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Biomedical subjects

M Trojano

Publications and source records attributed to M Trojano.

At least 19 recordsLinked to original sources
PubMed2006

Italian Multiple Sclerosis Database Network.

The Multiple Sclerosis Database Network (MSDN) is the first Italian multiple sclerosis (MS) registry. The preliminary results on the MSDN cohort demonstrated that the risk of disability progression, in a sample of 2090 MS patients, was reduced by about four- to five-fold in patients exposed to IFNbeta for more than 4 years compared with patients exposed for up to 2 years. More recent results showed, in a subset of 1170 relapsing-remitting MS patients, of whom 918 were treated with IFNbeta and 252 were untreated, that IFNbeta-treated patients had a differential reduction in EDSS score change of -0.055 for each year of follow-up in comparison with the untreated group. These results provide significant information on the effectiveness of IFNbeta treatment on long-term disability progression in MS.

Computer Communication Networks↗
PubMed2006

Cognitive dysfunction in patients with relapsing-remitting multiple sclerosis.

Cognitive dysfunction is considered one of the clinical markers of multiple sclerosis (MS). However, in the literature there are inconsistent reports on the prevalence of cognitive dysfunction, and separate data for the relapsing-remitting (RR) type of the disease are not always presented. In this study, we submitted 461 RRMS patients to a battery of neuropsychological tests to investigate their impairment in various cognitive domains. As a consequence of the exclusion criteria, the sample is not fully representative of the entire population of RRMS patients. In this selected sample, when only the eight scores of a core battery (Mental Deterioration Battery) were considered (with respective cutoffs), it emerged that 31% of the patients were affected by some degree of cognitive deficit. In particular, 15% had mild, 11.2% moderate and 4.8% had severe impairment. Information processing speed was the most frequently impaired area, followed by memory. When two other tests (SDMT and MCST) were added and cognitive domains were considered, it emerged that 39.3% of the patients were impaired in two or more domains. When four subgroups were obtained by means of cluster analysis and then compared, it emerged that information processing speed and memory deficits differentiated the still cognitively unimpaired from the mildly impaired MS patients. Significant associations were found between cognitive and clinical characteristics. However, due to the large sample size, clinically irrelevant relationships may also have emerged. Even with the limitations imposed by the sample selection and the possible underestimation of the prevalence and severity of cognitive dysfunction, these results seem to provide further evidence that information processing speed deficit may be an early and important marker of cognitive impairment in MS patients.

Adult↗
PubMed2005

Glatiramer acetate induces pro-apoptotic mechanisms involving Bcl-2, Bax and Cyt-c in peripheral lymphocytes from multiple sclerosis patients.

Apoptotic deletion of autoreactive T-cells is defective in patients with multiple sclerosis (MS). Glatiramer acetate (GA) treatment seems to restore apoptosis of detrimental T-cells. We analyzed the mitochondria membrane pro- (Bax) and anti-apoptotic (Bcl- 2) and cytosolic pro-apoptotic (Cyt-c, APAF-1) proteins expression in peripheral lymphocytes from relapsing-remitting (RR) MS patients during GA treatment. Blood samples were collected from 8 healthy controls (HCs) and from 8 RR MS patients prior to and every three months during the 9 months of GA treatment. Peripheral blood mononuclear cells (PBMNCs) Bcl-2, Bax, Cyt-c and APAF-1 were quantified by western blot followed by densitometric scanning and Bax/Bcl-2, cytosolic Cyt-c/Bcl-2 and APAF-1/Bcl-2 ratios were calculated. T-cells were in vitro tested for oxygen consumption by a respirometric analysis. Bax/Bcl-2, cytosolic Cyt-c/Bcl-2 and APAF-1/Bcl-2 ratios in untreated MS patients were significantly (p < 0.05) lower than in HCs. Bax/Bcl-2 ratio increased (p = 0.03) and Cyt-c/Bcl-2 ratio showed a trend to increase during the 9 months of GA treatment in MS patients. A reduction of 58% and 59% in oxygen consumption by PBMNCs was evident after GA treatment in vitro or when GA treated patients' cells were compared with those from HCs, respectively. Our findings suggest that GA exerts a regulatory effect on peripheral T lymphocytes through pro-apoptosis mechanisms involving mitochondria and cytosolic proteins.

