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Biomedical subjects

B Ferrero

Publications and source records attributed to B Ferrero.

At least 19 recordsLinked to original sources
PubMed2006

Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis (INCOMIN Trial) II: analysis of MRI responses to treatment and correlation with Nab.

BACKGROUND: In RRMS, clinical exacerbations are usually associated with different types of active lesions at MRI, including: hyperintense lesions on T1-weighted post-gadolinium sequences; new hyperintense lesions or enlarging old lesions on PD/T2-weighted scans; or new hypointense lesions on T1-weighted pre-Gd sequences. OBJECTIVE/METHODS: Primary outcome was the occurrence of patients with at least one active MRI lesion of the different types indicated above during treatment with 250 microg every other day (EOD) interferon beta (IFNbeta)-1b or 30 microg once weekly (OW) IFNbeta-1a in outpatients with RRMS (INCOMIN Trial). RESULTS: The number of patients with at least one 'active' lesion, evaluated over the two-year follow-up, was significantly (P = 0.014) lower in the EOD IFNbeta-1 b arm (1 3/76, 17%) then in the OW IFNbeta-1a arm (25/73, 34%). NAb frequency over two-year follow-up was 22/65 (33.8%) in the EOD IFNbeta-1b arm and 4/62 (6.5%) in the OW IFNbeta-1a arm, significantly greater in the EOD IFNbeta-1b arm. CONCLUSIONS: The development of MRI active lesions is strongly reduced by EOD-IFNbeta-1b compared with OW-IFNbeta-1a, indicating that EOD-IFNbeta-1b is more effective than OW-IFNbeta-1a in reducing ongoing inflammation and demyelination in MS. Logistic regression showed that NAb status did not affect the risk of MRI activity.

Adjuvants, Immunologic↗
PubMed2002

High-dose intravenous immunoglobulin G treatment of myasthenia gravis.

IVIg is a safe and effective adjunctive treatment for myasthenia gravis, but there are no well established guidelines for the use of IVIg in this disease, lacking controlled randomized trials to assess its efficacy in homogeneous group of patients. The main advantages of IVIg are the rapid onset of the effect, the lack of long-term toxicity, and the possibility to reduce the required doses of immunosuppressive drugs. IVIg appears to have a role as an acute treatment in rapidly progressive myasthenia gravis weakness, particularly in situations when therapeutic apheresis is not feasible. In addition, IVIg is safer than plasma exchange (PE) in patients with hypotension or autonomic instability, in children, in patients of older age (>65 years), and in those suffering from sepsis. For these reasons, at present, IVIg are recommended during crises of myasthenia gravis in older patients when PE is contraindicated or not feasible IVIg can be also used as a chronic maintenance therapy when other immunosuppressive treatments have failed or cannot be used. Periodic administration of IVIg on a bimonthly or monthly basis may be able to stabilize chronic, nonresponding patients.

Autoantibodies↗
PubMed2002

Hypothalamic-pituitary-adrenal axis function and cytokine production in multiple sclerosis with or without interferon-beta treatment.

OBJECTIVES: Pro-inflammatory cytokines mediate brain damage in multiple sclerosis (MS); they can also influence the hypothalamic-pituitary-adrenal (HPA) axis function. We evaluated the possible abnormalities of HPA axis function in relapsing-remitting MS (RR-MS). MATERIAL AND METHODS: IFN-gamma, TNF-alpha and IL-6 production by ex-vivo lymphocytes from 10 normal volunteers and 10 RR-MS patients before and during IFN-beta therapy was assessed; pituitary-adrenal function was evaluated by means of CRH and ACTH stimulation tests. RESULTS: In untreated patients the production of IFN-gamma, TNF-alpha, IL-6 was increased, and was significantly decreased by IFN-beta. Neither basal, nor stimulated ACTH, cortisol, DHEA, DHEAs, 17-alpha-OH-progesterone levels differed between controls and RR-MS patients, both before and during treatment. Moreover, no correlation was found between endocrine and immune parameters. CONCLUSION: In MS the HPA axis function seems normal and not influenced by IFN-beta treatment. This result is discussed in relation to the increased production of pro-inflammatory cytokines found in this disease.

