Showing papers by "Marco Salvetti published in 2003"

The effect of Bacille Calmette-Guérin on the evolution of new enhancing lesions to hypointense T1 lesions in relapsing remitting MS.

Abstract: Sirs: A recent crossover trial documented that a single Bacille Calmette-Guérin (BCG) vaccination decreased the disease activity on magnetic resonance imaging (MRI) in a cohort of 12 relapsingremitting multiple sclerosis (RRMS) patients [1]. A reduction in MRI disease activity is an expression of the influence of the drug on the inflammatory component of the disease. However, this does not necessarily imply an effect on tissue damage. Hence, there is a need for testing the effect of new potential therapies additional to this component of MRI measures, namely of tissue destruction (brain atrophy, black holes). Methods are available for this purpose [2, 3, 4]. The assessment of the percentage of new enhancing lesions (NEL) that evolve into black holes is a measure of tissue damage that may result either from the severity of the inflammatory process or from primary axonal damage. This has been already exploited in studies on the effects of disease modifying treatments (interferon-β, glatiramer acetate) [5, 6].We used this approach to investigate whether BCG vaccination affects the proportion of NEL that develop into black holes. Study design and clinical characteristics of patients included in the present study have been described elsewhere [1]. Briefly, 12 RRMS patients were followed-up monthly with Gd-enhanced MRI for 6 months of run-in and for 6 months after BCG. Three further scans were performed 6-monthly after the completion of the monthly scans (a follow-up period of 24 months after the vaccination). None of these patients underwent disease-modifying therapies during the follow-up. Brain MRI was performed with a superconductive 0.5 T magnet. The MRI protocol included axial PD and T2-w spinecho and T1-w before and after injection of a single dose of gadolinium. All NEL occurring both in the run-in and post-BCG phase were identified by consensus of two experienced observers and then marked on the hardcopies. Imaging from the previous month was checked to ensure that all marked enhancing lesions were absent in T2and T1-weighted images. For each NEL we evaluated: a) location; b) size; c) persistence of enhancement d) possible re-enhancement at 18, 24 month scans. Afterwards, the two observers verified for each NEL whether the lesion corresponded to a black hole on the 24-month scan. The definition of a black hole was based on visual analysis and defined as a lesion that has lower signal intensity than grey matter and corresponding to a hyperintense region on T2weighted image. Statistical analysis was carried out using chi square (likelihood) test and Fisher’s exact test. Four patients did not show NEL during the run-in and post-BCG phase. Hence, this study’s data refer to 8 patients who had at least one NEL in the run-in and one NEL in the post-BCG period. Table 1 summarizes significant differences in number and outcome of NEL between the two phases. A reduction of NEL was observed after BCG pulse (58 vs 28; p < 0.01, by chi square). No significant differences were found between the two periods in the location or size of NEL. Gd-enhancement persisted at subsequent months in 18/58 (31 %) NEL of the run-in phase and in 1/28 (4 %) NEL of the post-BCG phase (p < 0.01 by chi square). We observed no re-enhancements on 18 and 24 month scans. The number of NEL evolving to black holes was 28/58 (46 %) for those of the run-in phase and 6/28 (21 %) for those of the post-BCG period (P < 0.01 by chi square). The analysis per subject demonstrated that, in each patient, the proportion of NEL evolving into black holes was lower in the post-BCG phase LETTER TO THE EDITORS

T Cell Response to Amyloid-β and to Mitochondrial Antigens in Alzheimer’s Disease

Abstract: Despite the vast amount of literature on non-specific immune mechanisms in Alzheimer’s disease (AD), little is known about the role of antigen-specific immune responses. We investigated T cell reactivity to fragment 1–42 of amyloid-β (Aβ) and to N-terminal peptides of human mitochondrial and control microbial proteins. Thirty subjects with a diagnosis of probable AD according to NINCDS-ADRDA criteria and 30 sex- and age-matched healthy controls were enrolled. T cell responses to Aβ fragment showed no significant differences between AD patients and controls. By contrast, the mean number of positive T cell responses to both human mitochondrial and microbial peptides was significantly decreased in AD patients compared to control subjects. No significant correlation was found between T cell responses and both the severity of cognitive impairment and duration of the disease. Our results suggest that antigen-specific immune responses are impaired in AD. Protective immune responses to harmful amyloidogenic substances may also be impaired, thus favoring their accumulation in the brain.

Physiopathology of multiple sclerosis

Abstract: Pleiotropy and redundancy are distinctive elements of the immune response. Recent research into the inflammatory component of multiple sclerosis (MS) indicates that, as expected, pleiotropy and redundancy characterize various physiopathological mechanisms of the disease. A certain degree of redundancy is becoming apparent also as far as the degenerative component is concerned. Cumulatively, these data suggest that treatments that target single pathogenetic pathways are unlikely to provide a definitive solution. Combination therapies may offer, in principle, some advantage, although there is a need for more information on the aetiology of the disease.

[Twins in biomedical research and the creation of the "National Twin Registry"].

Abstract: Twins are a valuable resource for the study of complex traits. The twin method is substantially based on the comparison between correlations and concordance in monozygotic (MZ) and dizygotic (DZ) twins and allows several applications in biomedical and molecular genetic research. It allows either the qualitative and quantitative evaluation of the influences that genetic and environmental factors exert on phenotypes or the estimation of trait variability. Moreover, classical genetic linkage analysis is more powerful if performed in DZ twins. However, the twin method has some pitfalls, such as the necessity that collected samples be representative of both twin and general population. For this reason, over the last few years, a number of Countries have established population-based twin registers, which guarantee the maximum level of representation and, consequently, are of extreme value for epidemiological studies. Italy is also implementing a national twin register. The following is the description of the procedure that led to the establishment of the Italian Twin Registry.