Adult↗
PubMed2005

Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity.

BACKGROUND: There is no consensus method for determining progression of disability in patients with multiple sclerosis (MS) when each patient has had only a single assessment in the course of the disease. METHODS: Using data from two large longitudinal databases, the authors tested whether cross-sectional disability assessments are representative of disease severity as a whole. An algorithm, the Multiple Sclerosis Severity Score (MSSS), which relates scores on the Expanded Disability Status Scale (EDSS) to the distribution of disability in patients with comparable disease durations, was devised and then applied to a collection of 9,892 patients from 11 countries to create the Global MSSS. In order to compare different methods of detecting such effects the authors simulated the effects of a genetic factor on disability. RESULTS: Cross-sectional EDSS measurements made after the first year were representative of overall disease severity. The MSSS was more powerful than the other methods the authors tested for detecting different rates of disease progression. CONCLUSION: The Multiple Sclerosis Severity Score (MSSS) is a powerful method for comparing disease progression using single assessment data. The Global MSSS can be used as a reference table for future disability comparisons. While useful for comparing groups of patients, disease fluctuation precludes its use as a predictor of future disability in an individual.

Adult↗
PubMed2005

The IFNbeta treatment of multiple sclerosis (MS) in clinical practice: the experience at the MS Center of Bari, Italy.

This independent, population-based surveillance study monitored, in clinical practice, the efficacy of interferon beta (IFNbeta) products in 1173 patients with multiple sclerosis (MS) from the Department of Neurological and Psychiatric Sciences, University of Bari, Italy. Relapses and Expanded Disability Status Scale (EDSS) scores were evaluated for up to 6 years for Avonex, Betaferon and Rebif 22 groups, and for up to 3 years for the Rebif 44 group. IFNbeta products produced significant reductions from baseline in relapse rates at 2, 4 and >4 years (p<0.0001), with no differences among treatments (p=0.2). A modest significant (p<0.05) increase of EDSS was observed in all treatment groups from baseline to 48 months, followed thereafter by a plateau. The IFNbeta-1b group showed more withdrawals (19%) compared with Avonex (6%) and Rebif (7%) at 6 years.

Adjuvants, Immunologic↗
PubMed2005

Serum MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in multiple sclerosis: relationships with different magnetic resonance imaging measures of disease activity during IFN-beta-1a treatment.

Matrix metalloproteinase-9 (MMP-9) is involved in blood-brain barrier (BBB) disruption in active multiple sclerosis (MS), while MMP-2 seems to be associated with the chronic progressive phase of the disease. Recombinant interferon beta-1a (rIFNbeta-1a) is effective in restoring the BBB. We studied the relationships between serum MMP-9, MMP-2, TIMP-1 and TIMP-2 and different magnetic resonance imaging (MRI) measures of disease activity in MS patients during treatment with rIFNbeta-1a. Twenty-one relapsing-remitting (RR) MS patients underwent longitudinally simultaneous blood withdrawals and MRI (before and after standard dose (SD) and triple dose (TD) of gadolinium (Gd)) examinations before and during 48 weeks of rIFNbeta-1a (Rebif 22 mcg three times a week) treatment. Serum MMP-9, MMP-2, TIMP-1 and TIMP-2 were measured, MMP-9 to TIMP-1 and MMP-2 to TIMP-2 ratios were calculated and the numbers of Gd-SD, Gd-TD, new-Gd-SD, new-Gd-TD and new-T2 lesions counted. Serum MMP-9/TIMP-1 ratio (P < 0.0001), as well as the numbers of 'active' lesions (P ranging from 0.0004 to 0.005) decreased during treatment Moreover, serum MMP-9/TIMP-1 ratio proved to be a good positive predictor (estimate = 0.85; P < 0.05) of the numbers of MRI Gd-TD active lesions. These data confirm that serum MMP-9/TMIP-1 ratio may be viewed as a reliable marker and may be predictive of MRI activity in RR MS.

Adjuvants, Immunologic↗
PubMed2005

Disease-modifying drugs in childhood-juvenile multiple sclerosis: results of an Italian co-operative study.