Adjuvants, Immunologic↗
PubMed2002

Autoantibodies in multiple sclerosis patients before and during IFN-beta 1b treatment: are they correlated with the occurrence of autoimmune diseases?

Autoimmune side effects, namely autoantibody (autoAb) occurrence and thyroid function alteration, have been described during interferon-beta (IFN-beta) treatment for multiple sclerosis (MS). AutoAb occurrence and autoimmune thyroid diseases are also frequently detected in MS patients free of any treatment. The aim of this study was to evaluate the relationship between IFN-beta 1b treatment, autoAb occurrence, and autoimmune diseases in MS. Thyroid and liver function and serum autoAb (antithyroid, antinuclear, anti-liver, anti-kidney microsomes, anti-smooth muscle and parietal cell antigens) occurrence were evaluated in 156 relapsing-remitting MS (RRMS) patients before and every 3 months after starting IFN-beta 1b treatment (8 MIU subcutaneously [s.c.] on alternate days). The probability of having liver or thyroid function alteration or autoAb occurrence was analyzed longitudinally with the generalized estimating equations (GEE) approach. At baseline, 16.1% of patients had autoAb. During treatment, autoAb occurred de novo in 7.2% of patients. GEE analysis showed that the probability of having autoAb at any time during IFN-beta 1b treatment did not change significantly compared with baseline. AutoAb occurring de novo rarely persisted during treatment and significantly less than those already present at baseline. Positivity for autoAb at baseline or during treatment was not correlated with the development of thyroid or liver function alteration during IFN-beta 1b treatment. Our study indicates that IFN-beta treatment is a safe treatment for MS patients, free of risk of autoimmunity and of associated liver or thyroid function alteration.

Adjuvants, Immunologic↗
PubMed2001

Liver and thyroid function and autoimmunity during interferon-beta 1b treatment for MS.

BACKGROUND: The occurrence or recurrence of autoimmune diseases or of autoantibodies (autoAb) has been reported during type I interferon (IFN) treatment. OBJECTIVE: To define the frequency of thyroid and liver dysfunction and of autoimmunity during IFN-beta 1b (IFNB) treatment of MS. METHODS: Prospective 1-year multicenter follow-up of 156 patients with MS recruited by 18 centers was conducted. Thyroid-stimulating hormone and anti-thyroid autoAb were measured by an immunoradiometric method, thyroid hormones by chromatographic assay, and non-organ-specific autoAb by indirect immunofluorescence. Tests were repeated every 3 months. The probability of having liver, thyroid, or autoAb alterations was analyzed longitudinally with the generalized estimating equations (GEE) method. RESULTS: Thyroid dysfunction was observed in 5.3% of cases at baseline and 8.3% de novo during IFNB treatment. GEE analysis showed that the probability of having thyroid alteration did not change significantly during treatment compared with baseline. Liver alteration was observed in 4.6% of cases at baseline and 37.5% de novo during IFNB treatment (p < 0.0001). GEE analysis showed that the probability of having liver alteration was higher (p < 0.002) at months 3 and 6 compared with baseline, returning to values similar to baseline by month 9. AutoAb were detected in 16.1% of patients at baseline and in 20% during IFNB. GEE analysis showed that the probability of having autoAb did not change significantly during treatment compared with baseline. Thyroid or liver alteration or autoAb occurring de novo during IFNB were usually transient. CONCLUSIONS: Differently from the frequency of liver function alteration (which significantly increased during the first months of IFNB treatment, suggesting a probable causal relationship with IFNB), the frequency of thyroid dysfunction or of autoimmunity showed random and insignificant changes over time, probably not related to IFNB treatment.

Adjuvants, Immunologic↗
PubMed2001

Anti-GM1 and anti-sulfatide antibodies in polyneuropathies. Threshold titers and accuracy.

