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Biomedical subjects

G Savettieri

Publications and source records attributed to G Savettieri.

At least 19 recordsLinked to original sources
PubMed2006

APOE epsilon variation in multiple sclerosis susceptibility and disease severity: some answers.

BACKGROUND: Previous studies have examined the role of APOE variation in multiple sclerosis (MS), but have lacked the statistical power to detect modest genetic influences on risk and disease severity. The meta- and pooled analyses presented here utilize the largest collection, to date, of MS cases, controls, and families genotyped for the APOE epsilon polymorphism. METHODS: Studies of MS and APOE were identified by searches of PubMed, Biosis, Web of Science, Cochrane Review, and Embase. When possible, authors were contacted for individual genotype data. Meta-analyses of MS case-control data and family-based analyses were performed to assess the association of APOE epsilon genotype with disease risk. Pooled analyses of MS cases were also performed to assess the influence of APOE epsilon genotype on disease severity. RESULTS: A total of 22 studies (3,299 MS cases and 2,532 controls) were available for meta-analysis. No effect of epsilon2 or epsilon4 status on MS risk was observed (summary OR 1.14, 95% CI 0.96-1.34 and OR 0.89, 95% CI 0.78-1.01). Results obtained from analyses of APOE genotypes in 1,279 MS families were also negative (p = 0.61). Finally, results from pooled analyses of 4,048 MS cases also argue strongly that APOE epsilon status does not distinguish a relapsing-remitting from primary progressive disease course, or influence disease severity, as measured by the Expanded Disability Status Scale and disease duration. CONCLUSION: Overall, these findings do not support a role for APOE in multiple sclerosis, and underscore the importance of using large sample sizes to detect modest genetic effects, particularly in studies of genotype-phenotype relationships.

Alleles↗
PubMed2006

Treatment of multiple sclerosis with interferon beta in clinical practice: 2-year follow-up data from the South Italy Mobile MRI Project.

This follow-up study assessed the 2-year clinical and magnetic resonance imaging (MRI) outcomes of patients with multiple sclerosis (MS) originally enrolled in an MRI study conducted at eight centres in south Italy (the South Italy Mobile MRI Project). Of the 597 MS patients recruited at baseline, 391 returned for the follow-up study. Of these, 363 provided 2-year clinical and MRI follow-up data, and 215 were still undergoing treatment with one of four interferon beta regimens: Avonex, 30 mcg intramuscularly once weekly; Betaferon, 250 mcg subcutaneously (sc) every other day; Rebif 22 mcg sc three times weekly (tiw; Rebif 22); or Rebif 44 mcg sc tiw (Rebif 44). Over the 2-year follow-up period, patients receiving the higher dose of Rebif were more likely to remain free from relapses [odds ratio (OR) = 2.23] and from developing both new T2 (OR = 0.15) and new T1 black hole lesions (OR = 0.22), when compared with patients in the Avonex group. Despite some limitations in the trial design, the results from this follow-up study provide helpful clinical and MRI data on the efficacy of interferon beta regimens in MS patients treated in the clinical setting.

Analysis of Variance↗
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

Brain atrophy and lesion load in a large population of patients with multiple sclerosis.

OBJECTIVE: To measure white matter (WM) and gray matter (GM) atrophy and lesion load in a large population of patients with multiple sclerosis (MS) using a fully automated, operator-independent, multiparametric segmentation method. METHODS: The study population consisted of 597 patients with MS and 104 control subjects. The MRI parameters were abnormal WM fraction (AWM-f), global WM-f (gWM-f), and GM fraction (GM-f). RESULTS: Significant differences between patients with MS and control subjects included higher AWM-f and reduced gWM-f and GM-f. MRI data showed significant differences between patients with relapsing-remitting and secondary progressive forms of MS. Significant correlations between MRI parameters and between MRI and clinical data were found. CONCLUSIONS: Patients with multiple sclerosis have significant atrophy of both white matter (WM) and gray matter (GM); secondary progressive patients have significantly more atrophy of both WM and GM than do relapsing-remitting patients and a significantly higher lesion load (abnormal WM fraction); lesion load is related to both WM and even more to GM atrophy; lesion load and WM and GM atrophy are significantly related to Expanded Disability Status Scale score and age at onset (suggesting that the younger the age at disease onset, the worse the lesion load and brain atrophy); and GM atrophy is the most significant MRI variable in determining the final disability.

