiopathogenetic factors. Kaposi sarcoma (KS) is a multicentric neoplasm of vascular origin and perhaps viral etiology. Four forms of KS are known: classic or Mediterranean, endemic or African, posttransplant, and epidemic or acquired immunodeficiency syndrome-associated KS. In its classic form KS mainly affects elderly people and often has a long and indolent course that occasionally allows other malignancies to appear. Previous studies of the possible association between human immunodeficiency virus (HIV) negative KS and lymphoproliferative disorders (LDs) have produced discordant results. METHODS: To verify a possibly significant association between HIV negative KS and LDs, data relating to 250 evaluable Italian patients with HIV negative KS were evaluated retrospectively. RESULTS: Of the 250 KS patients, only 6 (2.4%) were found to have had an LD: 2 with Hodgkin lymphoma, 1 with non-Hodgkin lymphoma, 1 with cutaneous T-cell lymphoma, 1 with acute promyelocytic leukemia, and 1 with B-chronic lymphocytic leukemia. CONCLUSIONS: No significant association was found between HIV negative KS and LDs in the patient population in the current study. The authors believe that age, LD, or therapy-related immunodepression played a role in the cases in which KS appeared after the LD by determining the passing to the lytic phase of the herpes-virus HHV8 already present in anatomic sites of latency/persistence.

Adult↗
PubMed1999

Regional effects of cholecystokinin octapeptide on colonic phasic and tonic motility in healthy humans.

The aim of this study was to assess in nine healthy subjects the effects of CCK octapeptide (CCK-8) on colonic tonic activity, measured by a barostat, and phasic activity, measured by manometry. On 2 consecutive days, recordings were performed in the unprepared proximal and distal colons during intravenous infusion of saline and CCK-8 at 5, 20, and 40 ng. kg-1. h-1. In the proximal colon CCK-8 induced, at the 20 and 40 ng. kg-1. h-1 doses, a tonic relaxation with an increase in barostat bag volume to 156 +/- 25 and 157 +/- 19% of basal (P < 0.01) and a decrease in phasic activity to 72 +/- 7 and 76 +/- 7% of basal (P < 0.01). In the distal colon, CCK-8 induced, at the 20 and 40 ng. kg-1. h-1 doses, a tonic relaxation (increase in intrabag volume to 133 +/- 12 and 149 +/- 15%, respectively; P < 0.01), whereas phasic activity increased (128 +/- 8 and 132 +/- 6%, respectively; P < 0.01). Effects of CCK-8 on tonic and phasic activities are different according to the colonic segment. Because meals induce colonic tonic contraction, our results suggest that CCK, as a hormone, is not an important mediator of the response of the colon to feeding in humans.

Adult↗
PubMed1997

Vinorelbine therapy for Kaposi's sarcoma in a kidney transplant patient.

We report the case of a patient with Kaposi's sarcoma after kidney transplantation. Despite the discontinuation of azathioprine and a reduction in the cyclosporin dosage, the disease continued to evolve, and antineoplastic treatment became necessary. After 14 cycles of vinorelbine chemotherapy, there was a 75% regression of the initial lesions, despite the continuation of cyclosporin A.

Antineoplastic Agents, Phytogenic↗
PubMed1994

Mediterranean Kaposi's sarcoma in the elderly. A randomized study of oral etoposide versus vinblastine.

BACKGROUND: This Phase III trial was performed to compare the roles of oral etoposide and intravenous (i.v.) vinblastine in the treatment of Mediterranean Kaposi's Sarcoma (MEKS) in elderly patients with severe disease (Stages II, Ac/B, III, and IV). PATIENTS AND METHODS: Sixty-five patients were randomized to receive either oral etoposide (60 mg/m2 on Days 1-3 during the first course; 60 mg/m2 on Days 1-4 during the second course, and 60 mg/m2 on Days 1-4 during the second course, and 60 mg/m2 on Days 1-5 during the third course; the courses were recycled every 3 weeks) or an i.v. bolus of vinblastine (3 mg/m2 weekly for 3 weeks, and then 6 mg/m2 every 3 weeks). RESULTS: No significant difference between the two drugs was observed in terms of response rates (etoposide, 73.5% vs. vinblastine, 58%; P = 0.3), duration of response, or survival (median not yet reached at a median follow-up of 38 months). Side effects of both treatments were limited, although myelotoxicity was more evident in the vinblastine arm. CONCLUSIONS: Although it is feasible and well tolerated, the oral administration of etoposide at these doses and in this regimen does not appear superior to vinblastine in the treatment of MEKS. Further evaluation of a more intensive schedule in large cooperative clinical trials is needed to establish the role of this drug in comparison with reference treatments.

Administration, Oral↗
PubMed1988

Annular elastolytic giant cell granuloma.

We treated a 13-year-old girl who had annular erythematous lesions with central atrophic areas, which had been present on her trunk and limbs for 4 months. Histological examination revealed patchy dermal lymphohistocytic infiltration with multinucleated giant cells which were phagocytosing elastic fibers, causing them to disappear. The active border of the lesions regressed after intradermal injection of corticosteroids. The classification of the disease and its differential diagnosis from the usual granuloma annulare, inflammatory anetoderma, O'Brien's actinic granuloma, and Convit's disease are discussed.

Adolescent↗
PubMed1988

Oral etoposide for Kaposi's Mediterranean sarcoma.

22 patients affected by locally aggressive or generalized form of Kaposi's Mediterranean sarcoma were treated with oral etoposide (VP16) as single-drug therapeutic regimen. Of the 17 evaluable patients, 10 were pretreated with other chemotherapeutic regimens. VP16 was administered at the dose of 100 mg daily for 3-5 days every 3 weeks for 3 times during induction, then every 4 weeks for 10-12 times during maintenance. Hematological (35.2%) and gastrointestinal (64.7%) toxicities were always mild and swiftly reversible. Good percentages of objective responses were achieved in both nonpretreated (85.6%) and pretreated (70%) patients. The chemotherapeutic regimen employed, the way of drug administration, the results as well as the comparison to another study with vinblastine are discussed.

Administration, Oral↗