OBJECTIVES: To determine threshold titers and diagnostic accuracy of anti-GM1 and anti-sulfatide antibodies (Ab) for autoimmune polyneuropathies (PN) in overall and for particular subtypes of them. MATERIALS AND METHODS: In this study 84 PN patients, 120 epileptics and 93 healthy controls' sera were tested by enzyme-linked immunosorbent assay for autoAbs and results confirmed by thin-layer chromatography. Frequencies of positive patients at increasing cut-off were compared to determine threshold titers. Accuracy was determined by Receiver Operator Characteristic analysis. RESULTS: A 1:2,000 titer for IgM anti-GM1 and a 1:4,000 titer for IgM anti-sulfatide Ab resulted to be threshold titers for autoimmune PN in overall. IgM anti-GM1 and anti-sulfatide Ab had low discriminating capacity between autoimmune PN and other PN, but good discriminating capacity between motor neuropathy (for anti-GM1 Ab) or PN in IgM-paraproteinemia or chronic painful sensory axonal PN (for anti-sulfatide Ab) and other PN. CONCLUSION: Our results suggest that testing IgM anti-GM1 or anti-sulfatide Ab is useful only for diagnostic confirmation of specific subtypes of autoimmune PN.

Aged↗
PubMed2001

Thyroid function and autoimmunity during interferon beta-1b treatment: a multicenter prospective study.

Thyroid dysfunction and autoimmunity have been reported during type I interferon therapy, namely interferon-alpha for chronic hepatitis or interferon-beta for multiple sclerosis. To define the frequency of thyroid dysfunction and autoimmunity during interferon-beta treatment, 156 multiple sclerosis patients were prospectively followed up by 18 centers for 1 yr after starting interferon-beta-1b treatment. Serial clinical assessments and tests of thyroid and liver function and antithyroid autoantibodies (all performed by the same centralized laboratory) were conducted every 3 months. TSH and antithyroid autoantibodies against human TG or thyroid microsomal antigens were measured by immunoradiometric methods; free T3 and T4 were measured by chromatographic assays. Longitudinal occurrence of thyroid or liver alterations or of autoantibodies was analyzed with the generalized estimating equations method, correcting for the correlation of repeated measurements of the same subject over time. Pretreatment comparison with a control group of 437 healthy blood donors did not show significant differences in the frequency of thyroid dysfunction or antithyroid autoantibody positivity. During interferon-beta treatment, the de novo frequency of thyroid alteration was 8.3%, that of liver alteration was 37.5%, and that of antithyroid autoantibody was 4.5%. Generalized estimating equations analysis demonstrated that the frequency of liver alteration significantly increased during treatment compared with the baseline value (odds ratio, 7.03; confidence interval, 2.49-19.9), whereas that of thyroid alteration or of antithyroid autoantibodies did not. The frequency of thyroid dysfunction during interferon-beta treatment showed random, nonsignificant changes over time and, in addition, was not correlated to antithyroid autoantibody positivity.

Adolescent↗
PubMed1999

Autoimmune events during interferon beta-1b treatment for multiple sclerosis.

Autoimmune events, although rarely reported during interferon beta-1b (IFNB) treatment of relapsing-remitting (RR) multiple sclerosis (MS), may be more frequent than expected due to the many immunologic abnormalities associated with this disease. We report the prospective two-year follow-up of autoimmune events in 40 RR MS patients treated with IFNB and in 21 untreated MS controls. Thyroid and liver function and serum level of 12 autoantibodies (autoAbs) against organ- (thyroid, gastric, pancreatic) and non-organ-specific antigens were serially monitored. In contrast to control patients, autoAbs (anti-nuclear, -smooth muscle or -thyroid antigens) were detected in 13 IFNB-treated patients, and these were associated with thyroid or liver function alteration in many cases. Persistent autoimmune thyroid dysfunction occurred in three IFNB-treated patients, all of whom were women with a familial history of thyroid disease or baseline anti-thyroid autoAb positivity. For improvement of the MS relapse rate, thyroid dysfunction was adequately treated without stopping IFNB. Liver function alteration (17 IFNB-treated patients, associated with non-organ-specific autoAbs in four) was transient and did not require IFNB treatment to be stopped, with the exception of one patient who was already suffering from a drug-induced hepatopathy at baseline. During the IFNB treatment of MS, several autoimmune events may occur, indicating that thyroid and liver function and autoAbs must be carefully monitored.

Adult↗
PubMed1997

Modified and improved anti-acetylcholine receptor (AchR) antibody assay: comparison of analytical and clinical performance with conventional anti-AChR antibody assay.