OBJECTIVE: Immunomodulatory drugs (IDs) (interferon beta (IFNgamma) and glatiramer acetate (GA)) reduce relapse rate and disease progression in relapsing remitting multiple sclerosis (RRMS) but extensive data are not available on the effectiveness and tolerability of these drugs in childhood or adolescence. The aim of this study was to evaluate the impact of IFNbeta and GA in MS patients treated before 16 years of age. METHODS: A research group (Immunomodulatory Treatment of Early onset MS (ITEMS)) was promoted in Italy to collect a large series of patients affected by clinically definite and RRMS and treated with IDs before 16 years of age. Fifteen centres recognized subjects suitable for inclusion: 76 patients (52 females) were collected with a mean age at onset of 12.4 (SD 2.5) years, a mean disease duration of 18.6 (SD 14.7) and a relapse rate of 3.1 (SD 2.9). RESULTS: Results were evaluated in 65 (45 females) subjects with a pretreatment and a treatment duration >3 months: 38 were treated with IFNbeta-1a once weekly (Avonex), 18 with IFNbeta three times weekly (16 with Rebif, 2 with Betaferon) and nine with GA (Copaxone). The mean pretreatment period was respectively 20, 18 and 9.2 months. The treatment duration lasted respectively 23.3, 40.7 and 33.3 months. The mean annualized relapse rate decreased dramatically during the treatment: from 2.4 to 0.4 in the Avonex group, from 3.2 to 0.8 in the Rebif-Betaferon group and from 2.8 to 0.25 in the GA group. The mean final EDSS scores were respectively (in brackets the initial scores): 1.3 (1.4), 1.6 (1.8) and 0.6 (1.1). In the whole group, the final score was unchanged or reduced in all subjects except eight. Clinical side effects were recorded in 41/65 subjects (mainly in subjects treated with IFNbeta), abnormal laboratory findings were observed in 13/65 subjects: they were transient in most cases. IFNgamma was stopped in six cases: in four because of inefficacy and in two cases because of side effects. CONCLUSIONS: Sixty-five clinically definite MS subjects were treated during childhood or adolescence with IDs. The treatment reduced the relapse rate and the progression of the disease in most cases. Side effects were common in subjects treated with IFNbeta but were well tolerated in most cases.

Adjuvants, Immunologic↗
PubMed2004

The prevalence of pain in multiple sclerosis: a multicenter cross-sectional study.

In a multicenter cross-sectional study, the authors assessed pain in patients with multiple sclerosis (MS) using a symptom-oriented approach. Out of 2,077 questionnaires, we used 1,672 for data analysis. Pain and frequencies included trigeminal neuralgia 2%, Lhermitte's sign 9%, dysesthetic pain 18.1%, back pain 16.4%, and painful tonic spasms 11%. Comparison between different groups showed significant differences for age, Expanded Disability Status Scale, disease duration, and disease course, but not for sex. This study underlines the relevance of pain in the clinical history of MS.

Adolescent↗
PubMed2004

A double blind, placebo-controlled, phase II, add-on study of cyclophosphamide (CTX) for 24 months in patients affected by multiple sclerosis on a background therapy with interferon-beta study denomination: CYCLIN.

The authors present and discuss a new protocol for active multiple sclerosis (MS) patients. A double blind randomized controlled multicenter study was planned to study the effects of a combination regimen therapy: cyclophosphamide plus beta interferon versus beta interferon alone on both relapsing-remitting and secondary MS patients with active disease. The primary endpoint of this study is the number of new gadolinium enhancing lesions at MRI evaluation. Secondary endpoints are new T2 lesions, new T1 lesions, T2 lesion load, T1 lesion load, cerebral atrophy, number of patients who were relapse-free, number of patients who improved, yearly relapses, quality of life, disability and cognitive impairment, frequency of neutralizing antibodies, safety of the combination therapy (cyclophosphamide + beta interferon). The study will enroll 225 patients in 25 Italian MS centers. Eligible for the study are patients with either relapsing-remitting or secondary MS according McDonald criteria on 6-24 months beta interferon treatment with active disease (new gadolinium enhancing lesion or who experienced a new relapse on beta interferon treatment). Clinical evaluation will be performed every 4 months, MRI yearly. Vital signs and eventual adverse events will be collected monthly. The study will last 36 months, 12 for the enrollment phase and 24 for the treatment phase. The study will start on April 2004.