Adolescent↗
PubMed2005

Long-term survival of Parkinson's disease: a population-based study.

In a set of a population- based study, long-term survival of 59 prevalent PD patients was compared with that of individuals free of neurological diseases matched 1:2 by sex and age of enrolment. PD individuals, compared with reference subjects, showed a two-fold increased risk of death (OR 2.1; 95 % CI 1.4, 3.1). Among causes of death, pneumonia and cachexia were significantly more frequent among PD patients than among individuals free of neurological diseases. We confirmed in a long-term follow-up study an increased mortality among PD individuals compared with that of the general population.

Age Factors↗
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 HLA locus and multiple sclerosis in Sicily.

The authors report the analysis of HLA-class II allelic heterogeneity in a well characterized multiple sclerosis (MS) Sicilian dataset. Family-based association analysis revealed evidence for excess transmission to affected individuals for alleles HLA-DRB1*1501, DRB1*04, and DQB1*0302. When analyzed as haplotypes, the authors observed excess transmission for the DRB1*0400-DQB1*0302 haplotype. Sicilian patients share the HLA-DRB1*1501 susceptibility allele with affected living in continental Italy, but also display the allelic heterogeneity that characterizes Mediterranean populations.

Adolescent↗
PubMed2005

A novel mutation of the extracellular matrix protein 1 gene (ECM1) in a patient with lipoid proteinosis (Urbach-Wiethe disease) from Sicily.

BACKGROUND: Lipoid proteinosis (LP), also known as Urbach-Wiethe disease, is a rare autosomal recessive disorder characterized by a hoarse voice, warty skin infiltration and scarring. Mutations within the extracellular matrix protein 1 (ECM1) gene cause LP. OBJECTIVES: We report the molecular analysis of the ECM1 gene in a Sicilian patient with LP in order to extend the mutation spectrum of this genodermatosis. METHODS: We studied a 32-year-old female born from consanguineous parents who was diagnosed at the age of 11 years as having LP. She has a clinical phenotype corresponding to Urbach-Wiethe disease characterized by papules/nodules, indurated plaques and sometimes ulcerated lesions primarily involving the skin and mucous membranes, and extracutaneous features such as epilepsy, hoarseness of the voice and neuropsychiatric abnormalities. Samples of clinically affected skin obtained by biopsies were analysed after staining with haematoxylin and eosin, periodic acid-Schiff (PAS), and PAS-diastase. The whole ECM1 gene was analysed by direct sequencing. RESULTS: We identified a homozygous nonsense mutation in exon 6 of the ECM1 gene, C589T (Q197Ter). CONCLUSIONS: Over 60% of mutations occur in exons 6 and 7. Exon 7 is alternatively spliced and frameshift mutations in exon 7 lead to ablation of the ECM1a transcript, but not the shorter ECM1b transcript that normally lacks this exon. Homozygous nonsense or frameshift mutations in exon 6 are predicted to affect both full-length ECM1a and ECM1b transcripts, whereas ECM1b should be unaffected for similar types of mutation in exon 7. It has been suggested that individuals with mutations in exon 7 have a slightly milder phenotype than those with exon 6 mutations. This is the first report with respect to a novel mutation of the ECM1 gene responsible for recessive LP in Sicily.

Adult↗
PubMed2004

Risk of Parkinson disease in women: effect of reproductive characteristics.