We developed a modified anti-acetylcholine receptor (AChR) antibody (Ab) assay based on a radioreceptor assay and a calibration curve. We compared the analytical and clinical performances of this modified assay with those of the conventional anti-AChR Ab radioreceptor assay. Serum specimens were from patients with myasthenia gravis (MG) (n = 156) and from control subjects (n = 106). The modified assay demonstrated lower within-assay (4.0-6.6%) and between-assay (5.3-7.8%) CVs, greater linearity, lower cost, and shorter assay time than the conventional method. ROC curve analysis indicated almost identical specificity and sensitivity (> 0.92) for these two anti-AChR Ab assays. The modified and conventional assays were also equivalent for blocking anti-AChR Ab assay. Moreover, the modified anti-AChR Ab assay, differently from the conventional assay, allowed us to reveal anti-AChR Ab concentration differences among different clinical grades of MG.

Adolescent↗
PubMed1996

Systemic high-dose recombinant-alpha-2a-interferon therapy modulates lymphokine production in multiple sclerosis.

Chronic systemic high-dose recombinant alpha 2a-interferon (rIFNA) therapy reduces exacerbation rate and MRI signs of disease activity in relapsing/remitting multiple sclerosis (RR MS) patients. In order to clarify the possible mechanisms underlying the clinical efficacy of rIFNA in MS, several immunologic studies were performed as a part of a pilot clinical trial. Twenty RR MS patients were treated with 9 x 10(6) IU of rIFNA (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Cytokine production by cultured lymphocytes, major histocompatibility complex class II (MHC-II) antigen expression on cultured macrophages, peripheral blood (PB) and cerebrospinal fluid (CSF) lymphocyte phenotype, and IgG and beta 2 microglobulin levels were studied before therapy, after 6 months of therapy, and 6 months after stopping therapy. rIFNA therapy was associated with reduction of interferon-gamma and tumor necrosis factor-alpha production by PB lymphocytes (p < 0.04), and with slight, not significant, increase of transforming growth factor-beta 2 or interleukin (IL)-10 production. IL-4 was undetectable in the culture supernatants both before and after therapy. rIFNA therapy had no effect on macrophage MHC-II molecule expression. An increased percentage of CD8+, CD8+ high CD11b+ low, and CD3- CD16+ CD56+ cells, and of CD4+ absolute cell number was observed in CSF after rIFNA therapy. After rIFNA administration, IgG level significantly increased both systemically (p < 0.02) and intrathecally (p < 0.001). Serum beta 2 microglobulin level increased (p < 0.01), as well. Only 1 out of the 12 rIFNA treated patients developed neutralizing antibodies against rIFNA during therapy. Six months after stopping therapy all the immunologic changes returned to baseline. These data suggest that the beneficial effect of rIFNA therapy on MS disease activity is probably mediated by a downregulation of proinflammatory cytokine synthesis by PB lymphocytes rather than by macrophage MHC-II antigen expression. The immunologic effects of high-dose systemic rIFNA therapy are temporary and restricted to the period of drug administration.

Antibodies↗
PubMed1996

Long term recombinant interferon alpha treatment in MS with special emphasis to side effects.

Twenty relapsing-remitting (RR) clinically definite MS patients were treated with 9 MIU intramuscular recombinant interferon alpha-2a (rIFNA) (Roferon-A, Roche) (n = 12) or placebo (n = 8) every other day for 6 months and followed up for a further 6 months after stopping treatment. Numbers of active lesions at MRI and of patients with clinical-MRI signs of disease activity and lymphocyte interferon gamma production, which were decreased during treatment, returned to values similar to baseline and placebos after stopping treatment. rIFNA chronic therapy seems therefore needed in order to maintain drug efficacy. Side effect profile was monitored, too, for over 1 year in the same 20 patients plus 25 additional RR MS patients. Besides the typical side effects of type I interferon therapy (fever, fatigue, depression, lymphopenia, hepatic enzyme elevation), occurrence of serum autoAbs was noted in 30% patients (in 60% antinuclear and in 80% antithyroid autoAbs). In two patients rIFNA treatment was stopped, in one case for antithyroid autoAbs and hypothyroidism, in the other for antinuclear autoAbs and a five-fold increase of ALT. A careful monitoring of serum autoAbs and of signs of thyroid or liver damage must always precede and accompany longterm type I IFN therapy.