Central Nervous System↗
PubMed2004

Atypical forms of multiple sclerosis or different phases of a same disease?

Multiple sclerosis (MS) patients complain with the first symptoms of the disease in a range period which varies from childhood to adult life. The extent to which clinical presentation, disease course and demographic features may differ between childhood and adult onset has been the object of investigation. This paper aims to demonstrate that the different clinical phenotypes in young and old patients might simply reflect different phases of a same pathological process.

Adolescent↗
PubMed2003

Adhesion molecules and matrix metalloproteinases in Multiple Sclerosis: effects induced by Interferon-beta.

In Multiple Sclerosis (MS) pathology, early inflammation involves leukocyte migration across the blood-brain barrier (BBB) within the central nervous system. In this process, adhesion molecules (AMs), both membrane-bound and soluble-circulating forms, and matrix metalloproteinases (MMPs) certainly play a regulatory role. In MS, recombinant Interferon-beta (rIFNbeta) is effective in reducing gadolinium contrast-enhancing lesions on magnetic resonance imaging and this suggests that it may reduce BBB damage or even restore its integrity by different mechanisms that include interference with both AM and MMP pathways. This review will highlight the effects induced by rIFNbeta, both in vitro and in vivo, on cell-bound and soluble forms of AMs and on MMPs.

Animals↗
PubMed2003

The transition from relapsing-remitting MS to irreversible disability: clinical evaluation.

The development of a progressive course is by far the most deleterious event in the case of a multiple sclerosis (MS) patient. It occurs in about 90% of relapsing remitting patients by 20-25 years from onset. The clinical transition to secondary progressive MS is phenotypically distinctive and both patients and physicians acknowledge that a fundamental shift in the degree of responsiveness to anti-inflammatory therapies has occurred. This review discusses the clinical studies that provided important findings relating to our understanding on different mechanisms that may contribute to irreversible disability in MS.

Adult↗
PubMed2002

Intrathecal synthesis of matrix metalloproteinase-9 in patients with multiple sclerosis: implication for pathogenesis.

Matrix metalloproteinase-9 (MMP-9) was detected by zymography and enzyme-linked immunosorbent assay (ELISA) in matched serum and cerebrospinal fluid (CSF) samples from patients with neurological diseases. Patients with relapsing-remitting multiple sclerosis (RR-MS) had serum and CSF MMP-9 levels comparable to those from patients with inflammatory neurological diseases (INDs), but higher than patients with non-inflammatory neurological diseases (NINDs) and healthy donors (HDs). MMP-9 increased in active RR-MS in comparison with inactive RR-MS implying that MMP-9 in MS is related with clinical disease activity. A correlation between the CSF/serum albumin (Q(AIb)) and CSF/serum MMP-9 (Q(MMP-9)) was observed in IND and NIND but not in RR-MS patients, indicating that CSF MMP-9 levels in NIND and IND patents could be influenced by serum MMP-9 and blood-brain barrier (BBB) permeability properties. MS patients had higher values of Q(MMP-9):Q(Alb)(MMP-9 index) than IND and NIND patients suggesting that in MS the increase in CSF MMP-9 could be due to intrathecal synthesis of MMP-9. A significant inverse correlation was found between MMP-9 and its endogenous inhibitor TIMP-1 in RR-MS indicating that in MS patients both the increase in MMP-9 and the decrease in TIMP-1 serum levels could contribute to BBB disruption and T-lymphocyte entry into the CNS.

Adult↗
PubMed2001

LFA-1 expression on CD4(+)CD45RO(+) peripheral blood T-lymphocytes in RR MS: effects induced by rIFNbeta-1a.