OBJECTIVE: To investigate the association between some fertile life characteristics and Parkinson disease (PD) in women. METHODS: Women affected by PD and control subjects were matched one to one by age (+/-2 years). One hundred thirty-one women with idiopathic PD and 131 matched control subjects were interviewed. Controls were randomly selected from the resident list of the same municipality of residence of cases. All subjects had a Mini-Mental State Examination score of > or =24. Cumulative length of pregnancies, age at menarche, age and type of menopause, and estrogen use before and after menopause were investigated in cases and controls through a structured questionnaire. Models of matched pair univariate analysis and conditional logistic regression analyses were used to calculate adjusted odds ratio (OR), 95% CI, and two-tailed p values for the investigated variables. RESULTS: PD was significantly associated with a fertile life length shorter than 36 years (OR 2.07; 95% CI 1.00 to 4.30) and a cumulative length of pregnancies longer than 30 months (OR 2.19; 95% CI 1.22 to 3.91). An inverse association between PD and surgical menopause (adjusted OR 0.30; 95% CI 0.13 to 0.77) was also found. CONCLUSIONS: An association between factors reducing estrogen stimulation during life and PD was found. These results support the hypothesis that endogenous estrogens play a role in the development of PD.

Age of Onset↗
PubMed2004

Bovine spongiform encephalopathy and Creutzfeldt-Jakob disease: facts and uncertainties underlying the causal link between animal and human diseases.

Following an outbreak of bovine spongiform encephalopathy (BSE) in dairy cows in the United Kingdom (UK), 153 definite and probable human cases of new variant Creutzfeldt-Jakob disease (nvCJD) have been reported, almost exclusively in the UK. Although exposure to the BSE agent is the most plausible interpretation for the occurrence of nvCJD, the causal link between the BSE prion and nvCJD is still debated. This review discusses the pros and cons of nvCJD as a separate nosographic entity, the scientific basis for a correlation between BSE and nvCJD, the validity of the current diagnostic criteria for CJD and nvCJD, the contribution of epidemiology to the detection of a causal relation between BSE and nvCJD, and the present and future directions of the epidemiological research on BSE, CJD and nvCJD.

Animals↗
PubMed2004

The relapse rate of multiple sclerosis changes during pregnancy: a cohort study.

OBJECTIVE: To evaluate the influence of pregnancy and puerperium on the relapse rate of multiple sclerosis (MS). METHODS: We determined retrospectively the yearly mean relapse rate (MRR) during pregnancies occurring in the course of relapsing-remitting MS. We compared the MRR of pregnancy-time with that of non-pregnancy time by paired t-test. Relative risk (RR) of relapses during the pregnancy-time was also compared with that of non-pregnancy time by chi(2) analysis and 95% confidence intervals. RESULTS: From a population of 351 women affected by clinically definite MS, only 70 reported pregnancies during their relapsing-remitting phase of MS for a total of 98 pregnancies. Both MRR (P = 0.006) and RR (RR = 0.63, 95% CI = 0.40-0.94) decreased during the three trimesters of pregnancy. RR increased in the first 3 months of puerperium, although this was not statistically significant (RR = 1.36, 95% CI = 0.79-2.20). CONCLUSION: Our study confirms that in MS the relapse rate decreases throughout pregnancy and increases during puerperium. This suggests a complex interplay between hormonal and immune factors.

Adolescent↗
PubMed2002

A transcranial magnetic stimulation study evaluating methylprednisolone treatment in multiple sclerosis.

OBJECTIVE: To investigate the efficacy of two different high doses of intravenous methylprednisolone (IVMP) during Multiple Sclerosis (MS) relapses. BACKGROUND: Transcranial Magnetic Stimulation (TMS) is the most sensitive neurophysiological ascertainment to quantify motor disability, to follow the recovery from an MS relapse, and to detect the response to treatment. DESIGN AND METHOD: Twenty-four clinically definite relapsing - remitting MS patients presenting a relapse were randomly assigned to a treatment for 5 days with IVMP 1 or 2 g/day. The response to treatment of each patient was evaluated through Expanded Disability Status Scale (EDSS), Medical Research Council (MRC) score, and TMS by means of motor evoked potential (MEP) parameters. RESULTS: Motor threshold (MT), central motor conduction time (CMCT) and MRC showed a higher improvement with the highest dose of IVMP. Silent period and EDSS improved with both treatments. CONCLUSION: The dose of 2 g/day of IVMP is more effective in MS relapse.