Autoantibodies↗
PubMed1996

Interferon alpha-2a treatment of relapsing-remitting multiple sclerosis: disease activity resumes after stopping treatment.

We evaluated the long-lasting effects of systemic high-dose recombinant interferon alpha-2a (rIFNA) in relapsing-remitting (RR) MS after discontinuing treatment in a single-blind randomized placebo-controlled trial with 20 RR clinically definite MS patients using either nine million IU intramuscular rIFNA (n = 12) or placebo (n = 8) every other day for 6 months. Follow-up continued for a further 6 months without IFN treatment. In rIFNA-treated patients, main outcome measures, significantly different from placebo during treatment, returned, after discontinuing treatment, to values similar to placebo or baseline. Active MRI lesions per patient increased from 0.08 +/- 0.08 to 1.2 +/- 0.4 (p < 0.02), number of patients with clinical MRI signs of disease activity from 2 of 12 to 8 to 12 (P < 0.04), lymphocyte IFN gamma production from 3.0 +/- 0.7 to 12.4 +/- 2.2 IU/mL (p < 0.01), lymphocyte tumor necrosis factor alpha production from 5.8 +/- 0.9 to 18.9 +/- 6.3 pg/mL (p < 0.05). All side effects of rIFNA treatment disappeared after discontinuing the drug. The reduction of clinical MRI signs of disease activity and the immunologic effects were temporary and restricted to the period of rIFNA administration. The depression of many immunologic and clinical MRI responses during drug administration and their simultaneous return to baseline after discontinuing the drug strongly argue all observed changes were related to drug administration.

Adult↗
PubMed1995

Treatment of recurrent and/or metastatic squamous cell head and neck carcinoma with a combination of vinorelbine, cisplatin, and 5-fluorouracil: a multicenter phase II trial.

PURPOSE: Vinorelbine has been demonstrated to be active against squamous cell carcinomas of the head/neck (SCHNC) and lung. This multicenter phase II trial was carried out to evaluate the activity and tolerability of the combination of vinorelbine, cisplatin, and 5-fluorouracil given on an outpatient schedule in a series of 80 patients with recurrent SCHNC. PATIENTS AND METHODS: Eighty patients with recurrent and/or metastatic SCHNC were treated with a combination of CDDP 80 mg/m2on day 1, 5-FU 600 mg/m2 as a 4-hour infusion on days 2-5, and vinorelbine 25 mg/m2 on days 2 + 8. This cycle was repeated every 28 days. Most patients had oral cavity, larynx, or oropharynx carcinoma (88%). Forty-seven had previously received surgery alone, two radiotherapy alone, and 31 surgery plus radiotherapy. Seventy-two patients had locoregional recurrency, and eight had distant metastases. RESULTS: According to an intent-to-treat analysis, complete response (CR) of a mean duration of 12.7+ months was achieved in 13% of cases (95% CI 5%-21%), and partial response of 8.3+ months in 45% of patients (95% CI 33%-56%), for an overall response rate of 55% (95% CI 43%-65%). Nine patients (11%) showed no change, and 22 (28%) progressed. Five patients were not evaluable for response and toxicity. CR were seen more frequently in patients pretreated with only surgery than in those who had also received radiotherapy (15% vs. 9%; p = 0.7). No statistically significant differences in response rate according to site of primary tumor were found (p = 0.8, NS). The received dose intensities of 5-FU, CDDP, and VNR were 90%, 92%, and 82%, respectively. The overall survival of the series as a whole was 9.7+ months (range 4-27). Toxicity was generally acceptable. Grades 3 and 4 leukopenia were recorded in 11% and 5% of patients, respectively. Noteworthy was the occurrence of pain at the tumor site after vinorelbine administration in 5 patients. CONCLUSION: The combination regimen of CDDP, 5-FU and vinorelbine is quite active in the treatment of metastatic and/or recurrent SCHNC. This regimen should be tested as initial treatment in previously untreated patients and compared to a standard regimen in recurrent SCHNC.