We investigate the in vivo and in vitro effects of short-term treatment with recombinant Interferon beta-1a (rIFNbeta-1a) on CD4(+)CD45RO(+) activated/memory peripheral blood T-lymphocytes (PBTLs) expressing Leukocyte Function Antigen-1 (LFA-1; CD11a/CD18) in relapsing-remitting (RR) Multiple Sclerosis (MS) patients. Blood samples were obtained from 10 RR MS patients before and after 2, 4 and 6 months of rIFNbeta-1a (Avonex) treatment. For each sample, the percentage of CD4(+)CD45RO(+)CD11a(+) (CD11a(dim) and CD11a(bright)) T-cells was evaluated in in vivo PBTLs and in untreated or rIFNbeta-1a (1000 U/ml) or recombinant soluble Intercellular Adhesion Molecule-1 (ICAM-1, the ligand for LFA-1) (400 ng/ml) treated cultured PBTLs by triple fluorescence flow-cytometry (FACS analysis). Soluble ICAM-1 (sICAM-1) serum levels were evaluated by ELISA. In vivo, the percentage of CD4(+)CD45RO(+), CD4(+)CD45RO(+)CD11a(+), CD4(+)CD45RO(+)CD11a(dim) PBTLs increased after 4 and 6 months of rIFNbeta-1a treatment compared to pretreatment and 2 months of treatment (p<0.05). The CD11a expression per se did not change during the time course. Soluble ICAM-1 (sICAM-1) serum levels also increased (p<0.05) after 4 and 6 months of treatment. When T-cells, obtained from the blood of the same patients before and during in vivo treatment, were cultured either untreated or treated with rIFNbeta-1a, they showed an increase in the percentage of CD4(+)CD45RO(+) T-cells expressing CD11a(bright) (p<0.05). The addition of recombinant sICAM-1 to untreated cultures decreased the percentage of CD4(+)CD45RO(+) T-cells expressing CD11a. This last finding seems to support an indirect effect in vivo of rIFNbeta-1a via sICAM-1 on this T-cell subset, since the ICAM-1 soluble form, induced in vivo in serum by rIFNbeta-1a but lacking in in vitro conditions, keeps the percentage of CD11a(+) unchanged within CD4(+)CD45RO(+) T-cells and induces their expression of CD11a(dim), probably preventing T-cells from transmigrating.

Adjuvants, Immunologic↗
PubMed2001

The differential diagnosis of multiple sclerosis: classification and clinical features of relapsing and progressive neurological syndromes.

In the absence of pathognomonic clinical features or a definitive laboratory test, multiple sclerosis (MS) remains ultimately a diagnosis of exclusion. Accurate diagnosis is increasingly important with available disease modifying therapy. Unfortunately the rate of misdiagnosis remains around 5%-10%, indicating that 1 in 20 patients thought to have MS has, instead, a condition resembling MS. In this review we describe conditions that may be confused with MS because they can present as lesions disseminated in time, space, or both. Conditions often confused with MS may be inflammatory (systemic lupus erythematosus, Sjögren's syndrome, vasculitis, sarcoidosis, Behçet's disease), infectious (Lyme disease, syphilis, progressive multifocal leukoencephalopathy, HTLV-1 infection, herpes zoster), genetic (lysosomal disorders, adrenoleukodystrophy, mitochondrial disorders, CADASIL), metabolic (vitamin B12 deficiency), neoplastic (CNS lymphoma) and spinal (degenerative and vascular malformations) diseases. The key to the accurate diagnosis of MS is vigilance for atypical features, suggesting the possibility of an alternative diagnosis.

Central Nervous System Diseases↗
PubMed2001

A genome screen for multiple sclerosis in Italian families.

We have screened the whole genome for linkage in 40 Italian multiplex families with multiple sclerosis using 322 markers. The GENEHUNTER-PLUS program was used to analyse these data and revealed eight regions of potential linkage where the lod score exceeds the nominal 5% significance level (0.7). No region of linkage with genome-wide significance was identified and none of the markers showed evidence of statistically significant transmission disequilibrium. Overall these results have refined the linkage data relating to this disease in Italians modestly supporting some previously identified areas of interest and helping to exclude others.

Genetic Testing↗
PubMed2001

IFN-beta1a modulates the expression of CTLA-4 and CD28 splice variants in human mononuclear cells: induction of soluble isoforms.

Recently, mRNA encoding soluble isoforms of CD28 and CTLA-4 have been described in human lymphocytes. We demonstrate that interferon-beta1a (IFN-beta1a) can enhance the expression of these transcripts in human mononuclear cells. Because soluble CD28 and CTLA-4 molecules might affect T cell activation, our findings suggest an additional means whereby IFN-beta therapy might exert its immunomodulatory effects in multiple sclerosis (MS).

Abatacept↗