Adult↗
PubMed2001

High incidence and increasing prevalence of MS in Enna (Sicily), southern Italy.

Twenty years after a first survey, a follow-up study was performed on the prevalence of MS in Enna (Sicily), southern Italy. The prevalence of definite MS rose from 53 to 120.2 per 100,000 population. The incidence of definite MS for the period 1986 to 1995 was 5.7 per 100,000 per year. The innermost part of Sicily shows an elevated prevalence of MS, second only to Sardinia in the Mediterranean area.

Adolescent↗
PubMed2001

Functional feature of a novel model of blood brain barrier: studies on permeation of test compounds.

Drug delivery to the central nervous system (CNS) is subject to the permeability limitations imposed by the blood-brain barrier (BBB). Several systems in vitro have been described to reproduce the physical and biochemical behavior of intact BBB, most of which lack the feature of the in vivo barrier. We developed a fully formed monolayer of RBE4.B immortalized rat brain microvessel endothelial cells (ECs), grown on top of polycarbonate filter inserts with cortical neuronal cells grown on the outside. Neurons induce ECs to synthesize and sort occludin to the cell periphery. Occludin localization is regulated by both compositions of the substratum and soluble signals released by cortical co-cultured neurons. The observed effects do not require strict physical contact among cells and neurons. To assess the physiological function of the barrier we examined the transendothelial transfer of three test compounds: dopamine, L-tryptophan and L-DOPA. Polycarbonate filter inserts, where ECs were co-cultured with neurons, were assumed as open two compartments vertical dynamic models. Permeation studies demonstrated that the ECs/neurons co-cultures possess permeability characteristics approaching those of a functional BBB: the system behaved as a selective interface that excludes dopamine permeation, yet permits L-tryptophan and L-DOPA to cross. The movement of test compounds from the donor to the acceptor compartment was observed at a distinct time from the start of co-culture. Transfer was determined using standard kinetic equations. Different performance was observed after 5 and 7 days of co-culture. After 5 days dopamine, L-tryptophan and L-DOPA passively permeate through the membrane as indicated by fittings with a first-order kinetic process equation. After 7 days of co-culture, occludin localizes at ECs periphery, dopamine does not cross the barrier to any further extent, while the transfer of L-tryptophan and L-DOPA fits well with a saturable Michaelis-Menten kinetic process, thus indicating the involvement of a specific carrier-mediated transport mechanism. Permeation studies confirmed that culture of ECs in the presence of neurons induces the characteristic permeability limitations of a functional BBB.

Animals↗
PubMed2001

The parkin gene is not involved in late-onset Parkinson's disease.

Mutations in the parkin gene have been reported in patients with early onset PD. The authors investigated the parkin gene in 118 patients who had an onset of PD after age 45 years: 95 subjects were sporadic patients and 23 subjects were from 18 families with a probable autosomal recessive inheritance. No pathogenetic mutations in the parkin gene were detected either in familial or in sporadic patients. Moreover, no differences were found between patients and 100 age-matched normal controls in the allele and genotype frequencies of four exonic parkin polymorphisms.

Age of Onset↗
PubMed2001

Epidemiology of multiple sclerosis in Sicily.

From epidemiological data obtained over more than 20 years by surveys conducted in different parts of Sicily, it is evident that Sicily is a high-risk area for multiple sclerosis (MS). This is in sharp contrast with the gradient hypothesis. High frequencies have been found in different parts of the island having different geoclimatic features, but at least two cities (Monreale and Enna) had had a prolonged Norman domination. This is in agreement with the hypothesis that MS originated in Northern Europe and spread around the world throughout the raids of the northern peoples. The increase in frequency estimated by follow-up and incidence studies is well established and is only in part linked to the improvement in diagnostic techniques. Finally, it is noteworthy that in the islands of Malta, a few sea miles away from Sicily, the MS prevalence rates are in the range of 4-8 cases per 100000 persons. This occurrence represents a natural model to investigate MS etiology through analytic studies and genetic analyses.

Age Factors↗