Adult↗
PubMed1995

Apomorphine SC treatment in parkinsonian patients with long-term L-dopa syndrome during L-dopa drug holiday.

The Long-Term Dopa Syndrome (LTDS) is one of the main problems in the management of advanced parkinsonian patients. A transient L-Dopa withdrawal (Drug Holiday, DH) can be useful to improve the drug response after DH, even if this approach presents risks due to patient akinesia. We tried to verify if Apomorphine sc administration during DH (DH with Apomorphine, DHA) can: a) reduce the risks connected with DH: b) maintain the benefits of DH: c) standardize the duration of DH. Twenty-five parkinsonian patients with LTDS were treated with Apomorphine sc during DH (14 days). No patient had any severe side effects. The follow-up at 180 days, conducted using the Unified Parkinson's Disease Rating Scale, demonstrated a significant improvement in the clinical conditions of about 70% of the patients, allowing a 27.1% reduction in daily L-dopa dosage. DHA can represent a valid therapeutical approach for parkinsonian patients with LTDS.

Adult↗
PubMed1995

Interferon alpha treatment of relapsing-remitting multiple sclerosis: long-term study of the correlations between clinical and magnetic resonance imaging results and effects on the immune function.

Interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) are proinflammatory cytokines which may be involved in the pathogenesis of MS. IFN-alpha counteracts many of the proinflammatory actions of IFN-gamma and TNF-alpha. We treated 20 patients with relapsing-remitting (RR) MS with 9 MIU of recombinant IFN-alpha-2a (rIFN-alpha) (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Clinical exacerbations or new or enlarging lesions at serial MRI occurred in 2/12 rIFN-alpha-treated and in 7/8 placebo-treated patients (P < 0.005). Only one new MRI lesion was detected in the rIFN-alpha group, while 27 new or enlarging lesions were detected in placebo group (P < 0.01). Baseline lymphocyte IFN-gamma (19.10 +/- 7.12 U ml-1) and TNF-alpha (18.05 +/- 5.34 pg ml-1) production significantly decreased to 3.03 +/- 0.66 (P < 0.04) (for IFN-gamma) and to 5.78 +/- 0.90 (P < 0.04) (for TNF-alpha) after rIFN-alpha treatment. IFN-gamma and TNF-alpha production was unchanged in the placebo group. rIFN-alpha was tolerated without drop-outs or serious side-effects, but fever, malaise, fatigue (interfering with daily activities in two patients) and leukopenia frequently occurred. High-dose chronic systemic rIFN-alpha might reduce clinical and MRI signs of disease activity in RRMS. The changes in cytokine production suggest that the effect is probably mediated by a down-regulation of proinflammatory cytokine.

Adolescent↗
PubMed1994

Chronic systemic high-dose recombinant interferon alfa-2a reduces exacerbation rate, MRI signs of disease activity, and lymphocyte interferon gamma production in relapsing-remitting multiple sclerosis.

We report a randomized, double-blind, placebo-controlled pilot trial of systemic high-dose recombinant interferon alfa-2a (rIFNA) in 20 patients with relapsing-remitting (RR) multiple sclerosis (MS). Patients received 9 million IU rIFNA (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Clinical exacerbations or new or enlarging lesions on serial MRI occurred in two of 12 rIFNA-treated and in seven of eight placebo-treated patients (p < 0.005). There was only one enlarging MRI lesion in the rIFNA group, whereas 27 new or enlarging lesions were present in the placebo group (p < 0.01). Baseline lymphocyte interferon gamma production of 19.10 +/- 7.12 IU/ml significantly decreased to 3.03 +/- 0.66 IU/ml (p < 0.04) in the rIFNA group, whereas production was unchanged in the placebo group. The rIFNA was tolerated without dropouts or serious side effects, but fever, malaise, fatigue (interfering with daily activities in two patients), and leukopenia occurred frequently. Neuropsychological tests excluded neurotoxicity. High-dose systemic rIFNA might reduce clinical and MRI signs of disease activity in RR MS and should be investigated in larger trials.

Adolescent↗